The Mechanisms and Quantification of the Selective Permeability in Transport Across Biological Barriers: the Example of Kyotorphin

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The Mechanisms and Quantification of the Selective Permeability in Transport Across Biological Barriers: the Example of Kyotorphin

Isa D. Serranoa,#

, João M. Freirea,#

, Miguel V. Carvalhoa, Mafalda Neves

a, Manuel N. Melo

b,*and

Miguel A.R.B. Castanhoa,*

aInstituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz,

1649-028 Lisboa, Portugal; bGroningen Biomolecular Sciences and Biotechnology Institute, Rijksuniversiteit

Groningen, 9747 AG Groningen, The Netherlands

Abstract: This paper addresses the mechanisms behind selective endothelial permeability and their regulations. The

singular properties of each of the seven blood-tissues barriers. Then, it further revisits the physical, quantitative meaning

of permeability, and the way it should be measured based on sound physical chemistry reasoning and methodologies.

Despite the relevance of permeability studies one often comes across inaccurate determinations, mostly from

oversimplified data analyses. To worsen matters, the exact meaning of permeability is being lost along with this loss of

accuracy. The importance of proper permeability calculation is illustrated with a family of derivatives of kyotorphin, an

analgesic dipeptide.

Keywords: Blood-tissue barriers, Drug, Kinetics, Kyotorphin, Permeability, Transepithelial transport.

1. INTRODUCTION

In spite of the significance of epithelial permeability in pharmacology, toxicology and biochemistry, its meaning and proper quantitative approaches for its determination are frequently overlooked. Molecular transport across epithelia is of paramount importance in biochemistry and pharmacology [1]. Nutrients and drugs, for instance, need to cross cell barriers such as the intestinal epithelium in order to be absorbed and distributed. Once in systemic circulation, molecules often have to translocate across additional cellular barriers to reach their target tissues [2-4]. Among these barriers, the blood-brain barrier (BBB) is probably the most challenging [5] for its impermeability to most molecules that have no specific transporters. Yet, cellular barriers in lungs, eyes and many other organs make epithelia permeability an issue of broad interest to a very large scientific community. This topic is deem to be of high importance and this is reflected on the Food and Drug Administration (FDA) Biopharmaceuticals Classification System (http://www.fda.gov/ AboutFDA/CentersOffices/CDER/ucm128219.htm), which uses permeability as one of the two key parameters to set the classes that constitute the classification of drugs.

Despite the relevance of permeability one often comes across ambiguous determinations, mostly from oversimplified data analyses. It is now common that permeability

*Address correspondence to these authors at the Instituto de Medicina

Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal; Tel: (+351) 217985136; Fax: (+351)

217999477; E-mail: [email protected]; and Groningen Biomolecular Sciences and Biotechnology Institute, Rijksuniversiteit Groningen, 9747 AG

Groningen, The Netherlands; E-mail: [email protected]

#These authors contributed equally.

measurements are replaced in many studies [6, 7] by relative determinations, such as the ratio between a measured signal (e.g. spectroscopic, electric) obtained in samples and control. Yet, the theoretical background of this analysis remains elusive. It is therefore urgent and of utmost importance to revisit the meaning of permeability and the way it should be measured. The permeability of analgesic kyotorphin (KTP) derivatives on an artificial model of lipid membranes will be evaluated and correlated with their in vivo efficacy, therefore serving as illustrative example.

2. SELECTIVE PERMEABILITY OF THE ENDO-

THELIAL BARRIERS – MECHANISMS AND REGU-

LATION

2.1. Cellular Adhesion and Disruption

Endothelial cells constitute the interface between the plasma and the underlying interstitial fluid, being adapted to the organ in which they reside [8]. These cells are able to regulate the permeability and transport of molecules due to the presence of junctional proteins [8]. Junctional proteins include tight junctions, adherens junctions - forming zipper like junctions between cells, and gap junctions responsible for transmembrane channels [9, 10]. It is recognized that both tight and adherens junctions contribute for cell-cell adhesion, in particular vascular endothelial (VE)-cadherins play a preponderant role in cell cohesion [11-13].

The expression of the endothelial cells proteins is mediated by a variety of stimuli which actively contribute for the regulation of the endothelial cell permeability: nutrients [14], immune cells [14, 15], inflammatory mediators like thrombin, bradykinin, histamine [10, 16], and the actin cytoskeleton [17].

100 Mini-Reviews in Medicinal Chemistry, 2014, Vol. 14, No. 2 Serrano et al.

When the adhesion between cells is disrupted, the passage

of toxic compounds follows and triggers the development of

a pathological state. Therefore, cell-cell disruption has a

profound impact on the maintenance of endothelial barrier

function and integrity [15]. Disruption may occur due to the

presence of an inflammatory condition. Inflammation increases

endothelial cell permeability by creating intercellular gaps

or altering the inward tension [11, 13]. Intercellular gaps are

produced via an increase of the cytosolic Ca2+

concentration

[13], and of the endogenous levels of nitric oxide [18].

Generally, a rise in Ca2+

concentration causes an inhibition

of the enzyme adenylyl cyclase, which catalyzes the conversion of ATP to cyclic adenosine monophosphate (cAMP), and

so cAMP levels are decreased, leading to an increased

permeability. However, in the microvasculature, the agonists increasing Ca

2+concentration do not decrease cAMP levels.

The maintenance of cAMP levels prevents inflammatory

mediators from increasing permeability. This is as an important protection mechanism restricted to the microvascular

endothelium and contributing to enhanced barrier properties

[13, 19].

2.2. The Significance of Polarization, Cellular Hetero-

geneity and Microenvironment

The directionality of the endothelial transport of molecules

is mainly influenced by the polarization and heterogeneity of endothelial cells (a) and by the surrounding microenvironment

(b) [20]:

(a) Polarization of the endothelial plasma membrane refers to a different composition from the luminal (apical) to

the abluminal (basal) side, shown by a disparity of receptors,

proteins, and enzymes from the lumen to the albumen [20]. Another feature of the blood-vessel endothelium is a

phenotypic heterogeneity in terms of structure and function.

Consequently, both polarization and heterogeneity of endothelial cells lead to transport differences between macro-

and microvessels, and between venular, arteriolar, and the

capillary endothelium of microvessels [8, 20].

(b) The microenvironment surrounding endothelial cells,

specifically the extracellular matrix and the glycocalyx, is of

extreme importance for modulating the endothelial barrier function and permeability [10]. The extracellular matrix

contains a broad diversity of proteins, such as collagen IV,

fibronectin, and laminin prompted to protect and remodel the endothelium after an assault [10, 21]. The glycocalyx is

a mucopolysaccharide layer on the luminal side of the

endothelial cells [22]. The thickness of the layer varies with the diameter of the vessel; for instance it has approximately

8 "m thickness in the endothelial cells lining capillaries

[23]. Several functions had been attributed to glycocalyx [22], but especially it protects the endothelium from the

blood-flow due to the negative charge of the coat [10, 24].

Several components of discarded glycocalyx are increased in the blood of seriously sick patients [25, 26], showing that

this layer is extremely fragile and need to be protected from

enzymatic degradation, or at least de novo synthesized, with the aid of new drugs [27].

2.3. Transport Systems

2.3.1. Influx System: Transcytosis Versus the Paracellular

Pathway

In capillary endothelial cells, caveolae and small non-clathrin coated vesicles are the predominant transport vehicles. The translocation of caveolae and vesicles begin with the budding and fission from the plasma membrane, translocation across the cell, and finally fusion with the plasma membrane at the opposite location [8]. Otherwise their cargo may be directed to the lysosome and degraded [28, 29].

Caveolae are non-clathrin coated vesicles with 70 nm diameter on average [8, 10]. Their presence in the cell surface of endothelial cells is huge, around 10,000 caveolae per cell [8], and approximately 95% of the cell surface vesicles are caveolae [28, 29].

Clathrin-coated vesicles are less frequent than caveolae and their use may be illustrated by few microbes which can pass through cells not destroying its integrity [30]. Microbes bind to a receptor forming a complex, and then the complex activates a signaling pathway that leads to the encapsulation of the microbe into a clathrin-coated vesicle. The vesicle will then bud off from the endothelium and cross the cell. It has been suggested that some pathogens can subvert the proteins responsible for the vesicle targeting pathway, leading the vesicle to the cell exterior rather than of being destroyed by lysosomes [30, 31].

The dynamic expression of caveolae and vesicles in the surface of endothelial cells (7,000 m

2area corresponding to

6$1013

cells), confer endothelial cells the capacity to regulate transcytosis [8].

Nicolae Simionescu in 1979 [32] created the concept of transcytosis as a mechanism of transcellular transport. Transcytosis of plasma molecules occurs primarily at the level of capillaries [8], and it can succeed through non-specific (fluid-phase and adsorptive) or through specific (receptor mediated) transcytosis [20, 33]. At fluid-phase transcytosis, the uptake rate depends on the size of the vesicle or channel opening, the solute concentration, and the steric competition [20, 33]. Examples of molecules that make use of fluid-phase transcytosis include glycogen, dextran, and ferritin [8]. In adsorptive transcytosis, the uptake rate depends on the number and affinity of the binding sites at the vesicle. Some plasma proteins may use both fluid-phase and adsorptive transcytosis [8]. In receptor mediated transcytosis there is specificity for a receptor at the caveolae [10, 20, 33]. Low-density lipoproteins (LDL), transferrin, insulin, and albumin are examples of receptor mediated transcytosis [8]. LDL and albumin use both receptor mediated endocytosis and transcytosis through caveolae [20].

The paracellular route conveys passive diffusion between cells and is regulated by adhesive cellular forces and actinomyosin-derived oppose adhesive forces [10]. Paracellularity was first reported in 1961 [34]. The authors observed than an inflammatory condition predisposed the formation of cells gaps between cells induced by the

Selective Permeability in Transport Across Biological Barriers Mini-Reviews in Medicinal Chemistry, 2014, Vol. 14, No. 2 101

presence of histamine. Small molecules, ions and metabolites employ the paracellular pathway. Water may cross endothelial cells whether using paracellular or the transcelullar route, via aquaporins membrane channels, at similar frequency [10, 35]. Paracellular and transcellular are not totally independent pathways [36].

2.3.2. The Efflux System

The efflux system is characterized by ABC transporters which use the energy balance of ATP hydrolysis to carry translocation from the cytosol to the exterior of the cell. P-glycoprotein (P-gp), an ABCB1-transporter, is the best characterized multidrug transporter encoded by the mdr1 gene. It has a huge importance at protecting several tissues against external assaults. P-gp action has three main pharmacological consequences related to its localization: 1) due to its presence at the luminal side of enterocytes membrane (intestinal absorptive cell) it limits the passage of drugs after oral administration, 2) being expressed in kidney cells and hepatocytes it promotes the drug elimination via urine and bile, respectively, 3) if the drug reaches systemic distribution, its presence at blood-barriers limit the drug entry into organs, such as the brain, testis, and placenta [37].

3. PERMEABILITY AT THE SEVEN BLOOD-TISSUES BARRIERS

Human body encloses seven barriers separating the blood from several tissues: brain, cerebrospinal fluid, placenta, testis, urine, lung (or air – the barrier is on the lungs region where gas exchange occurs), and thymus. Blood-tissue barriers are critical for the function of those organ systems and help maintain homeostasis.

All blood-tissue barriers consist of an endothelial cell monolayer with high permeability restriction but each barrier has its own distinctive features.

3.1. Blood-Brain Barrier (BBB)

The Blood-Brain Barrier and the Blood-CerebroSpinal Fluid Barrier (BCSFB) have a proximal localization near the brain and share the main purpose of brain protection and homeostasis maintenance [38]. The surface of the BBB is 1000-fold larger than the Blood-CerebroSpinal Fluid Barrier [38]; in effect capillaries occupy a total surface area of 10-20m

2in the human brain, which makes it the chief influx

barrier separating brain tissue from the blood [39, 40].

The BBB separates the lumen of cerebral blood vessels, coated by brain capillary endothelial cells (BCEC), from the brain parenchyma. Outside the BCEC, at the central nervous system (CNS), is a basement membrane surrounding the pericytes, and nearby the astrocytic endfeet processes of neighboring astrocytes (Fig. 1).

All these structures are referred to as the neurovascular unit, and the cross talk between them is decisive for the formation and maintenance of a functional BBB [41]. The tight endothelial cells, as well as the scarcity of paracellular leakage, and the nearly absent intracellular fenestrae and fluid phase pinocytosis create a high electrical resistance interface (2,000-8,000 ! • cm

2) at the BBB [42], turning the

brain difficult to reach for polar molecules [40].

The efflux system is of particular importance at the BBB. The presence of the P-gp at the luminal membrane of capillary endothelial cells affects more the concentration of drugs and xenobiotics at the brain than at any other organ [37, 43, 44]. The function of P-gp at protecting the brain gathers negative and positive outcomes. On one side, P-gp is the major responsible for the exclusion of nearly 95% of developed drugs from the brain, even when acceptable doses of the drugs are administered [45], causing difficulty in the treatment of brain diseases. On the other side, it is responsible for the entrance blockage of disease-causing pathogens, preventing the development of brain pathologies.

Besides a physical barrier formed by BCEC, the BBB ensures metabolic and enzymatic functions [41]. The best recognized example is the transfer of dopamine between the blood and the brain. It is well known that dopamine cannot reach the brain. Its precursor, L-DOPA, uses the LAT-1 amino acid carrier to enter endothelial cells and reach the brain tissue, where it is converted by DOPA-decarboxylase to dopamine [46]. The integrity of the BBB may be compromised through BBB disruption, TJ opening, and altered BBB transport system, leading to the development of several neurodegenerative diseases (such as Alzheimer’s and Parkinson’s disease), brain tumors, and inflammation-associated diseases including stroke, vascular dementia, and multiple sclerosis [47]. Therefore, the BBB plays an important role preventing the development of such pathologies [47, 48]. In summary, BBB is the interface between the CNS and circulatory system with regulatory functions at nutritional, homeostatic and communication levels.

3.2. Blood-CerebroSpinal Fluid Barrier (BCSFB)

The BCSFB is a barrier formed between the choroid plexus blood vessels and the cerebrospinal fluid (CSF). The BCSFB is a barrier composed by three units: besides choroid plexus it encloses the arachnoid membrane, and periventricular organs including the pinal gland, area postrema, median eminence and neurohypophysis. The choroid plexus is formed by a layer of capillary endothelial cells and epithelial cells. The endothelial cells facing the blood are fenestrated, highly permeable and show intracellular gaps, whereas the layer of modified cuboidal epithelium secretes CSF and is connected by the tight and adherens junctions [38, 49, 50] (Fig. 1). Tight junctions of the BCSFB are slightly looser and more permeable than those of the BBB [38].

The choroid plexus, specifically the CSF, displays several actions including brain shield against acute blood- pressure changes, protection from brain injury, establishment of a neutral buoyancy to the brain, and regulation of the entrance of nutrients and hormones avoiding the passage of deleterious compounds [50]. It also carries an enzymatic detoxification system important for the clearance of toxins and drugs [38, 51]. The choroid plexus contributes to other distinct activities, for example the modulation of the neurohumoral system and mediation of the neuroimmune system interaction [38, 50-52]. More recently, this barrier has renewed importance because the CSF has been used for the detection of certain diseases biomarkers, such as the Alzheimer’s disease [53] and Parkinson disease [54]. The symptoms of chronic


neurodegenerative diseases occur up to 20 years after the beginning of the pathology. Therefore, any therapeutic treatments occur late and are particularly difficult [55]. The CSF is an accessible source of proteins derived from the brain, and any pathological alteration in the brain can be mirrored in the concentration of certain CSF biomarkers [53, 54, 56]. Candidate CSF biomarkers for both PD and AD include Total Tau Protein (T-TAU) and Beta-Amyloid (1-42) (Abeta42) [53, 54]. Therefore, biomarkers may be useful for the development of a treatment for such diseases [56].

3.3. Blood-Placenta Barrier (BPB)

At the outer surface of the villi, the maternal and fetal bloods are separated by thin epithelial layers of multinucleated syncytiotrophoblasts of the placental barrier [57]. This barrier regulates the transport between maternal and fetal circulation; water, nutrients and oxygen are supplied and waste products (e.g. carbon dioxide, urea and bilirubin) are removed [57]. In syncytiotrophoblast, the transporters

facing the mother’s blood at the apical membrane and the ones facing the fetal capillaries at the basolateral membrane are different, leading to a polarized transport [58-60].

In a comprehensive study about drug transporters in the BPB [60], the most frequent were ABC transporters, namely ABCB-1/P-gp, ABCG-2/BCRP (a breast cancer resistance protein), and ABCC1-3/MRP1-3 (a multidrug resistance-associated protein). The ABCG-2/BCRP transporter is down regulated by the tumor necrosis factor (TNF-!), and consequently it has been suggested to be engaged in the protection of the trophoblast from TNF-induced apoptosis [60, 61]. A number of other drug transporters are present, like the organic anion (OAT) and cation transporters, 5-HT serotonin, and noradrenalin transporters [60, 62, 63]. Most of these transporters are expressed at the apical membrane protecting the placental tissues and fetus against external insults, such as xenobiotics.

A singular aspect of the placental barrier is its structural and functional changes during gestation: the expression of

Fig. (1). At left: Illustration of the location of blood-brain and blood-cerebrospinal fluid barriers in the adult brain. a) The BBB. Detail of

the endothelial cells near to astrocytes and microglia. Picture at right: Endothelial cells (End. Cells) have luminal tight junctions

(represented as opposite triangles) limiting the movement of molecules between the brain and the blood. The basement membrane is

outside of the endothelial cells, at the CNS, surrounding the pericytes. The astrocytes and neurons are contiguous to these structures. b)

The BCSF. The ciliated cuboidal epithelial cells of the choroid plexus have apical tight junctions and face the CSF. The endothelial cells

facing the blood are fenestrated and form a non-cohesive barrier (arrows).


transporters is affected [60], and the thickness of the syncytiotrophoblast layer is decreased to improve the exchange of materials between the maternal and fetal circulation [57].

3.4. Blood-Testis Barrier (BTB)

The testis is chiefly composed of an interstitial space and seminiferous tubules [64]. Leydig cells are expressed in the interstititial space. These cells are testosterone producers, which help to maintain the spermatogenesis process [64, 65] and the male secondary sex characteristics [64]. In the interstititial space, the blood and lymphatic vessels, lymphocytes and macrophages, as well as connective tissue, are also present [64, 66]. Sertoli cells and germ cells are expressed in the seminiferous epithelium, which is the site of spermatogenesis [64]. The testis is partially surrounded by the epididymis, it isolates spermatozoa from the blood creating an appropriate microenvironment for germ cells to develop (mitosis, meiosis and differentiation), and mature [64, 67]. The epididymis belongs to the blood-epididymis barrier (BEB) [64, 68]. A third adjacent barrier, the blood-vas deferens barrier secludes spermatozoa during their transfer to the exterior, preventing potential contacts between the older germ cells and the blood circulation [68].

The BTB and BEB work together to create a polyvalent barrier coordinated in three functions: anatomic, physiologic and immunologic [64]. Anatomically, the tight junctions of each barrier restrain molecules from entering the lumen of the seminiferous tubules and the lumen of epididymis [64, 69]. The anatomical barrier consists of a basal and apical membrane, and of tight junctions between Sertoli cells at the BTB and between the epididymal epithelium at the BEB. The Sertoli cells display a singular trait at being located at the basal membrane and not at the apex [64, 69]. Physiologically, specific transporters at both basal and apical membranes regulate the passage of molecules [64, 70]. At the immunological level, the whole testis is considered to be privileged, i.e. antigens are tolerated in testicles without causing an inflammatory response: the epididymal cells form a primary immunological barrier limiting the passage of immune cells, and sequester antigens that will be protected from the immune system [64]; the BTB reinforces the former actions and locally produce anti-inflammatory cytokines by Sertoli and Leydig cells, testicular macrophages and lymphocytes [64, 71]. These defenses are able to control the immune system response that would damage the testicular tissue if not hampered [64]. The immune-privilege is also present in the placental barrier.

3.5. Blood-Urine Barrier (BUB)

Urothelium is the urinary bladder epithelium. This barrier lines the urinary tract from the renal pelvis to the urethra [72, 73]. It is formed by an apical layer formed by umbrella cells, a basal, and an intermediate layer. Umbrella cells are hexagonal cells [72, 74, 75] with specialized membrane lipids, asymmetric unit membrane particles, and a plasma membrane with rigid plaques [72, 74, 75]. Each of one plaque has approximately one thousand subunits of proteins named uroplakins. Due to its composition, the tighten umbrella cells have barrier properties reducing the permeability of the urothelium to small molecules, and protecting the

underlying bladder nerve and smooth muscle tissues [72, 74-76]. Urothelium is not a passive barrier as it can regulate the composition of urine (water, urea, protons, and inorganic/ organic compounds) and its volume [73, 77], probably by an aquaporin-mediated mechanism [73, 78].

BUB shows singular traits, such as the use of signal-transducing mechanisms to detect physiological stimuli as sensory neurons do [72, 73]. Examples of sensor cells are the receptors for bradykinin [79], and for acetylcholine (nicotinic, [72] and muscarinic [80]). Another remarkable property of the urothelial barrier is that it is the most restrict in terms of permeability and the most tighter barrier in the human body, due to the high transendothelial apical layer resistance ranging from 10,000 to over 75,000 " • cm

2 [81].

3.6. Blood-Lung Barrier (BThB)

The specialized barrier of the lung epithelium separates the air from fluid-filled tissues [82, 83]. The human lung is extremely thin, approximately 0.2 "m, and occupies a large area, 50-100 m

2, to facilitate gas exchange through passive

diffusion [84]. The optimization of the lung interfacial area is achieved by the miniaturization of lung structures, namely alveoli [85]. Alveoli are small structures, and approximately 4.8&10

8are present in the human lung [86].

The alveoli populate the terminal airspaces of the lung and provide the physical barrier to paracellular fluid permeability that keeps the alveoli relatively dry due to the presence of tight junctions. The BThB consists of an alveolar epithelium, capillary endothelium, and an extracellular matrix between them [87]. Type I and II pneumocytes are expressed in the alveolar epithelium. Type I cells are large and thin cells covering over 90% of the alveolar surface area and are the primary site of gas exchange. Type I cells contain the majority of tight junctions, whereas type II cells are dispersed along the alveoli, and exhibit other functions like the production of surfactant to maintain open airspaces [83].

3.7. Blood-Thymus Barrier (BTB)

In adults, the blood–thymus barrier is formed in the thymic cortex by five layers: tighten capillary endothelial cells, epithelial reticular cells, and the perivascular space between the basal lamina of the endothelium and epithelial-reticular cells [88, 89]. At the thymus, immature cortical T-lymphocytes from the bone marrow find an appropriate microenvironment to develop and become immunocompetent. The most significant function of BTB in postnatal life is to prevent the entrance of exogenous antigens into the thymus preventing the immature T lymphocytes from contacting antigens that would be lethal [88]. The barrier is less effective in the medulla, which facilitates the discharge of immunocompetent T-lymphocytes to the medulla, and eventually to the blood circulation [89].

4. THE MEANING OF PERMEABILITY

Epithelial permeability (P) was defined more than 50 years ago [90] from an experimental setup as the one depicted in (Fig. 2 A). In this setup an intact epithelium or any other biological barrier divides two chambers (“basal” and “apical”) of solvent; a traceable molecule, S, is then added


to the apical chamber at time t=0 and allowed to diffuse freely. If transepithelial transport occurs there will be a net flux of molecules across the epithelium described by:

SAP SB

k1

k-1 Eq. (1)

where SAP and SB are the apical (AP) and basal (B) amounts

of S, and k1 and k-1 the direct and reverse rate constants of

the transport process, respectively.

The working definition of permeability was the number

of molecules crossing a unit area of the permeable cellular

epithelia per unit concentration in the apical side at t=0:

P =CB(t) - CB(t = 0)

t A CAP (t = 0) Eq. (2)

A is the area of the permeable epithelium. Concentration,

C, variation due to permeation is usually measured from the

appearance of the solute in the basal chamber (hence CB(t)-CB(t=0)) rather than its disappearance from the apical

chamber for increased sensitivity because CB(t=0) = 0 in

most experimental setups.

Naturally, CB(t=0)/t is not constant over time and (2) is

only valid for periods very close to t=0, which has been

overlooked since the pioneering works of permeability quantification [90]. Moreover, the exact critical instant (tmax)

from which (2) can no longer be applied has never been

formally defined (to the best of our knowledge). Assuming that the kinetics of the process described in equation (1) is

of first order relative to both the direct and inverse process:

CB(t) = CB (t = ) . (1 –e–k1

.R.t) Eq. (3)

where R is the reciprocal of the molar fraction of S in

chamber B at equilibrium (t=!). Complete deduction of

equation (3) is available in the Supplementary material on-

line. R is related to CB(t=!):

R =VAP "CAP (t = 0)

VB "CB (t = ) Eq. (4)

where V is the volume of each chamber, apical (AP) or basal (B), which may differ from each other. CB and CAP are

usually not measured directly; instead a spectroscopic (e.g.

fluorescence intensity or UV-Vis absorption), radioactive or chromatographic signal (I) is measured, directly proportional

to concentration. So:

CB(t)

CAP (t = 0)=

IB(t)

IAP (t = 0)=

VAP

VBR(1- e-k1 R t )

Eq. (5)

For a short interval starting at t=0 and/or slow diffusion (see Supplementary material on-line):

IB(t)

IAP (t = 0)

VAP

VB

" k1 " t

Eq. (6)

So, plotting IB(t)/(IAP(t=0)) vs. t and performing a linear regression fitting to the data in the linear regime at short times, k1 can be obtained from the slope, m:

m =VAP

VB

k1

Eq. (7)

k1 is related to the permeability in a quite straightforward way (see Supplementary material on-line):

P = k1. VAP

. A

-1 Eq. (8)

which in terms of the fitted parameters reads:

P = m . VB

.A

-1 Eq. (9)

It is worth stressing that this result is only valid if k1 is such that the linear regression fitting was carried out up to a critical time that sets the limit of validity of equation (6). The critical limit instant for the validity of equation (9) depends on the relative deviation allowed between the left- and right-hand side terms in equation (6) (depicted in (Fig. 1 B and Table S1) in Supplementary material on-line). This time limit will be shorter the faster equilibrium is attained, which in turn depends on the values of k1 and R. It can be seen that to be within 1% deviation between the terms in equation (6), the valid time window is up to:

tmax =0.02

k1 R Eq. (10)

Equation (10) can be adapted to other accuracy limits by using appropriate values for the numerator. A maximum deviation of 5%, for example, is obtained for intervals up to tmax=0.098/(k1·R) — see the Supplementary material on-line for the deduction of equation (10) and the computation of numerator values.

5. PERMEABILITY CALCULATION

5.1. Measuring Permeabilities in Free Standing Barriers

The previous section shows that P is quantitatively related to k1 and can be considered constant within the limits of validity of (6). Therefore, P is indeed a measure of the kinetics of the passage of a solute through an epithelium, at short times, assuming the fraction of the solute retained by the cells is negligible.

There are two ways to calculate P, both requiring a priori knowledge on A, VB and VAP.

In the first case (5) should be used to fit the data and both k1 and R are retrieved (Fig. 2 C). k-1 can be obtained from k-1=k1(R-1). P is calculated from (8). Comparison between P values obtained in different systems is then possible. Permeability referent to k-1 may be calculated as P-1=k-1·VB/A. If the asymptotic limit of equation (5) is VAP/(VAP+VB) (i.e. R=(VA+VB)/VB), the process is purely passive.

Contrary to the initial rate methods, described in the next section, a non-linear fit should be performed on data taken up to longer times, where the curvature of IB(t)/(IAP(t=0)) vs. t is noticeable. When applied to few data points too close to t=0, there will be too little information for the proper determination of R.


5.1.1. Linear Regression Fitting – the Initial Rate Approach

In this case, (6) should be used to fit the data. P is obtained directly from the slope, m (9). Equation (9) justify why some groups calculate P accounting for the volume of the basal chamber [4, 91].

This approach has been the traditional choice for its simplicity. However, non-linear data fits are nowadays trivial to compute and the use of the complete IB(t)/(IAP(t=0)) vs. t curves provide much more insight into the properties of the system. On the other hand, non-linear regression fitting demands data obtained for a wide range of k1·R·t in order to reach close enough to the asymptotic value. This is not

always possible, mainly for very short R and k1 (i.e. slow and very extensive processes).

It is important to know exactly how long is too long

before one can no longer assume IB(t)/(IAP(t=0)) vs. t to be locally linear. An easy way to judge this comes from the

data points themselves, which will not conform to a straight

line (Fig. 2 C). A linear regression of such data will have a positive intercept, whereas data in the linear IB(t)/(IAP(t=0))

vs. t regime should yield a regression with a zero intercept.

An intercept different from zero may be indicative of a too large time interval being used (Fig. 2 C). When determining

initial rates, fits must be repeated using data in progressively

Fig. (2). A- Schematic experimental setup for the determination of permeability, P. A solute is placed in an apical chamber that is

separated from a basal chamber by an epithelium (e.g. endothelial tissue). The concentration in the apical chamber, CAP, will decrease until

equilibrium. B- The concentration in the basal chamber, CB, may be monitored directly or indirectly, to calculate the permeability, either

using the whole kinetic curve (line, 1) or an initial rate approach (line, 2). C- Initial rate approaches demand a judicious choice of the time

interval where a linear regression to the data will be applied. A valid interval implies a zero intercept and a reasonable maximal deviation

from experimental data (lines 3 in panels B and C). An upper limit for the interval may be estimated from R and k1. Endpoint

measurements are alternatives in case the admissible upper limit for t is too short and/or CB cannot be sampled over time. Non-linear

regression fitting to experimental data is also represented (curve 1).


narrower time ranges until a zero intercept is obtained.

Should there be too few points close to t=0 to allow a proper

fit, the “Endpoint approach” presented in the Supplementary material on-line should be used instead (Figs. 2 B and C).

5.2. Measuring Permeabilities in Transwell and Other

Filter-supported Barriers Devices

In practice, it became standard procedure to measure permeability in a transwell device, in which the biological barrier is placed on the top of a filter (not free standing, in contrast with Fig. 2). This setup is very practical because monolayers of cells can be grown on the top of the filter until complete coverage (confluence), or lipid bilayers may be deposited on the top of the filter to measure transbilayer permeation.

Nevertheless, the presence of the filter poses problems and challenges to permeability determination that are often overlooked. The filter itself is a barrier; even in the absence of a biological barrier covering the filter, drugs are not totally free to diffuse from the apical to the basal chamber as the fractional area of the holes in the filter may be considerably small. For instance, in the realistic case of a 0.33 cm

2total area filter with 0.4 "m pore diameter and a

nominal pore density of 4.106

pores/cm2, the area available

for translocation is 1.66$10-3

cm2

(total pores integrated area). To worsen matters, the nominal pore density is an approximate value given by the manufacturer, which may lead to rough errors during data analysis; and when the membrane is a tortuous mesh membrane such as polytetrafluoroethylene it cannot be measured by any means. As such, when using transwell systems it is recommended the use of the relative permeability (PR), the ratio between the apparent permeability in the presence and absence of the biological barrier, therefore avoiding misconceptions and biased estimates due to effective area available for translocation in the filter.

PR =m VB A-1

m0 VB,0 A0

-1=

m

m0 Eq. (11)

(Subscript 0 in equation (11) refers to the absence of cells or other biological barrier).

Overall, relative permeability offers two significant advantages: simple and accurate data analysis, and permeability values delimited between zero and one. It is of our belief that it will ultimately benefit the process of drug discovery and development reducing drug failures as well as the time expected for the drugs launching process [92].

6. ORIGINAL EXAMPLE: THE RELATIVE PER-

MEABILITY OF KYOTORPHIN DERIVATIVES

Kyotorphin (KTP) is a small endogenous dipeptide of

L-Tyr and L-Arg, firstly isolated from a bovine brain in

1979 [93, 94], and later detected in the brain of humans and

other mammals [95]. KTP has a strong antinociceptive

action being 4-fold more effective than endogenous opioids

[96] but only when administered directly in the central

nervous system, most probably due to its incapability to

cross the blood-brain barrier [97]. Nevertheless, KTP is a

dipeptide and potentially able to bind to peptide transporters

in the BBB. The interaction of KTP with brain peptide

transporters was firstly studied by Fujita et al. [98]. The

activity of the transporter was evaluated by measuring

the uptake of the dipeptide glycyl-sarcosine (Gly-Sar), a

prototypical substrate for the peptide transporter, in the

presence of H+-gradient. It was found that KTP

significantly inhibited the Gly–Sar uptake in rat

synaptosomes in a concentration-dependent manner. The

results indicate that the peptide transport system PEPT2

could be responsible for the transport of KTP [98]. Recent

molecular cloning studies have shown the existence of two

distinct peptide transporters, PEPT1 and PEPT2, whose

substrates are small peptides [99]. PEPT1 is a low-affinity

and the latter a high-affinity transporter. Substrate

specificity is similar for both. Therefore, it is possible that

KTP is also a substrate for PEPT1 but with a lower affinity

compared with PEPT2 [100]. Altogether these results suggest

that KTP binds to peptide transporters but it returns to blood

through efflux systems. Some KTP-derivatized drugs may

however avoid the efflux systems and/or explore additional

routes, such as the transcellular lipophilic pathway (for drugs

with high lipid affinity) or adsorptive transcitosys. For this

reason, the strategy chosen to overcome the limited BBB

crossing was to chemically modify KTP to improve its lipid

affinity. High lipid affinity facilitates all processes

occurring at membrane level, including binding to receptors

[101]. New derivatives were synthesized based on amidation

(KTP-NH2) and/or conjugation to ibuprofen (ibKTP and

ibKTP-NH2), a toxicologically safe nonsteroidal anti-

inflammatory drug. Previous studies using acute and chronic

pain models demonstrated that following systemic

administration, ibKTP-NH2 was the most potent analgesic

drug (from 25 "mol/kg) [102], and that KTP-NH2 had a

smaller analgesic effect, suggesting that ibKTP-NH2 is the

most effective in crossing the BBB. We performed permeability

assays in a transwell system with a polyester filter with 0.33

cm2

area and 0.4 "m diameter perforations covered with

fluid lipid bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-

phosphocholine (POPC). The deposition method was

described elsewhere [103] and it forms a tight barrier of

bilayers suitable to measure passive drug permeability. The

fluorescence at both apical and basal chamber in model and

blank filters was plotted against time and represented at

Fig. 3. The apical data was used to calculate PR according to

equation (11); the linear part of the curves representing

steady state flux rate was obtained with the first time points

(10 h period) and used to calculate the slopes, m, for model

and blank filters.

The relative permeability of ibKTP-NH2 (0.76±0.05) was

significantly higher than that of kyotorphin, KTP (0.58±0.06)

(P < 0.05) or KTP-NH2 (0.49±0.06) (P < 0.01), whereas the

ibKTP PR (0.36±0.06) was significantly lower (P < 0.01) than

that of KTP and not significantly different from KTP-NH2

(Fig. 4). Statistical analysis was performed with one-way

ANOVA P < 0.0001 followed by Tukey’s post test. Relative

permeability revealed a correlation between transmembrane

translocation efficacy and pharmacological activity.


Fig. (3). Fluorescence intensity of KTP, KTP-NH2, ibKTP, and ibKTP-NH2 at apical (squares) and basal (circles) chambers at both model

(filled) and blank (non-filled) filters, at each time point. Each group is an average of three independent measures. Data shown as mean ±

SD. Lines represent guide to the eyes.

Fig. (4). Relative permeability of ibKTP-NH2, KTP, KTP-NH2

and ibKTP calculated using apical data. Data shown as means ±

SD; each group is an average of three independent measures. **P

< 0.01, *P < 0.05 and ns not significant, versus KTP; !!P < 0.01 and

ns! not significant versus KTP-NH2.

7. CONCLUSIONS

We anticipate that the present revisitation of the meaning of permeability and its experimental determination

will enhance value to drug transport-models studies, enabling to achieve more reliable and informative P values, able to be inter-compared and related to quantitative structure–activity relationship (QSAR) parameters.

We show that permeability is directly related to the velocity constant of the apical-to-basal transport and is obtainable from simple kinetic considerations under the formulation of equation (1). Moreover, the link between these and the kinetics of the reverse transport process were shown, which can be an informative addition to permeability studies. Permeability is now a well defined kinetic concept with unequivocal methodologies to be calculated.

The usefulness of permeability determination was illustrated with original data that solves an open matter of debate in the literature: it was previously suggested that the analgesic efficacy of ibKTP-NH2 is due to its ability to cross the BBB but no experimental data supported until now this speculation. PR determination now shows that ibKTP-NH2 is much more effective than any other of the tested molecules in crossing lipid membranes, corroborating the previous suggestion that this drug is able to cross the BBB.

CONFLICT OF INTEREST

The authors confirm that this article content has no conflicts of interest.

� ✁ ✂ ✄ ☎ ✆ ☎ ✝ ✞ ✟ ✠ ☎ ✟ ✡ ☛ ☎ ✆ ✄ ✟ ☞ ☎ ✌ ☎ ✆ ✍ ✎ ✏ ✑ ✟ ✒ ☎ ☛ ✓ ✔ ✕ ✖ ✗ ✁ � ✘ ✖ ✙ ✚ ✎ ✛ ✜ ✢ ✖ ✣ ✚ ✛ ✤ ✥ ✟ ✔ ✔ ✍ ✆ ✚ ✟ ✓ ✍ ✎ ✛✦ ✧ ★ ✩ ✪ ✫ ✬ ✭ ✮ ✯ ✭ ✰ ✭ ✩ ✱ ✲✳ ✴ ✵ ✶ ✷ ✸ ✴ ✹ ✺ ✻ ✸ ✴ ✶ ✼ ✽ ✸ ✹ ✾ ✷ ✼ ✿ ✶ ❀ ❁ ✹ ❂ ✶ ✺ ✶ ✶ ❃ ❄ ❅ ✼ ❆ ❄ ✶ ✵✳ ✵ ❆ ✼ ✹ ❇ ✹ ❈ ❄ ✶ ❉ ❊ ❄ ✼ ❄ ✻ ✸ ❋ ✺ ❄ ✹ ✿ ✶ ❃ ❄ ❅ ✼ ❆ ❄ ✶ ● ✳ ✵ ❆ ✼ ✹ ❇ ✹ ❈ ❄ ✶ ✵ ❍ ✼ ✻ ❄ ✼ ✹■ ✷ ❂ ✵ ✺ ❄ ✹ ✺ ❏ ✾ ❃ ✳ ❑ ❊ ❃ ✳ ❍ ■ ● ▲ ✹ ✺ ✸ ✷ ❈ ✶ ❇ ▼ ✶ ✼ ✿ ❍ ❃ ❑ ✾ ▲ ◆ ❊ ✶ ✺ ❄ ✵ ❃ ✷ ✺ ❄ ✵❖ ✼ ✿ ✷ ✻ ✸ ✺ P ❑ ◗ ❆ ✶ ✿ ✵ ❘ ❄ ✶ ▲ ✶ ✺ ✸ ✼ ✵ ✺ ✻ ✴ ❄ ❂ ✻ ✶ ✼ ✿ ▲ ✶ ✸ ✴ ❙ ✶ P ✻ ❏ ❖ ◗ ▲ ▲ ▼ ●❚ ✺ ✶ ✼ ✸ ✼ ❯ ❱ ❲ ❳ ❨ ❩ ❬ ❑ ▲ ✵ ❂ ❱ ❭ ✺ ✶ ❄ ✼ ❪ ✹ ✺ ❪ ❄ ✼ ✶ ✼ ❆ ❄ ✶ ❇ ✻ ✷ ❂ ❂ ✹ ✺ ✸ ✸ ✹ ✸ ✴ ✵❂ ✺ ✹ ❫ ✵ ❆ ✸ ✻ ▲ ✳ ❴ ❃ ❵ ❛ ❜ ❖ ❵ ❨ ❝ ❝ ❲ ◆ ❵ ❱ ❳ ❳ ❨ ✶ ✼ ✿ ▲ ✳ ❴ ❃ ❵ ❛ ❜ ❖ ❑ ❭ ❖ ❛ ❵❞ ❞ ❱ ❝ ❱ ❝ ❵ ❱ ❳ ❳ ❝ ❡ ✾ ❃ ✳ ❑ ❊ ❃ ✳ ❍ ■ ❄ ✻ ✶ ❇ ✻ ✹ ✶ ❆ ✽ ✼ ✹ ❙ ❇ ✵ ✿ ❈ ✵ ✿ ❪ ✹ ✺ ❪ ✷ ✼ ✿ ❄ ✼ ❈▲ ✹ ✻ ✸ ❑ ✿ ✹ ❆ ❪ ✵ ❇ ❇ ✹ ❙ ✻ ✴ ❄ ❂ ■ ✾ ❢ ❣ ❵ ❭ ▲ ❴ ❵ ❲ ◆ ❝ ❝ ❤ ❵ ❱ ❳ ❳ ◆ ✸ ✹ ❖ ❡ ■ ✵ ✺ ✺ ✶ ✼ ✹✶ ✼ ✿ ▲ ✴ ❴ ❪ ✵ ❇ ❇ ✹ ❙ ✻ ✴ ❄ ❂ ■ ✾ ❢ ❣ ❵ ❭ ❴ ❵ ◆ ❳ ❬ ❱ ❲ ❵ ❱ ❳ ❞ ❳ ✸ ✹ ✐ ❡ ✾ ✺ ✵ ❄ ✺ ✵ ❡✲ ❥ ❦ ❦ ✬ ✭ ✰ ✭ ✩ ✱ ✦ ❧ ♠ ✰ ✦ ✱ ✭ ❧ ♥ ✦ ✬ ✲■ ✷ ❂ ❂ ❇ ✵ ❘ ✵ ✼ ✸ ✶ ✺ P ❘ ✶ ✸ ✵ ✺ ❄ ✶ ❇ ❄ ✻ ✶ ♦ ✶ ❄ ❇ ✶ ♣ ❇ ✵ ✹ ✼ ✸ ✴ ✵ ❂ ✷ ♣ ❇ ❄ ✻ ✴ ✵ ✺ q ✻❙ ✵ ♣ ✻ ❄ ✸ ✵ ✶ ❇ ✹ ✼ ❈ ❙ ❄ ✸ ✴ ✸ ✴ ✵ ❂ ✷ ♣ ❇ ❄ ✻ ✴ ✵ ✿ ✶ ✺ ✸ ❄ ❆ ❇ ✵ ❡r ❄ ✼ ✵ ✶ ✺ ✺ ✵ ❈ ✺ ✵ ✻ ✻ ❄ ✹ ✼ ● ✼ ✹ ✼ ❑ ❇ ❄ ✼ ✵ ✶ ✺ ✺ ✵ ❈ ✺ ✵ ✻ ✻ ❄ ✹ ✼ ● ✶ ✼ ✿ ✵ ✼ ✿ ❂ ✹ ❄ ✼ ✸✶ ❂ ❂ ✺ ✹ ✶ ❆ ✴ ✵ ✻ ✸ ✹ ❂ ✵ ✺ ❘ ✵ ✶ ♣ ❄ ❇ ❄ ✸ P s ✷ ✶ ✼ ✸ ❄ ❪ ❄ ❆ ✶ ✸ ❄ ✹ ✼ ❡✦ t t ❧ ✭ ✉ ♥ ✦ ✱ ♥ ✪ ✩ ✲❭ ❭ ❭ ✈ ❭ ❇ ✹ ✹ ✿ ❑ ♣ ✺ ✶ ❄ ✼ ♣ ✶ ✺ ✺ ❄ ✵ ✺❭ ❃ ❍ ❃ ✈ ❭ ✺ ✶ ❄ ✼ ❆ ✶ ❂ ❄ ❇ ❇ ✶ ✺ P ✵ ✼ ✿ ✹ ✸ ✴ ✵ ❇ ❄ ✶ ❇ ❆ ✵ ❇ ❇ ✻❭ ❃ ■ ✾ ❭ ✈ ❭ ❇ ✹ ✹ ✿ ❑ ❆ ✵ ✺ ✵ ♣ ✺ ✹ ✻ ❂ ❄ ✼ ✶ ❇ ❪ ❇ ✷ ❄ ✿ ♣ ✶ ✺ ✺ ❄ ✵ ✺❭ ❍ ❭ ✈ ❭ ❇ ✹ ✹ ✿ ❑ ✵ ❂ ❄ ✿ ❄ ✿ P ❘ ❄ ✻ ♣ ✶ ✺ ✺ ❄ ✵ ✺❭ r ❭ ✈ ❭ ❇ ✹ ✹ ✿ ❑ r ✷ ✼ ❈ ❭ ✶ ✺ ✺ ❄ ✵ ✺❭ ▲ ❭ ✈ ❭ ❇ ✹ ✹ ✿ ❑ ▲ ❇ ✶ ❆ ✵ ✼ ✸ ✶ ❭ ✶ ✺ ✺ ❄ ✵ ✺❭ ✳ ❭ ✈ ❭ ❇ ✹ ✹ ✿ ❑ ✸ ✵ ✻ ✸ ❄ ✻ ❭ ✶ ✺ ✺ ❄ ✵ ✺❭ ✳ ✴ ❭ ✈ ❭ ❇ ✹ ✹ ✿ ❑ ✳ ✴ P ❘ ✷ ✻ ❭ ✶ ✺ ✺ ❄ ✵ ✺❭ ❜ ❭ ✈ ❭ ❇ ✹ ✹ ✿ ❑ ❜ ✺ ❄ ✼ ✵ ❭ ✶ ✺ ✺ ❄ ✵ ✺❆ ◗ ❊ ▲ ✈ ❃ P ❆ ❇ ❄ ❆ ✶ ✿ ✵ ✼ ✹ ✻ ❄ ✼ ✵ ❘ ✹ ✼ ✹ ❂ ✴ ✹ ✻ ❂ ✴ ✶ ✸ ✵❃ ✇ ■ ✈ ❃ ✵ ✼ ✸ ✺ ✶ ❇ ✼ ✵ ✺ ♦ ✹ ✷ ✻ ✻ P ✻ ✸ ✵ ❘❃ ■ ✾ ✈ ❃ ✵ ✺ ✵ ♣ ✺ ✹ ✻ ❂ ❄ ✼ ✶ ❇ ❪ ❇ ✷ ❄ ✿✾ ❴ ◗ ✈ ✾ ✹ ✹ ✿ ✶ ✼ ✿ ✿ ✺ ✷ ❈ ✶ ✿ ❘ ❄ ✼ ❄ ✻ ✸ ✺ ✶ ✸ ❄ ✹ ✼❄ ♣ ① ✳ ▲ ✈ ① P ✹ ✸ ✹ ✺ ❂ ✴ ❄ ✼ ❆ ✹ ✼ ❫ ✷ ❈ ✶ ✸ ✵ ✿ ✸ ✹ ❄ ♣ ✷ ❂ ✺ ✹ ❪ ✵ ✼ ●❄ ♣ ① ✳ ▲ ❑ ✇ ❣ ② ✈ ◗ ❘ ❄ ✿ ✶ ✸ ✵ ✿ ✽ P ✹ ✸ ✹ ✺ ❂ ✴ ❄ ✼ ❆ ✹ ✼ ❫ ✷ ❈ ✶ ✸ ✵ ✿ ✸ ✹❄ ♣ ✷ ❂ ✺ ✹ ❪ ✵ ✼① ✳ ▲ ✈ ① P ✹ ✸ ✹ ✺ ❂ ✴ ❄ ✼① ✳ ▲ ❑ ✇ ❣ ② ✈ ◗ ❘ ❄ ✿ ✶ ✸ ✵ ✿ ✽ P ✹ ✸ ✹ ✺ ❂ ✴ ❄ ✼r ❴ r ✈ r ✹ ❙ ❑ ✿ ✵ ✼ ✻ ❄ ✸ P ❇ ❄ ❂ ✹ ❂ ✺ ✹ ✸ ✵ ❄ ✼ ✻▲ ✈ ❍ ❂ ❄ ✸ ✴ ✵ ❇ ❄ ✶ ❇ ❂ ✵ ✺ ❘ ✵ ✶ ♣ ❄ ❇ ❄ ✸ P▲ ❑ ❈ ❂ ✈ ❂ ❑ ❈ ❇ P ❆ ✹ ❂ ✺ ✹ ✸ ✵ ❄ ✼▲ ③ ▲ ❃ ✈ ❞ ❑ ❂ ✶ ❇ ❘ ❄ ✸ ✹ P ❇ ❑ ❱ ❑ ✹ ❇ ✵ ✹ P ❇ ❑ ✻ ✼ ❑ ❈ ❇ P ❆ ✵ ✺ ✹ ❑ ❲ ❑❂ ✴ ✹ ✻ ❂ ✴ ✹ ❆ ✴ ✹ ❇ ❄ ✼ ✵ ❡▲ ❢ ✈ ❢ ✵ ❇ ✶ ✸ ❄ ♦ ✵ ❂ ✵ ✺ ❘ ✵ ✶ ♣ ❄ ❇ ❄ ✸ P✳ ✇ ✾ ✈ ✳ ✷ ❘ ✹ ✺ ✼ ✵ ❆ ✺ ✹ ✻ ❄ ✻ ❪ ✶ ❆ ✸ ✹ ✺❧ ✭ ④ ✭ ❧ ✭ ✩ ✧ ✭ ✲⑤ ⑥ ⑦ ⑧ ⑨ ⑩ ⑩ ❶ ❷ ❸ ⑨ ❹ ❺ ❻ ❼ ❻ ❽ ❾ ❿ ➀ ➁ ➂ ➃ ➄ ❹ ❼ ❻ ➅ ❻ ➆ ⑩ ➃ ➄ ❿ ➇ ➈ ⑩ ➉ ❶ ➄ ❸ ➊ ➇ ❶ ➉ ➁ ⑨ ➋ ❶ ➃ ❹ ➌ ➀ ➃ ❷ ⑨ ➂ ❶ ➀➍ ⑩ ⑨ ❿ ❿ ➎ ➄ ➀ ➏ ➐ ⑨ ➑ ➒ ➈ ⑩ ➓ ❹ � ➔ → ✗ ❻⑤ ➣ ⑦ ↔ ⑨ ⑩ ➂ ➃ ➄ ➄ ❿ ❹ ❺ ❻ ➎ ❻ ❽ ↕ ➄ ❸ ⑨ ⑩ ❹ ➙ ❻ ➊ ❻ ❽ ➛ ⑨ ➁ ⑨ ❹ ➛ ❻ ❽ ➍ ⑨ ➉ ⑨ ⑩ ❿ ❹ ➛ ❻ ❽ ➛ ❶ ⑩ ➓ ➇ ➃ ➉ ⑩ ❶ ➀ ➓ ❹➜ ❻ ❼ ❻ ➅ ➝ ➄ ❸ ⑨ ➇ ❶ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➀ ⑨ ➋ ➋ ➋ ❶ ➄ ⑨ ❿ ❶ ➄ ➀ ➈ ➀ ➝ ➋ ➉ ➝ ⑩ ⑨ ➑ ❶ ➉ ➁ ➁ ➝ ➂ ➃ ➄ ➇ ➝ ➋ ➂ ➈ ➄ ➃ ⑩ ➞

➂ ❶ ➀ ⑩ ➈ ➟ ➃ ❿ ➀ ➝ ➋ ➃ ⑩ ⑨ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➀ ⑨ ➋ ➋ ❿ ➏ ❷ ⑨ ➟ ⑨ ➋ ➈ ➇ ➂ ⑨ ➄ ➉ ➈ ➠ ➃ ➄ ➃ ➋ ➟ ⑨ ➈ ➋ ➈ ➡➀ ➃ ➇ ❶ ➋ ➋ ➃ ⑩ ➞ ➢ ➃ ⑩ ⑩ ❶ ⑨ ⑩ ➤ ➥ ➦ ➤ ➧ ➨ ➩ ❻ ➫ ➭ ➯ ➲ ➳ ➥ ➦ ➵ ➸ ➧ ❻ ❹ ✗ ✁ ✁ ✘ ❹ ➺ ➻ ➼ ➽ ➾ ❹ ➚ ➪ ➽ ➡ ➚ ➶ ➣ ❻⑤ ➪ ⑦ ➙ ➝ ➢ ➃ ❿ ❹ ➹ ❻ ❽ ➜ ⑩ ➈ ➂ ➑ ⑨ ➋ ➋ ❹ ❺ ❻ ➊ ❻ ❽ ❺ ⑩ ❿ ➄ ➞ ❹ ➙ ❻ ❼ ❻ ❽ ➎ ➄ ❸ ➋ ⑨ ❹ ➘ ❻ ❽ ➊ ➋ ❶ ➃ ❿ ❹ ➛ ❻ ➌ ❻➌ ➄ ❶ ➄ ➉ ⑨ ❸ ⑩ ➃ ➉ ⑨ ❷ ➂ ⑨ ➉ ➁ ➈ ❷ ➉ ➈ ❷ ⑨ ➉ ⑨ ⑩ ➂ ❶ ➄ ⑨ ⑨ ➇ ❶ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➉ ⑩ ➃ ➄ ❿ ➇ ➈ ⑩ ➉ ➃ ➄ ❷➢ ❶ ➈ ➃ ➀ ➉ ❶ ➟ ❶ ➉ ➞ ➈ ➠ ➈ ⑩ ➃ ➋ ❷ ⑩ ➝ ❸ ➀ ➃ ➄ ❷ ❶ ❷ ➃ ➉ ⑨ ❿ ➤ ➥ ➦ ➤ ➧ ➨ ➩ ❻ ➴ ➷ ➭ ➨ ➬ ➲ ➮ ➵ ➸ ❻ ❹ � ➔ ➔ ➱ ❹✃ ❐ ➼ ⑥ ➾ ❹ ➣ ➪ ➡ ➣ ➽ ❻⑤ ❒ ⑦ ➙ ➝ ➢ ➃ ❿ ❹ ➹ ❻ ❽ ❼ ⑨ ❮ ➞ ➓ ❹ ➐ ❻ ❽ ➘ ⑩ ➃ ❿ ❿ ❹ ➘ ❻ ❺ ❻ ➜ ➈ ➂ ➇ ➃ ⑩ ❶ ❿ ➈ ➄ ➈ ➠ ➉ ➁ ⑨➇ ⑨ ⑩ ➂ ⑨ ➃ ➢ ❶ ➋ ❶ ➉ ➞ ➀ ➁ ➃ ⑩ ➃ ➀ ➉ ⑨ ⑩ ❶ ❿ ➉ ❶ ➀ ❿ ➈ ➠ ➃ ➁ ➝ ➂ ➃ ➄ ➀ ➈ ➋ ➈ ➄ ❶ ➀ ⑨ ➇ ❶ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➼ ➜ ➃ ➀ ➈ ➡➣ ➾ ➀ ⑨ ➋ ➋ ➋ ❶ ➄ ⑨ ➉ ➈ ➀ ➈ ➋ ➈ ➄ ➈ ➠ ⑩ ➃ ➢ ➢ ❶ ➉ ❹ ➂ ➈ ➄ ➓ ⑨ ➞ ❹ ➃ ➄ ❷ ❷ ➈ ❸ ❶ ➄ ➉ ⑨ ❿ ➉ ❶ ➄ ⑨ ➃ ➄ ❷➁ ➝ ➂ ➃ ➄ ❷ ⑩ ➝ ❸ ➃ ➢ ❿ ➈ ⑩ ➇ ➉ ❶ ➈ ➄ ❻ ➴ ➷ ➭ ➨ ➬ ➲ ➮ ➵ ➸ ➲ ❹ � ➔ ➔ ❰ ❹ ✃ Ï ➼ ⑥ ➾ ❹ ⑥ ⑥ ➪ ➡ ⑥ ⑥ Ð ❻⑤ ➶ ⑦ ⑧ ⑨ ⑩ ➄ ➃ ❿ ❹ ❺ ❻ ❼ ❻ ❽ ➜ ➃ ⑩ ❷ ➈ ❿ ➈ ❹ Ñ ❻ ➅ ❻ ❽ Ò ➃ ➋ ⑨ ➞ ❹ Ó ❻ ➛ ❻ ❽ ➹ ⑨ ❶ ➄ ➃ ➄ ❷ ❹ ❺ ❻ ➊ ❻ ❽➜ ➃ ➂ ➇ ➈ ❿ ❹ ➌ ❻ ➙ ❻ ❽ Ñ ⑨ ⑩ ⑩ ⑨ ❶ ⑩ ➃ ❹ ➌ ❻ ❼ ❻ ❽ ↔ ➈ ➞ ❶ ➄ ❸ ❹ ❼ ❻ ⑧ ❻ ❽ ➹ ❶ ➉ ➉ ⑨ ❹ ❺ ❻ ↔ ❻ ❽ ⑧ ⑩ ❶ ➉ ⑨ ❿ ❹Ò ❻ ❽ ➍ ⑨ ⑩ ❿ ❶ ❷ ❿ ➓ ➞ ❹ ➒ ❻ ❽ ➙ ➃ ➂ ❶ ⑩ ⑨ ❮ ❹ Ó ❻ ↔ ❻ ❽ ⑧ ⑩ ❶ ➉ ➈ ❹ ❺ ❻ ➌ ❻ ➊ ❿ ➉ ➃ ➢ ➋ ❶ ❿ ➁ ➂ ⑨ ➄ ➉ ➈ ➠➇ ⑩ ❶ ➂ ➃ ⑩ ➞ ➀ ➝ ➋ ➉ ➝ ⑩ ⑨ ❿ ➈ ➠ ➁ ➝ ➂ ➃ ➄ ➢ ⑩ ➃ ❶ ➄ ➂ ❶ ➀ ⑩ ➈ ➟ ➃ ❿ ➀ ➝ ➋ ➃ ⑩ ⑨ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➀ ⑨ ➋ ➋ ❿ ➉ ➈➇ ⑩ ➈ ➟ ❶ ❷ ⑨ ➃ ➄ ➤ ➥ ➦ ➤ ➧ ➨ ➩ ➀ ⑨ ➋ ➋ ➝ ➋ ➃ ⑩ ➂ ➈ ❷ ⑨ ➋ ➈ ➠ ➉ ➁ ⑨ ➢ ➋ ➈ ➈ ❷ ➡ ➢ ⑩ ➃ ❶ ➄ ➢ ➃ ⑩ ⑩ ❶ ⑨ ⑩ ❻ Ô ➭ ➧ ➲➴ ➨ ➩ ➧ ➩ Õ ➲ ❹ ✗ ✁ � ✁ ❹ Ö ➼ ➚ ➾ ❹ ⑥ ➣ ➽ ➶ ➡ ⑥ ➣ ➚ ➣ ❻⑤ ➽ ⑦ ⑧ ➃ ➋ ❷ ➃ ❹ ❺ ❻ ❹ ➃ ➄ ❷ ➛ ❻ ❺ ➃ ➉ ➉ ⑨ ⑩ ❹ Ó ❶ ❮ ⑨ ➡ ❿ ⑨ ➋ ⑨ ➀ ➉ ❶ ➟ ⑨ ➃ ❿ ❿ ⑨ ❿ ❿ ➂ ⑨ ➄ ➉ ➈ ➠ ➉ ❶ ❸ ➁ ➉× ➝ ➄ ➀ ➉ ❶ ➈ ➄ ➇ ➃ ⑩ ➃ ➀ ⑨ ➋ ➋ ➝ ➋ ➃ ⑩ ➇ ⑨ ⑩ ➂ ⑨ ➃ ➢ ❶ ➋ ❶ ➉ ➞ ➝ ❿ ❶ ➄ ❸ ➠ ➋ ➝ ➈ ⑩ ⑨ ❿ ➀ ⑨ ➄ ➉ ➋ ➞ ➋ ➃ ➢ ⑨ ➋ ➋ ⑨ ❷❷ ⑨ Ø ➉ ⑩ ➃ ➄ ❿ ❻ ➎ ➄ ➢ ➂ ❸ ➋ ➃ ➢ ➉ ⑨ ➀ ➁ ➏ ✗ ✁ ✁ → ❽ Ù ➈ ➋ ❻ ⑥ ❻⑤ ➚ ⑦ ➜ ➁ ❶ ➄ ❹ ➌ ❻ ➜ ❻ ❽ Ù ⑨ ⑩ ❸ ➄ ➈ ➋ ➋ ⑨ ❹ ➐ ❻ ❽ ❺ ➃ ➀ ➐ ➃ ➝ ❸ ➁ ➉ ➈ ➄ ❹ ➹ ❻ ➛ ❻ ❽ ➹ ➃ ➋ ➋ ➃ ➀ ⑨ ❹ ❼ ❻ ➅ ❻ ❽↔ ➈ ➋ ➋ ⑨ ➄ ➢ ⑨ ⑩ ❸ ❹ ❺ ❻ Ò ❻ ❽ ⑧ ➝ ⑩ ⑨ ➉ ❹ ➌ ❻ ➘ ❻ ➍ ⑩ ➈ ➉ ⑨ ❶ ➄ ➃ ❿ ⑨ ➡ ➃ ➀ ➉ ❶ ➟ ➃ ➉ ⑨ ❷ ⑩ ⑨ ➀ ⑨ ➇ ➉ ➈ ⑩ ⑥➃ ➀ ➉ ❶ ➟ ➃ ➉ ❶ ➈ ➄ ❶ ➄ ❷ ➝ ➀ ⑨ ❿ ⑨ ➇ ❶ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➃ ➇ ➈ ➇ ➉ ➈ ❿ ❶ ❿ ➃ ➄ ❷ ❶ ➄ ➀ ⑩ ⑨ ➃ ❿ ⑨ ❿ ❶ ➄ ➉ ⑨ ❿ ➉ ❶ ➄ ➃ ➋➇ ⑨ ⑩ ➂ ⑨ ➃ ➢ ❶ ➋ ❶ ➉ ➞ ❻ ➴ ➨ ➩ Õ ➲ Ô ➭ ➧ Ú ➲ Û Õ ➭ Ü ➲ Ý Õ ➤ ➲ Þ ß à ß á â ã ✗ ✁ ✁ ❰ ❹ ✃ Ï Ï ➼ ⑥ ä ➾ ❹ ⑥ ⑥ ⑥ å ❒ ➡⑥ ⑥ ⑥ å ä ❻⑤ Ð ⑦ Ó ❶ ➂ ❶ ➈ ➄ ⑨ ❿ ➀ ➝ ❹ ❺ ❻ ❽ ➍ ➈ ➇ ➈ ➟ ❹ Ò ❻ ❽ Ó ❶ ➂ ➃ ❹ ➌ ❻ ➊ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➉ ⑩ ➃ ➄ ❿ ➀ ➞ ➉ ➈ ❿ ❶ ❿ ❶ ➄➁ ⑨ ➃ ➋ ➉ ➁ ➃ ➄ ❷ ❷ ❶ ❿ ⑨ ➃ ❿ ⑨ ❻ æ ➵ Ú Ú ç ➤ ➸ ➸ è ➵ ➮ ➵ ➸ ❻ ❹ ✗ ✁ ✁ ➔ ❹ ❐ ❐ Ö ➼ ⑥ ➾ ❹ ➣ ➚ ➡ ❒ å ❻⑤ ä ⑦ ⑧ ➃ ❮ ❮ ➈ ➄ ❶ ❹ ➘ ❻ ❽ Ò ⑨ × ➃ ➄ ➃ ❹ ➊ ❻ ➊ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➀ ⑨ ➋ ➋ ➡ ➉ ➈ ➡ ➀ ⑨ ➋ ➋ × ➝ ➄ ➀ ➉ ❶ ➈ ➄ ❿ ➏➂ ➈ ➋ ⑨ ➀ ➝ ➋ ➃ ⑩ ➈ ⑩ ❸ ➃ ➄ ❶ ❮ ➃ ➉ ❶ ➈ ➄ ➃ ➄ ❷ ⑩ ➈ ➋ ⑨ ❶ ➄ ➟ ➃ ❿ ➀ ➝ ➋ ➃ ⑩ ➁ ➈ ➂ ⑨ ➈ ❿ ➉ ➃ ❿ ❶ ❿ ❻ ➴ ➷ é ➸ ➤ ➩ Ú ➲➮ ➵ ➦ ➲ ❹ ✗ ✁ ✁ ✘ ❹ ➺ ➻ ➼ ➪ ➾ ❹ Ð ➽ ä ➡ ä å ⑥ ❻⑤ ⑥ å ⑦ ❺ ⑨ ➁ ➉ ➃ ❹ Ò ❻ ❽ ❺ ➃ ➋ ❶ ➓ ❹ ➌ ❻ ⑧ ❻ Ó ❶ ❸ ➄ ➃ ➋ ❶ ➄ ❸ ➂ ⑨ ➀ ➁ ➃ ➄ ❶ ❿ ➂ ❿ ⑩ ⑨ ❸ ➝ ➋ ➃ ➉ ❶ ➄ ❸⑨ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➇ ⑨ ⑩ ➂ ⑨ ➃ ➢ ❶ ➋ ❶ ➉ ➞ ❻ ➴ ➷ é ➸ ➤ ➩ Ú ➲ ➮ ➵ ➦ ❻ ❹ ✗ ✁ ✁ ➱ ❹ ➺ ê ➼ ⑥ ➾ ❹ ➣ ➚ ä ➡ ➪ ➽ ➚ ❻⑤ ⑥ ⑥ ⑦ ➜ ➈ ⑩ ➃ ❷ ➃ ❹ ❺ ❻ ❽ ❺ ➃ ⑩ ❶ ➈ ➉ ➉ ❶ ❹ ❺ ❻ ❽ ➆ ➁ ➝ ⑩ ❿ ➉ ➈ ➄ ❹ ➘ ❻ ❽ Ó ➂ ❶ ➉ ➁ ❹ ➛ ❻ ❽ ➛ ➝ ➄ ➓ ⑨ ➋ ❹ ➙ ❻ ❽⑧ ⑩ ➈ ➀ ➓ ➁ ➃ ➝ ❿ ❹ ❺ ❻ ❽ ➅ ➃ ➂ ➇ ➝ ❸ ➄ ➃ ➄ ❶ ❹ ❺ ❻ ➘ ❻ ❽ ❺ ➃ ⑩ ➉ ❶ ➄ ➡ ➍ ➃ ❷ ➝ ⑩ ➃ ❹ ➎ ❻ ❽ Ó ➉ ➈ ➇ ➇ ➃ ➀ ➀ ❶ ➃ ⑩ ➈ ❹➌ ❻ ❽ ➙ ➝ ➀ ➈ ❹ ➅ ❻ ❽ ❺ ➀ Ò ➈ ➄ ➃ ➋ ❷ ❹ Ò ❻ ❺ ❻ ❽ ➹ ➃ ⑩ ❷ ❹ ➍ ❻ ➌ ❻ ❽ Ò ⑨ × ➃ ➄ ➃ ❹ ➊ ❻ Ù ➃ ❿ ➀ ➝ ➋ ➃ ⑩⑨ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➡ ➀ ➃ ❷ ➁ ⑨ ⑩ ❶ ➄ ❶ ❿ ➃ ➄ ❶ ➂ ➇ ➈ ⑩ ➉ ➃ ➄ ➉ ❷ ⑨ ➉ ⑨ ⑩ ➂ ❶ ➄ ➃ ➄ ➉ ➈ ➠ ➂ ❶ ➀ ⑩ ➈ ➟ ➃ ❿ ➀ ➝ ➋ ➃ ⑩❶ ➄ ➉ ⑨ ❸ ⑩ ❶ ➉ ➞ ➤ ➥ ➦ ➤ ➦ ➩ ❻ ➴ ➨ ➩ Õ ➲ Ô ➭ ➧ Ú ➲ Û Õ ➭ Ü ➲ Ý Õ ➤ ➲ ë ➲ Ý ➲ Û ❻ ❹ � ➔ ➔ ➔ ❹ ì ê ➼ ⑥ ➚ ➾ ❹ ä Ð ⑥ ➶ ➡ä Ð ➣ å ❻⑤ ⑥ ➣ ⑦ Ò ⑨ × ➃ ➄ ➃ ❹ ➊ ❻ ❽ ➜ ➈ ⑩ ➃ ❷ ➃ ❹ ❺ ❻ ❽ ➅ ➃ ➂ ➇ ➝ ❸ ➄ ➃ ➄ ❶ ❹ ❺ ❻ ➘ ❻ ➊ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➀ ⑨ ➋ ➋ ➡ ➉ ➈ ➡➀ ⑨ ➋ ➋ × ➝ ➄ ➀ ➉ ❶ ➈ ➄ ❿ ❻ í á à î ï ð ❻ ❹ � ➔ ➔ ñ ❹ ì ➼ ⑥ å ➾ ❹ ä ⑥ å ➡ ä ⑥ Ð ❻⑤ ⑥ ➪ ⑦ Ó ➉ ⑨ ➟ ⑨ ➄ ❿ ❹ ➆ ❻ ❽ ➘ ➃ ⑩ ➀ ❶ ➃ ❹ ❼ ❻ ➘ ❻ ❽ Ó ➁ ➃ ❿ ➢ ➞ ❹ Ò ❻ ❺ ❻ ❽ ⑧ ➁ ➃ ➉ ➉ ➃ ➀ ➁ ➃ ⑩ ➞ ➃ ❹ ❼ ❻ ❽ ❺ ➃ ➋ ❶ ➓ ❹➌ ❻ ⑧ ❻ ❺ ⑨ ➀ ➁ ➃ ➄ ❶ ❿ ➂ ❿ ⑩ ⑨ ❸ ➝ ➋ ➃ ➉ ❶ ➄ ❸ ⑨ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➀ ⑨ ➋ ➋ ➢ ➃ ⑩ ⑩ ❶ ⑨ ⑩ ➠ ➝ ➄ ➀ ➉ ❶ ➈ ➄ ❻ ò ó ôð ➲ ➴ ➷ é ➸ ➤ ➩ Ú ➲ ➫ è ➥ õ æ ➵ Ú Ú ö ➩ Ú ➲ ➴ ➷ é ➸ ➤ ➩ Ú ❻ ❹ ✗ ✁ ✁ ✁ ❹ ÷ ø ì ➼ ➪ ➾ ❹ ➅ ❒ ⑥ ä ➡ ❒ ➣ ➣ ❻⑤ ⑥ ❒ ⑦ ➐ ➝ ❿ ⑩ ➃ ➉ ❹ ➌ ❻ ❽ ➆ ➝ ⑩ ➄ ⑨ ⑩ ❹ ❼ ❻ ➙ ❻ ❽ ❺ ➃ ❷ ➃ ⑩ ➃ ❹ ❼ ❻ ➅ ❻ ❺ ➈ ➋ ⑨ ➀ ➝ ➋ ➃ ⑩ ➇ ➁ ➞ ❿ ❶ ➈ ➋ ➈ ❸ ➞ ➃ ➄ ❷➇ ➃ ➉ ➁ ➈ ➇ ➁ ➞ ❿ ❶ ➈ ➋ ➈ ❸ ➞ ➈ ➠ ➉ ❶ ❸ ➁ ➉ × ➝ ➄ ➀ ➉ ❶ ➈ ➄ ❿ ❻ ➎ Ù ❻ ➙ ⑨ ❸ ➝ ➋ ➃ ➉ ❶ ➈ ➄ ➈ ➠ ➉ ❶ ❸ ➁ ➉× ➝ ➄ ➀ ➉ ❶ ➈ ➄ ❿ ➢ ➞ ⑨ Ø ➉ ⑩ ➃ ➀ ⑨ ➋ ➋ ➝ ➋ ➃ ⑩ ❿ ➉ ❶ ➂ ➝ ➋ ❶ ➏ ➄ ➝ ➉ ⑩ ❶ ⑨ ➄ ➉ ❿ ❹ ➀ ➞ ➉ ➈ ➓ ❶ ➄ ⑨ ❿ ❹ ➃ ➄ ❷❶ ➂ ➂ ➝ ➄ ⑨ ➀ ⑨ ➋ ➋ ❿ ❻ ò ó ô ð ➲ ù ➷ ú ➸ ➤ ➩ Ú ➲ û ➭ ➸ ➧ ➨ ➩ ➤ ➥ ➧ ➵ ➸ ➧ ➲ ➫ ➤ ➦ ➵ ➨ ➴ ➷ é ➸ ➤ ➩ Ú ❻ ❹ ✗ ✁ ✁ ✁ ❹÷ ø ì ➼ ➶ ➾ ❹ ➘ Ð ➶ ⑥ ➡ Ð ➶ ➚ ❻⑤ ⑥ ➶ ⑦ ➊ ❷ ⑨ ➄ ❿ ❹ ↔ ❻ ➌ ❻ ❽ ➍ ➃ ⑩ ➓ ➈ ❿ ❹ ➜ ❻ ➌ ❻ ❺ ➈ ❷ ➝ ➋ ➃ ➉ ❶ ➈ ➄ ➈ ➠ ⑨ ➇ ❶ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➃ ➄ ❷ ⑨ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋➇ ➃ ⑩ ➃ ➀ ⑨ ➋ ➋ ➝ ➋ ➃ ⑩ ➇ ⑨ ⑩ ➂ ⑨ ➃ ➢ ❶ ➋ ❶ ➉ ➞ ➢ ➞ ➋ ⑨ ➝ ➓ ➈ ➀ ➞ ➉ ⑨ ❿ ❻ ò ü ý ô þ ➨ è õ þ ➵ Ú ➤ ➦ ➲ ➮ ➵ ➦ ❻ ❹✗ ✁ ✁ ✁ ❹ ➻ ✃ ➼ ➪ ➾ ❹ ➪ ⑥ ➶ ➡ ➪ ➣ Ð ❻⑤ ⑥ ➽ ⑦ Ò ➝ ❷ ⑨ ➓ ❹ Ó ❻ ❺ ❻ ❽ ➘ ➃ ⑩ ➀ ❶ ➃ ❹ ❼ ❻ ➘ ❻ ➜ ➞ ➉ ➈ ❿ ➓ ⑨ ➋ ⑨ ➉ ➃ ➋ ⑩ ⑨ ❸ ➝ ➋ ➃ ➉ ❶ ➈ ➄ ➈ ➠ ➇ ➝ ➋ ➂ ➈ ➄ ➃ ⑩ ➞➟ ➃ ❿ ➀ ➝ ➋ ➃ ⑩ ➇ ⑨ ⑩ ➂ ⑨ ➃ ➢ ❶ ➋ ❶ ➉ ➞ ❻ ð ➲ Û ÿ ÿ Ú ➲ ➴ ➷ é ➸ ➤ ➩ Ú ❻ ❹ ✗ ✁ ✁ � ❹ ì ✃ ➼ ❒ ➾ ❹ ⑥ ❒ Ð ➚ ➡ ⑥ ➶ å å ❻⑤ ⑥ ➚ ⑦ ➙ ➈ ❷ ❸ ⑨ ⑩ ❿ ❹ ➅ ❻ Ó ❻ ❽ Ñ ➃ ➄ ➄ ❶ ➄ ❸ ❹ ➌ ❻ Ó ❻ ➙ ⑨ ❸ ➝ ➋ ➃ ➉ ❶ ➈ ➄ ➈ ➠ ⑨ ➇ ❶ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➇ ⑨ ⑩ ➂ ⑨ ➃ ➢ ❶ ➋ ❶ ➉ ➞➢ ➞ ➉ ➁ ⑨ ➃ ➀ ➉ ❶ ➄ ➀ ➞ ➉ ➈ ❿ ➓ ⑨ ➋ ⑨ ➉ ➈ ➄ ❻ ➜ ➞ ➉ ➈ ❿ ➓ ⑨ ➋ ⑨ ➉ ➈ ➄ ➼ ↔ ➈ ➢ ➈ ➓ ⑨ ➄ ➾ ❹ ✗ ✁ � � ❹ ê ➺ ➼ ⑥ ➣ ➾ ❹➽ ➶ ➪ ➡ ➽ ➽ å ❻⑤ ⑥ Ð ⑦ ⑧ ⑩ ➈ ➑ ➄ ❹ ➘ ❻ ➜ ❻ ➐ ❶ ➉ ⑩ ❶ ➀ ➈ Ø ❶ ❷ ⑨ ➃ ➄ ❷ ➄ ⑨ ➝ ⑩ ➈ ➄ ➃ ➋ ❷ ⑨ ➃ ➉ ➁ ❻ Ô ➤ ➧ ➨ ➤ Õ � ✁ ➤ Ü ➵ ❹ ✗ ✁ � ✁ ❹÷ ❐ ➼ ➪ ➾ ❹ ⑥ ➶ ➪ ➡ ⑥ ➽ ➶ ❻⑤ ⑥ ä ⑦ Ó ➉ ⑨ ➟ ⑨ ➄ ❿ ❹ ➆ ❻ ❽ ➜ ⑩ ⑨ ❶ ❸ ➁ ➉ ➈ ➄ ❹ ❼ ❻ ❽ ➆ ➁ ➈ ➂ ➇ ❿ ➈ ➄ ❹ ➹ ❻ ❼ ❻ ➜ ➈ ➄ ➉ ⑩ ➈ ➋ ➈ ➠ ➀ ➌ ❺ ➍ ❶ ➄➋ ➝ ➄ ❸ ⑨ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➀ ⑨ ➋ ➋ ➇ ➁ ⑨ ➄ ➈ ➉ ➞ ➇ ⑨ ❿ ❻ ➎ ➂ ➇ ➋ ❶ ➀ ➃ ➉ ❶ ➈ ➄ ❿ ➠ ➈ ⑩ ➀ ➈ ➄ ➉ ⑩ ➈ ➋ ➈ ➠➢ ➃ ⑩ ⑩ ❶ ⑨ ⑩ ➠ ➝ ➄ ➀ ➉ ❶ ➈ ➄ ❻ ò ó ô ð ➲ ➴ ➷ é ➸ ➤ ➩ Ú ❻ ❹ � ➔ ➔ ➔ ❹ ÷ ø ø ➼ ⑥ ➍ ➉ ⑥ ➾ ❹ ➅ ⑥ ⑥ ä ➡ ⑥ ➣ ➽ ❻⑤ ➣ å ⑦ Ó ❶ ➂ ❶ ➈ ➄ ⑨ ❿ ➀ ➝ ❹ ❺ ❻ ❽ ➘ ➃ ➠ ⑨ ➄ ➀ ➝ ❹ ➌ ❻ ❽ ➌ ➄ ➉ ➈ ➁ ⑨ ❹ Ñ ❻ ➆ ⑩ ➃ ➄ ❿ ➀ ➞ ➉ ➈ ❿ ❶ ❿ ➈ ➠ ➇ ➋ ➃ ❿ ➂ ➃➂ ➃ ➀ ⑩ ➈ ➂ ➈ ➋ ⑨ ➀ ➝ ➋ ⑨ ❿ ❶ ➄ ⑨ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ➀ ⑨ ➋ ➋ ❿ ➏ ➃ ➀ ⑨ ➋ ➋ ➢ ❶ ➈ ➋ ➈ ❸ ❶ ➀ ➃ ➋ ❿ ➝ ⑩ ➟ ⑨ ➞ ❻ö ➤ Õ ➨ ➩ ➸ Õ ➲ ➮ ➵ ➸ ➲ ç ➵ Õ ➷ ❻ ❹ ✗ ✁ ✁ ✗ ❹ Ö ø ➼ ➶ ➾ ❹ ➣ ➽ ä ➡ ➣ Ð Ð ❻⑤ ➣ ⑥ ⑦ ➛ ➃ ➋ ➋ ➝ ⑩ ❶ ❹ ➙ ❻ ⑧ ➃ ❿ ⑨ ➂ ⑨ ➄ ➉ ➂ ⑨ ➂ ➢ ⑩ ➃ ➄ ⑨ ❿ ➏ ❿ ➉ ⑩ ➝ ➀ ➉ ➝ ⑩ ⑨ ❹ ➃ ❿ ❿ ⑨ ➂ ➢ ➋ ➞ ➃ ➄ ❷ ⑩ ➈ ➋ ⑨ ❶ ➄➉ ➝ ➂ ➈ ➝ ⑩ ➃ ➄ ❸ ❶ ➈ ❸ ⑨ ➄ ⑨ ❿ ❶ ❿ ❻ Ô ➭ ➧ ➲ ➮ ➵ ➦ ➲ æ ✂ ➥ Õ ➵ ✄ ❹ ✗ ✁ ✁ ❰ ❹ ❐ ➼ ➽ ➾ ❹ ❒ ➣ ➣ ➡ ❒ ➪ ➪ ❻⑤ ➣ ➣ ⑦ ➹ ⑨ ❶ ➄ ➢ ➃ ➝ ➂ ❹ Ó ❻ ❽ ➆ ➃ ⑩ ➢ ⑨ ➋ ➋ ❹ ❼ ❻ ❺ ❻ ❽ Ò ➃ ➂ ❶ ➃ ➄ ➈ ❹ ➊ ❻ ➙ ❻ ➆ ➁ ⑨ ❿ ➉ ⑩ ➝ ➀ ➉ ➝ ⑩ ⑨ ➃ ➄ ❷➠ ➝ ➄ ➀ ➉ ❶ ➈ ➄ ➈ ➠ ➉ ➁ ⑨ ⑨ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ❸ ➋ ➞ ➀ ➈ ➀ ➃ ➋ ➞ Ø ➋ ➃ ➞ ⑨ ⑩ ❻ Û ➥ ➥ è ➮ ➵ ➦ ➲ ☎ ➤ ➩ ➬ ➵ Ü ➲✆ ➥ õ ➲ ❹ ✗ ✁ ✁ → ❹ ì ❹ ⑥ ➣ ⑥ ➡ ⑥ ➽ ➚ ❻⑤ ➣ ➪ ⑦ ➅ ❶ ➝ ➁ ➃ ➄ ⑨ ➄ ❹ Ó ❻ ❽ Ó ➃ ➋ ➋ ❶ ❿ ➃ ➋ ➂ ❶ ❹ ❺ ❻ ❽ ➍ ⑨ ➉ ➉ ❶ ➋ ➃ ❹ Ù ❻ ❽ ❾ ➓ ❿ ➃ ➋ ➃ ❹ ➐ ❻ ❽ ➆ ⑨ ➄ ➁ ➝ ➄ ⑨ ➄ ❹ ❼ ❻➎ ➄ ❷ ❶ ⑩ ⑨ ➀ ➉ ➂ ⑨ ➃ ❿ ➝ ⑩ ⑨ ➂ ⑨ ➄ ➉ ➈ ➠ ➉ ➁ ⑨ ➟ ➃ ❿ ➀ ➝ ➋ ➃ ⑩ ⑨ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ❸ ➋ ➞ ➀ ➈ ➀ ➃ ➋ ➞ Ø ➋ ➃ ➞ ⑨ ⑩➉ ➁ ❶ ➀ ➓ ➄ ⑨ ❿ ❿ ❶ ➄ ➁ ➝ ➂ ➃ ➄ ❿ ➝ ➢ ➂ ➝ ➀ ➈ ❿ ➃ ➋ ➀ ➃ ➇ ❶ ➋ ➋ ➃ ⑩ ❶ ⑨ ❿ ➑ ❶ ➉ ➁ ➃ ➇ ➋ ➝ ❸ ➡ ❶ ➄ ➠ ➈ ⑩ ➎ ➂ ➃ ❸ ⑨ ❻ð ➲ æ ➩ ➬ ÿ è ➧ ➲ ö ➵ ➧ ➷ ➩ Ü ➸ ➴ ➨ ➩ õ ➨ ➭ ➬ ➸ ☎ ➤ ➩ ➬ ➵ Ü ❻ ❹ ✗ ✁ � ❰ ❹ ✃ ✃ Ï ➼ ⑥ ➾ ❹ ➪ Ð ➡ ❒ ➚ ❻⑤ ➣ ❒ ⑦ ➍ ⑩ ❶ ⑨ ❿ ❹ ➌ ❻ ➙ ❻ ❽ Ó ⑨ ➀ ➈ ➂ ➢ ❹ ➆ ❻ ➹ ❻ ❽ ➘ ➃ ⑨ ➁ ➉ ❸ ⑨ ➄ ❿ ❹ ➍ ❻ ➆ ➁ ⑨ ⑨ ➄ ❷ ➈ ➉ ➁ ⑨ ➋ ❶ ➃ ➋ ❿ ➝ ⑩ ➠ ➃ ➀ ⑨➋ ➃ ➞ ⑨ ⑩ ❻ ➴ ✝ Ú è õ ➵ ➨ ➸ Û ➨ Õ ➷ ❻ ❹ ✗ ✁ ✁ ✁ ❹ ➻ ➻ Ï ➼ ➶ ➾ ❹ ➽ ➶ ➪ ➡ ➽ ➽ ➽ ❻

✞ ✟ ✠ ✟ ✡ ☛ ☞ ✌ ✟ ✍ ✟ ✎ ✏ ✟ ✑ ✒ ☞ ✠ ☞ ☛ ✓ ☞ ✔ ✕ ✎ ✑ ✔ ✖ ✗ ✘ ✎ ☛ ✙ ✡ ✎ ✘ ✖ ✖ ✚ ☞ ✘ ✠ ✘ ✛ ☞ ✡ ✑ ✠ ✚ ✑ ✎ ✎ ☞ ✟ ✎ ✖ ✜ ☞ ✔ ☞ ✢ ✣ ✟ ✌ ☞ ✟ ✤ ✖ ☞ ✔ ✜ ✟ ✥ ☞ ✡ ☞ ✔ ✑ ✠ ✦ ✧ ✟ ✏ ☞ ✖ ☛ ✎ ✓ ★ ✩ ✪ ✫ ✬ ★ ✭ ✘ ✠ ✮ ✯ ✰ ★ ✱ ✘ ✮ ✲ ✫ ✪ ✳✴ ✵ ✶ ✷ ✸ ✹ ✺ ✻ ✻ ✼ ✽ ✾ ✿ ❀ ❁ ❂ ❃ ❄ ✺ ❅ ✾ ✸ ❀ ❁ ❆ ❇ ✽ ❈ ✺ ✾ ❉ ❀ ❁ ❉ ❅ ✺ ✽ ✽ ✺ ❅ ✾ ❊ ❀ ❁ ❂ ✺ ✽ ❅ ❋ ● ❍ ✾ ■ ❀ ❁■ ✼ ❅ ✹ ❋ ✽ ✾ ❏ ❀ ❁ ❑ ✺ ❋ ✹ ▲ ✾ ✿ ❀ ❁ ❂ ❃ ❄ ▼ ✼ ✽ ✽ ✾ ◆ ❀ ❁ ❑ ✺ ❋ ❖ ✼ ✽ P ✾ ■ ❀ ◗ ❀ ✸ ✺ ✻ ❘ ❋ ❘ ✼ ✽ P▼ ✼ ❙ ❃ ❅ ✼ ❚ P ❃ ▼ ❋ ✽ ✼ ❯ ❘ ❇ ❅ ❖ ✺ ❅ ❱ ❯ ✺ ✼ P ✹ ❃ ❄ ❯ ✼ ❈ ❋ ✽ ❖ ❃ ❄ ✹ ❍ ✺ ✺ ✽ P ❃ ✹ ❍ ✺ ❯ ❋ ✼ ❯ ❖ ❯ ❱ ● ❃ ● ✼ ❯ ❋ ❲ ❀❳ ❨ ❩ ❬ ❭ ❪ ❨ ❫ ❴ ❵ ❀ ✾ ✩ ✪ ✫ ✫ ✾ ❛ ❜ ❝ ❞ ❡ ❢ ✾ ❡ ❣ ❤ ✐ ❡ ❥ ❡ ❀✴ ✵ ❤ ✷ ❦ ✼ ❖ ▼ ❇ ❅ ✾ ❏ ❀ ❁ ❧ ❃ ● ❍ ✾ ◗ ❀ ❁ ❂ ✼ ❇ ▼ ✼ ✽ ✽ ✾ ■ ❀ ❁ ❧ ❅ ✼ ▼ ✼ ✽ ✽ ✾ ♠ ❀ ❁ ❊ ❅ ✼ ❇ ✹ ♥ ✺ ❋ ✽ ✾♦ ❀ ❁ ❊ ✼ ● ❈ ✺ ✾ ❆ ❀ ❂ ❱ ✼ ❯ ❇ ❅ ❃ ✽ ✼ ✽ ❘ ✺ ❅ ❇ ▼ ● ❃ ✽ ● ✺ ✽ ✹ ❅ ✼ ✹ ❋ ❃ ✽ ❘ ✼ ❅ ✺ ✺ ❯ ✺ ♣ ✼ ✹ ✺ P ❋ ✽● ❅ ❋ ✹ ❋ ● ✼ ❯ ❯ ❱ ❋ ❯ ❯ ✻ ✼ ✹ ❋ ✺ ✽ ✹ ❘ ✼ ✽ P ✼ ❘ ❘ ❃ ● ❋ ✼ ✹ ✺ P ♥ ❋ ✹ ❍ P ❋ ❘ ✺ ✼ ❘ ✺ ❘ ✺ ♣ ✺ ❅ ❋ ✹ ❱ ❀ q r s t ❨✉ s ✈ ✇ ① ❴ ② ❨ ✾ ✩ ✪ ✫ ✩ ✾ ③ ❝ ❞ ❡ ✐ ✵ ❢ ✾ ④ ✵ ✐ ④ ⑤ ❀✴ ✵ ⑤ ✷ ❉ ✺ ● ❈ ✺ ❅ ✾ ❉ ❀ ❆ ❀ ❁ ♦ ❍ ✼ ✻ ✻ ✺ ❯ ❯ ✾ ⑥ ❀ ❁ ❉ ❅ ❇ ✺ ❖ ❖ ✺ ❅ ✾ ⑥ ❀ ❁ ◗ ✽ ✽ ✺ ● ❈ ✺ ✾ ❊ ❀ ❁ ✿ ✼ ● ❃ ❚ ✾ ■ ❀❊ ❍ ✺ ❅ ✼ ✻ ✺ ❇ ✹ ❋ ● ❘ ✹ ❅ ✼ ✹ ✺ ❖ ❋ ✺ ❘ ✹ ✼ ❅ ❖ ✺ ✹ ❋ ✽ ❖ ✹ ❍ ✺ ✺ ✽ P ❃ ✹ ❍ ✺ ❯ ❋ ✼ ❯ ❖ ❯ ❱ ● ❃ ● ✼ ❯ ❱ ❲ ⑦ ✼ ● ❇ ✹ ✺P ✺ ❄ ❋ ● ❋ ✹ ❘ ✾ ❚ ❇ ✹ ❖ ❅ ✺ ✼ ✹ ✻ ❃ ✹ ✺ ✽ ✹ ❋ ✼ ❯ ❀ q ⑧ ⑨ ⑩ s ✈ ❶ ⑧ ❵ ✇ ❨ ❫ ❴ ❵ ❀ ✾ ✩ ✪ ✫ ✪ ✾ ❷ ❸ ❞ ✵ ❢ ✾ ❣ ❹ ❹ ✐❣ ❡ ❹ ❀✴ ✵ ④ ✷ ■ ❋ ✽ ❘ ❍ ✼ ❯ ❯ ✾ ♠ ❀ ⑥ ❀ ❁ ❊ ❋ ❅ ❇ ✻ ✻ ✼ ✹ ❍ ❋ ✾ ♦ ❀ ❁ ❺ ❃ ❖ ✺ ❯ ✾ ✸ ❀ ■ ❀ ❁ ■ ✼ ❯ ❋ ❈ ✾ ◗ ❀ ❉ ❀ ❺ ✺ ❘ ❋ ● ❯ ✺❄ ❃ ❅ ▼ ✼ ✹ ❋ ❃ ✽ ✼ ✽ P ✹ ❅ ✼ ❄ ❄ ❋ ● ❈ ❋ ✽ ❖ ❋ ✽ ✺ ✽ P ❃ ✹ ❍ ✺ ❯ ❋ ✼ ❯ ● ✺ ❯ ❯ ❘ ✼ ✽ P ❅ ✺ ❖ ❇ ❯ ✼ ✹ ❋ ❃ ✽ ❃ ❄✺ ✽ P ❃ ✹ ❍ ✺ ❯ ❋ ✼ ❯ ❚ ✼ ❅ ❅ ❋ ✺ ❅ ❄ ❇ ✽ ● ✹ ❋ ❃ ✽ ❀ ❻ s ❵ ❼ ✈ ✇ ① ❴ ② ❨ q ❴ r r ✉ s ✈ r ❀ ✾ ✩ ✪ ✪ ✩ ✾ ❛ ❛ ❸ ❞ ✵ ❢ ✾❡ ❹ ✶ ✐ ❡ ❡ ✵ ❀✴ ✵ ❽ ✷ ❾ ❅ ✺ P ✺ ❘ ● ❇ ✾ ⑥ ❀ ❁ ❾ ✼ ❯ ✼ P ✺ ✾ ❿ ❀ ❏ ❀ ❾ ❯ ✼ ❘ ▼ ✼ ❯ ✺ ▼ ▼ ✼ ❯ ♣ ✺ ❘ ❋ ● ❯ ✺ ❘ ❅ ✺ ✻ ❅ ✺ ❘ ✺ ✽ ✹ ✹ ❍ ✺❯ ✼ ❅ ❖ ✺ ✻ ❃ ❅ ✺ ❘ ❱ ❘ ✹ ✺ ▼ ❃ ❄ ● ❃ ✽ ✹ ❋ ✽ ❇ ❃ ❇ ❘ ▼ ❋ ● ❅ ❃ ♣ ✼ ❘ ● ❇ ❯ ✼ ❅ ✺ ✽ P ❃ ✹ ❍ ✺ ❯ ❋ ❇ ▼ ❀ ➀ ➁ ➂❳ ❨ ➃ ① ➄ ❵ s ✈ r ❨ ✾ ✫ ✳ ✳ ➅ ✾ ➆ ❜ ❝ ❞ ✵ ❾ ✹ ✵ ❢ ✾ ❂ ⑤ ✵ ✶ ✐ ⑤ ❣ ❣ ❀✴ ❣ ❹ ✷ ♠ ✼ P ❋ ✽ ✾ ✿ ❀ ➇ ❀ ❁ ➈ ❅ ❋ ❍ ❇ ✺ ❯ ✼ ✾ ♦ ❀ ✿ ❀ ❁ ■ ❇ ❅ ✹ ❋ ✾ ❿ ❀ ❁ ❿ ❇ ❖ ❯ ❋ ✺ ❯ ▼ ❃ ✾ ♦ ❀ ❁ ■ ❇ ❅ ❅ ✼ ❱ ✾ ❾ ❀✿ ❀ ❁ ❊ ❇ ❃ ▼ ✼ ✽ ✺ ✽ ✾ ❏ ❀ ➉ ❀ ❚ ✺ ✹ ✼ ✐ ◗ ❅ ❅ ✺ ❘ ✹ ❋ ✽ ❡ ✻ ✼ ❅ ✹ ❋ ● ❋ ✻ ✼ ✹ ✺ ❘ ❋ ✽ ✻ ❯ ✼ ✹ ✺ ❯ ✺ ✹ ✐✼ ● ✹ ❋ ♣ ✼ ✹ ❋ ✽ ❖ ❄ ✼ ● ✹ ❃ ❅ ❅ ✺ ● ✺ ✻ ✹ ❃ ❅ ✐ ▼ ✺ P ❋ ✼ ✹ ✺ P ✺ ✽ P ❃ ● ❱ ✹ ❃ ❘ ❋ ❘ ❃ ❄ ✸ ✹ ❅ ✺ ✻ ✹ ❃ ● ❃ ● ● ❇ ❘✻ ✽ ✺ ❇ ▼ ❃ ✽ ❋ ✼ ✺ ❀ ➊ t ➋ ❴ ✇ ❼ ❨ ➊ ② ② ❬ t ❀ ✾ ✩ ✪ ✪ ➌ ✾ ❸ ➍ ❞ ❡ ✵ ❢ ✾ ⑤ ④ ✵ ⑤ ✐ ⑤ ④ ❣ ✶ ❀✴ ❣ ❡ ✷ ⑥ ❇ ✻ ❅ ✺ ✾ ⑥ ❀ ✿ ❀ ❁ ♦ ❍ ✺ ✽ ✾ ➎ ❀ ❁ ➏ ✺ ❿ ❃ ❇ ❋ ❯ ❯ ✾ ♦ ❀ ❁ ❊ ❍ ✺ ❅ ❋ ✼ ❇ ❯ ✹ ✾ ♦ ❀ ❁ ❾ ✼ ❅ ✺ ✽ ✹ ✾ ✿ ❀ ➏ ❀ ❁♠ ❃ ❯ ✼ ✐ ❾ ❯ ✺ ❘ ▲ ● ▲ ❱ ✽ ❘ ❈ ❋ ✾ ■ ❀ ❁ ✸ ✹ ✼ ✽ ❈ ❃ ♣ ✼ ✾ ✿ ❀ ❊ ❅ ✼ ❄ ❄ ❋ ● ❈ ❋ ✽ ❖ ✾ ❇ ❚ ❋ ➐ ❇ ❋ ✹ ❋ ✽ ✼ ✹ ❋ ❃ ✽ ✾✼ ✽ P P ❃ ♥ ✽ ✐ ❅ ✺ ❖ ❇ ❯ ✼ ✹ ❋ ❃ ✽ ❃ ❄ ✹ ❍ ✺ ❍ ❇ ▼ ✼ ✽ ✻ ❯ ✼ ✹ ✺ ❯ ✺ ✹ ✐ ✼ ● ✹ ❋ ♣ ✼ ✹ ❋ ✽ ❖ ❄ ✼ ● ✹ ❃ ❅❅ ✺ ● ✺ ✻ ✹ ❃ ❅ ❀ ❳ ❨ ✉ s ✈ r ❨ q ① ❴ ② ❀ ✾ ✩ ✪ ✪ ➅ ✾ ➆ ❸ ❷ ❞ ❥ ④ ❢ ✾ ❥ ④ ✵ ✵ ④ ✐ ❥ ④ ✵ ❣ ✶ ❀✴ ❣ ✵ ✷ ✸ ❋ ▼ ❋ ❃ ✽ ✺ ❘ ● ❇ ✾ ➇ ❀ ➉ ✽ ⑦ ◗ P ♣ ✼ ✽ ● ✺ ❘ ❋ ✽ ❋ ✽ ❄ ❯ ✼ ▼ ▼ ✼ ✹ ❋ ❃ ✽ ❅ ✺ ❘ ✺ ✼ ❅ ● ❍ ❁❑ ✺ ❋ ❘ ❘ ▼ ✼ ✽ ✾ ❿ ❀ ❁ ✸ ✼ ▼ ❇ ✺ ❯ ❘ ❘ ❃ ✽ ✾ ❉ ❀ ❁ ❾ ✼ ❃ ❯ ✺ ✹ ✹ ❋ ✾ ♠ ❀ ✾ ❏ P ❘ ❀ ♠ ✼ ♣ ✺ ✽ ⑦ ➇ ✺ ♥❦ ❃ ❅ ❈ ✾ ✫ ✳ ➑ ✳ ❁ ❺ ❃ ❯ ❀ ❡ ✾ ✻ ✻ ❤ ❡ ✐ ⑤ ❹ ❀✴ ❣ ❣ ✷ ❾ ❅ ✺ P ✺ ❘ ● ❇ ✾ ✸ ❀ ◗ ❀ ❁ ❾ ❅ ✺ P ✺ ❘ ● ❇ ✾ ⑥ ❀ ➇ ❀ ❁ ■ ✼ ❯ ❋ ❈ ✾ ◗ ❀ ❉ ❀ ■ ❃ ❯ ✺ ● ❇ ❯ ✼ ❅ P ✺ ✹ ✺ ❅ ▼ ❋ ✽ ✼ ✽ ✹ ❘❃ ❄ ✺ ✽ P ❃ ✹ ❍ ✺ ❯ ❋ ✼ ❯ ✹ ❅ ✼ ✽ ❘ ● ❱ ✹ ❃ ❘ ❋ ❘ ✼ ✽ P ✹ ❍ ✺ ❋ ❅ ❅ ❃ ❯ ✺ ❋ ✽ ✺ ✽ P ❃ ✹ ❍ ✺ ❯ ❋ ✼ ❯ ✻ ✺ ❅ ▼ ✺ ✼ ❚ ❋ ❯ ❋ ✹ ❱ ❀➀ ➁ ➂ ❳ ❨ ➃ ① ➄ ❵ s ✈ r ❨ ➒ ❬ t ❪ q ❴ r r ➓ ✈ r ❨ ➃ ① ➄ ❵ s ✈ r ❀ ✾ ✩ ✪ ✪ ➑ ✾ ➆ ➔ ➍ ❞ ❥ ❢ ✾ ➏ ④ ✵ ❣ ✐ ➏ ④ ❥ ✵ ❀✴ ❣ ❥ ✷ ■ ✼ ❙ ✽ ❃ ✾ ❿ ❀ ❁ ❾ ✼ ❯ ✼ P ✺ ✾ ❿ ❀ ❏ ❀ ✸ ✹ ❇ P ❋ ✺ ❘ ❃ ✽ ❋ ✽ ❄ ❯ ✼ ▼ ▼ ✼ ✹ ❋ ❃ ✽ ❀ ❡ ❀ ❊ ❍ ✺ ✺ ❄ ❄ ✺ ● ✹ ❃ ❄❍ ❋ ❘ ✹ ✼ ▼ ❋ ✽ ✺ ✼ ✽ P ❘ ✺ ❅ ❃ ✹ ❃ ✽ ❋ ✽ ❃ ✽ ♣ ✼ ❘ ● ❇ ❯ ✼ ❅ ✻ ✺ ❅ ▼ ✺ ✼ ❚ ❋ ❯ ❋ ✹ ❱ ⑦ ✼ ✽ ✺ ❯ ✺ ● ✹ ❅ ❃ ✽▼ ❋ ● ❅ ❃ ❘ ● ❃ ✻ ❋ ● ❘ ✹ ❇ P ❱ ❀ ❳ ❨ ✉ s ✈ → ① ➄ ❵ ❨ ✉ s ✈ ✇ ① ❴ ② ❨ q ➄ ❼ ✈ r ❀ ✾ ✫ ✳ ➣ ✫ ✾ ❛ ❛ ✾ ✶ ⑤ ❡ ✐ ❤ ❹ ✶ ❀✴ ❣ ✶ ✷ ■ ❋ ● ❍ ✺ ❯ ✾ ♦ ❀ ♦ ❀ ❁ ♦ ❇ ❅ ❅ ❱ ✾ ❆ ❀ ❏ ❀ ■ ❋ ● ❅ ❃ ♣ ✼ ❘ ● ❇ ❯ ✼ ❅ ✻ ✺ ❅ ▼ ✺ ✼ ❚ ❋ ❯ ❋ ✹ ❱ ❀ ➃ ① ➄ ❵ s ✈ r ❨❫ ❴ ❶ ❀ ✾ ✫ ✳ ✳ ✳ ✾ ❸ ➔ ❞ ❣ ❢ ✾ ⑤ ❹ ❣ ✐ ⑤ ❤ ❡ ❀✴ ❣ ❤ ✷ ❧ ❃ ▼ ✼ ❅ ❃ ♣ ✼ ✾ ❦ ❀ ❁ ■ ✼ ❯ ❋ ❈ ✾ ◗ ❀ ❉ ❀ ♠ ✺ ❖ ❇ ❯ ✼ ✹ ❋ ❃ ✽ ❃ ❄ ✺ ✽ P ❃ ✹ ❍ ✺ ❯ ❋ ✼ ❯✻ ✺ ❅ ▼ ✺ ✼ ❚ ❋ ❯ ❋ ✹ ❱ ♣ ❋ ✼ ✻ ✼ ❅ ✼ ● ✺ ❯ ❯ ❇ ❯ ✼ ❅ ✼ ✽ P ✹ ❅ ✼ ✽ ❘ ● ✺ ❯ ❯ ❇ ❯ ✼ ❅ ✹ ❅ ✼ ✽ ❘ ✻ ❃ ❅ ✹ ✻ ✼ ✹ ❍ ♥ ✼ ❱ ❘ ❀↔ t t ❬ ❨ ❫ ❴ ❶ ❨ ➃ ① ➄ ❵ s ✈ r ❀ ✾ ✩ ✪ ✫ ✪ ✾ ❸ ➆ ✾ ❥ ❤ ❣ ✐ ❥ ❽ ❣ ❀✴ ❣ ⑤ ✷ ❆ ❅ ❃ ▼ ▼ ✾ ■ ❀ ❆ ❀ ➉ ▼ ✻ ❃ ❅ ✹ ✼ ✽ ● ✺ ❃ ❄ ❾ ✐ ❖ ❯ ❱ ● ❃ ✻ ❅ ❃ ✹ ✺ ❋ ✽ ✼ ✹ ❚ ❯ ❃ ❃ P ✐ ✹ ❋ ❘ ❘ ❇ ✺❚ ✼ ❅ ❅ ❋ ✺ ❅ ❘ ❀ ↕ ⑨ ❴ t ⑩ ❵ ➃ ① ⑧ ⑨ ② ⑧ ✇ ✈ r ❨ ➙ ✇ s ❀ ✾ ✩ ✪ ✪ ✬ ✾ ➆ ❝ ❞ ④ ❢ ✾ ❥ ✵ ❣ ✐ ❥ ✵ ❽ ❀✴ ❣ ④ ✷ P ✺ ➏ ✼ ✽ ❖ ✺ ✾ ❏ ❀ ♦ ❀ ■ ❀ ❾ ❃ ✹ ✺ ✽ ✹ ❋ ✼ ❯ ❅ ❃ ❯ ✺ ❃ ❄ ◗ ❉ ♦ ✹ ❅ ✼ ✽ ❘ ✻ ❃ ❅ ✹ ✺ ❅ ❘ ✼ ❘ ✼P ✺ ✹ ❃ ❲ ❋ ❄ ❋ ● ✼ ✹ ❋ ❃ ✽ ❘ ❱ ❘ ✹ ✺ ▼ ✼ ✹ ✹ ❍ ✺ ❚ ❯ ❃ ❃ P ✐ ♦ ✸ ❆ ❚ ✼ ❅ ❅ ❋ ✺ ❅ ❀ ➀ ➛ ➜ ➂ ➝ ⑨ ❬ ❪➝ ❴ r s ❶ ❴ ⑨ ➄ ❫ ❴ ❶ ❀ ✾ ✩ ✪ ✪ ✬ ✾ ❝ ❜ ❞ ❡ ✵ ❢ ✾ ❡ ⑤ ❽ ❣ ✐ ❡ ④ ❹ ❽ ❀✴ ❣ ❽ ✷ P ✺ ❉ ❃ ✺ ❅ ✾ ◗ ❀ ❿ ❀ ❁ ❿ ✼ ❋ ❯ ❯ ✼ ❅ P ✾ ❾ ❀ ✿ ❀ ⑥ ❅ ❇ ❖ ✹ ✼ ❅ ❖ ✺ ✹ ❋ ✽ ❖ ✹ ❃ ✹ ❍ ✺ ❚ ❅ ✼ ❋ ✽ ❀ ↔ t t ❬ ❨❫ ❴ ❶ ❨ ➃ ① ⑧ ⑨ ② ⑧ ✇ ✈ r ❨ ↕ ✈ ➞ s ✇ ✈ r ❨ ✾ ✩ ✪ ✪ ➑ ✾ ③ ❸ ✾ ❣ ✵ ❣ ✐ ❣ ✶ ✶ ❀✴ ❥ ❹ ✷ ❾ ✼ ❅ P ❅ ❋ P ❖ ✺ ✾ ❑ ❀ ■ ❀ ❉ ❯ ❃ ❃ P ✐ ❚ ❅ ✼ ❋ ✽ ❚ ✼ ❅ ❅ ❋ ✺ ❅ P ✺ ❯ ❋ ♣ ✺ ❅ ❱ ❀ ➝ ⑨ ❬ ❪ ➝ s ❵ ✇ ✈ ❶ ❨↕ ✈ ⑩ ⑧ ➄ ✾ ✩ ✪ ✪ ➑ ✾ ❛ ➆ ❞ ❡ ✐ ✵ ❢ ✾ ✶ ❥ ✐ ❤ ❡ ❀✴ ❥ ❡ ✷ ⑥ ✺ ❯ ❋ ✾ ■ ❀ ◗ ❀ ➉ ✽ ⑦ ⑥ ✺ ❯ ❋ ♣ ✺ ❅ ❱ ✼ ✽ P ➟ ➠ ➡ ➢ ❾ ❅ ❃ ❚ ❯ ✺ ▼ ❘ ❃ ❄ ⑥ ❅ ❇ ❖ ❘ ✼ ✽ P⑥ ❅ ❇ ❖ ✐ ♦ ✼ ✽ P ❋ P ✼ ✹ ✺ ❘ ❁ ❧ ✼ ❅ ❃ ❯ ❱ ✾ ❊ ❀ ❁ ■ ❃ ✽ ❋ ❈ ✼ ✾ ❺ ❀ ✾ ❏ P ❘ ❀ ❉ ✺ ✽ ✹ ❍ ✼ ▼ ✸ ● ❋ ✺ ✽ ● ✺❾ ❇ ❚ ❯ ❋ ❘ ❍ ✺ ❅ ❘ ⑦ ✩ ✪ ✫ ✫ ❀✴ ❥ ✵ ✷ ❉ ✼ ✽ ❈ ❘ ✾ ❑ ❀ ◗ ❀ ⑥ ✺ ❯ ❋ ♣ ✺ ❅ ❱ ❃ ❄ ✻ ✺ ✻ ✹ ❋ P ✺ ❘ ✹ ❃ ✹ ❍ ✺ ❚ ❅ ✼ ❋ ✽ ⑦ ✺ ▼ ✻ ❍ ✼ ❘ ❋ ❘ ❃ ✽✹ ❍ ✺ ❅ ✼ ✻ ✺ ❇ ✹ ❋ ● P ✺ ♣ ✺ ❯ ❃ ✻ ▼ ✺ ✽ ✹ ❀ ✉ s ✈ → ✈ r ➄ ② ❴ ⑨ ❵ ✾ ✩ ✪ ✪ ➤ ✾ ➔ ➥ ❞ ✶ ❢ ✾ ✶ ④ ❽ ✐ ✶ ❽ ❥ ❀✴ ❥ ❣ ✷ ❧ ❋ ▼ ✾ ♠ ❀ ❉ ❀ ❁ ❆ ❅ ❃ ▼ ▼ ✾ ■ ❀ ❆ ❀ ❁ ❑ ✼ ✽ P ✺ ❯ ✾ ♦ ❀ ❁ ➏ ✺ ✼ ❈ ✺ ✾ ❉ ❀ ❁ ❑ ❃ ❃ P ✾ ◗ ❀ ✿ ❀ ❁♠ ❃ P ✺ ✽ ✾ ⑥ ❀ ■ ❀ ❁ ❑ ❋ ❯ ❈ ❋ ✽ ❘ ❃ ✽ ✾ ❿ ❀ ♠ ❀ ❊ ❍ ✺ P ❅ ❇ ❖ ✹ ❅ ✼ ✽ ❘ ✻ ❃ ❅ ✹ ✺ ❅ ❾ ✐❖ ❯ ❱ ● ❃ ✻ ❅ ❃ ✹ ✺ ❋ ✽ ❯ ❋ ▼ ❋ ✹ ❘ ❃ ❅ ✼ ❯ ✼ ❚ ❘ ❃ ❅ ✻ ✹ ❋ ❃ ✽ ✼ ✽ P ❚ ❅ ✼ ❋ ✽ ✺ ✽ ✹ ❅ ❱ ❃ ❄ ❂ ➉ ❺ ✐ ❡✻ ❅ ❃ ✹ ✺ ✼ ❘ ✺ ❋ ✽ ❍ ❋ ❚ ❋ ✹ ❃ ❅ ❘ ❀ ❳ ❨ q r s t ❨ ➊ t ❶ ❴ ❵ ❼ ❀ ✾ ✫ ✳ ✳ ➤ ✾ ❛ ➥ ❛ ❞ ✵ ❢ ✾ ✵ ④ ❽ ✐ ✵ ❽ ❥ ❀✴ ❥ ❥ ✷ ✸ ● ❍ ❋ ✽ ❈ ✺ ❯ ✾ ◗ ❀ ❂ ❀ ❁ ❑ ✼ ❖ ✺ ✽ ✼ ✼ ❅ ✾ ❏ ❀ ❁ ■ ❃ ❯ ✾ ♦ ❀ ◗ ❀ ❁ ♣ ✼ ✽ ⑥ ✺ ✺ ▼ ✹ ✺ ❅ ✾ ➏ ❀ ❾ ✐❖ ❯ ❱ ● ❃ ✻ ❅ ❃ ✹ ✺ ❋ ✽ ❋ ✽ ✹ ❍ ✺ ❚ ❯ ❃ ❃ P ✐ ❚ ❅ ✼ ❋ ✽ ❚ ✼ ❅ ❅ ❋ ✺ ❅ ❃ ❄ ▼ ❋ ● ✺ ❋ ✽ ❄ ❯ ❇ ✺ ✽ ● ✺ ❘ ✹ ❍ ✺❚ ❅ ✼ ❋ ✽ ✻ ✺ ✽ ✺ ✹ ❅ ✼ ✹ ❋ ❃ ✽ ✼ ✽ P ✻ ❍ ✼ ❅ ▼ ✼ ● ❃ ❯ ❃ ❖ ❋ ● ✼ ❯ ✼ ● ✹ ❋ ♣ ❋ ✹ ❱ ❃ ❄ ▼ ✼ ✽ ❱ P ❅ ❇ ❖ ❘ ❀ ❳ ❨q r s t ❨ ➊ t ❶ ❴ ❵ ❼ ❀ ✾ ✫ ✳ ✳ ➣ ✾ ➔ ❸ ❞ ❡ ❡ ❢ ✾ ✵ ✶ ❡ ⑤ ✐ ✵ ✶ ✵ ❥ ❀✴ ❥ ✶ ✷ ❾ ✼ ❅ P ❅ ❋ P ❖ ✺ ✾ ❑ ❀ ■ ❀ ❑ ❍ ❱ ❋ ❘ ✹ ❍ ✺ ❖ ❯ ❃ ❚ ✼ ❯ ♦ ➇ ✸ ✻ ❍ ✼ ❅ ▼ ✼ ● ✺ ❇ ✹ ❋ ● ✼ ❯ ▼ ✼ ❅ ❈ ✺ ✹❘ ❃ ❇ ✽ P ✺ ❅ ✐ ✻ ✺ ✽ ✺ ✹ ❅ ✼ ✹ ✺ P ➦ ➝ ⑨ ❬ ❪ ➝ s ❵ ✇ ✈ ❶ ❨ ↕ ✈ ⑩ ⑧ ➄ ✾ ✩ ✪ ✪ ✩ ✾ ❸ ❞ ❡ ❢ ✾ ✶ ✐ ⑤ ❀✴ ❥ ❤ ✷ ❉ ✺ ✹ ▲ ✾ ◗ ❀ ➏ ❀ ❁ ❿ ❃ ❯ P ❘ ✹ ✺ ❋ ✽ ✾ ❿ ❀ ❑ ❀ ✸ ✻ ✺ ● ❋ ✼ ❯ ❋ ▲ ✺ P ✻ ❅ ❃ ✻ ✺ ❅ ✹ ❋ ✺ ❘ ✼ ✽ P ❘ ❃ ❯ ❇ ✹ ✺✹ ❅ ✼ ✽ ❘ ✻ ❃ ❅ ✹ ❋ ✽ ❚ ❅ ✼ ❋ ✽ ● ✼ ✻ ❋ ❯ ❯ ✼ ❅ ❋ ✺ ❘ ❀ ↔ t t ❬ ❨ ❫ ❴ ❶ ❨ ➃ ① ➄ ❵ s ✈ r ❀ ✾ ✫ ✳ ➤ ➣ ✾ ③ ❷ ✾ ✵ ❥ ❡ ✐✵ ✶ ❹ ❀✴ ❥ ⑤ ✷ ❾ ✺ ❅ ❘ ❋ P ❘ ❈ ❱ ✾ ❦ ❀ ❁ ♠ ✼ ▼ ❋ ❅ ✺ ▲ ✾ ✸ ❀ ❂ ❀ ❁ ❂ ✼ ❃ ❅ ✼ ❍ ✾ ✿ ❀ ❁ ❧ ✼ ✽ ▼ ❃ ❖ ✽ ✺ ✾ ❿ ❀ ⑥ ❀❉ ❯ ❃ ❃ P ✐ ❚ ❅ ✼ ❋ ✽ ❚ ✼ ❅ ❅ ❋ ✺ ❅ ⑦ ❘ ✹ ❅ ❇ ● ✹ ❇ ❅ ✼ ❯ ● ❃ ▼ ✻ ❃ ✽ ✺ ✽ ✹ ❘ ✼ ✽ P ❄ ❇ ✽ ● ✹ ❋ ❃ ✽ ❇ ✽ P ✺ ❅✻ ❍ ❱ ❘ ❋ ❃ ❯ ❃ ❖ ❋ ● ✼ ✽ P ✻ ✼ ✹ ❍ ❃ ❯ ❃ ❖ ❋ ● ● ❃ ✽ P ❋ ✹ ❋ ❃ ✽ ❘ ❀ ❳ ❨ ➧ ❴ ❬ ⑨ ✈ s ② ② ❬ t ❴ ➃ ① ⑧ ⑨ ② ⑧ ✇ ✈ r ❨ ✾✩ ✪ ✪ ➣ ✾ ❛ ❞ ❣ ❢ ✾ ✵ ✵ ❣ ✐ ✵ ❣ ❤ ❀✴ ❥ ④ ✷ ♠ ❋ ❚ ✺ ❋ ❅ ❃ ✾ ■ ❀ ■ ❀ ❁ ♦ ✼ ❘ ✹ ✼ ✽ ❍ ❃ ✾ ■ ❀ ◗ ❀ ❁ ✸ ✺ ❅ ❅ ✼ ✽ ❃ ✾ ➉ ❀ ➊ t ❶ s ❼ ⑨ ✈ ❚ ❯ ❃ ❃ P ✐ ❚ ❅ ✼ ❋ ✽❚ ✼ ❅ ❅ ❋ ✺ ❅ ▼ ❃ P ✺ ❯ ❘ ✐ ✐ ❯ ✼ ✹ ✺ ❘ ✹ ✼ P ♣ ✼ ✽ ● ✺ ❘ ✼ ✽ P ✹ ❍ ✺ ❅ ✼ ✻ ✺ ❇ ✹ ❋ ● ✼ ✻ ✻ ❯ ❋ ● ✼ ✹ ❋ ❃ ✽ ❘ ❋ ✽ ✼

● ❍ ❅ ❃ ✽ ❃ ❯ ❃ ❖ ❋ ● ✼ ❯ ✻ ✺ ❅ ❘ ✻ ✺ ● ✹ ❋ ♣ ✺ ❀ ➓ s t s ❫ ❴ ❶ ❨ ➓ ❴ ⑩ ❨ q ① ❴ ② ❀ ✾ ✩ ✪ ✫ ✪ ✾ ❛ ➥ ❞ ❣ ❢ ✾✵ ❤ ✵ ✐ ✵ ⑤ ❹ ❀✴ ❥ ❽ ✷ ❂ ✼ ♥ ❈ ❋ ✽ ❘ ✾ ❉ ❀ ❊ ❀ ❁ ⑥ ✼ ♣ ❋ ❘ ✾ ❊ ❀ ❾ ❀ ❊ ❍ ✺ ❚ ❯ ❃ ❃ P ✐ ❚ ❅ ✼ ❋ ✽ ❚ ✼ ❅ ❅ ❋ ✺ ❅ ➨ ✽ ✺ ❇ ❅ ❃ ♣ ✼ ❘ ● ❇ ❯ ✼ ❅❇ ✽ ❋ ✹ ❋ ✽ ❍ ✺ ✼ ❯ ✹ ❍ ✼ ✽ P P ❋ ❘ ✺ ✼ ❘ ✺ ❀ ➃ ① ⑧ ⑨ ② ⑧ ✇ ✈ r ❨ ❫ ❴ ❶ ❀ ✾ ✩ ✪ ✪ ➌ ✾ ❝ ❸ ❞ ✵ ❢ ✾ ❡ ⑤ ❣ ✐ ❡ ④ ✶ ❀✴ ✶ ❹ ✷ ♠ ✺ P ▲ ❋ ● ✾ ➎ ❀ ■ ❃ ❯ ✺ ● ❇ ❯ ✼ ❅ ❚ ❋ ❃ ❯ ❃ ❖ ❱ ❃ ❄ ✹ ❍ ✺ ❚ ❯ ❃ ❃ P ✐ ❚ ❅ ✼ ❋ ✽ ✼ ✽ P ✹ ❍ ✺ ❚ ❯ ❃ ❃ P ✐● ✺ ❅ ✺ ❚ ❅ ❃ ❘ ✻ ❋ ✽ ✼ ❯ ❄ ❯ ❇ ❋ P ❚ ✼ ❅ ❅ ❋ ✺ ❅ ❘ ⑦ ❘ ❋ ▼ ❋ ❯ ✼ ❅ ❋ ✹ ❋ ✺ ❘ ✼ ✽ P P ❋ ❄ ❄ ✺ ❅ ✺ ✽ ● ✺ ❘ ❀ ➩ r ❬ s ⑩ ❵✉ ⑧ ⑨ ⑨ s ❴ ⑨ ❵ q ➧ ➙ ✾ ✩ ✪ ✫ ✫ ✾ ❷ ❞ ❡ ❢ ✾ ❣ ❀✴ ✶ ❡ ✷ ✸ ✹ ❅ ✼ ▲ ❋ ✺ ❯ ❯ ✺ ✾ ➇ ❀ ❁ ❿ ❍ ✺ ❅ ❘ ❋ ✐ ❏ ❖ ✺ ✼ ✾ ✿ ❀ ❆ ❀ ⑥ ✺ ▼ ❃ ✽ ❘ ✹ ❅ ✼ ✹ ❋ ❃ ✽ ❃ ❄ ✼ ● ❃ ❇ ✻ ❯ ✺ P▼ ✺ ✹ ✼ ❚ ❃ ❯ ❋ ❘ ▼ ✐ ✺ ❄ ❄ ❯ ❇ ❲ ✻ ❅ ❃ ● ✺ ❘ ❘ ✼ ✹ ✹ ❍ ✺ ● ❍ ❃ ❅ ❃ ❋ P ✻ ❯ ✺ ❲ ❇ ❘ ✼ ❘ ✼ ▼ ✺ ● ❍ ✼ ✽ ❋ ❘ ▼❃ ❄ ❚ ❅ ✼ ❋ ✽ ✻ ❅ ❃ ✹ ✺ ● ✹ ❋ ❃ ✽ ✹ ❃ ♥ ✼ ❅ P ❲ ✺ ✽ ❃ ❚ ❋ ❃ ✹ ❋ ● ❘ ❀ ❳ ❨ ➧ ❴ ❬ ⑨ ✈ ❵ ✇ s ❀ ✾ ✫ ✳ ✳ ✳ ✾ ❛ ➔ ❞ ❡ ✶ ❢ ✾❤ ✵ ⑤ ✶ ✐ ❤ ✵ ④ ❽ ❀✴ ✶ ✵ ✷ ✸ ✹ ❅ ✼ ▲ ❋ ✺ ❯ ❯ ✺ ✾ ➇ ❀ ❁ ❿ ❍ ✺ ❅ ❘ ❋ ✐ ❏ ❖ ✺ ✼ ✾ ✿ ❀ ❆ ❀ ♦ ❍ ❃ ❅ ❃ ❋ P ✻ ❯ ✺ ❲ ❇ ❘ ❋ ✽ ✹ ❍ ✺ ● ✺ ✽ ✹ ❅ ✼ ❯✽ ✺ ❅ ♣ ❃ ❇ ❘ ❘ ❱ ❘ ✹ ✺ ▼ ⑦ ❉ ❋ ❃ ❯ ❃ ❖ ❱ ✼ ✽ P ✻ ❍ ❱ ❘ ❋ ❃ ✻ ✼ ✹ ❍ ❃ ❯ ❃ ❖ ❱ ❀ ❳ ❨ ➧ ❴ ❬ ⑨ ✈ → ⑧ ❼ ① ✈ r ❀➫ ➞ → ❨ ➧ ❴ ❬ ⑨ ✈ r ❀ ✾ ✩ ✪ ✪ ✪ ✾ ❝ ➔ ❞ ⑤ ❢ ✾ ✶ ❤ ❡ ✐ ✶ ⑤ ❥ ❀✴ ✶ ❣ ✷ ❾ ✼ ✻ ✼ ❯ ❋ ✼ ❖ ❈ ✼ ❘ ✾ ❺ ❀ ❊ ❀ ❊ ❍ ✺ ♠ ❃ ❯ ✺ ❃ ❄ ♦ ✺ ❅ ✺ ❚ ❅ ❃ ❘ ✻ ❋ ✽ ✼ ❯ ❆ ❯ ❇ ❋ P ❉ ❋ ❃ ▼ ✼ ❅ ❈ ✺ ❅ ❘❄ ❃ ❅ ◗ ❯ ▲ ❍ ✺ ❋ ▼ ✺ ❅ ➭ ❘ ⑥ ❋ ❘ ✺ ✼ ❘ ✺ ⑥ ❋ ✼ ❖ ✽ ❃ ❘ ❋ ❘ ❀ ❑ ❍ ✺ ❅ ✺ ✼ ❅ ✺ ♥ ✺ ➇ ❃ ♥ ➦ ❫ ❴ ✇ ❴ t ❼➃ ⑧ ❼ ❨ q ➧ ➙ ➝ ⑨ ❬ ❪ ➝ s ❵ ✇ ✈ ❶ ❀ ✾ ✩ ✪ ✫ ➅ ✾ ❷ ❞ ❡ ❢ ✾ ⑤ ❹ ✐ ⑤ ④ ❀✴ ✶ ❥ ✷ ❾ ✼ ❅ ✽ ✺ ✹ ✹ ❋ ✾ ➏ ❀ ❁ ♦ ✼ ❘ ✹ ❅ ❋ ❃ ✹ ❃ ✾ ◗ ❀ ❁ ♦ ❍ ❋ ✼ ❘ ❘ ✺ ❅ ❋ ✽ ❋ ✾ ⑥ ❀ ❁ ❾ ✺ ❅ ❘ ❋ ● ❍ ✺ ✹ ✹ ❋ ✾ ❏ ❀ ❁❊ ✼ ▼ ❚ ✼ ❘ ● ❃ ✾ ➇ ❀ ❁ ❏ ❯ ✐ ◗ ❖ ✽ ✼ ❄ ✾ ➈ ❀ ❁ ♦ ✼ ❯ ✼ ❚ ❅ ✺ ❘ ❋ ✾ ❾ ❀ ♦ ✺ ❅ ✺ ❚ ❅ ❃ ❘ ✻ ❋ ✽ ✼ ❯ ❄ ❯ ❇ ❋ P❚ ❋ ❃ ▼ ✼ ❅ ❈ ✺ ❅ ❘ ❋ ✽ ❾ ✼ ❅ ❈ ❋ ✽ ❘ ❃ ✽ P ❋ ❘ ✺ ✼ ❘ ✺ ❀ ➧ ⑧ ❼ ❨ ❫ ❴ ❶ ❨ ➧ ❴ ❬ ⑨ ✈ r ❀ ✾ ✩ ✪ ✫ ➅ ✾ ➔ ❞ ❣ ❢ ✾❡ ❣ ❡ ✐ ❡ ❥ ❹ ❀✴ ✶ ✶ ✷ ✸ ❍ ✺ ❋ ✽ ✺ ❅ ▼ ✼ ✽ ✾ ❧ ❀ ✸ ❀ ❁ ◆ ▼ ✼ ✽ ❘ ❈ ❱ ✾ ✸ ❀ ♠ ❀ ♦ ❋ ❅ ● ❇ ❯ ✼ ✹ ❋ ✽ ❖ ● ✺ ❯ ❯ ✐ ❄ ❅ ✺ ✺ ▼ ❋ ● ❅ ❃ ♠ ➇ ◗✼ ❘ ❚ ❋ ❃ ▼ ✼ ❅ ❈ ✺ ❅ ❘ ❄ ❃ ❅ ❘ ● ❅ ✺ ✺ ✽ ❋ ✽ ❖ ✾ P ❋ ✼ ❖ ✽ ❃ ❘ ❋ ❘ ✼ ✽ P ▼ ❃ ✽ ❋ ✹ ❃ ❅ ❋ ✽ ❖ ❃ ❄✽ ✺ ❇ ❅ ❃ P ✺ ❖ ✺ ✽ ✺ ❅ ✼ ✹ ❋ ♣ ✺ P ❋ ❘ ✺ ✼ ❘ ✺ ❘ ✼ ✽ P ❃ ✹ ❍ ✺ ❅ ✽ ✺ ❇ ❅ ❃ ❯ ❃ ❖ ❋ ● ✻ ✼ ✹ ❍ ❃ ❯ ❃ ❖ ❋ ✺ ❘ ❀➩ ⑨ ✈ t ❼ ❨ q ❴ r r ➧ ❴ ❬ ⑨ ✈ ❵ ✇ s ❀ ✾ ✩ ✪ ✫ ➅ ✾ ❸ ✾ ❡ ✶ ❹ ❀✴ ✶ ❤ ✷ ♦ ❃ ✽ ❘ ✹ ✼ ✽ ✹ ❋ ✽ ✺ ❘ ● ❇ ✾ ♠ ❀ ❁ ■ ❃ ✽ P ✺ ❯ ❯ ❃ ✾ ✸ ❀ ♦ ✺ ❅ ✺ ❚ ❅ ❃ ❘ ✻ ❋ ✽ ✼ ❯ ❄ ❯ ❇ ❋ P ❚ ❋ ❃ ▼ ✼ ❅ ❈ ✺ ❅● ✼ ✽ P ❋ P ✼ ✹ ✺ ❘ ❄ ❃ ❅ ✻ ✼ ❅ ❈ ❋ ✽ ❘ ❃ ✽ ❋ ✼ ✽ P ❋ ❘ ❃ ❅ P ✺ ❅ ❘ ❀ ➩ ⑨ ✈ t ❼ ❨ ➧ ❴ ❬ ⑨ ✈ r ❀ ✾ ✩ ✪ ✫ ➅ ✾ ➍ ✾❡ ④ ⑤ ❀✴ ✶ ⑤ ✷ ❊ ❃ ▼ ❋ ✾ ■ ❀ ❁ ➇ ❋ ❘ ❍ ❋ ▼ ❇ ❅ ✼ ✾ ❊ ❀ ❁ ➇ ✼ ❈ ✼ ❘ ❍ ❋ ▼ ✼ ✾ ❏ ❀ ■ ❃ ✹ ❍ ✺ ❅ ✐ ✹ ❃ ✐ ❄ ✺ ✹ ❇ ❘ ✹ ❅ ✼ ✽ ❘ ❄ ✺ ❅❃ ❄ ✼ ✽ ✹ ❋ ♣ ❋ ❅ ✼ ❯ P ❅ ❇ ❖ ❘ ✼ ✽ P ✹ ❍ ✺ ❋ ✽ ♣ ❃ ❯ ♣ ✺ ▼ ✺ ✽ ✹ ❃ ❄ ✹ ❅ ✼ ✽ ❘ ✻ ❃ ❅ ✹ ✺ ❅ ❘ ✼ ✹ ✹ ❍ ✺✻ ❯ ✼ ● ✺ ✽ ✹ ✼ ❯ ❚ ✼ ❅ ❅ ❋ ✺ ❅ ❀ ❳ ❨ ➃ ① ⑧ ⑨ ② ❨ ➙ ✇ s ❨ ✾ ✩ ✪ ✫ ✫ ✾ ❛ ➥ ➥ ❞ ❽ ❢ ✾ ❣ ⑤ ❹ ④ ✐ ❣ ⑤ ❡ ④ ❀✴ ✶ ④ ✷ ❏ ♣ ❘ ✺ ✺ ✽ ❈ ❃ ✾ ⑥ ❀ ❁ ❾ ✼ ❲ ✹ ❃ ✽ ✾ ✿ ❀ ❑ ❀ ❁ ❧ ✺ ✺ ❯ ✼ ✽ ✾ ✿ ❀ ◗ ❀ ◗ ● ✹ ❋ ♣ ✺ ✹ ❅ ✼ ✽ ❘ ✻ ❃ ❅ ✹ ✼ ● ❅ ❃ ❘ ❘✹ ❍ ✺ ❍ ❇ ▼ ✼ ✽ ✻ ❯ ✼ ● ✺ ✽ ✹ ✼ ⑦ ❋ ▼ ✻ ✼ ● ✹ ❃ ✽ P ❅ ❇ ❖ ✺ ❄ ❄ ❋ ● ✼ ● ❱ ✼ ✽ P ✹ ❃ ❲ ❋ ● ❋ ✹ ❱ ❀ ➫ ➞ → ❴ ⑨ ❼➯ → s t ❨ ➝ ⑨ ❬ ❪ ➓ ❴ ❼ ⑧ ➲ ❨ ↕ ✈ ➞ s ✇ ✈ r ❀ ✾ ✩ ✪ ✪ ➣ ✾ ➆ ❞ ❡ ❢ ✾ ✶ ❡ ✐ ❤ ❽ ❀✴ ✶ ❽ ✷ ✸ ❱ ▼ ✺ ✾ ■ ❀ ♠ ❀ ❁ ❾ ✼ ❲ ✹ ❃ ✽ ✾ ✿ ❀ ❑ ❀ ❁ ❧ ✺ ✺ ❯ ✼ ✽ ✾ ✿ ❀ ◗ ❀ ⑥ ❅ ❇ ❖ ✹ ❅ ✼ ✽ ❘ ❄ ✺ ❅ ✼ ✽ P▼ ✺ ✹ ✼ ❚ ❃ ❯ ❋ ❘ ▼ ❚ ❱ ✹ ❍ ✺ ❍ ❇ ▼ ✼ ✽ ✻ ❯ ✼ ● ✺ ✽ ✹ ✼ ❀ q r s t ❨ ➃ ① ⑧ ⑨ ② ⑧ ✇ ✈ ➳ s t ❴ ❼ ❀ ✾ ✩ ✪ ✪ ✬ ✾③ ➍ ❞ ④ ❢ ✾ ❥ ④ ⑤ ✐ ✶ ❡ ❥ ❀✴ ❤ ❹ ✷ ❺ ✼ ❍ ✼ ❈ ✼ ✽ ❖ ✼ ❘ ✾ ❧ ❀ ❁ ■ ❱ ❯ ❯ ❱ ✽ ✺ ✽ ✾ ❾ ❀ ⑥ ❅ ❇ ❖ ✹ ❅ ✼ ✽ ❘ ✻ ❃ ❅ ✹ ✺ ❅ ❘ ❋ ✽ ✹ ❍ ✺ ❍ ❇ ▼ ✼ ✽❚ ❯ ❃ ❃ P ✐ ✻ ❯ ✼ ● ✺ ✽ ✹ ✼ ❯ ❚ ✼ ❅ ❅ ❋ ✺ ❅ ❀ ✉ ⑨ ❨ ❳ ❨ ➵ ① ➸ ❭ ➺ ➸ ✇ ✈ r ❀ ✾ ✩ ✪ ✪ ✳ ✾ ❛ ❝ ❷ ❞ ❣ ❢ ✾ ❤ ❤ ✶ ✐ ❤ ⑤ ④ ❀✴ ❤ ❡ ✷ ❏ ♣ ❘ ✺ ✺ ✽ ❈ ❃ ✾ ⑥ ❀ ◗ ❀ ❁ ❾ ✼ ❲ ✹ ❃ ✽ ✾ ✿ ❀ ❑ ❀ ❁ ❧ ✺ ✺ ❯ ✼ ✽ ✾ ✿ ❀ ◗ ❀ ➉ ✽ P ✺ ✻ ✺ ✽ P ✺ ✽ ✹❅ ✺ ❖ ❇ ❯ ✼ ✹ ❋ ❃ ✽ ❃ ❄ ✼ ✻ ❋ ● ✼ ❯ ✼ ✽ P ❚ ✼ ❘ ❃ ❯ ✼ ✹ ✺ ❅ ✼ ❯ P ❅ ❇ ❖ ✹ ❅ ✼ ✽ ❘ ✻ ❃ ❅ ✹ ✺ ❅ ✺ ❲ ✻ ❅ ✺ ❘ ❘ ❋ ❃ ✽✼ ✽ P ❄ ❇ ✽ ● ✹ ❋ ❃ ✽ ❋ ✽ ✻ ❯ ✼ ● ✺ ✽ ✹ ✼ ❯ ✹ ❅ ❃ ✻ ❍ ❃ ❚ ❯ ✼ ❘ ✹ ❘ ❚ ❱ ● ❱ ✹ ❃ ❈ ❋ ✽ ✺ ❘ ✾ ❘ ✹ ✺ ❅ ❃ ❋ P ❘ ✾ ✼ ✽ P❖ ❅ ❃ ♥ ✹ ❍ ❄ ✼ ● ✹ ❃ ❅ ❘ ❀ ➝ ❭ ❬ ❪ ➓ ❴ ❼ ⑧ ➲ ❨ ➝ s ❵ → ✈ ❵ ❀ ✾ ✩ ✪ ✪ ➑ ✾ ➍ ❝ ❞ ❥ ❢ ✾ ✶ ❽ ✶ ✐ ❤ ❹ ❡ ❀✴ ❤ ✵ ✷ ➇ ❋ ❘ ❍ ❋ ▼ ❇ ❅ ✼ ✾ ■ ❀ ❁ ➇ ✼ ❋ ✹ ❃ ✾ ✸ ❀ ❊ ❋ ❘ ❘ ❇ ✺ ✐ ❘ ✻ ✺ ● ❋ ❄ ❋ ● ▼ ♠ ➇ ◗ ✺ ❲ ✻ ❅ ✺ ❘ ❘ ❋ ❃ ✽✻ ❅ ❃ ❄ ❋ ❯ ✺ ❘ ❃ ❄ ❍ ❇ ▼ ✼ ✽ ◗ ❊ ❾ ✐ ❚ ❋ ✽ P ❋ ✽ ❖ ● ✼ ❘ ❘ ✺ ✹ ✹ ✺ ✼ ✽ P ❘ ❃ ❯ ❇ ✹ ✺ ● ✼ ❅ ❅ ❋ ✺ ❅✹ ❅ ✼ ✽ ❘ ✻ ❃ ❅ ✹ ✺ ❅ ❘ ❇ ✻ ✺ ❅ ❄ ✼ ▼ ❋ ❯ ❋ ✺ ❘ ❀ ➝ ⑨ ❬ ❪ ➓ ❴ ❼ ⑧ ➲ ❨ ➃ ① ⑧ ⑨ ② ⑧ ✇ ✈ ➳ s t ❴ ❼ ❀ ✾ ✩ ✪ ✪ ➌ ✾➆ ➥ ❞ ❤ ❢ ✾ ❥ ✶ ✵ ✐ ❥ ⑤ ⑤ ❀✴ ❤ ❣ ✷ ➇ ❋ ❘ ❍ ❋ ▼ ❇ ❅ ✼ ✾ ■ ❀ ❁ ➇ ✼ ❋ ✹ ❃ ✾ ✸ ❀ ❊ ❋ ❘ ❘ ❇ ✺ ✐ ❘ ✻ ✺ ● ❋ ❄ ❋ ● ▼ ♠ ➇ ◗ ✺ ❲ ✻ ❅ ✺ ❘ ❘ ❋ ❃ ✽✻ ❅ ❃ ❄ ❋ ❯ ✺ ❘ ❃ ❄ ❍ ❇ ▼ ✼ ✽ ❘ ❃ ❯ ❇ ✹ ✺ ● ✼ ❅ ❅ ❋ ✺ ❅ ✹ ❅ ✼ ✽ ❘ ✻ ❃ ❅ ✹ ✺ ❅ ❘ ❇ ✻ ✺ ❅ ❄ ✼ ▼ ❋ ❯ ❋ ✺ ❘ ❀ ➝ ⑨ ❬ ❪➓ ❴ ❼ ⑧ ➲ ❨ ➃ ① ⑧ ⑨ ② ⑧ ✇ ✈ ➳ s t ❴ ❼ ❨ ✾ ✩ ✪ ✪ ➤ ✾ ➆ ➍ ❞ ❡ ❢ ✾ ✵ ✵ ✐ ❥ ❥ ❀✴ ❤ ❥ ✷ ■ ❋ ✹ ✼ ❯ ✾ ❾ ❀ ❁ ❂ ❋ ✽ ✹ ❃ ✽ ✾ ❉ ❀ ❊ ❀ ❁ ⑥ ❇ ❄ ❃ ❇ ❅ ✾ ✿ ❀ ■ ❀ ❊ ❍ ✺ ❚ ❯ ❃ ❃ P ✐ ✹ ✺ ❘ ✹ ❋ ❘ ✼ ✽ P ❚ ❯ ❃ ❃ P ✐✺ ✻ ❋ P ❋ P ❱ ▼ ❋ ❘ ❚ ✼ ❅ ❅ ❋ ✺ ❅ ❘ ✼ ❅ ✺ ▼ ❃ ❅ ✺ ✹ ❍ ✼ ✽ ❙ ❇ ❘ ✹ ✹ ❍ ✺ ❋ ❅ ✹ ❋ ❖ ❍ ✹ ❙ ❇ ✽ ● ✹ ❋ ❃ ✽ ❘ ❨ ✉ s ✈ r ❨❫ ❴ → ⑨ ✈ ⑩ ❀ ✾ ✩ ✪ ✫ ✫ ✾ ❷ ③ ❞ ✶ ❢ ✾ ④ ✶ ❡ ✐ ④ ✶ ④ ❀✴ ❤ ✶ ✷ ❉ ✼ ❅ ✹ ❯ ✺ ✹ ✹ ✾ ✿ ❀ ■ ❀ ❁ ❑ ✺ ❋ ✽ ❚ ✼ ❇ ✺ ❅ ✾ ❿ ❀ ❆ ❀ ❁ ➇ ❋ ✺ ❘ ● ❍ ❯ ✼ ❖ ✾ ❏ ❀ ⑥ ❋ ❄ ❄ ✺ ❅ ✺ ✽ ✹ ❋ ✼ ❯ ✺ ❄ ❄ ✺ ● ✹ ❘❃ ❄ ❆ ✸ ❂ ✼ ✽ P ✹ ✺ ❘ ✹ ❃ ❘ ✹ ✺ ❅ ❃ ✽ ✺ ❃ ✽ ✹ ❍ ✺ ▼ ✼ ❋ ✽ ✹ ✺ ✽ ✼ ✽ ● ✺ ❃ ❄ ❘ ✻ ✺ ❅ ▼ ✼ ✹ ❃ ❖ ✺ ✽ ✺ ❘ ❋ ❘ ❋ ✽✹ ❍ ✺ ✼ P ❇ ❯ ✹ ❍ ❱ ✻ ❃ ✻ ❍ ❱ ❘ ✺ ● ✹ ❃ ▼ ❋ ▲ ✺ P ❅ ✼ ✹ ❀ ❳ ❨ ➫ t ⑩ ✈ ✇ ⑨ s t ✈ r ❀ ✾ ✫ ✳ ➤ ✳ ✾ ❛ ➆ ❛ ❞ ❡ ❢ ✾❥ ❽ ✐ ✶ ④ ❀✴ ❤ ❤ ✷ ❆ ✼ ♥ ● ✺ ✹ ✹ ✾ ⑥ ❀ ❑ ❀ ❁ ➇ ✺ ✼ ♣ ✺ ❘ ✾ ❑ ❀ ❉ ❀ ❁ ❆ ❯ ❃ ❅ ✺ ❘ ✾ ■ ❀ ➇ ❀ ♦ ❃ ▼ ✻ ✼ ❅ ✼ ✹ ❋ ♣ ✺❃ ❚ ❘ ✺ ❅ ♣ ✼ ✹ ❋ ❃ ✽ ❘ ❃ ✽ ❋ ✽ ✹ ✺ ❅ ✹ ❇ ❚ ❇ ❯ ✼ ❅ ❯ ❱ ▼ ✻ ❍ ✼ ✹ ❋ ● ❘ ✼ ✽ P ✹ ❍ ✺ ❃ ❅ ❖ ✼ ✽ ❋ ▲ ✼ ✹ ❋ ❃ ✽ ❃ ❄✹ ❍ ✺ ❋ ✽ ✹ ✺ ❅ ❘ ✹ ❋ ✹ ❋ ✼ ❯ ✹ ❋ ❘ ❘ ❇ ✺ ❃ ❄ ✹ ❍ ✺ ▼ ✼ ▼ ▼ ✼ ❯ ❋ ✼ ✽ ✹ ✺ ❘ ✹ ❋ ❘ ❀ ✉ s ✈ r ❨ ❫ ❴ → ⑨ ✈ ⑩ ❀ ✾ ✫ ✳ ➑ ➅ ✾➔ ❞ ✶ ❢ ✾ ✶ ❹ ❹ ✐ ✶ ❣ ✵ ❀✴ ❤ ⑤ ✷ ✸ ✺ ✹ ● ❍ ✺ ❯ ❯ ✾ ❉ ❀ ❾ ❀ ❊ ❍ ✺ ❆ ❇ ✽ ● ✹ ❋ ❃ ✽ ✼ ❯ ✐ ✸ ❋ ❖ ✽ ❋ ❄ ❋ ● ✼ ✽ ● ✺ ❃ ❄ ✹ ❍ ✺ ❉ ❯ ❃ ❃ P ✐ ❊ ✺ ❘ ✹ ❋ ❘❉ ✼ ❅ ❅ ❋ ✺ ❅ ❀ ❳ ❨ ↔ t ⑩ ⑨ ✈ r ❨ ✾ ✫ ✳ ➤ ✪ ✾ ❛ ❞ ❡ ❢ ✾ ❣ ✐ ❡ ❹ ❀✴ ❤ ④ ✷ ❾ ✺ ❯ ❯ ✺ ✹ ❋ ✺ ❅ ✾ ♠ ❀ ■ ❀ ❊ ❍ ✺ ❚ ❯ ❃ ❃ P ✐ ✹ ✺ ❘ ✹ ❋ ❘ ❚ ✼ ❅ ❅ ❋ ✺ ❅ ⑦ ✹ ❍ ✺ ❙ ❇ ✽ ● ✹ ❋ ❃ ✽ ✼ ❯ ✻ ✺ ❅ ▼ ✺ ✼ ❚ ❋ ❯ ❋ ✹ ❱ ✾✹ ❍ ✺ ✻ ❅ ❃ ✹ ✺ ❋ ✽ ❘ ✼ ✽ P ✹ ❍ ✺ ❯ ❋ ✻ ❋ P ❘ ❀ ➵ ❭ ✈ ❪ ❨ ❻ s ❵ ❼ ✈ ✇ ① ❴ ② ❨ q ➄ ❼ ✈ ✇ ① ❴ ② ❨ ✾ ✩ ✪ ✫ ✫ ✾③ ❜ ❞ ✵ ❢ ✾ ❥ ❽ ✐ ❡ ✵ ⑤ ❀✴ ❤ ❽ ✷ ■ ✼ ✺ P ✼ ✾ ❊ ❀ ❁ ❿ ❃ ✹ ❃ ✾ ◗ ❀ ❁ ❧ ❃ ❚ ✼ ❱ ✼ ❘ ❍ ❋ ✾ ⑥ ❀ ❁ ❊ ✼ ▼ ✼ ❋ ✾ ➉ ❀ ❊ ❅ ✼ ✽ ❘ ✻ ❃ ❅ ✹ ❃ ❄❃ ❅ ❖ ✼ ✽ ❋ ● ● ✼ ✹ ❋ ❃ ✽ ❘ ✼ ● ❅ ❃ ❘ ❘ ✹ ❍ ✺ ❚ ❯ ❃ ❃ P ✐ ✹ ✺ ❘ ✹ ❋ ❘ ❚ ✼ ❅ ❅ ❋ ✺ ❅ ❨ ➓ ✈ r ❨ ➃ ① ⑧ ⑨ ② ❀ ✾ ✩ ✪ ✪ ➑ ✾③ ❞ ❥ ❢ ✾ ❤ ❹ ❹ ✐ ❤ ❹ ⑤ ❀✴ ⑤ ❹ ✷ ✸ ✺ ✹ ● ❍ ✺ ❯ ❯ ✾ ❉ ❀ ❾ ❀ ❉ ❯ ❃ ❃ P ✐ ✹ ✺ ❘ ✹ ❋ ❘ ❚ ✼ ❅ ❅ ❋ ✺ ❅ ✾ ❙ ❇ ✽ ● ✹ ❋ ❃ ✽ ✼ ❯ ✼ ✽ P ✹ ❅ ✼ ✽ ❘ ✻ ❃ ❅ ✹✻ ❅ ❃ ✹ ✺ ❋ ✽ ❘ ✼ ✽ P ❘ ✻ ✺ ❅ ▼ ✼ ✹ ❃ ❖ ✺ ✽ ✺ ❘ ❋ ❘ ❀ ➀ ➛ ➜ ➂ ➫ ➞ → ❨ ➓ ❴ ⑩ ❨ ✉ s ✈ r ❀ ✾ ✩ ✪ ✪ ➤ ✾ ❜ ➍ ❜ ✾✵ ❡ ✵ ✐ ✵ ❣ ❣ ❀✴ ⑤ ❡ ✷ ❆ ❋ ❙ ✼ ❈ ✾ ■ ❀ ❁ ■ ✺ ❋ ✽ ❍ ✼ ❅ P ✹ ✾ ◗ ❀ ❊ ❍ ✺ ✹ ✺ ❘ ✹ ❋ ❘ ❋ ✽ ❋ ▼ ▼ ❇ ✽ ✺ ✻ ❅ ❋ ♣ ❋ ❯ ✺ ❖ ✺ ❀ ➊ ② ② ❬ t ✈ r ❨❫ ❴ ❶ ❀ ✾ ✩ ✪ ✪ ➣ ✾ ➆ ❛ ➍ ✾ ❤ ❤ ✐ ④ ❡ ❀

➻ ➻ ➼ ➽ ➾ ➚ ➾ ➪ ➶ ➹ ➘ ➾ ➹ ➴ ➷ ➾ ➚ ➽ ➹ ➬ ➾ ➮ ➾ ➚ ➱ ✃ ❐ ❒ ➹ ❮ ➾ ➷ ❰ Ï Ð Ñ Ò ➼ ➻ Ó Ñ Ô Õ ✃ Ö × Ø Ñ Ù Õ Ö Ú Û ➹ Ï Ï ➱ ➚ Õ ➹ ❰ ➱ ✃ ÖÜ Ý Þ ß à á â ã ä â å æ ç è ç é ê â ä ë ì í î ï ð ñ ë í ò í â â á ä â ó ð â ê ë ì ä ô á ð õ í ñ í ã â ð ö ë í â ö ä ë÷ ê â ð â á î í â ø ò ô í ã ã ä â ù í á î ç ú û ü ý þ ÿ � ✁ ✂ ✄ ☎ ✆ þ ✝ ✞ ✟ ✠ ✆ ÿ � ✁ ✂ ✄ ☎ ✆ ç å Ò ➼ ➼ ✡ å☛ ☞ ✌ ✍ ✎ ✏ å ✑ ✒ ✓ ✔ ✕ ✑ ✒ ✔ ✖ çÜ Ý ✎ ß ✗ â ä ÷ ë å é ç ✘ ç ✙ ✚ ð ã ê ✛ ô á î å ✜ ç ✙ ✢ ä ✣ ä â î á ✛ å ✗ ç ✙ ✤ ê õ á ì å ✤ ç ✑ ê â õ í ë á ê î í î ãõ í á î ë ä î í î ✥ ä ê ÷ ò ô ê ê ã ✕ ð â á î ä ò í â â á ä â á î ð â ê ë ì ä ô á ð õ ç ÿ ✦ ☎ ✧ ☎ ★ ✆ ✠ ✂ ✩ ✠ åÒ ➼ ➻ ➼ å ☛ ✪ ✫ ✍ ✬ ✕ ✒ ✏ å ✎ ✕ ✬ ✒ çÜ Ý ✒ ß è ù ê ã í ✥ í å ✭ ç ✮ ì ä ð â ê ä ù á ë ì ä ô á ð õ ó ✯ ê ë ï ð ñ ë í ù í ñ ñ á ✰ ä ò í â â á ä â ç ✱ ✦ ✠ ✲ ✲ ✄ ✳ åÒ ➼ ➼ Ó å ✴ ✍ ✎ ✏ å ✬ ✬ Ý ✕ ✬ Þ ✓ çÜ Ý ✖ ß æ ä ✵ á ñ å ✜ ç è ç ✘ ✰ ä â ø ë ì á î ö ø ê ð ✵ í î ë ä ã ë ê ✛ î ê ✵ í ò ê ð ë ë ì ä ò ô í ã ã ä âä ù á ë ì ä ô á ð õ ò ð ë ✵ ä â ä í ÷ â í á ã ë ê í ñ ✛ ç ú û ü ý þ ÿ � ✁ ✂ ✄ ☎ ✆ þ ✝ ✞ ✟ ✠ ✆ ÿ � ✁ ✂ ✄ ☎ ✆ ç åÒ ➼ ➼ ➼ å ☛ ✶ ☞ ✍ ✷ ✏ å ✑ ✓ ✷ Ý ✕ ✑ ✓ Ý ✒ çÜ Ý ✷ ß è ✥ ì í â ø í å ✸ ç ✙ à ä ✥ ✛ ä ô å ✢ ç ✙ ✤ ð á ✣ å ✹ ç ✭ ç ✙ ✹ í î ö å ✘ ç ✙ ✤ ê ï í ñ å ✤ ç ✙ à á â ã ä â åæ ç ✙ è ù ê ã í ✥ í å ✭ ç ✺ á ñ ë â á ò ð ë á ê î ê ÷ ë ì ä ë á ö ì ë ï ð î ✥ ë á ê î ù â ê ë ä á î ñ ✻ ✼ ✕ ✬ åê ✥ ✥ ô ð ã á î å í î ã ✥ ô í ð ã á î ✕ ✒ å ✕ ✓ å í î ã ✕ ✬ Þ á î ò ô í ã ã ä â ä ù á ë ì ä ô á ð õ ç ú û ü ✽ þÿ � ✁ ✂ ✄ ☎ ✆ þ ✾ ✞ ✟ ✿ ✆ ÿ � ✁ ✂ ✄ ☎ ✆ þ å Ò ➼ ➼ Ó å ☛ ☞ ✶ ✍ Þ ✏ å ✑ ✎ ❀ ✖ ✕ ✑ ✎ ✬ ✓ çÜ Ý Ý ß ✜ ì í ÷ á ✛ å è ç ✙ ✜ ì í ÷ á ✛ å ❁ ç ✙ ✘ ô ✜ á ò í á å ✼ ç ✙ ✜ ì í ÷ á ✛ å è ç è ç ❂ ì í î ö ä ñ á î ë ì äð â á î ä ✥ ê õ ù ê ñ á ë á ê î ã ð â á î ö á ë ñ ù í ñ ñ í ö ä ë ì â ê ð ö ì ë ì ä ð â ä ë ä â ç è ✥ ê î ✥ ä ù ëê ÷ ð â ê ë ì ä ô á í ô ÷ ð î ✥ ë á ê î ç ❃ ✦ ☎ þ ✝ ✞ ✂ ç å Ò ➼ ➼ ✡ å ❄ ❄ ✍ ✷ ✏ å ✒ Þ ✷ ✕ ✒ Þ ✓ çÜ Ý ✓ ß ✜ ù ä ✥ ë ê â å ✺ ç è ç ✙ ❅ í î ö å ❆ ç ✙ æ á ð å ✢ ç ✙ ✹ í ã ä å ✢ ç à ç ✘ ❇ ù â ä ñ ñ á ê î åô ê ✥ í ô á ✣ í ë á ê î å í î ã â ä ö ð ô í ë á ê î ê ÷ ð â ä í ë â í î ñ ù ê â ë ä â à á î â í ë ð â ê ë ì ä ô á í çú û ü ✽ þ ÿ � ✁ ✂ ✄ ☎ ✆ þ ✝ ✞ ✟ ✠ ✆ ÿ � ✁ ✂ ✄ ☎ ✆ ç å Ò ➼ ➼ Ó å ☛ ☞ ✶ ✍ ✬ ✏ å ✑ ✬ ❀ Þ ✕ ✬ ❀ ✓ çÜ Ý ✔ ß ❂ ì ê ù â í å à ç ✙ à í â â á ✥ ✛ å ✜ ç ✤ ç ✙ é ä ø ä â ñ å ✜ ç ✙ à ä ✥ ✛ ä ô å ✢ ç é ç ✙ ✻ ä á ã ä ô å é çæ ç ✙ ✑ ê â ã å è ç ✸ ç ✺ ç ✹ ç ✙ ã ä ✭ â ê í ë å ✹ ç ❂ ç ✙ à á â ã ä â å æ ç è ç ✘ ❇ ù â ä ñ ñ á ê îí î ã ÷ ð î ✥ ë á ê î ê ÷ ò â í ã ø ✛ á î á î à ✬ í î ã à Þ â ä ✥ ä ù ë ê â ñ á î î ê â õ í ô í î ãá î ÷ ô í õ ä ã â í ë ð â á î í â ø ò ô í ã ã ä â ð â ê ë ì ä ô á ð õ ç ✽ þ ÿ � ✁ ✂ ✄ ☎ ✆ þ ❈ ❉ ☎ ✟ ❊ ❋ å Ò ➼ ➼ ✡ å✴ ✫ ☛ ✍ ✎ ✏ å ✓ ✖ ✔ ✕ ✓ Ý ✬ çÜ ✓ ❀ ß ❂ ì ä ñ ñ ✕ ✹ á ô ô á í õ ñ å ✤ ç é ð ñ ✥ í â á î á ✥ â ä ✥ ä ù ë ê â ñ ê ÷ ë ì ä ð â á î í â ø ò ô í ã ã ä â óã ä ë â ð ñ ê â å ð â ê ë ì ä ô á í ô í î ã ù â ä ï ð î ✥ ë á ê î í ô ç ● ❍ ✧ ☎ ✟ þ ● ❍ ✧ ✠ ✳ ☎ ✄ ❊ þ ÿ � ✠ ✦ ✩ ✠ ✳ ☎ ✆ þ åÒ ➼ ➼ Ò å ☛ ☛ ✍ ✎ ✏ å ✬ ✎ ✎ ✕ ✬ ✒ ✖ çÜ ✓ ✬ ß ✯ ä ö â ä ë ä å ✚ ç ✼ ç ✙ æ í ✰ ä ô ô ä å ✢ ç ✸ ç ✙ à ä â ö å ✢ ç ✙ æ ä ✵ á ñ å ✜ ç è ç ✙ ✻ ä á ã ä ô å é ç æ ç✸ ä â õ ä í ò á ô á ë ø ù â ê ù ä â ë á ä ñ ê ÷ ë ì ä á î ë í ✥ ë õ í õ õ í ô á í î ò ô í ã ã ä âä ù á ë ì ä ô á ð õ ç ú û ü ✽ þ ÿ � ✁ ✂ ✄ ☎ ✆ ç å ➻ ■ ■ ❏ å ☛ ✶ ❑ ✍ ✒ ✸ ë Þ ✏ å ✑ ✓ ✓ ✷ ✕ ✓ ✔ ✒ çÜ ✓ Þ ß ✗ á õ å ✗ ç ✢ ç ✙ é í ô á ✛ å è ç à ç ✸ â ê ë ä á î ë â í î ñ ù ê â ë í ✥ â ê ñ ñ ë ì ä ô ð î öä ù á ë ì ä ô á í ô ò í â â á ä â ç ú û ü ✽ þ ÿ � ✁ ✂ ✄ ☎ ✆ þ ❉ ❍ ✟ ▲ ▼ ✞ ✆ ✆ ◆ ☎ ✆ þ ÿ � ✁ ✂ ✄ ☎ ✆ ç å Ò ➼ ➼ ❖ å☛ ☞ ✪ ✍ Þ ✏ å æ Þ ✒ Ý ✕ Þ ✖ ✔ çÜ ✓ ✎ ß ✼ ✰ ä â ö í í â ã å ❂ ç ✘ ç ✙ é á ë ✥ ì ä ô ô å æ ç è ç ✙ ✗ ê ✰ í ô å é ç ✤ ê ô ä ñ ÷ ê â ✥ ô í ð ã á î ñ á îí ô ✰ ä ê ô í â ä ù á ë ì ä ô á í ô ò í â â á ä â ÷ ð î ✥ ë á ê î ç ● ✟ ✟ þ P þ ◗ ❘ ● ✳ ✠ ❊ þ ❙ ✳ ✄ ç å Ò ➼ ➻ Ò å❑ ☛ ✴ ✶ å ✬ ✷ Ý ✕ ✬ Ý ✒ çÜ ✓ ✒ ß ✹ ä ñ ë å ✢ ç à ç ✮ ì ê ð ö ì ë ñ ê î ë ì ä ù ð ô õ ê î í â ø ò ô ê ê ã ✕ ö í ñ ò í â â á ä â ç ú û ü ✽ þÿ � ✁ ✂ ✄ ☎ ✆ þ ❉ ❍ ✟ ▲ ▼ ✞ ✆ ✆ ◆ ☎ ✆ þ ÿ � ✁ ✂ ✄ ☎ ✆ þ å Ò ➼ ➼ ❖ å ☛ ☞ ✴ ✍ ✎ ✏ å æ ✖ ❀ ✬ ✕ ✖ ✬ ✎ çÜ ✓ ✖ ß ✚ ê ô ô ä î ì ê â ñ ë å é ç ❁ ç ✙ ✤ á ✥ ì ë ä â å ✗ ç ✙ ✑ â ê î á ð ñ å é ç ❁ ê î ë â í î ñ ù ê â ë ò øù ð ô õ ê î í â ø ä ù á ë ì ä ô á í ç ✽ þ ❚ ✄ ☎ ✩ ✞ ❊ þ ❚ ✄ ☎ ✧ ✞ ✳ � ✟ ☎ ✆ ç å Ò ➼ ➻ ➻ å ☛ ❯ ❑ ❑ å ✬ Ý ✒ ✎ ❀ ✷ çÜ ✓ ✷ ß ✼ ✥ ì ñ å é ç ✙ ✯ ø ä î ö í í â ã å ✢ ç ✤ ç ✙ ✢ ð î ö å è ç ✙ ✗ î ð ã ñ ä î å æ ç ✙ ❱ ê á ö ë å é ç ✙✹ í ì ô ä â ñ å ✮ ç ✙ ✤ á ✥ ì ë ä â å ✢ ç ✙ ✭ ð î ã ä â ñ ä î å ✚ ç ✢ ç ✮ ì ä î ð õ ò ä â ê ÷ í ô ✰ ä ê ô áá î ë ì ä ì ð õ í î ô ð î ö ç ú û ü ✽ þ ✝ ✞ ✂ ★ ✄ ✦ þ ▼ ✦ ✄ ✧ þ ▼ ✠ ✦ ✞ ◆ ✞ ❊ ç å Ò ➼ ➼ Ó å ❑ ✫ ✌ ✍ ✬ ✏ å✬ Þ ❀ ✕ ✬ Þ ✒ çÜ ✓ Ý ß ✹ ä ñ ë å ✢ ç à ç ✙ é í ë ì á ä ð ✕ ❂ ê ñ ë ä ô ô ê å ✼ ç ✜ ë â ä î ö ë ì ê ÷ ë ì ä ù ð ô õ ê î í â øò ô ê ê ã ✕ ö í ñ ò í â â á ä â ç ✝ ✞ ✂ ★ ✄ ✦ þ ÿ � ✁ ✂ ✄ ☎ ✆ ç å ➻ ■ ■ Ò å ☞ ☞ ✍ ✬ ✕ Þ ✏ å ✬ ✒ ✬ ✕ ✬ ✒ ✓ çÜ ✓ ✓ ß à ð ò í î ê ✰ á ✥ å ❁ ç ❱ ç ✑ í á ô ð â ä ê ÷ ò ô ê ê ã ✕ ë ì ø õ ð ñ ò í â â á ä â í ñ í õ ä ✥ ì í î á ñ õê ÷ ë ð õ ê â í î ã ë â ê ù ì ê ò ô í ñ ë ä ñ ✥ í ù ä ç ◆ ✞ ❊ þ ❲ ✁ ★ ☎ ✧ � ✞ ✂ ✞ ✂ å Ò ➼ ➼ ❖ å ✫ ❯ ✍ ✎ ✏ å✎ ✬ ✖ ✕ ✎ Þ ❀ ç

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ñ ê ÷ æ ✕ ë ì ø â ê ñ ø ô ✕ æ ✕í â ö á î á î ä ✍ ✛ ø ê ë ê â ù ì á î ✏ ê î ë ì ä ò ä ì í ✰ á ê â ê ÷ â í ë ñ í î ã ö ê ô ã ÷ á ñ ì çÿ ✞ ★ ✧ ✄ ❊ ✞ ✂ å Ò ➼ ➼ ➼ å ☛ ❑ ✍ ✔ ✏ å ✬ ✎ ✎ ✬ ✕ ✬ ✎ ✎ ✷ çÜ ✔ ✷ ß ✜ ì á ê õ á å ✚ ç ✙ ❴ ä ã í å ✚ ç ✙ ✮ í ✛ í ö á å ✚ ç ❁ ñ ê ô í ë á ê î í î ã á ã ä î ë á ÷ á ✥ í ë á ê î ê ÷ í îí î í ô ö ä ñ á ✥ ê ù á ê á ã ã á ù ä ù ë á ã ä ✛ ø ê ë ê â ù ì á î ✍ ✮ ø â ✕ è â ö ✏ ÷ â ê õ ò ê ✰ á î äò â í á î ç P ✞ ❍ ✦ ☎ ★ � ✠ ✦ ✩ ✠ ✳ ☎ ✆ ☎ ▲ ✁ å ➻ ■ ❜ ➻ å ☛ ❯ ✍ Ý ✏ å ✷ ✎ ✎ ✕ ✷ ✎ ✓ çÜ ✔ Ý ß ❂ ì ä î å ✸ ç ✙ à ê ã ê â å ✯ ç ✙ ✹ ð å ✹ ç é ç ✙ ✸ â ê ✛ í á å æ ç ✜ ë â í ë ä ö á ä ñ ë ê ë í â ö ä ë✛ ø ê ë ê â ù ì á î í î í ô ê ö ð ä ñ ë ê ë ì ä ò â í á î ç ý þ ◆ ✞ ❊ þ ▼ � ✞ ✩ ç å ➻ ■ ■ ❜ å ✪ ❑ ✍ Þ ❀ ✏ å✎ Ý Ý ✎ ✕ ✎ Ý ✓ ✬ çÜ ✔ ✓ ß ✑ ð ï á ë í å ✮ ç ✙ ✗ á ñ ì á ã í å ✮ ç ✙ ✼ ✛ í ã í å ✯ ç ✙ ✭ í î í ù í ë ì ø å ❱ ç ✙ æ ä á ò í ✥ ì å ✑ ç ✚ ç ✙❅ í õ í õ ê ë ê å è ç ❁ î ë ä â í ✥ ë á ê î ê ÷ ✛ ø ê ë ê â ù ì á î í î ã ò â í á î ù ä ù ë á ã äë â í î ñ ù ê â ë ä â á î ñ ø î í ù ë ê ñ ê õ ä ñ ù â ä ù í â ä ã ÷ â ê õ â í ë ✥ ä â ä ò ä ô ô ð õ óá õ ù ô á ✥ í ë á ê î ê ÷ ì á ö ì í ÷ ÷ á î á ë ø ë ø ù ä ✚ ❝ ❞ ù ä ù ë á ã ä ë â í î ñ ù ê â ë ä â ✸ ✘ ✸ ✮ Þõ ä ã á í ë ä ã ë â í î ñ ù ê â ë ñ ø ñ ë ä õ ç P ✞ ❍ ✦ ☎ ✂ ✳ ✄ þ ❉ ✞ ✧ ✧ ç å ➻ ■ ■ ■ å ☛ ✶ ❑ ✍ Þ ✏ å ✬ ✬ Ý ✕ ✬ Þ ❀ çÜ ✔ ✔ ß ✑ ð ï á ë í å ✮ ç ✙ ✗ á ñ ì á ã í å ✮ ç ✙ ✹ í ã í å é ç ✙ ✼ ✛ í ã í å ✯ ç ✙ ❅ í õ í õ ê ë ê å è ç ✙æ ä á ò í ✥ ì å ✑ ç ✚ ç ✙ ✭ í î í ù í ë ì ø å ❱ ç ✑ ð î ✥ ë á ê î í ô ✥ ì í â í ✥ ë ä â á ✣ í ë á ê î ê ÷ ò â í á îù ä ù ë á ã ä ë â í î ñ ù ê â ë ä â á î â í ë ✥ ä â ä ò â í ô ✥ ê â ë ä ❇ ó á ã ä î ë á ÷ á ✥ í ë á ê î ê ÷ ë ì äì á ö ì ✕ í ÷ ÷ á î á ë ø ë ø ù ä ✚ ❝ ❞ ù ä ù ë á ã ä ë â í î ñ ù ê â ë ä â ✸ ✘ ✸ ✮ Þ ç ❚ ✦ ✠ ✄ ✟ ✝ ✞ ✂ ç åÒ ➼ ➼ Ó å ✌ ✌ ✶ ✍ ✬ ✏ å ✖ Þ ✕ ✷ ✬ çÜ ✬ ❀ ❀ ß ✭ í î í ù í ë ì ø å ❱ ç ✙ é á ø í ð ✥ ì á å ✜ ç ✮ â í î ñ ù ê â ë ñ ø ñ ë ä õ ñ ÷ ê â ê ù á ê á ãù ä ù ë á ã ä ñ á î õ í õ õ í ô á í î ë á ñ ñ ð ä ñ ç ● ✠ ★ ✂ ý ç å Ò ➼ ➼ ✡ å ✶ ✍ ✒ ✏ å ✘ ✓ ✖ Þ ✕ ✓ ✖ ✷ çÜ ✬ ❀ ✬ ß ❂ í ñ ë í î ì ê å é ç è ç ✙ ✑ ä â î í î ã ä ñ å é ç ❡ ç æ á ù á ã õ ä õ ò â í î ä ✕ á î ã ð ✥ ä ãê ù ë á õ á ✣ í ë á ê î ÷ ê â ô á ö í î ã ✕ â ä ✥ ä ù ë ê â ã ê ✥ ✛ á î ö ó â ä ✥ ä î ë ë ê ê ô ñ í î ã á î ñ á ö ì ë ñ÷ ê â ë ì ä ❢ õ ä õ ò â í î ä ✥ í ë í ô ø ñ á ñ ❢ õ ê ã ä ô ç ❵ ❍ ✦ þ ❚ ✄ ☎ ★ � ✁ ✂ þ ✽ ç å Ò ➼ ➼ ❏ å ❄ ✴ ✍ Þ ✏ å✔ Þ ✕ ✬ ❀ ✎ çÜ ✬ ❀ Þ ß ✤ á ò ä á â ê å é ç é ç ✙ ✸ á î ë ê å è ç ✤ ç ✙ ✺ ê õ á î ö ð ä ñ å é ç é ç ✙ ✜ ä â â í î ê å ❁ ç ✙ ✚ ä â í ñ åé ç ✙ à í â ã í ï á å ✘ ç ✤ ç ✙ ✮ í ✰ í â ä ñ å ❁ ç ✙ ❂ í ñ ë í î ì ê å é ç è ç ❂ ì ä õ á ✥ í ô ✥ ê î ï ð ö í ë á ê îê ÷ ë ì ä î ä ð â ê ù ä ù ë á ã ä ✛ ø ê ë ê â ù ì á î í î ã á ò ð ù â ê ÷ ä î ä î ì í î ✥ ä ñ ò â í á îë í â ö ä ë á î ö í î ã í î í ô ö ä ñ á í ç ◆ ☎ ✆ þ ÿ � ✠ ✦ ✩ ç å Ò ➼ ➻ ➻ å ☞ ✍ ✖ ✏ å ✬ ✔ Þ ✔ ✕ ✬ ✔ ✒ ❀ çÜ ✬ ❀ ✎ ß ✑ ô í ë ä î å ✭ ç ✘ ç ✙ ✺ ì í î á ✛ ð ô í å è ç à ç ✙ æ ð ë ì õ í î å ✗ ç ✙ à â í î ã ô å é ç ✺ â ð öù ä â õ ä í ò á ô á ë ø í ✥ â ê ñ ñ í ù ì ê ñ ù ì ê ô á ù á ã ✰ ä ñ á ✥ ô ä ò í ñ ä ã ò í â â á ä â ó í î ê ✰ ä ôí ù ù â ê í ✥ ì ÷ ê â ñ ë ð ã ø á î ö ù í ñ ñ á ✰ ä ã á ÷ ÷ ð ñ á ê î ç ❵ ❍ ✦ þ ✽ þ ÿ � ✠ ✦ ✩ þ ❙ ✳ ✄ ç åÒ ➼ ➼ ❏ å ☛ ✶ ✍ ✬ ✏ å ✓ ❀ ✕ ✔ ❀ ç✤ ä ✥ ä á ✰ ä ã ó ✜ ä ù ë ä õ ò ä â ✬ ✓ å Þ ❀ ✬ ✎ ✤ ä ✰ á ñ ä ã ó ✺ ä ✥ ä õ ò ä â ✬ ✓ å Þ ❀ ✬ ✎ è ✥ ✥ ä ù ë ä ã ó ✢ í î ð í â ø ❀ ✎ å Þ ❀ ✬ ✒❣ ❤ ✐ ❥ ❦ ❧ ❤ ♠ ♥ ♦ ♣ q r s t ✉ ✈ ✇ s t ① ② ③ ④ ⑤ s r t ⑥ ✉ s s ⑦ ⑧ ⑨ ✉ ⑤ ③ ⑥ r s ⑩ ③ ⑦ ♥ ⑧ ⑨ ✉ ❶ t r s t ⑩ ✈ ❷ ⑧ ① ③ ⑦ ② ❸ ✈ ⑦ ② r s ✉ t ⑥ ③ ⑥ ✈ ❷ ② r s ❹ t ② s ① ③ t ⑤ ⑥ ⑧ ① ✈ ✇ ③ ⑩ s ⑩ ✉ ❺ ② r s t ⑨ ② r ✈ ① ❻ q r s♥ ⑩ ③ ② ✈ ① ③ t ⑤ ❣ s ⑧ t ① ② ❹ s ⑦ ② ① s ⑥ s ① ✇ s ⑥ ② r s ① ③ ❼ r ② ② ✈ ❹ t ❽ s ❹ ③ ⑦ ✈ ① ❹ ✈ ⑩ ③ ❷ ③ ④ t ② ③ ✈ ⑦ ⑥ ❷ ✈ ① ❷ ⑨ ① ② r s ① ③ ❹ ⑧ ① ✈ ✇ s ❹ s ⑦ ② ✈ ❷ ② r s ❹ t ⑦ ⑨ ⑥ ④ ① ③ ⑧ ② ❻❾ ❿ ➀ ➁ ➂ ➃ ➄ ➄ ➅ ➆ ➃ ➆ ➇

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