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In this paper, the authors proposed new wave solutions of time- space fractional Dodd-Bullough-Mikhailov, Tzitzica-Dodd-Bullough and Tzitzica equations by using a reliable analytical method called sub-equation method. The fractional derivatives considered in this study are handled in conformable sense. Conformable derivative is an easy and applicable type of fractional derivative which satisfies the basic properties of known derivative with integer order such as Leibniz rule, quotient rule, chain rule. With these properties, conformable derivatives superior to other famous fractional deriva- tives such as Caputo and Riemann-Liouville. [ABSTRACT FROM AUTHOR]

Bu çalışmanın amacı, ergenliğin orta evresi içerisinde yer alan lise öğrencilerinin kişilerarasıilişki tarzlarınıetkileyen faktörleri belirlemektir. Bu araştırma, lise öğrencilerinin kişilerarasıilişki tarzlarının; bağlanma stilleri, iletişim becerileri ve problem çözme becerileri ile olan ilişkisini açıklamaya dönük betimsel bir çalışmadır. Araştırma, amacına uygun olarak tesadüfi küme örnekleme seçimi ile Muğla il merkezindeki dört farklılisede öğrenim gören 400 kişi üzerinde 200 kız; 200 erkek gerçekleştirilmiştir. Araştırmada Bilgi Formu, Kişilerarası İlişkiler TarzıÖlçeği, İlişki Ölçekleri Anketi, İletişim Becerileri Envanteri ve Problem Çözme Envanteri kullanılmıştır. Veri analizleri için SPSS/WINDOWS -14.0- programıkullanılmıştır. Veriler, çok yönlü hiyerarşik regresyon analizi ve korelasyon kullanılarak SPSS/WINDOWS programıile incelenmiştir. Araştırma bulguları, bağlanma stilleri, iletişim becerileri ve problem çözme becerilerinin kişilerarasıilişki tarzlarının önemli yordayıcılarıolduğunu göstermiştir. Araştırma sonuçları, önceki bulgular ışığında kişilerarasıilişki tarzlarıkapsamında başka araştırma ve uygulamalara da yol gösterecek bağlamda tartışılmıştır.

Bu çalışmanın amacıkişilerarasıilişkilerinde yaşadıklarıproblemler bağlamında üniversite öğrencilerinin reddedilme duyarlıklarıile sosyal kaygıdüzeylerini cinsiyet, sosyo-ekonomik düzey ve ebeveyn tutumlarıaçısından incelemektir. Bu çalışma betimsel yöntem kullanılarak yapılmıştır. Araştırma, amacına uygun olarak Karadeniz Teknik Üniversitesi Fatih Eğitim Fakültesinin çeşitli bölümlerinden farklıkategorilerde tesadüfi seçimle 360 kişi üzerinde 180 kız; 180 erkek gerçekleştirilmiştir. Araştırmada Bilgi Formu, Reddedilme DuyarlığıÖlçeği ve Sosyal KaygıÖlçeği kullanılmıştır. Veri analizleri için SPSS/WINDOWS programıkullanılmıştır. Gruplar arasıfarklılığıbelirlemek için “ttesti” ve “varyans analizi”, değişkenler arasındaki ilişkileri belirlemek için “korelasyon” kullanılmıştır. Reddedilme duyarlığıüzerinde cinsiyetler ve ebeveyn tutumlarıarasında; sosyal kaygıya ilişkin “sosyal kaçınma”, “eleştirilme kaygısı” ve “bireysel değersizlik” alt boyutlarıüzerinde cinsiyetler ve sosyo-ekonomik düzeyler arasında, “eleştirilme kaygısı” ve “bireysel değersizlik” alt boyutlarıüzerinde ebeveyn tutumlarıarasında da farklılığa rastlanmıştır. Araştırma sonuçlarıönceki bulgular ışığında kişilerarasıilişkilerde reddedilme duyarlığıve sosyal kaygıkapsamında başka araştırma ve uygulamalara da yol gösterecek bağlamda tartışılmıştır.

Introduction: This study investigates the Health-Led Growth Hypothesis (HLGH) within OECD countries, examining how health expenditures influence economic growth and the role of different health financing systems in this relationship., Methods: Utilizing a comprehensive analysis spanning 2000 to 2019 across 38 OECD countries, advanced econometric methodologies were employed. Both second-generation panel data estimators (Dynamic CCEMG, CS-ARDL, AMG) and first-generation models (Panel ARDL with PMG, FMOLS, DOLS) were utilized to test the hypothesis., Results: The findings confirm the positive impact of health expenditures on economic growth, supporting the HLGH. Significant disparities were observed in the ability of health expenditures to stimulate economic growth across different health financing systems, including the Bismarck, Beveridge, Private Health Insurance, and System in Transition models., Discussion: This study enriches the ongoing academic dialog by providing an exhaustive analysis of the relationship between health expenditures and economic growth. It offers valuable insights for policymakers on how to optimize health investments to enhance economic development, considering the varying effects of different health financing frameworks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Atilgan, Ertuğrul, Baycan and Ulucan.)

Background: The metacarpophalangeal joint blocking orthosis (MCPJ-BO) is one of the first-line orthotic treatment for patients with trigger finger (TF). Relative motion extension orthosis (RME-O) has recently emerged as a treatment option for various hand disorders involving TF., Purpose: The primary objective of this study was to compare the effectiveness of 6 weeks of orthotic treatment with the MCPJ-BO and the RME-O for pain relief. Function and satisfaction with the orthosis were assessed as secondary objectives., Study Design: Randomized clinical study., Methods: Thirty patients with an average age of 50 years with Froimson stage 1-3 A1 pulley triggering participated in the study. They were randomly assigned to either the MCPJ-BO (n = 15; 10 females, five males) or the RME-O group (n = 15; 12 females, three males). The orthoses were worn full time for 6 weeks. All patients received patient education, activity modification, and flexor tendon gliding exercises as part of the rehabilitation program. Pre- and post-assessments included Numeric Pain Rating Scale, Disability of the Arm, Shoulder, and Hand questionnaire, and Quebec User Evaluation of Satisfaction with Assistive Technology questionnaire. The Mann-Whitney U test was conducted to analyze the difference between the two groups., Results: There were no significant differences between the two groups in pain and function before treatment (p < 0.05). Within-group comparisons indicated that both orthoses relieved pain, but the MCPJ-BO group achieved greater pain relief (p = 0.001). There was a significant improvement in function in the MCPJ-BO group, with a mean change of 12.7 (p = 0.0001). The overall success rates for the MCPJ-BO group and RME-O group were 60% and 27%, respectively. Patients in both groups had high satisfaction with the orthosis., Conclusions: MCPJ-BO and RME-O could be used for pain relief in the treatment of TF. The MCPJ-BO appears to be more effective than the RME-O in improving function., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Patellofemoral pain syndrome (PFPS) is a set of symptoms that negatively affect the daily life activities of the individual, leading to functional disability and significant loss of labor, especially in young adults. PFPS is usually due to weakness of the vastus medialis obliquus (VMO) resulting in abnormal patellar tracking and pain. Our study aims to compare the efficacy of high-intensity laser therapy (HILT) on pain and lower extremity function in the treatment of PFPS with different electrophysical agents (EPAs). The study was designed as a single-blind randomized controlled trial. Forty-five people with PFPS (aged 25-45 years) were included in the study. The patients were randomly divided into three groups and a total of ten sessions of treatment were administered to all three groups for 2 weeks, 5 days a week. High-intensity laser (HILT) and exercise program were applied to group 1. Ultrasound (US), transcutaneous electrical nerve stimulation (TENS), and exercise program were applied to group 2. In group 3, US, interferential current (IFC), and exercise program were applied. Both groups underwent three evaluations: pre-treatment, post-treatment, and 12 weeks after treatment. Outcome measures included the visual analog scale for pain severity (VAS), knee flexion range of motion (FROM), Q angle, pain threshold, muscle strength of quadriceps and hamstring, Kujala patellofemoral scoring, lower extremity functional scale (LEFS), and Timed Up and Go Test (TUG). The ANOVA was used for comparing the data of the groups, and two-way repeated measure ANOVA was used to compare at the pre-post and post-intervention 3rd month. The LSD and Bonferroni post hoc tests were also used to identify the between-group differences. Groups 2 and 3 were statistically effective in pain and functionality (p < 0.05). Group 1 was found to be statistically more effective than other groups in reducing pain (95% confidence interval (CI), 0.000/0.000; p = 0.000), increasing knee flexion angle (95% CI, 127.524/135.809; p = 0.000), and increasing lower extremity function (95% CI, 75.970/79.362; p = 0.000). This study indicated that high-intensity laser therapy was found to be a more effective method in the treatment of patellofemoral pain syndrome after 3 months of follow-up compared to US-TENS combination and US-interferential current combination treatments. Also, HILT can be used as an effective method in combination with an appropriate exercise program including vastus medialis strengthening to reduce pain and increase functionality in the patients with PFPS., (© 2024. The Author(s).)

Objectives . This study aimed to examine the effects of a short opponens splint and hand exercise program on pain, hand functionality, daily activities, and work efficacy in computer engineers with wrist pain. Methods . Forty-five engineers were randomized into three groups: group 1 ( n  = 15) utilized both splints and exercises, group 2 ( n  = 15) engaged in exercises only and group 3 ( n  = 15) received no treatment, across 8 weeks, thrice weekly. Only exercises were applied to group 2 ( n  = 15). No treatment was applied for group 3 ( n  = 15). The progress of subjects was controlled periodically each week. Outcome measurements including the Jamar hand dynamometer, pinchmeter, nine-hole peg test (9-NHPT), visual analog scale, Boston carpal tunnel syndrome questionnaire and Michigan hand outcome questionnaire (MHQ) were evaluated pre and post treatment during the study period. Results . Comparing the outcome measurements of the three groups showed a statistically significant difference between them except for the 9-NHPT and MHQ pain and esthetics ( p  < 0.05). According to post-hoc tests, groups 1 and 2 had more significant differences than group 3. Also, there was no statistically significant difference in any parameter between group 1 and group 2 ( p  > 0.017). Conclusion. Non-restrictive minimal orthosis or exercise programs are advisable for individuals with wrist pain.

Objectives: To compare the effectiveness of pharmacological (PT) and nonpharmacological treatments (NPT) in women with primary dysmenorrhea (PD) and determine the most effective treatment method., Material and Methods: We enrolled 85 PD participants with PD who were randomly classified into five groups: pharmacological groups; naproxen sodium (NS) and micronized purified flavanoid fraction (MPFF), nonpharmacological groups; motor imagery focused pelvic floor exercise (MOPEXE) and acupressure, and no treatment group; control. Initial assessment was conducted in all groups on the first day of the menstrual cycle. After the end ofthe third menstrual cycle, the specialist physiotherapist and the obstetrician conducted a final evaluation. Intensity and nature of pain were evaluated with the Short-Form McGill Pain Questionnaire (SF-MPQ), and menstrual attitudes and behaviors were evaluated using the Menstruation Attitude Questionnaire (MAQ)., Results: In the total pain dimension scores, which are the sum of the affective dimension of pain and sensory dimension scores, the pre-post treatment difference was the highest in the mean of the total pain dimension. The highest was for MOPEXE (15.12 ± 4.44), followed by MPFF (7.53 ± 6.8); acupressure (7.47 ± 5.28) and NS (4.47 ± 4.91) showed more significant change than the control group (p = 0.001). The mean difference in visual analog scale (VAS) scores was highest in MOPEXE (4.53 ± 1.5), followed by acupressure (2.35 ± 1.66); MPFF (1.88 ± 1.73) and NS (1.65 ± 1.84) scores were more significant than the control group (p= 0.001). Regarding total pain intensity, the highest was MOPEXE (2.59 ± 0.94), followed by MPFF (1.18 ± 0.88); acupressure (1.06 ± 0.83) and NS (0.82 ± 1.01) scores were more significant compared to the control group (p = 0.001). There was no significant change in the pre-post difference values in the MAQ subparameters: menstruation as deliberate event, menstruating as bothersome event, menstruation as natural event, anticipation and prediction of the onset of menstruation, and denial of any effects of menstruation; menstruation as a natural event resulted in insignificant changes in parameters (p = 0.579, p = 0.074, p = 0.892, p = 0.056, p = 0. 377)., Conclusions: PT and NPT methods in the study were effective in coping with PD-associated pain. MPFF was more effective than the NS group in terms of relieving pain. In terms of pain, MOPEXE and acupressure groups were as effective as PT. The most effective of these treatment methods was the MOPEXE group created by the researcher.

Altered energy metabolism and changes in glycolytic and oxidative phosphorylation pathways are hallmarks of all cancer cells. The expression of select genes associated with the production of various enzymes and proteins involved in glycolysis and oxidative phosphorylation were assessed in the clonal plasma cells derived from patients with newly diagnosed multiple myeloma (NDMM) enrolled in the Multiple Myeloma Research Foundation (MMRF) CoMMpass data set. A scoring system consisting of assigning a point for every gene where their fragments per kilobase of transcript per million (FPKM) was above the median yielded a minimum of 0 and a maximum of 12 for the set of genes in the glycolytic and oxidative phosphorylation pathways to create a total energy metabolism molecular signature (EMMS) score. This EMMS score was independently associated with worse progression free survival (PFS) and overall survival (OS) outcomes of patients with NDMM. A higher EMMS score was more likely to be present in clonal plasma cells derived from Multiple myeloma (MM) patients than those from patients with monoclonal gammopathy of undetermined significance (MGUS). This was functionally confirmed by the clonal plasma cells from MM patients having a higher rate of mitochondrial and glycolysis-derived ATP formation than clonal plasma cells from MGUS patients. Thus, this study provides evidence for the effect of energy metabolism within clonal plasma cells on pathogenesis and outcomes of patients with MM. Exploiting the energy-producing metabolic pathways within clonal plasma cells for diagnostic and therapeutic purposes in MM should be explored in the future., (© 2022 Wiley Periodicals LLC.)

Background and Objective: Caring for a child with a disability affects musculoskeletal system pain, fatigue, sleep quality, and anxiety of the mothers. The purpose of the study was to determine the effectiveness of breathing exercises in mothers with chronic non-specific low back pain (NLBP)., Methods: Forty-three mothers with chronic NLBP were randomly assigned to the experimental group (n= 23) and the control group (n= 20). The experimental group received breathing exercises with core stabilization exercises (BSET) for three sessions a week for 8 weeks, and the control group performed stabilization exercises (SET) only, for the same period. Pain severity, fatigue, anxiety, and sleep quality were evaluated before and after the treatment programs., Results: After the treatment programs, significant differences were observed in pain, fatigue, and sleep quality in both groups (p< 0.05). However, the BSET group showed a significantly better improvement in anxiety levels and sleep quality than the SET group (p< 0.05)., Conclusions: The improvements in pain, fatigue and sleep quality were seen in both groups after treatment programs. It is recommended breathing exercises are added to core stabilization programs to provide greater improvements in anxiety level and sleep quality for mothers of children with disabilities, who have NLBP.

Objective: This study has been conducted to examine the effects of posture, cervical region and oropharyngeal exercises in patients with Obstructive Sleep Apnea Syndrome (OSAS)., Method: Thirty patients with OSAS have been randomly divided into two groups. The first group received supervised exercise program including oropharyngeal, posture and cervical region exercises for 12 weeks. The patients in the control group have been informed about the posture but the exercise was not recommended. Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), Short Form 36 (SF-36), International Physical Activity Questionnaire-Short Form (IPAQ-SF) and 6 Minute Walk Test (6MWT) have been used in the evaluation of individuals participating in the study. Evaluations have been made at the beginning of the treatment and at the end of the 12-week exercise program., Results: Statistically significant improvements have been observed in the exercise group in PSQI total value, ESS score, SF-36 General Health Subscale and 6MWT (p< 0.05). Statistical significance could not be reached for other parameters., Conclusions: Sleep quality, general health, and functional capacity have been found to improve in OSAS patients with oropharyngeal exercises.

The well-known health-led growth hypothesis claims a positive correlation between health expenditure and economic growth. The aim of this paper is to empirically investigate the health-led growth hypothesis for the Turkish economy. The bound test approach, autoregressive-distributed lag approach (ARDL) and Kalman filter modeling are employed for the 1975-2013 period to examine the co-integration relationship between economic growth and health expenditure. The ARDL model is employed in order to investigate the long-term and short-term static relationship between health expenditure and economic growth. The results show that a 1 % increase in per-capita health expenditure will lead to a 0.434 % increase in per-capita gross domestic product. These findings are also supported by the Kalman filter model's results. Our findings show that the health-led growth hypothesis is supported for Turkey.

Objective: This study aimed to evaluate postural awareness and changes in posture and flexibility of students who took Clinical Pilates class as an elective course at the undergraduate level., Methods: The study conducted from 2013-2016 included 98 students who took Clinical Pilates class at the Department of Physical Therapy and Rehabilitation, School of Health Sciences, Istanbul Medipol University, Turkey. The flexibility levels of the study participants were measured before and after the Clinical Pilates education using finger-to-floor test and modified Schober's test. Observational posture analysis and postural awareness were recorded using the scale prepared by the researchers., Results: The post-education evaluations showed that postural distortions were fixed, and a significant increase in the postural awareness of the students was observed compared with the pre-education period. The results of both modified Schober's test and finger-to-floor test, which were used to measure the flexibility levels, showed a statistically significant increase in post-education scores compared with those of the pre-education period., Conclusion: This study showed that the Clinical Pilates course increased postural awareness and flexibility of physical therapy students and fixed postural distortions. Thus, the inclusion of Clinical Pilates class in the undergraduate education is considered to be important., Competing Interests: Declaration of interest: None.

Effects of microbial transglutaminase (MTGase), fibrin/thrombin combination (fibrimex), alginate or combination of these binding agents on physicochemical parameters of cooked ground beef with reduced salt level were investigated. Seventeen treatments included three control (no binding agent) groups incorporated with varying concentrations of salt (0.5, 1, 2%, w/w) and fourteen treatment groups produced with MTGase or fibrimex or alginate or their combinations at 0.5 or 1% salt levels. The samples were analyzed for cooking loss (CL), pH, color, moisture, fat, protein, ash, salt, texture and TBARS. The results indicated that the use of MTGase or fibrimex or MTGase/fibrimex combination had significant effect on preventing textural deterioration caused by salt reduction. Even though the use of MTGase resulted in higher CL values, formulation of ground beef with fibrimex or alginate or MTGase/fibrimex/alginate combinations reduced CL when compared with the control groups. The use of fibrimex in ground beef resulted in a decrease in TBARS, lightness, redness and pH values. However, the use of alginate caused an increase in pH, lightness and redness values of ground beef. Based on the present study, the use of fibrimex or a combination of fibrimex with MTGase in the product formulation can be an effective strategy to reduce cooking loss, to improve or maintain the textural properties and to extend shelf life of cooked ground beef with reduced salt level.

The shape of walled cells such as fungi, bacteria, and plants are determined by the cell wall. Models for cell morphogenesis postulate that the effects of turgor pressure and mechanical properties of the cell wall can explain the shapes of these diverse cell types. However, in general, these models await validation through quantitative experiments. Fission yeast Schizosaccharomyces pombe are rod-shaped cells that grow by tip extension and then divide medially through formation of a cell wall septum. Upon cell separation after cytokinesis, the new cell ends adopt a rounded morphology. Here, we show that this shape is generated by a very simple mechanical-based mechanism in which turgor pressure inflates the elastic cell wall in the absence of cell growth. This process is independent of actin and new cell wall synthesis. To model this morphological change, we first estimate the mechanical properties of the cell wall using several approaches. The lateral cell wall behaves as an isotropic elastic material with a Young's modulus of 50 ± 10 MPa inflated by a turgor pressure estimated to be 1.5 ± 0.2 MPa. Based upon these parameters, we develop a quantitative mechanical-based model for new end formation that reveals that the cell wall at the new end expands into its characteristic rounded shape in part because it is softer than the mature lateral wall. These studies provide a simple example of how turgor pressure expands the elastic cell wall to generate a particular cell shape., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In hair cells, mechanotransduction channels are located in the membrane of stereocilia tips, where the base of the tip link is attached. The tip-link force determines the system of other forces in the immediate channel environment, which change the channel open probability. This system of forces includes components that are out of plane and in plane relative to the membrane; the magnitude and direction of these components depend on the channel environment and arrangement. Using a computational model, we obtained the major forces involved as functions of the force applied via the tip link at the center of the membrane. We simulated factors related to channels and the membrane, including finite-sized channels located centrally or acentrally, stiffness of the hypothesized channel-cytoskeleton tether, and bending modulus of the membrane. Membrane forces are perpendicular to the directions of the principal curvatures of the deformed membrane. Our approach allows for a fine vectorial picture of the local forces gating the channel; membrane forces change with the membrane curvature and are themselves sufficient to affect the open probability of the channel., (Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Cell shape is an important cellular parameter that influences the spatial organization and function of cells. However, it has often been challenging to study the effects of cell shape because of difficulties in experimentally controlling cell shape in a defined way. We describe here a method of physically manipulating sea urchin cells into specified shapes by inserting them into micro-fabricated chambers of different shapes. This method allows for generation of large systematic and quantitative data sets and may be adaptable for different cell types and contexts.

The mechanism by which spindle microtubules (MTs) determine the site of cell division in animal cells is still highly controversial. Putative cytokinesis "signals" have been proposed to be positioned by spindle MTs at equatorial cortical regions to increase cortical contractility and/or at polar regions to decrease contractility [Rappaport, 1986; von Dassow, 2009]. Given the relative paucity of MTs at the future division site, it has not been clear how MTs localize cytokinesis factors there. Here, we test cytokinesis models using computational and experimental approaches. We present a simple lattice-based model in which signal-kinesin complexes move by transient plus-end directed movements on MTs interspersed with occasions of uniform diffusion in the cytoplasm. In simulations, complexes distribute themselves initially at the spindle midzone and then move on astral MTs to accumulate with time at the equatorial cortex. Simulations accurately predict cleavage patterns of cells with different geometries and MT arrangements and elucidate several experimental observations that have defied easy explanation by previous models. We verify this model with experiments on indented sea urchin zygotes showing that cells often divide perpendicular to the spindle at sites distinct from the indentations. These studies support an equatorial stimulation model and provide a simple mechanism explaining how cytokinesis factors localize to the future division site., (Copyright © 2012 Wiley Periodicals, Inc.)

In hair cells, although mechanotransduction channels have been localized to tips of shorter stereocilia of the mechanically sensitive hair bundle, little is known about how force is transmitted to the channel. Here, we use a biophysical model of the membrane-channel complex to analyze the nature of the gating spring compliance and channel arrangement. We use a triangulated surface model and Monte Carlo simulation to compute the deformation of the membrane under the action of tip link force. We show that depending on the gating spring stiffness, the compliant component of the gating spring arises from either the membrane alone or a combination of the membrane and a tether that connects the channel to the actin cytoskeleton. If a bundle is characterized by relatively soft gating springs, such as those of the bullfrog sacculus, the need for membrane reinforcement by channel tethering then depends on membrane parameters. With stiffer gating springs, such as those from rat outer hair cells, the channel must be tethered for all biophysically realistic parameters of the membrane. We compute the membrane forces (resultants), which depend on membrane tension, bending modulus, and curvature, and show that they can determine the fate of the channel., (Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

In order to measure the nucleation of nouveau adhesions on the ventral surface of a cell, we have combined phase shifting laser feedback interferometry with a high numerical aperture inverted fluorescence microscope. We use fluorescence to image molecules at the adhesion site and stage scanning interference microscopy in order to measure the distance between the ventral surface of a cell and the substratum with several nanometer precision. Our analytic and Monte Carlo simulations of integrin mediated adhesions predict several features of these nouveau adhesions. An analysis of the energetics of membrane bending and the effects of a composite system of freely diffusing repellers and receptors and a fixed network of ligands on the extracellular matrix predicts that a small bundle of actin filaments should be able to push the membrane down to the extracellular matrix and nucleate a nouveau adhesion with critical radius below the diffraction limit. We have obtained a map of the reflectivity of the ventral surface of fixed metastatic mammary adenocarcinoma cells and we have shown that the data are correlated with markers for a focal adhesion adaptor protein. We are modeling the interference of the incident electric field with the field reflected from the ventral surface so as to obtain the surface topography at focal adhesions from the optical phase data.

We present a model that provides a mechanistic understanding of the processes that govern the formation of the earliest integrin adhesions ex novo from an approximately planar plasma membrane. Using an analytic analysis of the free energy of a dynamically deformable membrane containing freely diffusing receptors molecules and long repeller molecules that inhibit integrins from binding with ligands on the extracellular matrix, we predict that a coalescence of polymerizing actin filaments can deform the membrane toward the extracellular matrix and facilitate integrin binding. Monte Carlo simulations of this system show that thermally induced membrane fluctuations can either zip-up and increase the radius of a nucleated adhesion or unzip and shrink an adhesion, but the fluctuations cannot bend the ventral membrane to nucleate an adhesion. To distinguish this integrin adhesion from more mature adhesions, we refer to this early adhesion as a nouveau adhesion.

Stochastic methods have been a staple for understanding complex systems in chemistry and physics. In the biological context, they are useful for understanding phenomena ranging from molecular-level fluctuations to cellular movement. We review the basic formalism behind stochastic methods and outline how they can be implemented for quantifying gene expression, movement of molecular motors, and the dynamics of cytoplasmic components. We show that stochastic methods are quantitative checks for proposed molecular mechanisms and can pose new questions for experiments. Structural information of cellular components can be incorporated into stochastic models to reveal new biological insights.

In the cell, the plasma membrane is often densely decorated by transmembrane proteins. The morphology and dynamics of the membrane are strongly influenced by the presence of proteins. In this paper, we use a coarse-grained model to explore the composite membrane-protein system and develop a simulation methodology based on thermodynamic integration to examine free energy changes during membrane shape transitions. The authors show that a critical concentration of conical membrane proteins or proteins with nonzero spontaneous curvature can drive the formation of small vesicles. The driving force of vesicle budding stems from the preference of proteins to gather in regions of high curvature. A sufficiently high concentration of proteins therefore can influence the topology of the membrane. The biological significance of our results is discussed.

Motile cells explore their surrounding milieu by extending thin dynamic protrusions, or filopodia. The growth of filopodia is driven by actin filament bundles that polymerize underneath the cell membrane. We compute the mechanical and dynamical features of the protrusion growth process by explicitly incorporating the flexible plasma membrane. We find that a critical number of filaments are needed to generate net filopodial growth. Without external influences, the filopodium can extend indefinitely up to the buckling length of the F-actin bundle. Dynamical calculations show that the protrusion speed is enhanced by the thermal fluctuations of the membrane; a filament bundle encased in a flexible membrane grows much faster. The protrusion speed depends directly on the number and spatial arrangement of the filaments in the bundle and whether the filaments are tethered to the membrane. Filopodia also attract each other through distortions of the membrane. Spatially close filopodia will merge to form a larger one. Force-velocity relationships mimicking micromanipulation experiments testing our predictions are computed.

Lamellipodium extension, incorporating actin filament dynamics and the cell membrane, is simulated in three dimensions. The actin filament network topology and the role of actin-associated proteins such as Arp2/3 are examined. We find that the orientational pattern of the filaments is in accord with the experimental data only if the spatial orientation of the Arp2/3 complex is restricted during each branching event. We hypothesize that branching occurs when Arp2/3 is bound to Wiskott-Aldrich syndrome protein (WASP), which is in turn bound to Cdc42 signaling complex; Arp2/3 binding geometry is restricted by the membrane-bound complex. Using mechanical and energetic arguments, we show that any membrane protein that is conical or trapezoidal in shape preferentially resides at the curved regions of the plasma membrane. We hypothesize that the transmembrane receptors involved in the recruitment of Cdc42/WASP complex has this property and concentrate at the leading edge. These features, combined with the mechanical properties of the cell membrane, explain why lamellipodium is a flat organelle.

Jarzynski's relation and the fluctuation theorem have established important connections between nonequilibrium statistical mechanics and equilibrium thermodynamics. In particular, an exact relationship between the equilibrium free energy and the nonequilibrium work is useful for computer simulations. In this paper, we exploit the fact that the free energy is a state function, independent of the pathway taken to change the equilibrium ensemble. We show that a generalized expression is advantageous for computer simulations of free energy differences. Several methods based on this idea are proposed. The accuracy and efficiency of the proposed methods are evaluated with a model problem., ((c) 2004 American Institute of Physics.)

A genuinely three-dimensional system, viz. the hyperbolic four-sphere scattering system, is investigated with classical, semiclassical, and quantum mechanical methods at various center-to-center separations of the spheres. The efficiency and scaling properties of the computations are discussed by comparisons to the two-dimensional three-disk system. While in systems with few degrees of freedom modern quantum calculations are, in general, numerically more efficient than semiclassical methods, this situation can be reversed with increasing dimension of the problem. For the four-sphere system with large separations between the spheres, we demonstrate the superiority of semiclassical versus quantum calculations, i.e., semiclassical resonances can easily be obtained even in energy regions which are unattainable with the currently available quantum techniques. The four-sphere system with touching spheres is a challenging problem for both quantum and semiclassical techniques. Here, semiclassical resonances are obtained via harmonic inversion of a cross-correlated periodic orbit signal.

A singular value decomposition based harmonic inversion signal processing scheme is applied to the semiclassical initial value representation (IVR) calculation of molecular vibrational states. Relative to usual IVR procedure of Fourier analysis of a signal made from the Monte Carlo evaluation of the phase space integral in which many trajectories are needed, the new procedure obtains acceptable results with many fewer trajectories. Calculations are carried out for vibrational energy levels of H2O to illustrate the overall procedure., ((c) 2004 American Institute of Physics)