Miracle-dz/UniFAR-FTUs huggingface dataset:
The occluding loop in cathepsin B defines the pH dependence of inhibition by its propeptide.

Papain-like proenzymes are prone to autoprocess under acidic pH conditions. Similarly, peptides derived from the proregion of cathepsin B are potent pH-dependent inhibitors of that enzyme; i.e., at pH 6.0 the inhibition of human cathepsin B by its propeptide is defined by slow binding kinetics with a Ki of 3.7 nM and at pH 4.0 by classical kinetics with a Ki of 82 nM. This pH dependency is essentially eliminated either by the removal of a portion of the enzyme's occluding loop through deletion mutagenesis or by the mutation of either residue Asp22 or His110 to alanine; e.g., the mutant enzyme His110Ala is inhibited by its propeptide with Ki's of 2.0 +/- 0.3 nM at pH 4.0 and 1.1 +/- 0.2 nM at pH 6.0. For the His110Ala mutant the inhibition also displays slow binding kinetics at both pH 4.0 and pH 6.0. As shown by the crystal structure of mature cathepsin B [Musil, D. , et al. (1991) EMBO J. 10, 2321-2330] Asp22 and His110 form a salt bridge in the mature enzyme, and it has been shown that this bridge stabilizes the occluding loop in its closed position [Nägler, D. K. , et al. (1997) Biochemistry 36, 12608-12615]. Thus the pH dependency of propeptide binding can be explained on the basis of a competitive binding between the occluding loop and the propeptide. At low pH, when the Asp22-His110 pair forms a salt bridge stabilizing the occluding loop in its closed conformation, the loop more effectively competes with the propeptide than at higher pH where deprotonation of His110 and the concomitant destruction of the Asp22-His110 salt bridge results in a destabilization of the closed form of the loop. The rate of autocatalytic processing of procathepsin B to cathepsin B correlates with the affinity of the enzyme for its propeptide rather than with its catalytic activity, thus suggesting a possible influence of occluding loop stability on the rate of processing.
A novel efficiency improvement technique for Doherty power amplifiers

A new efficiency improvement technique is proposed for Doherty power amplifiers (PA), which combines supply switching with load modulation. The proposed technique was demonstrated with a commercial prototype GaN PA. Measurement and simulation results for the Doherty PA, using a 5 MHz LTE signal, showed that the proposed technique significantly improved the average power-added efficiency (PAE) to ~55 %.
Angiotensin II Impairs Endothelial Progenitor Cell Number and Function In Vitro and In Vivo: Implications for Vascular Regeneration

Endothelial progenitor cells (EPCs) contribute to endothelial regeneration. Angiotensin II (Ang II) through Ang II type 1 receptor (AT1-R) activation plays an important role in vascular damage. The effect of Ang II on EPCs and the involved molecular mechanisms are incompletely understood. Stimulation with Ang II decreased the number of cultured human early outgrowth EPCs, which express both AT1-R and Ang II type 2 receptor, mediated through AT1-R activation and induction of oxidative stress. Ang II redox-dependently induced EPC apoptosis through increased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase phosphorylation; decreased Bcl-2 and increased Bax expression; and activation of caspase 3 but had no effect on the low cell proliferation. In addition, Ang II impaired colony-forming and migratory capacities of early outgrowth EPCs. Ang II infusion diminished numbers and functional capacities of EPCs in wild-type (WT) but not AT1a-R knockout mice (AT1a−/−). Reendothelialization after focal carotid endothelial injury was decreased during Ang II infusion. Salvage of reendothelialization by intravenous application of spleen-derived progenitor cells into Ang II-treated WT mice was pronounced with AT1a−/− cells compared with WT cells, and transfusion of Ang II–pretreated WT cells into WT mice without Ang II infusion was associated with less reendothelialization. Transplantation of AT1a−/− bone marrow reduced atherosclerosis development in cholesterol-fed apolipoprotein E–deficient mice compared with transplantation of apolipoprotein E–deficient or WT bone marrow. Randomized treatment of patients with stable coronary artery disease with the AT1-R blocker telmisartan significantly increased the number of circulating CD34/KDR-positive EPCs. Ang II through AT1-R activation, oxidative stress, and redox-sensitive apoptosis signal-regulating kinase 1–dependent proapoptotic pathways impairs EPCs in vitro and in vivo, resulting in diminished vascular regeneration.
Renal neurogenic mediation of intracerebroventricular angiotensin II hypertension in rats raised on high sodium chloride diet.

Chronic elevation of sodium intake may affect the sensitivity of the central nervous system to intracerebroventricular (I.C.V.) angiotensin II (Ang II) infusion. Experiments were conducted to determine the influence of raising Sprague-Dawley rats from 2 to 3 weeks of age on low (5.0 mmol/L per kg food), normal (50 mmol/L per kg food), or high (250 mmol/L per kg food) NaCl diets on renal and cardiovascular responses to low-dose I.C. V. Ang II infusion. At 12 weeks of age, Sprague-Dawley rats were instrumented for chronic study, including brain lateral ventricular cannulation. Artificial cerebrospinal fluid was infused (0.25 microL/min I.C.V.) during control and recovery, whereas Ang II (20 ng/min) was infused for 5 days. During the experiment, respective sodium intakes were infused intravenously over 24 hours. In rats fed high sodium, control mean arterial pressure was 115+/-2 mm Hg and increased to 132+/-4 mm Hg by day 5 of I.C. V. Ang II infusion. This increase in arterial pressure was associated with significant (P<.05) decreases in sodium excretion, leading to the retention of 5.4+/-0.6 mmol/L total sodium over the 5 days of Ang II infusion. In rats raised on low and normal sodium intakes from weaning and in 10-week-old rats exposed to a high sodium diet for only 2 weeks, arterial pressure was not increased and sodium was not retained during I.C. V. Ang II infusion at 20 ng/min. In rats raised on the high sodium diet, bilateral renal denervation abolished the arterial hypertension and reduced the sodium retention over 5 days of I.C. V. Ang II infusion. Thus, chronic elevation of sodium intake increases the hypertensive response to low-dose I.C. V. Ang II infusion, which is dependent on intact renal nerves. We conclude that elevated postnatal NaCl intake enhances the pressor sensitivity of the brain to Ang II.
Mutations in the mitochondrial complex I assembly factor NDUFAF1 cause fatal infantile hypertrophic cardiomyopathy

Background Hypertrophic cardiomyopathy (HCM) is frequently fatal in infancy. Mitochondrial disease causing infantile HCM is characterised by extreme biochemical and genetic heterogeneity, but deficiency of respiratory chain complex I is observed relatively frequently. Identification of the precise genetic basis has prognostic implications for the likelihood of neurological involvement. Objective The authors' objective is to report two heterozygous missense mutations in the NDUFAF1 gene as a cause of fatal infantile HCM in a patient with isolated complex I deficiency. Methods The authors investigated a cohort of 30 paediatric patients with complex I deficiency using biochemical and genetic approaches. The patients were clinically heterogeneous; phenotypes included HCM, Leigh syndrome, other encephalomyopathies and multisystem disease. Complex I assembly was evaluated using Blue Native polyacrylamide gel electrophoresis. Results Sequence analysis of NDUFAF1 revealed compound heterozygous missense mutations (c.631C>T;p.Arg211Cys and c.733G>A;p.Gly245Arg) in one patient with fatal infantile HCM. These changes were absent in 240 ethnically matched control alleles. No NDUFAF1 mutations were observed in the remaining patients. Functional studies demonstrated a severe reduction in NDUFAF1 protein in Western blots of patient fibroblasts and accumulation of abnormal complex I assembly intermediates on Blue Native polyacrylamide gel electrophoresis. Conclusions The authors report a case of fatal infantile HCM caused by missense mutations in NDUFAF1 associated with complex I misassembly. Establishing a genetic diagnosis in mitochondrial cardiomyopathy is challenging and achieved in only a minority of cases because of complex genetics. A precise genetic diagnosis is important to provide accurate prognostic and genetic counselling advice regarding recurrence risks and to guide future reproductive options.
A Hybrid Clustering and SVD-Based Approach for Fuzzy-Neural System Modeling ∗

We propose a fuzzy-neural modeling approach for automatically constructing a fuzzy-neural model from a set of input-output data. The proposed approach consists of two phases, structure identification and parameter identification. In the structure identification phase, rough TSK fuzzy rules are extracted through a clustering algorithm. Then a fuzzy neural network is built in the parameter identification phase for refining the parameters in each rule. To increase the learning speed, we adopt a hybrid learning which is a combination of recursive SVD-based least squares estimator and gradient descent method. Experimental results have shown that our proposed method is able to achieve lower approximation error and faster convergence rate.
Emerging targets for the treatment of depressive disorder

New agents offering novel mechanisms of action are required in the treatment of depressive disorder. Established agents targeting monoamine systems are unsatisfactory because of full and partial treatment resistance, delay in the onset of their effect and the occurrence of side effects. The monoamine hypothesis of depression is now recognised to provide an incomplete explanation of the pathophysiology of depression. New theories have recently developed and new targets for treatment have emerged. We briefly review some important candidate systems and therapeutic targets in depression: the hypothalamic-pituitary-adrenal axis (HPA) and the glucocorticoid and corticotrophin-releasing factor receptors, synaptic plasticity and neurotrophins and the N-methyl-D-aspartate (NMDA) receptor. The putative role of the neuropeptides substance P and neuropeptide Y, the nicotinic system and the potential therapeutic benefits of cannabinoids are also reviewed. Vagal nerve stimulation (VNS) and transcranial magnetic stimulation, serendipitous advances in treatment, are discussed briefly.
Fuzzy–synthetic minority oversampling technique: Oversampling based on fuzzy set theory for Android malware detection in imbalanced datasets

In previous work, imbalanced datasets composed of more benign samples (the majority class) than the malicious one (the minority class) have been widely adopted in Android malware detection. These imbalanced datasets bias learning toward the majority class, so that the minority class examples are more likely to be misclassified. To solve the problem, we propose a new oversampling method called fuzzy–synthetic minority oversampling technique, which is based on fuzzy set theory and the synthetic minority oversampling technique method. As the sample size of the majority class increases relative to that of the minority class, fuzzy–synthetic minority oversampling technique generates more synthetic examples for each minority class examples in the fuzzy region, where the minority examples have a low degree of membership to the minority class and are more likely to be misclassified. Using the new synthetic examples, the classifiers build larger decision regions that contain more minority examples, and they are no longer biased to the majority class. Compared with synthetic minority oversampling technique and Borderline–synthetic minority oversampling technique methods, fuzzy–synthetic minority oversampling technique achieves higher accuracy on both the minority class and the entire datasets.
Senior Project Report Dimension Reduction of the SIFT descriptor and its Object Recognition Application

3 Introduction . 4 Stage (I) . 6 Overview: . 6 (1.1) Brief introduction to OpenCV . 6 (1.2) A simple SIFT feature matching Experiment using brute force approach . 7 (1.3) Finding “Strong” SIFT Keypoints. 9 (1.4) Compare Average Models . 12 (1.5) Compute Probability Density Function and Confusion Probabilities . 14 Stage (2) . 17 Overview . 17 (2.1) SIFT keypoints ranking system . 17 (2.2) Reduce dimensionality of SIFT feature descriptors using t-SNE . 19 (2.3) A simple object classifier . 22 Summary and Possible Future Works . 24 Reference . 24 Appendix . 26 Functional Requirements: . 26 Object Identification: . 26 Program Input: . 26 Program Output: . 27 Non-functional Requirements: . 27 Object recognition . 27 Development/Usage platform . 27
Quantification non invasive de l'hétérogénéité de la perfusion du myocarde par analyse markovienne en imagerie nucléaire SPECT

Les maladies cardiovasculaires representent la premiere cause de mortalite dans le monde, et un tiers de ces deces sont causes par la maladie coronaire et la rupture de plaques d'atherome vulnerables. L'alteration heterogene de la microcirculation coronaire est un phenomene precoce lie a de nombreux facteurs de risque cardiovasculaire qui peut fortement presager du developpement ulterieur de la maladie coronaire, et conduire a l'apparition d'une heterogeneite de la perfusion myocardique. La medecine nucleaire permet l'etude de la perfusion myocardique en routine clinique grâce a la realisation de scintigraphies apres injection d'un traceur radioactif du debit sanguin coronaire. L'analyse des images scintigraphiques de la perfusion permet actuellement le depistage de l'ischemie myocardique, mais la capacite de la technique a mesurer l'heterogeneite de la perfusion dans des zones apparemment normalement perfusees est inconnue. La premiere partie de cette these porte sur une etude clinique retrospective visant a determiner la faisabilite de la quantification de l'heterogeneite de la perfusion du myocarde mesuree par tomographie d'emission monophotonique (TEMP) au Thallium-201 chez des patients diabetiques par rapport a des sujets sains. L'etude clinique a demontre la capacite du Thallium-201 en imagerie TEMP de routine a quantifier une heterogeneite de la perfusion du myocarde plus importante chez des patients diabetiques par rapport a des individus normaux. La seconde partie de cette these teste l'hypothese que l'heterogeneite de la perfusion du myocarde pourrait etre quantifiee en imagerie du petit animal TEMP au Thallium-201 et/ou au Technetium-99m-MIBI par une etude experimentale chez deux modeles animaux de diabete, et serait en correlation avec des alterations histologiques. L'absence de difference d'heterogeneite de la perfusion myocardique entre les animaux diabetiques et controles suggere que les modeles animaux sont peu adaptes, ou que la technologie actuellement disponible ne semble pas satisfaisante pour obtenir des resultats similaires a l'etude clinique.
Predator Cognition Permits Imperfect Coral Snake Mimicry

Batesian mimicry is often imprecise. An underexplored explanation for imperfect mimicry is that predators might not be able to use all dimensions of prey phenotype to distinguish mimics from models and thus permit imperfect mimicry to persist. We conducted a field experiment to test whether or not predators can distinguish deadly coral snakes (Micrurus fulvius) from nonvenomous scarlet kingsnakes (Lampropeltis elapsoides). Although the two species closely resemble one another, the order of colored rings that encircle their bodies differs. Despite this imprecise mimicry, we found that L. elapsoides that match coral snakes in other respects are not under selection to match the ring order of their model. We suggest that L. elapsoides have evolved only those signals necessary to deceive predators. Generally, imperfect mimicry might suffice if it exploits limitations in predator cognitive abilities.
Bile salt–dependent efflux of cellular phospholipids mediated by ATP binding cassette protein B4

Human ABCB4 (multidrug resistance [MDR]3 P‐glycoprotein) is expressed in the canalicular membrane of the hepatocyte. ABCB4 has been shown to be required for phosphatidylcholine (PC) secretion into the bile and to translocate PC across the plasma membrane. To further investigate the function of ABCB4, we established a cell line stably expressing ABCB4 (human embryonic kidney [HEK]/ABCB4). The efflux of phospholipids from HEK/ABCB4 cells was remarkably increased by the addition of taurocholate. In addition, the cholesterol efflux from HEK/ABCB4 cells was also enhanced in the presence of taurocholate. Light scattering measurements suggested that the taurocholate monomer plays an important role in ABCB4‐mediated lipid secretion. On the other hand, the efflux of phospholipids and cholesterol was not mediated by ABCB1 (MDR1) even in the presence of taurocholate. Taurocholate promoted the efflux of phospholipids and cholesterol from HEK/ABCB4 cells more efficiently than glycocholate and cholate. ABCB4‐K435M and ABCB4‐K1075M, Walker A lysine mutants, did not mediate the phospholipid and cholesterol efflux in the presence of taurocholate, suggesting that ATP hydrolysis is essential for the efflux. Verapamil completely inhibited the taurocholate‐dependent efflux of phospholipids and cholesterol from HEK/ABCB4 cells. Mass spectrometry revealed that, in the presence of taurocholate, HEK/ABCB4 cells preferentially secreted PC compared to sphingomyelin. PC vesicles induced cholesterol diffusion from cell membrane, but did not accept cholesterol from ABCB4. Conclusion: ABCB4 mediates the efflux of phospholipids into the canalicular lumen in the presence of bile salts, and plays a crucial role in bile formation and lipid homeostasis. (HEPATOLOGY 2007.)
Location and orientation of panel on the screen as a structural visual element to highlight text displayed

ABSTRACT Searching for information on the internet has become a daily activity. It is considered to be a complex cognitive activity that involves visual attention. Many studies have demonstrated that users’ information search are affected both by the spatial configuration of words and the elements displayed on the screen: elements that are used to structure web pages. One of these elements, the web panel, contains information. Web panel is a rectangular area with a colored background that was used to highlighting content presented in this specific rectangular area. Our general hypothesis was that the presence of a panel on a web page would affect the structure of a word display, as a result, information search accuracy. We carried out an experiment in which we manipulated the presence vs. the absence of a panel, as well as its orientation on the screen (vertical vs. horizontal). Twenty participants were asked to answer questions while their eye movements were recorded. Results showed that the presence of a panel resulted in reduced accuracy and shorter response times. Panel orientation affected scanpaths, especially when they were orientated vertically. We discuss these findings and suggest ways in which this research could be developed further in future.
Optimization of Near-Infrared Fluorescent Sentinel Lymph Node Mapping in Cervical Cancer Patients

Objective: In early cervical cancer, a total pelvic lymphadenectomy is the standard of care, even though most patients have negative nodes and thus undergo lymphadenectomy unnecessarily. Although the value of sentinel lymph node (SLN) mapping in early-stage cervical cancer has not yet been established, near-infrared (NIR) fluorescence imaging is a promising technique to perform this procedure. Near-infrared fluorescence imaging is based on invisible NIR light and can provide high sensitivity, high-resolution, and real-time image guidance during surgery. Methods: Clinical trial subjects were 9 consecutive cervical cancer patients undergoing total pelvic lymphadenectomy. Before surgery, 1.6 mL of indocyanine green adsorbed to human serum albumin (ICG:HSA) was injected transvaginally and submucosally in 4 quadrants around the tumor. Patients were allocated to 500-, 750-, or 1000-&mgr;M ICG:HSA concentration groups. The Mini-FLARE imaging system was used for NIR fluorescence detection and quantitation. Results: Sentinel lymph nodes were identified in all 9 patients. An average of 3.4 ± 1.2 SLNs was identified per patient. No differences in signal to background of the SLNs between the 500-, 750-, and 1000-&mgr;M dose groups were found (P = 0.73). In 2 patients, tumor-positive lymph nodes were found. In both patients, tumor-positive lymph nodes confirmed by pathology were also NIR fluorescent. Conclusions: This study demonstrated preliminary feasibility to successfully detect SLNs in cervical cancer patients using ICG:HSA and the Mini-FLARE imaging system. When considering safety, cost-effectiveness, and pharmacy preferences, an ICG:HSA concentration of 500 &mgr;M was optimal for SLN mapping in cervical cancer patients.
A Twenty-Year Citation Analysis of the Knowledge Outflow and Inflow Patterns from the Journal of Product Innovation Management

Since its inception in 1984, an emphasis on cross-functionality and interdisciplinary research was encrypted into the DNA of the Journal of Product and Innovation Management (JPIM). This essay explores the extent to which the journal has served as a platform for exchange of ideas between different disciplines by examining knowledge outflow and inflow with other scientific journals and disciplines over a 20-year period (1994-2013). Based on an extensive bibliometric database, we gain insights about how JPIM has evolved. We show that the journal has become a gatekeeper, importing knowledge mostly from the marketing and management literatures, and exporting knowledge to the technology and innovations management and the operations management domains.
Public-Private Partnerships For A Sustainable Tourism Development of Urban Destinations. The Case of Braşov, Romania

Considering that there are few success chances for isolated businesses, public-private partnerships represent the basis of tourism businesses’ sustainable development, aiming to attract increasing numbers of visitors in tourism destinations. Within this context, the main aim of the present paper is to identify tourism stakeholders’ intentions to participate in public-private partnerships for a sustainable tourism development of urban destinations. Focused on the increased importance of partnerships between tourism stakeholders, with the common goal of sustainable tourism development, a survey was conducted among the tourism service providers from the Romanian urban destination, Brasov. The research results outline the defi ciencies in the analyzed destination, which lead to a low notoriety of the destination’s management and marketing organization among local tourism stakeholders. In addition, the results show a low level of involvement of tourism operators in supporting the collaboration efforts of this organization. Based on the research results, a theoretical model was proposed for the identifi cation of the signifi cant factors which infl uence local stakeholders’ intentions to participate in public-private partnerships for a sustainable tourism development.
Influence of Leadership Behaviors on Organizational Commitment Among Millennials Working in Commercial Banks in Kenya

XII CHAPTER ONE: INTRODUCTION . 1 1.1 BACKGROUND OF THE STUDY . 1 1.1.1 Leadership behaviors . 3 1.1.2 Organizational Commitment . 5 1.1.3 The Concept of Millennial Employees . 6 1.1.4 Banking sector in Kenya . 7 1.1. 5 Commercial Banks in Kenya . 8 1.2 RESEARCH PROBLEM . 9 1.3 RESEARCH OBJECTIVE . 11 1.4 VALUE OF THE STUDY . 11 CHAPTER TWO: LITERATURE REVIEW . 13 2.