Miracle-dz/UniFAR-FTUs huggingface dataset:
SHPS‐1 regulates integrin‐mediated cytoskeletal reorganization and cell motility

The transmembrane glycoprotein SHPS‐1 binds the protein tyrosine phosphatase SHP‐2 and serves as its substrate. Although SHPS‐1 has been implicated in growth factor‐ and cell adhesion‐induced signaling, its biological role has remained unknown. Fibroblasts homozygous for expression of an SHPS‐1 mutant lacking most of the cytoplasmic region of this protein exhibited increased formation of actin stress fibers and focal adhesions. They spread more quickly on fibronectin than did wild‐type cells, but they were defective in subsequent polarized extension and migration. The extent of adhesion‐induced activation of Rho, but not that of Rac, was also markedly reduced in the mutant cells. Activation of the Ras–extracellular signal‐regulated kinase signaling pathway and of c‐Jun N‐terminal kinases by growth factors was either unaffected or enhanced in the mutant fibroblasts. These results demonstrate that SHPS‐1 plays crucial roles in integrin‐mediated cytoskeletal reorganization, cell motility and the regulation of Rho, and that it also negatively modulates growth factor‐induced activation of mitogen‐activated protein kinases.
Polarized secretion of an ectopic protein in Drosophila salivary glands in vivo.

Epithelial cells can secrete specific proteins in a polarized manner, either from the apical or basolateral surface. Intracellular protein sorting which results in polarized secretion has previously been studied using epithelial tissue culture cells. We describe here the use of Drosophila larval salivary glands for the study of polarized secretion by epithelia in vivo, and address whether an ectopically synthesized secretory protein can be sorted and targeted to the correct cell surface for secretion. Larval cuticle proteins (LCPs) and salivary gland secretion (Sgs) proteins of Drosophila melanogaster are apically secreted proteins that are produced respectively by the epidermis and salivary glands. We have transformed Drosophila with a hybrid gene consisting of the sgs‐4 promoter sequence and the coding sequence for a variant (LCP‐f2) of LCP‐2. We have found that transgenic late third instar larvae produce LCP‐f2 only in the salivary glands and that LCP‐f2 is properly secreted in vivo in a polarized manner from only the apical surface of the cells into the gland lumen. The results indicate that apical secretion does not depend on a tissue‐specific targeting signal contained within the protein.
A Knotless Flexor Tendon Repair Technique Using a Bidirectional Barbed Suture: An Ex Vivo Comparison of Three Methods

Background: Flexor tendon repairs using conventional suture require knots that enlarge the cross-sectional area at the repair site. This enlargement increases the force of finger flexion and jeopardizes the integrity of a nascent tendon repair during rehabilitation. The authors hypothesized that a knotless flexor tendon repair using bidirectional barbed suture has similar strength and with reduced cross-sectional area compared with traditional techniques. Methods: Sixty-six fresh porcine flexor digitorum profundus tendons were divided randomly into three groups. Tendons were transected and repaired with one of the following techniques: two-strand Kessler technique, four-strand Savage technique, or four-strand knotless technique. The cross-sectional area of each tendon was calculated at the repair site before and after repair. All tendons underwent mechanical testing to assess the 2-mm-gap formation force and ultimate strength. Results: The 2-mm-gap formation force and ultimate strength of the Savage and knotless technique groups were not significantly different; however, both were significantly greater than those of the Kessler repair group (p < 0.05). The repair-site cross-sectional area of tendons repaired with the knotless technique was significantly smaller than that of tendons repaired with the Kessler or Savage technique (p < 0.01). Tendons repaired with the knotless technique also had a significantly smaller change in repair-site cross-sectional area (p < 0.01). Conclusions: The authors demonstrate that knotless flexor tendon repair with barbed suture has equivalent strength and reduced repair-site cross-sectional area compared with traditional techniques. The smaller tendon profile may decrease gliding resistance, thus reducing the risk for postsurgical tendon rupture during rehabilitation.
A study on the gross deployment of bank credit to various sectors in the economy

A wide range of financial institutions exist in the country to provide credit to various sectors of the economy. They provide a variety of credit facilities such as short-term working loans to corporate, medium and long-term loans for financing large infrastructure projects and retail loans for various purposes. Unlike other segments of the financial market, the credit market is well spread throughout the country and it touches the lives of all segments of the population. One of the clearest indicators of whether economic growth has picked up or not is the growth (or degrowth) in the bank credits. There are various factors that influences the growth of bank credit. Some of the factors are: Gross domestic factor, interest rates on lending by banks, financial performance of banks (NPAs of banks, asset quality, capital adequacy ratio etc.), commodities prices and propensity to consume has also a role to play. Also, shifting in demand to other forms of credit too influences the growth in the bank credit. Today, various other credit sources such as commercial papers, bonds etc. are available with lucrative borrowing rates.
Is China’s Manufacturing Industry Efficient? Evidence from an Energy-Rebound Effect Perspective

ABSTRACT Majority of the increase in global energy consumption is from China; hence, studying energy issues, especially in China’s manufacturing industry (CMI), is worthwhile and of much interest in the academic field. Based on the translog cost function, we develop a research framework to study the rebound effect of CMI. Considering the effect of asymmetric energy price, we augment the energy-cost function with asymmetric influence constraint of energy price. Again, we add time series data of CMI’s capital, labor, energy, and mid-input to the model to calculate the direct rebound effect of CMI. We find that the rebound effect of CMI is 44.2%, and CMI still has large energy-conservation potentials. Based on the results of this study, some policy recommendations are provided.
NQO1 rs1800566 C>T polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population

Abstract Background. Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90% of esophageal cancers. Genetic factors may play an important role in the carcinogenesis of ESCC. Methods. We conducted a hospital-based case–control study to evaluate functional NAD(P)H:quinone oxidoreductase 1 (NQO1) rs1800566 C>T and NQO2 rs2070999 G>A single-nucleotide polymorphisms on the risk of ESCC. A total of 629 patients with ESCC and 686 controls were recruited for this study. The genotypes were determined using the ligation detection reaction method. Results. When the NQO1 rs1800566 CC homozygote genotype was used as the reference group, the TT genotype was associated with a significantly decreased risk of ESCC. In the recessive model, when the NQO1 rs1800566 CC/CT genotypes were used as the reference group, the TT homozygote genotype was associated with a 31% decreased risk of ESCC. A significantly decreased risk of ESCC was evident in patients with the NQO1 rs1800566 C>T polymorphism among females, those of a younger age (<63 years), those who had never smoked, those who consumed alcohol and those who did not. There was no association found between the NQO2 rs2070999 G>A polymorphism and ESCC risk. Conclusion. The NQO1 rs1800566 TT genotype was associated with a decreased risk of ESCC in a Chinese population. The association was evident among female patients, younger patients, patients who had never smoked, patients who consumed alcohol and those who did not. These findings need to be confirmed by repeating the study in a larger cohort of patients.
High-affinity binding of progesterone to the plasma membrane of Xenopus oocytes: characteristics of binding and hormonal and developmental control.

Progesterone induces maturation of the amphibian oocyte through its action on the plasma membrane. However, whether or not this action requires high-affinity binding to a specific receptor is unclear. In this study, the binding activity of progesterone was characterized in plasma membranes from whole ovaries or defolliculated oocytes of Xenopus laevis. Membrane-bound, radiolabeled progesterone was isolated by filtration of membrane suspensions and quantified by liquid scintillation. The association of progesterone to membrane preparations reached equilibrium within 15 min. Progesterone binding activity was directly proportional to the sample concentration, was significantly reduced by trypsin digestion, and was pH-dependent and temperature-sensitive. Also, binding activity was observed in membrane preparations from whole ovaries and defolliculated oocytes but not in those from somatic cells, indicating that progesterone binding is restricted to the oocyte membrane. Scatchard analysis indicated a single class of high-affinity (average KD, 10(-9) M), low-capacity (average concentration, 10(-12) mol/mg protein) binding sites for progesterone in all oocyte membrane preparations tested. Progesterone binding activity was also detected in preparations from albino frog ovaries, indicating that the binding activity is not an artifact of melanin contamination. Competition studies showed the following order of affinities: progesterone > pregnenolone > 17 alpha, 20 beta, 21-trihydroxy-4-pregnen-3-one > 11-deoxycorticosterone > 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one > 11-deoxycortisol > estradiol > R5020 > corticosterone > aldosterone > cortisol > androstenedione > ouabain. (ABSTRACT TRUNCATED AT 250 WORDS)
Progesterone Modulates the Expression of Interleukin‐6 in Cultured Term Human Uterine Cervical Fibroblasts

Citation Kim M‐G, Shim J‐Y, Pak JH, Jung B‐K, Won H‐S, Lee P‐R, Kim A. Progesterone modulates the expression of interleukin‐6 in cultured term human uterine cervical fibroblasts. Am J Reprod Immunol 2012; 67: 369–375
The Challenges of NEMO in 6LoWPAN Smart Building Area

The network mobility (NEMO) management for a mobile network of IPv6 low-power personal area network (6LoWPAN) in smart buildings has attracted much interest recently, this is partly due to the emergence of the internet of things (IoT). For the specific case of hospital environments, NEMO provides continued connectivity with the Internet for patients attached with 6LoWPAN mobile nodes (MNs) regardless of patients' locations. NEMO comprises a set of mobile network nodes (MNNs) that could move together as a single unit, and each of these mobile networks has a mobile router (MR) that can change its attachment point to the Internet as the network moves together. Even though NEMO has a low signaling cost, but there is a need to understand their challenges for a 6LoWPAN mobile network in smart buildings. If the MR loses its energy, the connectivity with the network will be lost. In this paper, to illustrate the challenges of NEMO in smart buildings like hospital environments, the traffic load at MR will be evaluated against the number of MNNs, number of handovers, and data arrival rate. This has been simulated by OMNet++4.3. 1 and Contiki.
Approaches to Ras signaling modulation and treatment of Ras-dependent disorders: a patent review (2007 – present)

Introduction: Ras proteins are small GTPases molecular switches that cycle through two alternative conformational states, a GDP-bound inactive state and a GTP-bound active state. In the active state, Ras proteins interact with and modulate the activity of several downstream effectors regulating key cellular processes including proliferation, differentiation, survival, senescence, migration and metabolism. Activating mutations of RAS genes and of genes encoding Ras signaling members have a great incidence in proliferative disorders, such as cancer, immune and inflammatory diseases and developmental syndromes. Therefore, Ras and Ras signaling represent important clinical targets for the design and development of pharmaceutically active agents, including anticancer agents. Areas covered: The authors summarize methods available to down-regulate the Ras pathway and review recent patents covering Ras signaling modulators, as well as methods designed to kill specifically cancer cells bearing activated RAS oncogene. Expert opinion: Targeted therapy approach based on direct targeting of molecules specifically altered in Ras-dependent diseases is pursued with molecules that down-regulate expression or inhibit the biological function of mutant Ras or Ras signaling members. The low success rate in a clinical setting of molecules targeting activated members of the Ras pathway may require development of novel approaches, including combined and synthetic lethal therapies.
Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation.

BACKGROUND & AIMS Interferon alfa-based regimens used to treat recurrent hepatitis C virus (HCV) infection after liver transplantation are poorly tolerated, associated with generally modest efficacy, and can interact with immunosuppressive agents. We evaluated the efficacy and safety of an interferon-free regimen of the nucleotide polymerase inhibitor sofosbuvir combined with ribavirin for 24 weeks in treating post-transplantation HCV infection. METHODS In a prospective, multicenter, open-label pilot study, we enrolled patients with compensated recurrent HCV infection of any genotype after a primary or secondary liver transplantation. All patients received 24 weeks of sofosbuvir 400 mg daily and ribavirin starting at 400 mg daily, which was adjusted according to creatinine clearance and hemoglobin values. The primary end point was sustained virologic response 12 weeks after treatment. RESULTS Of the 40 patients enrolled and treated, 78% were male, 85% were white, 83% had HCV genotype 1, 40% had cirrhosis (based on biopsy), and 88% had been previously treated with interferon. Sustained virologic response 12 weeks after treatment was achieved by 28 of 40 patients (70%; 90% confidence interval: 56%-82%). Relapse accounted for all cases of virologic failure. No patients had detectable viral resistance during or after treatment. The most common adverse events were fatigue (30%), diarrhea (28%), and headache (25%). In addition, 20% of the subjects experienced anemia. Two patients discontinued study treatment because of adverse events, which were considered unrelated to study treatment. No deaths, graft losses, or episodes of rejection occurred. No interactions with any concomitant immunosuppressive agents were reported. CONCLUSIONS Sofosbuvir and ribavirin combination therapy for 24 weeks is an effective and well-tolerated interferon-free treatment for post-transplantation HCV infection. EudraCT, Number: 2012-002417-19; ClinicalTrials.gov, Number: NCT01687270.
La participation citoyenne au sein d'une table de quartier : autonomie ou participation programmée?

Etant percue par plusieurs comme etant une alternative a la crise du modele de representation politique, la participation citoyenne est devenue un element incontournable pour plusieurs municipalites. Au Quebec, en plus des lieux de participation publics (conseils municipaux, conseils de quartier a Quebec, ou Office de consultation publique de Montreal (OCPM) par exemple), des instances de concertation locale rassemblent les acteurs-cles d’un territoire, y compris les citoyens, en vue d'ameliorer les conditions de vie des residents. Ces instances deploient diverses strategies pour inciter la population locale a participer a la transformation de son milieu. A Montreal, ces concertations locales sont appelees les Tables de quartier. Comme plusieurs programmes de financements des pouvoirs publics et de fondations ont comme objectif de stimuler la participation citoyenne, nous avons voulu explorer la question suivante : Comment les intervenants œuvrant au sein des Tables de quartier percoivent-ils, d'une part, la participation citoyenne dans les activites de ces Tables de quartier et, d'autre part, l'influence des bailleurs de fonds sur les dispositifs mis en place pour favoriser cette participation? En utilisant une etude de cas, le Conseil Local des Intervenants Communautaires (CLIC) de Bordeaux-Cartierville, nous avons procede a une analyse de contenu de 36 documents produits par la Table de quartier (rapports annuels, plans d'action, etc.) ainsi que les propos de 10 acteurs-cles du milieu. En vue de repondre a notre question de recherche, nous analysons d'abord le dispositif de participation citoyenne mis en place par le CLIC, puis nous explorons les sources d'influence potentielle du dispositif de participation et les motifs lies a son deploiement. Nous mettons en evidence, d'une part, que le dispositif de participation citoyenne de cette Table de quartier est constitue d'une variete de modalites de participation et, d'autre part, que les facteurs principaux pouvant expliquer la mise en œuvre de ce dispositif participatif sont « l'expertise developpee a travers le temps » ainsi que « l'equipe de travail » et que le motif principal vise est celui de « favoriser la construction de la societe civile ». Nous concluons que les bailleurs de fonds, bien que favorisant la participation citoyenne, ont peu d'influence sur les dispositifs mis en œuvre et que dans le cas a l'etude, ce dispositif participatif est surtout explique par des facteurs intrinseques a l'organisme. _____________________________________________________________________ MOTS-CLES DE L’AUTEUR : Participation citoyenne, mobilisation citoyenne, table de quartier, concertation, urbanisme participatif, developpement local social.
Development of a Microscale Cell Culture Analog To Probe Naphthalene Toxicity

Prediction of human response to drugs or chemicals is difficult as a result of the complexity of living organisms. We describe an in vitro model that can realistically and inexpensively study the adsorption, distribution, metabolism, elimination, and potential toxicity (ADMET) of chemicals. A microscale cell culture analog (μCCA) is a physical replica of the physiologically based pharmacokinetics (PBPK) model. Such a microfabricated device consists of a fluidic network of channels to mimic the circulatory system and chambers containing cultured mammalian cells representing key functions of animal “organ” systems. This paper describes the application of a two‐cell system, four‐chamber μCCA (“lung”‐“liver”‐“other tissue”‐“fat”) device for proof‐of‐concept study using naphthalene as a model toxicant. Naphthalene is converted into reactive metabolites (i.e., 1,2‐naphthalenediol and 1,2‐naphthoquinone) in the “liver” compartment, which then circulate to the “lung” depleting glutathione (GSH) in lung cells. Such microfabricated in vitro devices are potential human surrogates for testing chemicals and pharmaceutics for toxicity and efficacy.
Isoniazid hepatotoxicity associated with treatment of latent tuberculosis infection: a 7-year evaluation from a public health tuberculosis clinic.

OBJECTIVES To determine the overall incidence of isoniazid (INH) hepatotoxicity in a public health tuberculosis clinic over a 7-year period, and to determine if systematic, limited aspartate aminotransferase (AST) monitoring would be of benefit in detecting INH hepatotoxicity. METHODS Evaluation of INH hepatotoxicity in adults aged > or = 25 years from a database maintained from fall 1996 to 2003 in a public health department clinic. Hepatotoxicity was defined as AST levels more than five times the upper limit of normal (ULN). RESULTS Among 3,377 patients started on INH therapy, 19 patients had AST levels more than five times the ULN, or a rate of 5.6 per 1,000 patients. Only 1 of 19 patients had prodromal symptoms associated with hepatotoxicity. After 1 month, 3 months, and 6 months of therapy, the numbers of hepatotoxic events per 1,000 patients were 2.75, 7.20, and 4.10. The age-specific numbers of hepatotoxic events per 1,000 patients were 4.40 for those from 25 to 34 years of age, inclusive; 8.54 for those between 35 to 49 years of age, inclusive; and 20.83 for those > or = 50 years old. Age > 49 years (p < 0.02) and baseline AST greater than ULN (p < 0.0003) were risk factors for hepatotoxicity. CONCLUSIONS Consistent with earlier trials, INH hepatoxicity is age related. Our results suggest hepatotoxicity is also related to baseline AST greater than ULN. Moderate-to-severe hepatotoxicity frequently occurs without symptoms, suggesting the value of more widespread AST monitoring.
Assessing outcomes of curricular change: a view from program graduates.

Graduates of dental programs constitute a stakeholder group that is able to provide unique information concerning the effectiveness of the dental curriculum in preparing them for dental careers. Following the implementation of planned curricular changes, graduates of the former and the new curricula were surveyed. Results indicate that, while both groups perceive themselves to have been adequately prepared by their D.D.S. program for practice, graduates of the new curriculum indicated a higher level of preparedness in several areas, especially regarding selecting, prescribing and administering pharmacotherapeutic agents. In addition, the results suggest that the change in the first two years from an emphasis on basic sciences and preclinical laboratory work to an early introduction to live dental patients and the integration of foundation sciences and clinical courses were endorsed. The evidence gathered from this alumni survey indicates that the reforms implemented in the dental curriculum were appropriate. Areas requiring further investigation are also discussed.
Pattern regulation in the stripe of zebrafish suggests an underlying dynamic and autonomous mechanism

The mechanism by which animal markings are formed is an intriguing problem that has remained unsolved for a long time. One of the most important questions is whether the positional information for the pattern formation is derived from a covert prepattern or an autonomous mechanism. In this study, using the zebrafish as the model system, we attempted to answer this classic question. We ablated the pigment cells in limited areas of zebrafish skin by using laser irradiation, and we observed the regeneration of the pigmentation pattern. Depending on the area ablated, different patterns regenerated in a specific time course. The regenerated patterns and the transition of the stripes during the regeneration process suggest that pattern formation is independent of the prepattern; furthermore, pattern formation occurs by an autonomous mechanism that satisfies the condition of “local self-enhancement and long-range inhibition. ” Because the zebrafish is the only striped animal for which detailed molecular genetic studies have been conducted, our finding will facilitate the identification of the molecular and cellular mechanisms that underlie skin pattern formation.
Reactive Oxygen Species‐Caspase‐3 Relationship in Mediating Blood–Brain Barrier Endothelial Cell Hyperpermeability Following Oxygen–Glucose Deprivation and Reoxygenation

Microvascular hyperpermeability that occurs due to breakdown of the BBB is a major contributor of brain vasogenic edema, following IR injury. In microvascular endothelial cells, increased ROS formation leads to caspase‐3 activation following IR injury. The specific mechanisms, by which ROS mediates microvascular hyperpermeability following IR, are not clearly known. We utilized an OGD‐R in vitro model of IR injury to study this.