Miracle-dz/UniFAR-FTUs huggingface dataset:
A Structural Basis for the Acute Effects of HIV Protease Inhibitors on GLUT4 Intrinsic Activity*

Human immunodeficiency virus (HIV) protease inhibitors (PIs) act as reversible noncompetitive inhibitors of GLUT4 with binding affinities in the low micromolar range and are known to contribute to alterations in glucose homeostasis during treatment of HIV infection. As aspartyl protease inhibitors, these compounds all possess a core peptidomimetic structure together with flanking hydrophobic moieties. To determine the molecular basis for GLUT4 inhibition, a family of related oligopeptides containing structural elements found in PIs was screened for their ability to inhibit 2-deoxyglucose transport in primary rat adipocytes. The peptide oxybenzylcarbonyl-His-Phe-Phe-O-ethyl ester (zHFFe) was identified as a potent inhibitor of zero-trans glucose flux with a Ki of 26 μm. Similar to PIs, transport inhibition by this peptide was acute, noncompetitive, and reversible. Within a Xenopus oocyte expression system, zHFFe acutely and reversibly inhibited GLUT4-mediated glucose uptake, whereas GLUT1 activity was unaffected at concentrations as high as 1 mm. The related photoactivatable peptide zHFF-p-benzoylphenylalanine-[125I]Tyr-O-ethyl ester selectively labeled GLUT4 in rat adipocytes and indinavir effectively protected against photolabeling. Furthermore, GLUT4 bound to a peptide affinity column containing the zHFF sequence and was eluted by indinavir. These data establish a structural basis for PI effects on GLUT4 activity and support the direct binding of PIs to the transport protein as the mechanism for acute inhibition of insulin-stimulated glucose uptake.
Adaptive 3-D Object Recognition from Multiple Views

The authors address the problem of generating representations of 3-D objects automatically from exploratory view sequences of unoccluded objects. In building the models, processed frames of a video sequence are clustered into view categories called aspects, which represent characteristic views of an object invariant to its apparent position, size, 2-D orientation, and limited foreshortening deformation. The aspects as well as the aspect transitions of a view sequence are used to build (and refine) the 3-D object representations online in the form of aspect-transition matrices. Recognition emerges as the hypothesis that has accumulated the maximum evidence at each moment. The 'winning' object continues to refine its representation until either the camera is redirected or another hypothesis accumulates greater evidence. This work concentrates on 3-D appearance modeling and succeeds under favorable viewing conditions by using simplified processes to segment objects from the scene and derive the spatial agreement of object features. >
Assessment of impacts from human activities on ecosystem components in the Bay of Biscay in the early 1990s

The ecosystem-based approach to fisheries management and, more specifically, the European Marine Strategy Framework Directive require the assessment of the state and dynamics of an ecosystem in order to determine suitable management strategies. This paper takes an analytical approach to assess the state of the Bay of Biscay ecosystem in the early 1990s, chosen as a period of reference because key monitoring data series have been collected since then. To assess the state of the ecosystem, the pressures exerted by six broad categories of human activities were examined. A literature review of the ecosystem components was made and a component tree was tailored according to data availability. Data rich components were subdivided into subcomponents for their assessment while data poor components were assessed at an aggregated level. The component tree of the ecosystem comprised six main branches, four of which further divided into sub-components. In total, assessments were carried out at the level of 19 components. For four of these (fished species, sensitive fish species, marine mammals and turtles) the overall assessments were made combining the status of individual species. Impact from human activities were categorised as (i) “widespread” over the whole Bay of Biscay or “local” and (ii) “possible” when they could be logically expected or “documented” when they were reported in the literature. Fishing appeared to be the only activity exerting widespread documented impacts on several ecosystem components. Terrestrial activities had some possible and documented widespread impacts. With the exception of marine transport impacting seabirds at the regional scale through oil pollution, other activities had only local impacts, mostly nearshore. The reference state in the early 1990s, suggests that continuation of monitoring of vertebrates as well as estuarine and coastal habitats must be central to the monitoring programme and management strategies to be set in the context of the Marine Strategy Framework Directive. Additional monitoring is also required for benthos, substrate and micro-organisms.
Combination of themTOR Inhibitor Ridaforolimus and the Anti-IGF1R Monoclonal Antibody Dalotuzumab: Preclinical Characterization and Phase I Clinical Trial

Purpose: Mammalian target of rapamycin (mTOR) inhibition activates compensatory insulin–like growth factor receptor (IGFR) signaling. We evaluated the ridaforolimus (mTOR inhibitor) and dalotuzumab (anti-IGF1R antibody) combination. Experimental Design: In vitro and in vivomodels, and a phase I study in which patients with advanced cancer received ridaforolimus (10–40 mg/day every day 5/week) and dalotuzumab (10 mg/kg/week or 7.5 mg/kg/every other week) were explored. Results: Preclinical studies demonstrated enhanced pathway inhibition with ridaforolimus and dalotuzumab. With 87 patients treated in the phase I study, main dose-limiting toxicities (DLT) of the combination were primarily mTOR-related stomatitis and asthenia at doses of ridaforolimus lower than expected, suggesting blockade of compensatory pathways in normal tissues. Six confirmed partial responses were reported (3 patients with breast cancer); 10 of 23 patients with breast cancer and 6 of 11 patients with ERþ/high-proliferative breast cancer showed antitumor activity. Conclusions: Our study provides proof-of-concept that inhibiting the IGF1R compensatory response to mTOR inhibition is feasible with promising clinical activity in heavily pretreated advanced cancer, particularly in ERþ/high-proliferative breast cancer (ClinicalTrials.gov identifier: NCT00730379). Clin Cancer Res; 21(1); 49–59. 2014 AACR.
Cervical cytological screening results of 8,495 cases in Turkey--common inflammation but infrequent epithelial cell abnormalities?

BACKGROUND Cervical cancer is the ninth most common cancer among females in Turkey. Cervical smear is a routine screening test used for the detection of cervical abnormalities and also it detects certain infections of the cervix. OBJECTIVE To analyze cervical smear results of our clinic in order to determine most frequent pathology of the women in North Eastern Anatolia Region of Turkey. MATERIALS AND METHODS In a retrospective study design, 8,495 cervical cytology cases diagnosed at the Pathology Department of the Regional Education and Research Hospital in Erzurum over the last one and half years extending from August 2012 to December 2013 were investigated. RESULTS The most common diagnosis was found to be inflammation, 65.5 % (5,566 out of 8,495), and the least was squamous epithelial abnormalities 0.2% (13 out of 8,495). There was some variation among the three pathologists regarding diagnosis but findings for the latter. CONCLUSIONS Regular cervical smear tests are one of the most important strategies in early diagnosis of cervical cancer but there are conflicting data regarding the prevalence of epithelial cell abnormalities in Turkey, and the reasons of this should be investigated.
TDP‐43 and FUS/TLS: sending a complex message about messenger RNA in amyotrophic lateral sclerosis?

TAR DNA binding protein of 43 kDa (TDP‐43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS) have recently been linked to the pathology of amyotrophic lateral sclerosis (ALS). These proteins share many common features that include interaction with either DNA or RNA, participation in the formation of RNP complexes, the formation of pathological aggregates in degenerating motor neurons in ALS, and the ability to impact the RNA metabolism pathway at multiple levels from transcription to translation. Coupled with the observation that mutations in either TDP‐43 or FUS/TLS are associated with ALS, this provides further support for the integral role of altered RNA metabolism in ALS.
Intestinal Permeability and Systemic Endotoxemia After Laparotomic or Laparoscopic Cholecystectomy

Objective:Because laparoscopic cholecystectomy (LC) is widely recognized as a “mild” or “mini-invasive” kind of surgery, in this prospective nonrandomized study, we investigated the effect of intestinal manipulation on intestinal permeability and endotoxemia, in patients undergoing elective cholecystectomy by comparing the laparoscopic with the laparotomic approach. Summary Background Data:The intestine is susceptible to operations at remote locations, and the barrier function is altered during intestinal manipulation, leading to bacterial or endotoxin translocation into the systemic circulation. Methods:Forty-three patients undergoing elective cholecystectomy were divided into either the laparotomic (n = 22) or laparoscopic (n = 21) approach. Intestinal permeability was measured preoperatively and at day 1 and day 3 after surgery using the lactulose/mannitol absorption test. Serial venous blood samples were taken at 0, 30, 60, 90, 120, and 180 minutes, and at 12, 24, and 48 hours after surgery, for endotoxin measurement using the chromogenic limulus amoebocyte lysate assay. Results:Intestinal permeability was significantly increased at day 1 [0.106 ± 0.005 (mean ± SEM)] in the laparotomic group compared with the preoperative level (0.019 ± 0.005, P < 0.05) and to the laparoscopic group at day 1 (0.019 ± 0.005, P < 0.05), which showed no change in comparison with the preoperative level. A significantly higher concentration of systemic endotoxin was detected intraoperatively in the laparotomic group of patients in comparison to the laparoscopic group (P < 0.05). There was a significant positive correlation between systemic endotoxemia and intestinal permeability (rs = 0.958; P = 0.001). Conclusions:An increase in intestinal permeability and a greater degree of systemic endotoxemia are observed during laparotomic cholecystectomy. This suggests that intestinal manipulation may impair gut mucosal barrier function and contribute to the systemic inflammatory response see in open cholecystectomy.
Erste Ergebnisse der GymNAST-Studie

Zusammenfassung Lang andauernde intensivmedizinische Behandlung verursacht häufig eine Schwäche der Muskulatur. Betroffen sind sowohl die Extremitäten als auch die Atmung. Die Beatmungsentwöhnung ist erschwert, die Mortalität steigt. Eine Studie hat nun den Versuch unternommen, die Dauer der Intensivbehandlung zu bestimmen und Prädiktoren für Alltagsbewegungen zu entwickeln, um Therapien entsprechend anpassen zu können.
Influence of Age on Gastric Emptying in Healthy Chinese

Radionuclide gastric emptying studies, including solid and liquid phases, were used to evaluate the gastric motility of healthy Chinese. Forty-eight patients (18-76 years old) and 38 volunteers (27-79 years old) accepted solid or liquid food gastric emptying studies, respectively. The solid meal was two fried eggs mixed with 500 µCi Tc-99m phytate and two pieces of toast to form a sandwich. The liquid meal was 500 ml of water with 5% glucose and 500 µCi Tc-99m phytate. Studies were performed with the subjects in the supine position and a gamma camera in a left anterior oblique (LAO) position while data were collected for 90 minutes and 30 minutes after finishing the solid and liquid meal, respectively. The gastric emptying time was presented as a half-time (t½) of the food emptying from the stomach. The study results showed that the t½ is 89.0 ± 17.8 in older patients (>60 years old) and 88.0 ± 18.2 in younger patients (≤60 years old) for the solid phase studies (P>0.05), and that the t½ is 46.2 ± 11.1 in older patients (>60 years old) and 31.9 ± 11.3 in younger patients (≤60 years old) for the liquid phase studies (P<0.05). We concluded that the age effects of gastric emptying in healthy Chinese occurred only in the liquid phase.
Steatosis in chronic hepatitis C: Relationship to the virus and host risk factors

Background: Steatosis occurs frequently in hepatitis C. However, the mechanisms leading to this lesion are still unknown, and the role of steatosis in the progression of the disease remains controversial. The aim of the present paper was to determine the prevalence of steatosis in hepatitis C and its association with hepatitis C virus (HCV) genotype, viral load and the presence of risk factors for steatosis, and to analyze the association between steatosis and the intensity of liver disease.
Temperature-dependent Block of Capacitative Ca2+ Influx in the Human Leukemic Cell Line KU-812*

The mechanism by which depletion of intracellular Ca2+ stores activates Ca2+ influx is not understood. We recently showed that primaquine, an inhibitor of vesicular transport, blocks the activation of the calcium release-activated calcium current (ICRAC) in rat megakaryocytes (Somasundaram, B., Norman, J. C., and Mahaut-Smith, M. P. (1995) Biochem. J. 309, 725-729). Since it is well established that vesicular transport is temperature-sensitive, we have investigated the effect of temperature on both the activation and maintenance of store-mediated Ca2+ and Mn2+ influx in the human leukemic cell line KU-812 using a combination of whole cell ICRAC recordings and measurements of Mn2+ photoquench of fura-2. Activation of ICRAC was temperature-sensitive, showing a nonlinear reduction when the temperature was lowered from 27 to 17°C with an abrupt change at 21-22°C and complete inhibition at 17°C. Once activated, ICRAC also displayed an abrupt reduction at 21-22°C but was not completely blocked even when the temperature was reduced to 14°C, suggesting that at least one of the temperature-sensitive components is exclusively involved in ICRAC activation. Activation of store-mediated Mn2+ influx also showed similar nonlinear temperature sensitivity and complete inhibition at 19°C. However, in contrast to ICRAC measurements, lowering the temperature following maximal activation of the influx pathway at 37°C did not result in any detectable residual Mn2+ entry below 19°C. We conclude that the mechanism of store-mediated Ca2+ influx involves temperature-dependent steps in both its maintenance and activation, suggesting dependence on a lipid membrane environment.
Capture and synthesis of human motion in video sequences

We present a knowledge-based framework to capture and represent human walkers in video. The system models the human body as an articulated object of twelve rigid body-parts whose motions are almost periodic and subject to dynamic constraints. The resulting representation is compact and composed of the motion, shape, and texture for each of the body-parts. We apply the representation to regenerate the original sequence and to synthesize articulated 3D human actions.
Phage Display of an Intracellular Carboxylesterase of Bacillus subtilis: Comparison of Sec and Tat Pathway Export Capabilities

ABSTRACT Using the phage display technology, a protein can be displayed at the surface of bacteriophages as a fusion to one of the phage coat proteins. Here we describe development of this method for fusion of an intracellular carboxylesterase of Bacillus subtilis to the phage minor coat protein g3p. The carboxylesterase gene was cloned in the g3p-based phagemid pCANTAB 5E upstream of the sequence encoding phage g3p and downstream of a signal peptide-encoding sequence. The phage-bound carboxylesterase was correctly folded and fully enzymatically active, as determined from hydrolysis of the naproxen methyl ester with Km values of 0.15 mM and 0.22 mM for the soluble and phage-displayed carboxylesterases, respectively. The signal peptide directs the encoded fusion protein to the cell membrane of Escherichia coli, where phage particles are assembled. In this study, we assessed the effects of several signal peptides, both Sec dependent and Tat dependent, on the translocation of the carboxylesterase in order to optimize the phage display of this enzyme normally restricted to the cytoplasm. Functional display of Bacillus carboxylesterase NA could be achieved when Sec-dependent signal peptides were used. Although a Tat-dependent signal peptide could direct carboxylesterase translocation across the inner membrane of E. coli, proper assembly into phage particles did not seem to occur.
Hairy Root Culture for Mass-Production of High-Value Secondary Metabolites

ABSTRACT Plant cell cultivations are being considered as an alternative to agricultural processes for producing valuable phytochemicals. Since many of these products (secondary metabolites) are obtained by direct extraction from plants grown in natural habitat, several factors can alter their yield. The use of plant cell cultures has overcome several inconveniences for the production of these secondary metabolites. Organized cultures, and especially root cultures, can make a significant contribution in the production of secondary metabolites. Most of the research efforts that use differentiated cultures instead of cell suspension cultures have focused on transformed (hairy) roots. Agrobacterium rhizogenes causes hairy root disease in plants. The neoplastic (cancerous) roots produced by A. rhizogenes infection are characterized by high growth rate, genetic stability and growth in hormone free media. These genetically transformed root cultures can produce levels of secondary metabolites comparable to that of intact plants. Hairy root cultures offer promise for high production and productivity of valuable secondary metabolites (used as pharmaceuticals, pigments and flavors) in many plants. The main constraint for commercial exploitation of hairy root cultivations is the development and scaling up of appropriate reactor vessels (bioreactors) that permit the growth of interconnected tissues normally unevenly distributed throughout the vessel. Emphasis has focused on designing appropriate bioreactors suitable to culture the delicate and sensitive plant hairy roots. Recent reactors used for mass production of hairy roots can roughly be divided as liquid-phase, gas-phase, or hybrid reactors. The present review highlights the nature, applications, perspectives and scale up of hairy root cultures for the production of valuable secondary metabolites.
UAV Remote Sensing for Urban Vegetation Mapping Using Random Forest and Texture Analysis

Unmanned aerial vehicle (UAV) remote sensing has great potential for vegetation mapping in complex urban landscapes due to the ultra-high resolution imagery acquired at low altitudes. Because of payload capacity restrictions, off-the-shelf digital cameras are widely used on medium and small sized UAVs. The limitation of low spectral resolution in digital cameras for vegetation mapping can be reduced by incorporating texture features and robust classifiers. Random Forest has been widely used in satellite remote sensing applications, but its usage in UAV image classification has not been well documented. The objectives of this paper were to propose a hybrid method using Random Forest and texture analysis to accurately differentiate land covers of urban vegetated areas, and analyze how classification accuracy changes with texture window size. Six least correlated second-order texture measures were calculated at nine different window sizes and added to original Red-Green-Blue (RGB) images as ancillary data. A Random Forest classifier consisting of 200 decision trees was used for classification in the spectral-textural feature space. Results indicated the following: (1) Random Forest outperformed traditional Maximum Likelihood classifier and showed similar performance to object-based image analysis in urban vegetation classification; (2) the inclusion of texture features improved classification accuracy significantly; (3) classification accuracy followed an inverted U relationship with texture window size. The results demonstrate that UAV provides an efficient and ideal platform for urban vegetation mapping. The hybrid method proposed in this paper shows good performance in differentiating urban vegetation mapping. The drawbacks of off-the-shelf digital cameras can be reduced by adopting Random Forest and texture analysis at the same time.
Prenatal maternal restraint stress exposure alters the reproductive hormone profile and testis development of the rat male offspring

Abstract Several studies have demonstrated that the presence of stressors during pregnancy induces adverse effects on the neuroendocrine system of the offspring later in life. In the present work, we investigated the effects of early programming on the male reproductive system, employing a prenatal stress (PS) paradigm. This study found that when pregnant dams were placed in a plastic restrainer three times a day during the last week of pregnancy, the offspring showed reduced anogenital distance and delayed testicular descent. Serum luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels were decreased at postnatal day (PND) 28 and testosterone was decreased at PND 75. Increased testosterone plus dihydrotestosterone (T + DHT) concentrations correlated with increased testicular 5α Reductase-1 (5αR-1) mRNA expression at PND 28. Moreover, PS accelerated spermatogenesis at PND 35 and 60, and increased mean seminiferous tubule diameter in pubertal offspring and reduced Leydig cell number was observed at PND 35 and 60. PS offspring had increased androgen receptor (AR) mRNA level at PND 28, and at PND 35 had increased the numbers of Sertoli cells immunopositive for AR. Overall, the results confirm that stress during gestation can induce long-term effects on the male offspring reproductive system. Of particular interest is the pre-pubertal imbalance of circulating hormones that probably trigger accelerated testicular development, followed by an increase in total androgens and a decrease in testosterone concentration during adulthood. Exposure to an unfavourable intrauterine environment might prepare for harsh external conditions by triggering early puberty, increasing reproductive potential.