Miracle-dz/UniFAR-FTUs huggingface dataset:
Vesicular gamma-aminobutyric acid transporter expression in amacrine and horizontal cells.

The vesicular gamma-aminobutyric acid (GABA) transporter (VGAT), which transports the inhibitory amino acid transmitters GABA and glycine, is localized to synaptic vesicles in axon terminals. The localization of VGAT immunoreactivity to mouse and rat retina was evaluated with light and electron microscopy by using well-characterized VGAT antibodies. Specific VGAT immunoreactivity was localized to numerous varicose processes in all laminae of the inner plexiform layer (IPL) and to the outer plexiform layer (OPL). Amacrine cell somata characterized by weak VGAT immunoreactivity in the cytoplasm were located in the ganglion cell layer and proximal inner nuclear layer (INL) adjacent to the IPL. In rat retina, VGAT-immunoreactive cell bodies also contained GABA, glycine, or parvalbumin (PV) immunoreactivity, suggesting vesicular uptake of GABA or glycine by these cells. A few varicose VGAT-immunoreactive processes entered the OPL from the IPL. VGAT immunoreactivity in the OPL was predominantly localized to horizontal cell processes. VGAT and calcium binding protein-28K immunoreactivities (CaBP; a marker for horizontal cells) were colocalized in processes and terminals distributed to the OPL. Furthermore, VGAT immunoreactivity overlapped or was immediately adjacent to postsynaptic density-95 (PSD-95) immunoreactivity, which is prominent in photoreceptor terminals. Preembedding immunoelectron microscopy of mouse and rat retinae showed that VGAT immunoreactivity was localized to horizontal cell processes and their terminals. Immunoreactivity was distributed throughout the cytoplasm of the horizontal cell processes. Taken together, these findings demonstrate VGAT immunoreactivity in both amacrine and horizontal cell processes, suggesting these cells contain vesicles that accumulate GABA and glycine, possibly for vesicular release.
The avian organizer.

The development of avian embryos is characterized by the large amount of yolk present from the one-cell stage until late phases of organogenesis. In the chick, an axis of bilateral symmetry is established already before egg laying, when the egg rotates in the uterus. There is evidence for an active Wnt-catenin pathway in the vegetal cells in the periphery of the multi-cellular embryo. It overlaps with the posteriorly restricted expression of genes characterizing the vegetal hemisphere in amphibia. The zone of overlap bears several functional characteristics of a Nieuwkoop center, which is first apparent in the posterior marginal zone, but continues into the early primitive streak. Only the anterior part of the late streak is capable of direct neural induction, and only its tip, Hensen's node, can induce an anterior neural identity. This latter activity leaves the node together with the cells representing the anterior mesendoderm. Thus, although the constraints and dynamics of avian development make comparisons with the amphibian situation a complex undertaking, Hensen's node comes as close as possible to an organizer in Spemann and H. Mangold's definition.
The relationship between urbanization and economic growth of Sichuan Province

This paper reviewed the relationship between urbanization and economic growth,based on 1978-2007 in Sichuan province of urbanization and economic growth time series for the Granger causality validation study of empirical measurement.The results showed that the reform and opening up,economic growth in Sichuan Province,the role of urbanization is relatively strong,but the development of urbanization role in promoting economic growth is not obvious.The need to accelerate the development level of urbanization in Sichuan Province,Sichuan Province in the analysis of the problems of urbanization,based on the Sichuan Province to speed up the urbanization of the measures and approaches.
Landscape attributes affecting patch occupancy by howler monkeys (Alouatta palliata mexicana) at Los Tuxtlas, Mexico

Understanding how forest cover is related to patch attributes such as size, shape, and isolation, and how this influences the occurrence of a species in fragmented landscapes is an important question in landscape ecology and conservation biology. To study the effects of fragmentation on patch occupancy by the critically endangered Mexican mantled howler monkey (Alouatta palliata mexicana) in the Los Tuxtlas region of Mexico, we selected three landscapes of ca. 5,000 ha, which differed in their remaining forest cover (24, 11, and 4%). For each landscape, we related patch occupancy to forest cover, patch size and shape, and four isolation parameters. Landscape attributes varied according to forest cover, and the percentage of occupation was greater in landscapes with more forest cover. The attributes affecting the probability of occupancy differed among landscapes. Occupancy was positively related to patch size in all landscapes, but in the northernmost landscape, shape irregularity had a negative effect on occupancy, whereas in the southernmost landscape, occupancy was favored by greater distances to the nearest village. The results show that not only the total amount of forest cover but also patch configuration need to be taken into consideration when designing management strategies for the conservation of the Mexican mantled howler monkey. Am. J. Primatol. 70:69–77, 2008. © 2007 Wiley‐Liss, Inc.
Fibrosis correlates with a ductular reaction in hepatitis C: Roles of impaired replication, progenitor cells and steatosis

The mechanisms for progressive fibrosis and exacerbation by steatosis in patients with chronic hepatitis C (HCV) are still unknown. We hypothesized that proliferative blockade in HCV‐infected and steatotic hepatocytes results in the default activation of hepatic progenitor cells (HPC), capable of differentiating into both biliary and hepatocyte lineages, and that the resultant ductular reaction promotes portal fibrosis. To study this concept, 115 liver biopsy specimens from subjects with HCV were scored for steatosis, inflammation, and fibrosis. Biliary epithelium and HPC were decorated by cytokeratin 7 immunoperoxidase, and the replicative state of hepatocytes was assessed by p21 and Ki‐67 immunohistochemistry. A ductular reaction at the portal interface was common. There was a highly significant correlation between the area of ductular reaction and fibrosis stage (r = 0.453, P < .0001), which remained independently associated after multivariate analysis. HPC numbers also correlated with fibrosis (r = 0.544, P < .0001) and the ductular area (r = 0.624, P < .0001). Moreover, steatosis correlated with greater HPC proliferation (r = 0.372, P = .0004) and ductular reaction (r = 0.374, P < .0001) but was not an obligate feature. Impaired hepatocyte replication by p21 expression was independently associated with HPC expansion (P = .002) and increased with the body mass index (P < .001) and lobular inflammation (P = .005). In conclusion, the strong correlation between portal fibrosis and a periportal ductular reaction with HPC expansion, the exacerbation by steatosis, and the associations with impaired hepatocyte replication suggest that an altered regeneration pathway drives the ductular reaction. We believe this triggers fibrosis at the portal tract interface. This may be a stereotyped response of importance in other chronic liver diseases. (HEPATOLOGY 2005;41:809–818.)
Twenty-Four Hour Ambulatory Simultaneous Impedance and pH Monitoring: A Multicenter Report of Normal Values From 60 Healthy Volunteers

OBJECTIVES:Impedance monitoring is a new diagnostic method for gastroesophageal reflux disease (GERD) where multiple impedance electrode pairs are placed on a standard pH catheter. It detects reflux of a liquid and/or gas bolus into the esophagus, as well as its distribution, composition, and clearing. The aim of this collaborative study is to define normal values for 24-h ambulatory simultaneous impedance and pH monitoring (24-h Imp-pH), and compare bolus parameters by impedance monitoring to changes in [H+] measured by pH monitoring.METHODS:Sixty normal volunteers without GER symptoms underwent 24-h Imp-pH with impedance measured at six sites (centered at 3, 5, 7, 9, 15, and 17 cm above lower esophageal sphincter) and pH 5 cm above the LES. Reflux detected by impedance was characterized by the pH probe as either acid, weakly acidic, nonacid, or superimposed acid reflux. Proximal reflux was defined as reflux that reached the impedance site 15 cm above the LES.RESULTS:Reflux frequency was common upright (median-27, 25th and 75th quartile-16, 42), but rare recumbent (median-1; 0, 4). A median of 34% (14%, 49%) of upright reflux reached the proximal esophagus. There was a similar number of mixed composition (liquid + gas; 49%) and liquid-only reflux (51%). Acid reflux was two-fold more common than weakly acidic reflux (p < 0.001). Superimposed acid reflux and nonacid reflux were rare. Acid neutralization to pH 4 took twice as long as volume clearance measured by impedance.CONCLUSIONS:Combining impedance and pH monitoring improves the detection and characterization of GER. This study characterizes the frequency, duration, and extent of reflux in health and provides normal values for 24-h Imp-pH for future comparison with GERD patients.
Endomorphins: potential roles and therapeutic indications in the development of opioid peptide analgesic drugs

The application of endomorphins as clinical available analgesic drugs has been impeded by their relatively poor receptor selectivity compared with alkaloid analgesics, rapid degradation in vivo, inefficient to penetrate the blood–brain barrier (BBB), and undesirable or toxic effects, such as acute tolerance and physical dependence, respiratory depression, and inhibition of gastrointestinal motility. Extensive studies have been performed so far striving to conquer these problems. In this article we review and discuss conformational and topographical modifications of the peptide amide bond and amino acid side groups to attain the most appropriate receptor binding affinity and high receptor selectivity; diverse strategies such as insertion of unnatural amino acids, covalent or noncovalent constraints as well as cyclization of linear peptides to enhance the enzymatic stability; designing of peptidomimetic ligands, glycopeptides, and N‐terminal amidinationed analogues (such as incorporating guanidine into endomorphins) to penetrate the BBB. Also, several pertinent examples of bivalent and/or multivalent (such as mixed µ‐agonist/δ‐antagonist profile) compounds are discussed based on the existing literature and current data intending to give an insight into the development of opioid peptides expressing low tendency to produce acute tolerance and physical dependence. © 2011 Wiley Periodicals, Inc. Med Res Rev, 32, No. 3, 536–580, 2012
Methods of effective use of solar power system

The paper presents the results of simulation and study of operating modes of a photovoltaic power plant with the maximum power point tracking controller. A number of search methods are considered: constant voltage method, open voltage method, short circuit method, method of observing perturbations and incremental conductance method. A complex model of the photovoltaic power plant with the controller has been developed. The simulation results are presented. The model validity was evaluated by the known technical characteristics of the Solarex MSX 60 module. The calculation results proved that the obtained volt-ampere and volt-watt characteristics of the model are compatible with those of the manufacturer. The review of various methods of searching the maximum power point for the solar battery and analysis of their performance under different climatic conditions can be of interest for a broad range of experts in the field of photovoltaics.
Pro- and Anti-Apoptotic Effects of Nitric Oxide in Irradiated Keratinocytes: The Role of Superoxide

Ultraviolet radiation (UV) induces apoptosis in keratinocytes by both p53- and death receptor-dependent pathways. It also generates free radicals in keratinocytes, including the synthesis of nitric oxide (NO) by constitutive and inducible NO synthases (NOS). NO has both pro- and anti-apoptotic effects. We wished to determine which of these was predominant in keratinocytes. Human CCD1106 keratinocytes were irradiated with UVB in the presence and absence of several NOS antagonists. Apoptosis was measured by flow cytometry with annexin V binding. NOS antagonism consistently altered UVB-induced apoptosis measured 18 h after irradiation. In 9 of 13 experiments, NOS antagonism increased apoptosis. However, in 4 of 13 experiments, NOS antagonism reduced apoptosis. We postulated that the variable effects of NO might be due to a critical balance between UVB-induced NO and superoxide production. We predicted that NO would be anti-apoptotic in the presence of low O–2, but pro-apoptotic when NO combined with O–2 to form peroxynitrite. Though superoxide dismutase reduced apoptosis after UVB, addition of peroxynitrite did not affect apoptosis. We conclude that NO released by UV irradiation is anti-apoptotic; however, the levels of O–2 may be a determinant of NO action.
Steel slag used in landfill cover liners: laboratory and field tests

Stricter rules for landfilling within the EU have led to the closure of many landfills and a need for large amounts of cover liner materials. Therefore, the potential utilization of mixtures of electric arc furnace slag (EAFS) and ladle slag (LS), which are currently deposited in landfills, as a material for use as landfill liner was investigated. Laboratory analyses showed the mixtures to have similar compression strength to that of high-strength concrete and low hydraulic conductivity (< 10-11 m s-1 in some cases). However, both their hydraulic conductivity and compaction properties were strongly affected by the time between adding water to the mixtures and compacting them (tests showed that a delay of 24 h can lead to an increase in hydraulic conductivity, so it should be compacted as soon as possible after mixing the material with water). In addition, the performance of a cover liner constructed using EAFS and LS was studied in a 2-year field trial on a landfill for municipal solid waste, in which the average amount of leachate collected from ten lysimeters was only 27 L m-2 year-1, easily meeting Swedish criteria for the permeability of covers on non-hazardous waste landfills (≤50 L m-2 year-1). Thus, the material seems to have promising potential for use in barrier constructions.
Intrasynovial Flexor Tendon Repair: An Experimental Study Comparing Low and High Levels of in Vivo Force During Rehabilitation in Canines

Background: Rehabilitation methods that generate increased tendon force and motion have been advocated to improve results following intrasynovial flexor tendon repair. However, the effects of rehabilitation force and motion on tendon-healing may be masked by the high stiffness produced by newer suture methods. Our objective was to determine whether the biomechanical properties of tendons repaired by one of two multistrand suture methods were sensitive to an increased level of applied rehabilitation force. Methods: Two hundred and fourteen flexor digitorum profundus tendons from 107 adult dogs were transected and repaired. Dogs were assigned to one of four groups based on the rehabilitation method (low force [<5 N] or high force [17 N]) and the repair technique (four-strand or eight-strand core suture) and were killed between five and forty-two days after the procedure. Repair-site structural properties were determined by tensile testing, and digital range of motion was assessed with use of a motion-analysis system. Results: Tensile properties did not differ between the low and high-force rehabilitation groups, regardless of the repair technique (p > 0.05). In contrast, tensile properties were strongly affected by the repair technique, with tendons in the eight-strand group having an approximately 35% increase in ultimate force and rigidity compared with those in the four-strand group (p < 0.05). Ultimate force did not change significantly with time during the first twenty-one days (p > 0.05); there was no evidence of softening in either of the repair or rehabilitation groups. Force increased significantly from twenty-one to forty-two days, while rigidity increased throughout the forty-two-day period (p < 0.05). Conclusions: Increasing the level of force applied during postoperative rehabilitation from 5 to 17 N did not accelerate the time-dependent accrual of stiffness or strength. Suture technique was of primary importance in providing a stiff and strong repair throughout the early healing interval. Clinical Relevance: Our findings suggest that there be a reexamination of the concept that increases in force produced by more vigorous mobilization protocols are beneficial to tendon-healing. While more vigorous rehabilitation may help to improve hand function, we found no evidence that it enhances tissue-healing or strength in the context of a modern suture repair.
Blinatumomab: A novel, bispecific, T-cell engaging antibody.

PURPOSE The pharmacology, pharmacodynamics, pharmacokinetics, efficacy in clinical trials, safety and tolerability, and place in therapy of blinatumomab are reviewed. SUMMARY Blinatumomab is a novel, bispecific, T-cell engaging antibody that targets tumor-associated antigens CD19 and CD3. Blinatumomab was approved through an accelerated pathway for the treatment of Philadelphia (Ph) chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). One Phase II trial found 16 of 21 patients to be negative for minimal residual disease (MRD) after one cycle of treatment, resulting in a response rate of 80%. Another Phase II trial showed an 82% MRD response, even in heavily pretreated patients. The most common adverse events of any grade noted were pyrexia, febrile neutropenia, hypokalemia, and anemia. The most frequently occurring grade 3 or 4 adverse events were febrile neutropenia, neutropenia, and anemia. Cycle 1 is dosed as a 9- μg/ day continuous i.v. infusion on days 1-7 and a 28-μg/day continuous i.v. infusion on days 8-28 administered as a four-week continuous i.v. infusion, followed by at least two weeks of no treatment. Subsequent cycles are dosed as a 28-μg/day continuous i.v. infusion on days 1-28, followed by at least two weeks of no treatment, for up to five treatment cycles. CONCLUSION Blinatumomab is approved as an option for Ph chromosome-negative relapsed or refractory B-cell precursor ALL and is a needed addition to the limited treatment options for this difficult-to-treat patient population. Two Phase II clinical trials resulted in impressive results when using blinatumomab as a single agent, resulting in the drug's approval.
Task Dynamics & the (Ecological) Information They Create

Embodied cognition is the hypothesis that behavior is not simply caused by the brain. Instead, behavior emerges from the interactions between brains in particular kinds of bodies embedded in environments that provide certain kinds of opportunities for activity. Theories of embodied cognition require a mechanism to support how these distributed resources can remain in contact with one another so that they can be assembled into task-specific solutions to problems. These theories of embodied cognition, especially the nonrepresentational kinds, typically rely on James J. Gibson’s (1979) notion of ecological information as the relevant mechanism, and there is extensive empirical support for the claim that this information both exists and is used by organisms to coordinate and control their activity.
Pharmacokinetics and Bioequivalence of 2 Tablet Formulations of Olanzapine in Healthy Chinese Volunteers: a Randomized, Open-Label, Single-Dose Study

Abstract Background: Olanzapine is a widely used agent for the treatment of schizophrenia. Objective: The aim of this study was to evaluate bioequivalence of two 10-mg tablet formulations of olanzapine following single oral dose in adult male volunteers. Methods: This was a randomized, single-dose, open-label, crossover bioequivalence study. Plasma samples were collected before dosing and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0, 72.0, 96.0, 120.0 and 144.0 h after dosing. Plasma concentrations of olanzapine were determined by using a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. Statistical analysis of the pharmacokinetic parameters Cmax, AUC0–144, and AUC0–∞ was conducted to determine bioequivalence. Adverse events were monitored, recorded and evaluated by investigators throughout the study. Results: 24 healthy male Chinese volunteers between the ages of 18–40 years with a body mass index (BMI) between 19 and 24 kg/m2 were enrolled in the study. The mean (SD) Cmax, AUC0–144, and AUC0–∞ values after administration of the test and reference formulations, respectively, were as follows: 18.91 (5.320) vs. 18.44 (4.758) ng/mL, 582.9 (118.23) vs. 587.3 (127.12) ng/mL · h, and 615.4 (131.39) vs. 615.8 (137.45) ng/mL · h. The 90% CIs for the ratios of AUC0–144 and Cmax were 96.9% to 102.4% and 93.7% to 110.2%, respectively. The relative bioavailability of the test formulation to reference formulation was 100.1%. Both formulations were generally well tolerated and no serious AEs were reported in the study. Conclusions: The 90% CIs for the ratios of mean Cmax, AUC0–144, and AUC0–∞ met the regulatory criteria for bioequivalence.
Human kidney glomerulus proteome and biomarker discovery of kidney diseases

The kidney glomerulus is the site of plasma filtration and production of primary urine in the kidney. The structure not only plays a pivotal role in ultrafiltration of plasma into urine but also is the locus of kidney diseases progressing to chronic renal failure. Patients afflicted with these glomerular diseases frequently progress to irreversible loss of renal function and inevitably require replacement therapies. The diagnosis and treatment of glomerular diseases are now based on clinical manifestations, urinary protein excretion level, and renal pathology of needle biopsy specimens. The molecular mechanisms underlying the progression of glomerular diseases are still obscure despite a great number of clinical and experimental studies. Proteomics is a particularly promising approach for the discovery of proteins relevant to physiological and pathophysiological processes, and has been recently employed in nephrology. Although until now most efforts of proteomic analysis have been conducted with urine, the biological fluid that is easily collected without invasive procedures, proteomic analysis of the glomerulus, the tissue most proximal to the disease loci, is the most straightforward approach. In this review, we attempt to outline the current status of clinical proteomics of the glomerulus and provide a perspective of protein biomarker discovery of glomerular diseases.