Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteomic analysis of epithelium-denuded human amniotic membrane as a limbal stem cell niche.

PURPOSE A new strategy of treating ocular surface reconstruction is to transplant a bioengineered graft by expanding limbal stem cells (SCs) ex vivo on the amniotic membrane (AM). The reasons for the exceptional success on the AM are not fully understood but are believed to be related to its unique composition. We investigated the proteome of the epithelium-denuded AM to increase our understanding of the mechanisms by which AM may confer its beneficial effects. METHODS We compared the epithelially denuded-human AM with matrigel and collagen on the expansion of limbal SCs by evaluating the expression of specific markers. The protein pattern of the epithelium-denuded AM was analyzed using two dimensional electrophoresis (2-DE) coupled with mass spectrometry (MS) identification of proteins. RESULTS Epithelial outgrowth of limbal explants on AM expressed more p63 and K19 (SC markers) and less K3 and connexin 43 (corneal differentiation markers) in comparison with other extracellular matrices (ECMs). Moreover, in all groups, the cells expressed ABCG2, K19, K12, p63, and Pax6 as shown by reverse transcription polymerase chain reaction (RT-PCR). Out of about 600 protein spots analyzed on six 2-DE gels, 515 spots could be detected in all replicates. A high average correlation coefficiency (CC) of 0.926 implied good intra-sample reproducibility. Forty major proteins of AM were identified using MALDI TOF/TOF MS of which different isoforms of lumican and osteoglycin were responsible for around 23% of the total proteome on gels. CONCLUSIONS Our results showed that epithelium-denuded AM provides a superior niche for limbal SC proliferation and phenotype maintenance in vitro and the denuded human AM is a protein enriched ECM. This will prove critical to the future understanding of the biological and therapeutic mechanisms involved in AM transplantation and regeneration. The identification of highly abundant proteins in denuded-AM, such as lumican, osteoglycin/memican, collagen alpha type IV, and fibrinogen, further explains its unique properties and will assist in the efforts to generate bioengineered and artificial AM constructs.
Dual-Mode Low-Drop-Out Regulator/Power Gate With Linear and On–Off Conduction for Microprocessor Core On-Die Supply Voltages in 14 nm

A dual-mode digital power gate (PG) and linear low-drop-out regulator (LDO) has been demonstrated in 14 nm. A modified flipped source follower driver circuit is used to minimize dI/dt droops. The LDO has a novel compensation method which utilizes capacitance multiplication and can drive a 1-7 μF load without any external compensation elements. This LDO exhibits high-current drive capability (3 A) at low-dropout voltages (<; 60 mV) and high-current efficiency (> 99%), making it suitable to drive a microprocessor core.
Molecular Dynamics Simulation of Spinodal Decomposition in Three-Dimensional Binary Fluids.

Using large-scale molecular dynamics simulations of a two-component Lennard-Jones model in three dimensions, we show that the late-time dynamics of spinodal decomposition in concentrated binary fluids reaches a viscous scaling regime with a growth exponent $n\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}1$, in agreement with experiments and a theoretical analysis for viscous growth.
The Human Immunodeficiency Virus Type 1 Vpu Protein Inhibits NF-κB Activation by Interfering with βTrCP-mediated Degradation of IκB*

The human immunodeficiency virus type 1 (HIV-1) Vpu protein binds to the CD4 receptor and induces its degradation by cytosolic proteasomes. This process involves the recruitment of human βTrCP (TrCP), a key member of the SkpI-Cdc53-F-box E3 ubiquitin ligase complex that specifically interacts with phosphorylated Vpu molecules. Interestingly, Vpu itself, unlike other TrCP-interacting proteins, is not targeted for degradation by proteasomes. We now report that, by virtue of its affinity for TrCP and resistance to degradation, Vpu, but not a phosphorylation mutant unable to interact with TrCP, has a dominant negative effect on TrCP function. As a consequence, expression of Vpu in HIV-infected T cells or in HeLa cells inhibited TNF-α-induced degradation of IκB-α. Vpu did not inhibit TNF-α-mediated activation of the IκB kinase but instead interfered with the subsequent TrCP-dependent degradation of phosphorylated IκB-α. This resulted in a pronounced reduction of NF-κB activity. We also observed that in cells producing Vpu-defective virus, NF-κB activity was significantly increased even in the absence of cytokine stimulation. However, in the presence of Vpu, this HIV-mediated NF-κB activation was markedly reduced. These results suggest that Vpu modulates both virus- and cytokine-induced activation of NF-κB in HIV-1-infected cells.
[Association between dyspepsia and upper endoscopic findings].

BACKGROUND/AIMS We aimed to estimate the proportion of significant endoscopic findings and their association with dyspeptic symptoms and to evaluate the predictors for significant endoscopic findings. METHODS Total of 3,872 subjects (58.3% men, mean age 43.6±9.3 years) who had undergone endoscopy were enrolled at the health promotion center. Each subject completed validated questionnaires, including data on gastrointestinal symptoms, socio-demographic history and medical history. Significant endoscopic findings were included peptic ulcer disease, reflux esophagitis, gastric cancer, Barrett's esophagus and gastro-duodenal erosions. Multiple logistic regression models were used to assess the predictors for significant endoscopic findings. RESULTS The proportion of significant endoscopic findings was 39.1%. There was no significant difference of endoscopic findings between the dyspepsia and asymptomatic group (41.0% vs. 37.4%, p>0.05). There was no difference of the incidence of reflux esophagitis or peptic ulcer between subjects with and without dyspepsia. Peptic ulcer was more frequently present in subjects with reflux symptoms than asymptomatic subjects (12.3% vs. 9.0%, p=0.03). Male gender (odds ratio [OR], 3.91; 95% confidence interval [CI], 3.18-4.81) increased the risk for having endoscopic abnormality and having symptoms of functional dyspepsia according to Rome III criteria (OR, 0.75; 95% CI, 0.57-0.97) significantly decreased this risk. CONCLUSIONS About 40% of subjects with dyspepsia had abnormal endoscopic findings, and the dyspepsia symptoms may not predict the significant endoscopic findings. Diagnostic criteria of functional dyspepsia by Rome III may be useful to predict not having significant upper endoscopic findings.
ECOSYSTEM EFFECTS OF BIODIVERSITY MANIPULATIONS IN EUROPEAN GRASSLANDS

We present a multisite analysis of the relationship between plant diversity and ecosystem functioning within the European BIODEPTH network of plant-diversity manipulation experiments. We report results of the analysis of 11 variables addressing several aspects of key ecosystem processes like biomass production, resource use (space, light, and nitrogen), and decomposition, measured across three years in plots of varying plant species richness at eight different European grassland field sites. Differences among sites explained substantial and significant amounts of the variation of most of the ecosystem processes examined. However, against this background of geographic variation, all the aspects of plant diversity and composition we examined (i.e., both numbers and types of species and functional groups) produced significant, mostly positive impacts on ecosystem processes. Analyses using the additive partitioning method revealed that complementarity effects (greater net yields than predicted from monocultures due to resource partitioning, positive interactions, etc.) were stronger and more consistent than selection effects (the covariance between monoculture yield and change in yield in mixtures) caused by dominance of species with particular traits. In general, communities with a higher diversity of species and functional groups were more productive and utilized resources more completely by intercepting more light, taking up more nitrogen, and occupying more of the available space. Diversity had significant effects through both increased vegetation cover and greater nitrogen retention by plants when this resource was more abundant through N2 fixation by legumes. However, additional positive diversity effects remained even after controlling for differences in vegetation cover and for the presence of legumes in communities. Diversity effects were stronger on above- than belowground processes. In particular, clear diversity effects on decomposition were only observed at one of the eight sites. The ecosystem effects of plant diversity also varied between sites and years. In general, diversity effects were lowest in the first year and stronger later in the experiment, indicating that they were not transitional due to community establishment. These analyses of our complete ecosystem process data set largely reinforce our previous results, and those from comparable biodiversity experiments, and extend the generality of diversity–ecosystem functioning relationships to multiple sites, years, and processes.
Endovascular therapy after intravenous t-PA versus t-PA alone for stroke.

BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain. METHODS We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). RESULTS The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], -6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8-19, indicating moderately severe stroke, or ≥20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, -4.4 to 18.1) and those with a score of 19 or lower (-1.0 percentage point; 95% CI, -10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P=0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P=0.83). CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenous t-PA alone. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00359424.).
The Impact of Fair Trade Coffee on Economic Efficiency and the Distribution of Income

Introduction Fair Trade CertifiedTM coffee is receiving increasing attention both by the public and by academic researchers. Fair Trade emerged as a response to the adverse conditions faced by small-scale coffee producers in developing countries. Individual small-scale producers have no direct access to international markets and must sell their coffee to local intermediaries. These intermediaries are widely perceived to have monopsonistic pow in the coffee market at the level of rural communities. The weak bargaining power of producers results in the producers receiving prices below market value, an amount which ultimately as little as two to four percent of the final retail price of coffee (Tran er
The Bone Lining Cell: Its Role in Cleaning Howship's Lacunae and Initiating Bone Formation

In this study we investigated the role of bone lining cells in the coordination of bone resorption and formation. Ultrastructural analysis of mouse long bones and calvariae revealed that bone lining cells enwrap and subsequently digest collagen fibrils protruding from Howship's lacunae that are left by osteoclasts. By using selective proteinase inhibitors we show that this digestion depends on matrix metalloproteinases and, to some extent, on serine proteinases. Autoradiography revealed that after the bone lining cells have finished cleaning, they deposit a thin layer of a collagenous matrix along the Howship's lacuna, in close association with an osteopontin‐rich cement line. Collagenous matrix deposition was detected only in completely cleaned pits. In bone from pycnodysostotic patients and cathepsin K‐deficient mice, conditions in which osteoclastic bone matrix digestion is greatly inhibited, bone matrix leftovers proved to be degraded by bone lining cells, thus indicating that the bone lining cell “rescues” bone remodeling in these anomalies. We conclude that removal of bone collagen left by osteoclasts in Howship's lacunae is an obligatory step in the link between bone resorption and formation, and that bone lining cells and matrix metalloproteinases are essential in this process.
High-Resolution AoA Estimation for Hybrid Antenna Arrays

Communication with unlicenced 60-GHz band is attractive for wireless networks since a free-of-charge bandwidth of 7 GHz is available. The antenna array, conducting transmitter/receiver beamforming, is often used to enhance the transmission range. However, to conduct beamforming, the transceivers have to know the angles of signal arrival. Many angle-of-arrival (AoA) estimation algorithms are well known. Unfortunately, most of them are developed for digital arrays, requiring an analog-to-digital-converter (ADC) and a digital-to-analog converter (DAC) for each antenna element. For an array with a large number of antennas, the implementation cost will be very high. Recently, hybrid antenna array, in which multiple antennas share an ADC/DAC, was proposed as a low-cost solution. However, the existing AoA estimation algorithms for hybrid arrays can only support one AoA; their applications are then limited in multipath indoor environments. In this paper, we propose new AoA estimation algorithms to solve the problem. Using an augmented beam-space approach, we extend the use of the well-known AoA estimation algorithms, MUSIC and ESPRIT developed for digital arrays, to the scenario of hybrid antenna arrays. Simulations show that the proposed algorithms, although developed for hybrid arrays, can have similar performance as MUSIC and ESPRIT in digital arrays.
Jackknife Bias Reduction in the Presence of a Near-Unit Root

This paper analyses the properties of jackknife estimators of the first-order autoregressive coefficient when the time series of interest contains a unit root. It is shown that, when the sub-samples do not overlap, the sub-sample estimators have different limiting distributions from the full-sample estimator and, hence, the jackknife estimator in its usual form does not eliminate fully the first-order bias as intended. The joint moment generating function of the numerator and denominator of these limiting distributions is derived and used to calculate the expectations that determine the optimal jackknife weights. Two methods of avoiding this procedure are proposed and investigated, one based on inclusion of an intercept in the regressions, the other based on adjusting the observations in the sub-samples. Extensions to more general augmented Dickey-Fuller (ADF) regressions are also considered. In addition to the theoretical results extensive simulations reveal the impressive bias reductions that can be obtained with these computationally simple jackknife estimators and they also highlight the importance of correct lag-length selection in ADF regressions.
Complications associated with venous access devices:part two.

In the second of two articles the author discusses the secondary complications that can arise following insertion of venous access devices (VADs). Part one, published last week, examined the primary complications that can arise when inserting VADs. This article aims to provide an introduction to the secondary complications that can arise following the insertion of central and peripheral venous access devices (VADs). It offers guidance on how to identify, avoid and resolve such complications.
Antiphospholipid antibody testing and standardization

The laboratory criteria that define patients with antiphospholipid syndrome (APS) include lupus anticoagulant (LAC), anticardiolipin antibodies and anti‐β2 glycoprotein I antibodies (aβ2GPI). All assays show methodological shortcomings and the combination of the three tests, each with different sensitivity and specificity, and hence, differences in clinical utility make the laboratory diagnosis of APS challenging. Consensus guidelines and proposals for antiphospholipid antibodies (aPL) testing have been published in the last 20 years and have led to a substantial improvement. Despite efforts so far, standardization is not reached yet, but progress has been made. On‐going efforts to reduce the interlaboratory/interassay variations remain important; even an absolute standardization cannot be feasibly achieved. Taking into account the methodological shortcomings of the means we have available, more detailed guidelines may help in adequate performance of aPL testing. This review will focus on the efforts and achievements in standardization and on the weaknesses and strengths of the current available laboratory methods.
Uptake of antigen by afferent lymph dendritic cells mediated by antibody

Dendritic cells isolated from sheep afferent lymph were examined for their ability to bind soluble protein and peptide antigens labeled with fluorescein both in in vitro assays and following intradermal injection of antigen in vivo. Analysis of dendritic cells by flow cytometry revealed weak direct binding of proteins and peptide antigens. However, the degree of uptake was greatly enhanced in the presence of specific antibody in vitro or if antigen was injected intradermally into antigen‐primed sheep. About 60% of dendritic cells possessed the ability to take up antigen in both the in vitro and in vivo experiments. The uptake of antigen occurred very rapidly, reaching maximum values in terms of cell numbers and fluorescence intensity in less than 5 min in vitro and 20–40 min following in vivo challenge. Both sheep IgG subclasses could mediate this effect, but F(ab')2 fragments were ineffective. Procedures adopted to remove complement components from the in vitro test mixtures did not result in any reduction in the binding of antigen by dendritic cells. Two‐color flow cytometry analysis of the dendritic cell population further showed that 43% of cells taking up the antigen/antibody complexes were CD1+, suggesting a relationship between these cells and Langerhans' cells or other dendritic cells in skin. The results, thus, indicate that approximately two thirds of sheep afferent lymph dendritic cells bind antigen/antibody complexes via an Fc receptor, a mechanism which could be important in the accentuated accessory function of these cells known to occur following secondary antigen challenge.
Heterogeneous distribution of AMPA glutamate receptor subunits at the photoreceptor synapses of rodent retina

In the retina the segregation of different aspects of visual information starts at the first synapse in signal transfer from the photoreceptors to the second‐order neurons, via the neurotransmitter glutamate. We examined the distribution of the four AMPA glutamate receptor subunits GluR1–GluR4 at the photoreceptor synapses in mouse and rat retinae by light and immunoelectron microscopy and serial section reconstructions. On the dendrites of OFF‐cone bipolar cells, which make flat, noninvaginating contacts postsynaptic at cone synaptic terminals, the subunits GluR1 and GluR2 were predominantly found. Horizontal cell processes postsynaptic at both rod and cone synaptic terminals preferentially expressed the subunits GluR2, GluR2/3 and GluR4. An intriguing finding was the presence of GluR2/3 and GluR4 subunits on dendrites of putative rod bipolar cells, which are thought to signal through the sign‐inverting metabotropic glutamate receptor 6, mGluR6. Furthermore, at the rod terminals, horizontal cell processes and rod bipolar cell dendrites showed labelling for the AMPA receptor subunits at the ribbon synaptic site or perisynaptically at their site of invagination into the rod terminal. The wide distribution of AMPA receptor subunits at the photoreceptor synapses suggests that AMPA receptors play an important role in visual signal transfer from the photoreceptors to their postsynaptic partners.
Profiles of Epstein-Barr Virus Associated Gastric Carcinomas in Brunei Darussalam

Background: Gastric cancer is the second most common gastrointestinal cancer and is largely attributed to Helicobacter pylori (H. pylori) infection. In addition, studies have also shown association with Epstein-Barr virus (EBV) in 10% of gastric cancers. This study assessed the characteristics of EBV associated gastric cancers (EBVaGC) in Brunei Darussalam. Materials and Methods: This study included gastric cancers diagnosed between 2008 and 2012, registered with the Department of Pathology RIPAS Hospital, Brunei Darussalam. Clinical case notes were systematically reviewed. Histology specimens were all stained for EBV and also assessed for intestinal metaplasia and H. pylori . Results: There were a total of 81 patients (54 male and 27 females) with a mean age of 65.8±14.8 years included in the study. Intestinal metaplasia and active H. pylori infection were detected in 40.7% and 30.9% respectively. A majority of the tumors were proximally located (55.6%), most poorly differentiated (well differentiated 16%, moderately differentiated 30.9% and poorly differentiated 53.1%) and the stages at diagnosis were; stage I (44.4%), stage II (23.5%), stage III (8.6%) and stage IV (23.5%). EBV positivity (EBVaGC) was seen in 30.9%. Between EBVaGC and EBV negative gastric cancers, there were no significant differences (age, gender, ethnic group, presence of Intestinal metaplasia, tumor locations, stages of disease and degree of tumor differentiation). Conclusions: This study showed that a third of gastric cancers in Brunei Darussalam were positive for EBV, higher than what have been reported in the literature. However, there were no significant differences between EBVaGC and EBV negative gastric cancers. This suggests that the role of EBV in gastric cancer may be mostly incidental rather than any causal relation. However, further studies are required.
Glutamate Increases Glycogen Content and Reduces Glucose Utilization in Primary Astrocyte Culture

The glycogen content of primary cultured astrocytes was approximately doubled by incubation with 1 mM L‐glutamate or L‐aspartate. Other amino acids and excitatory neurotransmitters were without effect. The increase in glycogen level was not blocked by the glutamate receptor antagonist kynurenic acid but was completely blocked by the glutamate uptake inhibitor threo‐3‐hydroxy‐D,L‐aspartate and by removal of Na+ from the medium. Incubation with radiolabeled glucose and glutamate revealed that the increased glycogen content was derived almost entirely from glucose. Glutamate at 1 mM was also found to cause a 53 ± 12% decrease in glucose utilization and a 112 ± 69% increase in glucose‐6‐phosphate levels. These results suggest that the glycogen content of astrocytes is linked to the rate of glucose utilization and that glucose utilization can, in turn, be affected by the availability of alternative metabolic substrates. These relationships suggest a mechanism by which brain glycogen accumulation occurs during decreased neuronal activity.