Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelial protease‐activated receptor‐2 induces tissue factor expression and von Willebrand factor release

A second protease‐activated receptor (PAR‐2) that could be activated by trypsin or more physiologically by mast cell tryptase has been recently cloned. Both the structure and activation mechanism of PAR‐2 was similar to the functional thrombin receptor (PAR‐1). Although many effects of the coagulation protease thrombin on the vascular endothelium could be attributed to PAR‐1 activation, very little is known about the physiological and pathophysiological role of PAR‐2. We investigated whether stimulation of PAR‐2 on endothelial cells induced two cellular responses that play a central role in primary and secondary haemostasis: the release of high molecular weight von Willebrand factor (hmw‐VWF) from Weibel‐Palade bodies and the de novo synthesis of tissue factor (TF) mRNA and protein. Human umbilical vein endothelial cells (HUVEC) were incubated with agonists for PAR‐2 at 37°C. Both trypsin and SLIGKV increased TF mRNA and activity and induced the release of hmw‐VWF due to elevated levels of cytosolic Ca2+. Trypsin (10 nm) induced a 6‐fold increase of TF mRNA and reduced time until fibrin clot formation to 37%, indicating trebling of the cell surface located TF activity. Stimulation of HUVEC with the PAR‐2 agonist peptide SLIGKV induced a dose‐dependent increase of TF mRNA up to 6 times and TF activity up to 3 times. Release of hmw‐VWF was achieved both after incubation of HUVEC with trypsin and SLIGKV and was directly depending on intracellular Ca2+ mobilization. To make results comparable to the functional thrombin receptor, homologous experiments were carried out using the PAR‐1 agonists thrombin and SFLLRN.
Are orphans at increased risk of malnutrition in Malawi?

The objective of this study was to compare the nutritional status and health problems of village orphans, non-orphans and orphanage children, and to identify factors associated with undernutrition. A cross-sectional study was conducted in three orphanages and two villages near Blantyre, Malawi. Seventy-six orphanage children, 137 village orphans and 80 village non-orphans were recruited. Anthropometric measurement was done and guardians were interviewed. In the group of children aged < 5 years, the prevalence of undernutrition in orphanage children was 54.8% compared with 33.3% and 30% of village orphans and non-orphans, respectively. Sixty-four per cent of young orphanage children were stunted compared with 50% of village orphans and 46.4% of non-orphans. The mean (SD) Z-score of height/age was significantly lower in the orphanage group, -2.75 (1.29) compared with -2.20 (1.51) and -1.61 (1.57) in the village orphan and non-orphan groups (p < 0.05). Conversely, older orphanage children (> or = 5 years) were less stunted and wasted than orphans and non-orphans in villages. Illness of children in the last month was reported to be higher in the non-orphan group, especially diarrhoeal disease, which occurred in 30% compared with 10.8% of village orphans and 6.6% of orphanage children. More than three children in a family being cared for by guardians was significantly associated with undernutrition. Orphanage girls were more likely to be malnourished than orphanage boys. Children who had been admitted to an orphanage for more than a year were less malnourished. In village orphans, there was no association between undernutrition and duration of stay in extended families. Age and education of guardians were not associated with the nutritional status of children. We conclude that young orphanage children are more likely to be undernourished and more stunted than village children. Older orphanage children seem to have better nutrition than village orphans. There was no significant difference in nutritional status between village orphans and non-orphans.
Adenoviral p53 gene transfer inhibits human Tenon’s capsule fibroblast proliferation

Background/aim: Although antiproliferative drugs have been used successfully to prevent scarring after filtration surgery in patients with glaucoma, complications associated with their use (such as hypotony or endophthalmitis) energise the search for an alternative treatment. Single application of β radiation leads to long term growth arrest and expression of p53 in human Tenon’s capsule fibroblasts (hTf). The authors assume that the activation of p53 is one of the cellular triggers. Their aim was to analyse the effect of p53 overexpression on hTf and to determine which pathways are involved. Methods: A recombinant adenoviral vector (rAd.p53) containing transgenes encoding for human p53 and green fluorescent protein (GFP) was used to induce overexpression of p53 in hTF and a control vector (rAd.GFP). Transgene expression was detected by western blot (p53 and p21WAF-1/Cip1). Cell proliferation and viability were investigated using cell counts, 5′-bromodeoxyuridine incorporation (BrdU assay) and tetrazolium reduction (MTT assay). Results: Infection of hTf with rAd.p53 resulted in significant inhibition of cell proliferation, DNA synthesis, and metabolic activity in vitro. Western blot showed increased levels of p53 and p21WAF-1/Cip1 in rAd.p53 infected cells, but not in rAd.GFP and uninfected cells. Apoptosis was excluded with flow cytometry. Conclusions: Adenoviral p53 gene transfer leads to significant growth inhibition in hTf. P53 induces p21WAF-1/Cip1 expression and does not cause apoptosis in hTf in vitro. p53 as an antiproliferative drug has the potential to replace mitomycin C and 5-fluorouracil in glaucoma surgery.
The reclamation of a desert by the combination of ancient and modern water systems

A well-developed system of harvesting the scanty rainfall of the Negev desert in run-off channels enabled farmers 1500 years ago to grow crops of grain and fruit, and produce oil and wine. Restoration of some of these early systems has shown that the principles hold good today and may be applicable in arid and semi-arid areas of other countries, particularly if they are used in combination with modern techniques such as drip irrigation and the use of brackish water.
Membrane Antioxidants

In this chapter, I have discussed both lipid-soluble and water-soluble antioxidants that exert protective action with respect to inhibiting lipid, and in some cases, protein oxidation in both natural and artificial membranes. In addition, recent work has begun to clarify exactly how antioxidant enzymes can protect membranes against peroxidative damage. Although we have some understanding of the mechanisms of several of these antioxidants, much work remains to be done before we can begin making dietary recommendations that may have profound implications with respect to aging, cancer, and the many other human diseases that have been associated with radical-induced damage.
Facilitating intermediate node discovery for decentralized offloading in High Performance Computing centers

Modern high-performance computing applications use large scale simulations to facilitate scientific discovery, such as studying the impact of sub-atomic interactions or searching for a cure for diseases. These applications increasingly use data that is growing exponentially in size. Thus, management of data at High Performance Computing (HPC) centers is a critical problem, and addressing data-related issues is considered a major step towards realization of efficient resource usage. Result-data offloading is a promising technique that can improve efficiency of HPC centers by moving the application result data quickly to user-specified remote locations. This also increases the overall center serviceability. However, identifying suitable remote locations for use in such decentralized offloading remains an open problem. In this paper, we explore several methods for locating intermediate nodes using peer-to-peer techniques. We facilitate node discovery at each level of the offload, and structure the discovered nodes to support efficient data transfer that can satisfy the Service Level Agreements between the HPC center and the job submission site. Our evaluation, using realistic simulations and actual measurements on the PlanetLab distributed test-bed, shows that, compared to a naïve random discovery, controlled routing-table-based advertisements offer an efficient and effective method for discovering appropriate resources: it discovers 211% more nodes in total, and achieves quick discovery by finding 184% more nodes in less than 27% of the time compared to a random-broadcast based approach. Thus, this work provides promising node discovering mechanisms that can facilitate the HPC data offloading process.
Effectiveness of Social Host and Fake Identification Laws on Reducing Underage Drinking Driver Fatal Crashes

Objective: The public generally assumes that the minimum legal drinking age of 21 (MLDA-21) legislation in the United States is embodied in a single law and therefore all states have the same law. Actually, the MLDA-21 state laws consist of multiple provisions that support the core MLDA-21 laws and include a family of policies directed at controlling underage drinking and underage drinking and driving. Because social host and fake identification laws have recently garnered interest by policy makers in the states, this study was designed to determine their effectiveness. Methods: The effective dates for 2 types of social host laws and 3 fake identification laws were documented using the Alcohol Policy Information System (APIS), the Substance Abuse and Mental Health Services Administration's (SAMHSA) 2011 Report to Congress on the Prevention and Reduction of Underage Drinking, and legal research tools. These laws include social host prohibitions (SHPs) and social host civil liability (SHCL), the use of fake identification (FID), retailer support for FID, and transfer/production of FID. We used a pre–post design to evaluate the influence on underage drinking-and-driving fatal crashes of these 5 laws using the Fatality Analysis Reporting System (FARS) data set for the years 1982 through 2010. The data were analyzed using structural equation modeling (SEM) controlling for as many variables as possible. Results: For those drivers younger than aged 21 years, FID supplier laws were associated with significant decreases in FARS ratios after states adopted these laws (−1.0%, P =.030). Conclusions: The 24 states that have adopted FID supplier laws are saving an estimated 14 lives per year in the United States. An additional 16 lives could be saved if the remaining states adopted this law. FID supplier laws prohibit the production of a FID or transfer of an ID or FID to another person. The more stringent the law (i.e., whether a state prohibits only one element [weaker law] compared to both transferring and manufacturing a FID [stronger]) the more effective a deterrent it becomes to supplying a minor with a FID. States without FID supplier laws should consider adopting them.
Saccharomyces cerevisiae chromatin-assembly factors that act during DNA replication function in the maintenance of genome stability

Some spontaneous gross chromosomal rearrangements (GCRs) seem to result from DNA-replication errors. The chromatin-assembly factor I (CAF-I) and replication-coupling assembly factor (RCAF) complexes function in chromatin assembly during DNA replication and repair and could play a role in maintaining genome stability. Inactivation of CAF-I or RCAF increased the rate of accumulating different types of GCRs including translocations and deletion of chromosome arms with associated de novo telomere addition. Inactivation of CAF-I seems to cause damage that activates the DNA-damage checkpoints, whereas inactivation of RCAF seems to cause damage that activates the DNA-damage and replication checkpoints. Both defects result in increased genome instability that is normally suppressed by these checkpoints, RAD52-dependent recombination, and PIF1-dependent inhibition of de novo telomere addition. Treatment of CAF-I- or RCAF-defective cells with methyl methanesulfonate increased the induction of GCRs compared with that seen for a wild-type strain. These results indicate that coupling of chromatin assembly to DNA replication and DNA repair is critical to maintaining genome stability.
Impact of total lymph node count on staging and survival after gastrectomy for gastric cancer: data from a large US-population database.

BACKGROUND Prognosis of potentially curable (M0), completely resected gastric cancer is primarily determined by pathologic T and N staging criteria. The optimal regional dissection extent during gastrectomy for gastric adenocarcinoma continues to be debated. METHODS A gastric cancer data set was created through structured queries to the Surveillance, Epidemiology, and End Results database (1973 to 1999). Relationships between the number of lymph nodes (LNs) examined and survival were analyzed for the stage subgroups T1/2N0, T1/2N1, T3N0, and T3N1. RESULTS In every stage subgroup, overall survival was highly dependent on the number of LNs examined. Multivariate prognostic variables in the T1/2N0M0 subgroup were number of LNs examined, age (for both, P < .0001), race (P = .0004), sex (P = .0006), and tumor size (P = .02). A linear trend for superior survival based on more LNs examined could be confirmed for all four stage subgroups. Baseline model-predicted 5-year survival with only one LN examined was 56% (T1/2N0), 35% (T1/2N1), 29% (T3N0), or 13% (T3N1). For every 10 extra LNs dissected, survival improved by 7.6% (T1/2N0), 5.7% (T1/2N1), 11% (T3N0), or 7% (T3N1). A cut-point analysis yielded the greatest survival difference at 10 LNs examined but continued to detect significantly superior survival differences for cut points at up to 40 LNs, always in favor of more LNs examined. CONCLUSION Although the impact of stage migration versus improved regional disease control cannot be separated on basis of the available information, the data provide support in favor of extended lymphadenectomy during potentially curative gastrectomy for gastric cancer.
Vascular endothelial growth factor as a marker of tumor endothelium.

Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that is a primary stimulant of the vascularization of solid tumors. VEGF production is induced by oncogenic gene mutations in the tumor cells and by hypoxic conditions inside the tumor mass. Hypoxia and the locally increased concentration of VEGF lead to an up-regulation of VEGF receptor expression on tumor endothelial cells. Therefore, in the tumor microenvironment, there is an up-regulation of both VEGF and its receptor, leading to a high concentration of occupied receptor on tumor vascular endothelium. The VEGF:receptor complex presents an attractive target for the specific delivery of drugs or other effectors to tumor endothelium. In the present study, several hybridomas that secrete monoclonal antibodies against the VEGF:receptor (Flk-1) complex or against VEGF itself have been raised. Three of the antibodies (3E7, GV39M, and 11B5) bind with high affinity to the VEGF:Flk-1 complex in ELISA and to tumor endothelium in frozen sections of human tumors, rodent tumors, and human tumor xenografts. 3E7 and GV39M localize selectively to tumor endothelium after i.v. injection into mice bearing human tumor xenografts. Additionally, one antibody (2C3) was raised that blocks the interaction between VEGF and KDR/Flk-1. 2C3 inhibits VEGF-mediated growth of endothelial cells in vitro and localizes strongly to connective tissue in tumors after injection into mice bearing human tumor xenografts. These findings suggest that 3E7, GV39M, and 2C3 are candidates for targeting and imaging the vasculature or connective tissue of tumors.
Short‐term effect of dexamethasone on fatty acid and cholesterol synthesis in isolated rat hepatocytes

The short‐term effect of dexamethasone, a synthetic glucocorticoid, on both fatty acid and cholesterol synthesis has been investigated in rat hepatocyte cultures. Within 4h following hormone addition to the cultures, a noticeable stimulation of labelled acetate incorporation into fatty acids was observed. Similar behaviour was noticed when [3H]H20 was used as an independent index of the lipogenic activity. In the same cultures, however, cholesterol synthesis from both [14C]acetate or [3H]H20 was significantly reduced by dexamethasone addition. In these conditions, no significative variation of cholesterol synthesis starting from labelled mevalonate was observed.
Hormonal factors in the control of the browning of white adipose tissue

Abstract Adipose tissue has been historically classified into anabolic white adipose tissue (WAT) and catabolic brown adipose tissue (BAT). Recent studies have revealed the plasticity of WAT, where white adipocytes can be induced into ‘brown-like’ heat-producing adipocytes (BRITE or beige adipocytes). Recruiting and activating BRITE adipocytes in WAT (so-called ‘browning’) is believed to provide new avenues for the treatment of obesity-related diseases. A number of hormonal factors have been found to regulate BRITE adipose development and activity through autocrine, paracrine and systemic mechanisms. In this mini-review we will discuss the impact of these factors on the browning process, especially those hormonal factors identified with direct effects on white adipocytes.
GOLD classifications and mortality in chronic obstructive pulmonary disease: the HUNT Study, Norway

Background How different Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications of chronic obstructive pulmonary disease (COPD) predict mortality is unclear. Objective To examine the association of spirometric GOLD grades and the new ABCD groups with mortality, and to compare their informativeness in relation to mortality. Methods We studied 1540 people with post-bronchodilator COPD who participated in the Norwegian Nord-Trøndelag Health Study 1995–1997 and were followed up on all-cause mortality until May 2012. The associations of spirometric GOLD grades and ABCD groups with mortality were estimated by sex specific adjusted HRs from Cox regression and standardised mortality ratios. To assess the informativeness of spirometric GOLD grades and ABCD groups at predicting mortality we used the difference in twice the log-likelihood of a Cox regression model with and without each COPD classification. Results The distribution of participants was 28% in GOLD 1, 57% in GOLD 2, 13% in GOLD 3 and 2% in GOLD 4, in contrast to 61% in group A, 18% in group B, 12% in group C and 10% in group D. During a median of 14.6 years of follow-up, 837 people (54%) died. Mortality increased gradually from GOLD 1 to 4, while it was generally similar in groups A and B, and in groups C and D. Spirometric GOLD grades were substantially more informative than ABCD groups at predicting mortality. Conclusions Spirometric GOLD grades predicted mortality better than the new ABCD groups among people with COPD from a Norwegian general population.
Dynamics of water storage in mature subalpine Picea abies: temporal and spatial patterns of change in stem radius.

Internal water reserves in bark and foliage of trees contribute to transpiration (T) and play an essential role in optimizing water transport by buffering extreme peaks of water consumption. We examined patterns of stem shrinkage and their relationship to tree water dynamics. We measured fluctuations in root radius and stem radius at different stem heights, T of twigs at the top of the crown and sap flow velocities in stem sections of mature subalpine Norway spruce (Picea abies (L.) Karst. ) trees over 2 years. The output of each sensor was coupled by physical functions to a mechanistic flow and storage model of tree water relations. The data verified the model-predicted lag in water storage depletion in response to the onset of transpiration and the lag increased with increasing distance from the crown periphery. Between the crown and stem base, the delay ranged from a few minutes to several hours, depending on microclimatic conditions and tree water status. Stem volume changes were proportional to the amount of water exchanged between the elastic tissues of the bark and the rigid xylem, indicating that the "peristaltic" wave of stem contraction along the flow path represented depletion of water stored in bark. On a daily basis, stems lost between 0.2 and 0.5% of their volume as a result of bark dehydration, corresponding to about 2 to 5 l of water. This water contributed directly to T. According to the model based on hydraulic principles, there are three main components underlying the dynamics of water storage depletion: flow resistance, storage capacities of needles and bark, and T of each tree section. The resistances and capacities were proportional to the response delay, whereas T in the lower parts of the tree was inversely proportional. The pattern of T within the crown depended on water intercepted by the branches. Because of these weather-dependent factors, there was no time constant for the response delay along the flow path. Nevertheless, the upper crown and the root section tended to have longer response delays per meter of flow path than the stem. The diurnal course of stem radius fluctuations represents the sum of all external and internal conditions affecting tree water relations; stem radius fluctuations, therefore, provide a sensitive measure of tree water status.
Online junction temperature measurement using peak gate current

A new method for junction temperature measurement of MOS-gated power semiconductor switches is presented. The measurement method involves detecting the peak voltage over the external gate resistor of an IGBT or MOSFET during turn-on. This voltage is directly proportional to the peak gate current and fluctuates with temperature due to the temperature-dependent resistance of the internal gate resistance. A measurement circuit can be integrated into a gate driver with no disruption to converter operation. The method is immune to dependence on load current, and allows autonomous and high frequency measurements through a measurement circuit directly controlled via the gate signal.
People capability: A strategic capability for enhancing organizational excellence of construction firms

Purpose This paper aims to find out how construction organizations can achieve excellence and enhance excellence through knowledge and workforce management. The combination of knowledge and workforce management, referred to here as the People Capability, is the key area of concern in this study. Design/methodology/approach The European Foundation for Quality Management (EFQM) model of organizational excellence is used as the basis for organizational excellence assessment and system dynamics is used as the modeling tool. Scenario analysis is conducted to identify the enabling factors that are more significant for organizational excellence, as well as how these factors operate and interact. Findings Based on the outcomes of the model, human resource development and training is the most important enabling factor that enhances organizational capabilities. Both workforce management and knowledge management are key components of People Capability, and they play crucial roles in the performance of construction firms. There is a high degree of dependence on these two components. Human resource development and training affect all capability areas and are key to the effective implementation of capability building programs. Originality/value Organizations might have various options in choosing different policies, and those policies can be planned and expressed in different manners and scales. How can an organization determine which scenarios end up producing desired performance results? Simulation techniques, especially system dynamics, have been used to answer these types of questions due to their ability to model causal relationships among various system components. The results of this research can help construction organizations identify effective knowledge and workforce management policies and capability-building programs that improve their organizational capabilities.