Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative studies of endotoxin uptake by isolated rat Kupffer and peritoneal cells

The process of uptake of endotoxin by cells of the reticuloendothelial system is of current interest. Rabbit peritoneal macrophages have been used to study macrophage-endotoxin interactions and have suggested a receptor-mediated process. It is generally believed that the site of in vivo endotoxin clearance is the liver and that this clearance involves the Kupffer cell population. In the current report, the uptake characteristics of iodine-125-labeled Salmonella minnesota lipopolysaccharide (LPS) were compared in both isolated rat Kupffer cells and elicited rat peritoneal cells. Both types of cells were isolated from male Sprague-Dawley rats fed a semisynthetic AIN-76 5% saturated-fat diet either by peritoneal lavage for peritoneal cells or by collagenase perfusion followed by purification on a 17.5% metrizamide gradient for Kupffer cells. Hot phenol water-extracted S. minnesota LPS was labeled with iodine by the chloramine-T method following a reaction with methyl-p-hydroxybenzimidate. The in vitro uptake of [125I]LPS by Kupffer cells was unsaturable up to concentrations of 33.33 micrograms/ml, while peritoneal cells became saturated at between 16.67 and 25 micrograms of LPS per ml. Uptake by both types of cells could be inhibited by a 10-fold excess of unlabeled LPS. Kinetic experiments demonstrated that Kupffer cells were unsaturable after 60 min of incubation, while peritoneal cells were saturable after 40 min of incubation. Pretreatment with 75 mM colchicine inhibited uptake by peritoneal cells but not Kupffer cells, while pretreatment with 12 mM 2-deoxyglucose inhibited uptake by Kupffer cells but not peritoneal cells. These results are consistent with a process of receptor-mediated endocytosis for peritoneal cells, while Kupffer cells may internalize endotoxins by absorptive pinocytosis. These results suggest that studies of peritoneal cell-endotoxin interactions do not accurately describe the physiologic process within the liver, the major site for the clearance of gut-derived endotoxins.
Carboxymethyllysine in Dermal Tissues of Diabetic and Nondiabetic Patients with Chronic Renal Failure: Relevance to Glycoxidation Damage

Carboxymethyllysine (CML) is currently recognized as a major advanced glycation end product and a marker for glycoxidation. Plasma CML levels are increased in patients with chronic renal failure (CRF). However, significance and mechanism of CML accumulation in these patients are poorly understood. The objective of the present study was to analyze CML in soluble and collagen-binding fractions of the dermis to investigate CML deposition and formation and collagen damage related to CML accumulation in patients with CRF. Skin samples (among them autopsy samples) were obtained from 33 subjects: 8 nondiabetic CRF patients, 7 diabetic predialysis patients with CRF (CRF-DM), 7 hemodialysis patients, and 11 control subjects without either CRF or DM. The dermal samples were extracted sequentially by phosphate-buffered normal saline, pepsin, and collagenase. The extracts were referred to as the soluble fraction and the proteinase-extracted fraction (including pepsin-extracted and collagenase-extracted fractions). Our ELISA assay for CML in dermal collagen from predialysis patients with CRF (CRF and CRF-DM groups) demonstrated that the levels of CML in both the soluble fraction (containing soluble CML which was mainly determined by serum clearance) and the structural collagen-binding proteinase-extracted fraction (in which high CML levels could be a strong indication of in situ formation) were increased and could not be completely reduced after hemodialysis in CRF-DM and CRF groups. These results suggest that accumulation of CML may be due to both a low serum clearance and/or increased in situ CML formation in CRF. CML contents in the proteinase extracted fraction inversely correlated with the susceptibility of collagen to extraction by proteinases (n = 33, r = –0.59, p < 0.001). Our results provide the first biochemical evidence that CML level is increased in both the soluble and collagen-binding fractions and that increased CML level resulted in increased fractions of proteinase-resistant collagen in dermal extracts of patients with CRF.
Beneficial effect of glutamine on exercise-induced apoptosis of rat neutrophils.

INTRODUCTION/PURPOSE The effect of a single bout of intensive exercise on apoptosis of rat neutrophils and the possible prevention by glutamine administration was examined. The experiments were performed in sexually immature and sexually mature male rats as to examine the possible involvement of sexual maturation in the effect of exercise. METHODS Exercise was carried out on a treadmill for 1 h before rats were killed by decapitation. Aqueous solution of glutamine was given by gavage (1 g.kg-1 body weight), 1 h before exercise. Neutrophils were obtained by intraperitoneal lavage with phosphate-buffered saline (PBS), 4 h after injection of oyster glycogen solution. The cells were then analyzed for apoptosis by flow cytometry and fluorescence microscopy. Pro- and antiapoptotic gene expression was evaluated by reverse transcriptase chain reaction (RT-PCR). RESULTS Neutrophils obtained from immature and mature exercised rats showed an increase in DNA fragmentation, chromatin condensation, and phosphatidylserine externalization. This suggests that all neutrophils suffered apoptosis. To study the possible mechanism involved, the production of reactive oxygen metabolites, expression of genes involved in apoptosis and mitochondrial transmembrane potential were examined. Acute exercise raised reactive oxygen metabolites production by neutrophils. Exercise did not change the expression of antiapoptotic (bcl-xL) and apoptotic (bax and bcl-xS) genes in neutrophils from immature rats but caused a significant increase of bax and bcl-xS expression and provoked a significant decrease of bcl-xL expression in cells from mature rats. Exercise also induced a marked loss of mitochondrial depolarization in neutrophils. Oral glutamine supplementation partially prevented the exercise-induced apoptosis in neutrophils from sexually immature and mature rats. CONCLUSION The protective effect of glutamine on neutrophil apoptosis induced by acute exercise possibly occurs by preservation of mitochondrial function.
Ultrasonically guided fine‐needle aspiration biopsy of gastrointestinal mass lesions.

Ultrasonically guided fine‐needle aspiration biopsy was performed in 78 patients with ultrasonically demonstrable typical gastrointestinal mass lesions. Of these patients, 61 later proved to have malignant lesions (18 in the stomach, three in the small intestine, and 40 in the colon or rectum), and 17 had benign lesions. In 50 of 61 cases of malignant lesions, the cytologic diagnosis was positive for cancer. There were no false positives. It is concluded that when a structure with the ultrasonic characteristics of a gastrointestinal mass lesion is disclosed, fine‐needle aspiration biopsy can safely and conveniently differentiate between malignant and benign lesions in most cases. The ultrasonically guided biopsy is suggested as an alternative to endoscopically guided biopsy.
The role of blockchain and IoT in recruiting participants for digital clinical trials

Our personal data is now more valuable than ever. The uncontrolled growth of internet-centered services has led us to accept many compromises about how we share it. In the era of Internet of Things, personal data is collected continuously. Now, more than ever, we are in need of privacy-preserving applications where users always retain control of their personal data. In this paper, we present a secure way to control the flow of personal data in the specific case of the recruitment of participants for clinical trials. We take special care to protect the interests of both parties: the individual can keep its data private until an agreement is reached, and the Clinical Research Institute can be assured that it is acquiring useful and authentic data. We provide a proof-of-concept implementation and study its performance based on a real-world evaluation.
CXCL9 and CXCL10 Expression Are Critical for Control of Genital Herpes Simplex Virus Type 2 Infection through Mobilization of HSV-Specific CTL and NK Cells to the Nervous System1

CXCL9 and CXCL10 mediate the recruitment of T lymphocytes and NK cells known to be important in viral surveillance. The relevance of CXCL10 in comparison to CXCL9 in response to genital HSV-2 infection was determined using mice deficient in CXCL9 (CXCL9−/−) and deficient in CXCL10 (CXCL10−/−) along with wild-type (WT) C57BL/6 mice. An increased sensitivity to infection was found in CXCL10−/− mice in comparison to CXCL9−/− or WT mice as determined by detection of HSV-2 in the CNS at day 3 postinfection. However, by day 7 postinfection both CXCL9−/− and CXCL10−/− mice possessed significantly higher viral titers in the CNS in comparison to WT mice consistent with mortality (18–35%) of these mice within the first 7 days after infection. Even though CXCL9−/− and CXCL10−/− mice expressed elevated levels of CCL2, CCL3, CCL5, and CXCL1 in the spinal cord in comparison to WT mice, there was a reduction in NK cell and virus-specific CD8+ T cell mobilization to this tissue, suggesting CXCL9 and CXCL10 are critical for recruitment of these effector cells to the spinal cord following genital HSV-2 infection. Moreover, leukocytes from the spinal cord but not from draining lymph nodes or spleens of infected CXCL9−/− or CXCL10−/− mice displayed reduced CTL activity in comparison to effector cells from WT mice. Thus, the absence of CXCL9 or CXCL10 expression significantly alters the ability of the host to control genital HSV-2 infection through the mobilization of effector cells to sites of infection.
Do Transitions to Adulthood Converge in Europe? An Optimal Matching Analysis of Work–Family Trajectories of Men and Women from 20 European Countries

This paper addresses the question of the convergence of transitions to adulthood in 20 European countries using data from the third round of the European Social Survey (2006). Pathways are derived from five events – employment, leaving-home, union formation, marriage and childbearing – retrospectively observed for men and women over 35 years old (N = 26,351), over four birth cohorts and described with optimal matching and cluster analyses. Using correspondence analysis, we find a convergence between male and female patterns in the passage to adulthood in Northern and Western Europe. Despite some convergence, the transition to adulthood in European countries remains marked by their historical family systems.
Making the Cut

Selection of trainees for surgical training is widely acknowledged to be both complex and important. Doctors embarking on surgical careers expend considerable time and resources in training, as do those responsible for facilitating their learning. The aim of surgical training is to prepare surgeons to be competent, effective, ethical practitioners in unsupervised clinical practice as consultant surgeons (Carroll, Kennedy, Traynor & Gallagher, 2009; Elfenbein, Sippel, McDonald, Watson, Scarborough & Migaly, 2015). The aim of selection must be to admit those who are most likely to succeed in surgical training and beyond. Admitting candidates who are inadequately suited to surgical training can result in trainees who unduly struggle or are unable to satisfy training requirements, and may ultimately jeopardise patient safety. In contrast, not accepting candidates who are well-suited to surgical training may be unfair to both candidates and communities that miss out on skillful surgeons. These aspects are among those that make selection to surgical training an extremely ‘highstakes’ activity. Those responsible for selection grapple with assessing candidates’ current skills and attributes, and with ascertaining their likely future performance. Limitations of, and tensions between interacting elements—human agency, requirement specifications, instruments, processes, influences—in selection to surgical training, mean that the long-term outcomes of selection can never be assured. This study identifies principal elements in selection to surgical training, discusses influences on, and interrelationships between the elements, and reviews connections between selection and surgical training assessments. This study has appraised the current instruments used for selection into the Royal Australasian College of Surgeons’ (RACS) General Surgery (GS) training program in Australia and New Zealand, to establish their effectiveness in predicting trainees’ performance in assessments during the first two years of training. Data were considered for selection and assessment items for trainees for three yearly cohorts, selected in 2008, 2009, and 2010. The
Binding of phosphatidic acid by NsD7 mediates the formation of helical defensin–lipid oligomeric assemblies and membrane permeabilization

Significance Direct attack of target cell membranes by protein oligomerization is a powerful innate defense mechanism used widely throughout nature. Defensins are ubiquitous innate immunity mediators that are able to recognize certain phospholipids, and subsequently oligomerize to attack target cell membranes. We now show that the plant defensin NsD7 is able to bind the cellular phospholipid, phosphatidic acid (PA), which triggers defensin oligomerization in a unique manner. Our crystal structure of the NsD7–PA oligomer revealed a striking double-helical defensin–lipid oligomer that features a novel phospholipid-binding site mediating PA binding and membrane permeabilization. This demonstrates that defensins use their conserved small fold in a remarkably flexible way to specifically recognize a range of phospholipids during innate defense using different binding sites. Defensins are cationic antimicrobial peptides that serve as important components of host innate immune defenses, often by targeting cell membranes of pathogens. Oligomerization of defensins has been linked to their antimicrobial activity; however, the molecular basis underpinning this process remains largely unclear. Here we show that the plant defensin NsD7 targets the phospholipid phosphatidic acid (PA) to form oligomeric complexes that permeabilize PA-containing membranes. The crystal structure of the NsD7–PA complex reveals a striking double helix of two right-handed coiled oligomeric defensin fibrils, the assembly of which is dependent upon the interaction with PA at the interface between NsD7 dimers. Using site-directed mutagenesis, we demonstrate that key residues in this PA-binding site are required for PA-mediated NsD7 oligomerization and coil formation, as well as permeabilization of PA-containing liposomes. These data suggest that multiple lipids can be targeted to induce oligomerization of defensins during membrane permeabilization and demonstrate the existence of a “phospholipid code” that identifies target membranes for defensin-mediated attack as part of a first line of defense across multiple species.
Genetics of metalaxyl resistance in Phytophthora infestans.

Several sexual crosses involving isolates of Phytophthora infestans of diverse sensitivities to metalaxyl were studied. Metalaxyl sensitivity was determined by comparing the growth of an isolate on metalaxyl-amended agar medium (5 microg/ml) with growth on medium containing no metalaxyl. When both parents had the same phenotype for metalaxyl sensitivity (both resistant or both sensitive), all F1 progeny had the parental phenotype. In two crosses (75 and 76) each involving one sensitive and one resistant parent, however, the progeny segregated 1:1, suggesting that the common resistant parent (Bg8) was heterozygous for metalaxyl sensitivity. When an F2 progeny was constructed from resistant F1 isolates in cross 76, the progeny segregated 1:3 (sensitive:resistant), indicating that metalaxyl resistance in Bg8 is conferred by a single dominant gene. Variation in the progeny sensitivity appears to involve minor genes. A correlation study between metalaxyl resistance and fitness components did not reveal any association.
Development Economics: An Institutional Bastion

What binds most of the disparate writings by institutional economists (broadly defined), from the earlier progenitors, such as Veblen, Keynes and Galbraith, to the modern institutionalists, including Means, Fusfield and Hodgson, is their questioning of many of the tenets of neoclassical theory. Within this same broad paradigm, there has also been an emergence of ‘new institutional economics’, whose chief protagonists are Oliver Williamson and Douglas C. North. However, for the latter, the relationship between institutions and markets across time and space starts from the basic propositions of rational individualism and competition pertaining to neoclassical economics, with the inclusion of more institutional detail than is usual for neoclassical models. This paper seeks to explore as yet an uncharted area, that is, that development economics, from the writings of Arthur Lewis to those of Amartya Sen, has long been the bastion of institutional economics. Despite the concerted attacks by neoclassicists on the discipline in the early 1980s, development economics has never been persuaded by the strength of argument of the mainstream neoclassical case. Arguably, the common ground of development economics as an identifiable branch of the discipline has been its concern with the impact of institutional factors (cultural values in civil society, politico-bureaucratic states, global economic organisations) on resource allocation. Concepts such as dependency, unequal exchange, entitlements the neo-colonial state, urban bias, the East Asian miracle and transnational corporations have strong institutional roots. This paper will examine the shifting views on institutional factors in development economics and attempt to integrate the New Institutional Economics into a more general theory.
5-HT1B Receptor Knockout Mice Exhibit an Enhanced Response to Constant Light

Serotonin (5-HT) can act presynaptically at 5-HT1B receptors on retinal terminals in the suprachiasmatic nucleus (SCN) to inhibit glutamate release, thereby modulating the effects of light on circadian behavior. 5-HT1B receptor agonists (1) inhibit light-inducedphase shifts of circadian activity rhythms, (2) attenuate light-induced Fos expression in the SCN, and (3) reduce the amplitude of optic nerve–evoked excitatory postsynaptic currents in SCN neurons in vitro. To determine whether functional disruption of the 5-HT1B presynaptic receptors would result in an amplified response of the SCN to light, the period ([.tau]) of the circadian rhythm of wheel-running activity was estimated under several different conditions in 5-HT1B receptor knockout (KO) mice and genetically matched wild- typeanimals. Under constant light (LL) conditions, the [. tau] of 5-HT1B receptor KO mice was significantly greater than the [. tau] of wild-type mice. Aquantitative analysis of the wheel-running activity revealed no differences between wild-type and KO mice in either total activity or the temporal distribution of activity under LL conditions, suggesting that the observed increase in [. tau] was not a function of reduced activity. Under constant dark conditions, the period of the circadian rhythm of wheel-running activity of wild-type and 5-HT1B receptor KO mice was similar. In addition, no differences were noted between wild-type and 5-HT1Breceptor KO mice in the rate of reentrainment toa6h phase advance in the 12:12 light:dark cycle or in phase shifts in response to a 10 min light pulse presented at circadian time 16. The enhanced response of the SCN circadian clock of the 5- HT1B receptor KO mice to LLconditions is consistent with the hypothesis that the endogenous activation of 5-HT1B presynaptic receptors modulates circadian behavior by attenuating photic input to the SCN.
The use of toluidine blue in the detection of pre-malignant and malignant oral lesions.

INTRODUCTION The purpose of this study was to evaluate the efficacy of the toluidine blue (TB) test as a diagnostic tool in the detection of malignant and dysplastic lesions of the oral cavity. This study was carried out because of a lack of consensus among different authors on the utility of TB, as well as to determine useful adjuncts to detect oral pre-cancer and cancer. MATERIALS AND METHODS The study included 160 patients with oral mucosal disorders that included suspicious or malignant lesions detected at clinical visual examination, confirmed by histopathological evaluation. All lesions were submitted to TB staining. RESULTS The sensitivity and specificity for the detection of malignant or dysplastic lesions by this test were 65.5% and 73.3%, respectively. Overall, the detection rate with TB (sensitivity) was slightly lower compared with those reported by other authors but the specificity was comparable to several reports. Positive predictive value (35.2%) was also lower than previous studies, whereas negative predictive value (90.6%) was similar. CONCLUSIONS The simplicity of the test procedure and the validity of derived values suggest TB staining can be a valuable adjunct to the diagnostic process, as long as it is carefully correlated with the clinical characteristics of the mucosal disorder and histopathological diagnosis.
The capacity of random wireless networks

We analyze how the capacity of the random wireless network scales with node density for stationary nodes, taking jointly into account link adaptation, media access control (MAC), routing and retransmission for error recovery (ARQ). For the purpose, we propose a generic per-hop-based routing scheme, in which relay probability is a key parameter, and use the routing scheme as a basis for our analysis. By jointly optimizing the above factors, we derive the capacity of the random network. Our analysis shows that the per-node throughput of a static random wireless network composed of n source-destination pairs is O(1/radic(n log n)). This capacity estimation is similar to that of Gupta and Kumar, even if the assumptions are quite different.We also use simulations to investigate how node mobility affects the capacity of a random network. We have found that mobility can increase network capacity, by giving the nodes more chances to be close to each other. Our simulation results empirically show that the capacity of the random network under a mobility condition declines in the order of O(1/radicn).
Effect of chronic treatment with three varieties of Lepidium meyenii (Maca) on reproductive parameters and DNA quantification in adult male rats

The aim of this study was to evaluate the chronic effect of different varieties of Lepidium meyenii (Red Maca, Yellow Maca and Black Maca). Male rats were treated by gavage with aqueous extract of each variety of maca equivalent to 1 g hypocotyl kg−1 body weight (BW) for 84 days. At the end of the treatment, daily sperm production (DSP), epididymal sperm count (ESC) and sperm count in vas deferens (SCVD) were assessed. In addition, testis DNA quantification was also determined. Any toxic effect was assessed in liver and spleen by histological studies. The results indicate that Yellow Maca and Black Maca improved ESC and that three varieties of maca increased the SCVD without affecting DSP. Moreover, testis DNA levels were not affected by treatment with any of the three varieties of maca. Histological picture of the liver in animals treated with the three varieties of maca was similar to that observed in controls. In conclusion, Yellow and Black Maca increased epididymal sperm count after 84 days of treatment without affecting DSP. Maca seems to act as a modulator of sperm count at the reproductive tract level.