Miracle-dz/UniFAR-FTUs huggingface dataset:
Cross-reactivity of anti-human immunodeficiency virus type 1 gp41 antibodies with human astrocytes and astrocytoma cell lines

An antigen expressed by astrocytes in human brain tissue and by various human astrocytoma cell lines was shown to cross-react with a monoclonal antibody generated against amino acids (aa) 584 to 609 of the transmembrane protein gp41 of human immunodeficiency virus type 1 (HIV-1). This region is an immunodominant segment of gp41, and high levels of antibodies against this epitope have been detected in both serum and cerebrospinal fluid of HIV-infected individuals at all stages of HIV infection. Immunohistochemistry with this monoclonal antibody demonstrated the presence of a cross-reactive antigen in human brain tissue, with an increased frequency and intensity of staining in HIV-positive individuals when compared with HIV-negative controls. By using a panel of HIV-positive and -negative sera, we show that antibodies in HIV-positive serum specifically bound to the surfaces of human astrocytoma cells. HIV-positive sera depleted of antibodies recognizing gp41 aa 584 to 609 showed a significant diminution in cell surface binding. Conversely, the serum antibodies that bound to and were eluted from the aa 584 to 609 peptide also bound to the astrocyte cell surface. To identify the target antigen, the immunoreactivity of three astrocytoma cell lines was examined. By immunoprecipitation of metabolically labeled cell lysates and Western blot (immunoblot) analysis, we identified a protein of approximately 100 kDa as the target antigen. Cross-reactive antibodies between HIV proteins and astrocyte epitopes, such as this 100-kDa protein and others previously reported, suggests that an autoimmune response against these target antigens may disrupt the normal functions of astrocytes.
Functions and Regulation of Circular Dorsal Ruffles

ABSTRACT Cells construct a number of plasma membrane structures to meet a range of physiological demands. Driven by juxtamembrane actin machinery, these actin-based membrane protrusions are essential for the operation and maintenance of cellular life. They are required for diverse cellular functions, such as directed cell motility, cell spreading, adhesion, and substrate/matrix degradation. Circular dorsal ruffles (CDRs) are one class of such structures characterized as F-actin-rich membrane projections on the apical cell surface. CDRs commence their formation minutes after stimulation as flat, open, and immature ruffles and progressively develop into fully enclosed circular ruffles. These “rings” then mature and contract centrifugally before subsiding. Serving a critical function in receptor internalization and cell migration, CDRs are thus highly dynamic but transient formations. Here, we review the current state of knowledge concerning the regulation of circular dorsal ruffles. We focus specifically on the biochemical pathways leading to CDR formation in order to better define the roles and functions of these enigmatic structures.
IgE Binding to Pepsin-Digested Food Extracts

Background: Pepsin resistance of allergens like lipid transfer protein and 2S albumin has been suggested as explanation for the severity of symptoms often induced by these allergens. Component-resolved diagnosis with purified labile and stable allergens has therefore been proposed to better characterize the risk involved in a positive in vitroIgE test. However, for many foods, purified allergens are not (yet) available. Objective: It was the aim of this study to evaluate the potential of pepsin-digested whole-food extracts to distinguish between IgE responses to stable (potentially severe) and labile (mild) allergens. Methods: Sera (n = 143) from Italian, Spanish and Dutch patients with hazelnut and/or apple ingestion-related symptoms were analyzed for residual IgE binding to pepsin-resistant hazelnut and/or apple allergens. Control and pepsin-digested hazelnut and apple extracts were used for radioallergosorbent test analysis and immunoblot analysis. Results: Pepsin digestion of food extracts, like from hazelnut and apple used for in vitro diagnostic tests, provides a way to distinguish sensitization to pepsin-resistant allergens from that to pepsin-susceptible allergens. In this selected group of patients, IgE reactivity to pepsin-digested extracts correlated with sensitization to the stable allergen lipid transfer protein. The analysis further revealed that the use of soluble pepsin can result in false-positive in vitro tests (2/143). Conclusion: Pepsin-digested food extracts are a convenient tool to identify patients with IgE antibodies against potentially dangerous stable allergens, in particular for those foods where the relevant stable allergens have not yet been identified. This can increase the clinical prognostic value of food allergy serology.
Supporting Research in Area Studies: A Guide for Academic Libraries

The study of other countries or regions of the world often crosses traditional disciplinary boundaries in the humanities and social sciences. Supporting Research in Area Studies is a comprehensive guide for academic libraries supporting these communities of researchers. This book explores the specialist requirements of these researchers in information resources, resource discovery tools, and information skills, and the challenges of working with materials in multiple languages. It makes the case that by adapting their systems and procedures to meet these needs, academic libraries find themselves better placed to support their institution's�� international agenda more widely. The first four chapters cover the academic landscape and its history, area studies librarianship and acquisitions. Subsequent chapters discuss collections management, digital products, and the digital humanities, and their role in academic projects. The final chapter explores information skills and the various disciplinary skills that facilitate the needs of researchers during their careers.
Characterization of Insulin Resistance and NIDDM in Transgenic Mice With Reduced Brown Fat

We recently created a new model of murine obesity through transgenic ablation of brown adipose tissue (BAT) using a tissue-specific toxigene (6). The goal of the present study was to further define the altered glucose homeostasis and insulin resistance in these transgenic animals. Despite an ∼30% increase in total body lipid, no abnormalities were observed in 6-week-old transgenic animals. At the age of 22–26 weeks, marked obesity in transgenic mice was associated with significant increases in blood glucose and plasma insulin levels and an abnormal response to both intraperitoneal glucose and insulin tolerance tests. Glucose transport in soleus muscle was reduced, with the response to insulin stimulation blunted by up to 85% in males and 55% in females. The total number of insulin receptors was decreased by 36% in muscle and 59% in adipose tissue of transgenic animals. Insulin receptor tyrosine kinase activity, which was assessed following maximal insulin stimulation in vivo, was reduced in transgenic animals by 59% in muscle and 56% in fat. GLUT4 mRNA and protein was unchanged in muscle of transgenic animals compared with in that of controls but was significantly reduced in adipose tissue. In conclusion, primary BAT deficiency results in the development of glucose intolerance or diabetes and severe insulin resistance with both receptor and postreceptor components. These animals should be a useful model for studies of obesity-linked diabetes and insulin resistance and related complications.
Dimemorfan protects rats against ischemic stroke through activation of sigma‐1 receptor‐mediated mechanisms by decreasing glutamate accumulation

Dimemorfan, an antitussive and a sigma‐1 (σ1) receptor agonist, has been reported to display neuroprotective properties. We set up an animal model of ischemic stroke injury by inducing cerebral ischemia (for 1 h) followed by reperfusion (for 24 h) (CI/R) in rats to examine the protective effects and action mechanisms of dimemorfan against stroke‐induced damage. Treatment with dimemorfan (1.0 μg/kg and 10 μg/kg, i.v.) either 15 min before ischemia or at the time of reperfusion, like the putative σ1 receptor agonist, PRE084 (10 μg/kg, i.v.), ameliorated the size of the infarct zone by 67–72% or 51–52%, respectively, which was reversed by pre‐treatment with the selective σ1 receptor antagonist, BD1047 (20 μg/kg, i.v.). Major pathological mechanisms leading to CI/R injury including excitotoxicity, oxidative/nitrosative stress, inflammation, and apoptosis are all downstream events initiated by excessive accumulation of extracellular glutamate. Dimemorfan treatment (10 μg/kg, i.v., at the time of reperfusion) inhibited the expressions of monocyte chemoattractant protein‐1 and interleukin‐1β, which occurred in parallel with decreases in neutrophil infiltration, activation of inflammation‐related signals (p38 mitogen‐activated protein kinase, nuclear factor‐κB, and signal transducer and activator of transcription‐1), expression of neuronal and inducible nitric oxide synthase, oxidative/nitrosative tissue damage (lipid peroxidation, protein nitrosylation, and 8‐hydroxy‐guanine formation), and apoptosis in the ipsilateral cortex after CI/R injury. Dimemorfan treatment at the time of reperfusion, although did not prevent an early rise of glutamate level, significantly prevented subsequent glutamate accumulation after reperfusion. This inhibitory effect was lasted for more than 4 h and was reversed by pre‐treatment with BD1047. These results suggest that dimemorfan activates the σ1 receptor to reduce glutamate accumulation and then suppresses initiation of inflammation‐related events and signals as well as induction of oxidative and nitrosative stresses, leading to reductions in tissue damage and cell death. In conclusion, our results demonstrate for the first time that dimemorfan exhibits protective effects against ischemic stroke in CI/R rats probably through modulation of σ1 receptor‐dependent signals to prevent subsequent glutamate accumulation and its downstream pathologic events.
Lactoferrin decreases LPS-induced mitochondrial dysfunction in cultured cells and in animal endotoxemia model

Lactoferrin is a non-heme iron-binding glycoprotein, produced by mucosal epithelial cells and granulocytes in most mammalian species. It is involved in regulation of immune responses, possesses anti-oxidant, anti-carcinogenic, anti-inflammatory properties, and provides protection against various microbial infections. In addition, lactoferrin has been implicated in protection against the development of insult-induced systemic inflammatory response syndrome (SIRS) and its progression into septic conditions in vivo. Here we show a potential mechanism by which lactoferrin lessens oxidative insult at the cellular and tissue levels after lipopolysaccharide (LPS) exposure. Lactoferrin pretreatment of cells decreased LPS-mediated oxidative insults in a dose-dependent manner. Lipopolysaccharide-induced oxidative burst was found to be of mitochondrial origin, and release of reactive oxygen species (ROS) was localized to the respiratory complex III. Importantly, lactoferrin nearly abolished LPS-induced increases in mitochondrial ROS generation and the accumulation of oxidative damage in the DNA. In vivo, pretreatment of experimental animals with lactoferrin significantly (P<0.05) lowered LPS-induced mitochondrial dysfunction as shown by both decreased release of H2O2 and DNA damage in the mitochondria. In contrast, deferoxamine, an iron chelating compound, provided only partial protection in LPS-treated animals. Together, these data suggest that lactoferrin protects against oxidative insult at the mitochondrial level, and indicate a potential utility of lactoferrin in prevention and treatment of SIRS.
Crystal and solution structures of an odorant-binding protein from the southern house mosquito complexed with an oviposition pheromone

Culex mosquitoes introduce the pathogens responsible for filariasis, West Nile virus, St. Louis encephalitis, and other diseases into humans. Currently, traps baited with oviposition semiochemicals play an important role in detection efforts and could provide an environmentally friendly approach to controlling their populations. The odorant binding proteins (OBPs) in the female's antenna play a crucial, if yet imperfectly understood, role in sensing oviposition cues. Here, we report the X-ray crystallography and NMR 3D structures of OBP1 for Culex quinquefasciatus (CquiOBP1) bound to an oviposition pheromone (5R,6S)-6-acetoxy-5-hexadecanolide (MOP). In both studies, CquiOBP1 had the same overall six-helix structure seen in other insect OBPs, but a detailed analysis revealed an important previously undescribed feature. There are two models for OBP-mediated signal transduction: (i) direct release of the pheromone from an internal binding pocket in a pH-dependent fashion and (ii) detection of a pheromone-induced conformational change in the OBP·pheromone complex. Although CquiOBP1 binds MOP in a pH-dependent fashion, it lacks the C terminus required for the pH-dependent release model. This study shows that CquiOBP binds MOP in an unprecedented fashion using both a small central cavity for the lactone head group and a long hydrophobic channel for its tail.
Cultivating innovation and equity in co-production of commercialized spring water in peri-urban Bandung, Indonesia

Water resources management today has shifted from a purely technical response to one that involves multiple stakeholders to allow for cross-cultural and cross-issue discussion and cooperative management. However, the integration of indigenous knowledge and local people into mainstream natural resources management is still restricted due to epistemological and institutional obstacles. This research explores the differences in perceptions of the nature of water resources, and their consequent management, existing between local people and the government in the Gam River Basin of Vietnam, concentrating on the views of the majority Tay and Dao peoples. We focus on how knowledge differences can be communicated and how water management can integrate different ways of knowing. We identify barriers to, and opportunities for, the involvement of indigenous knowledge and local people in water resources management at the research site. We argue that local needs and aspirations in relation to the use and management of water resources do indeed have a role in the modern world, contrary to the views of many scientists and government officers. Therefore, indigenous knowledge needs to be considered in water resources management schemes, to achieve the effective and sustainable use of water in areas such as the Gam River Basin.
A Physiological Role for Saccharomyces cerevisiae Copper/Zinc Superoxide Dismutase in Copper Buffering (*)

The copper toxicity of yeast lacking the CUP1 metallothionein is suppressed by overexpression of the CRS4 gene. We now demonstrate that CRS4 is equivalent to SOD1, encoding copper/zinc superoxide dismutase (SOD). While overexpression of SOD1 enhanced copper resistance, a deletion of SOD1, but not SOD2 (encoding manganese SOD), conferred an increased sensitivity toward copper. This role of SOD1 in copper buffering appears unrelated to its superoxide scavenging activity, since the enzyme protected against copper toxicity in anaerobic as well as aerobic conditions. The distinct roles of SOD1 in copper and oxygen radical homeostasis could also be separated genetically: the pmr1, bsd2, and ATX1 genes that suppress oxygen toxicity in sod1 mutants failed to suppress the copper sensitivity of these cells. The Saccharomyces cerevisiae SOD1 gene is transcriptionally induced by copper and the ACE1 trans-activator, and we demonstrate here that this induction of SOD1 promotes protection against copper toxicity but is not needed for the SOD1-protection against oxygen free radicals. Collectively, these findings indicate that copper/zinc SOD functions in the homeostasis of copper via mechanisms distinct from superoxide scavenging.
Non‐uniform phase sensitivity in spatial frequency maps of the human visual cortex

Just as a portrait painting can come from a collection of coarse and fine details, natural vision can be decomposed into coarse and fine components. Previous studies have shown that the early visual areas in the brain represent these components in a map‐like fashion. Other studies have shown that these same visual areas can be sensitive to how coarse and fine features line up in space. We found that the brain actually jointly represents both the scale of the feature (fine, medium, or coarse) and the alignment of these features in space. The results suggest that the visual cortex has an optimized representation particularly for the alignment of fine details, which are crucial in understanding the visual scene.
EM lens-clustering based direction of arrival estimation in massive antenna systems

Direction of arrival (DoA) estimation in the massive antenna systems with reduced hardware and signal processing complexity is a challenging task. To address the issue, this paper presents an approach to estimate the DoA in a large number of antennas system combined with an electromagnetic (EM) lens. An EM lens has the ability to focus the received signal energy as a function of the angle of arrival (AoA) to a small subset/area of the antenna array at the base station (BS). Thus, it helps to estimate the DoA efficiently while minimizing the number of radio frequency (RF) chains and the associated signal processing costs. Moreover, by defining a cluster over a group of closely spaced subsets, the computational efforts of the DoA estimation algorithm can be further reduced.
Detectability of Early Brain Meningitis with Magnetic Resonance Imaging

RATIONALE AND OBJECTIVESThe ability of high-field (1.5 T) magnetic resonance imaging (MRI) to detect early brain meningitis was evaluated in a canine model. Contrast dose, timing postinjection, and imaging technique (specifically the use of magnetization transfer) were assessed. METHODSImaging of five canines was performed at 1.5 T 24 hours after injection of Cowans staphylococcus into the cisterna magna. Two control animals also were imaged using the same protocol, with one animal receiving a cisternal injection of nutrient broth only and the other no injection. Contrast doses of 0.1, 0.3, and 0.8 mmol/kg gadotcridol (Gd HP-DO3A or Pro- Hance) were compared. Scans were performed at 2, 12, and 22 minutes after an initial injection of 0.1 mmol/kg. At each time point, paired T1 -weighted scans with and without magnetization transfer (MT) were acquired. Thirty minutes after the initial injection of contrast, a supplemental dose of 0.2 mmol/kg was given (for a cumulative dose of 0.3 mmol/kg). Scans were then repeated at 2, 12, and 22 minutes after this dose was administered. A second supplemental contrast injection of 0.5 mmol/kg (for a cumulative dose of 0.8 mmol/kg) was given at 70 minutes, and immediate postinjection scans with and without MT were acquired. RESULTSIn the animals receiving a cisternal injection of bacteria, the degree of meningcal enhancement was greatest at 0.8 mmol/kg, intermediate at 0.3 mmol/kg, and least at 0.1 mmol/kg. These conclusions were constant whether imaging was performed with or without MT. Scans in control studies did not demonstrate abnormal meningeal enhancement. Highcontrast dose, MT, and acquisition of immediate postcontrast scans all resulted in statistically significant improvement. On masked film review, abnormal meningcal enhancement was noted in only 2 of 5 experimental dogs at a dose of 0.1 mmol/kg (regardless of the use of MT) compared with all animals at a dose of 0.3 mmol/kg. In 18 of 37 dogs (paired scans with and without MT), when abnormal enhancement was noted, the use of MT improved the visualization of abnormal meningcal enhancement. CONCLUSIONSIn early brain meningitis, high-contrast dose (0.3 mmol/kg), MT, and scanning immediately after injection improve detection of abnormal meningeal enhancement, thus facilitating the diagnosis of meningitis. Of these factors, contrast dose is the most important.
Tight Mixed Integer Linear Programming Formulations for the Unit Commitment Problem

This paper examines the polytope of feasible power generation schedules in the unit commitment (UC) problem. We provide computational results comparing formulations for the UC problem commonly found in the literature. We introduce a new class of inequalities, giving a tighter description of feasible operating schedules for generators. Computational results show that these inequalities can significantly reduce overall solution times.
Membrane permeability and antimicrobial kinetics of cecropin P1 against Escherichia coli

The interaction of cecropin P1 (CP1) with Escherichiacoli was investigated to gain insight into the time‐dependent antimicrobial action. Biophysical characterizations of CP1 with whole bacterial cells were performed using both fluorescent and colorimetric assays to investigate the role of membrane permeability and lipopolysaccharide (LPS) binding in lytic behavior. The kinetics of CP1 growth inhibition assays indicated a minimal inhibitory concentration (MIC) of 3 µM. Bactericidal kinetics at the MIC indicated rapid killing of E.coli (<30 min). Membrane permeability studies illustrated permeation as a time‐dependent event. Maximum permeability at the MIC occurred within 30 min, which correlates to the bactericidal action. Further investigation showed that the immediate permeabilizing action of CP1 is concentration‐dependent, which correlates to the concentration‐dependent nature of the inhibition assays. At the MIC and above, the immediate permeability was significant enough that the cells could not recover and exhibit growth. Below the MIC, immediate permeability was evident, but the level was insufficient to inhibit growth. Dansyl polymyxin B displacement studies showed LPS binding is essentially the same at all concentrations investigated. However, it does appear that only the immediate interaction is important, because binding continued to increase over time beyond cell viability. Our studies correlated CP1 bactericidal kinetics to membrane permeability suggesting CP1 concentration‐dependent killing is driven by the extent of the immediate permeabilizing action of the peptide. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.