Miracle-dz/UniFAR-FTUs huggingface dataset:
Immune responses during spontaneous control of HIV and AIDS: what is the hope for a cure?

HIV research has made rapid progress and led to remarkable achievements in recent decades, the most important of which are combination antiretroviral therapies (cART). However, in the absence of a vaccine, the pandemic continues, and additional strategies are needed. The ‘towards an HIV cure’ initiative aims to eradicate HIV or at least bring about a lasting remission of infection during which the host can control viral replication in the absence of cART. Cases of spontaneous and treatment-induced control of infection offer substantial hope. Here, we describe the scientific knowledge that is lacking, and the priorities that have been established for research into a cure. We discuss in detail the immunological lessons that can be learned by studying natural human and animal models of protection and spontaneous control of viraemia or of disease progression. In particular, we describe the insights we have gained into the immune mechanisms of virus control, the impact of early virus–host interactions and why chronic inflammation, a hallmark of HIV infection, is an obstacle to a cure. Finally, we enumerate current interventions aimed towards improving the host immune response.
Are laboratory-based antibiograms reliable to guide the selection of empirical antimicrobial treatment in patients with hospital-acquired infections?

OBJECTIVES Antibiograms are often taken into account to define a rational selection of an empirical antimicrobial therapy for treating patients with hospital-acquired infections. In this study, we performed a paired comparison between the antibiogram constructed with laboratory-based data and that formed with data subjected to prior clinical validation. METHODS Between 2003 and 2005, the laboratory of microbiology printed in duplicate every individual susceptibility report corresponding to hospitalized patients and the copy was sent to the department of infection control. Every individual report was assessed in real time at the bedside of the patient by a multidisciplinary team for clinical significance and appropriateness of the specimen, as well as for the type, source and origin of the infection. Cumulative resistance rates were estimated in parallel at the laboratory with the whole data, and at the infection control department with data subjected to prior clinical validation. These rates were designated as 'laboratory-based' and 'clinically based', respectively. RESULTS A total of 2305 individual susceptibility reports were assessed. Only 1429 (62.0%) were considered as clinically significant by the multidisciplinary team. Escherichia coli, Enterobacter cloacae, Citrobacter freundii group, Klebsiella species and Proteus mirabilis resistant to broad-spectrum cephalosporins, as well as methicillin-resistant Staphylococcus aureus, were significantly more frequent in the clinically based rates (P < or = 0.03). CONCLUSIONS Laboratory-based data underestimate the frequency of several major resistant organisms in patients with hospital-acquired infection. Previous clinical validation of the individual susceptibility reports seems to be a suitable strategy to get more reliable data.
International Conference on Pattern Recognition and Information Processing  International Associations for Pattern Recognition

Proceedings contain papers accepted for publication and presentation at the Tenth International Conference " Pattern Recognition and Information Processing " that will be held in May 19-21, Minsk, Belarus. Proceedings are prepared for publication by PRIP'2009 Program Committee and Belarusian Association for Image Analysis and Recognition. Proceedings will be useful for students and researchers working in the following areas: pattern recognition and image analysis; knowledge processing and representation; knowledge based decision support system, fuzzy mathematics and systems, applications of pattern recognition and image analysis. Papers are approved by Program Committee and are printed as submitted by authors. " 19-21 2009 PRIP'200.
The reaming of life: based on the 2010 Jim Gray eScience Award Lecture

We are well into the era of data intensive‐digital scientific discovery, an era defined by Jim Gray as the Fourth Paradigm. From my own perspective of the life sciences, much has been accomplished, but there is much to do if we are to maximize our understanding of biological systems given the data we have today, let alone what is coming. In my 2010 Jim Gray eScience Award Lecture, I gave my own thoughts on what needs to be accomplished, and with an additional year of hindsight, I expand on that here. Copyright © 2012 John Wiley & Sons, Ltd.
Distribution of glycine‐immunoreactive profiles in the monkey spinal cord: A light microscopic and ultrastructural study

The present study analyzed the relationships of glycine (GLY)‐immunoreactive (‐IR) and unlabeled profiles in the primate spinal cord. Light microscopic analysis demonstrated GLY‐IR profiles in laminae III‐VII, with fewer labeled profiles in laminae I, II, VIII, IX and X. The dorsal part of the lateral funiculus and the dorsal funiculus contained few labeled axons, in contrast to all other areas of white matter, which were heavily labeled. At the electron microscopic level, GLY‐IR terminals in monkeys contained mainly round, with occasional pleomorphic, clear vesicles; however, F‐type GLY‐IR terminals synapsing on motoneurons contained pleomorphic vesicles. This seems to be an important species difference because vesicles in GLY‐IR terminals in rat and cat are predominantly oval or elliptical.
Vibrational Spectrum of Gum Agar in Pure and D 2 O Exchange state by FTIR Analysis

Gum Agar is an important biomaterial consists of a mixture of agarose and agaropectin. Agarose is a linear polymer. In this work Fourier transformed infrared (FTIR) absorption and Attenuated total reflectance (ATR) spectrum of Gum Agar samples at different polymerized state with H2O and D2O are analyzed and compared. The changes in characteristics bond vibration due to environmental variation are detected clearly. The obtained shift of the characteristics frequencies and absence of some peaks are caused due to change in molecular structure in the types of specimens.
Biosynthetic growth hormone changes the collagen and elastin contents and biomechanical properties of the rat aorta.

The biomechanical and biochemical properties of aortas from female rats treated with biosynthetic human GH (b-hGH) for 80 days were investigated. b-hGH was administered at a dose of 5 mg.kg-1.d-1. Treatment with b-hGH increased the body weight by 75% and the diameter of the aorta by 14% compared with the control group. The concentration of collagen and the relative amount of collagen type I were increased, and the concentration of elastin was decreased. Aortas from the b-hGH-treated group showed increased extensibility in the regions corresponding to physiological load values (i.e. 100-200 mmHg), and increased stiffness in regions with higher load values. The increased extensibility at low load values corresponds well with the loss of elastin, and the increased stiffness at higher load values with the increase of collagen and relative increase of collagen type I. These alterations induced by the growth hormone treatment might influence the elasticity and recoiling properties of the aorta.
Prevalence of Mild Cognitive Impairment and Its Subtypes in the Mexican Population

Background/Aim: To estimate the prevalence of mild cognitive impairment (MCI) and its subtypes, taking into account education and health status. Methods: This is the first report of our Study on Aging and Dementia in Mexico. This study included 2,944 elderly individuals 60 years old or more with in-home assessment for cognitive impairment. The prevalence of MCI was based on Petersen criteria. MCI was classified as amnestic of single domain (a-MCI-s) or multiple domain (a-MCI-md) or nonamnestic of single domain (na-MCI-s) or multiple domain (na-MCI-md). In addition to a battery of neuropsychological measures, a self-report depression measure and a medical history including history of stroke, heart disease and other health conditions were recorded. Results: The global estimated prevalence of MCI in the Mexican population was 6.45%. Of these subjects, 2.41% met criteria for a-MCI-s, 2.56% for a-MCI-md, 1.18% for na-MCI-s and 0.30% for na-MCl-md. Women showed a higher prevalence of MCI than men (63.7 vs. 36.3%, respectively). The analysis showed that heart disease [odds ratio (OR) 1.5], stroke (OR 1.2) and depression (OR 2.1) were associated with an increased risk of MCI. Conclusions: The prevalence of MCI in Mexico is similar to that in other countries. The results suggest that stroke, heart disease and depression may have an important role in the etiology of MCI.
Time-Resolved Measurement of State-Specific P2X2 Ion Channel Cytosolic Gating Motions

ATP-gated P2X2 channels undergo permeability changes through a process that is incompletely understood. In the present study, we used fluorescence resonance energy transfer (FRET) and electrophysiology to measure cytosolic gating motions in P2X2 channels as they enter a state with increased permeability. P2X2 channels underwent permeability changes with a time course that was similar to decreases in FRET between cyan fluorescent protein and yellow fluorescent protein attached to the cytosolic domain of P2X2 channels. Wild-type and mutant channels that did not undergo permeability changes also did not show evidence of cytosolic gating motions. Moreover, immobilizing the cytosolic domain by tethering it to the plasma membrane prevented the switch in permeability and impaired the cytosolic gating motions. Both of these phenotypes were restored when the immobilizing tether was cleaved. The data provide a time-resolved measure of state-specific gating motions and suggest how a cytosolic domain may control ion channel permeability.
Mobile Middleware

Basic Concepts 146 Distributed Systems 146 The Middleware Layer 148 Middleware Requirements for Fixed Distributed Systems 150 How Mobility Affects Middleware Design 151 Mobile Middleware Requirements 152 Context Management 155 Connection Management 157 Resource Management 158 Middleware for Nomadic Systems 159 Middleware for Ad Hoc Systems 161 Available Technologies for Mobile Middleware 162 Mobile Agent Technology 162 Grid Computing Paradigm 163 References 164 AU3833_C07. fm Page 145 Monday, August 14, 2006 3:17 PM
Monitoring Drug-Induced γH2AX as a Pharmacodynamic Biomarker in Individual Circulating Tumor Cells

Purpose: Circulating tumor cells (CTC) in peripheral blood of patients potentially represent a fraction of solid tumor cells available for more frequent pharmacodynamic assessment of drug action than is possible using tumor biopsy. However, currently available CTC assays are limited to cell membrane antigens. Here, we describe an assay that directly examines changes in levels of the nuclear DNA damage marker γH2AX in individual CTCs of patients treated with chemotherapeutic agents. Experimental Design: An Alexa Fluor 488–conjugated monoclonal γH2AX antibody and epithelial cancer cell lines treated with topotecan and spiked into whole blood were used to measure DNA damage–dependent nuclear γH2AX signals in individual CTCs. Time-course changes in both CTC number and γH2AX levels in CTCs were also evaluated in blood samples from patients undergoing treatment. Results: The percentage of γH2AX-positive CTCs increased in a concentration-dependent manner in cells treated with therapeutically relevant concentrations of topotecan ex vivo. In samples from five patients, percent γH2AX-positive cells increased post-treatment from a mean of 2% at baseline (range, 0-6%) to a mean of 38% (range, 22-64%) after a single day of drug administration; this increase was irrespective of increases or decreases in the total CTC count. Conclusions: These data show promise for monitoring dynamic changes in nuclear biomarkers in CTCs (in addition to CTC count) for rapidly assessing drug activity in clinical trials of molecularly targeted anticancer therapeutics as well as for translational research. Clin Cancer Res; 16(3); 1073–84
Motif detection in Arabidopsis: Correlation with gene expression data

The genes having similar expression profiles are considered to have common regulatory mechanisms and are controlled by the binding of transcription factors to the regulatory elements present in their upstream regions. The detection of cis-regulatory elements can help in further understanding of co-expression of genes. This paper deals with the detection of motifs in the upstream regions of genes involved in diurnal rhythms of Arabidopsis and also deals with the correlation of expression data with sequence information. We detected motifs in the upstream regions of genes involved in diurnal cycles and checked for their presence in circadian regulated, dark induced and in light induced genes of Arabidopsis. Ten motifs were reported in this study, out of which five were already reported in available transcription factor databases as the elements involved in light responsiveness. Significance study of ten motifs was done by taking random sets of same data size. One of the ten motifs namely GGCCCA, which was found without any base variations in 62 genes, was further studied by analyzing the expression profiles of its respective genes within the set of diurnal regulated genes using SOM clustering method. It was found that the genes were clustered together into two major groups, out of which one group had glycine rich proteins and the second group had genes belonging to dehydrogenase and oxidoreductase family.
Suppression of Endothelial Nitric Oxide Production After Withdrawal of Statin Treatment Is Mediated by Negative Feedback Regulation of Rho GTPase Gene Transcription

Background—Statins improve endothelial function by upregulating endothelial nitric oxide (NO) production that is mediated by inhibiting the isoprenylation of rho GTPase. Withdrawal of statin treatment could suppress endothelial NO production and may impair vascular function. Methods and Results—To test this hypothesis, mice were treated for 14 days with 10 mg/kg atorvastatin per day; this led to the upregulation of endothelial NO synthase expression and activity by 2.3- and 3-fold, respectively. Withdrawal of statins resulted in a dramatic, 90% decrease of NO production after 2 days. In mouse aortas and cultured endothelial cells, statins upregulated the expression of rho GTPase in the cytosol, but statins blocked isoprenoid-dependent rho membrane translocation and GTP-binding activity. Inhibiting the downstream targets of rho showed that rho expression is controlled by a negative feedback mechanism mediated by the actin cytoskeleton. Measuring rho mRNA half-life and nuclear run-on assays demonstrated that statins or disruption of actin stress fibers increased rho gene transcription but not rho mRNA stability. Therefore, treatment with statins leads to the accumulation of nonisoprenylated rho in the cytosol. Withdrawing statin treatment restored the availability of isoprenoids and resulted in a massive membrane translocation and activation of rho, causing downregulation of endothelial NO production. Conclusions—Withdrawal of statin therapy in normocholesterolemic mice results in a transient increase of rho activity, causing a suppression of endothelial NO production. The underlying molecular mechanism is a negative feedback regulation of rho gene transcription mediated by the actin cytoskeleton.
Discriminant substrokes for online handwriting recognition

A discriminant-based framework for automatic recognition of online handwriting data is presented in this paper. We identify the substrokes that are more useful in discriminating between two online strokes. A similarity/dissimilarity score is computed based on the discriminatory potential of various parts of the stroke for the classification task. The discriminatory potential is then converted to the relative importance of the substroke. Experimental verification on online data such as numerals, characters supports our claims. We achieve an average reduction of 41% in the classification error rate on many test sets of similar character pairs.
Mortality from desiccation contributes to a genotype–temperature interaction for cold survival in Drosophila melanogaster

SUMMARY Survival at cold temperatures is a complex trait, primarily because of the fact that the physiological cause of injury may differ across degrees of cold exposure experienced within the lifetime of an ectothermic individual. In order to better understand how chill-sensitive insects experience and adapt to low temperatures, we investigated the physiological basis for cold survival across a range of temperature exposures from −4 to 6°C in five genetic lines of the fruit fly Drosophila melanogaster. Genetic effects on cold survival were temperature dependent and resulted in a significant genotype–temperature interaction for survival across cold temperature exposures that differ by as little as 2°C. We investigated desiccation as a potential mechanism of injury across these temperature exposures. Flies were dehydrated following exposures near 6°C, whereas flies were not dehydrated following exposures near −4°C. Furthermore, decreasing humidity during cold exposure decreased survival, and increasing humidity during cold exposure increased survival at 6°C, but not at −4°C. These results support the conclusion that in D. melanogaster there are multiple physiological mechanisms of cold-induced mortality across relatively small differences in temperature, and that desiccation contributes to mortality for exposures near 6°C but not for subzero temperatures. Because D. melanogaster has recently expanded its range from tropical to temperate latitudes, the complex physiologies underlying cold tolerance are likely to be important traits in the recent evolutionary history of this fruit fly.
Bijective census and random generation of Eulerian planar maps with prescribed vertex degrees

We give a bijection between Eulerian planar maps with prescribed vertex degrees, and some plane trees that we call balanced Eulerian trees. To enumerate the latter, we introduce conjugation classes of planted plane trees. In particular the result answers a question of Bender and Caneld in [BC94] and allows uniform random generation of Eulerian planar maps with restricted vertex degrees. Using a well known correspondence between 4-regular planar maps with n vertices and planar maps with n edges we obtain an algorithm to generate uniformly such maps with complexity O(n). Our bijection is also rened to give a combinatorial interpretation of a parameterization of Arques ([Arq87]) of the generating function of planar maps with respect to vertices and faces.
The Blood-Retinal Barrier in the Management of Retinal Disease: EURETINA Award Lecture

Retinal diseases are the main causes of blindness in the Western world. Diabetic retinopathy and age-related macular degeneration continue to increase in prevalence and as main causes of vision loss. Intravitreal anti-VEGF and steroid injections have raised new expectations for their successful treatment. These agents act by stabilizing the blood-retinal barrier (BRB). Our group defined the BRB by identifying for the first time the tight junctions that unite retinal endothelial cells and are the basis for the inner BRB, an observation later confirmed in retinal pigment epithelial cells and in brain vessels. A major role of active transport processes was also identified. Today, the BRB is understood to play a fundamental role in retinal function in both health and disease. Retinal edema, an ubiquitous manifestation of retinal disease, is directly associated with breakdown of the BRB and with vision loss. In its most common form (i.e., vasogenic edema), due to breakdown of the BRB, Starling's law of capillary filtration may be used to interpret the mechanisms of fluid accumulation in the retina. The main factors involved in the development of retinal edema are BRB permeability, capillary hydrostatic pressure, tissue hydrostatic pressure, tissue osmotic pressure, and plasma osmotic pressure. In the clinical environment, breakdown of the BRB has been identified by fluorescein angiography and vitreous fluorometry, requiring the intravenous administration of fluorescein. An OCT-based method, OCT-Leakage, recently introduced by our group is capable of noninvasively identifying and quantifying sites of alteration of the BRB by mapping areas of lower-than-normal optical reflectivity, thus reflecting changes in the retinal extracellular fluid. We found good correspondence between the location of increased areas of low optical reflectivity identified by OCT-Leakage and the main sites of leakage on fluorescein angiography. Furthermore, with OCT-Leakage the areas of abnormal fluid accumulation can be identified in specific retinal layers, clearly offering more information than previously obtained with fluorescein angiography. OCT angiography has become available, replacing much of the information yielded by fluorescein angiography in a noninvasive manner. However, OCT angiography cannot visualize the leakage, i.e., the alteration of the BRB. OCT-Leakage is able to identify the locations of increases in extracellular fluid in the different layers of the retina. The complementarity of these 2 methods is of potential great interest for the diagnosis and management of several retinal diseases in which the presence and amount of fluid, as a marker of severity and activity, is paramount to treatment and management decisions in clinical practice.
Overview and taxonomy of techniques for privacy-preserving record linkage

Record linkage is the process of identifying which records in two or more databases correspond to the same real-world entity. Three major challenges of this process are (1) achieving high linkage quality, (2) scalability to linking very large databases, and (3) protecting the privacy and confidentiality of personal identifying data that are used in the linkage process. This presentation provides an overview of the various techniques that have been developed to facilitate the linking of data across organisations in such ways that no private or confidential information is being revealed. We then characterise such privacy-preserving record linkage techniques along fifteen dimensions. This provides us with a taxonomy that allows us to highlight shortcomings of current techniques and discuss future research directions.
The Who and the How of Experience

Does consciousness require a self ? 1 In what follows, I argue that it does not. I concede at the outset that this is a counterintuitive thesis. For, a central feature of conscious states is that their mode of appearance (i.e. how they are given) exhibits an irreducibly first-personal nature. My experiences are distinctly my own, given to me and only me. This first-personal ‘how’ of consciousness is what secures its phenomenal character. And it seems natural to assume that this how points back to a ‘who’: a stable, enduring, conscious subject at the receiving end of phenomenal states. But is the assumption that a how requires a who warranted? I will argue below that, just because the subjective character of consciousness gives rise to a sense of self—that is, the felt sense of being a stable who, or owner of conscious episodes—it does not follow that this who really exists in any autonomous or enduring sense. First, I do some background work, briefly discussing the phenomenological notion of the ‘minimal self ’ before then looking at a Buddhist conception of selfless subjectivity. Next, I examine the minimal self more carefully, along with what is sometimes termed the ‘narrative self ’, and argue for the experiential primacy of the former. I then argue that the phenomenal character of consciousness, which the minimal self-model is supposed to