Miracle-dz/UniFAR-FTUs huggingface dataset:
V3 Recombinants Indicate a Central Role for CCR5 as a Coreceptor in Tissue Infection by Human Immunodeficiency Virus Type 1

ABSTRACT Binding of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 to both CD4 and one of several chemokine receptors (coreceptors) permits entry of virus into target cells. Infection of tissues may establish latent viral reservoirs as well as cause direct pathologic effects that manifest as clinical disease such as HIV-associated dementia. We sought to identify the critical coreceptors recognized by HIV-1 tissue-derived strains as well as to correlate these coreceptor preferences with site of infection and dementia diagnosis. To reconstitute coreceptor use, we cloned HIV-1 envelope V3 sequences encoding the primary determinants of coreceptor specificity from 13 brain-derived and 6 colon-derived viruses into an isogenic (NL4-3) viral background. All V3 recombinants utilized the chemokine receptor CCR5 uniformly and efficiently as a coreceptor but not CXCR4, BOB/GPR15, or Bonzo/STRL33. Other receptors such as CCR3, CCR8, and US28 were inefficiently and variably used as coreceptors by various envelopes. CCR5 without CD4 present did not allow for detectable infection by any of the tested recombinants. In contrast to the pathogenic switch in coreceptor specificity frequently observed in comparisons of blood-derived viruses early after HIV-1 seroconversion and after onset of AIDS, the characteristics of these V3 recombinants suggest that CCR5 is a primary coreceptor for brain- and colon-derived viruses regardless of tissue source or diagnosis of dementia. Therefore, tissue infection may not depend significantly on viral envelope quasispeciation to broaden coreceptor range but rather selects for CCR5 use throughout disease progression.
Total cavopulmonary conversion and maze procedure for patients with failure of the Fontan operation.

OBJECTIVES Hemodynamic abnormalities and refractory atrial arrhythmias in patients late after the Fontan operation result in significant morbidity and mortality. We review our experience with conversion to total cavopulmonary artery connections and arrhythmia surgery. METHODS Between 1994 and 2001, 40 patients underwent Fontan conversion and arrhythmia surgery. Significant hemodynamic lesions such as aortic aneurysm (n = 1), atrioventricular valve insufficiency (n = 8), and pulmonary arterioplasty (n = 9) were repaired concomitantly. Thirty-four patients were in New York Heart Association class III or IV. Mean age at the original Fontan operation was 7.5 +/- 6.5 years and mean age at Fontan conversion was 18.7 +/- 9.0 years. Arrhythmia surgery has evolved from isthmus cryoablation in 10 patients to right-sided maze in 16 patients for atrial reentry tachycardia. The maze-Cox III operation was used for 14 patients with atrial fibrillation. Atrial (n = 33) and dual-chamber (n = 5) pacemakers were placed. RESULTS There has been no early mortality. Chest tubes were removed on postoperative day 9.0 +/- 6.0. Hospital stay was 11.8 +/- 6.6 days. Three patients required cardiac transplantation at 8 days, 9 months, and 33 months postoperatively. There was 1 death 2 years postoperatively from acute myocardial infarction. For the entire series, arrhythmia recurrence is 12.5%, with only 10% of patients receiving long-term antiarrhythmic medications; these patients were among the first 8 patients in our series. Most patients are in New York Heart Association class I or II. Bruce protocol in 12 patients showed increased tolerance (P <.05). CONCLUSIONS Fontan conversion to total cavopulmonary connection with concomitant arrhythmia surgery is excellent therapy for patients whose Fontan repair has failed. Fontan conversion is safe, improves New York Heart Association class, improves exercise tolerance, and has a low incidence of recurrent arrhythmias.
Imatinib mesylate for the treatment of gastrointestinal stromal tumours: best monitored with FDG PET

BackgroundThe new anti-cancer drug imatinib mesylate inhibits the tyrosine kinase growth factor receptor, c-KIT, and has shown spectacular activity in patients with gastrointestinal stromal tumours (GISTs). ObjectiveTo assess whether fluorodeoxyglucose positron emission tomography (FDG PET) is suitable for response evaluation of this new type of tumour treatment. MethodsSixteen consecutive patients with irresectable or metastasized GIST or another c-KIT (CD117) positive mesenchymal tumour underwent FDG PET before and 1 week after the start of treatment with imatinib mesylate (Glivec®). Visual findings and standard uptake values (SUVs) were compared with the overall response to treatment, based on clinical and radiological response. ResultsPET visualized all known and some unknown tumour locations. The separation by PET after 1 week of treatment in ‘PET responders’ (11/16 patients, mean SUV reduction 65%) versus ‘PET non-responders’ (5/16 patients, mean SUV increase 16%) appeared to match almost perfectly with overall treatment response and proved correct in 14/15 patients (prediction sensitivity 93%). FDG uptake changes after 1 week of treatment were of greater magnitude than tumour volume changes on computed tomography at 8 weeks. Progression-free survival was significantly better in patients with a PET response (P=0.002). PET response predicted treatment outcome better than the radiological response. Finally, PET was helpful during follow-up, in discriminating side effects from tumour progression. ConclusionFDG PET is a valuable tool in patients with gastrointestinal stromal tumours treated with imatinib mesylate. It improves staging, accurately separates responders from non-responders in an early phase, and is helpful during follow-up.
Incontinence in the frail elderly: Report from the 4th international consultation on incontinence

To summarize current knowledge on the etiology, assessment, and management of urinary incontinence (UI) in frail older persons. “Frail” here indicates a person with a clinical phenotype combining impaired physical activity, mobility, muscle strength, cognition, nutrition, and endurance, associated with being homebound or in care institutions and a high risk of intercurrent disease, disability, and death.
Moral distress experienced by nurses

Nurses are frequently confronted with ethical dilemmas in their nursing practice. As a consequence, nurses report experiencing moral distress. The aim of this review was to synthesize the available quantitative evidence in the literature on moral distress experienced by nurses. We appraised 19 articles published between January 1984 and December 2011. This review revealed that many nurses experience moral distress associated with difficult care situations and feel burnout, which can have an impact on their professional position. Further research is required to examine worksite strategies to support nurses in these situations and to develop coping strategies for dealing with moral distress.
Analysis of gamma rhythms in the rat hippocampus in vitro and in vivo.

1. We have shown previously, with experimental and computer models, how a ‘40 Hz’ (gamma) oscillation can arise in networks of hippocampal interneurones, involving mutual GABAA‐mediated synaptic inhibition and a source of tonic excitatory input. Here, we explore implications of this model for some hippocampal network phenomena in the rat in vitro and in vivo. 2. A model network was constructed of 1024 CA3 pyramidal cells and 256 interneurones. AMPA (alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid), NMDA (N‐methyl‐D‐aspartate), GABAA and GABAB receptors were simulated on pyramidal cells and on interneurones. 3. In both model and experiment, the frequency of network oscillations, in the gamma range, depended upon three parameters: GABAA conductance and decay time constant in interneurone‐‐>interneurone connections, and the driving current to the interneurones. 4. The model of gamma rhythm predicts an average zero phase lag between firing of pyramidal cells and interneurones, as observed in the rat hippocampus in vivo. The model also reproduces a gamma rhythm whose frequency changes with time, at theta frequency (about 5 Hz). This occurs when there is 5 Hz modulation of a tonic signal to chandelier and basket cells. 5. Synchronized bursts can be produced in the model by several means, including partial blockade of GABAA receptors or of AMPA receptors on interneurones, or by augmenting AMPA‐mediated EPSCs. In all of these cases, the burst can be followed by a ‘tail’ of transiently occurring gamma waves, a phenomenon observed in the hippocampus in vivo following sharp waves. This tail occurs in the model because of delayed excitation of the interneurones by the synchronized burst. A tail of gamma activity was found after synchronized epileptiform bursts both in the hippocampal slice (CA3 region) and in vivo. 6. Our data suggest that gamma‐frequency EEG activity arises in the hippocampus when pools of interneurones receive a tonic or slowly varying excitation. The frequency of the oscillation depends upon the strength of this excitation and on the parameters regulating the inhibitory coupling between the interneurones. The interneurone network output is then imposed upon pyramidal neurones in the form of rhythmic synchronized IPSPs.
Cross-linguistic variation in temporal adjunct clauses

A particular meaning can be realized by morphosyntactically distinct expressions across languages. One of the challenges for cross-linguistic research is to account for convergence in meaning in light of morphosyntactic variation. This paper examines cross-linguistic variation in the distribution and interpretation of tense in temporal adjunct clauses (TACs, e.g. English John crossed the street before/after he fell) in English, Japanese and Russian. The cross-linguistic variation exhibited by these three languages with respect to TACs has received analyses that rely on syntax to varying degrees (Ogihara 1994, Ogihara 1996, Arregui and Kusumoto 1998). After introducing the pattern in section 2, we develop a semantic analysis in section 3 that accounts for the variation solely on the basis of the meanings of the tenses and the temporal connectives realized in these constructions. A comparison of our analysis to the previous ones in section 4 identifies both empirical and theoretical advantages. Section 5 concludes the paper.
Trunk Posture and Trapezius Muscle Load While Working in Standing, Supportedstanding, and Sitting Positions

A study of standing, supported-standing (“riding” on a rounded seat), and sitting postures was carried out on persons simulating assembly work in places with poor leg space. These postures and the upper trapezius muscle load were examined using statometric and electromyographic methods, respectively. While supported-standing or sitting, the lumbar spine moved toward kyphosis, even where there was no backward rotation of the pelvis. In adopting the position for anteriorly placed work, the upper arms were raised 30° forward or more; then, if a greater reach was necessary, the trunk was flexed as well. It is concluded that if leg space is poor, variation between supported-standing and standing should be encouraged, and an ordinary office chair avoided. Working level should be arranged so that it is lower than 5 cm above elbow level if no arm/wrist support is possible.
AKT and PAX3-FKHR cooperation enforces myogenic differentiation blockade in alveolar rhabdomyosarcoma cell

The chimeric PAX3-FKHR transcription factor is present in a majority of alveolar rhabdomyosarcoma (ARMS), an aggressive skeletal muscle cancer of childhood. PAX3-FKHR-mediated aberrant myogenic gene expression resulting in escape from terminal differentiation program is believed to contribute in ARMS development. In skeletal muscle differentiation, activation of AKT pathway leads to myogenic gene activation and terminal differentiation. Here, we report that AKT acts, in part, by modulating PAX3-FKHR transcriptional activity via phosphorylation in the maintenance of the myogenic differentiation blockade in established mouse models of ARMS cells. We observed that low levels of AKT activity are associated with elevated levels of PAX3-FKHR transcriptional activity, and AKT hyperactivation results in PAX3-FKHR phosphorylation coupled with decreased activity once cells are under differentiation-permissible conditions. Subsequent data shows that attenuated AKT activity-associated PAX3-FKHR activity is required to suppress the function of MyoD, a key myogenic regulator of muscle differentiation. Conversely, decreased PAX3-FKHR activity results in the eradication of MyoD expression and subsequent suppression of the myogenic differentiation. Thus, AKT regulation of the PAX3- FKHR suppresses myogenic gene expression in ARMS cells, causing a failure in differentiation. Evidence is presented that provides a novel molecular link between AKT and PAX3-FKHR in maintaining myogenic differentiation blockade in ARMS.
Stent retriever technology: concept, application and initial results

Stent retrievers are increasingly used for flow restoration and thrombectomy in acute embolic stroke. First clinical results support the potential of these new devices, in particular the ability to rapidly restore flow and effectively retrieve clots from large intracranial arteries, with favorable clinical results in preliminary patient series. This article reviews the concept and technical aspects of this new technique of endovascular stroke treatment and summarizes the first clinical results.
Strategies for Doped Nanocrystalline Silicon Integration in Silicon Heterojunction Solar Cells

Carrier collection in silicon heterojunction (SHJ) solar cells is usually achieved by doped amorphous silicon layers of a few nanometers, deposited at opposite sides of the crystalline silicon wafer. These layers are often defect-rich, resulting in modest doping efficiencies, parasitic optical absorption when applied at the front of solar cells, and high contact resistivities with the adjacent transparent electrodes. Their substitution by equally thin doped nanocrystalline silicon layers has often been argued to resolve these drawbacks. However, low-temperature deposition of highly crystalline doped layers of such thickness on amorphous surfaces demands sophisticated deposition engineering. In this paper, we review and discuss different strategies to facilitate the nucleation of nanocrystalline silicon layers and assess their compatibility with SHJ solar cell fabrication. We also implement the obtained layers into devices, yielding solar cells with fill factor values of over 79% and efficiencies of over 21.1%, clearly underlining the promise this material holds for SHJ solar cell applications.
“It Happens to Girls All the Time”: Examining Sexual Assault Survivors’ Reasons for Not Using Campus Supports

Sexual assault is a prevalent problem in higher education, and despite the increasing availability of formal supports on college campuses, few sexual assault survivors use them. Experiencing sexual assault can have devastating consequences on survivors' psychological and educational wellbeing, which may intensify if survivors do not receive adequate care. Drawing from existing theoretical frameworks and empirical research, this study used a mixed methodological approach to examine why survivors did not use three key campus supports-the Title IX Office, the sexual assault center, and housing staff-and if these reasons differed across the three supports. Using data from 284 women who experienced sexual assault in college, our qualitative findings identified four overarching themes, including logistical issues (e.g., lacking time and knowledge), feelings, beliefs, and responses that made it seem unacceptable to use campus supports, judgments about the appropriateness of the support, and alternative methods of coping. Quantitative findings revealed that survivors' reasons for not seeking help differed across supports. Collectively, our findings suggest that community norms and institutional policies can make it challenging for survivors to use campus supports. We propose several suggestions for institutional change (e.g., taking a stronger stance against "less serious" forms of sexual assault, reducing a quasi-criminal justice approach to investigation and adjudication, limiting mandated reporting).
On the Two-Phase Structure of Protogalactic Clouds

In the gaseous envelope of protogalaxies, thermal instability leads to the formation of a population of cool fragments that are confined by the pressure of a residual hot background medium. In order to remain in a quasi-hydrostatic equilibrium, the residual gas evolves at approximately the virial temperature of the dark matter halo. Its density is determined by the requirements of thermal equilibrium. The hot gas is heated by compression and shock dissipation. The heating is balanced by direct energy loss due to bremsstrahlung emission and by conductive losses into the cool clouds, which are efficient radiators. The cool fragments are photoionized and heated by the extragalactic UV background and nearby massive stars. Several processes interact to determine the size distribution of the cool fragments. The smallest are evaporated due to conductive heat transfer from the hot gas. All fragments are subject to disruption due to hydrodynamic instabilities. The fragments also gain mass as a result of collisions and mergers and of condensation from the hot gas due to conduction. The size distribution of the fragments in turn determines the rate and efficiency of star formation during the early phase of galactic evolution. We have performed one-dimensional hydrodynamic simulations of the evolution of the hot and cool gas. The cool clouds are assumed to follow a power-law size distribution, and fall into the galactic potential, subject to drag from the hot gas. The relative amounts of the hot and cool gas are determined by the processes discussed above, and star formation occurs at a rate sufficient to maintain the cool clouds at 104 K. We present density distributions for the two phases and also for the stars for several cases, parameterized by the circular speeds of the potentials. Under some conditions, primarily low densities of the hot gas, conduction is more efficient than radiative processes at cooling the hot gas, limiting the X-ray radiation from the halo gas.
The Emerging Use of TNF-α Inhibitors in Orbital Inflammatory Disease

Orbital inflammatory diseases, such as thyroid-associated orbitopathy (TAO) and idiopathic orbital inflammation (IOI), are frequently encountered by comprehensive ophthalmologists and are among the most common disorders seen by orbital surgeons. Although corticosteroids remain the mainstay of medical therapy for these diseases, the relatively high rate of treatment failures and the myriad of side effects from chronic use of these drugs have motivated the search to find other treatments to control symptoms of inflammation. A new class of medications that inhibits the effects of tumor necrosis factor a (TNF-a), a proinflammatory cytokine, has shown considerable efficacy in treating a diverse group of autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Although the use of these medications in orbital inflammatory disease is still limited, there is considerable optimism from early studies that these drugs might become important additions to current therapeutic options. This paper seeks to review the mechanism of action, pharmacology and side-effect profile of these drugs and to evaluate early use of these medications in the treatment of orbital inflammatory disease. Studies evaluating TNF-a inhibitors in ocular inflammatory diseases such as uveitis and scleritis are also reviewed. It is our hope that this paper will be useful to ophthalmologists and orbital surgeons considering treating patients with these medications.
Microsatellite Typing as a New Tool for Identification of Saccharomyces cerevisiae Strains

ABSTRACT Since Saccharomyces cerevisiae appears to be an emerging pathogen, there is a need for a valuable molecular marker able to distinguish among strains. In this work, we investigated the potential value of microsatellite length polymorphism with a panel of 91 isolates, including 41 clinical isolates, 14 laboratory strains, and 28 strains with industrial relevance. Testing seven polymorphic regions (five trinucleotide repeats and two dinucleotide repeats) in a subgroup of 58 unrelated strains identified a total of 69 alleles (6 to 13 per locus) giving 52 different patterns with a discriminatory power of 99.03%. We found a cluster of clinical isolates sharing their genotype with a bakery strain, suggesting a digestive colonization following ingestion of this strain with diet. With the exception of this cluster of isolates and isolates collected from the same patient or from patients treated with Saccharomyces boulardii, all clinical isolates gave different and unique patterns. The genotypes are stable, and the method is reproducible. The possibility to make the method portable is of great interest for further studies using this technique. This work shows the possibility to readily identify S. boulardii (a strain increasingly isolated from invasive infections) using a unique and specific microsatellite allele.
A General Condition for Monge Solutions in the Multi-Marginal Optimal Transport Problem

We develop a general condition on the cost function which is sufficient to imply a Monge solution and uniqueness results in the multi-marginal optimal transport problem. This result unifies and generalizes several results in the rather fragmented literature on multi-marginal problems. We also provide a systematic way to generate new examples from existing ones.
Antimicrobial activity of the red palm weevil Rhynchophorus ferrugineus

The red palm weevil, Rhynchophorus ferrugineus (Olivier) (Coleoptera Dryophthoridae), is an important pest of palms. Knowl- edge of both its natural enemies and its defensive mechanisms against predators and microorganisms is important to develop methods for an integrated pest control. Antimicrobial activity of the cuticular surface of adults and larvae, as well as of eggs, of this invasive species was investigated. This activity was tested against the Gram-positive bacteria Bacillus subtilis (Ehrenberg) Cohn and Bacillus thuringiensis Berliner, the Gram-negative bacterium Escherichia coli Escherich, and the entomopathogenic fungi Beauveria bassiana (Balsamo) Vuillemin and Metarhizium anisopliae (Metchnikoff) Sorokin. A similar analysis was con- ducted with the hemolymph of R. ferrugineus' larvae infected by Pseudomonas aeruginosa (Schroter) Migula, E. coli and Staphy- lococcus aureus Rosenbach. Polar surface fraction of extracts from adults and large larvae inhibits Gram-positive bacteria and the B. bassiana's growth, but not the growth of E. coli and M. anisopliae. Similarly, the hemolymph of larvae and the surface extracts of both small larvae and eggs seemed not to show any inhibition. Chemical analyses of the fraction exhibiting antimicrobial activ- ity show the presence of some polar compounds ranging between 1000 and 1500 Dalton. This study improves our knowledge on the biology of R. ferrugineus and helps to suggest strategies for the biocontrol of this pest.