gebhart/patrepeval huggingface dataset:
Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study (2013)

Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs]) whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs); instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.
Systematic Approach to Develop a Colloidal Silica Based Gel System for Water Shut-Off (2017)

Abstract Undesirable water production can significantly affect the economic life of producing wells. Excess water production results in loss of productivity, corrosion, and scaling. Also, the need for water handling facilities and reinjection of unwanted water can further add to the total cost of the project, which consequently increases the cost of production. In offshore operations, produced water can have an adverse impact on the environment. The use of a colloidal silica based fluid system was developed for water shutoff application. A systematic experimental study was conducted to evaluate the effect of key parameters on the gelation properties of this system; that is: particle size, pH, temperature, and silica concentration. Also, the effect of different salts, as an activator agent, were tested to initiate in-situ gelation of colloidal silica. The performance of this system was evaluated by conducting static gelation tests as well as high pressure and high temperature viscosity measurements up to 150°C. Colloidal silica solutions exhibit low viscosity. Proper selection of suitable activators can lead to in-situ gelation and formation of a high viscous gel to block the pore space. The permanent sealing of formation porosity can be achieved by building the viscosity of colloidal silica. The colloidal silica gelation time can be tailored by varying the activator type and concentration to match the field operation requirements. Kinetics of colloidal silica gelation at elevated temperatures showed quicker viscosity buildup. The gelation time can be varied by controlling the initial pH of the system. A stable system and good dispersion was achieved for the colloidal silica solution without using an activator, as confirmed from the Zeta potential results. Increasing the salt concentration and temperature or lowering the pH of the system results in unstable system that triggers the gelation process. The existence of more than one of the above factors (i.e., salt, temperature, and lower pH) results in further reduction in gelation time. Colloidal silica has a low viscosity and can penetrate deeper into the formation matrix before transforming into a gel. The fluid system presented in this paper was developed to address the needs of water shutoff applications. The environmentally friendly system is comprised of two components; colloidal silica and an activator.
T-tubule disorganization and defective excitation-contraction coupling in muscle fibers lacking myotubularin lipid phosphatase (2009)

Skeletal muscle contraction is triggered by the excitation-contraction (E-C) coupling machinery residing at the triad, a membrane structure formed by the juxtaposition of T-tubules and sarcoplasmic reticulum (SR) cisternae. The formation and maintenance of this structure is key for muscle function but is not well characterized. We have investigated the mechanisms leading to X-linked myotubular myopathy (XLMTM), a severe congenital disorder due to loss of function mutations in the MTM1 gene, encoding myotubularin, a phosphoinositide phosphatase thought to have a role in plasma membrane homeostasis and endocytosis. Using a mouse model of the disease, we report that Mtm1-deficient muscle fibers have a decreased number of triads and abnormal longitudinally oriented T-tubules. In addition, SR Ca(2+) release elicited by voltage-clamp depolarizations is strongly depressed in myotubularin-deficient muscle fibers, with myoplasmic Ca(2+) removal and SR Ca(2+) content essentially unaffected. At the molecular level, Mtm1-deficient myofibers exhibit a 3-fold reduction in type 1 ryanodine receptor (RyR1) protein level. These data reveal a critical role of myotubularin in the proper organization and function of the E-C coupling machinery and strongly suggest that defective RyR1-mediated SR Ca(2+) release is responsible for the failure of muscle function in myotubular myopathy.
Recombinant HDL-Like Nanoparticles:  A Specific Contrast Agent for MRI of Atherosclerotic Plaques (2004)

A new contrast agent for MRI based on recombinant HDL-like nanoparticles has been prepared. It shows a great potential as a contrast agent for atherosclerotic plaques in a relative short time (24 h post-injection) as it is selective for the plaques and is an endogenous molecule. It also can distinguish between different types of plaques as the enhancement obtained is different, depending on plaque composition.
Solid-Phase Synthesis of Piperazinones via Disrupted Ugi Condensation (2014)

The first application of aziridine aldehyde dimers in solid-phase synthesis is reported. The solid-supported disrupted Ugi condensation between an aziridine aldehyde dimer, isonitrile, and backbone-anchored amino acids delivered N-acyl aziridine intermediates, which were reacted with nucleophiles to yield the corresponding piperazinones. Subsequent cleavage from the resin provided a diverse set of 2,3,6-trisubstituted piperazinones starting from various amino acids, aziridine aldehydes, and nucleophiles.
Marrow stimulating technique to augment meniscus repair (2003)

Several techniques exist to increase the rate of healing of meniscal tears after repair. We describe a simple arthroscopic technique of microfracture to the intercondylar notch. This technique can provide marrow elements to the site of meniscus repair to aid in meniscal healing at the time of repair.
Myocardial angiogenesis induction with bone protein derived growth factors (animal experiment) (2001)

Myocardial angiogenesis induction with vascular growth factors constitutes a potential strategy for patients whose coronary artery disease is refractory to conventional treatment. The importance of angiogenesis in bone formation has led to the development of growth factors derived from bovine bone protein. Twelve pigs (mean weight, 73 +/- 3 kg) were chosen for the study. In the first group (n = 6, growth factor group) five 100 micrograms boluses of growth factors derived from bovine bone protein, diluted in Povidone 5%, were injected in the lateral wall of the left ventricle. In the second group (n = 6, control group), the same operation was performed but only the diluting agent was injected. All the animals were sacrificed after 28 days and the vascular density of the left lateral wall (expressed as the number of vascular structures per mm2) as well as the area of blood vessel profiles per myocardial area analysed were determined histologically with a computerised system. The growth factor group had a capillary density which was significantly higher than that of the control group: 12.6 +/- 0.9/mm2 vs 4.8 +/- 0.5/mm2 (p < 0.01). The same holds true for the arteriolar density: 1 +/- 0.2/mm2 vs 0.3 +/- 0.1/mm2 (p < 0.01). The surface ratios of blood vessel profiles per myocardial area were 4900 +/- 800 micron 2/mm2 and 1550 +/- 400 micron 2/mm2 (p < 0.01) respectively. In this experimental model, bovine bone protein derived growth factors induce a significant neovascularisation in healthy myocardium, and appear therefore as promising candidates for therapeutic angiogenesis.
[Circulating recipient cells contribute to graft coronary arteriosclerosis]. (2002)

Blood cells include progenitors of smooth muscle cells, which attach to the graft endothelia, differentiate into smooth muscle cells and proliferate, thus contributing to neointima formation. Our findings suggest a new therapeutic strategy that involves targeting of homing, differentiation and proliferation of putative smooth muscle progenitor cells to prevent proliferative vascular diseases.
Hypoxia-Inducible Factor Linked to Differential Kidney Cancer Risk Seen with Type 2A and Type 2B VHL Mutations (2007)

Clear cell carcinoma of the kidney is a major cause of mortality in patients with von Hippel-Lindau (VHL) disease, which is caused by germ line mutations that inactivate the VHL tumor suppressor gene. Biallelic VHL inactivation, due to mutations or hypermethylation, is also common in sporadic clear cell renal carcinomas. The VHL gene product, pVHL, is part of a ubiquitin ligase complex that targets the alpha subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF) for destruction under well-oxygenated conditions. All VHL mutations linked to classical VHL disease compromise this pVHL function although some missense mutations result in a low risk of kidney cancer (type 2A VHL disease) while others result in a high risk (type 2B VHL disease). We found that type 2A mutants were less defective than type 2B mutants when reintroduced into VHL-/- renal carcinoma cells with respect to HIF regulation. A stabilized version of HIF2alpha promoted tumor growth by VHL-/- cells engineered to produce type 2A mutants, while knock-down of HIF2alpha in cells producing type 2B mutants had the opposite effect. Therefore, quantitative differences with respect to HIF deregulation are sufficient to account for the differential risks of kidney cancer linked to VHL mutations.
AIDS: Etiology, Diagnosis, Treatment, and Prevention. (1985)

This book presents the latest information from leading authorities involved in ongoing AIDS research and developments. Featured in this new edition are chapters on the laboratory diagnosis of the HIV infection; TB and other bacterial infections; cytomegaloviruses and other infections; Kaposi's sarcoma in AIDS; neurological manifestation in the HIV infected patient; counselling of the HIV-infected individual, their families and partners; and risk exposure to the health care worker.
Effects of a sphingolipid synthesis inhibitor on membrane transport through the secretory pathway (1992)

We investigated the effects of an inhibitor of sphingolipid biosynthesis, 1-phenyl-2-(decanoyl-amino)-3-morpholino-1-propanol (PDMP), on cells in culture. Two Golgi-associated enzymes were affected by incubation of cells with PDMP. The synthesis of glucosylceramide was inhibited at low concentrations of PDMP (2.5-10 microM), and in the presence of higher concentrations (greater than or equal to 25 microM), synthesis of sphingomyelin was also reduced. Transport of vesicular stomatitis virus G protein through the Golgi complex was progressively retarded by increasing concentrations of PDMP. In the presence of 75 microM PDMP, the half-times of VSV-G protein arrival at the cis, medial, and trans Golgi and the cell surface were increased 1.5-, 2.1-, 2.4-, and 2.8-fold, respectively, compared to control values. Transport of fluorescent sphingolipids, synthesized de novo at the Golgi complex from fluorescent ceramide precursors, to the cell surface was retarded by approximately 20% in the presence of 50 microM PDMP and by approximately 50% in the presence of 100 microM PDMP. Control experiments demonstrated that PDMP had minimal effects on cell morphology and physiology (including microtubule and endoplasmic reticulum structure, mitochondrial function, and endocytosis). Although incubation of cells with relatively high concentrations of PDMP was required to see the effects on protein and sphingolipid transport, use of a fluorescent analogue of PDMP demonstrated that most cell-associated PDMP was sequestered in lysosomes, while the concentration at the Golgi complex, the site of the target synthetic enzymes, was relatively low. Taken together, these results suggest that transport of proteins and sphingolipids through the secretory pathway may be coupled to sphingolipid synthesis.
DNA methylation, vernalization, and the initiation of flowering. (1993)

Late-flowering ecotypes and mutants of Arabidopsis thaliana and the related crucifer Thlaspi arvense flower early after cold treatment (vernalization). Treatment with the DNA demethylating agent 5-azacytidine induced nonvernalized plants to flower significantly earlier than untreated controls. Cytidine at similar concentrations had no effect on time to flower. In contrast, late-flowering mutants that are insensitive to vernalization did not respond to 5-azacytidine treatment. Normal flowering time was reset in the progeny of plants induced to flower early with 5-azacytidine, paralleling the lack of inheritance of the vernalized condition. Arabidopsis plants, either cold-treated or 5-azacytidine-treated, had reduced levels of 5-methylcytosine in their DNA compared to nonvernalized plants. A Nicotiana plumbaginifolia cell line also showed a marked decrease in the level of 5-methylcytosine after treatment with either 5-azacytidine or low temperature. We suggest that DNA methylation provides a developmental control preventing early flowering in Arabidopsis and Thlaspi ecotypes. Vernalization, through its general demethylating effect, releases the block to flowering initiation. We propose that demethylation of a gene critical for flowering permits its transcription. We further suggest, on the basis of Thlaspi data, that the control affects transcription of kaurenoic acid hydroxylase, a key enzyme in the gibberellic acid biosynthetic pathway.
Molecular Characterization of Lantibiotic-synthesizing Enzyme EpiD Reveals a Function for Bacterial Dfp Proteins in Coenzyme A Biosynthesis (2000)

The lantibiotic-synthesizing flavoprotein EpiD catalyzes the oxidative decarboxylation of peptidylcysteines to peptidyl-aminoenethiols. The sequence motif responsible for flavin coenzyme binding and enzyme activity is conserved in different proteins from all kingdoms of life. Dfp proteins of eubacteria and archaebacteria and salt tolerance proteins of yeasts and plants belong to this new family of flavoproteins. The enzymatic function of all these proteins was not known, but our experiments suggested that they catalyze a similar reaction like EpiD and/or may have similar substrates and are homododecameric flavoproteins. We demonstrate that the N-terminal domain of the Escherichia coli Dfp protein catalyzes the decarboxylation of (R)-4'-phospho-N-pantothenoylcysteine to 4'-phosphopantetheine. This reaction is essential for coenzyme A biosynthesis.
An Analysis of Efficient Multi-Core Global Power Management Policies: Maximizing Performance for a Given Power Budget (2006)

Chip-level power and thermal implications will continue to rule as one of the primary design constraints and performance limiters. The gap between average and peak power actually widens with increased levels of core integration. As such, if per-core control of power levels (modes) is possible, a global power manager should be able to dynamically set the modes suitably. This would be done in tune with the workload characteristics, in order to always maintain a chip-level power that is below the specified budget. Furthermore, this should be possible without significant degradation of chip-level throughput performance. We analyze and validate this concept in detail in this paper. We assume a per-core DVFS (dynamic voltage and frequency scaling) knob to be available to such a conceptual global power manager. We evaluate several different policies for global multi-core power management. In this analysis, we consider various different objectives such as prioritization and optimized throughput. Overall, our results show that in the context of a workload comprised of SPEC benchmark threads, our best architected policies can come within 1% of the performance of an ideal oracle, while meeting a given chip-level power budget. Furthermore, we show that these global dynamic management policies perform significantly better than static management, even if static scheduling is given oracular knowledge
Haloperidol-induced catalepsy: a model for screening antidepressants effective in treatment of depression with Parkinson's disease. (1997)

Incidence of severe depression is very common in Parkinson's disease (PD). Use of antidepressants in such cases is known to improve or worsen the existing PD. However, prediction of the effect of antidepressant on symptoms of PD is limited due to lack of suitable animal model. The present study examines the possibility of using haloperidol-induced catalepsy model in rats for this purpose. Antidepressants showed distinct effect on haloperidol-induced catalepsy, although most of them reduced forced-swimming induced immobility. In general, antidepressants with greater noradrenergic reuptake inhibition (desipramine, imipramine, amitriptyline, nortriptyline, protriptyline and maprotiline) reduced, whereas those with serotonergic reuptake inhibition (fluoxetine and clomipramine) increased haloperidol-induced catalepsy. Mianserin, an atypical antidepressant, and alprazolam, a benzodiazepine receptor analogue had no effect on haloperidol-induced catalepsy. The results suggest that haloperidol-induced catalepsy model in rats needs to be incorporated in the screening procedure when evaluating the utility of antidepressant drugs for the treatment of depression associated with PD.
Latanoprost Stimulates Ocular Lymphatic Drainage: An In Vivo Nanotracer Study (2013)

This is the first evidence that a prostaglandin drug widely prescribed for glaucoma, enhances lymphatic drainage from the eye. The pharmacological stimulation of this newly identified outflow pathway may be highly relevant to treatments aimed at lowering IOP to prevent blindness from glaucoma.
High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets (2010)

Developing T cells face a series of cell fate choices in the thymus and in the periphery. The role of the individual T cell receptor (TCR) in determining decisions of cell fate remains unresolved. The stochastic/selection model postulates that the initial fate of the cell is independent of TCR specificity, with survival dependent on additional TCR/coreceptor "rescue" signals. The "instructive" model holds that cell fate is initiated by the interaction of the TCR with a cognate peptide-MHC complex. T cells are then segregated on the basis of TCR specificity with the aid of critical coreceptors and signal modulators [Chan S, Correia-Neves M, Benoist C, Mathis (1998) Immunol Rev 165: 195-207]. The former would predict a random representation of individual TCR across divergent T cell lineages whereas the latter would predict minimal overlap between divergent T cell subsets. To address this issue, we have used high-throughput sequencing to evaluate the TCR distribution among key T cell developmental and effector subsets from a single donor. We found numerous examples of individual subsets sharing identical TCR sequence, supporting a model of a stochastic process of cell fate determination coupled with dynamic patterns of clonal expansion of T cells bearing the same TCR sequence among both CD4(+) and CD8+ populations.
Synthesis and some properties of nucleotidyl- and oligonucleotidyl-(5→N)-amino acids (peptides) (1978)

Uridylyl-(5 '-* N)-alanyl-alanine,-tetraalanine,-alanyl-leucyl-alanyl-valine ethyl esters and some oligonucleotidyl-(P-*N)amino acids were synthesized by means of step-by-step elongation of the peptide and oligonucleotide chains. Chemical hydrolysis and the action of hydroxylamine and pronase were investigated. It was shown that the chemical properties of uridylyl-(5'-N)acids (peptides) depend on the length of the peptide chain and on the composition of the amino acids.
An expression meta-analysis of predicted microRNA targets identifies a diagnostic signature for lung cancer (2008)

This study focuses on predicted targets of three lung-enriched miRNAs, compares their expression patterns in lung cancer by their GO terms, and identifies a minimal set of genes differentially expressed in AD and SCC, followed by validating this gene signature in multiple published datasets. Expression of this gene signature in bronchial epithelial cells of cigarette smokers also has a great sensitivity to predict the patients having lung cancer if combined with cytopathology of the cells.
PP.21.26 (2015)

Objective: Hemodynamic abnormalities in hypertensive patients who require a combination of three or more classes of antihypertensive medications to achieve the goals defined by office or out-of-office systolic (SBP) and diastolic (DBP) blood pressures are not well characterized.Design and method: A total of 73 hypertensive patients (68.5 ± 11.4 years, 47.9% males) who received three or more classes of antihypertensive medications were enrolled in this study. Another 73 age- and sex-matched never-treated hypertensive patients were randomly selected from a community survey. Office and out-of-office (by 24-hour ambulatory blood pressure monitoring) SBP, DBP, pulse pressure (PP), central-femoral pulse wave velocity (cf-PWV), amplitudes of the forward and reflected pressure waves from a decomposed carotid pressure wave (Pf and Pb, respectively), cardiac output (CO), total peripheral resistance (TPR), and left ventricular mass index (LVMI) were measured for every participant. Results: Compared with the never-treated patients, the treated patients had significantly lower office and 24-h SBP, DBP and HR (average 24-h SBP/DBP = 124/68 mmHg). The treated patients had significantly lower Pf, but the two groups had similar 24-h PP, Pb, CO, TPR, and LVMI. Moreover, the treated patients had significantly higher cf-PWV than the never-treated patients (11.9 ± 4.3 m/sec vs. 9.2 ± 2.3 m/sec, P < 0.001). Multi-variable regression analysis revealed that SBP (office or 24-h) was a significant independent determinant of LVMI in the never-treated patients. In contrast, PP (office or 24-h) but not SBP was a significant independent determinant of LVMI in the treated patients. Furthermore, cf-PWV and Pb were the significant independent determinants of 24-h PP. Conclusions: Hypertensive patients whose SBP and DBP are controlled by a combination of three or more antihypertensive medications may still have abnormal hemodynamics (arterial stiffness and wave reflections in particular) and LVMI that are not significantly different from those of the never-treated hypertensive patients.