gebhart/patrepeval huggingface dataset:
Acquisition of regulatory function by human CD8+ T cells treated with anti‐CD3 antibody requires TNF (2010)

Anti-CD3 mAb can modulate graft rejection and attenuate autoimmune diseases but their mechanism(s) of action remain unclear. CD8(+) T cells with regulatory function are induced in vitro by Teplizumab, a humanized anti-CD3 antibody and inhibit responses of autologous and allogeneic T cells. They inhibit CD4(+) T-cell proliferation by mechanisms involving TNF and CCL4, and by blocking target cell entry into G2/M phase of cell cycle but neither kill them, nor compete for IL-2. CD8(+) Treg can be isolated from peripheral blood following treatment of patients with Type 1 diabetes with Teplizumab, but not from untreated patients. The induction of CD8(+) Treg by anti-CD3 mAb requires TNF and signaling through the NF-κB cascade. The CD8(+) Treg express CD25, glucocorticoid-induced TNF receptor family, CTLA-4, Foxp3, and TNFR2, and the combined expression of TNFR2 and CD25 identifies a potent subpopulation of CD8(+) Treg. These studies have identified a novel mechanism of immune regulation by anti-CD3 mAb and markers that may be used to track inducible CD8(+) Treg in settings such as chronic inflammation or immune therapy.
Novel <I>In-Situ</I> Decoration of Single-Walled Carbon Nanotube Transistors with Metal Nanoparticles (2010)

The carbon nanotube-metal nanoparticle complex has attracted a lot of research interest because of their potential applications in catalysis and gas sensing. Here we introduce a novel electrochemical method to realize in-situ decoration of single-walled carbon nanotube field effect transistors (CNT-FET) with metal nanoparticles using a sacrificial electrode. In this process, metal atoms are first ionized into an electrolyte solution by applying a potential difference between the sacrificial electrode and the grounded source/drain electrodes connecting the nanotube of the CNT-FET. The positive metal ions migrate under the influence of the electric field, and deposit on the grounded nanotube as metal nanoparticles. This method provides for better control over the quantity and size of the deposited nanoparticles compared to other decoration methods. We demonstrate successful deposition of Au and Ag nanoparticles on carbon nanotube field effect devices, with the quantity and size of the nanoparticles varying as a function of the applied potential. We show that the metal nanoparticle size can vary from 10 nm to over 300 nm, and the spatial distribution can change from very scarce decoration to a near continuous coating. Such metal nanoparticles have potential applications in chemical sensors, as they interact with gas molecules and generate an electrical signal in the nanotube, which can be detected. They can also be explored as biological anchoring sites for bio-functionalization of the nanotube, which is critical to developing highly sensitive and selective bio-sensors.
Systematic Review of the Use of Dried Blood Spots for Monitoring HIV Viral Load and for Early Infant Diagnosis (2014)

PROSPERO Registration #: CRD42013003621.
Pancreatic Lipase-related Protein-2 (PLRP2) Can Contribute to Dietary Fat Digestion in Human Newborns (2011)

In newborn mice, PLRP2 is essential for fat digestion. In human infants, the role of PLRP2 in fat digestion is unclear, as it has poor activity against long-chain triglycerides in vitro. Also, many infants carry a genetic polymorphism resulting in a truncated protein, PLRP2 W340X, which may impact function significantly. We re-examined the properties of recombinant human PLRP2 and studied the impact of W340X mutation on its function. In the presence of bile salt micelles and colipase, human PLRP2 hydrolyzed long-chain tri-, di-, and monoglycerides. It hydrolyzed triolein at a level much lower than that of pancreatic triglyceride lipase, but close to that of carboxyl ester lipase, after a long lag phase, which could be eliminated by the addition of oleic acids. Human PLRP2 W340X was poorly secreted and largely retained inside the cell. The retention of the mutant protein triggered endoplasmic reticulum stress and unfolded protein responses. Our results show that earlier studies underestimated human PLRP2 activity against triolein by employing suboptimal assay conditions. In vivo, dietary fat emulsions contain fatty acids as a result of the action of gastric lipase. Consequently, PLRP2 can contribute to fat digestion during early infancy. Furthermore, infants with homozygous W340X alleles will not secrete functional PLRP2 and may have inefficient dietary fat digestion, particularly when breastfeeding is unavailable. Additionally, the aberrant folding of W340X mutant may cause chronic cellular stress and increase susceptibility of pancreatic exocrine cells to other metabolic stressors.
Role of altered growth factor receptor-mediated JAK2 signaling in growth and maintenance of human acute myeloid leukemia stem cells (2014)

Acute myeloid leukemia (AML) is sustained by small populations of leukemia stem cells (LSCs) that can resist available treatments and represent important barriers to cure. Although previous studies have shown increased signal transducer and activator of transcription (STAT)3 and STAT5 phosphorylation in AML leukemic blasts, the role of Janus kinase (JAK) signaling in primary AML compared with normal stem cells has not been directly evaluated. We show here that JAK/STAT signaling is increased in LSCs, particularly from high-risk AML. JAK2 inhibition using small molecule inhibitors or interference RNA reduced growth of AML LSCs while sparing normal stem cells both in vitro and in vivo. Increased JAK/STAT activity was associated with increased expression and altered signaling through growth factor receptors in AML LSCs, including receptor tyrosine kinase c-KIT and FMS-related tyrosine kinase 3 (FLT3). Inhibition of c-KIT and FLT3 expression significantly inhibited JAK/STAT signaling in AML LSCs, and JAK inhibitors effectively inhibited FLT3-mutated AML LSCs. Our results indicate that JAK/STAT signaling represents an important signaling mechanism supporting AML LSC growth and survival. These studies support continued evaluation of strategies for JAK/STAT inhibition for therapeutic targeting of AML LSCs.
The role of TGFBI (βig-H3) in gastrointestinal tract tumorigenesis (2015)

Our data suggest that TGFBI functions as a promoter of certain gastrointestinal tract cancers. It provides a survival advantage to cells with DNA damage. Over a long time span, this advantage could translate into increased tumor risks.
Adjuvant Approaches to Enhance Cryosurgery (2009)

Molecular adjuvants can be used to enhance the natural destructive mechanisms of freezing within tissue. This review discusses their use in the growing field of combinatorial or adjuvant enhanced cryosurgery for a variety of disease conditions. Two important motivations for adjuvant use are: (1) increased control of the local disease in the area of freezing (i.e., reduced local recurrence of disease) and (2) reduced complications due to over-freezing into adjacent tissues (i.e., reduced normal functional tissue destruction near the treatment site). This review starts with a brief overview of cryosurgical technology including probes and cryogens and major mechanisms of cellular, vascular injury and possible immunological effects due to freeze-thaw treatment in vivo. The review then focuses on adjuvants to each of these mechanisms that make the tissue more sensitive to freeze-thaw injury. Four broad classes of adjuvants are discussed including: thermophysical agents (eutectic forming salts and amino acids), chemotherapuetics, vascular agents and immunomodulators. The key issues of selection, timing, dose and delivery of these adjuvants are then elaborated. Finally, work with a particularly promising vascular adjuvant, TNF-alpha, that shows the ability to destroy all cancer within a cryosurgical iceball is highlighted.
Pancreatic beta-cell glucokinase: closing the gap between theoretical concepts and experimental realities. (1998)

There remains a wide gap between theoretical concepts and experimental realities in the enzyme kinetics and biochemical genetics of the pancreatic beta-cell glucokinase-glucose sensor. It is the goal of present efforts in many laboratories to bridge this gap. This perspective intends to provide a timely review of this crucial aspect of research in glucose homeostasis. It deals briefly with some fundamentals of glucokinase enzyme kinetics, offers some pertinent biochemical genetic considerations, takes stock of the current experimental database of the field by emphasizing human studies and referring to recent mouse studies, and ventures a few extrapolations into the future of this endeavor.
Androgens and Coronary Artery Disease (2003)

A significant and independent association between endogenous testosterone (T) levels and coronary events in men and women has not been confirmed in large prospective studies, although cross-sectional data have suggested coronary heart disease can be associated with low T in men. Hypoandrogenemia in men and hyperandrogenemia in women are associated with visceral obesity; insulin resistance; low high-density lipoprotein (HDL) cholesterol (HDL-C); and elevated triglycerides, low-density lipoprotein cholesterol, and plasminogen activator type 1. These gender differences and confounders render the precise role of endogenous T in atherosclerosis unclear. Observational studies do not support the hypothesis that dehydroepiandrosterone sulfate deficiency is a risk factor for coronary artery disease. The effects of exogenous T on cardiovascular mortality or morbidity have not been extensively investigated in prospective controlled studies; preliminary data suggest there may be short-term improvements in electrocardiographic changes in men with coronary artery disease. In the majority of animal experiments, exogenous T exerts either neutral or beneficial effects on the development of atherosclerosis. Exogenous androgens induce both apparently beneficial and deleterious effects on cardiovascular risk factors by decreasing serum levels of HDL-C, plasminogen activator type 1 (apparently deleterious), lipoprotein (a), fibrinogen, insulin, leptin, and visceral fat mass (apparently beneficial) in men as well as women. However, androgen-induced declines in circulating HDL-C should not automatically be assumed to be proatherogenic, because these declines may instead reflect accelerated reverse cholesterol transport. Supraphysiological concentrations of T stimulate vasorelaxation; but at physiological concentrations, beneficial, neutral, and detrimental effects on vascular reactivity have been observed. T exerts proatherogenic effects on macrophage function by facilitating the uptake of modified lipoproteins and an antiatherogenic effect by stimulating efflux of cellular cholesterol to HDL. In conclusion, the inconsistent data, which can only be partly explained by differences in dose and source of androgens, militate against a meaningful assessment of the net effect of T on atherosclerosis. Based on current evidence, the therapeutic use of T in men need not be restricted by concerns regarding cardiovascular side effects. Available data also do not justify the uncontrolled use of T or dehydroepiandrosterone for the prevention or treatment of coronary heart disease.
Structure-Based Design of Bacterial Nitric Oxide Synthase Inhibitors (2014)

Inhibition of bacterial nitric oxide synthase (bNOS) has the potential to improve the efficacy of antimicrobials used to treat infections by Gram-positive pathogens Staphylococcus aureus and Bacillus anthracis. However, inhibitor specificity toward bNOS over the mammalian NOS (mNOS) isoforms remains a challenge because of the near identical NOS active sites. One key structural difference between the NOS isoforms is the amino acid composition of the pterin cofactor binding site that is adjacent to the NOS active site. Previously, we demonstrated that a NOS inhibitor targeting both the active and pterin sites was potent and functioned as an antimicrobial ( Holden , , Proc. Natl. Acad. Sci. U.S.A. 2013 , 110 , 18127 ). Here we present additional crystal structures, binding analyses, and bacterial killing studies of inhibitors that target both the active and pterin sites of a bNOS and function as antimicrobials. Together, these data provide a framework for continued development of bNOS inhibitors, as each molecule represents an excellent chemical scaffold for the design of isoform selective bNOS inhibitors.
Failure Isn't What It Used to Be ... But Neither Is Success (1998)

CHICAGO-- Until now, researchers have assumed that if virus levels go up in patients on the new AIDS treatments that are helping HIV-infected people live longer, healthier lives, the treatment has failed. But new data presented here at the Fifth Conference on Retroviruses and Opportunistic Infections indicate that immune-cell levels can remain high even when the virus is thriving--perhaps because other factors besides viral levels can affect immune-cell production, powerful new tests suggest. But 12 groups also reported a down side to this good news: Long-term treatment with protease inhibitors causes a puzzling redistribution of body fat that could be an omen of other, more serious side effects.
Conservation of Glutamine-Rich Transactivation Function between Yeast and Humans (2000)

Several eukaryotic transcription factors such as Sp1 or Oct1 contain glutamine-rich domains that mediate transcriptional activation. In human cells, promoter-proximally bound glutamine-rich activation domains activate transcription poorly in the absence of acidic type activators bound at distal enhancers, but synergistically stimulate transcription with these remote activators. Glutamine-rich activation domains were previously reported to also function in the fission yeast Schizosaccharomyces pombe but not in the budding yeast Saccharomyces cerevisiae, suggesting that budding yeast lacks this pathway of transcriptional activation. The strong interaction of an Sp1 glutamine-rich domain with the general transcription factor TAF(II)110 (TAF(II)130), and the absence of any obvious TAF(II)110 homologue in the budding yeast genome, seemed to confirm this notion. We reinvestigated the phenomenon by reconstituting in the budding yeast an enhancer-promoter architecture that is prevalent in higher eukaryotes but less common in yeast. Under these conditions, we observed that glutamine-rich activation domains derived from both mammalian and yeast transcription factors activated only poorly on their own but strongly synergized with acidic activators bound at the remote enhancer position. The level of activation by the glutamine-rich activation domains of Sp1 and Oct1 in combination with a remote enhancer was similar in yeast and human cells. We also found that mutations in a glutamine-rich domain had similar phenotypes in budding yeast and human cells. Our results show that glutamine-rich activation domains behave very similarly in yeast and mammals and that their activity in budding yeast does not depend on the presence of a TAF(II)110 homologue.
Novel Cannabinol Probes for CB1 and CB2 Cannabinoid Receptors (2000)

The observation that the phenolic hydroxyl of THCs was important for binding to the CB1 receptor but not as critical for binding to the CB2 receptor prompted us to extend this finding to the cannabinol (CBN) series. To study the SAR of CBN analogues, CBN derivatives with substitution at the C-1, C-3, and C-9 positions were chosen since these positions have played a key role in the SAR of THCs. CBN-3-(1',1'-dimethylheptyl) analogues were prepared by sulfur dehydrogenation of Delta(8)-THC-3-(1',1'-dimethylheptyl) analogues. 9-Substituted CBN analogues were prepared by the standard sulfur dehydrogenation of 9-substituted Delta(8)-THC analogues (Scheme 1), which in turn were prepared following our previous procedure using selenium dioxide oxidation of the corresponding Delta(8)-THCs followed by sodium chlorite oxidation to give the 9-carboxy-Delta(8)-THC derivatives. 11-Hydroxy-CBN analogues were prepared from the corresponding 9-carbomethoxy-CBN analogues by reduction with LiAlH(4). Deoxy-CBN analogue 14 was prepared from the corresponding Delta(8)-THC analogue 11 by conversion of the phenolic hydroxyl to the phosphate derivative 12, followed by lithium ammonia reduction to provide the deoxy-Delta(8)-THC analogue 13, which in turn was dehydrogenated with sulfur to provide the deoxy-CBN analogue 14 (Scheme 2). The various analogues were assayed for binding both to the brain and the peripheral cannabinoid receptors (CB1 and CB2). We have found that the binding profile differs widely between the CBN and the THC series. Specifically, in the CBN series the removal of the phenolic hydroxyl decreases binding affinity to both the CB1 and CB2 receptors, whereas in the THC series, CB1 affinity is selectively reduced. Thus, in the CBN series, the selectivity of binding observed with the removal of the hydroxy group is decreased severalfold as compared to what occurs in the THC series. Generally, high affinity for the CB2 receptor was found in analogues when the phenolic hydroxyl was present. The 3-(1', 1'-dimethylheptyl) derivatives were found to have much higher affinities than the CBN analogues, which is in complete agreement with previously reported work by Rhee et al.
Pathogenetic role of no-reflow phenomenon in experimental subarachnoid hemorrhage in dogs (1977)

✓ The real pathogenetic role of no-reflow phenomenon in clinical situations such as the acute stage of subarachnoid hemorrhage (SAH) is not yet known. To study this problem, we carried out the following experiment in dogs: SAH was induced by withdrawing a needle previously inserted into the internal carotid artery through a small craniectomy in the lateral base of the skull. Complete dural repair and cranioplasty was done to avoid cerebrospinal fluid leakage. Cortical cerebral blood flow (CBF) changes, measured by a double-needle type thermocouple, intracranial pressure (ICP), electroencephalogram (EEG), and sensory evoked response were monitored under controlled ventilation for 3 hours after SAH. At the end of the experiment, the brain was perfused with carbon black solution at a pressure of 120 mm Hg. The 32 episodes of SAH thus induced yielded two basic patterns of ICP changes which simulated those previously reported with human SAH. In the first pattern, reactive hyperemia was always observed, followed by complete or incomplete recovery of cerebral function. Perfusion defects were frequently seen in the thalamus, basal ganglia, and parietooccipital cortex symmetrically. In the second pattern, prolonged elevation of ICP resulted in failure of recovery of both CBF and EEG. Carbon black filled only the pial arteries and the rest of the brain was totally unperfused. From the results, the pathogenetic role of the no-reflow phenomenon in the acute stage of SAH as influencing the prognosis is strongly suspected.
The Natural History of Community-Acquired Hepatitis C in the United States (1992)

Patients with community-acquired hepatitis C have a high rate of chronic hepatitis. HCV may be a major cause of chronic liver disease in the United States, and in most patients HCV infection seems to persist for at least several years, even in the absence of active liver disease.
Photostimulated luminescence of AgI clusters in zeolite-Y (1998)

AgI clusters in zeolite-Y (AgI/Y) were prepared by Ag+ exchange followed by reaction with NaI in solution. The formation of the clusters was determined by transmission electron microscopy and Auger electron spectroscopy. The clusters were uniform and even in size, 1.0–2.0 nm. The fluorescence spectrum of the clusters consists of two emission bands, which are attributed to AgI and Ag clusters, respectively. Photostimulated luminescence (PSL) is observed by stimulation at 675 or at 840 nm. The PSL spectrum of AgI/Y is consistent with the emission spectrum of Ag clusters and thus the PSL is considered to be caused by the charge transfer or carrier migration from the zeolite framework or from the AgI clusters to the Ag clusters. The appearance of PSL indicates that these materials may find application as a medium for erasable optical memory.
Piezocomposite and CMUT arrays assessment through in vitro imaging performances (2008)

Piezoelectric and capacitive micromachined ultrasound transducers (CMUT) are usually measured and compared in regards to acoustic and electro-acoustic performances. This paper is focused on the imaging performances of such transducers and propose a quantitative imaging assessment of B-mode images. In this purpose, fully integrated CMUT and piezocomposite-based probes were manufactured. Transducers were designed with close features (geometries, center frequency, interconnect and packaging) and plug on a clinical ultrasound system with a research interface. Major imaging performances (speckle to noise ratio, resolutions and contrast) of the probes are presented. Despite an environment dedicated to piezoelectric transducers, CMUT probe exhibits comparable image quality as compared to a state-of-the-art piezocomposite probe. Indeed, close resolutions are calculated, field of view is improved in phased-array imaging, and contrast is significantly improved.
Ion mobility–mass spectrometry (2008)

This review article compares and contrasts various types of ion mobility-mass spectrometers available today and describes their advantages for application to a wide range of analytes. Ion mobility spectrometry (IMS), when coupled with mass spectrometry, offers value-added data not possible from mass spectra alone. Separation of isomers, isobars, and conformers; reduction of chemical noise; and measurement of ion size are possible with the addition of ion mobility cells to mass spectrometers. In addition, structurally similar ions and ions of the same charge state can be separated into families of ions which appear along a unique mass-mobility correlation line. This review describes the four methods of ion mobility separation currently used with mass spectrometry. They are (1) drift-time ion mobility spectrometry (DTIMS), (2) aspiration ion mobility spectrometry (AIMS), (3) differential-mobility spectrometry (DMS) which is also called field-asymmetric waveform ion mobility spectrometry (FAIMS) and (4) traveling-wave ion mobility spectrometry (TWIMS). DTIMS provides the highest IMS resolving power and is the only IMS method which can directly measure collision cross-sections. AIMS is a low resolution mobility separation method but can monitor ions in a continuous manner. DMS and FAIMS offer continuous-ion monitoring capability as well as orthogonal ion mobility separation in which high-separation selectivity can be achieved. TWIMS is a novel method of IMS with a low resolving power but has good sensitivity and is well intergrated into a commercial mass spectrometer. One hundred and sixty references on ion mobility-mass spectrometry (IMMS) are provided.
Oxidant-Induced Apoptosis in Human Retinal Pigment Epithelial Cells: Dependence on Extracellular Redox State (2005)

The hRPE cells that are exposed to a more oxidized extracellular redox environment have increased susceptibility to oxidant-induced apoptosis through the intrinsic mitochondrial pathway, which could contribute to an age-related decline in cell populations in the retina and thereby provide a potential mechanism for the degenerative changes that are associated with age-related macular degeneration (ARMD).