gebhart/patrepeval huggingface dataset:
Regulatory T cells and intestinal homeostasis (2005)

Murine models of inflammatory bowel disease (IBD) are useful tools for the study of the pathogenesis and regulation of intestinal inflammation. Colitis can be induced in immune-deficient mice following transfer of populations of T cells or following infection with Helicobacter hepaticus and other intestinal pathogens. In these situations, colitis occurs as a result of the absence of a specialized population of regulatory cells, as transfer of CD4(+)CD25(+) T cells prevents disease. Importantly, from a clinical perspective, CD4(+)CD25(+) T cells can also reverse an established colitis. CD4(+)CD25(+) T cells proliferate both in the secondary lymphoid organs and at the site of inflammation, suggesting that regulation occurs both locally and systemically. CD4(+)CD25(+) T cells are not only capable of regulating other T cells but are also capable of suppressing components of the innate immune system. Control of colitis is dependent on the presence of the immunosuppressive cytokines interleukin-10 and transforming growth factor-beta, although their roles are divergent and complex. Regulatory T cells represent one of the host's mechanisms to prevent immune pathology during chronic immune stimulation. Enhancement of regulatory T-cell activity may be useful to control autoreactive T-cell responses and inhibit harmful inflammatory diseases such as asthma and IBD.
Small-molecule inhibitors of the HIF pathway and synthetic lethal interactions (2012)

Many of the therapeutic agents that are in clinical use inhibit downstream HIF target genes, but ideally a molecule specific to HIF will have a more potent effect in inhibiting multiple HIF pathways. However, many anti-HIF molecules have multiple targets, which may increase non-specific cytotoxicity. In addition, many anti-HIF agents cannot discriminate between the different isoforms of HIF-α. So, it is important to assess whether targeting both HIF-1α and HIF-2α or each subunit selectively will provide better therapeutic effects.
Dilated Intercellular Spaces (2006)

DIS can be detected and evaluated by light microscopy, and the image analysis used provides an objective quantification of DIS and supports the light microscopy evaluation. DIS are a morphological feature of GERD and esophagitis in infancy and childhood.
IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential (2012)

IL-17 (interleukin-17), a hallmark cytokine of Th17 (T-helper 17) cells, plays critical roles in host defence against bacterial and fungal infections, as well as in the pathogenesis of autoimmune diseases. The present review focuses on current knowledge of the regulation, functional mechanisms and targeting strategies of IL-17 in the context of inflammatory autoimmune diseases. Evidence shows that IL-17 is highly up-regulated at sites of inflammatory tissues of autoimmune diseases and amplifies the inflammation through synergy with other cytokines, such as TNF (tumour necrosis factor) α. Although IL-17 was originally thought to be produced mainly by Th17 cells, a newly defined T-cell subset with a specific differentiation programme and tight regulation, several other cell types (especially innate immune cells) are also found as important sources for IL-17 production. Although IL-17 activates common downstream signalling, including NF-κB (nuclear factor κB), MAPKs (mitogen-activated protein kinases), C/EBPs (CCAAT/enhancer-binding proteins) and mRNA stability, the immediate receptor signalling has been shown to be quite unique and tightly regulated. Mouse genetic studies have demonstrated a critical role for IL-17 in the pathogenesis of variety of inflammatory autoimmune diseases, such as RA (rheumatoid arthritis) and MS (multiple sclerosis). Importantly, promising results have been shown in initial clinical trials of monoclonal antibodies against IL-17 or its receptor (IL-17R) to block IL-17-mediated function in treating autoimmune patients with psoriasis, RA and MS. Therefore targeting IL-17/IL-17R, IL-17-producing pathways or IL-17-mediated signalling pathways can be considered for future therapy in autoimmune diseases.
Immunoglobulin Gene Diversification (2005)

Three processes alter genomic sequence and structure at the immunoglobulin genes of B lymphocytes: gene conversion, somatic hypermutation, and class switch recombination. Though the molecular signatures of these processes differ, they occur by a shared pathway which is induced by targeted DNA deamination by a B cell-specific factor, activation induced cytidine deaminase (AID). Ubiquitous factors critical for DNA repair carry out all downstream steps, creating mutations and deletions in genomic DNA. This review focuses on the genetic and biochemical mechanisms of diversification of immunoglobulin genes.
Simulation of Pore Formation in Lipid Bilayers by Mechanical Stress and Electric Fields (2003)

We describe computer simulations of pore formation and membrane rupture of phospholipid bilayers under mechanical and electrical stress. On the nanosecond simulation time scale, pores are induced by a lateral pressure exceeding −200 bar or by an applied electric field of 0.5 V/nm.
Low-dose estrogen therapy for prevention of osteoporosis: working our way back to monotherapy (2006)

The risks of low bone mineral density, osteoporosis and fractures, are major concerns in postmenopausal women. Although postmenopausal hormone therapy is effective for reducing these risks, safety issues have been raised by the results of studies such as the Women's Health Initiative. Although there are scientifically valid reasons to be wary of the general applicability of the Women's Health Initiative findings, the study has underscored the continuing need for research into new forms of menopausal hormone therapy. Low-dose transdermal estrogen monotherapy can preserve bone density while relieving vasomotor symptoms. Transdermal administration may offer advantages, including lack of first-pass liver metabolism, which permits the use of lower doses and avoids a negative impact on the lipid profile. Moreover, a recently published 2-year study of ultra-low-dose transdermal estrogen monotherapy in an older population similar to that of the WHI reported significant increases in bone mineral density, accompanied by significant reductions in markers of bone turnover, with no increased risk of endometrial hyperplasia or other side effects. Additional studies are warranted to shed further light on the possible benefits of low-dose estrogen monotherapy for the prevention of bone loss in postmenopausal women.
Laser gain characterization of near-atmospheric CO2:N2:He glows in a planar electrode geometry (1973)

Temporally and spatially resolved gain measurements are reported for near-atmospheric CO2:N2:He glow discharges in a contoured planar electrode configuration. When suitably preionized by rows of electrically stressed dielectric interfaces, the entire interelectrode volume is filled with a uniform glow discharge for large ranges of capacitor energy, voltage, and gas pressure. The 10.59-μm gain reaches a peak value of 2.8% cm−1 in 2 μsec, and decays exponentially with a 20-μsec time constant in near-optimum laser mixtures of 60 Torr CO2, 180 Torr N2, and 60 Torr He. Peak gain is uniform over the transverse dimensions to within 5%. Mathematical expressions are developed which relate the small-signal gain to the P and R branch rotational quantum numbers in a linear fashion. This analysis shows that for optimized laser conditions the 00°1–10°0 population inversion is [inverted lazy s]1.8×1017 cm−3 with a rotational temperature of [inverted lazy s]400 °K. This corresponds to a maximum 10.6-μm optical storage density of [inverted lazy s]31 J/liter and represents [inverted lazy s]17% of the electrical energy input to the discharge.
Polyacrylic acid pore-filled microporous membranes and their use in membrane-mediated synthesis of nanocrystalline ferrihydrite (1998)

A series of cation-exchange membranes were obtained by photoinitiated grafting of acrylic acid onto a polypropylene microporous support having 0.2 µm diameter pores. The poly(acrylic acid) was shown to be contained within the pores of the membrane. The ion-exchange capacities of these "pore-filled" membranes ranged from 65 to 80% of the theoretical values calculated on the basis of their measured graft yields, with water contents ranging from 72 to 77%. The membranes exhibited a chemical valve effect of flux as a function of pH. Treatment of a poly(acrylic acid) grafted membrane with a solution containing ferrous ions resulted in a large uptake of iron (&gt;24% by weight of iron with a membrane containing 152% graft yield of poly(acrylic acid)). Subsequent alkaline (pH 14) oxidation at 70°C with either oxygen or hydrogen peroxide led to the formation of a superparamagnetic nanocrystalline form of ferrihydrite, 5Fe 2 O 3 ·9H 2 O. The oxide was identified by temperature-dependent Mössbauer spectroscopy recorded from 300 K to 4.2 K. TEM micrographs of sectioned membranes that were treated with H 2 O 2 revealed the presence of two iron oxide morphologies, disk-shaped particles 3-4 nm in diameter and needle-like particles about 4 nm wide and 50 nm long. Only disk-shaped particles were observed in membranes treated with O 2 . Magnetization measurements indicate that the membranes are superparamagnetic above 50 K with a room temperature magnetization of 3.3 emu g -1 at 20 kOe.Key words: membrane, poly(acrylic acid); iron oxide, magnetic, Mössbauer spectroscopy; magnetization, photografting.
The Structure of a Complex of Recombinant Hirudin and Human α-Thrombin (1990)

The crystallographic structure of a recombinant hirudin-thrombin complex has been solved at 2.3 angstrom (A) resolution. Hirudin consists of an NH2-terminal globular domain and a long (39 A) COOH-terminal extended domain. Residues Ile1 to Tyr3 of hirudin form a parallel beta-strand with Ser214 to Glu217 of thrombin with the nitrogen atom of Ile1 making a hydrogen bond with Ser195 O gamma atom of the catalytic site, but the specificity pocket of thrombin is not involved in the interaction. The COOH-terminal segment makes numerous electrostatic interactions with an anion-binding exosite of thrombin, whereas the last five residues are in a helical loop that forms many hydrophobic contacts. In all, 27 of the 65 residues of hirudin have contacts less than 4.0 A with thrombin (10 ion pairs and 23 hydrogen bonds). Such abundant interactions may account for the high affinity and specificity of hirudin.
Inhibition of ICE Family Proteases by Baculovirus Antiapoptotic Protein p35 (1995)

The baculovirus antiapoptotic protein p35 inhibited the proteolytic activity of human interleukin-1β converting enzyme (ICE) and three of its homologs in enzymatic assays. Coexpression of p35 prevented the autoproteolytic activation of ICE from its precursor form and blocked ICE-induced apoptosis. Inhibition of enzymatic activity correlated with the cleavage of p35 and the formation of a stable ICE-p35 complex. The ability of p35 to block apoptosis in different pathways and in distantly related organisms suggests a central and conserved role for ICE-like proteases in the induction of apoptosis.
Language, skill and authenticity in the globalized new economy (2005)

This article focusses on the ways in which language plays a central role in the globalized new economy. Not only is language itself central as a means of production and as a product, but, contrary to expectations about the ways in which standardized English may be taking over the speech economy of the planet, in fact linguistic variability and multilingualism have become vital. The first part of the article discusses the ways in which language becomes part of work-related competence, whether as a measurable skill or as an innate talent. The second focusses on how this is linked to the market value of authenticity, in an economy where local and regional markets, and local authenticity, are sources of value in an economy based service and on symbolic value. Finally, it considers what the implications of these developments might be for the merging category of "language workers".
MillWheel (2013)

MillWheel is a framework for building low-latency data-processing applications that is widely used at Google. Users specify a directed computation graph and application code for individual nodes, and the system manages persistent state and the continuous flow of records, all within the envelope of the framework's fault-tolerance guarantees. This paper describes MillWheel's programming model as well as its implementation. The case study of a continuous anomaly detector in use at Google serves to motivate how many of MillWheel's features are used. MillWheel's programming model provides a notion of logical time, making it simple to write time-based aggregations. MillWheel was designed from the outset with fault tolerance and scalability in mind. In practice, we find that MillWheel's unique combination of scalability, fault tolerance, and a versatile programming model lends itself to a wide variety of problems at Google.
Toxicity of 5-aza-2'-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. (1994)

The deoxycytidine analog 5-aza-2'-deoxycytidine (5-azadCyd) has been widely used as a DNA methylation inhibitor to experimentally induce gene expression and cellular differentiation. Prior to the availability of mutant mice with altered DNA methyltransferase levels, treatment of cells with drugs has been the only means to experimentally manipulate the level of genomic DNA methylation in mammalian cells. Substitution of DNA with 5-azadCyd leads to covalent trapping of the enzyme, thereby depleting the cells of enzyme activity and resulting in DNA demethylation. 5-AzadCyd or 5-azacytidine treatment causes multiple changes in treated cells, including activation of silent genes, decondensation of chromatin, and induction of cellular differentiation, all of which are believed to be consequences of drug-induced demethylation. 5-AzadCyd is highly toxic in cultured cells and animals and is utilized as a potent antitumor agent for treatment of certain human cancers. It has been postulated that the toxicity of the drug in mammalian cells is also due to its inhibition of DNA methylation. The chemistry of the methylation reaction is consistent, however, with an alternative mechanism: the cytotoxic effect of 5-azadCyd may be directly mediated through the covalent binding of DNA methyltransferase to 5-azadCyd-substituted DNA. We have tested this possibility by using embryonic stem cells and mice with reduced levels of DNA methyltransferase due to a targeted mutation of the gene. When exposed to 5-azadCyd mutant embryonic stem cells or embryos were significantly more resistant to the toxic effects of the drug than wild-type cells and embryos, respectively. These results strongly suggest that the cellular DNA methyltransferase itself, rather than the secondary demethylation of genomic DNA, is the primary mediator of 5-azadCyd cytotoxicity. In light of our results, some conclusions from previous studies using 5-azadCyd in order to experimentally manipulate cellular methylation levels may have to be reassessed. Also, our data make clear predictions for cancer treatment: tumor cells with elevated DNA methyltransferase levels would be expected to be susceptible to treatment with 5-azadCyd, whereas tumors with reduced levels of the enzyme would be resistant.
A Road Map for Those Who Don't Know JAK-STAT (2002)

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway transmits information received from extracellular polypeptide signals, through transmembrane receptors, directly to target gene promoters in the nucleus, providing a mechanism for transcriptional regulation without second messengers. Evolutionarily conserved in eukaryotic organisms from slime molds to humans, JAK-STAT signaling appears to be an early adaptation to facilitate intercellular communication that has co-evolved with myriad cellular signaling events. This co-evolution has given rise to highly adapted, ligand-specific signaling pathways that control gene expression. In addition, the JAK-STAT signaling pathways are regulated by a vast array of intrinsic and environmental stimuli, which can add plasticity to the response of a cell or tissue.
Glycopeptide Synthesis and the Effects of Glycosylation on Protein Structure and Activity (2000)

Despite the omnipresence of protein glycosylation in nature, little is known about how the attachment of carbohydrates affects peptide and protein activity. One reason is the lack of a straightforward method to access biologically relevant glycopeptides and glycoproteins. The isolation of homogeneous glycopeptides from natural sources is complicated by the heterogeneity of naturally occuring glycoproteins. It is chemical and chemoenzymatic synthesis that is meeting the challenge to solve this availability problem, thus playing a key role for the advancement of glycobiology. The current art of glycopeptide synthesis, albeit far from being routine, has reached a level of maturity that allows for the access to homogeneous and pure material for biological and medicinal research. Even the ambitious goal of the total synthesis of an entire glycoprotein is within reach. It is demonstrated that with the help of synthetic glycopeptides the effects of glycosylation on protein structure and function can be studied in molecular detail. For example, in immunology, synthetic (tumour-specific) glycopeptides can be used as immunogens to elicit a tumour-cell-specific immune response. Again, synthetic glycopeptides are an invaluable tool to determine the fine specificity of the immune response that can be mediated by both carbohydrate-specific B and T cells. Furthermore, selected examples for the use of synthetic glycopeptides as ligands of carbohydrate-binding proteins and as enzyme substrates or inhibitors are presented.
Interfacial and Chemical Properties of Pt/TiO2, Pd/TiO2, and Pt/GaN Catalytic Nanodiodes Influencing Hot Electron Flow (2007)

The influence of physical and chemical properties of Pt/TiO2, Pd/TiO2, and Pt/GaN metal−semiconductor Schottky diodes on the yield of collected hot electron flow (number of hot electrons per product molecule) was investigated. We measured both the chemicurrent (electron flow) and chemical turnover rate during oxidation of carbon monoxide (at pressures of 100 Torr of O2 and 40 Torr of CO in the 373−513 K range) using reaction systems equipped for simultaneous reaction rate and current measurements. The chemicurrent was found to be correlated with the turnover rate and can be used to detect the turnover rate for the three diodes. Thermoelectric current was observed in the presence of O2 or CO gas in the absence of catalytic reaction. The chemicurrent was observed only under catalytic reaction condition. The chemicurrent yield of Pt/GaN ((3.5 ± 0.8) × 10-3) was higher than that of Pt/TiO2 or Pd/TiO2 ((2−3) × 10-4) by 1 order of magnitude. We found that the metal−semiconductor interface structure (roughness, grain size, and step−terrace) is important in controlling the magnitude of chemicurrent yield.
Fatty acids of Treponema pallidum and Borrelia burgdorferi lipoproteins (1994)

A fundamental ultrastructural feature shared by the spirochetal pathogens Treponema pallidum subsp. pallidum (T. pallidum) and Borrelia burgdorferi, the etiological agents of venereal syphilis and Lyme disease, respectively, is that their most abundant membrane proteins contain covalently attached fatty acids. In this study, we identified the fatty acids covalently bound to lipoproteins of B. burgdorferi and T. pallidum and examined potential acyl donors to these molecules. Palmitate was the predominant fatty acid of both B. burgdorferi and T. pallidum lipoproteins. T. pallidum lipoproteins also contained substantial amounts of stearate, a fatty acid not typically prevalent in prokaryotic lipoproteins. In both spirochetes, the fatty acids of cellular lipids differed from those of their respective lipoproteins. To characterize phospholipids in these organisms, spirochetes were metabolically labeled with [3H]palmitate or [3H]oleate; B. burgdorferi contained only phosphatidylglycerol and phosphatidylcholine, while T. pallidum contained phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and cardiolipin. Although palmitate predominated in the lipoproteins, there were no apparent differences in the incorporation of these two fatty acids into phospholipids (putative acyl donors). Phospholipase A1 and A2 digestion of phosphatidylcholine from B. burgdorferi and T. pallidum labeled with either [3H]palmitate or [3H]oleate also revealed that neither fatty acid was incorporated preferentially into the 1 and 2 positions (potential acyl donor sites) of the glycerol backbone. The combined findings suggest that fatty acid utilization during lipoprotein synthesis is determined largely by the fatty acid specificities of the lipoprotein acyl transferases. These findings also provide the basis for ongoing efforts to elucidate the relationship between lipoprotein acylation and the physiological functions and inflammatory activities of these molecules.
Lyme Neuroborreliosis: Manifestations of a Rapidly Emerging Zoonosis (2009)

Lyme disease has a worldwide distribution and is the most common vector-borne disease in the United States. Incidence, clinical manifestations, and presentations vary by geography, season, and recreational habits. Lyme neuroborreliosis (LNB) is neurologic involvement secondary to systemic infection by the spirochete Borrelia burgdorferi in the United States and by Borrelia garinii or Borrelia afzelii species in Europe. Enhanced awareness of the clinical presentation of Lyme disease allows inclusion of LNB in the imaging differential diagnosis of facial neuritis, multiple enhancing cranial nerves, enhancing noncompressive radiculitis, and pediatric leptomeningitis with white matter hyperintensities on MR imaging. The MR imaging white matter appearance of successfully treated LNB and multiple sclerosis display sufficient similarity to suggest a common autoimmune pathogenesis for both. This review highlights differences in the epidemiology, clinical manifestations, diagnosis, and management of Lyme disease in the United States, Europe, and Asia, with an emphasis on neurologic manifestations and neuroimaging.
Metabonomics Study on the Effects of the Ginsenoside Rg3 in a β-Cyclodextrin-Based Formulation on Tumor-Bearing Rats by a Fully Automatic Hydrophilic Interaction/Reversed-Phase Column-Switching HPLC−ESI-MS Approach (2008)

The goal of this study was the application of a novel, fully automatic column-switching approach in a metabonomics study combining the orthogonal selectivities of hydrophilic interaction chromatography (HILIC) and reversed-phase chromatography. The temporal, pharmacodynamic effects of the ginsenoside Rg3 on the metabonome in urine of healthy and liver-tumor-bearing rats have been investigated. Within a total analysis time of 52 min we detected 5686 polar, and on the second column an additional 1808 apolar, urinary metabolite ions. The administration of a single, high dose of Rg3 in a beta-cyclodextrin-based formulation led to a considerable change of the metabolic pattern in cancer rats during 3 days studied. Seventeen biomarker candidates including three apolar metabolites, which were not retained on the HILIC column, were detected. Overall, the results suggest that the developed liquid chromatography-mass spectrometry strategy is a promising tool in metabonomics studies for global analysis of highly complex biosamples. It may not only increase the number of discovered biomarkers but consequently improve the comprehensive information on metabolic changes in a fully automatic manner.