gebhart/patrepeval huggingface dataset:
Glass transition in DNA from molecular dynamics simulations. (1996)

Molecular dynamics simulations of the oligonucleotide duplex d(CGCGCG)2 in aqueous solution are used to investigate the glass transition phenomenon. The simulations were performed at temperatures in the 20 K to 340 K range. The mean square atomic fluctuations showed that the behavior of the oligonucleotide duplex was harmonic at low temperatures. A glass transition temperature at 223 K to 234 K was inferred for the oligonucleotide duplex, which is in agreement with experimental observations. The largest number of hydrogen bounds between the polar atoms of the oligonucleotide duplex and the water molecules was obtained at the glass transition temperature. With increasing temperature we observed a decrease in the average lifetime of the hydrogen bonds to water molecules.
Mechanisms of steroid action and resistance in inflammation and disease (2003)

The conference 'Mechanisms of Steroid Action and Resistance in Inflammation and Disease' was held in Trinity College Dublin in September 2003 and was the final thematic conference held under the auspices of the EUROSTERONE thematic network.
A Formal Basis for the Heuristic Determination of Minimum Cost Paths (1968)

Although the problem of determining the minimum cost path through a graph arises naturally in a number of interesting applications, there has been no underlying theory to guide the development of efficient search procedures. Moreover, there is no adequate conceptual framework within which the various ad hoc search strategies proposed to date can be compared. This paper describes how heuristic information from the problem domain can be incorporated into a formal mathematical theory of graph searching and demonstrates an optimality property of a class of search strategies.
Glucose and the Metabolism of Adenosine 3′:5′-Cyclic Monophosphate in Escherichia coli (1971)

Measurements of adenosine 3':5'-cyclic monophosphate (cAMP) concentrations have been made in Escherichia coli under various conditions. Different strains of E. coli accumulate different extracellular concentrations of cAMP (0.2-4 mum) at stationary phase. Mutation at the RNA control locus does not affect the accumulation pattern. Growth of the bacteria in minimalsalts medium leads to a greater accumulation of cAMP than growth in nutrient broth. Partition studies show that essentially all of the cAMP that is accumulated is found in the medium rather than in the cells. Kinetic studies show that most of the cAMP is formed coincidentally with exhaustion of glucose from the medium. Growth on high concentrations of glucose leads to inhibition of cAMP formation. Other carbon sources cannot substitute for glucose in this inhibitory effect. Measurements of enzyme activities indicate that glucose suppression of cAMP formation cannot be accounted for by a decreased activity of adenylate cyclase or an increased activity of cAMP phosphodiesterase (EC 3.1.3.7).
Murine Dendritic Cells Pulsed In Vitro withToxoplasma gondiiAntigens Induce Protective Immunity In Vivo (1998)

The activation of a predominant T-helper-cell subset plays a critical role in disease resolution. In the case of Toxoplasma gondii, the available evidence indicates that CD4(+) protective cells belong to the Th1 subset. The aim of this study was to determine whether T. gondii antigens (in T. gondii sonicate [TSo]) presented by splenic dendritic cells (DC) were able to induce a specific immune response in vivo and to protect CBA/J mice orally challenged with T. gondii cysts. CBA/J mice immunized with TSo-pulsed DC exhibited significantly fewer cysts in their brains after oral infection with T. gondii 76K than control mice did. Protected mice developed a strong humoral response in vivo, with especially high levels of anti-TSo immunoglobulin G2a antibodies in serum. T. gondii antigens such as SAG1 (surface protein), SAG2 (surface protein), MIC1 (microneme protein), ROP2 through ROP4 (rhoptry proteins), and MIC2 (microneme protein) were recognized predominantly. Furthermore, DC loaded with TSo, which synthesized high levels of interleukin-12 (IL-12), triggered a strong cellular response in vivo, as assessed by the proliferation of lymph node cells in response to TSo restimulation in vitro. Cellular proliferation was associated with gamma interferon and IL-2 production. Taken together, these results indicate that immunization of CBA/J mice with TSo-pulsed DC can induce both humoral and Th1-like cellular immune responses and affords partial resistance against the establishment of chronic toxoplasmosis.
Isolation and characterization of hirustasin, an antistasin‐type serine‐proteinase inhibitor from the medical leech Hirudo medicinalis (1994)

Antistasin, a potent inhibitor of the blood coagulation factor Xa, is the prototype of a novel family of serine-proteinase inhibitors. We have now isolated, sequenced and characterized an antistasin-type inhibitor from the medical leech Hirudo medicinalis. Hirustasin (Hirudo antistasin) was purified to apparent homogeneity by cation-exchange and affinity chromatography. Amino acid sequencing of the 55 amino acid protein (M(r) 5866) revealed that hirustasin is the only antistasin-type protein known to consist of one domain only; 27% and 32% sequence identity was found to the first and second domains of antistasin, respectively, and a nearly exact conservation of the spacing of the ten cysteine residues. Hirustasin is the first inhibitor of tissue kallikrein identified in leeches, and is also a tight-binding inhibitor of trypsin, chymotrypsin and neutrophil cathepsin G. However, despite the high similarity to antistasin, particularly in the vicinity of the putative reactive-site peptide bond, hirustasin neither inhibits blood coagulation in vitro nor amidolytic activity of isolated factor Xa. Thus, structural elements other than the reactive site sequence significantly influence the specificity of antistasin-type proteinase inhibitors.
Calcium Requirement and Inhibitor Spectrum for Intracellular HIV Type 1 gp160 Processing in Cultured HeLa Cells and CD4+ Lymphocytes: Similarity to Those of Viral Envelope Glycoprotein Maturase1 (1995)

We recently purified the calcium-independent processing protease named viral envelope glycoprotein maturase (VEM), that converts human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor gp160 to gp120 and gp41, from the human CD4+ T cell line, Molt-4 clone 8 [Kido, H., Kamoshita, K., Fukutomi, A., and Katunuma, N. (1993) J. Biol. Chem. 268, 13406-13413]. In this report, we deal with the inhibitor specificity and calcium requirement for intracellular gp160 processing in cultured HeLa cells and human CD4+ lymphocytes. Processing of gp160 in these cells infected with recombinant vaccinia virus encoding the gp160 gene was not affected by intracellular calcium depletion induced by the calcium ionophore A23187 and EGTA or by intracellular calcium administration. Processing of gp160 by the purified VEM in vitro was not inhibited by EDTA, EGTA, or the metallo-protease inhibitor phosphoramidon, but was specifically inhibited by a substrate analog, decanoyl-RVKR-chloromethylketone, and the trypsin-type protease inhibitors aprotinin, HI-30, and diisopropyl fluorophosphate (DFP). It was also inhibited by E-64 and thiol reagents. But intracellular gp160 processing was inhibited only by permeable, low molecular mass inhibitors of VEM, such as DFP, E-64, and thiol reagents. Syncytium formation induced by cell surface gp120 was also inhibited by permeable inhibitors of VEM. Taken together, our results indicate that calcium ions may not be essential for intracellular gp160 processing and so HIV-1 gp160 induced by recombinant vaccinia virus may be processed mainly by a protease(s) that does not require calcium ions, such as VEM in these cells.
Novel Associations of Multiple Genetic Loci With Plasma Levels of Factor VII, Factor VIII, and von Willebrand Factor (2010)

New genetic associations were discovered outside previously known biological pathways and may point to novel prevention and treatment targets of hemostasis disorders.
Rudimentary TCR Signaling Triggers Default IL-10 Secretion by Human Th1 Cells (2001)

Understanding the process of inducing T cell activation has been hampered by the complex interactions between APC and inflammatory Th1 cells. To dissociate Ag-specific signaling through the TCR from costimulatory signaling, rTCR ligands (RTL) containing the alpha1 and beta1 domains of HLA-DR2b (DRA*0101:DRB1*1501) covalently linked with either the myelin basic protein peptide 85-99 (RTL303) or CABL-b3a2 (RTL311) peptides were constructed to provide a minimal ligand for peptide-specific TCRs. When incubated with peptide-specific Th1 cell clones in the absence of APC or costimulatory molecules, only the cognate RTL induced partial activation through the TCR. This partial activation included rapid TCR zeta-chain phosphorylation, calcium mobilization, and reduced extracellular signal-related kinase activity, as well as IL-10 production, but not proliferation or other obvious phenotypic changes. On restimulation with APC/peptide, the RTL-pretreated Th1 clones had reduced proliferation and secreted less IFN-gamma; IL-10 production persisted. These findings reveal for the first time the rudimentary signaling pattern delivered by initial engagement of the external TCR interface, which is further supplemented by coactivation molecules. Activation with RTLs provides a novel strategy for generating autoantigen-specific bystander suppression useful for treatment of complex autoimmune diseases.
Recombinant Fv-Hsp70 Protein Mediates Neuroprotection After Focal Cerebral Ischemia in Rats (2010)

Fv-Hsp70 protected the ischemic brain in this experimental stroke model.
The plasmin-binding protein Plr of group A streptococci is identified as glyceraldehyde-3-phosphate dehydrogenase (1996)

Group A streptococci bind the serine protease plasmin with high affinity. Previously, a 41 kDa protein was identified as a candidate plasmin receptor protein (Plr) from group A streptococcal strain 64/14. The plr gene encoding Plr was cloned and the deduced amino acid sequence of Plr had significant similarity to glyceraldehyde-3-phosphate dehydrogenases (GAPDHs). In this study we have isolated cytoplasmic GAPDH of streptococcal strain 64/14. This enzyme was examined, on both structural and functional levels, for its relatedness to the Plr of strain 64/14 purified from mutanolysin extract and to recombinant Plr. We report here that no differences were detected between streptococcal Plr and cytoplasmic GAPDH on the basis of antibody reactivity, plasmin-binding activity, GAPDH activity, N-terminal amino acid sequence, peptide map analysis by V8 protease digestion and amino acid composition analysis. Furthermore, the plr gene appears to be present as a single copy in group A streptococci.
Mechanism of complement inactivation by glycoprotein C of herpes simplex virus (1997)

Glycoprotein C (gC) of both herpes simplex virus type 1 (HSV-1) and HSV-2 interacts with complement C3b and protects the virus from complement-mediated neutralization. To study the mechanism by which gC modulates complement activation, we expressed both gC-1 and gC-2 in a baculovirus expression system. Baculovirus recombinants containing gC genes spanning the entire gC-1 sequence (gC-1-TMR) or only the extracellular domain(s) of gC-1, gC-2, or a deletion mutant of gC-1 lacking residues 33 through 123 were expressed in sf9 insect cells. Binding of the expressed proteins to human C3 and C3 fragments was assessed by direct and competition ELISA. All four expressed proteins bound to C3, C3b, and C3c but not to C3d, suggesting 1) that the binding sites for these proteins are located in the C3c region of C3; and 2) that gC, in contrast to other C3-binding proteins, interacts with native C3. We have also examined the interaction of native C3 with gC-1 expressed on the HSV-1-infected cells. Analogous to recombinant proteins, gC-1 expressed on the infected cells also bound to native C3. The ability of baculovirus-expressed gCs to inhibit the interaction of C3b with its ligands was also analyzed. We found that gC-1, but not gC-2, inhibited the binding of C5 and properdin to C3b and also inhibited the alternative pathway-mediated lysis of rabbit erythrocytes. Inhibition of alternative pathway-mediated lysis and properdin binding to C3b, but not of C5 binding to C3b, required the transmembrane segment of the gC-1. The specificity of gC interactions was examined by studying the interaction of gC with C3 from various species. In contrast to properdin, both gCs bound to cobra C3; this finding suggests that gC-1 and properdin bind to different sites on C3b. Further analyses suggested that gC-1 sterically hindered access of C5 and properdin to C3b.
A Molecular Basis for MHC Class II—Associated Autoimmunity (1988)

Class II major histocompatibility (MHC) molecules have an immunoregulatory role. These cell-surface glycoproteins present fragments of protein antigens (or peptides) to thymus-derived lymphocytes (T cells). Nucleotide sequence polymorphism in the genes that encode the class II MHC products determines the specificity of the immune response and is correlated with the development of autoimmune diseases. This study identifies certain class II polymorphic amino acid residues that are strongly associated with susceptibility to insulin-dependent diabetes mellitus, rheumatoid arthritis, and pemphigus vulgaris. These findings implicate particular class II MHC isotypes in susceptibility to each disease and suggest new prophylactic and therapeutic strategies.
Liquid flow in microchannels: experimental observations and computational analyses of microfluidics effects (2003)

Experimental observations of liquid microchannel flows are reviewed and results of computer experiments concerning channel entrance, wall slip, non-Newtonian fluid, surface roughness, viscous dissipation and turbulence effects on the friction factor are discussed. The experimental findings are classified into three groups. Group I emphasizes 'flow instabilities' and group II points out 'viscosity changes' as the causes of deviations from the conventional flow theory for macrochannels. Group III caters to studies that did not detect any measurable differences between micro- and macroscale fluid flow behaviors. Based on numerical friction factor analyses, the entrance effect should be taken into account for any microfluidic system. It is a function of channel length, aspect ratio and the Reynolds number. Non-Newtonian fluid flow effects are expected to be important for polymeric liquids and particle suspension flows. The wall slip effect is negligible for liquid flows in microconduits. Significant surface roughness effects are a function of the Darcy number, the Reynolds number and cross-sectional configurations. For relatively low Reynolds numbers, Re < 2000, onset to turbulence has to be considered important because of possible geometric non-uniformities, e.g., a contraction and/or bend at the inlet to the microchannel. Channel-size effect on viscous dissipation turns out to be important for conduits with Dh < 100 µm.
Low-loss 1/spl times/2 multimode interference wavelength demultiplexer in silicon-germanium alloy (1999)

A low-loss multimode interference wavelength demultiplexer for 1.3- and 1.55-μm operations based on the silicon-germanium alloy material has been proposed and demonstrated. The device was fabricated by molecular beam epitaxy followed by lithography and plasma etching. The input/output facets were polished mechanically. The measured insertion losses are 4.29 and 4.28 dB and the extinction ratios are 25 and 22 dB at 1.3 and 1.55 μm, respectively.
COX-2 Inhibition, Apoptosis, and Chemoprevention by Nonsteroidal Anti-inflammatory Drugs. (2000)

Non-steroidal anti-inflammatory drugs (NSAIDs) have as their common mechanism the inhibition of cyclooxygenase (COX) enzymes, of which two isoforms (COX-1 and COX-2) exist. The effect of NSAIDs on chemoprevention and tumor regression has been shown in animal models, epidemiologic studies, and in treatment of patients. The exact biochemical and cellular mechanisms underlying each of these phenomena is only partially understood. Processes that have been recently implicated as being important include the inhibition of tumor cell growth, prevention of angiogenesis, and induction of apoptosis in neoplastic cells.
Virology : a practical approach (1985)

Abbreviations Purification, biophysical and biochemical characterisation of viruses with especial reference to plant viruses Growth, assay and purification of picorna-viruses Growth, titration and purification of toga-viruses Growth, purification and titration of rhabdo-viruses Pneumoviruses Growth, purification and titration of influenza viruses Double-stranded RNA viruses Simian virus 40 and polyoma virus: growth, titration, transforamtion and purification of viral components Growth, purification and titration of adeno-viruses Growth, purification and titration of herpes-viruses Techniques in clinical virology Index
Recombinant Interleukin‐2 (1994)

Recombinant interleukin (IL)-2 is a newly approved immunoregulatory protein produced by lymphocytes that exhibits a wide range of immunologic effects. It is a true biologic response modifier in that is has no known direct antitumor activity, but mediates its cytotoxicity through activation of effector cells including T cells, natural killer cells, and lymphokine-activated killer cells. Recombinant IL-2 has demonstrated activity in patients with renal cell carcinoma and melanoma, with objective response rates of approximately 15-20%. The median duration of response in renal cell carcinoma is 23 months. Toxicity experienced with high-dose IL-2 can be significant. The most common dose-limiting toxicities are hypertension, weight gain, oliguria, respiratory insufficiency, and neurotoxicity. These effects are generally manageable and reversible on discontinuation of therapy. Administration of low-dose IL-2 has emerged as a means of substantially reducing toxicity. At least in renal cell carcinoma, it appears that the response rate to low-dose IL-2 is comparable to that with higher dosages.
Diagnosis and Treatment of Low Back Pain: A Joint Clinical Practice Guideline from the American College of Physicians and the American Pain Society (2007)

RECOMMENDATION 1: Clinicians should conduct a focused history and physical examination to help place patients with low back pain into 1 of 3 broad categories: nonspecific low back pain, back pain potentially associated with radiculopathy or spinal stenosis, or back pain potentially associated with another specific spinal cause. The history should include assessment of psychosocial risk factors, which predict risk for chronic disabling back pain (strong recommendation, moderate-quality evidence). RECOMMENDATION 2: Clinicians should not routinely obtain imaging or other diagnostic tests in patients with nonspecific low back pain (strong recommendation, moderate-quality evidence). RECOMMENDATION 3: Clinicians should perform diagnostic imaging and testing for patients with low back pain when severe or progressive neurologic deficits are present or when serious underlying conditions are suspected on the basis of history and physical examination (strong recommendation, moderate-quality evidence). RECOMMENDATION 4: Clinicians should evaluate patients with persistent low back pain and signs or symptoms of radiculopathy or spinal stenosis with magnetic resonance imaging (preferred) or computed tomography only if they are potential candidates for surgery or epidural steroid injection (for suspected radiculopathy) (strong recommendation, moderate-quality evidence). RECOMMENDATION 5: Clinicians should provide patients with evidence-based information on low back pain with regard to their expected course, advise patients to remain active, and provide information about effective self-care options (strong recommendation, moderate-quality evidence). RECOMMENDATION 6: For patients with low back pain, clinicians should consider the use of medications with proven benefits in conjunction with back care information and self-care. Clinicians should assess severity of baseline pain and functional deficits, potential benefits, risks, and relative lack of long-term efficacy and safety data before initiating therapy (strong recommendation, moderate-quality evidence). For most patients, first-line medication options are acetaminophen or nonsteroidal anti-inflammatory drugs. RECOMMENDATION 7: For patients who do not improve with self-care options, clinicians should consider the addition of nonpharmacologic therapy with proven benefits-for acute low back pain, spinal manipulation; for chronic or subacute low back pain, intensive interdisciplinary rehabilitation, exercise therapy, acupuncture, massage therapy, spinal manipulation, yoga, cognitive-behavioral therapy, or progressive relaxation (weak recommendation, moderate-quality evidence).
Screening for mutations by RNA single-strand conformation polymorphism (rSSCP): comparison with DNA-SSCP (1992)

Single-strand conformation polymorphism (SSCP) is a simple method for detecting the presence of mutations in a segment of DNA, but the fraction of all mutations detected is unclear. We have evaluated SSCP for the detection of single-base mutations in the factor IX gene. Multiple conditions were examined including electrophoresis temperature, electrophoresis buffer concentration, acrylamide to bis-acrylamide ratio, and water-cooled versus fan-cooled gel apparatuses. Depending on conditions, 10-11 of 12 known mutations were detected in a 183 bp segment whereas only 11-14 of 22 known mutations were detected in a 307 bp segment. We hypothesized that single stranded RNA should have a larger repertoire of secondary structure because shorter hairpins form stable duplexes and the 2' hydroxyl group is available for sugar-base and sugar-sugar hydrogen bonds. By incorporating phage promoter sequences into PCR primers, RNA-SSCP (rSSCP) could be compared directly with standard DNA SSCP. rSSCP was generally superior to SSCP, especially for the 307 bp segment. In addition, the abundance of transcript produced as a result of rSSCP allows the rapid, nonradioactive detection of mutations by staining the gel with ethidium bromide. To gauge the utility of the method in a prospective manner, a blinded study was performed in which SSCP, rSSCP, and direct genomic sequencing were compared in 28 patients with hemophilia B. A total of 2.6 kb of factor IX genomic sequence was examined in nine regions ranging from 180 to 497 nucleotides of factor IX sequence. Sequence changes at 20 different sites were detected by direct genomic sequencing; 70% of these were detected by rSSCP while only 35% were detected by SSCP.
Imaging, Distribution, and Toxicity of Superparamagnetic Iron Oxide Magnetic Resonance Nanoparticles in the Rat Brain and Intracerebral Tumor (2005)

These studies demonstrate the safety and efficacy of iron oxide-based MRI contrast agents in the brain and provide imaging parameters and time course data for future studies in brain tumors and neurological lesions.