gebhart/patrepeval huggingface dataset:
Bioactive human recombinant tumor necrosis factor‐α: an unstable dimer? (1989)

As determined by native polyacrylamide gel electrophoresis (PAGE) and gel chromatography the molecular mass of native tumor necrosis factor (TNF)-alpha was approximately 35 kDa. When incubated at low concentrations (less than 1 nM) 125I-labeled TNF-alpha and unlabeled TNF-alpha rapidly multimerized or dissociated into monomers and bioactivity decreased. Sodium dodecyl sulfate (SDS)-PAGE analysis of cross-linked 125I-labeled TNF-alpha demonstrated bands of multi- and trimeric TNF-alpha in addition to dominating bands of dimers and monomers. Tri-, di- and monomeric TNF-alpha were recovered from SDS-PAGE gels and allowed to renature. Of the original receptor-binding activity, 10%-15% was obtained with cross-linked TNF-alpha dimers, whereas none was recovered from preparations of trimeric TNF-alpha. Multimeric and monomeric TNF-alpha exhibited little or no binding activity, and cell-bound, cross-linked TNF-alpha which was dissociated from cellular binding sites was mainly dimeric. 125I-labeled TNF-alpha bound to lymphokine-activated killer (LAK) cells and binding kinetics were much similar (Kd approximately 100 pM) to those reported in other normal cell types. The number of receptors per LAK cell was approximately 4 x 10(3). Cross-linking of TNF-alpha to binding sites in U-937 and LAK cells yielded a receptor-ligand complex of about 80/90 kDa. At 37 degrees C, 125I-labeled TNF-alpha was rapidly internalized and degraded in L-929, U-937 and LAK cells. Degradation of ligand and recycling of receptors were blocked in the presence of methylamine. Methylamine significantly inhibited TNF-alpha-mediated cytolysis of L-929 cells and caused a quantitatively corresponding reduction in cellular TNF-alpha uptake, indicating that L-929 lysis was mediated by receptors.
Agalactosyl glycoforms of IgG autoantibodies are pathogenic. (1994)

The glycosylation of IgG results in many different glycoforms. A large body of correlative data (including remission of arthritis during pregnancy) has suggested that IgG molecules lacking galactose were associated with rheumatoid arthritis. We now demonstrate that agalactosyl IgG glycoforms are directly associated with pathogenicity in murine collagen-induced arthritis. We show that passive transfer of an acute synovitis in T-cell-primed mice can be enhanced by using IgG containing autoantibodies to type II collagen when the antibodies are present as the agalactosyl glycoform. Thus, nonpathogenic doses of autoantibodies can be made pathogenic by altering their glycosylation state.
86. A novel pyrimidine synthesis. Part II. 4-Amino-5-arylpyrimidines (1945)

The first page of this article is displayed as the abstract.
Stiffness Estimates Using Portable Deflectometers (2004)

The use of falling weight deflectometers and portable falling weight deflectometers (PFWDs) is now common for field characterization of pavement system layers. In particular, the application of portable deflectometers in quality assurance of newly constructed granular base has become more widespread. Typically, these devices are used for an in situ assessment of the Young's modulus of the base layer. The traditional backcalculation uses an elastostatic half-space framework to relate Young's modulus of the pavement foundation to the stiffness estimates obtained from force and velocity measurements. The data interpretation method that is customarily used for stiffness estimation uses peak values of the force and displacement records in lieu of their static counterparts. The performance of a particular device, PRIMA 100, was examined with the newly developed beam verification tester (BVT) of known static stiffness. It was shown that the conventional, peak-based method of backanalysis produces incorrect estimates of the static stiffness of the BVT. An alternative, spectral-based data interpretation method was proposed. This method, based on ( a) concept and measurement of the frequency response function and ( b) a single-degree-of-freedom mechanical model, was employed to extract the true static stiffness from PRIMA 100 measurements. The results show a good agreement between the true static stiffness of the BVT and its PFWD estimates stemming from the modified approach. The BVT apparatus can therefore be used to assess the performance of the sensors and data interpretation of PRIMA 100-type deflectometers.
Development, Maturation, and Necessity of Transcription Factors in the Mouse Suprachiasmatic Nucleus (2011)

The suprachiasmatic nucleus (SCN) of the hypothalamus is the master mammalian circadian clock. The SCN is highly specialized because it is responsible for generating a near 24 h rhythm, integrating external cues, and translating the rhythm throughout the body. Currently, our understanding of the developmental origin and genetic program involved in the proper specification and maturation of the SCN is limited. Herein, we provide a detailed analysis of transcription factor (TF) and developmental-gene expression in the SCN from neurogenesis to adulthood in mice (Mus musculus). TF expression within the postmitotic SCN was not static but rather showed specific temporal and spatial changes during prenatal and postnatal development. In addition, we found both global and regional patterns of TF expression extending into the adult. We found that the SCN is derived from a distinct region of the neuroepithelium expressing a combination of developmental genes: Six3, Six6, Fzd5, and transient Rx, allowing us to pinpoint the origin of this region within the broader developing telencephalon/diencephalon. We tested the necessity of two TFs in SCN development, RORα and Six3, which were expressed during SCN development, persisted into adulthood, and showed diurnal rhythmicity. Loss of RORα function had no effect on SCN peptide expression or localization. In marked contrast, the conditional deletion of Six3 from early neural progenitors completely eliminated the formation of the SCN. Our results provide the first description of the involvement of TFs in the specification and maturation of a neural population necessary for circadian behavior.
Antidepressants for insomnia in adults (2018)

We identified relatively few, mostly small studies with short-term follow-up and design limitations. The effects of SSRIs compared with placebo are uncertain with too few studies to draw clear conclusions. There may be a small improvement in sleep quality with short-term use of low-dose doxepin and trazodone compared with placebo. The tolerability and safety of antidepressants for insomnia is uncertain due to limited reporting of adverse events. There was no evidence for amitriptyline (despite common use in clinical practice) or for long-term antidepressant use for insomnia. High-quality trials of antidepressants for insomnia are needed.
Immunogenicity of group B Streptococcus type III polysaccharide-tetanus toxoid vaccine in baboons (1996)

Maternal vaccination has been proposed as a rational approach for the prevention of neonatal group B streptococcal (GBS) disease. In this study, baboons were used as a nonhuman primate model to evaluate the immunogenicity of a GBS type III glycoconjugate vaccine. Type III-specific immunoglobulin G with opsonic activity was induced after vaccination with type III polysaccharide coupled to tetanus toxoid administered with an aluminum adjuvant. This suggests that baboons could be used in evaluating maternal transfer of GBS-specific antibodies by vaccination during pregnancy.
In vivoanalysis of the origin and characteristics of gaseous microemboli during catheter-mediated irreversible electroporation (2020)

Anodal IRE applications result in significantly less gas formation than both cathodal IRE applications and RF applications. This finding is supported by TOE observations.
Integrated path planning and dynamic steering control for autonomous vehicles (1986)

A method is presented for combining two previously proposed algorithms for path-planning and dynamic steering control into a computationally feasible scheme for real-time feedback control of autonomous vehicles in uncertain environments. In the proposed approach to vehicle guidance and control, Path Relaxation is used to compute critical points along a globally desirable path using a priori information and sensor data. Generalized potential fields are then used for local feedback control to drive the vehicle along a collision-free path using the critical points as subgoals. Simulation results are presented to demonstrate the control scheme.
Microparticle Immunoenzymatic Assay for Detection of Prostate Specific Antigen: Characterization of the Technique and Comparative Analysis with a Monoclonal Immunoradiometric Assay (1995)

Microparticle immunoenzymatic assay (MEIA) is a new, ultrasensitive technique recently introduced for detection of prostatic specific antigen (PSA). It is easily performed, totally automated, and cheaper and faster than radioimmunometric techniques. In this study, the levels of PSA in 194 males with urologic problems and healthy males, recorded by microparticle monoclonal ultrasensitive enzymoimmunoassay (MEIA) and immunoradiometric assay (IRMA), are comparatively evaluated. Variables recorded were age of patient, size and weight of the prostate, and PSA levels analyzed by the MEIA (MEIA-PSA) and IRMA (ELSA-PSA) techniques. Different determinations of PSA were performed in order to calculate the intra- and interassay variation coefficient for the MEIA-PSA assay. Means of prostatic length, width, and depth, recorded by ultrasonography, were 28.3, 35.8, and 31.4 mm, respectively, with a mean prostatic size of 19 ml and a mean prostatic weight of 23.9 g. Mean IRMA-PSA was 4.53 ng/ml and mean MEIA-PSA was 2.04 ng/ml. The difference between them was 2.49, and the ratio IRMA-PSA:MEIA-PSA was 3.17. Interassay and intraassay variation coefficients for MEIA-PSA were 6.58 and 9.96%, respectively. MEIA-PSA values correlated linearly with the age of the patients (r = 0.65, p = 0.0001), size of the prostate (r = 0.71, p = 0.0001), weight of the prostate (r = 0.71, p = 0.0001), and the value of IRMA-PSA (r = 0.80, p = 0.0001). Paired t tests showed that the values of PSA measured by MEIA and IRMA are statistically different (p = 0.0001), with independence of the level of PSA considered.
Absence of t(14;18) major and minor breakpoints and of Bcl-2 protein overproduction in Reed-Sternberg cells of Hodgkin's disease. (1991)

The t(14;18) translocation, found in most human follicular non-Hodgkin's lymphomas (NHLs), juxtaposes the Bcl-2 oncogene at 18q21 with the immunoglobulin heavy chain locus at 14q32. As a result, the Bcl-2 protein is markedly overproduced. Most of the breakpoints on chromosome 18 cluster at one of two sites, the major breakpoint region (mbr) and the minor cluster region (mcr). Recently, others used the polymerase chain reaction (PCR) to detect the t(14;18) mbr in 32% of specimens diagnosed as Hodgkin's disease (HD). In an attempt to confirm and extend those observations the authors used PCR to assay for both the mbr and mcr in HD specimens diagnosed at their institution and examined the specimens for Bcl-2 overproduction. The authors subjected the DNAs from 28 well-characterized HD tumors of 26 patients to PCR analyses using primers specific for the t(14;18) mbr and mcr breakpoints. Based on various PCR controls, the authors ascertained that 26 of the 28 specimens contained amplifiable template DNA. Southern blotting of the amplification products showed that none of the 26 HD DNAs had detectable t(14;18) mbr or mcr breakpoints. By admixing small amounts of t(14;18)-bearing NHL DNA with HD DNA samples, the authors directly demonstrated that the sensitivity of the PCR assays was adequate for the molecular detection of t(14;18)-bearing cells at a frequency comparable to that of Reed-Sternberg cells and their variants in HD. Immunohistochemical studies employing a highly specific anti-Bcl-2 antiserum under conditions optimized to detect t(14;18)-mediated overexpression of the Bcl-2 gene showed that the Reed-Sternberg cells and variants in all 19 HD tumors examined were negative for Bcl-2 immunostaining. In conclusion, the PCR and immunohistochemical data provided evidence that the t(14;18) translocation was not involved in the pathogenesis of the HD cases.
High Rate Deposition Copper Cvd (1991)

This report presents new copper CVD technology using gaseous H2O in addition to a Cu(HFA)2 and hydrogen reaction system. By this technique, the deposition rate was remarkably increased and the surface morphology was also improved. The selectivity and the step coverage were sufficient.
Policy Shaping: Integrating Human Feedback with Reinforcement Learning (2013)

A long term goal of Interactive Reinforcement Learning is to incorporate non-expert human feedback to solve complex tasks. Some state-of-the-art methods have approached this problem by mapping human information to rewards and val-ues and iterating over them to compute better control policies. In this paper we argue for an alternate, more effective characterization of human feedback: Policy Shaping. We introduce Advise, a Bayesian approach that attempts to maximize the information gained from human feedback by utilizing it as direct policy labels. We compare Advise to state-of-the-art approaches and show that it can outperform them and is robust to infrequent and inconsistent human feedback. 1
Selection of an RNA molecule that mimics a major autoantigenic epitope of human insulin receptor. (1995)

Autoimmunity often involves the abnormal targeting of self-antigens by antibodies, leading to tissue destruction and other pathologies. This process could potentially be disrupted by small ligands that bind specifically to autoantibodies and inhibit their interaction with the target antigen. Here we report the identification of an RNA sequence that binds a mouse monoclonal antibody specific for an autoantigenic epitope of human insulin receptor. The RNA ligand binds specifically and with high affinity (apparent Kd congruent to 2 nM) to the anti-insulin receptor antibody and not to other mouse IgGs. The RNA can also act as a decoy, blocking the antibody from binding the insulin receptor. Thus, it probably binds near the combining site on the antibody. Strikingly, the RNA cross-reacts with autoantibodies from patients with extreme insulin resistance. One simple explanation is that the selected RNA may structurally mimic the antigenic epitope on the insulin receptor protein. These results suggest that decoy RNAs may be used in the treatment of autoimmune diseases.
Rapid kinetic measurement of lactate in plasma with a centrifugal analyzer. (1975)

In this method, blood is collected in ammonium heparinized microhematocrit tubes and lactate is directly determined in the plasma, separated within 15 min from the erythrocytes. Lactate is assayed by mixing 10 mul of sample with NAD+ and lactate dehydrogenase in tris(hydroxymethyl)aminomethane hydrazine buffer. The rate of increase in absorbance of the NADH formed, measured at 340 nm, is proportional to lactate concentration. The assay is complete in 4 min and absorbance is linearly related to concentration from 0.625 to 15 mmol/liter. Analytical recoveries of lactate added to plasma averaged 104% (range, 91-116%). Results compared well for plasma samples analyzed by this method with the CentrifiChem and the Du Pont aca.
Extremum Seeking control of smart inverters for VAR compensation (2015)

Reactive power compensation is used by utilities to ensure customer voltages are within pre-defined tolerances and reduce system resistive losses. While much attention has been paid to model-based control algorithms for reactive power support and Volt Var Optimization (VVO), these strategies typically require relatively large communications capabilities and accurate models. In this work, a non-model-based control strategy for smart inverters is considered for VAR compensation. An Extremum Seeking control algorithm is applied to modulate the reactive power output of inverters based on real power information from the feeder substation, without an explicit feeder model. Simulation results using utility demand information confirm the ability of the control algorithm to inject VARs to minimize feeder head real power consumption. In addition, we show that the algorithm is capable of improving feeder voltage profiles and reducing reactive power supplied by the distribution substation.
Characterization of murine A-raf, a new oncogene related to the v-raf oncogene. (1986)

A 1.6-kilobase cDNA (A-raf) has been isolated from a murine spleen cDNA library which encodes part of a protein related to the raf oncogene. Its amino acid sequence has 85% homology to raf in a central portion of 100 amino acids. In contrast to raf, A-raf shows a highly restricted tissue distribution of expression, with highest levels observed in epididymis, followed by intestine. When incorporated into a retrovirus, the resulting gag-A-raf fusion gene causes transformation in vitro and induces tumors in newborn mice. Thus, A-raf represents a new proto-oncogene. Transformation by A-raf is independent of ras gene function, as is the case for raf and mos but not other oncogenes.
GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses (2017)

GS-5734 is a monophosphate prodrug of an adenosine nucleoside analog that showed therapeutic efficacy in a non-human primate model of Ebola virus infection. It has been administered under compassionate use to two Ebola patients, both of whom survived, and is currently in Phase 2 clinical development for treatment of Ebola virus disease. Here we report the antiviral activities of GS-5734 and the parent nucleoside analog across multiple virus families, providing evidence to support new indications for this compound against human viruses of significant public health concern.
DNA-protein binding assays from a single sea urchin egg: a high-sensitivity capillary electrophoresis method. (1996)

A capillary electrophoresis method has been developed to study DNA-protein complexes by mobility-shift assay. This method is at least 100 times more sensitive than conventional gel mobility-shift procedures. Key features of the technique include the use of a neutral coated capillary, a small amount of linear polymer in the separation medium, and use of covalently dye-labeled DNA probes that can be detected with a commercially available laser-induced fluorescence monitor. The capillary method provides quantitative data in runs requiring < 20 min, from which dissociation constants are readily determined. As a test case we studied interactions of a developmentally important sea urchin embryo transcription factor, SpP3A2. As little as 2-10 x 10(6) molecules of specific SpP3A2-oligonucleotide complex were reproducibly detected, using recombinant SpP3A2, crude nuclear extract, egg lysates, and even a single sea urchin egg lysed within the capillary column.
O‐acetylation of GD3 prevents its apoptotic effect and promotes survival of lymphoblasts in childhood acute lymphoblastic leukaemia (2008)

We have previously demonstrated induction of O-acetylated sialoglycoproteins on lymphoblasts of childhood acute lymphoblastic leukaemia (ALL). These molecules promote survival of lymphoblasts by preventing apoptosis. Although O-acetylated sialoglycoproteins are over expressed, the status of O-acetylation of gangliosides and their role in lymphoblasts survival remains to be explored in ALL patients. Here, we have observed enhanced levels of 9-O-acetylated GD3 (9-O-AcGD3) in the lymphoblasts of patients and leukaemic cell line versus disialoganglioside GD3 in comparison to the normal cells. Localization of GD3 and 9-O-AcGD3 on mitochondria of patient's lymphoblasts has been demonstrated by immuno-electron microscopy. The exogenous administration of GD3-induced apoptosis in lymphoblasts as evident from the nuclear fragmentation and sub G0/G1 apoptotic peak. In contrast, 9-O-AcGD3 failed to induce such apoptosis. We further explored the mitochondria-dependent pathway triggered during GD3-induced apoptosis in lymphoblasts. GD3 caused a time-dependent depolarization of mitochondrial membrane potential, release of cytochrome c and 7.4- and 8-fold increased in caspase 9 and caspase 3 activity respectively. However, under identical conditions, an equimolar concentration of 9-O-AcGD3 failed to induce similar effects. Interestingly, 9-O-AcGD3 protected the lymphoblasts from GD3-induced apoptosis when administered in equimolar concentrations simultaneously. In situ de-O-acetylation of 9-O-AcGD3 with sodium salicylate restores the GD3-responsiveness to apoptotic signals. Although both GD3 and 9-O-acetyl GD3 localize to mitochondria, these two structurally related molecules may play different roles in ALL-disease biology. Taken together, our results suggest that O-acetylation of GD3, like that of O-acetylated sialoglycoproteins, might be a general strategy adopted by leukaemic blasts towards survival in ALL.
Differences between adult and pediatric septic shock. (2011)

Sepsis is a significant public health problem that affects children and adults alike. Despite some similarities in the approach to pediatric and adult septic shock, there are key differences as it relates to pathophysiology, clinical presentation, and therapeutic approaches. In this review article, we discuss these differences under 4 headings: a) Developmental differences in the hemodynamic response, b) Activated Protein C, c) Thrombocytopenia associated multiple organ failure and d) Hemophagocytic Lymphohistiocytosis (HLH).
Bee Venom Phospholipase Inhibits Malaria Parasite Development in Transgenic Mosquitoes (2002)

Malaria kills millions of people every year, and new control measures are urgently needed. The recent demonstration that (effector) genes can be introduced into the mosquito germ line to diminish their ability to transmit the malaria parasite offers new hope toward the fight of the disease (Ito, J., Ghosh, A., Moreira, L. A., Wimmer, E. A. & Jacobs-Lorena, M. (2002) Nature, 417, 452-455). Because of the high selection pressure that an effector gene imposes on the parasite population, development of resistant strains is likely to occur. In search of additional antiparasitic effector genes, we have generated transgenic Anopheles stephensi mosquitoes that express the bee venom phospholipase A2 (PLA2) gene from the gut-specific and blood-inducible Anopheles gambiae carboxypeptidase (AgCP) promoter. Northern blot analysis indicated that the PLA2 mRNA is specifically expressed in the guts of transgenic mosquitoes with peak expression at approximately 4 h after blood ingestion. Western blot and immunofluorescence analyses detected PLA2 protein in the midgut epithelia of transgenic mosquitoes from 8 to 24 h after a blood meal. Importantly, transgene expression reduced Plasmodium berghei oocyst formation by 87% on average and greatly impaired transmission of the parasite to naive mice. The results indicate that PLA2 may be used as an additional effector gene to block the development of the malaria parasite in mosquitoes.
DNA duplex–quadruplex exchange as the basis for a nanomolecular machine (2003)

There is currently great interest in the design of nanodevices that are capable of performing linear or rotary movements. Protein molecular machines are abundant in biology but it has recently been proposed that nucleic acids could also act as nanomolecular machines in model systems. Several types of movements have been described with DNA machines: rotation and "scissors-like" opening and closing. Here we show a nanomachine that is capable of an extension-contraction movement. The simple and robust device described here is composed of a single 21-base oligonucleotide and relies on a duplex-quadruplex equilibrium that may be fueled by the sequential addition of DNA single strands, generating a DNA duplex as a by-product. The interconversion between two well defined topological states induces a 5-nm two-stroke, linear motor-type movement, which is detected by fluorescence resonance energy transfer spectroscopy.