gebhart/patrepeval huggingface dataset:
Plasma Versus Serum: Specific Differences in Biochemical Analyte Values (2002)

After blood is removed from an animal, the biochemical parameters begin to change immediately. To ensure that results of laboratory tests accurately reflect the true physiologic or pathologic state of an individual, care must be taken to minimize such artifactual changes. It is commonly thought that delayed centrifugation of avian blood may affect analyte values; however, there have been few studies documenting changes. Likewise, the occurrence of changes in blood analyte values during preparation of a standard serum sample has not been investigated formally. This study was conducted to document the differences between analyte values in plasma and serum processed using common standardized protocols. Paired plasma and serum samples were collected from chickens. Plasma samples were kept on ice and centrifuged immediately, and serum samples were allowed to clot at room temperature for 90 minutes and then were centrifuged. The paired plasma and serum samples were simultaneously analyzed for standard biochemical analytes. Significant differences between plasma and serum values were noted for 10 out of the 17 analytes determined. Briefly, serum values for albumin, albumin-globulin ratio, and potassium were much lower than corresponding values for plasma, and the serum chloride concentration was slightly lower than the plasma chloride value. The serum globulin mean concentration was almost 3 times the value for plasma, and serum values for creatine phosphokinase, calcium, magnesium, and phosphorus were higher than their plasma counterparts.
The collection of ions implanted in semiconductors. II. range distributions derived from collection and sputter-etch curves (1972)

Abstract Collection curves for the implantation of the heavy ions Kr and Tl into the semiconductors GaAs, Gap, Ge and Si are analysed using a previously published theory. Sputter-etch experiments in which previously implanted ions are released by further sputtering are also described. The data from both collection and sputter-etch experiments provide information on the implanted ion concentration profile and on the differential ion range probability distribution. Results indicate that the latter distribution is wider than the expected Gaussian and that values of the sputtering coefficient necessary to match the experimental range profiles to the theoretical profiles are far larger than would be expected for target erosion. These results show that other processes than simple target sputtering are important both in determining the saturation of a target in collection experiments and in the erosion of the target to reveal the implant profile in sputter-etch experiments. The very high implant concentrations reached in these studies will have metallurgical effects on the target with a resulting change in the sputtering process.
Interleukin-10–mediated regulatory T-cell responses to epitopes on a human red blood cell autoantigen (2002)

Regulatory T cells have been shown to control animal models of immune-mediated pathology by inhibitory cytokine production, but little is known about such cells in human disease. Here we characterize regulatory T-cell responses specific for a human red blood cell autoantigen in patients with warm-type autoimmune hemolytic anemia. Peripheral blood mononuclear cells from patients with autoimmune hemolytic anemia were found either to proliferate and produce interferon-gamma or to secrete the regulatory cytokine interleukin 10 when stimulated in vitro with a major red blood cell autoantigen, the RhD protein. Flow cytometric analysis confirmed that the majority of the responding cells were of the CD4(+) phenotype. Serial results from individual patients demonstrated that this bias toward proliferative or interleukin-10 responses was unstable over time and could reverse in subsequent samples. Epitope mapping studies identified peptides from the sequence of the autoantigen that preferentially induced interleukin-10 production, rather than proliferation, and demonstrated that many contain naturally processed epitopes. Responses to such peptides suppressed T-cell proliferation against the RhD protein, an inhibition that was mediated largely by interleukin 10 and dependent on cytotonic T lymphocyte-associated antigen (CTLA-4) costimulation. Antigenic peptides with the ability to stimulate specific regulatory cells may represent a new class of therapeutic agents for immune-mediated disease.
Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene eHand during murine heart development. (1997)

One of the first morphological manifestations of left/right (L/R) asymmetry in mammalian embryos is a pronounced rightward looping of the linear heart tube. The direction of looping is thought to be controlled by signals from an embryonic L/R axial system. We report here that morphological L/R asymmetry in the murine heart first became apparent at the linear tube stage as a leftward displacement of its caudal aspect. Beginning at the same stage, the basic helix-loop-helix (bHLH) factor gene eHand was expressed in a strikingly left-dominant pattern in myocardium, reflecting an intrinsic molecular asymmetry. In hearts of embryos lacking the homeobox gene Nkx2-5, which do not loop, left-sided eHand expression was abolished. However, expression was unaffected in Sc1-/- hearts that loop poorly because of hematopoietic insufficiency, and was right-sided in hearts of inv/inv embryos that display situs inversus. The data predict that eHand expression is enhanced in descendants of the left heart progenitor pool as one response to inductive signaling from the L/R axial system, and that eHand controls intrinsic morphogenetic pathways essential for looping. One aspect of the intrinsic response to L/R information falls under Nkx2-5 homeobox control.
Spatially resolved reflectance spectroscopy for diagnosis of cervical precancer: Monte Carlo modeling and comparison to clinical measurements (2006)

We present Monte Carlo modeling studies to provide a quantitative understanding of contrast observed in spatially resolved reflectance spectra of normal and highly dysplastic cervical tissue. Simulations have been carried out to analyze the sensitivity of spectral measurements to a range of changes in epithelial and stromal optical properties that are reported to occur as dysplasia develops and to predict reflectance spectra of normal and highly dysplastic tissue at six different source-detector separations. Simulation results provide important insights into specific contributions of different optical parameters to the overall spectral response. Predictions from simulations agree well with in vivo measurements from cervical tissue and successfully describe spectral differences observed in reflectance measurements from normal and precancerous tissue sites. Penetration depth statistics of photons detected at the six source-detector separations are also presented to reveal the sampling depth profile of the fiber-optic probe geometry simulated. The modeling studies presented provide a framework to meaningfully interpret optical signals obtained from epithelial tissues and to optimize design of optical sensors for in vivo reflectance measurements for precancer detection. Results from this study can facilitate development of analytical photon propagation models that enable inverse estimation of diagnostically relevant optical parameters from in vivo reflectance measurements.
Library‐directed Solution‐ and Solid‐phase Synthesis of 2,4‐Disubstituted Pyridines: One‐pot Approach through 6 π‐Azaelectrocyclization (2009)

An efficient one-pot synthetic procedure for the synthesis of 2,4-disubstituted pyridines has been successfully established. The method proceeds through a 6pi-azaelectrocyclization-aromatization sequence. Using this method, a wide variety of pyridine structures substituted at the 2-position have been rapidly constructed from vinyl stannanes, vinyl iodide, sulfonamide, and a palladium catalyst. The method was further applied to the solid-phase synthesis wherein the use of a "traceless" sulfonamide linker enabled the rapid preparation of a small library of pyridines with high purity, without any chromatographic separation.
Benzothiadiazole induces disease resistance in Arabidopsis by activation of the systemic acquired resistance signal transduction pathway (1996)

Benzothiadiazole (BTH) is a novel chemical activator of disease resistance in tobacco, wheat and other important agricultural plants. In this report, it is shown that BTH works by activating SAR in Arabidopsis thaliana. BTH-treated plants were resistant to infection by turnip crinkle virus, Pseudomonas syringae pv 'tomato' DC3000 and Peronospora parasitica. Chemical treatment induced accumulation of mRNAs from the SAR-associated genes, PR-1, PR-2 and PR-5. BTH treatment induced both PR-1 mRNA accumulation and resistance against P. parasitica in the ethylene response mutants, etr1 and ein2, and in the methyl jasmonate-insensitive mutant, jar1, suggesting that BTH action is independent of these plant hormones. BTH treatment also induced both PR-1 mRNA accumulation and P. parasitica resistance in transgenic Arabidopsis plants expressing the nahG gene, suggesting that BTH action does not require salicylic acid accumulation. However, because BTH-treatment failed to induce either PR-1 mRNA accumulation or P. parasitica resistance in the non-inducible immunity mutant, nim1, it appears that BTH activates the SAR signal transduction pathway.
1H- and 13C-nmr Assignments for Taxol, 7-epi-Taxol, and Cephalomannine (1992)

The 1H- and 13C-nmr spectra of taxol [1], 7-epi-taxol [2], and cephalomannine [3] were assigned using modern 1D and 2D nmr methods. Preliminary conformational information was obtained by nOe spectroscopy.
Activation of human cyclin-dependent kinases in vitro. (1992)

We have analyzed the activation of human cyclin-dependent kinases in a cell-free system. Human CDC2, cyclin-dependent kinase 2 (CDK2), cyclin A, and cyclin B1 were produced in insect cells by infection with recombinant baculoviruses. CDC2 or CDK2 monomers in lysates of infected cells could be activated by the addition of lysates containing cyclin A or B1. CDC2 activation by cyclin B1, as well as CDK2 activation by cyclins A and B1, was accompanied by the formation of high molecular weight complexes. In contrast, CDC2 did not bind effectively to cyclin A. CDC2 activation by cyclin B1 was studied in detail and was found to be accompanied by phosphorylation of CDC2 on Threonine 161. The binding of CDC2 to cyclin B1 also occurred under conditions where CDC2 phosphorylation was prevented, resulting in an inactive complex that could then be phosphorylated and activated on addition of cell extract. Highly purified CDC2 and cyclin B1 also formed inactive complexes that could be activated in an ATP-dependent fashion by unidentified components in crude cell extracts. These data suggest that the CDC2 activation process begins with cyclin binding, after which CDC2 phosphorylation, catalyzed by a separate enzyme, leads to activation.
Polymorphisms in the Insulin-Degrading Enzyme Gene Are Associated With Type 2 Diabetes in Men From the NHLBI Framingham Heart Study (2003)

Linkage studies have mapped a susceptibility gene for type 2 diabetes to the long arm of chromosome 10, where we have previously identified a quantitative trait locus that affects fasting blood glucose within the Framingham Heart Study cohort. One candidate gene in this region is the insulin-degrading enzyme (IDE), which, in the GK rat model, has been associated with nonobese type 2 diabetes. Single nucleotide polymorphisms (SNPs) were used to map a haplotype block in the 3' end of IDE, which revealed association with HbA(1c), fasting plasma glucose (FPG), and mean fasting plasma glucose (mFPG) measured over 20 years. The strongest associations were found in a sample of unrelated men. The lowest trait values were associated with a haplotype (TT, f approximately 0.32) containing the minor allele of rs2209772 and the major allele of the rs1887922 SNP (FPG P < 0.001, mFPG P < 0.003, HbA(1c) P < 0.025). Another haplotype (CC, f approximately 0.16) was associated with elevated HbA(1c) (P < 0.002) and type 2 diabetes (P < 0.001, odds ratio 1.96, 95% CI 1.28-3.00). The evidence presented supports the possibility that IDE is a susceptibility gene for diabetes in populations of European descent.
PPARγ Activation: A Potential Treatment For Pulmonary Hypertension (2009)

The pathobiology of pulmonary arterial hypertension (PAH) involves multiple molecular pathways and environmental modifiers and is characterized by progressive obliteration of pulmonary arterioles, leading to increased pulmonary vascular resistance (PVR), right heart failure, and death in approximately 40 to 60% of patients 5 years after diagnosis. There is emerging evidence that many key genes involved in PAH development are targets of the insulin-sensitizing transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma), and that pharmacological PPARgamma activation would lead to their beneficial induction or repression and subsequent antiproliferative, anti-inflammatory, proapoptotic, and direct vasodilatory effects in the vasculature. PPARgamma acts downstream of bone morphogenetic protein receptor II (BMP-RII), which is the cell surface receptor that is mutated or dysfunctional in many forms of PAH. Because our recent clinical observations indicate that insulin resistance may be an environmental risk factor or disease modifier ("second hit"), we suggest that PPARgamma-activating agents might be beneficial in the future treatment of both insulin-resistant and insulin-sensitive PAH patients with or without BMP-RII mutations.
Ex Vivo Expansion of CD4+CD25+FoxP3+ T Regulatory Cells Based on Synergy between IL-2 and 4-1BB Signaling (2007)

Naturally occurring CD4(+)CD25(+)FoxP3(+) T regulatory (Treg) cells require three distinct signals transduced via TCR, CD28, and IL-2R for their development and maintenance. These requirements served as the basis for several recently developed ex vivo expansion protocols that relied on the use of solid support-bound Abs to CD3 and CD28 in the presence of high dose IL-2. We report in this study that Treg cells up-regulate the expression of inducible costimulatory receptor 4-1BB in response to IL-2, and stimulation using this receptor via a novel form of 4-1BB ligand (4-1BBL) fused to a modified form of core streptavidin (SA-4-1BBL) was effective in expanding these cells up to 110-fold within 3 wk. Expanded cells up-regulated CD25, 4-1BB, and membranous TGF-beta, suppressed T cell proliferation, and prevented the rejection of allogeneic islets upon adoptive transfer into graft recipients. Importantly, SA-4-1BBL rendered CD4(+)CD25(-) T effector cells refractive to suppression by Treg cells. This dual function of signaling via 4-1BB, vis-à-vis Treg cell expansion and licensing T effector cells resistant to Treg cell suppression, as well as the up-regulation of 4-1BB by IL-2 may serve as important regulatory mechanisms for immune homeostasis following antigenic challenge. Stimulation using a soluble form of SA-4-1BBL represents a novel approach to expand Treg cells with potential therapeutic applications in autoimmunity and transplantation.
Diels–Alder Ligation of Peptides and Proteins (2006)

Abstract The development of the Diels–Alder cycloaddition as a new method for the site‐specific chemoselective ligation of peptides and proteins under mild conditions is reported. Peptides equipped with a 2,4‐hexadienyl ester and an N‐terminal maleimide react in aqueous media to give cycloadducts in high yields and depending on the amino acid sequence with high stereoselectivity. Except for the cysteine SH group the transformation is compatible with all amino acid side chain functional groups. For ligation to proteins the hexadienyl group was attached to avidin and streptavidin noncovalently by means of complex formation with a biotinylated peptide or by covalent attachment of a hexadienyl ester‐containing label to lysine side chains incorporated into the proteins. Site‐specific attachment of the hexadienyl unit into a Rab protein was achieved by means of expressed protein ligation followed by protection of the generated cysteine SH by means of Ellman's reagent. The protein reacted with different maleimido‐modified peptides under mild conditions to give the fully functional cycloadducts in high yield. The results demonstrate that the Diels–Alder ligation offers an advantageous and technically straightforward new opportunity for the site‐specific equipment of peptides and proteins with further functional groups and labels. It proceeds under very mild conditions and is compatible with most functional groups found in proteins. Its combination with other ligation methods, in particular expressed protein ligation is feasible.
Effect of ghrelin on septic shock in rats. (2003)

Treatment with ghrelin could correct partly the abnormalities of hemodynamics and metabolic disturbance in septic shock of rats.
High-Performance Real-Time Quantitative RT-PCR Using Lanthanide Probes and a Dual-Temperature Hybridization Assay (2002)

We report a time-resolved fluorescence-based, homogeneous approach for multiplex, real-time or end-point detection of PCR products. Signal generation consists of PCR associated digestion of a 5'-labeled oligonucleotide probe, rapid cooling of the reaction mixture, and hybridization of undigested probe oligonucleotides with a complementary, shorter probe that incorporates a quencher at its 3' end. The signal coming from intact fluorescent probe molecules is, thus, quenched. The fluorophores we have used are environmentally sensitive lanthanide chelates. Their signals can be measured in a time-resolved manner that eliminates most of the unspecific fluorescent background. Signal-to-noise ratios are further enhanced by the environmental sensitivity of these chelates; they exhibit a higher fluorescence intensity when free in solution than when coupled to intact probe molecules. Because of the minimal background fluorescence, the signal-to-noise ratios are higher and threshold cycles are lower than those obtained using conventional TaqMan probes. The multiplexing capacity of the assay chemistry is demonstrated through simultaneous amplification and detection of prostate specific antigen (PSA) cDNA and an internal standard mRNA (mmPSA) using probes labeled with terbium and europium. The applicability of the assay chemistry to routine clinical diagnostics is demonstrated through absolute quantification of PSA mRNA in peripheral blood.
Low pH hydrothermal synthesis and properties of lanthanide-organic frameworks with (410,65)(49,66) topology constructed from Ln-Hbptc building blocks (2007)

Two novel lanthanide-organic frameworks (LnOFs) with (4(10),6(5))(4(9),6(6)) topology, [Ln(Hbptc)(H(2)O)](n) (Ln = Eu(1), Gd(2); H(4)bptc = 3,3',4,4'-biphenyltetracarboxylic acid) were synthesized via the hydrothermal in situ reaction between lanthanide salts and 3,3',4,4'-biphenyltetracarboxylic dianhydride (bpta) under low pH conditions. In complexes 1 and 2, homohelix bundles with opposite chirality are assembled alternately and result in pillar-like 3D extended networks incorporated with coordinated water molecules, which show high thermal stability. The luminescence properties are illustrated by the Eu(III) complex (1) and its Gd-doped compound, which are intensive red emitters. The magnetic properties of complexes 1 and 2 are also investigated.
Elimination of Ligation Dependent Artifacts in T4 RNA Ligase to Achieve High Efficiency and Low Bias MicroRNA Capture (2014)

Adapter ligation is a critical first step in many microRNA analysis methods including microarray, qPCR, and sequencing. Previous studies have shown that ligation bias can have dramatic effects on both the fidelity of expression profiles and reproducibility across samples. We have developed a method for high efficiency and low bias microRNA capture by 3' adapter ligation using T4 RNA ligase that does not require pooled adapters. Using a panel of 20 microRNA, we investigated the effects of ligase type, PEG concentration, ligase amount, adapter concentration, incubation time, incubation temperature, and adapter design on capture efficiency and bias. Of these factors, high PEG% was found to be critical in suppressing ligation bias. We obtained high average capture efficiency and low CV across the 20 microRNA panel, both in idealized buffer conditions (86% ± 10%) and total RNA spiking conditions (64% ± 17%). We demonstrate that this method is reliable across microRNA species that previous studies have had difficulty capturing and that our adapter design performs significantly better than the common adapter designs. Further, we demonstrate that the optimization methodology must be specifically designed for minimizing bias in order to obtain the ideal reaction parameters.
Role of preterminal protein processing in adenovirus replication (1997)

Preterminal protein (pTP), the protein primer for adenovirus DNA replication, is processed at two sites by the virus-encoded protease to yield mature terminal protein (TP). Here we demonstrate that processing to TP, via an intermediate (iTP), is conserved in all serotypes sequenced to date; and in determining the sites cleaved in Ad4 pTP, we extend the previously published substrate specificity of human adenovirus proteases to include a glutamine residue at P4. Furthermore, using monoclonal antibodies raised against pTP, we show that processing to iTP and TP are temporally separated in the infectious cycle, with processing to iTP taking place outside the virus particles. In vitro and in vivo studies of viral DNA replication reveal that iTP can act as a template for initiation and elongation and argue against a role for virus-encoded protease in switching off DNA replication. Virus DNA with TP attached to its 5' end (TP-DNA) has been studied extensively in in vitro DNA replication assays. Given that in vivo pTP-DNA, not TP-DNA, is the template for all but the first round of replication, the two templates were compared in vitro and shown to have different properties. Immunofluorescence studies suggest that a region spanning the TP cleavage site is involved in defining the subnuclear localization of pTP. Therefore, a likely role for the processing of pTP-DNA is to create a distinct template for early transcription (TP-DNA), while the terminal protein moiety, be it TP or pTP, serves to guide the template to the appropriate subcellular location through the course of infection.
Titration-free massively parallel pyrosequencing using trace amounts of starting material (2010)

Continuous efforts have been made to improve next-generation sequencing methods for increased robustness and for applications on low amounts of starting material. We applied double-stranded library protocols for the Roche 454 platform to avoid the yield-reducing steps associated with single-stranded library preparation, and applied a highly sensitive Taqman MGB-probe-based quantitative polymerase chain reaction (qPCR) method. The MGB-probe qPCR, which can detect as low as 100 copies, was used to quantify the amount of effective library, i.e. molecules that form functional clones in emulsion PCR. We also demonstrate that the distribution of library molecules on capture beads follows a Poisson distribution. Combining the qPCR and Poisson statistics, the labour-intensive and costly titration can be eliminated and trace amounts of starting material such as precious clinical samples, transcriptomes of small tissue samples and metagenomics on low biomass environments is applicable.