gebhart/patrepeval huggingface dataset:
B lymphocyte deficiency in IgH‐transgenic rabbits (2007)

We developed IgH-transgenic rabbits carrying a productive VDJ-Cmu Tg and found the rabbits were B cell-deficient, with a 50-100% reduction in serum IgM and IgG levels. The bone marrow of newborn Tg rabbits contained severely reduced levels of preB cells and almost no B cells. The few preB cells present in the bone marrow were large, cycling cells that expressed the VDJ-Cmu Tg, indicating that the block in B cell development likely occurred at or before the transition from large (early) preB to small (late) preB cells. By immunoprecipitation, the Tg mu-chain paired with VpreB and lambda5, suggesting that the B cell deficiency is not due to an inability to form a preB cell receptor. Despite the block in B cell development, a few B cells, expressing predominantly endogenous mu-chains, began the second stage of development in GALT. B cells were localized in and beneath the follicle-associated epithelium of GALT prior to B cell follicle formation, suggesting to us that B cell follicle formation is initiated near the follicle-associated epithelium, possibly through contact with intestinal microbiota. These IgH-Tg rabbits should provide a useful model for studies of B cell development both in bone marrow and in GALT.
Changes in plasma renin activity and haemodynamics during vasodilator therapy in conscious dogs with myocardial infarction or chronic volume overload (1983)

The aim of the study was to compare the changes in plasma renin activity induced by a vasodilator in normal dogs and in dogs with an impaired cardiac reserve. In normal conscious dogs, a 60-min nitroprusside infusion increased plasma renin activity from 1.05 +/- 0.26 to 8.35 +/- 1.20 ng, angiotensin I ml-1 h-1 (P less than 0.002) and heart rate from 83 +/- 6 to 149 +/- 15 beats/min (P less than 0.002). In five dogs in which a aortocaval fistula had been created 4 weeks earlier, the same infusion still increased plasma renin activity but significantly less than in normal dogs (0.90 +/- 0.29 to 4.44 +/- 0.64 ng ml-1 h-1; P less than 0.01) and the heart rate was unchanged (134 +/- 4 to 139 +/- 7 beats/min; NS). Similarly, in five dogs with a previous myocardial infarction, the heart rats response to nitroprusside was blunted (108 to 107 beats/min;NS) and plasma renin activity increased less than in normal dogs. Plasma renin activity also increased acutely after hydralazine administration in dogs which myocardial infarction (1.05 +/- 0.26 to 8.99 +/- 0.79 ng ml-1 h-1; P less than 0.05); after 1 week of hydralazine, plasma volume had increased from 54.9 +/- 0.9 ml kg-1 to 74.5 +/- 4.9 ml kg-1 (P less than 0.05) and plasma renin activity remained higher than control (4.66 +/- 0.66 ng ml-1 h-1; P less than 0.01). In conclusion, vasodilator therapy rapidly activates vasoconstrictor forces and fluid retention even in dogs with limited cardiac reserve. Although the regulation of plasma renin secretion appears altered in these models of heart disease, the renin response remains sufficient to seriously limit the beneficial effects of vasodilator therapy.
Murine CD200+CK7+ trophoblasts in a poly (I:C)-induced embryo resorption model (2005)

Cytokeratin 7 (CK7) is currently regarded as the best marker for trophoblast cells, while CD200 (OX-2), known as 'tolerance signal', plays an important role in normal pregnancy. In this study, the status of CD200 expression was investigated in BALB/c x C57BL/6 and BALB/c x BALB/c mating combinations designed as allogeneic and syngeneic murine models of induced embryo resorption, in which the resorption rate was boosted by an i.p. injection of poly (I:C), a synthetic double-stranded RNA. The percentage of CD200+ cells in the CK7+ cell population (CD200+ CK7+ percentage) and the absolute number of these cells were determined with flow cytometry, using trophoblast cells collected at day 8.5 and day 13.5 of gestation. The potential effect of poly (I:C) on CD200 expression was also evaluated by detecting the CD200+ CK7+ percentage in trophoblast cells incubated in the presence or absence of poly (I:C), in vitro. The distribution pattern of CD200+ cells at the feto-maternal interface was evaluated by immunocytochemical examination. When 10(4) cells were analyzed at day 8.5 of gestation in each case, no significant difference was observed between the poly (I:C)-treated group and the control PBS group either in the CD200+ CK7+ percentage or in the absolute number of these cells. Similar results were observed both in BALB/c x C57BL/6 mice and in BALB/c x BALB/c mice. However, the CD200+ CK7+ percentage was significantly decreased in the poly (I:C)-treated group when evaluated at day 13.5 of gestation. Accordingly, a dramatically elevated rate of embryo resorption was observed at this time point of pregnancy after the administration of poly (I:C). In addition, the CD200+ CK7+ percentage was significantly lower in trophoblast cells incubated with poly (I:C) at a certain concentration, in vitro, while histocytochemical examination showed the CD200+ cells mainly scattered in placental tissue adjacent to the interface of the placenta and uterus. This indicates that sufficient expression of the CD200 molecule on CK7+ cells at the feto-maternal interface may be necessary for the maintenance of embryos during pregnancy in this rodent model, while poly (I:C) administration may increase embryo resorption, at least partially via direct inhibition of CD200 expression on CK7+ cells.
3-Dimensional Brain Source Imaging by Means of Laplacian Weighted Minimum Norm Estimate in a Realistic Geometry Head Model (2005)

We investigated the source localization performance of the Laplacian weighted minimum norm (LWMN) estimate technique in a realistic geometry (RG) head model in the present study. We simulated current sources at different brain regions with various noise levels. The present results show there is no obvious depth dependency on the three-dimensional (3D) source estimation. The average source localization error over all simulated cases is about 10 mm. The tangential sources exhibit larger localization errors than the radial sources when they are close to the epicortical surface. The localization error will increase when the noise level increases. The LWMN technique was applied to source imaging of motor potentials induced by finger movement in a human subject. Both activities in the motor and premotor cortex, which are related to the execution and coordinating of the finger movement, were reconstructed by the LWMN technique. The present study suggests that LWMN has great ability in 3D sources imaging.
Cytotoxic Isoprenylated Flavans of Broussonetia kazinoki (1998)

Two new prenylflavans [kazinols Q (1) and R (2)] and five known compounds [kazinols D (3), K (4), and H, 7,4'-dihydroxyflavan (5), and oleanolic acid] were isolated from the root bark of Broussonetia kazinoki. The cytotoxic activity of 1-5 was evaluated against several different cell lines.
Calicheamicin Derivatives Conjugated to Monoclonal Antibodies:  Determination of Loading Values and Distributions by Infrared and UV Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry and Electrospray Ionization Mass Spectrometry (1997)

Calicheamicin derivatives (MW approximately 1500) and monoclonal antibodies (MoAbs) conjugated to calicheamicin derivatives (MW approximately 150,000) were analyzed by UV-MALDI/MS, IR-MALDI/MS, and ESI/MS. These materials are potent anticancer agents. Calicheamicin derivatives and conjugates rapidly degrade upon UV irradiation but are relatively stable during IR irradiation and under ESI conditions. A unique feature of IR-MALDI/MS is a 2 times enhancement in resolution relative to UV-MALDI/MS for masses above approximately 50,000 Da resulting in a molecular ion envelope containing a series of partially resolved peaks of the calicheamicin-MoAb conjugates. The mass shift difference between the peak maxima corresponded to the mass change due to the covalent addition of calicheamicin derivatives to the monoclonal antibody. The distribution of the calicheamicin derivatives in the monoclonal antibodies was computed by deconvoluting the partially resolved peak envelope. A unique feature of the ESI mass spectra, under unit resolution conditions, is that the distribution of the carbohydrates can be well resolved for pure MoAbs and can be only partially resolved for conjugated MoAbs. Average loading values for calicheamicia derivatives when conjugated to MoAbs were computed from UV-MALDI/MS, IR-MALDI/MS, and ESI/MS data and the results compared with the average loading values obtained by UV absorption spectrometry. Very low average loading values were computed from UV-MALDI/MS data due to the degradation of the conjugated calicheamicin derivatives during the UV irradiation process. The IR-MALDI/MS average loading values, obtained with glycerol as the matrix, were consistent with the UV absorption spectrometry values for conjugates having hydrolytically stable linkers, but not when the linker contained a hydrolytically labile hydrazone. ESI/MS average loading values were generally lower than the corresponding values obtained by IR-MALDI/MS. The average loading values and distributions obtained using IR-MALDI/MS were more reliable than the corresponding ESI/MS values because the partially resolved, singly and doubly charged peaks in the IR-MALDI spectra can be mathematically deconvoluted, while the overlapping, highly multiply charged peaks of the electrospray spectra can only be partially deconvoluted.
A continuous-flow sample probe for fast atom bombardment mass spectrometry (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA continuous-flow sample probe for fast atom bombardment mass spectrometryRichard M. Caprioli, Terry. Fan, and John S. CottrellCite this: Anal. Chem. 1986, 58, 14, 2949–2954Publication Date (Print):December 1, 1986Publication History Published online1 May 2002Published inissue 1 December 1986https://doi.org/10.1021/ac00127a012RIGHTS & PERMISSIONSArticle Views237Altmetric-Citations292LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (672 KB) Get e-Alerts Get e-Alerts
Reliability Assessment Using Discriminative Sampling and Metamodeling (2005)

Reliability assessment is the foundation for reliability engineering and reliability-based design optimization. It has been a difficult task, however, to perform both accurate and efficient reliability assessment after decades of research. This work proposes an innovative method that deviates significantly from conventional methods. It applies a discriminative sampling strategy to directly generate more points close to or on the limit state. A sampling guidance function was developed for such a strategy. Due to the dense samples in the neighborhood of the limit state, a kriging model can be built which is especially accurate near the limit state. Based on the kriging model, reliability assessment can be performed. The proposed method is tested by using well-known problems in the literature. It is found that it can efficiently assess the reliability for problems of single failure region and has a good performance for problems of multiple failure regions. The features and limitations of the method are also discussed, along with the comparison with the importance sampling (IS) based assessment methods.
Expression of Hemin Receptor Molecule ChuA Is Influenced by RfaH in Uropathogenic Escherichia coli Strain 536 (2001)

The outer membrane protein ChuA responsible for hemin utilization has been recently identified in several pathogenic Escherichia coli strains. We report that the regulatory protein RfaH influences ChuA expression in the uropathogenic E. coli strain 536. In an rfaH mutant, the chuA transcript as well as the ChuA protein levels were significantly decreased in comparison with those in the wild-type strain. Within the chuA gene, a consensus motif known as the JUMPStart (just upstream of many polysaccharide associated gene starts) sequence was found, which is shared by RfaH-affected operons. Furthermore, the presence of two different subclasses of the chuA determinant and their distribution in E. coli pathogroups are described.
Interferon prevents the generation of spontaneous deletions at the left terminus of vaccinia virus DNA (1985)

In this report we have shown that Friend erythroleukemia cells persistently infected with vaccinia virus maintain the persistent infection even after 1 year of continuous interferon (IFN) treatment. The persistently infected cultures were responsive to IFN as determined by their ability to induce 2-5A synthetase, to increase the intracellular levels of 2-5A, and to cause rRNA cleavage. While large deletions at the left terminus of vaccinia DNA occurred readily in the virus population from untreated cells, IFN completely suppressed the generation of these spontaneous deletions. Removal of IFN from these cultures led to the appearance of similar deletions at the left terminus of the viral genome. The regions deleted contain more than half of the left-end inverted terminal repetition of the vaccinia genome. These findings show that IFN alters specific events associated with the generation of vaccinia DNA deletions.
Hepatitis B virus mutants associated with 3TC and famciclovir administration are replication defective (1998)

Hepatitis B virus (HBV) variant strains may develop during therapy for chronic infection with the nucleoside analog 2′,3′-dideoxy-3′-thiacytidine (3TC). HBV mutants result from isoleucine (I) or valine (V) substitutions in the methionine (M) of the YMDD motif in the viral reverse-transcriptase catalytic domain. In addition, other mutations in the reverse-transcriptase “B domain” involving either a phenylalanine (F)-to-leucine (L) at amino acid 501 (F501L) or an L-to-M substitution at amino acid 515 (L515M) have been observed during 3TC and Famciclovir therapy as well. To determine the biologic consequences of these mutations on viral replication, variant viral genomes were constructed and transiently transfected into hepatocellular carcinoma (HCC) and HEK 293 human embryo kidney-derived cell lines. In transiently transfected HCC cells, the viruses bearing the YI/VDD or F501L mutations had greatly impaired replication as compared to wild-type virus, whereas the virus carrying the L515M substitution showed the least defect. Double mutants with the L515M substitution showed intermediate defect between the YI/VDD or F501L and the L515M single-mutant strains. In contrast, when transfected into HEK 293 cells, the viruses bearing the YI/VDD or L515M mutation replicated as wild-type. However, under conditions of deoxynucleotide depletion produced by hydroxyurea treatment of HEK 293 cells, all mutants but not the wild-type virus exhibited a reduced replication phenotype similar to that observed in HCC cells. In both HCC and HEK 293 cells, the mutant viruses carrying the F501L substitution showed a decreased pregenomic RNA encapsidation level, suggesting that the defect in HBV DNA synthesis occurs at the RNA packaging level. These findings show that 3TC and Famciclovir selected mutations alter the properties of the HBV reverse transcriptase, resulting in impaired viral replication within the cell.
Adenine Nucleosides in Solution: Stabilisation of the anti‐Conformation by C‐5′ Substituents (1974)

Proton magnetic resonance spectra of 30 adenine nucleosides have been obtained in dilute (0.001 to 0.05 M) aqueous or dimethyl sulfoxide solutions and have been analysed with respect to structure‐dependent variations of the purine proton chemical shifts. In 2 H 2 O the resonance signal of H‐8 shows a marked dependence upon the nature of substituents linked to C‐4′ of adenine ribofuranoside derivatives and upon the presence of a 2′: 3′‐ O ‐isopropylidene group while H‐2 is relatively unaffected. Therefore the chemical shift difference, δH‐8–δH‐2 =Δδ, may serve as an indicator of intramolecular ribose‐base interact ons. Δδ varies with the chemical nature of C‐4′ or C‐5′ substituents in the order: ammonium, sulfonium (0 ppm) &lt; hydrogen &lt; hydroxyl ∼ amino &lt; thio &lt; halogen &lt; phosphate, carboxylate (0.4 ppm), and decreases with increasing chain length of these substituents. These results suggest the existence of electrostatic and dipolar repulsion or, in the majority of cases, attractive forces between the C‐5′ and C8‐H regions of adenine nucleosides which have been previously demonstrated for 5′‐nucleotides only. They imply a strong preference of most adenosine derivatives with unsubstituted 2′ and 3′‐hydroxyl groups for the anti ‐conformation range and the gauche, gauche C‐5′ conformation. In dimethyl sulfoxide, basically the same situation exists but different substituents exhibit smaller individual Δδ variations than in water, indicating different solvation shells. In this solvent two additional conformation‐stabilizing contributions can be recognized, viz. an interaction of the bridge oxygen (O‐4′) of ribose with adenine, and a hydrogen bond between H‐8 and a 5′‐carboxylate anion. This energetic stabilisation of the anti and g,g ‐conformers by most types of adenosine C‐5′ substituents supports the “rigidity” concept of nucleotides, extending it to the nucleoside level. The only exception found is 5′‐nitromethyladenosine in which ultraviolet, circular dichroism and magnetic resonance spectra suggest rotation of the adenine base to a “non‐classical” conformation due to base‐chain π‐electron interaction. The anti ‐conformation of the adenosine derivatives used in this study can in some cases be correlated with their enzymatic deamination by adenosine and AMP aminohydrolase.
Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons (2008)

Alzheimer's disease (AD) is associated with regional reductions in fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the cerebral metabolic rate for glucose, which may begin long before the onset of histopathological or clinical features, especially in carriers of a common AD susceptibility gene. Molecular evaluation of cells from metabolically affected brain regions could provide new information about the pathogenesis of AD and new targets at which to aim disease-slowing and prevention therapies. Data from a genome-wide transcriptomic study were used to compare the expression of 80 metabolically relevant nuclear genes from laser-capture microdissected non-tangle-bearing neurons from autopsy brains of AD cases and normal controls in posterior cingulate cortex, which is metabolically affected in the earliest stages; other brain regions metabolically affected in PET studies of AD or normal aging; and visual cortex, which is relatively spared. Compared with controls, AD cases had significantly lower expression of 70% of the nuclear genes encoding subunits of the mitochondrial electron transport chain in posterior cingulate cortex, 65% of those in the middle temporal gyrus, 61% of those in hippocampal CA1, 23% of those in entorhinal cortex, 16% of those in visual cortex, and 5% of those in the superior frontal gyrus. Western blots confirmed underexpression of those complex I-V subunits assessed at the protein level. Cerebral metabolic rate for glucose abnormalities in FDG PET studies of AD may be associated with reduced neuronal expression of nuclear genes encoding subunits of the mitochondrial electron transport chain.
MicroRNA Profiling by Simultaneous Selective Isotachophoresis and Hybridization with Molecular Beacons (2011)

We present and demonstrate a novel assay for the detection and quantification of microRNA (miRNA) that leverages isotachophoresis (ITP) and molecular beacon (MB) hybridization. We use ITP to selectively preconcentrate miRNA from total RNA. We simultaneously focus MBs and use the ITP zone as a 10 pL reactor with active mixing where MBs fluoresce upon hybridization to target miRNA. To increase both sensitivity and selectivity, we leverage a multistage ITP strategy composed of three discrete regions of different concentrations of denaturant, sieving matrix, and magnesium chloride. We show that ITP hybridization is specific and selective to the miRNA target. We demonstrate ITP hybridization of miRNA in a biologically relevant case by detecting and quantifying miR-122 in human kidney and liver. ITP hybridization is a cheap, simple, high-speed, and amplification-free miRNA profiling method which requires small amounts (order 100 ng) of sample. The technique therefore represents an attractive alternative to PCR or Northern blot for miRNAs.
In Situ Hybridization with Riboprobes: An Overview for Veterinary Pathologists (1998)

In situ hybridization using nonradioactively-labeled RNA probes is a technique that combines understanding of basic molecular biology and histopathologic interpretation. Recombinant or PCR technology can be used to produce probes that hybridize with a wide variety of cellular genes and infectious agents. Hybridization conditions can be optimized for each probe/target combination.
Allosteric Potentiators of the Metabotropic Glutamate Receptor 2 (mGlu2). Part 1. Identification and Synthesis of Phenyl‐tetrazolyl Acetophenones. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Kinesin ATPase: rate-limiting ADP release. (1988)

The ATPase rate of kinesin isolated from bovine brain by the method of S.A. Kuznetsov and V.I. Gelfand [(1986) Proc. Natl. Acad. Sci. USA 83, 8530-8534)] is stimulated 1000-fold by interaction with tubulin (turnover rate per 120-kDa peptide increases from approximately equal to 0.009 sec-1 to 9 sec-1). The tubulin-stimulated reaction exhibits no extra incorporation of water-derived oxygens over a wide range of ATP and tubulin concentrations, indicating that Pi release is faster than the reversal of hydrolysis. ADP release, however, is slow for the basal reaction and its release is rate limiting as indicated by the very tight ADP binding (Ki less than 5 nM), the retention of a stoichiometric level of bound ADP through ion-exchange chromatography and dialysis, and the reversible labeling of a bound ADP by [14C]ATP at the steady-state ATPase rate as shown by centrifuge gel filtration and inaccessibility to pyruvate kinase. Tubulin accelerates the release of the bound ADP consistent with its activation of the net ATPase reaction. The detailed kinetics of ADP release in the presence of tubulin are biphasic indicating apparent heterogeneity with a fraction of the kinesin active sites being unaffected by tubulin.
Nanometer-Scale Pattern Registration and Alignment by Directed Diblock Copolymer Self-Assembly (2004)

We describe a fabrication method that combines the alignment capabilities of optical lithography with the sub-lithographic dimensions achievable using self-assembled diblock copolymer films. We use surface topography to direct the assembly of in-plane cylindrical copolymer domains so as to subdivide larger patterns defined using optical lithography, in the process registering the location of each 20-nm polymer domain to the lithographic pattern. Our approach provides an application for self-assembly in the fabrication of complex microelectronic circuits entailing alignment of multiple patterned layers. We detail the influence of such process parameters as lithographic pattern dimensions and density, copolymer film thickness, and anneal time on the quality of the resulting nanometer-scale-domain registration.