gebhart/patrepeval huggingface dataset:
A protocol for initiating oestrus and ovulation earlypost partumin dairy cows (2001)

Abstract The objective of the present study was to evaluate the efficacy of a prostaglandin F 2α (PGF 2α ) and progesterone (P4) treatment in initiating oestrus and ovulation post partum (PP) in Holstein-Friesian cows. Using four herds, the treatment protocol consisted of a single intra-muscular injection of PGF 2α (Estrumate) between days 12 to 14 PP followed 48 h later by progesterone treatment via intra-vaginal CIDR insertion for a period of 7 days. Milk samples for progesterone determination were collected three times weekly from 7 to 65 days PP. The ovarian activity and reproductive performance of treated (T, no. = 153) animals and untreated control cows (C, no. = 315) were compared. Treatment was effective ( P &lt; 0·001) in reducing the mean interval to PP commencement of luteal activity from 29·62 (s.e. 0·82) days to 22·09 (s.e. 0·70) days. The mean interval to first PP oestrus in the T animals was significantly reduced ( P &lt; 0·001) from 55·62 (s.e. 1·58) days to 44·91 (s.e. 1·44) days and the incidence of silent ovulation in cycles between days 21 to 65 PP was reduced ( P &lt; 0·001) from 56·28% to 42·27%. In two herds under one management regime and with a similar block-calving pattern (no. = 280 animals), the treatment protocol was beneficial to the overall reproductive performance as there was a significant shortening in the mean interval to first PP service (75·82 (s.e. 1·93) v. 80·86 (s.e. 1·32) days) and in the interval to PP conception (83·07 (s.e. 2·49) v. 88·90 (s.e. 1·95) days), both P &lt; 0·05.
Measurement of non-rigid motion using contour shape descriptors (2002)

The problem of measuring the motion of deformable objects from image sequences is addressed. The approach is based upon modeling the overall boundary of the object as a deformable contour and then tracking local segments of the contour through the temporal sequence. Motion computation involves first matching the local segments between pairs of contours by minimizing the deformation between the segments using a measure of bending energy. Results from the match process are incorporated into an optimization functional, along with a general smoothness term, whose local minimum results in a smooth flow field that is consistent with the match data. The computation is performed for all pairs of frames in the temporal sequence, resulting in a composite flow field over the entire sequence. The technique is applied to synthetic contour sequences and the problem of tracking left ventricular (LV) endocardial motion from medical image sequences.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Strength of TCR–Peptide/MHC Interactions and In Vivo T Cell Responses (2011)

The TCR can detect subtle differences in the strength of interaction with peptide/MHC ligand and transmit this information to influence downstream events in T cell responses. Manipulation of the factor commonly referred to as TCR signal strength can be achieved by changing the amount or quality of peptide/MHC ligand. Recent work has enhanced our understanding of the many variables that contribute to the apparent cumulative strength of TCR stimulation during immunogenic and tolerogenic T cell responses. In this review, we consider data from in vitro studies in the context of in vivo immune responses and discuss in vivo consequences of manipulation of strength of TCR stimulation, including influences on T cell-APC interactions, the magnitude and quality of the T cell response, and the types of fate decisions made by peripheral T cells.
Self‐Assembled Microarrays of Attoliter Molecular Vessels (2003)

High-density microarrays of attoliter volume elements can be created (see figure) within minutes in a parallel and effortless manner by using self-assembly of nanometer-size components based on biological recognition. These ultrasmall volumes allow localization of single molecules, screening for (bio)chemical properties, and assessing the performance of confined chemical reactions.
Allelotype analysis of mouse lung carcinomas reveals frequent allelic losses on chromosome 4 and an association between allelic imbalances on chromosome 6 and K-ras activation. (1994)

We generated allelotypes of 38 methylene chloride-induced lung carcinomas from female C57BL/6J x C3H/6J F1 (hereafter called B6C3F1) mice. Two or more polymorphic markers per autosome, most of them microsatellites, were examined for loss of heterozygosity. Allelic losses throughout the genome were generally infrequent except for markers on chromosome 4, which were lost in approximately one-half of the carcinomas. Analysis of lung adenomas indicated that chromosome 4 loss was associated with malignant conversion. In addition, chromosome 4 loss were specific for lung carcinomas based on comparison to methylene chloride-induced liver tumors and additional studies of lung tumors from a variety of treatment protocols and different mouse strains. Preferential loss of the maternal chromosome 4 was observed in B6C3F1 carcinomas. Analyses of additional tumors induced in mice from two reciprocal crosses, A/J x C3H/HeJ F1 (hereafter called AC3F1) and C3H/HeJ x A/J F1 (hereafter called C3AF1), provided evidence for the inactivation of one allele of the putative chromosome 4 tumor suppressor gene by parental imprinting. Most B6C3F1 tumors lost all chromosome 4 markers examined, suggesting nondisjunction events. In contrast, several C3AF1 and AC3F1 tumors appeared to have interstitial deletions that defined the smallest region of overlap as a 9-cM interval between Ifa-2 and D4Nds2. The homologous region on human chromosome 9p21-22 is frequently lost in a variety of tumors including lung cancers. A candidate tumor suppressor gene, MTS1, is located in this region, which is homozygously deleted or mutated in cell lines derived from a variety of human tumors. Finally, an association between K-ras gene activation and allelic imbalances on chromosome 6 was observed for B6C3F1 lung tumors.
Progress in the analysis of membrane protein structure and function (2002)

Structural information on membrane proteins is sparse, yet they represent an important class of proteins that is encoded by about 30% of all genes. Progress has primarily been achieved with bacterial proteins, but efforts to solve the structure of eukaryotic membrane proteins are also increasing. Most of the structures currently available have been obtained by exploiting the power of X-ray crystallography. Recent results, however, have demonstrated the accuracy of electron crystallography and the imaging power of the atomic force microscope. These instruments allow membrane proteins to be studied while embedded in the bi-layer, and thus in a functional state. The low signal-to-noise ratio of cryo-electron microscopy is overcome by crystallizing membrane proteins in a two-dimensional protein-lipid membrane, allowing its atomic structure to be determined. In contrast, the high signal-to-noise ratio of atomic force microscopy allows individual protein surfaces to be imaged at sub-nanometer resolution, and their conformational states to be sampled. This review summarizes the steps in membrane protein structure determination and illuminates recent progress.
Helper virus-free transfer of human immunodeficiency virus type 1 vectors (1995)

Recombinant vectors based on the type 1 human immunodeficiency virus (HIV-1) can be used to deliver genes into cells expressing the HIV receptor, CD4. We have used a transient RNA packaging system to compare the safety and efficacy of HIV-1 vector transduction by wild-type and replication-deficient helper viruses. Helper virus-free vector transfer was consistently achieved when the helper virus gag-pol and env genes were expressed from separate plasmids such that two recombination events were required to form an infectious genome. Other forms of attenuation, such as deletion of the 5' phi region, were inadequate to prevent helper virus transmission. Vector transduction by the wild-type and non-replicating helper viruses occurred with comparable efficiency except in instances where efficient vector RNA expression was dependent upon transactivating factors supplied by the helper virus. These data demonstrate the feasibility of safe gene transfer using HIV-1 vectors.
High Serum Interleukin‐8 Levels in Afro‐Caribbean Women with Pre‐eclampsia. Relations with Tumor Necrosis Factor‐α, Duffy Negative Phenotype and Von Willebrand Factor (2002)

Higher IL-8 levels in pre-eclampsia may result from increased production (secondary to increased TNF-alpha levels) and/or reduced clearance (related to a high frequency of Duffy negative phenotype).
Heparin binding domain peptides of antithrombin III: Analysis by isothermal titration calorimetry and circular dichroism spectroscopy (1994)

The serine proteinase inhibitor antithrombin III (ATIII) is a key regulatory protein of intrinsic blood coagulation. ATIII attains its full biological activity only upon binding polysulfated oligosaccharides, such as heparin. A series of synthetic peptides have been prepared based on the proposed heparin binding regions of ATIII and their ability to bind heparin has been assessed by CD spectrometry, by isothermal titration calorimetry, and by the ability of the peptides to compete with ATIII for binding heparin in a factor Xa procoagulant enzyme assay. Peptide F123-G148, which encompasses both the purported high-affinity pentasaccharide binding region and an adjacent, C-terminally directed segment of ATIII, was found to bind heparin with good affinity, but amino-terminal truncations of this sequence, including L130-G148 and K136-G148 displayed attenuated heparin binding activities. In fact, K136-G148 appears to encompass only a low-affinity heparin binding site. In contrast, peptides based solely on the high-affinity binding site (K121-A134) displayed much higher affinities for heparin. By CD spectrometry, these high-affinity peptides are chiefly random coil in nature, but low microM concentrations of heparin induce significant alpha-helix conformation. K121-A134 also effectively competes with ATIII for binding heparin. Thus, through the use of synthetic peptides that encompass part, if not all, of the heparin binding site(s) within ATIII, we have further elucidated the structure-function relations of heparin-ATIII interactions.
The Reactivity of the Sh Group of Bovine Serum Albumin with Free Radicals (1991)

The reactivity of the SH group of bovine serum albumin (BSA) towards free radicals generated by several different systems including gamma-radiolysis and hydrogen peroxide/metal salt mixtures was investigated. On exposure of BSA (1 mg/ml and 5 mg/ml) to HO. radicals generated radiolytically the protein-SH concentration was found to decrease in a dose-dependent manner. At 40 mg/ml albumin no loss of SH was observed. O2-. and HO2. radicals were much less aggressive towards the SH group. The effect of divalent metal salts (copper or iron) plus hydrogen peroxide was studied separately and in combination. H2O2 alone caused a decrease in SH group concentration the rate of which was not decreased by the presence of desferrioxamine and so was apparently not due to reactions catalysed by adventitious metal ions. Copper alone caused a dose-dependent decrease in SH group concentration and the mixture of the two agents caused a greater loss of SH than each separate component. However, this latter effect was again resistant to the effects of desferrioxamine. The SH group of BSA was only moderately sensitive to the presence of ferrous iron alone and in a system containing both ferrous iron and H2O2 rates of SH oxidation were obtained that were identical to those obtained with H2O2 alone. Desferrioxamine again did not alter the rate of SH oxidation in these experiments. We suggest that the highly reactive free radical HO. is not able to reach and to oxidize the SH group of BSA when generated by metal/H2O2 mixtures, in contrast to HO. generated radiolytically. Less reactive radicals and non-radical species such as H2O2 have more potential for doing so.
Systematic Identification of Placental Epigenetic Signatures for the Noninvasive Prenatal Detection of Edwards Syndrome (2010)

Our data have shown that the methylated VAPA-APCDD1 DNA in maternal plasma is predominantly derived from the fetus. We have demonstrated that this novel fetal epigenetic marker in maternal plasma is useful for the noninvasive detection of fetal trisomy 18.
Parenteral Application of a Pseudomonas aeruginosa Flagella Vaccine Elicits Specific Anti-Flagella Antibodies in the Airways of Healthy Individuals (1995)

To test the hypothesis that a Pseudomonas aeruginosa flagella (FLA) vaccine, intramuscularly administered, elicits specific antibodies in the respiratory tract, antibody titers against FLA were determined in sera and bronchoalveolar lavage (BAL) fluids of 10 healthy human adults before and after immunization. Immunization produced significantly increased anti-FLA antibody titers in all sera (mean reciprocal titers: IgG: 26,711; IgA: 2,767; IgM: 421) and on respiratory epithelial lining fluids (mean reciprocal titers: IgG: 112; IgA: 76; slgA: 26). Significant differences in class-specific serum and BAL anti-FLA titers suggested airway antibody production. The study shows that parenteral immunization provides not only high systemic antibody titers but also local antibody production in the human respiratory tract.
Solid‐Phase Synthesis of 2′‐Deoxy‐2′‐fluoro‐ β‐D‐Oligoarabinonucleotides (2′F‐ANA) and Their Phosphorothioate Derivatives (2002)

This unit describes the chemical synthesis of 2'-deoxy-2'-fluoro-b-D-oligoarabinonucleotides (2'F-ANA), both with phosphodiester and phosphorothioate linkages. The protocols described herein include araF phosphoramidite preparation, assembly on DNA synthesizers, and final deprotection and purification of oligonucleotides.
The Majority of Human Peripheral Blood CD4+CD25highFoxp3+ Regulatory T Cells Bear Functional Skin-Homing Receptors (2006)

CD4+CD25+ T regulatory cells (Treg) are thought to be important in the peripheral tolerance. Recent evidence suggests that human peripheral blood CD4+CD25+ T cells are heterogeneous and contain both CD4+CD25(high) T cells with potent regulatory activity and many more CD4+CD25(low/med) nonregulatory T cells. In this study, we found that virtually all peripheral blood CD4+CD25(high)Foxp3+ Treg expressed high levels of the chemokine receptor CCR4. In addition, 80% of Treg expressed cutaneous lymphocyte Ag (CLA) and 73% expressed CCR6. These molecules were functional, as CLA+ Treg showed CD62E ligand activity and demonstrable chemotactic responses to the CCR4 ligands CCL22 and CCL17 and to the CCR6 ligand CCL20. The phenotype and chemotactic response of these Treg were significantly different from those of CD4+CD25(med) nonregulatory T cells. We further demonstrated that blood CLA+ Treg inhibited CD4+CD25- T cell proliferation induced by anti-CD3. Based on homing receptor profile, CLA+ Treg should enter normal skin. We next isolated CD4+CD25(high) T cells directly from normal human skin; these cells suppressed proliferation of skin CD4+CD25- T cells. Therefore, the majority of true circulating Treg express functional skin-homing receptors, and human Treg may regulate local immune responses in normal human skin.
Variance component linkage analysis indicates a QTL for femoral neck bone mineral density on chromosome 1p36 (2001)

Osteoporosis is a common condition characterized by reduced skeletal strength and increased susceptibility to fracture. Eight million Americans over the age of 50 have osteoporosis of the femoral neck. The most important risk factor for osteoporosis is low bone mineral density (BMD), and several epidemiological studies have shown the importance of genetic factors in determining variability of BMD. An initial genome screen in seven large pedigrees suggested that a candidate region conferring susceptibility to low BMD of the femoral neck was located on chromosome 1p36. We have now confirmed and extended this finding by analyzing nine microsatellite markers spanning a 40 cM interval across the candidate region in an expanded sample of 42 families. Heritability of femoral neck BMD was estimated as 0.51 +/- 0.13 in these families, after accounting for the effects of age, sex, body mass index, height and weight. Variance component linkage analysis yielded a maximum multipoint LOD score of 3.53 for linkage of femoral neck BMD to a quantitative trait locus (QTL) located near marker D1S214. The associated empirical P-value by simulation analysis was equal to 0.0001. The results strongly support the hypothesis that a major QTL controlling femoral neck BMD is located on chromosome 1p36.2-p36.3, and further analysis of candidate genes in this region is warranted.
Combining RISC and CISC in PC systems (1991)

RISC processors are being increasingly used in computers in which performance is a key feature. However, their take-up may be restricted by the limited availability of software compared to that available for established machines, normally based on CISC processors. The paper describes a method in which RISC and CISC processors have been combined into the same machine in order to offer compatibility with a wide software base (that of the PC) and, at the same time, access to state-of-the-art computing performance. The hardware and software issues involved and the level of integration which can be achieved are also considered.
Increased mast cells in the irritable bowel syndrome (2000)

Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS). The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls. Biopsy specimens were obtained from the caecum, ascending colon, descending colon and rectum of 28 patients: 14 IBS (Rome criteria); seven normal; and seven inflammatory controls. Tissue was stained immunohistochemically using a monoclonal mouse antibody for human mast cell tryptase (AA1). Tissue area occupied by tryptase-positive MC (volume density of mast cells) was quantified by image analysis. The number of plasma cells, lymphocytes, eosinophils, neutrophils and macrophages were each graded semiquantitatively (0-4) in haematoxylin and eosin stained sections. Mast cell volume density was significantly (P < 0.05) higher in IBS (0.91 +/- 0.18; CI 0.79; 1.0) than normal controls (0.55 +/- 0.14; CI 0.40; 0.69) in the caecum but not at other sites. Apart from MC, there was no evidence of increased cellular infiltrate in the IBS group. MC were significantly increased in the caecum of IBS patients compared to controls. The multiple effects of the intestinal mast cell alone, or as a participant of a persistent inflammatory response, may be fundamental to the pathogenesis of IBS.
Characterization of the Androgen-Regulated Prostate-Specific T Cell Receptor γ-Chain Alternate Reading Frame Protein (TARP) Promoter (2003)

TARP (T cell receptor gamma-chain alternate reading frame protein) is uniquely expressed in males in prostate epithelial cells and prostate cancer cells. Here we demonstrate that TARP expression is regulated by testosterone at the transcriptional level through specific binding of androgen receptor to an androgen response element in the proximal TARP promoter. We further demonstrate that the promoter specifically initiates reporter gene expression in TARP-positive prostate cancer cell lines. To develop a regulatory sequence for prostate-specific gene expression, we constructed a chimeric sequence consisting of the TARP promoter and the prostate-specific antigen (PSA) enhancer. We found that in the prostatic adenocarcinoma cell line LNCaP, the transcriptional activity of the regulatory sequence consisting of a TARP promoter and PSA enhancer is 20 times higher than the activity of a regulatory sequence consisting of the PSA promoter and PSA enhancer. Thus, our studies define a regulatory sequence that may be used to restrict expression of therapeutic genes to prostate cancer cells and may therefore play a role in prostate cancer gene therapy.
Improving in vivo folding and stability of a single-chain Fv antibody fragment by loop grafting (1997)

The complementary determining regions (CDRs) from the fluorescein-binding antibody 4-4-20, which yields almost no soluble protein in periplasmic expression in Escherichia coli, were transplanted to the framework of the humanized antibody 4D5. The resulting single-chain Fv fragment (scFv) 4D5Flu showed both a dramatic improvement in soluble expression, even at 37 degrees C, and an improved thermodynamic stability. Antigen affinity was maintained upon this engineering by paying attention to crucial framework-CDR contacts. This demonstrates that the use of superior frameworks is a robust strategy to improve the physical properties of scFv fragments. We also report that the grafted version was selected in phage display over several competing variants of the same antibody with identical binding constant but poorer folding or stability properties. The selection required four panning rounds and a temperature of 37 degrees C and we show that the underlying reason for this selection is a higher fraction of phages carrying functional scFv molecules.
All-Optical In Situ Histology of Brain Tissue with Femtosecond Laser Pulses (2013)

This protocol describes the application of laser pulses to image and ablate neuronal tissue for the purpose of automated histology. The histology is accomplished in situ using serial two-photon imaging of labeled tissue and removal of the imaged tissue with amplified, femtosecond pulses. Together with the use of endogenous fluorescent indicators and/or deep penetration of antibody labels and organic dyes, this method may be used to automatically image, reconstruct, and vectorize structures of interest across millimeter to centimeter regions of brain with micrometer resolution.
Simultaneous Wavelength-stabilization of 980-nm Pump Lasers (1993)

High power 980-nm strained QW semiconductor lasers connected to the input ports of a 4×4 fused fiber star coupler are simultaneously wavelength-locked through reflection from a single narrow-band fiber grating connected to one output port. This configuration enables simple pump wavelength control, inhibits deleterious pump-laser interactions, and improves amplifier reliability through pump redundancy.
Advances in Non-Viral DNA Vectors for Gene Therapy (2017)

Uses of viral vectors have thus far eclipsed uses of non-viral vectors for gene therapy delivery in the clinic. Viral vectors, however, have certain issues involving genome integration, the inability to be delivered repeatedly, and possible host rejection. Fortunately, development of non-viral DNA vectors has progressed steadily, especially in plasmid vector length reduction, now allowing these tools to fill in specifically where viral or other non-viral vectors may not be the best options. In this review, we examine the improvements made to non-viral DNA gene therapy vectors, highlight opportunities for their further development, address therapeutic needs for which their use is the logical choice, and discuss their future expansion into the clinic.