gebhart/patrepeval huggingface dataset:
Serotonergic Function, Behavioral Disinhibition, and Negative Affect in Children of Alcoholics: The Moderating Effects of Puberty (2000)

The moderating effects of puberty may help clarify inconsistencies in child/adolescent literature. Furthermore, there appears to be a relationship between 5-HT and negative affect which parallels that between 5-HT and behavioral disinhibition. Pubertal status may be an important variable to evaluate as a moderator in relation to the developmental context of the role 5-HT dysfunction may play in various models of behavior related to alcoholism over the early life course.
Role of Pericytes in Skeletal Muscle Regeneration and Fat Accumulation (2013)

Stem cells ensure tissue regeneration, while overgrowth of adipogenic cells may compromise organ recovery and impair function. In myopathies and muscle atrophy associated with aging, fat accumulation increases dysfunction, and after chronic injury, the process of fatty degeneration, in which muscle is replaced by white adipocytes, further compromises tissue function and environment. Some studies suggest that pericytes may contribute to muscle regeneration as well as fat formation. This work reports the presence of two pericyte subpopulations in the skeletal muscle and characterizes their specific roles. Skeletal muscle from Nestin-GFP/NG2-DsRed mice show two types of pericytes, Nestin-GFP-/NG2-DsRed+ (type-1) and Nestin-GFP+/NG2-DsRed+ (type-2), in close proximity to endothelial cells. We also found that both Nestin-GFP-/NG2-DsRed+ and Nestin-GFP+/NG2-DsRed+ cells colocalize with staining of two pericyte markers, PDGFRβ and CD146, but only type-1 pericyte express the adipogenic progenitor marker PDGFRα. Type-2 pericytes participate in muscle regeneration, while type-1 contribute to fat accumulation. Transplantation studies indicate that type-1 pericytes do not form muscle in vivo, but contribute to fat deposition in the skeletal muscle, while type-2 pericytes contribute only to the new muscle formation after injury, but not to the fat accumulation. Our results suggest that type-1 and type-2 pericytes contribute to successful muscle regeneration which results from a balance of myogenic and nonmyogenic cells activation.
Transparently interposing user code at the system interface (2003)

The author reports on the development of an object-oriented toolkit which substantially increases the ease of interposing user code between clients and instances of the system interface by allowing such code to be written in terms of the high-level objects provided by this interface, rather than in terms of the intercepted system calls themselves. This toolkit helps enable new interposition agents to be written which otherwise would not have been attempted. It is used to construct several agents including protected environments for running untrusted binaries, modified file system namespaces, logical devices implemented entirely in user space, transparent network data compression and/or encryption agents, and system call tracing tools. Examples of other agents which could be built include transactional software environments and emulators for other operating system environments.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Detection of Viral Infection and Gene Expression in Clinical Tissue Specimens Using Branched DNA (bDNA) In Situ Hybridization (2002)

In situ hybridization (ISH) methods for detection of nucleic acid sequences have proved especially powerful for revealing genetic markers and gene expression in a morphological context. Although target and signal amplification technologies have enabled researchers to detect relatively low-abundance molecules in cell extracts, the sensitive detection of nucleic acid sequences in tissue specimens has proved more challenging. We recently reported the development of a branched DNA (bDNA) ISH method for detection of DNA and mRNA in whole cells. Based on bDNA signal amplification technology, bDNA ISH is highly sensitive and can detect one or two copies of DNA per cell. In this study we evaluated bDNA ISH for detection of nucleic acid sequences in tissue specimens. Using normal and human papillomavirus (HPV)-infected cervical biopsy specimens, we explored the cell type-specific distribution of HPV DNA and mRNA by bDNA ISH. We found that bDNA ISH allowed rapid, sensitive detection of nucleic acids with high specificity while preserving tissue morphology. As an adjunct to conventional histopathology, bDNA ISH may improve diagnostic accuracy and prognosis for viral and neoplastic diseases.
Chemical and biochemical strategies for the randomization of protein encoding DNA sequences: library construction methods for directed evolution (2004)

Directed molecular evolution and combinatorial methodologies are playing an increasingly important role in the field of protein engineering. The general approach of generating a library of partially randomized genes, expressing the gene library to generate the proteins the library encodes and then screening the proteins for improved or modified characteristics has successfully been applied in the areas of protein-ligand binding, improving protein stability and modifying enzyme selectivity. A wide range of techniques are now available for generating gene libraries with different characteristics. This review will discuss these different methodologies, their accessibility and applicability to non-expert laboratories and the characteristics of the libraries they produce. The aim is to provide an up to date resource to allow groups interested in using directed evolution to identify the most appropriate methods for their purposes and to guide those moving on from initial experiments to more ambitious targets in the selection of library construction techniques. References are provided to original methodology papers and other recent examples from the primary literature that provide details of experimental methods.
Transdominant genetic analysis of a growth control pathway (1998)

Genetic selections that use proteinaceous transdominant inhibitors encoded by DNA libraries to cause mutant phenocopies may facilitate genetic analysis in traditionally nongenetic organisms. We performed a selection for random short peptides and larger protein fragments (collectively termed "perturbagens") that inhibit the yeast pheromone response pathway. Peptide and protein fragment perturbagens that permit cell division in the presence of pheromone were recovered. Two perturbagens were derived from proteins required for pheromone response, and an additional two were derived from proteins that may negatively influence the pheromone response pathway. Furthermore, three known components of the pathway were identified as probable perturbagen targets based on physical interaction assays. Thus, by selection for transdominant inhibitors of pheromone response, multiple pathway components were identified either directly as gene fragments or indirectly as the likely targets of specific perturbagens. These results, combined with the results of previous work [Holzmayer, T. A., Pestov, D. G. & Roninson, I. B. (1992) Nucl. Acids. Res. 20, 711-717; Whiteway, M., Dignard, D. & Thomas, D. Y. (1992) Proc. Natl. Acad. Sci. USA 89, 9410-9414; and Gudkov, A. V., Kazarov, A. R., Thimmapaya, R., Axenovich, S. A., Mazo, I. A. & Roninson, I. B. (1994) Proc. Natl. Acad. Sci. USA 91, 3744-3748], suggest that transdominant genetic analysis of the type described here will be broadly applicable.
PD-1 Blockade Enhances T-cell Migration to Tumors by Elevating IFN-γ Inducible Chemokines (2012)

Adoptive cell transfer (ACT) is considered a promising modality for cancer treatment, but despite ongoing improvements, many patients do not experience clinical benefits. The tumor microenvironment is an important limiting factor in immunotherapy that has not been addressed fully in ACT treatments. In this study, we report that upregualtion of the immunosuppressive receptor programmed cell death-1 (PD-1) expressed on transferred T cells at the tumor site, in a murine model of ACT, compared with its expression on transferred T cells present in the peripheral blood and spleen. As PD-1 can attenuate T-cell-mediated antitumor responses, we tested whether its blockade with an anti-PD-1 antibody could enhance the antitumor activity of ACT in this model. Cotreatment with both agents increased the number of transferred T cells at the tumor site and also enhanced tumor regressions, compared with treatments with either agent alone. While anti-PD-1 did not reduce the number of immunosuppressive regulatory T cells and myeloid-derived suppressor cells present in tumor-bearing mice, we found that it increased expression of IFN-γ and CXCL10 at the tumor site. Bone marrow-transplant experiments using IFN-γR-/- mice implicated IFN-γ as a crucial nexus for controlling PD-1-mediated tumor infiltration by T cells. Taken together, our results imply that blocking the PD-1 pathway can increase IFN-γ at the tumor site, thereby increasing chemokine-dependent trafficking of immune cells into malignant disease sites.
The aryl hydrocarbon receptor (AHR) transcription factor regulates megakaryocytic polyploidization (2011)

We propose that the aryl hydrocarbon receptor (AHR) is a novel transcriptional regulator of megakaryopoietic polyploidization. Functional evidence was obtained that AHR impacts in vivo megakaryocytic differentiation and maturation; compared to wild-type mice, AHR-null mice had lower platelet counts, fewer numbers of newly synthesized platelets, increased bleeding times and lower-ploidy megakaryocytes (Mks). AHR mRNA increased 3·6-fold during ex vivo megakaryocytic differentiation, but reduced or remained constant during parallel isogenic granulocytic or erythroid differentiation. We interrogated the role of AHR in megakaryopoiesis using a validated Mk model of megakaryopoiesis, the human megakaryoblastic leukaemia CHRF cell line. Upon CHRF Mk differentiation, AHR mRNA and protein levels increased, AHR protein shifted from the cytoplasm to the nucleus and AHR binding to its consensus DNA binding sequence increased. Protein and mRNA levels of the AHR transcriptional target HES1 also increased. Mk differentiation of CHRF cells where AHR or HES1 was knocked-down using RNAi resulted in lower ploidy distributions and cells that were incapable of reaching ploidy classes ≥16n. AHR knockdown also resulted in increased DNA synthesis of lower ploidy cells, without impacting apoptosis. Together, these data support a role for AHR in Mk polyploidization and in vivo platelet function, and warrant further detailed investigations.
Biocompatibility of lipid‐protein‐sugar particles containing bupivacaine in the epineurium (2001)

Novel lipid-protein-sugar particles (LPSPs) are potentially biocompatible because they are composed of naturally occurring ingredients and their expected tissue dwell times are relatively short. In this research, we used histological sections to study tissue reaction to LPSPs (4.4-microm median diameter) when used for sciatic nerve block in the rat. As a reference, we compared LPSPs to 60-microm median diameter poly(lactic-co-glycolic) acid (PLGA) microspheres (110,000 MW PLGA, glycolic/lactic ratio 65:35). Four days after injection, both particle types produced acute inflammation within the confines of the injectate, inflammation in adjacent tissues, and myotoxicity. Bupivacaine-free particles did not display myotoxicity, and inflammation in adjacent tissues was reduced. At 2 weeks, inflammation from LPSPs had almost disappeared, whereas PLGA microspheres had a foreign-body giant cell reaction until at least 8 weeks after injection. In contrast, 3.6-microm median diameter, 20,000-MW PLGA microspheres produced a primarily histiocytic reaction 2 weeks after injection. In summary, the LPSPs and PLGA microspheres studied herein have excellent biocompatibility, but tissue reaction to the former is of much shorter duration. Myotoxicity and inflammation of surrounding tissue is largely attributed to bupivacaine. Foreign-body giant cells may be attributed to particle size rather than a specific reaction to PLGA.
Eradication of human hepatic and pulmonary melanoma metastases in SCID mice by antibody-interleukin 2 fusion proteins. (1996)

Antibody-cytokine fusion proteins combine the unique targeting ability of antibodies with the multifunctional activity of cytokines. Here, we demonstrate the therapeutic efficacy of such constructs for the treatment of hepatic and pulmonary metastases of different melanoma cell lines. Two antibody-interleukin 2 (IL-2) fusion proteins, ch225-IL2 and ch14.18-IL2, constructed by fusion of a synthetic sequence coding for human IL-2 to the carboxyl end of the Cgamma1 gene of the corresponding antibodies, were tested for their therapeutic efficacy against xenografted human melanoma in vivo. Tumor-specific fusion proteins completely inhibited the growth of hepatic and pulmonary metastases in C.B-17 scid/scid mice previously reconstituted with human lymphokine-activated killer cells, whereas treatment with combinations of the corresponding antibodies plus recombinant IL-2 only reduced the tumor load. Even when treatment with fusion proteins was delayed up to 8 days after inoculation of tumor cells, it still resulted in complete eradication of micrometastases that were established at that time point. Selection of tumor cell lines expressing or lacking the targeted antigen of the administered fusion protein proved the specificity of the observed antitumor effect. Biodistribution analysis demonstrated that the tumor-specific fusion protein accumulated not only in subcutaneous tumors but also in lungs and livers affected with micrometastases. Survival times of animals treated with the fusion protein were more than doubled as compared to those treated with the combination of the corresponding antibody plus IL-2. Our data demonstrate that an immunotherapeutic approach using cytokines targeted by antibodies to tumor sites has potent effects against disseminated human melanoma.
Cytoplasmic domain requirement for incorporation of a foreign envelope protein into vesicular stomatitis virus (1993)

Incorporation of human immunodeficiency virus type 1 (HIV-1) envelope proteins into vesicular stomatitis virus (VSV) particles was studied in a system that allows expressed envelope proteins to rescue phenotypically a temperature-sensitive mutant of VSV (tsO45). This mutant exhibits defective transport of its own envelope glycoprotein (G) and can be rescued by simultaneous expression of wild-type G protein from cDNA. We report here that a hybrid HIV-1-VSV protein containing the extracellular and transmembrane domains of the HIV-1 envelope protein fused to the cytoplasmic domain of VSV G protein was able to rescue the tsO45 mutant lacking the G protein, while the wild-type HIV-1 envelope protein was not. The VSV(HIV) pseudotypes obtained infected only CD4+ cells and were neutralized specifically by anti-HIV-1 sera. Our results indicate that the cytoplasmic tail of the VSV glycoprotein contains an independent signal capable of directing a foreign protein into VSV particles. The VSV(HIV) pseudotypes generated here were prepared in the absence of HIV-1 and should be useful for identifying molecules that block HIV-1 entry.
The Best among Six Strategies for Selecting a Minute Target and the Determination of the Minute Maximum Size of the Targets on a Pen-Based Computer (1997)

This study concentrates on finding the relationship between target-pointing strategies and target sizes. Concretely, an evaluation experiment was performed in which the experimental system used five kinds of targets (1, 3, 5, 7 and 9 dot diameter circles in respectively, 0.36 mm per dot), eight pen-movement-directions and six strategies of systematic election on a pen-based computer. The results showed that the “Land-on2” strategy was the best strategy for selecting a minute target, in terms of error rates, selection time and subjective preferences. “The minute maximum size” of 5 dots was also determined to be the largest size among the targets which had a significant main effect on the six strategies in terms of error rates.
Adiós al CD (2015)

Y a la descarga. El furor por el streaming llega hasta a las marcas de consumo. Disqueras y artistas reconocen el potencial
The irregular xylem3 Locus of Arabidopsis Encodes a Cellulose Synthase Required for Secondary Cell Wall Synthesis (1999)

The irregular xylem3 (irx3) mutant of Arabidopsis has a severe deficiency in secondary cell wall cellulose deposition that leads to collapsed xylem cells. The irx3 mutation has been mapped to the top arm of chromosome V near the marker nga106. Expressed sequence tag clone 75G11, which exhibits sequence similarity to cellulose synthase, was found to be tightly linked to irx3, and genomic clones containing the gene corresponding to clone 75G11 complemented the irx3 mutation. Thus, the IRX3 gene encodes a cellulose synthase component that is specifically required for the synthesis of cellulose in the secondary cell wall. The irx3 mutant allele contains a stop codon that truncates the gene product by 168 amino acids, suggesting that this allele is null. Furthermore, in contrast to radial swelling1 (rsw1) plants, irx3 plants show no increase in the accumulation of beta-1,4-linked glucose in the noncrystalline cell wall fraction. IRX3 and RSW1 fall into a distinct subgroup (Csa) of Arabidopsis genes showing homology to bacterial cellulose synthases.
Rational clocking [digital systems design] (2002)

Communication between independently-clocked digital subsystems typically involves a finite probability of synchronization failure whose minimization introduces delays and consequent performance costs. This paper explores a technique that eliminates both the inherent unreliability of such communication and the performance overhead it implies. Our approach maintains a known phase relationship, between clocks whose frequencies are related by a rational factor, and exploits the predictability of their relative phases to algorithmically time communications without run-time arbitration contests.
A nucleotide insertion in the transcriptional regulatory region of FADS2 gives rise to human fatty acid delta-6-desaturase deficiency (2003)

Fatty acid delta-6-desaturase (FADS2) is the rate-limiting enzyme in mammalian synthesis of long-chain polyunsaturated fatty acids. We investigated the molecular mechanism of FADS2 deficiency in skin fibroblasts from a patient deficient in this enzyme. Expression analyses demonstrated an 80% to 90% decrease in the steady-state level of FADS2 mRNA in patient-derived cells compared with normal controls that was consistent with previous metabolic biochemical studies. In vitro transcription assays indicated an 80% decrease in the rate of transcriptional initiation in patient-derived cells, thus implicating transcriptional regulation as the mechanism for the decreased transcript levels. Sequence analysis of the 5' end of the gene revealed the insertion of a thymidine between positions -941 and -942 upstream of the translation start site in patient-derived cells compared with normal cells and published sequences. Promoter-reporter assays demonstrated a 6-fold decrease in promoter activity in the polymorphic variant FADS2 regulatory region compared with the normal gene, confirming the functional relevance of the insertion mutation to the decreased expression of the gene in the patient-derived cells. These findings indicate that fatty acid delta-6-desaturase deficiency and decreased FADS2 transcription are caused by a nucleotide insertion in the transcriptional regulatory region of the human FADS2 gene.
Cytokines and Cytokine Receptors in Advanced Heart Failure (2001)

Cytokines and cytokine receptors are independent predictors of mortality in patients with advanced heart failure. Moreover, circulating levels of cytokines are modified by age, sex, and cause of heart failure.
Factors Affecting the Pullout Strength of Cancellous Bone Screws (1996)

Screws placed into cancellous bone in orthopedic surgical applications, such as fixation of fractures of the femoral neck or the lumbar spine, can be subjected to high loads. Screw pullout is a possibility, especially if low density osteoporotic bone is encountered. The overall goal of this study was to determine how screw thread geometry, tapping, and cannulation affect the holding power of screws in cancellous bone and determine whether current designs achieve maximum purchase strength. Twelve types of commercially available cannulated and noncannulated cancellous bone screws were tested for pullout strength in rigid unicellular polyurethane foams of apparent densities and shear strengths within the range reported for human cancellous bone. The experimentally derived pullout strength was compared to a predicted shear failure force of the internal threads formed in the polyurethane foam. Screws embedded in porous materials pullout by shearing the internal threads in the porous material. Experimental pullout force was highly correlated to the predicted shear failure force (slope = 1.05, R2 = 0.947) demonstrating that it is controlled by the major diameter of the screw, the length of engagement of the thread, the shear strength of the material into which the screw is embedded, and a thread shape factor (TSF) which accounts for screw thread depth and pitch. The average TSF for cannulated screws was 17 percent lower than that of noncannulated cancellous screws, and the pullout force was correspondingly less. Increasing the TSF, a result of decreasing thread pitch or increasing thread depth, increases screw purchase strength in porous materials. Tapping was found to reduce pullout force by an average of 8 percent compared with nontapped holes (p = 0.0001). Tapping in porous materials decreases screw pullout strength because the removal of material by the tap enlarges hole volume by an average of 27 percent, in effect decreasing the depth and shear area of the internal threads in the porous material.
Purification of aromatic l-amino acid decarboxylase from bovine brain with a monoclonal antibody (1988)

Aromatic L-amino acid decarboxylase was purified from bovine brain for the first time by affinity chromatography using a monoclonal antibody to the enzyme, and it was compared with the decarboxylase purified from bovine adrenal medulla by the same procedure. The monoclonal antibody was produced from a hybridoma established for the enzyme highly purified from bovine adrenal medulla. The Mr values of brain and adrenal-medulla enzyme were both estimated to be approx. 100,000 by gel-permeation chromatography. SDS/polyacrylamide-gel electrophoresis revealed a single band with an apparent Mr of 50,000. Western immunoblot analysis showed that the antibody recognized each enzyme. With regard to substrate specificity, pH-dependence and effect of pyridoxal 5'-phosphate as a cofactor, both enzymes were similar.
Reductive amination of [18F]fluorobenzaldehydes: Radiosyntheses of [2‐18F]‐ and [4‐18F]fluorodexetimides (1990)

Abstract Two [ 18 F]‐labelled analogues of dexetimide, a potent muscarinic cholinergic receptor ligand, have been synthesised in good yields and at high specific activities. Reductive amination of [2‐ 18 F]‐ and [4‐ 18 F]fluorobenzaldehyde with norbenzyldexetimide and sodium cyanoborohydride gave, in a one‐pot reaction, good (≈︁20%) yields of high specific activity [2‐ 18 F]‐ and [4‐ 18 F]fluorodexetimide respectively. The labelled benzaldehydes may be useful synthetic precursors for the radiosyntheses of other complex radiotracers for use with positron emission tomography.