gebhart/patrepeval huggingface dataset:
Does immune-tolerance treatment with Alum-formulated GAD65 protect insulin-production in the pancreatic islet β cells? (2011)

Type 1 diabetes is a serious chronic disease in which the pancreatic islet beta cells are destroyed by autoimmunity specifically directed to intracellular autoantigens. Still undefined environmental factors are likely to initiate the disease process. One of the autoantigens is glutamic acid decarboxylase (GAD65) and attempts are made to induce immunological tolerance against this autoantigen. Alum-formulated GAD65 (Diamyd (®)) has been given subcutaneously in two injections with one month apart to recent onset type 1 diabetes patients with positive GAD65 autoantibodies. The injections were found to preserve residual β-cell function without treatment related serious adverse events. Phase III studies in children with recent onset type 1 diabetes are ongoing along with a study (DIAPREV-IT) aimed at testing whether Diamyd (®) may prevent the clinical onset of diabetes in non-diabetic children with GAD65 autoantibodies and at least one more islet autoantibody. Future studies may include investigation of Diamyd (®) in combination with other immunomodulating autoantigens.
Oral mucosal adhesive film containing local anesthetics:In vitro and clinical evaluation (1998)

In vitro and in vivo studies were conducted to gauge the effectiveness of a novel oral mucosa adhesive, moderately water-soluble, pliant polymer artificial dentifrice (AD) film containing dibucaine (DC) for relief of pain due to oral erosion. The film was prepared from a hydroxypropyl cellulose-M (HPC-M) ethanol solution containing varying amounts of DC, as well as polyethylene glycol. In the in vitro experiments, the disintegration of HPC-M showed a lag time of about 50 min, a much lower rate than that of drug release, which more or less leveled off after 50 min. Twenty-five percent of the DC was released from the film (0.113 and 0.225 mg/cm2) after the initial 5 min, which then reached about 80% after 50 min, the time at which the polymer began to break up. In the in vivo study, the local anesthetic effect of the film was evaluated in 23 patients (10 males, 13 females) suffering from the adverse effects of chemotherapy. When applied to the wet surface of the mucosa, the AD film absorbed moisture and showed excellent adhesion. Pain relief in patients lasted 2.2 +/- 0.21 and 4.3 +/- 0.25 h at DC doses of 0.113 and 0.225 mg/cm2, respectively. These results suggest that the AD film may cover mucositis sites of oral mucosa long enough to allow DC release and bring relief from pain arising from chemotherapy and/or radiotherapy.
BMP10 is essential for maintaining cardiac growth during murine cardiogenesis (2004)

During cardiogenesis, perturbation of a key transition at mid-gestation from cardiac patterning to cardiac growth and chamber maturation often leads to diverse types of congenital heart disease, such as ventricular septal defect (VSD), myocardium noncompaction, and ventricular hypertrabeculation. This transition, which occurs at embryonic day (E) 9.0-9.5 in murine embryos and E24-28 in human embryos, is crucial for the developing heart to maintain normal cardiac growth and function in response to an increasing hemodynamic load. Although, ventricular trabeculation and compaction are key morphogenetic events associated with this transition, the molecular and cellular mechanisms are currently unclear. Initially, cardiac restricted cytokine bone morphogenetic protein 10 (BMP10) was identified as being upregulated in hypertrabeculated hearts from mutant embryos deficient in FK506 binding protein 12 (FKBP12). To determine the biological function of BMP10 during cardiac development, we generated BMP10-deficient mice. Here we describe an essential role of BMP10 in regulating cardiac growth and chamber maturation. BMP10 null mice display ectopic and elevated expression of p57(kip2) and a dramatic reduction in proliferative activity in cardiomyocytes at E9.0-E9.5. BMP10 is also required for maintaining normal expression levels of several key cardiogenic factors (e.g. NKX2.5 and MEF2C) in the developing myocardium at mid-gestation. Furthermore, BMP10-conditioned medium is able to rescue BMP10-deficient hearts in culture. Our data suggest an important pathway that involves a genetic interaction between BMP10, cell cycle regulatory proteins and several major cardiac transcription factors in orchestrating this transition in cardiogenesis at mid-gestation. This may provide an underlying mechanism for understanding the pathogenesis of both structural and functional congenital heart defects.
The Correlation Analysis of Influencing Factors and Harmfulness of Expressway Traffic Accident (2016)

Highway traffic accidents are characterized by high death rate, large economic losses and so on.
In vitro cytocidal effect of novel lytic peptides on Plasmodium falciparum and Trypanosoma cruzi 1 (1988)

Plasmodium falciparum and Trypanosoma cruzi were killed by two novel lytic peptides (SB-37 and Shiva-1) in vitro. Human erythrocytes infected with P. falciparum, and Vero cells infected with T. cruzi, were exposed to these peptides. The result, in both cases, was a significant decrease in the level of parasite infection. Furthermore, the peptides had a marked cytocidal effect on trypomastigote stages of T. cruzi in media, whereas host eukaryotic cells were unaffected by the treatments. In view of the worldwide prevalence of these protozoan diseases and the lack of completely suitable treatments, lytic peptides may provide new and unique chemotherapeutic agents for the treatment of these infections.
A Maitland–Japp inspired synthesis of dihydropyran-4-ones and their stereoselective conversion to functionalised tetrahydropyran-4-ones (2015)

The Maitland-Japp reaction has been extended to the synthesis of highly functionalised dihydropyran-4-ones. These dihydropyran-4-ones can in turn be converted stereoselectively into tetrahydropyran-4-ones with tertiary and quaternary stereocentres via the one-pot addition of hydride or carbon nucleophiles and trapping with carbon electrophiles. The utility of this method is demonstrated by providing access to the functionalised tetrahydropyran units present in a component of the Civet fragrance and the anticancer polyketide lasonolide A.
Adoptive transfer of tumor cytotoxic macrophages generated in vitro from circulating blood monocytes: a new approach to cancer immunotherapy. (1990)

Cells of the macrophage lineage are considered to be of special importance in the defense of the host against tumor development and spread. Immunotherapeutic strategies to stimulate macrophage (MAC) tumor cytotoxicity make use of activating compounds such as gamma-interferon which are given systemically. However, there are several lines of evidence that in malignant disease the generation of cytotoxic effector MACs is impaired. Both defective cell maturation and loss of responsiveness to activation are described. Here, a first clinical phase I trial of adoptive immunotherapy in cancer patients using autologous MACs generated in vitro from blood monocytes (MOs) is reported. Mononuclear cells were isolated by cytapheresis and density centrifugation and cultured in hydrophobic Teflon bags for 7 days with 2% autologous serum and recombinant human gamma-interferon being present for the last 18 h. Cytotoxic MO-derived MACs were then purified by countercurrent elutriation and reinfused into the patient. A total of 72 therapies have been performed with patients being treated i.v. (n = 8) and i.p. (n = 7). In vitro generated MACs proved to be mature as judged by the expression of maturation-associated surface molecules (MAX antigens, CD16, CD51, CD71), were cytotoxic to U937 tumor cells, and were efficient secretory cells. Cell dose escalation was performed in the first patients beginning with 10(8) MACs to finally infuse the total number of cells recovered from one single cycle of isolation and culture. MAC yield varied from 1 to 17 x 10(8) representing 13-79% of MOs initially seeded. Adoptive MAc transfer was well tolerated. Side effects observed were low-grade fever (less than 38.5 degrees C), induction of the coagulation cascade, and abdominal discomfort after i.p. application. The procoagulant activity of MAC autografts was cell dose dependent and demonstrated by detection of circulating fibrin monomers and thrombin-antithrombin complexes. Biological responses observed included elevated serum neopterin levels and the appearance of interleukin-6 in sera and ascitic fluids. Indication of a possible therapeutic effect was only observed in i.p.-treated patients and consisted of disappearance of malignant ascites in 2 of 7 patients.
Non-fluoroscopic mapping as a guide for atrial ablation: current status and expectations for the future (2007)

Non-fluoroscopic, electroanatomic mapping technologies enable the display of the cardiac chambers and the relative position of ablation lesions. These three-dimensional (3D) systems are used to ablate various types of arrhythmia. The past decade has witnessed the development of an increasing number of AF ablation procedures largely based on anatomic considerations which prompted the explosive development of computer-based mapping for increasing accuracy. At present, 3D mapping and navigation technologies play a central role in the ablation of AF particularly in patients with long-lasting or permanent AF, regardless of whether pulmonary vein isolation or substrate modification is planned. Although no present mapping and navigation system may be considered ideal, their special features are discussed here. The purpose of this article is to review the current status and the clinical role of the available non-fluoroscopic mapping systems as well as expectations for the future.
Inhibitors of enzymes of androgen biosynthesis: cytochrome P45017α and 5α-steroid reductase (1998)

M. Jarman, H. John Smith, P. J. Nicholls and C. Simons, Nat. Prod. Rep., 1998, 15, 495 DOI: 10.1039/A815495Y
Right Hemisphere Dominance during Spatial Selective Attention and Target Detection Occurs Outside the Dorsal Frontoparietal Network (2010)

Spatial selective attention is widely considered to be right hemisphere dominant. Previous functional magnetic resonance imaging studies, however, have reported bilateral blood-oxygenation-level-dependent responses in dorsal frontoparietal regions during anticipatory shifts of attention to a location (Kastner et al., 1999; Corbetta et al., 2000; Hopfinger et al., 2000). Right-lateralized activity has mainly been reported in ventral frontoparietal regions for shifts of attention to an unattended target stimulus (Arrington et al., 2000; Corbetta et al., 2000). However, clear conclusions cannot be drawn from these studies because hemispheric asymmetries were not assessed using direct voxelwise comparisons of activity in left and right hemispheres. Here, we used this technique to measure hemispheric asymmetries during shifts of spatial attention evoked by a peripheral cue stimulus and during target detection at the cued location. Stimulus-driven shifts of spatial attention in both visual fields evoked right-hemisphere dominant activity in temporoparietal junction (TPJ). Target detection at the attended location produced a more widespread right hemisphere dominance in frontal, parietal, and temporal cortex, including the TPJ region asymmetrically activated during shifts of spatial attention. However, hemispheric asymmetries were not observed during either shifts of attention or target detection in the dorsal frontoparietal regions (anterior precuneus, medial intraparietal sulcus, frontal eye fields) that showed the most robust activations for shifts of attention. Therefore, right hemisphere dominance during stimulus-driven shifts of spatial attention and target detection reflects asymmetries in cortical regions that are largely distinct from the dorsal frontoparietal network involved in the control of selective attention.
Apolipoprotein B and A-I values in 147 576 Swedish males and females, standardized according to the World Health Organization–International Federation of Clinical Chemistry First International Reference Materials (1998)

Serum concentrations of apolipoprotein (apo) B and apo A-I were measured from 1985-1996 in a Swedish population sample of 83 112 males and 64 464 females, ages <20 to >80 years, using an automated immunoturbidimetric method calibrated against fresh pools of human serum and commercial calibrators. All values were recalculated in 1997 after calibration against the WHO-IFCC First International Reference Materials. The recalculation factor was 1.059 for apo B, whereas for apo A-I, the correction was: y = 0.989x + 0.101. The total CVs for both apo B and A-I were generally <7%. The mean value (+/- SD) for apo B was 1.31 +/- 0.35 g/L in all males and 1.22 +/- 0.36 g/L in all females. The mean apo A-I concentration was 1.36 +/- 0.22 g/L in males-10% lower than in females (1.51 +/- 0.24 g/L). The mean value of apo B increased up to 60 years of age in males and up to 70 years of age in females. apo A-I concentrations changed only slightly with age in both males and females. apo A-I concentrations among Swedes are nearly identical to those reported recently by two American studies and those obtained in a Finnish population sample. Mean apo B concentrations differ somewhat between the populations but mirror-as expected-differences in total cholesterol concentrations. The highest values were noted in Swedish subjects. The Swedish sample population is, to our knowledge, the largest describing the distribution of apo B and A-I in a general population of adult males and females of all ages determined with procedures standardized and traceable to the WHO-IFCC First International Reference Materials.
Microarray-Based Identification of a Novel Streptococcus pneumoniae Regulon Controlled by an Autoinduced Peptide (2000)

We have identified in the Streptococcus pneumoniae genome sequence a two-component system (TCS13, Blp [bacteriocin-like peptide]) which is closely related to quorum-sensing systems regulating cell density-dependent phenotypes such as the development of genetic competence or the production of antimicrobial peptides in lactic acid bacteria. In this study we present evidence that TCS13 is a peptide-sensing system that controls a regulon including genes encoding Blps. Downstream of the Blp TCS (BlpH R) we identified open reading frames (blpAB) that have the potential to encode an ABC transporter that is homologous to the ComA/B export system for the competence-stimulating peptide ComC. The putative translation product of blpC, a small gene located downstream of blpAB, has a leader peptide with a Gly-Gly motif. This leader peptide is typical of precursors processed by this family of transporters. Microarray-based expression profiling showed that a synthetic oligopeptide corresponding to the processed form of BlpC (BlpC*) induces a distinct set of 16 genes. The changes in the expression profile elicited by synthetic BlpC* depend on BlpH since insertional inactivation of its corresponding gene abolishes differential gene induction. Comparison of the promoter regions of the blp genes disclosed a conserved sequence element formed by two imperfect direct repeats upstream of extended -10 promoter elements. We propose that BlpH is the sensor for BlpC* and the conserved sequence element is a recognition sequence for the BlpR response regulator.
Fucosylated glycan inhibition of human hepatocellular carcinoma cell migration through binding to chemokine receptors (2009)

SMMC-7721 hepatocellular carcinoma cells (HCC) were incubated with fucosylated glycoproteins that had been isolated from retinoic acid-treated cells by affinity chromatography. HCC migration was significantly inhibited by AAL- and LCA-glycoproteins. Glycopeptides, obtained by digestion of the glycoproteins with trypsin and papain, were found to have a similar inhibitory effect on HCC migration as the corresponding glycoproteins. The inhibitory actions of the glycoproteins were almost abolished after digestion with alpha-L-1,3/4- or alpha-L-1,2-fucosidase. Induction of HCC migration with chemokines including interleukin-8 (IL-8), lymphotactin, monocyte chemoattractant protein-1, and stroma cell-derived factor-1 was examined and IL-8 was found to be the most potent. Interestingly, the isolated glycoproteins significantly inhibited HCC migration and F-actin aggregation induced by IL-8, whereas the glycans themselves did not induce F-actin assembly. From receptor binding analysis AAL-glycan was found to bind IL-8 receptors especially CXCR2 directly and such binding could be blocked by 3'- or 2'-fucosyllactose. After CXCR2 silence by target RNAi, the cells almost lost the response to AAL-glycan inhibition. Our findings suggest that fucosylation plays an important role in the interaction between IL-8 and its receptors inducing HCC migration.
Handbook of Food Engineering (2006)

Food engineering Daryl B. Lund University of Wisconsin-Madison. Foodproteins/food 73 Handbook of Indigenous Fermented Foods Second Edition, Revised. Food Engineering Handbook: Food Engineering Fundamentals provides a stimulating and up-to-date review of food engineering phenomena. Combining theory. Transport and storage of food products, in “Handbook of Food Engineering,” eds. and uses, in Food Polysaccharides and Their Applications: Second Edition.
Purification of CD45+ hematopoietic cells directly from human bone marrow using a flow‐based P‐selectin‐coated microtube (2008)

Recently, a flow-based selectin-dependent method for capture and enrichment of specific type blood cells (CD34+ hematopoietic stem and progenitor cells) from bone marrow and peripheral blood has been described. Using a similar approach, here we show isolation of CD45+ blood cells directly from human bone marrow to a high purity (90%-97%). The process mimics a ubiquitous mechanism of cell trafficking in the body for the recruitment of neutrophils during inflammation. The method is straightforward, rapid, and may represent a practical alternative to CD45+ cell enrichment procedures required for chimerism analysis following allogenic stem-cell transplantation.
Gr-1+ Myeloid Cells Derived from Tumor-Bearing Mice Inhibit Primary T Cell Activation Induced Through CD3/CD28 Costimulation (2000)

Activation of T cells is a necessary step in the development of a specific antitumor immune response. In the present study, we evaluated the ability of Gr-1+ myeloid cells, derived from the bone marrow or spleen of tumor-bearing mice, to inhibit CD3/CD28-mediated T cell activation. Using flow cytometry, we found that growth of a murine colon carcinoma (MCA-26) induces a significant increase in the number of Gr-1+ and Gr-1+/Mac-1+ myeloid cells in both bone marrow and spleen of the tumor host. The proliferative response of T cells was dramatically decreased when naive T cells were activated by anti-CD3 and anti-CD28 Abs in the presence of a myeloid-enriched cell fraction derived from spleen or bone marrow of tumor-bearing mice vs the bone marrow of naive mice. Reversal of the inhibitory effect could be achieved by adding a combination of MnTBAP (manganese [III] tetrakis [4-benzoic acid]) porphyrin and l -NMMA (NG-monomethyl-l -arginine), a superoxide dismutase mimetic and inducible NO synthase inhibitor, respectively, or by depletion of the Gr-1-positive cells. IFN-gamma, which is endogenously produced by CD3/CD28-stimulated naive T cells, is involved in induction of the inhibitory activity of myeloid cells. Importantly, when T cells pre-activated with anti-CD3 Abs were used as responder cells, the bone marrow- or spleen-derived Gr-1+ myeloid cells were unable to suppress CD3/CD28-induced T cell proliferation. Our findings suggest that one mechanism by which an increased number of immune suppressive Gr-1+ cells can induce T cell unresponsiveness or immune tolerance in tumor hosts could be through peroxynitrite production upon primary T cell activation.
Memory and long-term potentiation (LTP) dissociated: Normal spatial memory despite CA1 LTP elimination with Kv1.4 antisense (1998)

Long-term potentiation (LTP) in the hippocampal slice preparation has been proposed as an in vitro model for long-term memory. However, correlation of LTP with memory in living animals has been difficult to demonstrate. Furthermore, in the last few years evidence has accumulated that dissociate the two. Because potassium channels might determine the weight of synapses in networks, we studied the role of Kv1.4, a presynaptic A-type voltage-dependent K+ channel, in both memory and LTP. Reverse transcription-PCR and Western blot analysis with specific antibodies showed that antisense oligodeoxyribonucleotide to Kv1.4 microinjected intraventricularly into rat brains obstructed hippocampal Kv1.4 mRNA, "knocking down" the protein in the hippocampus. This antisense knockdown had no effect on rat spatial maze learning, memory, or exploratory behavior, but eliminated both early- and late-phase LTP and reduced paired-pulse facilitation (a presynaptic effect) in CA1 pyramidal neurons without affecting dentate gyrus LTP. This presynaptic Kv1.4 knockdown together with previous postsynaptic Kv1.1 knockdown demonstrates that CA1 LTP is neither necessary nor sufficient for rat spatial memory.
Elevated Aminotransferase Activity as an Indication of Muscular Dystrophy: Case Reports and Review of the Literature (1996)

Five male children are reported in whom incidental recognition of elevated serum alanine aminotransferase (ALT) activity initiated investigation to identity the cause of suspected hepatocellular injury. All five were later diagnosed with X chromosome-linked muscular dystrophy. The serum level of ALT, generally considered to be specific for hepatocellular injury, was increased two to 25 times above normal in all the reported cases. Paradoxically, the increase in ALT activity was greater than that of serum aspartate aminotransferase (three to 16 times normal), an enzyme whose elevation is generally recognized as being less specific and indicative of muscle, cardiac, kidney, pancreatic, red blood cell or hepatic injury. At presentation to the gastrointestinal service, one case, age 2.5 months, had no symptoms or signs of neuromuscular dysfunction, while the other four had previously unrecognized hypertrophy of the calves, proximal limb weakness, positive Gower's sign or delayed gross motor skills. All five patients had marked elevation of serum creatine kinase activity and histopathologically confirmed muscular dystrophy. The practical clinical implication of this report is that children with elevated serum ALT, in the absence of other signs and symptoms of hepatic injury, may have occult muscular disease--most frequently muscular dystrophy. Although the clinical signs of muscular dystrophy may be subtle or absent, early determination of creatine kinase will suggest the correct diagnosis and minimize extensive and invasive investigation focusing on hepatic injury.
Chemoselective Hydroxylation of Aliphatic sp3 C–H Bonds Using a Ketone Catalyst and Aqueous H2O2 (2014)

The first ketone-catalyzed method for the oxidation of aliphatic C-H bonds is reported. The reaction conditions employ aryl trifluoromethyl ketones in catalytic amounts and hydrogen peroxide as the terminal oxidant. Hydroxylation is stereospecific and chemoselective for tertiary over secondary C-H bonds. A catalytic cycle invoking a dioxirane as the active oxidant is proposed.