gebhart/patrepeval huggingface dataset:
Differentiation‐regulated loss of the polysialylated embryonic form and expression of the different polypeptides of the neural cell adhesion molecule by cultured oligodendrocytes and myelin (1989)

The expression of the neural cell adhesion molecule (N-CAM) on cultured murine oligodendrocytes, their precursors, and myelin was examined by indirect immunofluorescence, biosynthetic radiolabeling followed by immunoprecipitation and Western blot analysis, using antibodies specific for various forms of the molecule. In all culture systems studied, whether the oligodendrocytes were cultured as an enriched fraction containing precursor cells or in the presence of astrocytes and neurons, a similar differentiation-stage-related expression of N-CAM was seen. At early developmental stages many tetanus toxin receptor- and A2B5 antigen-positive putative oligodendrocyte precursors with bipolar morphology were seen and found to express N-CAM in its embryonic form. Of the 04 antigen-positive immature oligodendrocytes with few slender processes most expressed N-CAM, but few the embryonic form of N-CAM. The more mature 01 or 010 antigen-positive oligodendrocytes were found to express exclusively the adult form of N-CAM. Oligodendrocytes synthesized the 120 and 140 kD forms of N-CAM (N-CAM 120 and N-CAM 140), but not N-CAM 180, although with differentiation, N-CAM 120 predominated in oligodendrocytes and also in pure myelin. N-CAM 120 could be released from oligodendrocytes and myelin by phosphatidylinositol-specific phospholipase C, suggesting that in both oligodendrocytes and myelin N-CAM 120 is inserted into the membrane by covalent linkage to phosphatidylinositol.
High-level Expression and Purification of Recombinant 4-Aminobutyrate Aminotransferases in Escherichia coli (1996)

The protein coding sequence of the 4-aminobutyrate aminotransferase was amplified by polymerase chain reaction (PCR) from a previously cloned cDNA of pig brain using a pair of primers based on the published sequence. The amplified DNA was introduced into a T7 expression vector. Recombinant 4-aminobutyrate aminotransferases were overexpressed in Escherichia coli. The inclusion bodies were formed when enzyme was overexpressed. The unfolded, overproduced proteins were purified by chromatography with hydroxyapatite and refolded by a sequential dialysis method. The renatured 4-aminobutyrate aminotransferase regained the catalytic activity. However, the purified mutant protein did not show the catalytic function of 4-aminobutyrate aminotransferase.
Association between laminin‐8 and glial tumor grade, recurrence, and patient survival (2004)

The data suggest that laminin-8, which may facilitate tumor invasion, contributes to tumor regrowth after therapy. Laminin-8 may be used as a predictor of tumor recurrence and patient survival and as a potential molecular target for glioma therapy.
Fusobacterium nucleatum Induces Premature and Term Stillbirths in Pregnant Mice: Implication of Oral Bacteria in Preterm Birth (2004)

Fusobacterium nucleatum is a gram-negative anaerobe ubiquitous to the oral cavity. It is associated with periodontal disease. It is also associated with preterm birth and has been isolated from the amniotic fluid, placenta, and chorioamnionic membranes of women delivering prematurely. Periodontal disease is a newly recognized risk factor for preterm birth. This study examined the possible mechanism underlying the link between these two diseases. F. nucleatum strains isolated from amniotic fluids and placentas along with those isolated from orally related sources invaded both epithelial and endothelial cells. The invasive ability may enable F. nucleatum to colonize and infect the pregnant uterus. Transient bacteremia caused by periodontal infection may facilitate bacterial transmission from the oral cavity to the uterus. To test this hypothesis, we intravenously injected F. nucleatum into pregnant CF-1 mice. The injection resulted in premature delivery, stillbirths, and nonsustained live births. The bacterial infection was restricted inside the uterus, without spreading systemically. F. nucleatum was first detected in the blood vessels in murine placentas. Invasion of the endothelial cells lining the blood vessels was observed. The bacteria then crossed the endothelium, proliferated in surrounding tissues, and finally spread to the amniotic fluid. The pattern of infection paralleled that in humans. This study represents the first evidence that F. nucleatum may be transmitted hematogenously to the placenta and cause adverse pregnancy outcomes. The results strengthen the link between periodontal disease and preterm birth. Our study also indicates that invasion may be an important virulence mechanism for F. nucleatum to infect the placenta.
Benefit, Risk, and Outcomes in Drug Development: A Systematic Review of Sunitinib (2015)

Even for a successful drug, the risk/benefit balance of trials was similar to phase I cancer trials in general. Sunitinib monotherapy development showed worsening risk/benefit, and the testing of new indications responded slowly to evidence that sunitinib monotherapy would not extend to new malignancies. Research decision-making should draw on evidence from whole research programs rather than a narrow band of studies in the same indication.
Tiggers and DNA transposon fossils in the human genome. (1996)

We report several classes of human interspersed repeats that resemble fossils of DNA transposons, elements that move by excision and reintegration in the genome, whereas previously characterized mammalian repeats all appear to have accumulated by retrotransposition, which involves an RNA intermediate. The human genome contains at least 14 families and > 100,000 degenerate copies of short (180-1200 bp) elements that have 14- to 25-bp terminal inverted repeats and are flanked by either 8 bp or TA target site duplications. We describe two ancient 2.5-kb elements with coding capacity, Tigger1 and -2, that closely resemble pogo, a DNA transposon in Drosophila, and probably were responsible for the distribution of some of the short elements. The deduced pogo and Tigger proteins are related to products of five DNA transposons found in fungi and nematodes, and more distantly, to the Tc1 and mariner transposases. They also are very similar to the major mammalian centromere protein CENP-B, suggesting that this may have a transposase origin. We further identified relatively low-copy-number mariner elements in both human and sheep DNA. These belong to two subfamilies previously identified in insect genomes, suggesting lateral transfer between diverse species.
Renal Denervation for Resistant Hypertension? (2014)

Ever since Schlaich et al.1 first reported on a patient with a blood pressure of 161/107 mm Hg (despite treatment with seven different antihypertensive drugs) that decreased to 127/81 mm Hg after renal denervation, the medical community has been enamored with this procedure. Resistant hypertension evolved into a fashionable diagnosis, and the number of publications pertaining to it grew rapidly.2 Medical-device companies fancied renal denervation as the next big innovation and as a blockbuster therapy for millions of patients. A press release from the American Heart Association even touted renal denervation as a potential “cure” for mild hypertension.3 Trials such . . .
How bad is naive multicast routing? (2002)

In previous approaches to routing multicast connections in networks, the emphasis has been on the source transmitting to a fixed set of destinations (the multicast group). There are some applications where destinations will join and leave the multicast group. Under these conditions, computing an 'optimal' spanning tree after each modification may not be the best way to proceed. An alternative is to make modest alterations to an existing spanning tree to derive a new one. An extreme, though nonoptimal, variation of this is to use minimal cost source to destination routing for each destination, effectively ignoring the existing multicast tree. The authors examine just how nonoptimal these trees are in random general topology networks and conclude that they are worse by only a small factor. The factor is reduced still further if a hierarchy is imposed on the random network to give a more realistic model.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Identification of a Putative Receptor for Porcine Reproductive and Respiratory Syndrome Virus on Porcine Alveolar Macrophages (1998)

To identify the receptor which may determine the macrophage tropism of porcine reproductive and respiratory syndrome virus (PRRSV), monoclonal antibodies (MAbs) against porcine alveolar macrophages (PAM) were produced. Two MAbs (41D3 and 41D5) which completely blocked PRRSV infection of PAM were further characterized. It was found that they reduce the attachment of PRRSV to PAM and immunoprecipitate a 210-kDa membrane protein from PAM. This protein was detected on the cell membranes of PAM but not of PRRSV-nonpermissive cells. A colocalization was found between the reactive sites of MAb 41D3 and PRRSV on PAM membranes. All PRRSV-infected cells in tissues of experimentally infected pigs reacted with MAb 41D3. Taken together, all these data suggest that the identified 210-kDa membrane protein is a putative receptor for PRRSV on porcine macrophages.
Application of thermochromic colorants on textiles: temperature dependence of colorimetric properties (2013)

Commercial thermochromic colorants were applied to a conductive cotton fabric prepared by using nichrome/cotton core‐spun yarns in weft and 100% cotton in warp. The fabrics were pretreated and coloured with thermochromic pigments in isolation, in combination with each other, or in a mixture with a non‐thermochromic pigment. The weft yarns were joined to allow passage of current through the fabric to enable ohmic heat generation to increase fabric temperature. The heat generation and temperature rise could be controlled by monitoring the voltage applied. The colour of the samples changed gradually with an increase in temperature, and significantly so when the temperature of the fabric rose beyond the activation temperature of the thermochromic colorant. The temperature‐dependent properties of commercial thermochromic colorants were determined using a spectrophotometer. Wash fastness of the samples was found to be fair in all cases except with the yellow colorant. Predetermined colour effects, such as camouflage or novel design, can be produced by combining thermochromic colorants with conventional pigments or thermochromic colorants with different activation temperatures.
Subfemtomole MS and MS/MS Peptide Sequence Analysis Using Nano-HPLC Micro-ESI Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (2000)

Subfemtomole peptide sequence analysis has been achieved using microcapillary HPLC columns, with integrated nanoelectrospray emitters, coupled directly to a Fourier transform ion cyclotron resonance mass spectrometer. Accurate mass (+/-0.010 Da) peptide maps are generated from a standard six-protein digest mixture, whose principle components span a concentration dynamic range of 1000:1. Iterative searches against approximately 189000 entries in the OWL database readily identify each protein, with high sequence coverage (20-60%), from as little as 10 amol loaded on-column. In addition, a simple variable-flow HPLC apparatus provides for on-line tandem mass spectrometric analysis of tryptic peptides at the 400-amol level. MS/MS data are searched against approximately 280000 entries in a nonredundant protein database using SEQUEST. Accurate precursor and product ion mass information readily identifies primary amino acid sequences differing by asparagine vs aspartic acid (deltam = 0.98 Da) and glutamine vs lysine (deltam = 0.036 Da).
Members of the Kv1 and Kv2 Voltage-Dependent K+ Channel Families Regulate Insulin Secretion (2001)

In pancreatic beta-cells, voltage-dependent K(+) (Kv) channels are potential mediators of repolarization, closure of Ca(2+) channels, and limitation of insulin secretion. The specific Kv channels expressed in beta-cells and their contribution to the delayed rectifier current and regulation of insulin secretion in these cells are unclear. High-level protein expression and mRNA transcripts for Kv1.4, 1.6, and 2.1 were detected in rat islets and insulinoma cells. Inhibition of these channels with tetraethylammonium decreased I(DR) by approximately 85% and enhanced glucose-stimulated insulin secretion by 2- to 4-fold. Adenovirus-mediated expression of a C-terminal truncated Kv2.1 subunit, specifically eliminating Kv2 family currents, reduced delayed rectifier currents in these cells by 60-70% and enhanced glucose-stimulated insulin secretion from rat islets by 60%. Expression of a C-terminal truncated Kv1.4 subunit, abolishing Kv1 channel family currents, reduced delayed rectifier currents by approximately 25% and enhanced glucose-stimulated insulin secretion from rat islets by 40%. This study establishes that Kv2 and 1 channel homologs mediate the majority of repolarizing delayed rectifier current in rat beta-cells and that antagonism of Kv2.1 may prove to be a novel glucose-dependent therapeutic treatment for type 2 diabetes.
Molecular Characterization of a Neutralizing Domain of the Japanese Encephalitis Virus Structural Glycoprotein (1989)

Expression of antigenic fragments of the Japanese encephalitis virus envelope protein (E) in Escherichia coli has been used to define the boundaries of an antigenic domain that contains the binding sites for 10 anti-E monoclonal antibodies (MAbs). All of these antibodies neutralized the virus in vitro and some of them passively protected mice from a fatal virus challenge. We have shown previously that nine of these antibodies react with the antigenic determinants encoded by a 405 bp fragment of viral cDNA. To determine the amino acid sequences of specific determinants, truncated polypeptides were expressed as fusion proteins in E. coli following progressive Bal 31 exonuclease digestion of the 5' and 3' ends of the cDNA fragment. Examination of the immunoreactivity of these polypeptides revealed that the region from methionine 303 to tryptophan 396 was the shortest sequence capable of reacting with any of the 10 MAbs or with a polyclonal, antiviral hyperimmune mouse ascitic fluid. Biochemical tests showed that an intramolecular disulphide cross-linkage between cysteine 304 and cysteine 335 of the E protein sequence was required for presentation of the binding site(s) for these MAbs. Although this 95 amino acid antigenic domain appeared to be capable of forming several conformational neutralizing epitopes, it was not an effective immunogen for inducing neutralizing or protective antibodies in mice.
Higher potency of N-(4-hydroxyphenyl)retinamide than all-trans-retinoic acid in induction of apoptosis in non-small cell lung cancer cell lines. (1998)

Most human non-small cell lung cancer (NSCLC) cell lines are refractory to all-trans-retinoic acid (ATRA). Recently, N-(4-hydroxyphenyl)retinamide (4HPR) was found to induce apoptosis in various tumor cells. In this study, we compared and contrasted the effects of 4HPR and ATRA on the growth and apoptosis of 10 NSCLC cell lines and normal human bronchial epithelial (NHBE) cells. All of the cancer cell lines and the NHBE cells were sensitive to 10 microM 4HPR, and their numbers decreased to <20% of the controls after a 5-day treatment, whereas ATRA decreased cell numbers to about 50% of the controls in three cell lines and was less effective in the rest of the tumor cell lines. ATRA inhibited the growth of the NHBE cells by 70-80%. 4HPR induced apoptosis in most of the cells, including the ATRA-resistant ones, as evidenced by a DNA fragmentation assay. No correlation was found between growth inhibition by 4HPR and the expression of retinoic acid receptor beta (determined by Northern blotting and PCR), p53, or Bcl-2 proteins (analyzed by Western blotting). These results demonstrate that 4HPR is more potent than ATRA in inducing apoptosis in NSCLC cells and suggest that further clinical trials for prevention and therapy of NSCLC using 4HPR are warranted.
Comparison of techniques for the extraction of tobacco seed oil (2009)

Abstract The yield and fatty acid (FA) composition of the oil obtained from the seeds of a semi‐oriental tobacco ( Nicotiana tabacum L.) plant, type Otlja, by various recovery techniques, which are: Soxhlet extraction (SE), maceration (ME), indirect and direct ultrasonic extraction (IUE and DUE, respectively) and cold pressing (CP), were compared. The solvent extractions of ground tobacco seeds (TS) were carried out by n ‐hexane, while CP was used to recover the oil from the TS. The highest oil yield (32.9 g/100 g, i.e. 93% of the oil content in the seeds) was achieved by CP. Ultrasonically assisted solvent extractions appear to be inefficient in recovering the oil from the ground TS, as the oil yields were only 45–55% of the oil content, depending on the extraction conditions. Independently of the technique applied, linoleic acid was the major FA of the tobacco seed oil (TSO). The compositions of the TSO extracted by SE, ME, IUE and CP were very similar to each other, and the composition of the TSO recovered by DUE depended on the ultrasonic power input. The content of linoleic acid was reduced, while the content of saturated FA was increased by increasing the ultrasonic power from 5 to 50 W.
HIV Type 1 V3 Region Primer-Induced Antibody Suppression Is Overcome by Administration of C4-V3 Peptides as a Polyvalent Immunogen (1995)

The extreme variability of HIV-1 immunogenic regions has hampered attempts to design immunogens capable of inducing broadly reactive neutralizing anti-HIV antibody responses. We have begun to study the immune responses generated to a polyvalent mixture of HIV envelope gp120 synthetic peptides, and to determine the ability of each component of a polyvalent immunogen to prime and boost immune responses to each immunogen component. A major concern regarding the use of a polyvalent mixture of HIV-1 immunogens is that the phenomenon of "original antigenic sin," or HIV-1 primer-induced suppression of antibody responses to a subsequent boost by a second HIV-1 variant, may occur and prevent effective anti-HIV immune responses. Using a prototypic four-valent HIV peptide envelope immunogen in BALB/c mice, we observed two types of primer-induced antibody suppression: "original antigenic sin" with primer-induced suppression of antibody responses to only the boosting immunogen, and a second, novel form of primer-induced antibody suppression, with inhibition of antibody responses not only to the priming immunogen but also to all other immunogens in the polyvalent immunogen mixture as well. Importantly, either reversing the sequence of administration of the immunogens or administration of all four components as a polyvalent mixture completely overcame both forms of HIV-1 primer-induced antibody suppression.
Pembrolizumab (pembro) plus ipilimumab (ipi) for advanced melanoma: Results of the KEYNOTE-029 expansion cohort. (2016)

9506 Background: Pembro (MK-3475), an anti–PD-1 antibody that prevents PD-1 from binding to its ligands, PD-L1 and PD-L2, is approved in several countries for treating advanced melanoma. In KEYNOTE-006, pembro showed superior OS over the anti–CTLA-4 inhibitor ipi. In a phase 3 trial, combination therapy with reduced-dose nivolumab (anti–PD-1) and standard-dose ipi showed higher ORR and longer PFS than either checkpoint inhibitor alone but was associated with increased toxicity. Preliminary data from the phase 1 KEYNOTE-029 study (NCT02089685) suggested that standard-dose pembro + reduced-dose ipi was safe and provided robust antitumor activity. Here, we present data from a larger population of patients (pts) treated with pembro + ipi in the KEYNOTE-029 expansion cohort. Methods: Eligible pts had advanced melanoma, ECOG PS 0-1, no active brain metastases, and no prior immune checkpoint inhibitor therapy. Pts received pembro 2 mg/kg Q3W + ipi 1 mg/kg Q3W for 4 doses, then pembro 2 mg/kg Q3W until intolerable toxicity, progression, or 2 y. Response was assessed by RECIST v1.1 at wk 12, every 6 wk until wk 30, then every 12 wk thereafter. Results: Of 153 pts enrolled in the expansion, 107 had ≥18 wk of follow-up (median 6.4 mo, range 4.3-9.4) by the Oct 26, 2015, data cutoff and were eligible for analysis. 18% of pts had elevated LDH, 55% had stage M1c disease, 36% were BRAFV600mutant, 13% received ≥1 prior therapy, and 12% received a prior BRAF ± MEK inhibitor; 84% had PD-L1–positive tumors (ie, ≥1% staining in tumor and adjacent immune cells). 79 pts (74%) received all 4 ipi doses; 73 pts (68%) remained on pembro. 41 pts (38%) had ≥1 grade 3-4 drug-related AE (DRAE); 68% of these DRAEs resolved by data cutoff. DRAEs led to discontinuation of pembro and ipi in 9 pts (8%), ipi alone in 11 (10%), and pembro alone in 4 (4%); there were no treatment-related deaths. Immune-mediated AEs of any grade and grade 3-4 severity occurred in 57 (53%) and 21 (20%) pts. ORR by investigator review was 57%, with 5 (5%) CR and 56 (52%) PR; by central review, ORR was 51%, with 9% CR and 42% PR. Conclusions: Pembro 2 mg/kg in combination with 4 doses of ipi 1 mg/kg has a manageable toxicity profile and provides robust antitumor activity in pts with advanced melanoma. Clinical trial information: NCT02089685.
Growth of Refractory Crystals Using the Induction Plasma Torch (1961)

Apparatus is described for growing refractory crystals using the induction plasma torch in a Verneuil-type geometry. The plasma torch makes possible crystal growth at higher temperatures than can be achieved with flames and in inert or reactive atmospheres. Conditions are given for growth of sapphire, stabilized zirconia, and niobium crystals.
Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel (2010)

We suggest that 5-FU-loaded PEG-hydrogels could provide a useful tool for the development of an anticancer drug delivery system.
Search for Monotop Signatures in Proton-Proton Collisions ats=8  TeV (2015)

Results are presented from a search for new decaying massive particles whose presence is inferred from an imbalance in transverse momentum and which are produced in association with a single top quark that decays into a bottom quark and two light quarks. The measurement is performed using 19.7 fb^{-1} of data from proton-proton collisions at a center-of-mass energy of 8 TeV, collected with the CMS detector at the CERN LHC. No deviations from the standard model predictions are observed and lower limits are set on the masses of new invisible bosons. In particular, scalar and vector particles, with masses below 330 and 650 GeV, respectively, are excluded at 95% confidence level, thereby substantially extending a previous limit published by the CDF Collaboration.
Global Cancer Statistics, 2002 (2005)

Estimates of the worldwide incidence, mortality and prevalence of 26 cancers in the year 2002 are now available in the GLOBOCAN series of the International Agency for Research on Cancer. The results are presented here in summary form, including the geographic variation between 20 large "areas" of the world. Overall, there were 10.9 million new cases, 6.7 million deaths, and 24.6 million persons alive with cancer (within three years of diagnosis). The most commonly diagnosed cancers are lung (1.35 million), breast (1.15 million), and colorectal (1 million); the most common causes of cancer death are lung cancer (1.18 million deaths), stomach cancer (700,000 deaths), and liver cancer (598,000 deaths). The most prevalent cancer in the world is breast cancer (4.4 million survivors up to 5 years following diagnosis). There are striking variations in the risk of different cancers by geographic area. Most of the international variation is due to exposure to known or suspected risk factors related to lifestyle or environment, and provides a clear challenge to prevention.