gebhart/patrepeval huggingface dataset:
Human immunodeficiency virus type 1 envelope gene structure and diversity in vivo and after cocultivation in vitro (1992)

Nested-primer polymerase chain reaction (PCR) has been applied to the molecular cloning of 4.6-kb half-genome fragments of human immunodeficiency virus type 1 (HIV-1) taken directly from the peripheral blood mononuclear cells (PBMC) of an individual with neurological symptoms of HIV-1 infection. In a similar manner, gp120-coding portions of the envelope gene were cloned after PBMC from the same blood sample were cocultivated with uninfected PBMC for 28 days. The complete 1.6-kb nucleotide sequence of the gp120 gene was determined from each of 35 clones examined. Two of 13 (15%) PBMC-derived gp120 genes and 3 of 22 (14%) coculture-derived gp120 genes were defective as a result of frameshifts and an in-frame stop codon(s). Mean diversity between individual gp120-coding sequences in PBMC was fivefold greater (3.24%) than after coculture (0.65%). A predominant sequence of "strain" was found after coculture that was distinct from the diverse viral genotypes detected in vivo and therefore was selectively amplified during in vitro propagation. Multiple distinct third variable (V3) regions encoding the principal neutralizing domain of the envelope protein were detected in PBMC-derived genes, suggesting the presence of immunologic diversity of HIV env genes in vivo not reflected in the cocultured virus sample. The large size of the HIV fragments generated in this study will permit analysis of the diversity of immunologic reactivity, gene function, and pathogenicity of HIV genomes present within infected individuals, including the functional significance of the loss of diversity that occurs upon coculture.
The PP-Fold Solution Structure of Human Polypeptide YY and Human PYY3-36 As Determined by NMR, (2006)

PYY3-36 is a biopharmaceutical antiobesity agent under development as well as an endogenous satiety hormone, which is generated by dipeptidyl peptidase-IV digestion of polypetide YY (PYY), and in contrast to the parent hormone, PYY is highly selective for the Y2 versus the Y1 receptor. NMR analysis revealed a highly ordered, back-folded structure for human PYY in aqueous solution similar to the classical PP-fold structure of pancreatic polypeptide. The NMR analysis of PYY3-36 also showed a folded structure resembling a PP-fold, which however was characterized by far fewer long distance NOEs than the PP-fold observed in the full-length peptide. This suggests that either a conformational change has occurred in the N-terminal segment of PYY3-36 or that this segments is characterized by larger dynamics. The study supports the notion that the PP-fold is crucial for establishing simultaneous interactions with two subsites in the receptor for binding of, respectively, the N- and C-terminal ends of PYY. The Y2 receptor only requires recognition of the C-terminal segment of the molecule as displayed by the Y2 selective PYY3-36.
Abstract B141: Effects of AZD8055, a novel mTOR kinase inhibitor, in human cancer cells developing resistance to rapamycin (2009)

Abstract Background: Cancer cells are thought to adapt to rapamycin, an inhibitor of mTORC1, by activating AKT via mTORC2 and others mTORC1-independent survival pathways. In this study, we explored the effects of AZD8055, an ATP competitive inhibitor of mTOR, inhibiting both mTORC1 and mTORC2, in cancer cells with intrinsic and developing resistance to rapamycin. Materials and Methods: Antiproliferative effects and cellular growth inhibition of AZD8055 and rapamycin were evaluated in a panel of 20 human cancer cell lines by MTT assay. Baseline and phosphorylated protein levels were assessed usingWestern blot. mRNA expression was studied by qRT-PCR. Results: AZD8055 and rapamycin (48h exposures) displayed antiproliferative effects in our cell panel at IC50s ranging 0.005–&amp;gt;3µM and 0.04–20µM, respectively. CAKI1 and SK-HEP1 cells expressed high mRNA levels of mesenchymal markers (vimentin, N-cadherin, ZEB1, SIP1, SLUG, ACTA2, and HMGA2) and low levels of E-cadherin associated with intrinsic resistance to several receptor tyrosine kinase inhibitors. AZD8055 induced antiproliferative effects in CAKI1 and SK-HEP1 cells at concentrations &amp;lt;0.1µM. In CAKI1 and SK-HEP1 cells exposed to 0.1µM rapamycin for 5–24h, we observed the inhibition of p-S6 Ser235/236 but an activation of p-AKTser473. Consistent with its mechanism of action, exposure to 0.1µM AZD8055 led to the inhibition to p-S6, and p-4EBP1Ser65, without p-AKT ser473 activation. Downstream to mTORC2, PKC Ser657 was transiently activated by both rapamycin and AZD8055 in CAKI1 cells but not in SK-HEP1 cells. To study the acquired resistance to rapamycin, SK-HEP1 cells were grown with increased concentrations of rapamycin for &amp;gt;6 months, making these cells tolerant to ≥4-fold IC50 concentrations. In SK-RAP cells, we observed the transcriptional activation of IGF1R, TGFB2, the anti-apoptotic factors BCL2 and CDKN1Ap21, and the multidrug resistance ABCB1mdr1. In SK-RAP cells, sustained exposure to rapamycin increased pAKTser473 and decreased p-S6 and p-PKC. Consistent with the inhibition of mTOR kinase activity, exposure to AZD8055 for 5h almost completely abrogated rapamycin-induced AKTser473 activation in SK-RAP cells. Furthermore, SK-RAP cells were more sensitive to AZD8055 than to the parental SK-HEP1 cells (IC50: 0.1 versus &amp;gt;3µM, p=0.044), possibly due to the extended functions of AZD8055 against mTORC1 and inhibition of mTORC2. Conclusions: AZD8055, by inhibiting mTOR kinase activity, decreases mTORC1 substrates pS6 and p-4EBP1Ser65 and mTORC2 substrate AKTser473. AZD8055 decreases cancer cell proliferation in cell lines expressing mesenchymal markers displaying intrinsic and developing resistance to rapamycin, abrogating the hyperactivation of AKT observed in these cells after rapamycin exposure. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B141.
Pilot Study of Vaccination with Recombinant CEA-MUC-1-TRICOM Poxviral-Based Vaccines in Patients with Metastatic Carcinoma (2008)

This vaccine strategy seems to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this agent, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted.
Polycomb Proteins Targeted by a Short Repeat RNA to the Mouse X Chromosome (2008)

To equalize X-chromosome dosages between the sexes, the female mammal inactivates one of her two X chromosomes. X-chromosome inactivation (XCI) is initiated by expression of Xist, a 17-kb noncoding RNA (ncRNA) that accumulates on the X in cis. Because interacting factors have not been isolated, the mechanism by which Xist induces silencing remains unknown. We discovered a 1.6-kilobase ncRNA (RepA) within Xist and identified the Polycomb complex, PRC2, as its direct target. PRC2 is initially recruited to the X by RepA RNA, with Ezh2 serving as the RNA binding subunit. The antisense Tsix RNA inhibits this interaction. RepA depletion abolishes full-length Xist induction and trimethylation on lysine 27 of histone H3 of the X. Likewise, PRC2 deficiency compromises Xist up-regulation. Therefore, RepA, together with PRC2, is required for the initiation and spread of XCI. We conclude that a ncRNA cofactor recruits Polycomb complexes to their target locus.
Agonists of Toll-Like Receptors 3, 4, 7, and 9 Are Candidates for Use as Adjuvants in an Outer Membrane Vaccine againstNeisseria meningitidisSerogroup B (2007)

The bacterium Neisseria meningitidis is the causative agent of meningitis and sepsis. A generally effective vaccine against N. meningitidis serogroup B is not yet available, but outer membrane vesicle vaccines are in development. These vaccines contain lipopolysaccharide (LPS). The inclusion of N. meningitidis wild-type LPS in a vaccine is controversial because of its high toxicity. Therefore, the adjuvant activity of a panel of different Toll-like receptor (TLR) agonists in combination with LPS-deficient meningococcal outer membrane complexes was compared after immunization of mice. The results demonstrate that TLR3, TLR4, TLR7, and TLR9 agonists enhance immune responses against LPS-deficient outer membrane complexes. Their adjuvant activity was characterized by higher levels of antigen-specific immunoglobulin G (IgG), IgG2a, and IgG2b; a higher IgG2a/IgG1 ratio; lower total IgE levels; and most importantly, higher serum bactericidal antibody titers compared to LPS-deficient outer membrane complexes alone.
Lethality during continuous anthrax lethal toxin infusion is associated with circulatory shock but not inflammatory cytokine or nitric oxide release in rats (2004)

Although circulatory shock related to lethal toxin (LeTx) may play a primary role in lethality due to Bacillus anthracis infection, its mechanisms are unclear. We investigated whether LeTx-induced shock is associated with inflammatory cytokine and nitric oxide (NO) release. Sprague-Dawley rats with central venous and arterial catheters received 24-h infusions of LeTx (lethal factor 100 microg/kg; protective antigen 200 microg/kg) that produced death beginning at 9 h and a 7-day mortality rate of 53%. By 9 h, mean arterial blood pressure, heart rate, pH, and base excess were decreased and lactate and hemoglobin levels were increased in LeTx nonsurvivors compared with LeTx survivors and controls (diluent only) (P < or = 0.05 for each comparing the 3 groups). Despite these changes, arterial oxygen and circulating leukocytes and platelets were not decreased and TNF-alpha, IL-beta, IL-6, and IL-10 levels were not increased comparing either LeTx nonsurvivors or survivors to controls. Nitrate/nitrite levels and tissue histology also did not differ comparing LeTx animals and controls. In additional experiments, although 24-h infusions of LeTx and Escherichia coli LPS produced similar mortality rates (54 and 56%, respectively) and times to death (13.2 +/- 0.8 vs. 11.0 +/- 1.7 h, respectively) compared with controls, only LPS reduced circulating leukocytes, platelets, and IL-2 levels and increased TNF-alpha, IL-1 alpha and -1 beta, IL-6, IL-10, interferon-gamma, granulocyte macrophage-colony stimulating factor, RANTES, migratory inhibitory protein-1 alpha, -2, and -3, and monocyte chemotactic protein-1, as well as nitrate/nitrite levels (all P < or = 0.05 for the effects of LPS). Thus, in contrast to LPS, excessive inflammatory cytokine and NO release does not appear to contribute to the circulatory shock and lethality occurring with LeTx in this at model. Although therapies to modulate these host mediators may be applicable fo shock caused by LPS or other bacterial toxins, they may not with LeTx.
CHLOROPHYLL DEGRADATION (1999)

Although the loss of green color in senescent leaves and ripening fruits is a spectacular natural phenomenon, research on chlorophyll breakdown has been largely neglected until recently. This review summarizes knowledge about the fate of chlorophyll in degreening tissues that has been gained during the past few years. Structures of end- and intermediary products of degradation as well as the biochemistry of the porphyrin-cleaving reaction have been elucidated. The intracellular localization of the catabolic pathway is particularly important in the regulation of chlorophyll breakdown. None of the genes encoding the related catabolic enzymes has so far been isolated, which makes chlorophyll degradation an area of opportunity for future research.
Lecithins (2005)

Abstract Lecithin is a novel natural material that has multifunctional properties. Original material was isolated from egg yolk and is found in significant quantities in brain and nervous tissue. Actually lecithin is a normal constituent in all cell membranes. The main source today is found in soybeans and is commercially available in many colors, viscosities, and functionalities. This article gives a detailed description of the nature and composition of lecithin and its manufacture and uses. Lecithin has been an amphoteric surfactant for centuries but was not commercialized until soy processing started in the 1930's. It has many food applications and is also used in pharmaceutical preparations and natural food products. Lecithin has some unique properties in industrial applications from paints to fuel additives. The most prevalent use today is in chocolate and margarine manufacture and in nutritional beverages and supplements.
Switching Between Diversity and Multiplexing in MIMO Systems (2005)

Multiple-input multiple-output (MIMO) wireless communication systems can offer high data rates through spatial multiplexing or substantial diversity using transmit diversity. In this letter, switching between spatial multiplexing and transmit diversity is proposed as a simple way to improve the diversity performance of spatial multiplexing. In the proposed approach, for a fixed rate, either multiplexing or diversity is chosen based on the instantaneous channel state and the decision is conveyed to the transmitter via a low-rate feedback channel. The minimum Euclidean distance at the receiver is computed for spatial multiplexing and transmit diversity and is used to derive the selection criterion. Additionally, the Demmel condition number of the matrix channel is shown to provide a sufficient condition for multiplexing to outperform diversity. Monte Carlo simulations demonstrate improvement over either multiplexing or diversity individually in terms of bit error rate.
N*-N*-S* Tridentate ligand system as potential antitumor agents (1981)

Compounds containing an N*-N*-S* tridentate ligand were synthesized and tested for antitumor activity against P-388 lymphocytic leukemia in mice. Of these, only 2,2'-bipyridyl-6-carbothioamide (1a) showed antitumor activity at relatively high dosage levels. Compound 1a was also evaluated against L-1210 and S180 cells in culture and found to have significant activity.
Aspirin Dose for the Prevention of Cardiovascular Disease (2007)

Currently available clinical data do not support the routine, long-term use of aspirin dosages greater than 75 to 81 mg/d in the setting of cardiovascular disease prevention. Higher dosages, which may be commonly prescribed, do not better prevent events but are associated with increased risks of gastrointestinal bleeding.
Transcranial magnetic stimulation in neurology (2013)

Transcranial magnetic stimulation (TMS) is a neurophysiologic technique to noninvasively induce a controlled current pulse in a prespecified cortical target. This can be used to transiently disrupt the function of the targeted cortical region and explore causal relations to behavior, assess cortical reactivity, and map out functionally relevant brain regions, for example during presurgical assessments. Particularly when applied repetitively, TMS can modify cortical excitability and the effects can propagate trans-synaptically to interconnected cortical, subcortical, and spinal cord regions. As such, TMS can be used to assess the functional integrity of neural circuits and to modulate brain activity with potential therapeutic intent.
RANKL-Induced Expression of Tetraspanin CD9 in Lipid Raft Membrane Microdomain Is Essential for Cell Fusion During Osteoclastogenesis (2006)

These data suggest that function of tetraspanin CD9 and its expression in lipid rafts are crucial for cell fusion during osteoclastogenesis.
Poly(alkyl cyanoacrylate) Nanospheres for Oral Administration of Insulin (1997)

Poly(alkyl cyanoacrylate) nanocapsules have been successfully used for oral administration of insulin in diabetic rats. This work reports a suitable formulation for insulin-loaded nanospheres composed of full polymeric structures formed by polymerization of isobutyl cyanoacrylate (IBCA) in an acidic medium, insulin (15 U/mL) being added to the polymerization medium 60 min after the onset of polymerization. These nanospheres (MW 364) displayed a mean size of 145 nm and an association rate of 1 U of insulin/mg of polymer. They protected insulin from the degradation by proteolytic enzymes in vitro, especially when they were dispersed in an oily medium (Miglyol 812) containing surfactive agents (Poloxamer 188 and deoxycholic acid). When dispersed in the same medium, insulin-loaded nanospheres (100 U/kg of body weight), administered perorally in streptozotocin-induced diabetic rats, provoked a 50% decrease of fasted glycemia from the second hour up to 10-13 days. This effect was shorter (2 days) or absent when nanospheres were dispersed in water with surfactive agents or not. Using 14C-labeled nanospheres loaded with [125I]insulin, it was found that nanospheres increased the uptake of [125I]insulin or its metabolites in the gastrointestinal tract, blood, and liver while the excretion was delayed when compared to [125I]insulin nonassociated to nanospheres; in addition, 14C- and 125I-radioactivities disappeared progressively as a function of time, parallel to the biological effect. Thus insulin-loaded nanospheres can be considered as a convenient delivery system for oral insulin at the prerequisite that they were dispersed in an oily phase containing surfactants.
An immunohistochemical study of the distribution of epithelial antigens in the uterine cervix. (1983)

Neoplastic and nonneoplastic tissue from human uterine cervixes was stained immunohistochemically for three epithelial antigens--epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and cytoplasmic keratin. Anti-EMA serum stained four of 21 nonneoplastic cases and all cases of cervical intraepithelial neoplasia (CIN) (25) and invasive carcinoma (16); CEA was positive in six of ten of the nonneoplastic specimens, 19 of 23 CIN specimens, and six of seven invasive carcinomas tested. Cytoplasmic keratin did not survive fixation in formal saline and for this antigen tissue had to be fixed in methacarn; all the tissues examined were positive.
Design of an Optical See-through Multi-Focal-Plane Stereoscopic 3D Display Using Freeform Prisms (2012)

We presented the design of an optical see-through multi-focal-plane 3D display using wedge-shaped freeform eyepiece and compensator, which is capable of rendering near-accurate focus cues for a 3-diopter depth range with high image quality.
Recovering semantics of tables on the web (2011)

The Web offers a corpus of over 100 million tables [6], but the meaning of each table is rarely explicit from the table itself. Header rows exist in few cases and even when they do, the attribute names are typically useless. We describe a system that attempts to recover the semantics of tables by enriching the table with additional annotations. Our annotations facilitate operations such as searching for tables and finding related tables. To recover semantics of tables, we leverage a database of class labels and relationships automatically extracted from the Web. The database of classes and relationships has very wide coverage, but is also noisy. We attach a class label to a column if a sufficient number of the values in the column are identified with that label in the database of class labels, and analogously for binary relationships. We describe a formal model for reasoning about when we have seen sufficient evidence for a label, and show that it performs substantially better than a simple majority scheme. We describe a set of experiments that illustrate the utility of the recovered semantics for table search and show that it performs substantially better than previous approaches. In addition, we characterize what fraction of tables on the Web can be annotated using our approach.
Targeting of Metabotropic Glutamate Receptors for the Treatment of Schizophrenia (2011)

The glutamatergic system is involved in a wide range of physiological processes in the brain, and its dysfunction plays an important role in the etiology and pathophysiology of psychiatric disorders, including schizophrenia. Among the glutamate receptors, metabotropic receptors (mGlu receptors) have emerged as attractive therapeutic targets for the development of novel interventions for psychiatric disorders. Among them, group II mGlu receptors, such as mGlu2 and mGlu3 receptors, are of particular interest because of their unique distribution and the regulatory roles they have in neurotransmission. Recently, potent agonists for mGlu2/3 receptor have been synthesized, and their pharmacological roles have been intensively investigated in animal models. The efficacy for the treatment of schizophrenia has also been proven in a clinical trial. Recently, much attention has been paid to mGlu2 receptor potentiators, which potentiate the glutamate response without affecting the actual activity of the mGlu2 receptor. In addition, mGlu1 receptor antagonists have recently been proposed as an attractive approach to developing novel antipsychotics in animal models. This review describes the potential of both mGlu2/3 receptor agonists/potentiators and mGlu1 receptor antagonists for the treatment of schizophrenia.
Directed selection of recombinant human monoclonal antibodies to herpes simplex virus glycoproteins from phage display libraries. (1995)

Human monoclonal antibodies have considerable potential in the prophylaxis and treatment of viral disease. However, only a few such antibodies suitable for clinical use have been produced to date. We have previously shown that large panels of human recombinant monoclonal antibodies against a plethora of infectious agents, including herpes simplex virus types 1 and 2, can be established from phage display libraries. Here we demonstrate that facile cloning of recombinant Fab fragments against specific viral proteins in their native conformation can be accomplished by panning phage display libraries against viral glycoproteins "captured" from infected cell extracts by specific monoclonal antibodies immobilized on ELISA plates. We have tested this strategy by isolating six neutralizing recombinant antibodies specific for herpes simplex glycoprotein gD or gB, some of which are against conformationally sensitive epitopes. By using defined monoclonal antibodies for the antigen-capture step, this method can be used for the isolation of antibodies to specific regions and epitopes within the target viral protein. For instance, monoclonal antibodies to a nonneutralizing epitope can be used in the capture step to clone antibodies to neutralizing epitopes, or antibodies to a neutralizing epitope can be used to clone antibodies to a different neutralizing epitope. Furthermore, by using capturing antibodies to more immunodominant epitopes, one can direct the cloning to less immunogenic ones. This method should be of value in generating antibodies to be used both in the prophylaxis and treatment of viral infections and in the characterization of the mechanisms of antibody protective actions at the molecular level.