gebhart/patrepeval huggingface dataset:
Expression of Functional Metabotropic Glutamate Receptors in Primary Cultured Rat Osteoblasts (2000)

Osteoblasts and osteoclasts express functional N-methyl-d-aspartate (NMDA) receptors, which participate in regulation of bone matrix. In rat femoral osteoblasts held in whole cell clamp there is a robust NMDA current but little if any response to l-glutamate. We have investigated expression of metabotropic glutamate receptors (mGluRs) in these cells. By reverse transcription polymerase chain reaction, we have detected expression of mGluR1b (but not mGluR1a, 2, 3, 4, 5, or 6). Blockade of mGluRs with (+/-)-alpha-methyl-carboxyphenyl-glycine resulted in an enlarged l-glutamate-induced current that resembled the response to NMDA. Conversely, prior stimulation of mGluRs with trans-(+/-)-1-amino-1, 3-cyclopentanedicarboxylic acid (1S,3R-ACPD; mGluR agonist) reduced the NMDA-induced current by 77%. Monitoring of [Ca(2+)](i) showed that NMDA induced a sustained elevation of [Ca(2+)](i), which was dependent upon [Ca(2+)](o). Treatment with 1S,3R-ACPD generated an initial transient that was independent of [Ca(2+)](o), followed by a sustained, [Ca(2+)](o)-dependent phase, a response consistent with phospholipase C-mediated mobilization of stored Ca(2+). Investigations of the interaction between the two receptors confirmed inhibitory modulation of the NMDA receptor-induced rise in [Ca(2+)](i) by mGluRs. Parathyroid hormone, which also activates phospholipase C in osteoblasts, had a similar inhibitory effect on the NMDA receptor-induced [Ca(2+)](i) response. Elevation of [Ca(2+)](i) mediated by mGluR activation was reduced by subsequent stimulation of NMDA receptors. This is the first description of mGluRs in bone and shows that complex glutamatergic signaling can occur in this tissue.
Dirofilaria immitis in cats: diagnosis and management. (2008)

Imaging and laboratory studies can help with the diagnosis of heartworm disease in cats, but no test is definitive. Furthermore, even when the diagnosis can be reliably established, therapy directed at the heartworms does little to help the cat. Rather, management is directed at alleviating clinical signs, with an emphasis on prevention for all.
Ischemia/Reperfusion Injury Promotes and Granulocyte-Colony Stimulating Factor Inhibits Migration of Bone Marrow-Derived Stem Cells to Endometrium (2012)

The endometrium is a dynamic tissue that undergoes repeated rounds of regeneration in each reproductive (estrous or menstrual) cycle. We have previously shown that bone marrow (BM)-derived stem cells engraft the endometrium in rodents and humans; however, it is not known if these cells contribute physiologically to uterine cyclic regeneration or alternatively are primarily involved in uterine repair in response to injury. Here we performed male-to-female BM transplant and tested the ability of uterine injury to recruit BM-derived cells to endometrium in the presence and absence of sex steroids. Uterine ischemia/reperfusion injury resulted in an ~2-fold increase in BM-derived stem cell recruitment to the endometrium. The effect was independent of sex steroids or the existence of an estrous cycle. BM-derived mesenchymal stem cells (MSCs) are involved in uterine repair after injury, but not the cyclic regeneration of the endometrium in the estrous/menstrual cycle. Granulocyte-colony stimulating factor (G-CSF) is used to increase BM mobilization for transplant and has been proposed as a means of mobilizing stem cells to the uterus. Here G-CSF treatment led to decreased BM engraftment of the uterus after injury, likely by favoring mobilization of hematopoietic stem cells over the MSCs. G-CSF is unlikely to be of benefit in repair of uterine injury in humans. Taken together, we demonstrate that ischemic injury drives BM MSC engraftment of the uterus, independent of estrous cycle, sex steroids, or G-CSF.
Iodination of monoclonal antibodies for diagnosis and radiotherapy using a convenient one vial method. (1986)

We have developed a convenient system that can be used to iodinate monoclonal antibodies for diagnosis or therapy. A vial, previously coated with 1,3,4,6-tetrachloro-3a, 6a-diphenyl glycouril (iodogen), is used as a reaction vessel. Iodination and separation of bound and free iodide, using AG1-X8 ion exchange resin, are both accomplished in this vial. We found 90 +/- 4% of the iodide which was added was incorporated, respectively, into each of four different monoclonal antibodies evaluated. Approximately 90% of labeled antibody was recovered in each case. The monoclonal antibody OC125 was labeled to specific activities up to 25 mCi/mg. Immunoreactivities of 82 +/- 2% using 125I and 66 +/- 5% using 131I were achieved. As the radioiodination is done in one sealed vial and takes less than 15 min, this procedure is safe and can be performed in any nuclear medicine laboratory. The final product, which is sterile and apyrogenic, is suitable for diagnostic and radiotherapeutic applications.
Chlorination of Poultry Chiller Water: Chlorine Demand and Disinfection Efficiency (1992)

A study was conducted to determine the general composition of equilibrated poultry chiller water (near maximum solids content) from a commercial operation, the chlorine consumption by its components, and the chlorine dosage necessary to achieve its disinfection. The equilibrated chiller water contained .35% (CV, 40%) solids, which consisted of lipids (56%), ash (33%), and total nitrogen (4.2%). Residual chlorine and survival of aerobic bacteria were determined in chiller water dosed with chlorine levels ranging from 0 to 400 ppm. Initially, the added chlorine was rapidly consumed by the components of chiller water. However, the consumption rate quickly decreased to 1/1,000 of the initial rate after about 50 min. The change of residual chlorine with time was found to fit mathematically to a two-term exponential equation. The equilibrated chiller water had a chlorine demand greater than the highest chlorine dosage tested (400 ppm). No free chlorine was detected in the water after 30 min of exposure to 300 ppm chlorine. Because of the high chlorine demand, dosages of 100 to 150 ppm chlorine were required to reduce the number of bacteria by at least 99% within 3 to 5 min in laboratory tests. Increasing the time of exposure to chlorine resulted in further reduction, although at a slow rate, of surviving bacteria from treatments that gave incomplete destruction with short exposure.
Visual Tracking with Fully Convolutional Networks (2015)

We propose a new approach for general object tracking with fully convolutional neural network. Instead of treating convolutional neural network (CNN) as a black-box feature extractor, we conduct in-depth study on the properties of CNN features offline pre-trained on massive image data and classification task on ImageNet. The discoveries motivate the design of our tracking system. It is found that convolutional layers in different levels characterize the target from different perspectives. A top layer encodes more semantic features and serves as a category detector, while a lower layer carries more discriminative information and can better separate the target from distracters with similar appearance. Both layers are jointly used with a switch mechanism during tracking. It is also found that for a tracking target, only a subset of neurons are relevant. A feature map selection method is developed to remove noisy and irrelevant feature maps, which can reduce computation redundancy and improve tracking accuracy. Extensive evaluation on the widely used tracking benchmark [36] shows that the proposed tacker outperforms the state-of-the-art significantly.
Stochastic Analysis of Stepwise Fluorescence Quenching Reactions on Single-Walled Carbon Nanotubes: Single Molecule Sensors (2008)

The 1D quantum confinement of photogenerated excitons in single-walled carbon nanotubes (SWNT) can amplify the detection of molecular adsorption to where single-molecule discrimination is realizable, even from within living cells and tissues. Toward this aim, we present a type 1 collagen film, similar to those used as 3D cell scaffolds for tissue engineering, containing embedded SWNT capable of reporting single-molecule adsorption of quenching molecules. We utilize hidden Markov modeling to link single-molecule adsorption events to rate constants for H2O2, H+, and Fe(CN)6(3-). Among the three kinds of reactant molecules studied, H2O2 has the highest quenching equilibrium constant of 1.59 at 20 microM, whereas H+ is so insensitive that a similar equilibrium constant is achieved only with a concentration of 0.1 M (pH 1). The results were self-consistent because reverse (unquenching) rate constants (600 micros(-1) for H2O2, 1130 micros(-1) for H+ and 4000 micros(-1) for Fe(CN)6(3-)) were observed to be concentration-independent and the forward (quenching) rate constants varied monotonically with concentration. The quenching rate constants also increased with an increase in the redox potential of the quencher, indicating that electron transfer increases the adsorption equilibrium constant on the nanotube surface and, hence, the dwell time of the quencher. These developments provide the material, analytical, and mechanistic groundwork for SWNT to function as single-molecule stochastic biosensors.
Viral pneumonia and respiratory sepsis: Association, causation, or it depends?* (2007)

Inserm UMR-S 707, Université Pierre et Marie Curie-Paris 6, Paris, France The authors have not disclosed any potential conflicts of interest.
Membrane topology analysis of Escherichia coli K-12 Mtr permease by alkaline phosphatase and beta-galactosidase fusions (1995)

The mtr gene of Escherichia coli K-12 encodes an inner membrane protein which is responsible for the active transport of trypotophan into the cell. It has been proposed that the Mtr permease has a novel structure consisting of 11 hydrophobic transmembrane spans, with a cytoplasmically disposed amino terminus and a carboxyl terminus located in the periplasmic space (J.P. Sarsero, P. J. Wookey, P. Gollnick, C. Yanofsky, and A.J. Pittard, J. Bacteriol. 173:3231-3234, 1991). The validity of this model was examined by the construction of fusion proteins between the Mtr permease and alkaline phosphatase or beta-galactosidase. In addition to the conventional methods, in which the reporter enzyme replaces a carboxyl-terminal portion of the membrane protein, the recently developed alkaline phosphatase sandwich fusion technique was utilized, in which alkaline phosphatase is inserted into an otherwise intact membrane protein. A cluster of alkaline phosphatase fusions to the carboxyl-terminal end of the Mtr permease exhibited high levels of alkaline phosphatase activity, giving support to the proposition of a periplasmically located carboxyl terminus. The majority of fusion proteins produced enzymatic activities which were in agreement with the positions of the fusion sites on the proposed topological model of the permease. The synthesis of a small cluster of hybrid proteins, whose enzymatic activity did not agree with the location of their fusion sites within putative transmembrane span VIII or the preceding periplasmic loop, was not detected by immunological techniques and did not necessitate modification of the proposed model in this region. Slight alterations may need to be made in the positioning of the carboxyl-terminal end of transmembrane span X.
Introduction (1988)

I have not organised this book along either developmental or chronological lines. Instead, it is organised like a sampler of feminist critical techniques, theories, political positions, issues, explorations and theatre practices. Each chapter and each of its constituent sections is relatively complete in itself, allowing the reader either to read it in the order in which it appears, or to pick out for independent reference a section on a single author, such as Aphra Behn, a single position, such as materialist feminism, or a single theory, such as semiotics. However, in attempting to outline the overall relationship between the feminist movement and work in the theatre, I have built the discussion on three bases: history, practice and theory.
Strong Cytotoxic T Cell and Weak Neutralizing Antibody Responses in a Subset of Persons with Stable Nonprogressing HIV Type 1 Infection (1996)

Some individuals in well-defined cohorts have now been infected with HIV-1 for well over a decade and yet remain clinically asymptomatic with normal CD4 counts. To determine immunologic and virologic parameters in these individuals, we examined 10 persons from the San Francisco City Clinic with firmly documented infection of 11-15 years duration who had maintained stable CD4 counts above 500 cells/microliters. Our results indicate that long-term nonprogressors are a heterogeneous group with respect to viral load and HIV-1-specific immune responses, and that progression can occur even after 15 years of stable infection. However, in a subset of persons with the lowest viral loads and persistent nonprogressive infection, we detected strong CTL responses, whereas neutralizing antibody studies revealed weak to undetectable titers against a panel of 10 primary isolates. This study demonstrates that a vigorous in vivo activated HIV-1-specific CTL response can be part of the host immune response in stable nonprogressive HIV-1 infection, and that circulating activated CTL can be detected in the setting of an extremely low viral load. These results also indicate that long-term nonprogressing HIV-1 infection does not require the presence of broadly cross-reactive neutralizing antibodies.
Therapeutic treatment with an oral prodrug of the remdesivir parental nucleoside is protective against SARS-CoV-2 pathogenesis in mice (2022)

The coronavirus disease 2019 (COVID-19) pandemic remains uncontrolled despite the rapid rollout of safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, underscoring the need to develop highly effective antivirals. In the setting of waning immunity from infection and vaccination, breakthrough infections are becoming increasingly common and treatment options remain limited. In addition, the emergence of SARS-CoV-2 variants of concern, with their potential to escape neutralization by therapeutic monoclonal antibodies, emphasizes the need to develop second-generation oral antivirals targeting highly conserved viral proteins that can be rapidly deployed to outpatients. Here, we demonstrate the in vitro antiviral activity and in vivo therapeutic efficacy of GS-621763, an orally bioavailable prodrug of GS-441524, the parent nucleoside of remdesivir, which targets the highly conserved virus RNA-dependent RNA polymerase. GS-621763 exhibited antiviral activity against SARS-CoV-2 in lung cell lines and two different human primary lung cell culture systems. GS-621763 was also potently antiviral against a genetically unrelated emerging coronavirus, Middle East respiratory syndrome CoV (MERS-CoV). The dose-proportional pharmacokinetic profile observed after oral administration of GS-621763 translated to dose-dependent antiviral activity in mice infected with SARS-CoV-2. Therapeutic GS-621763 administration reduced viral load and lung pathology; treatment also improved pulmonary function in COVID-19 mouse model. A direct comparison of GS-621763 with molnupiravir, an oral nucleoside analog antiviral that has recently received EUA approval, proved both drugs to be similarly efficacious in mice. These data support the exploration of GS-441524 oral prodrugs for the treatment of COVID-19.
Prognostic Value of an Activation State Marker for Epidermal Growth Factor Receptor in Tissue Microarrays of Head and Neck Cancer (2006)

Overexpression and mutation of epidermal growth factor receptors (EGFR) have been shown to be important in the prognosis of several cancers, including head and neck cancers. However, our inability to define the activation status of these and other receptors limits our ability to assess the importance of these pathways and to exploit effectively new molecularly targeted treatments directed at their catalytic activities. Here we describe the use of automated, high-throughput fluorescence lifetime imaging microscopy to measure EGFR autophosphorylation status by fluorescence resonance energy transfer (FRET) in head and neck tumors. We have correlated FRET efficiency with the clinical and survival data. The results from head and neck arrays show that high FRET efficiency is correlated with worsening disease-free survival but not with overall survival. This powerful tool could be exploited as a new independent quantitative prognostic factor in clinical decisions and cancer management.
An overview of the MAGE gene family with the identification of all human members of the family. (2001)

The first human members of the MAGE gene family that have been described are expressed in tumor cells but silent in normal adult tissues except in the male germ line. Hence, they encode strictly tumor-specific antigens that represent attractive targets for cancer immunotherapy. However, other members of the family were recently found to be expressed in normal cells, indicating that the family is larger and more disparate than initially expected. We therefore performed a database screening to identify all of the recorded members of both classes of human MAGE genes. This report provides an overview of the MAGE family and proposes a general nomenclature for all of the MAGE genes identified thus far. We found that the MAGE-D genes were particularly well conserved between man and mouse, suggesting that they exert important functions. In addition, the genomic structure of the MAGE-D genes indicates that one of them corresponds to the founder member of the family, and that all of the other MAGE genes are retrogenes derived from that common ancestral gene. Intriguingly, the COOH-terminal domain of MAGE-D3 was found to be identical to trophinin, a previously described protein believed to be involved in embryo implantation.
Cartilage Dysplasia and Tissue Mineralization in the Rat Following Administration of a FGF Receptor Tyrosine Kinase Inhibitor (2005)

PD176067 is a reversible and selective inhibitor of fibroblast growth factor receptor tyrosine kinase, and was in preclinical development as an angiogenesis inhibitor for the treatment of solid tumors. A 14-day oral toxicity study of PD176067 in young female rats (7 weeks old) was conducted at doses of 2.5, 5, and 10 mg/kg/day (15, 30, and 60 mg/m(2), respectively). Skeletal changes, and vascular and soft tissue mineralization were observed as primary drug-related toxicities. To determine if these changes are specific to young, rapidly growing animals with increased vascular and osseous development, PD176067 was administered to mature (11 months old) rats. Female rats received PD176067 by gavage for 14 days at doses of 2.5, 5, and 10 mg/kg/day and necropsied on day 15. Clinical signs of toxicity were seen at > or =5 mg/kg and one death occurred at 10 mg/kg. Physeal dysplasia (distal femur, proximal tibia, sternum) occurred in all drug-treated animals and was characterized by dose-related increased thickness of the zones of chondrocyte proliferation and hypertrophy, and marked thickening of the zone of ossification. Cartilage hyperplasia was characterized by proliferation of chondrocytes along margins of the synchondrosis and subperiosteum of sternebrae. Serum phosphorus levels increased 47% and 166% at 5 and 10 mg/kg, respectively. Mineralization of cardiac myocytes, aorta, various arteries, renal tubules, and gastric mucosa and muscularis was seen at 10 mg/kg, and consistent with the presence of calcium-phosphorus deposition. Physeal changes occurred at similar plasma PD176067 exposures in young and mature rats (AUC > or = 4.83 microg.hr/mL). PD176067 produced morphologically similar lesions in young and adult rats.
Effect of a ZrO[sub 2] Coating on the Structure and Electrochemistry of Li[sub x]CoO[sub 2] When Cycled to 4.5 V (2002)

Recently, Cho et al. studied the effects of a coating on the electrochemical behavior of cells. They found that the capacity retention to 4.4 V was significantly improved for cells having electrodes incorporating coated material compared to those with uncoated They suggested that the thin coating suppressed the lattice expansion of during cycling, leading to improved behavior. Our results on coated with reported here, confirm the improved cycling behavior. X-ray diffraction (XRD) patterns collected with long counting times show that the coated material is nanocrystalline In situ XRD results indicate that the lattice of coated expands and contracts in exactly the same way as uncoated during charge and discharge. These results prove that the coating does not affect the lattice expansion of in contrast to the results reported by Cho et al. We believe that the improved cycling behavior is caused by a reduction in the contact area between and electrolyte. © 2002 The Electrochemical Society. All rights reserved.
Hexopyranosyl-Like Oligonucleotides (1994)

Oligonucleotides containing monomers l-(2,3-dideoxy-β-D-erythro-hexopyranosyl)thymine; 1-(2,4-dideoxy-β-D-erythro-hexopyranosyl)-thymine; 1-(3,4-dideoxy-β-D-erythro-hexo-pyranosyl)-thymine; 1-(2,3-dideoxy-α-D-erythro-hexopyranosyl)thymine; 1-[2,3-dideoxy-3-C-(hydroxymethyl)-α-L-threo-pentopyranosyl]-thymine; and 1,5-an-hydro-2,3-dideoxy-2-(thymin-1-yl)-D-arabinohexitol were modeled and synthesized. Only oligonucleotides constructed of 1,5-anhydrohexitol nucleosides are able to hybridize with natural DNA.
Expression of Valosin-Containing Protein in Colorectal Carcinomas as a Predictor for Disease Recurrence and Prognosis (2004)

A high expression level of VCP in tumors is a poor prognostic marker in patients with colorectal carcinomas.
Total Synthesis of Exochelin MN and Analogues (2002)

The first total synthesis of exochelin MN is described along with rationally designed analogues. The required L-threo-beta-hydroxyamino acid components were constructed using either Sharpless asymmetric aminohydroxylation reactions or an aldol reaction of imidazolidinone 19. A new concise procedure for the preparation of the constituent six-membered cyclic hydroxamate was developed. In addition, a plausible mechanism for exochelin MN-mediated iron(III) transport was proposed. Biological studies of these compounds will be used to evaluate this hypothesis.
Reasons for breast cancer heterogeneity (2008)

Breast cancers differ in many ways, such as in their cell of origin, the molecular alterations causing them and the susceptibility and defenses of the patient, and this makes it difficult to give the most appropriate treatment. Two recent papers have contributed to the establishment of a more precise molecular classification of breast tumors.
Methods of active immunotherapy and viral oncolysis in some forms of cancer. (1986)

In some cancers with a high antigenicity (gastric, intestinal, mammary, laryngeal, etc.) the authors associated to the classical treatment an autovaccine prepared by combining the tumoral extract (obtained by trituration, sonication and centrifugation, and stored at -80 degrees C) with some mitogens (phytohemagglutinin) and adjuvants (ovalbumin, tuberculin, lymphocyte promotion factor, etc.) obtaining a greater survival (4-6 years). The association of viruses with an oncolytic action (mumps virus) to the active unspecific immunotherapy in some cancerous structures (peritoneal, pleuropulmonary and synovial malignant mesothelioma, malignant cholangioma of the liver, hepatic metastases of some adenocarcinomas of the colon, gastric cirrhous, clearly differentiated macrocellular carcinomas of the lung, pulmonary mucoid adenocarcinomas, traditional recurrent carcinomas of the urinary bladder), in which all other oncotherapeutic resources have been exhausted, induced slow involution up to disappearance of the tumor and a favourable evolution of the patients without signs-of recurrence after 5-7 years in 73% of cases. To obtain the expected results it is mandatory to comply strictly with certain principles, established by the authors for each of the two original methods, expounded in detail in the text.