gebhart/patrepeval huggingface dataset:
Two-step radio-immunotargeting of renal-cell carcinoma xenografts in nude mice with anti-renal-cell-carcinoma X anti-DTPA bispecific monoclonal antibodies (1998)

The specificity of antibodies offers unique opportunities to target tumors with radionuclides. However, due to the slow clearance of radiolabeled antibody, relatively high back-ground is observed in non-target organs. Pre-targeting protocols using bispecific monoclonal antibodies (bsMAbs) and radiolabeled chelates may overcome this problem. We have evaluated the anti-renal-cell-carcinoma (RCC) X anti-DTPA bsMAb G250 x DTIn1 for 2-step targeting of RCC tumors in nude mice. Tumor uptake of 111In-DTPA was similar up to a 3-day interval between bsMAb and 111In-DTPA injections and decreased thereafter. The effect of G250 x DTIn1 protein dose was studied. High tumor uptake was seen at 1 to 4 micrograms, whereas at higher doses uptake decreased. Tumor was saturated with 15 micrograms bsMAb. At the saturating bsMAb dose the 111In-DTPA amount was varied. High tumor uptake was observed at a 10-fold molar excess 111In-DTPA, whereas at higher excess uptake decreased. After priming with 15 micrograms bsMAb and targeting with a 10-fold molar excess 111In-DTPA, the biodistribution of 111In-DTPA was studied for 1 to 48 hr after injection. Good tumor retention of 111In-DTPA was observed, while the radiolabel cleared rapidly from the blood. Consequently, tumor-to-blood ratios increased with time to 500 at 24 hr after injection. In conclusion, RCC xenografts can be targeted efficiently using G250 x DTIn1 and 111In-DTPA. However, this requires careful tuning of bsMAb protein dose and 111In-DTPA dose. Using the optimal protein dose and 111In-DTPA dose, high 111In-DTPA tumor uptake and tumor-to-blood ratios can be obtained, thus providing good perspectives for diagnostic and therapeutic use in humans.
Emergence of a Multidrug-Resistant Pandemic Influenza A (H1N1) Virus (2010)

N o v . 1 1 , 2 0 0 9 D e c . 3 , 2 0 0 9 D e c . 2 3 , 2 0
Transcriptional regulation of the ovalbumin and conalbumin genes by steroid hormones in chick oviduct. (1979)

Relative rates of ovalbumin and conalbumin mRNA transcription were measured in isolated oviduct nuclei by allowing endogenous RNA polymerases to synthesize [32P]RNA that was then hybridized to immobilized recombinant DNA containing the respective gene sequences. Administration of either estrogen or progesterone to withdrawn birds increased the rate of conalbumin mRNA (mRNA,,,) transcription 2- to 3-fold within 30 min. The rate of ovalbumin mRNA (mRNA,,) transcription was undetectable before hormone administration and increased at least 20-fold during the first 12 h. The maximum rates of transcription achieved after 12 h of hormonal stimulation are only 10 to 25% of those observed after several days of hormone treatment; these transcription rates are consistent with the low levels of nuclear estrogen or progesterone receptors measured during the first 12 h of induction. The induction of mRNA, and mRNAcon in oviduct explant cultures was quantitatively comparable to that observed in vivo. Relative rates of transcription were also measured in this system by pulse-labeling with [3H]uridine. In addition, absolute rates of transcription were determined by measuring the specific activity of the UTP pool during the labeling period. The accumulation of mRNA., sequences was consistent with the absolute rate of transcription measurements, indicating that this mRNA has a long
An algorithm for reasoning about equality (1978)

A simple technique for reasoning about equalities that is fast and complete for ground formulas with function symbols and equality is presented. A proof of correctness is given as well.
An Escherichia coli Mutant Defective in Lipid Export (2001)

Escherichia coli phospholipids and lipopolysaccharide, made on the inner surface of the inner membrane, are rapidly transported to the outer membrane by mechanisms that are not well characterized. We now report a temperature-sensitive mutant (WD2) with an A270T substitution in a trans-membrane region of the ABC transporter MsbA. As shown by (32)P(i) and (14)C-acetate labeling, export of all major lipids to the outer membrane is inhibited by approximately 90% in WD2 after 30 min at 44 degrees C. Transport of newly synthesized proteins is not impaired. Electron microscopy shows reduplicated inner membranes in WD2 at 44 degrees C, consistent with a key role for MsbA in lipid trafficking.
Evaluation of a Soluble Fibrin Assay in Patients with Suspected Deep Vein Thrombosis (1995)

This study demonstrates that the soluble fibrin assay used in the study has potential clinical utility as a diagnostic test in patients with clinically suspected DVT and supports further evaluation of this assay.
Identification of a Novel Antiviral Inhibitor of the Flavivirus Guanylyltransferase Enzyme (2012)

Arthropod-borne flavivirus infection causes serious morbidity and mortality worldwide, but there are currently no effective antiflaviviral chemotherapeutics available for human use. Therefore, it is critical that new therapeutics against virus-specific targets be developed. To identify new compounds that may be used as broadly active flavivirus therapeutics, we have performed a high-throughput screening of 235,456 commercially available compounds for small-molecule inhibitors of the dengue virus NS5 RNA capping enzyme. We identified a family of compounds, the 2-thioxothiazolidin-4-ones, that show potent biochemical inhibition of capping enzyme GTP binding and guanylyltransferase function. During the course of structure-activity relationship analysis, a molecule within this family, (E)-{3-[5-(4-tert-butylbenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]propanoic acid} (BG-323), was found to possess significant antiviral activity in a dengue virus subgenomic replicon assay. Further testing of BG-323 demonstrated that this molecule is able to reduce the replication of infectious West Nile virus and yellow fever virus in cell culture with low toxicity. The results of this study describe the first inhibitor that targets the GTP-binding/guanylyltransferase activity of the flavivirus RNA capping enzyme.
Can we prevent Parkinson's and Alzheimer's disease? (2004)

Parkinson's disease (PD) and Alzheimer's (AD) are major progressive neurological disorders, the risk of which increases with advancing age (65 years and over). In familial cases, however, early onset of disease (about 35 years) is observed. In spite of extensive basic and clinical research on PD and AD, no preventive or long-term effective treatment strategies are available. Several studies have indicated that oxidative stress is a major risk factor for the initiation and progression of sporadic PD and AD. Even a-synuclein and b-amyloid fragments that are associated with the PD and AD, respectively, mediate part of their action via oxidative stress. Therefore, reducing oxidative stress appears to be a rational choice for the prevention and reduction in the rate of progression of these neurological disorders. This review provides a brief description of the epidemiology and pathogenesis of PD and AD, and the scientific rationale for the use of multiple antioxidants in the prevention of these neurological diseases.
Treatment for swallowing difficulties (dysphagia) in chronic muscle disease (2004)

There are no trials that have adequately evaluated treatments in the management of dysphagia for chronic muscle disease. It is therefore not possible to decide on the most appropriate treatment for a given individual based on current evidence.
Highly Scalable Phase Change Memory with CVD GeSbTe for Sub 50nm Generation (2007)

first present a PRAM with confinement of chemically vapor deposited GeSbTe (CVD GST) within high aspect ratio 50nm contact for sub 50nm generation PRAMs. By adopting confined GST, we were able to reduce the reset current below ~260μA and thermally stable CVD Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Sb <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Te <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sub> compound having hexagonal phase was uniformly filled in a contact while maintaining constant composition along with 150nm depth. Our results indicate that the confined cell structure of 50nm contact is applicable to PRAM device below 50 nm design rule due to small GST size based on small contact and direct top electrode contact, reduced reset current, minimized etch damage, and low thermal disturbance effect.
The contribution of perceived fitness to physiological and self reported responses to laboratory stress (1999)

This study sought to evaluate the contribution of perceived physical fitness beyond the contributions of gender, body mass index (BMI), defensiveness, and estimated aerobic fitness on both physiological and self-reported stress responsivity to laboratory-induced stress. Ninety healthy individuals (45 males, 45 females) participated in the experiment. Participants completed a laboratory procedure measuring cardiovascular responses (i.e. pulse rate and blood pressure) and self-reported rating of anxiety (i.e. the anxiety scale from the Multiple Affective Checklist–Revised—MAACL–R) while performing stressful laboratory tasks (i.e. the Stroop Color Naming Test and Serial 7's). Estimated aerobic fitness (i.e. VO2max using the Bruce protocol) as well as perceived fitness (using a 10-point Likert scale) were also determined. Multiple regression and effect size results revealed that perceived fitness significantly contributed to the variance associated with both physiological and self-reported responses to laboratory stress. Specifically, perceived fitness significantly added to the variance beyond that attributed to gender, BMI, defensiveness, and estimated aerobic physical fitness while assessing pulse rate and MAACL–R anxiety scores. Overall results support the view that perception of fitness may be an important factor above and beyond aerobic fitness in its association with physiological and self-reported responses to stress.
Impairment of Cell-Mediated Immunity in Mutation Diabetic Mice (db/db) (1978)

Mutation diabetes in the mouse occurs in the C57BL/Ks strain. All homozygous animals (db/db) develop obesity, elevated blood sugar levels and increased or normal blood insulin concentration. The defects in cellular immunity in db/db mice and their littermate controls were examined both in vivo and in vitro. Significant suppression of delayed footpad swelling and first and second set skin allograft rejection time were observed. In addition, DNA synthesis in spleen cells after nonspecific mitogen stimulation was markedly inhibited. Diabetic animals with a mean blood sugar of 512 +/- 101 mg/100 ml did not respond to exogenous insulin therapy by lowering their blood sugar levels or reversing the defect in DNA synthesis. Adding insulin to spleen cell culture in vitro had no demonstrable effect on their response to mitogens. Thus, mutation diabetic mice with their known defect in the peripheral utilization of insulin have markedly suppressed cell-mediated immune mechanisms.
Mapping As You Go (2004)

The advent of high throughput molecular technologies has led to an expectation that breeding programs will use marker–trait associations to conduct marker‐assisted selection (MAS) for traits. Many challenges exist with this molecular breeding approach for so‐called complex traits. A major restriction to date has been the limited ability to detect and quantify marker–trait relationships, especially for traits influenced by the effects of gene‐by‐gene and gene‐by‐environment interactions. A further complication has been that estimates of quantitative trait loci (QTL) effects are biased by the necessity of working with a limited set of genotypes in a limited set of environments, and hence the applications of these estimates are not as effective as expected when used more broadly within a breeding program. The approach considered in this paper, referred to as the Mapping As You Go (MAYG) approach, continually revises estimates of QTL allele effects by remapping new elite germplasm generated over cycles of selection, thus ensuring that QTL estimates remain relevant to the current set of germplasm in the breeding program. Mapping As You Go is a mapping‐MAS strategy that explicitly recognizes that alleles of QTL for complex traits can have different values as the current breeding material changes with time. Simulation was used to investigate the effectiveness of the MAYG approach applied to complex traits. The results indicated that greater levels of response were achieved and these responses were less variable when estimates were revised frequently compared with situations where estimates were revised infrequently or not at all.
Hypermethylation leads to silencing of the SYK gene in human breast cancer. (2001)

A number of cancer-associated genes have been shown to be inactivated by hypermethylation of CpG islands during breast tumorigenesis. SYK, a candidate tumor suppressor, has been found not expressed in a subset of breast cancer cell lines, but the mechanism by which SYK is silenced is unclear. In this study, we examined the 5' CpG island methylation status of the SYK gene in breast cancer cell lines and primary breast cancer tissues. We found SYK 5' CpG hypermethylation in 30% (6/20) of breast cancer cell lines, and the aberrant methylation status was strongly associated with loss of SYK gene expression. Treatment of cells with a methylation inhibitor, 5-aza-2'-deoxycytidine, led to a reactivation of SYK expression in SYK-negative cells, as detected by reverse transcription-PCR. Using methylation-specific PCR, we demonstrated that SYK is hypermethylated in 32% (12/37) of unselected breast tumors, whereas all of the matched neighboring normal breast tissues exhibited unmethylated DNA status. We concluded that SYK is frequently inactivated through an epigenetic pathway in breast cancer. Because SYK has been shown to function as a tumor suppressor, and its loss of expression in breast cancer has been correlated with tumor invasiveness, the aberrant SYK methylation is responsible for the loss of expression and may consequently play a permissive role for tumor aggressiveness.
Synthesis of 4-amino-1H-pyrrolo[2,3-b]pyridine (1,7-dideazaadenine) and 1H-pyrrolo[2,3-b]pyridin-4-ol (1,7-dideazahypoxanthine) (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 4-amino-1H-pyrrolo[2,3-b]pyridine (1,7-dideazaadenine) and 1H-pyrrolo[2,3-b]pyridin-4-ol (1,7-dideazahypoxanthine)Stewart W. Schneller and Jiann-Kuan LuoCite this: J. Org. Chem. 1980, 45, 20, 4045–4048Publication Date (Print):September 1, 1980Publication History Published online1 May 2002Published inissue 1 September 1980https://pubs.acs.org/doi/10.1021/jo01308a021https://doi.org/10.1021/jo01308a021research-articleACS PublicationsRequest reuse permissionsArticle Views1669Altmetric-Citations27LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
The Hypothalamus and Hypertension (2001)

Most forms of hypertension are associated with a wide variety of functional changes in the hypothalamus. Alterations in the following substances are discussed: catecholamines, acetylcholine, angiotensin II, natriuretic peptides, vasopressin, nitric oxide, serotonin, GABA, ouabain, neuropeptide Y, opioids, bradykinin, thyrotropin-releasing factor, vasoactive intestinal polypeptide, tachykinins, histamine, and corticotropin-releasing factor. Functional changes in these substances occur throughout the hypothalamus but are particularly prominent rostrally; most lead to an increase in sympathetic nervous activity which is responsible for the rise in arterial pressure. A few appear to be depressor compensatory changes. The majority of the hypothalamic changes begin as the pressure rises and are particularly prominent in the young rat; subsequently they tend to fluctuate and overall to diminish with age. It is proposed that, with the possible exception of the Dahl salt-sensitive rat, the hypothalamic changes associated with hypertension are caused by renal and intrathoracic cardiopulmonary afferent stimulation. Renal afferent stimulation occurs as a result of renal ischemia and trauma as in the reduced renal mass rat. It is suggested that afferents from the chest arise, at least in part, from the observed increase in left auricular pressure which, it is submitted, is due to the associated documented impaired ability to excrete sodium. It is proposed, therefore, that the hypothalamic changes in hypertension are a link in an integrated compensatory natriuretic response to the kidney's impaired ability to excrete sodium.
Plant-Based Vaccine: Mice Immunized with Chloroplast-Derived Anthrax Protective Antigen Survive Anthrax Lethal Toxin Challenge (2005)

The currently available human vaccine for anthrax, derived from the culture supernatant of Bacillus anthracis, contains the protective antigen (PA) and traces of the lethal and edema factors, which may contribute to adverse side effects associated with this vaccine. Therefore, an effective expression system that can provide a clean, safe, and efficacious vaccine is required. In an effort to produce anthrax vaccine in large quantities and free of extraneous bacterial contaminants, PA was expressed in transgenic tobacco chloroplasts by inserting the pagA gene into the chloroplast genome. Chloroplast integration of the pagA gene was confirmed by PCR and Southern analysis. Mature leaves grown under continuous illumination contained PA as up to 14.2% of the total soluble protein. Cytotoxicity measurements in macrophage lysis assays showed that chloroplast-derived PA was equal in potency to PA produced in B. anthracis. Subcutaneous immunization of mice with partially purified chloroplast-derived or B. anthracis-derived PA with adjuvant yielded immunoglobulin G titers up to 1:320,000, and both groups of mice survived (100%) challenge with lethal doses of toxin. An average yield of about 150 mg of PA per plant should produce 360 million doses of a purified vaccine free of bacterial toxins edema factor and lethal factor from 1 acre of land. Such high expression levels without using fermenters and the immunoprotection offered by the chloroplast-derived PA should facilitate development of a cleaner and safer anthrax vaccine at a lower production cost. These results demonstrate the immunogenic and immunoprotective properties of plant-derived anthrax vaccine antigen.
Hard X-ray Emission from Magnetars : A Case Study for Simbol X (2008)

The magnetar model involves an isolated neutron star with a very high magnetic field (B ∼ 1014−15 G), and is invoked to explain the emission processes of two classes of sources, the Anomalous X-ray Pulsars (AXPs) and the Soft Gamma-Ray Repeaters (SGRs). Five of them have been recently identified to be persistent sources in the hard X-ray band (20–200 keV). AXPs, in particular, present the hardest known persistent spectra in the hard X/soft γ-ray energy range. The broad band modeling of their spectra still suffers from the non-simultaneity of the observations and from a lack of sensitivity above 20 keV. We present the Simbol X simulated observations of these objects and show that that this mission could surely help to disentangle the contribution of the different spectral components, and to understand how they contribute to the secular flux variations observed in these sources.
The roles of interdigitating cells and natural killer cells in the rapid rejection of allogeneic lymphocytes (1986)

The fate of radiolabeled allogeneic thoracic duct lymphocytes injected into congenitally athymic, nude rats was followed by autoradiography and electron microscopy. The allogeneic cells entered the host lymphoid organs at a normal rate, but once inside the lymphoid tissue they were rapidly phagocytozed by interdigitating cells (IDC) situated in the lymph node paracortex and the splenic periarteriolar lymphoid sheaths. Neither host nor donor T cells were required to initiate phagocytosis, as purified donor B cells were also avidly ingested by the athymic host IDC. Compared with fully allogeneic cells phagocytosis of semiallogeneic donor cells was much less efficient. When natural killer cell activity was blocked by preinjecting the recipients with antibodies against natural killer cells (anti-asialo GM1 or MRC OX-8) phagocytosis of the allogeneic cells was strongly reduced. As IDC did not bind these antibodies, the finding indicates that natural killer cells were needed to discriminate between own and foreign lymphocytes and to kill the allogeneic cells, which were then ingested by surrounding IDC. This was further supported by the observation that dendritic, constitutively Ia+ cells from peripheral lymph, phenotypically identical to IDC, did not lyse or phagocytoze allogeneic lymphocytes in vitro.
Multi-Ethnic Study of Atherosclerosis: Objectives and Design (2002)

The Multi-Ethnic Study of Atherosclerosis was initiated in July 2000 to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease (CVD) in a population-based sample of 6,500 men and women aged 45-84 years. The cohort will be selected from six US field centers. Approximately 38% of the cohort will be White, 28% African-American, 23% Hispanic, and 11% Asian (of Chinese descent). Baseline measurements will include measurement of coronary calcium using computed tomography; measurement of ventricular mass and function using cardiac magnetic resonance imaging; measurement of flow-mediated brachial artery endothelial vasodilation, carotid intimal-medial wall thickness, and distensibility of the carotid arteries using ultrasonography; measurement of peripheral vascular disease using ankle and brachial blood pressures; electrocardiography; and assessments of microalbuminuria, standard CVD risk factors, sociodemographic factors, life habits, and psychosocial factors. Blood samples will be assayed for putative biochemical risk factors and stored for use in nested case-control studies. DNA will be extracted and lymphocytes will be immortalized for genetic studies. Measurement of selected subclinical disease indicators and risk factors will be repeated for the study of progression over 7 years. Participants will be followed through 2008 for identification and characterization of CVD events, including acute myocardial infarction and other coronary heart disease, stroke, peripheral vascular disease, and congestive heart failure; therapeutic interventions for CVD; and mortality.