gebhart/patrepeval huggingface dataset:
Retroviral cDNA Integration: Stimulation by HMG I Family Proteins (2000)

To replicate, a retrovirus must synthesize a cDNA copy of the viral RNA genome and integrate that cDNA into a chromosome of the host. We have investigated the role of a host cell cofactor, HMG I(Y) protein, in integration of human immunodeficiency virus type 1 (HIV-1) and Moloney murine leukemia virus (MoMLV) cDNA. Previously we reported that HMG I(Y) cofractionates with HIV-1 preintegration complexes (PICs) isolated from freshly infected cells. PICs depleted of required components by treatment with high concentrations of salt could be reconstituted by addition of purified HMG I(Y) in vitro. Here we report studies using immunoprecipitation that indicate that HMG I(Y) is associated with MoMLV preintegration complexes. In mechanistic studies, we show for both HIV-1 and MoMLV that each HMG I(Y) monomer must contain multiple DNA binding domains to stimulate integration by HMG I(Y)-depleted PICs. We also find that HMG I(Y) can condense model HIV-1 or MoMLV cDNA in vitro as measured by stimulation of intermolecular ligation. This reaction, like reconstitution of integration, depends on the presence of multiple DNA binding domains in each HMG I(Y) monomer. These data suggest that binding of multivalent HMG I(Y) monomers to multiple cDNA sites compacts retroviral cDNA, thereby promoting formation of active integrase-cDNA complexes.
Direct synthesis of 2,4‐diaminoquinazolines from 2‐fluorobenzonitriles (1988)

Abstract In a search for new methods for preparing 2,4‐diaminoquinazolines having a diversity of substituents in the benzenoid ring, it was found that the reaction of 2,6‐difluorobenzonitrile with guanidine carbonate gave 2,4‐diamino‐5‐fluoroquinazoline in excellent yield. Extension of this approach to other 2‐fluorobenzonitriles, some of which were elaborated for the first time, showed that this reaction possesses considerable generality. The cyclization was successful even when electron donating groups were present at position six. Only in two cases where a primary or secondary amino group was also present ortho to the cyano group was this transformation unsuccessful.
Rezymogenation of active urokinase induced by an inhibitory antibody (2012)

An important regulatory mechanism of serine proteases is the proteolytic conversion of the inactive pro-enzyme, or zymogen, into the active enzyme. This activation process is generally considered an irreversible process. In the present study, we demonstrate that an active enzyme can be converted back into its zymogen form. We determined the crystal structure of uPA (urokinase-type plasminogen activator) in complex with an inhibitory antibody, revealing that the antibody 'rezymogenizes' already activated uPA. The present study demonstrates a new regulatory mechanism of protease activity, which is also an extreme case of protein allostery. Mechanistically, the antibody binds a single surface-exposed loop, named the autolysis loop, thereby preventing the stabilization of uPA in its active conformation. We argue that this autolysis loop is a key structural element for rezymogenation of other proteases, and will be a new target site for pharmacological intervention with serine protease activity.
Stent Implantation Activates Akt in the Vessel Wall (2003)

Mechanical stretch of the vascular wall during stent deployment may contribute to ISR by activating the Akt pathway.
Polymerization shrinkage of visible-light-cured composites. (2001)

This study investigated the long-term dimensional changes of a conventional and a polyacid-modified composite resin and the effects of hydration on polymerization shrinkage. A strain-monitoring device was used to measure the linear polymerization shrinkage of the composites in the free state when stored in water at 37 degrees C or air at 26 degrees C over a one-month period. Results showed that the polymerization reaction of both conventional and polyacid-modified composite resins was accompanied by a dimensional shrinkage change. The rate of shrinkage for both composites was greatest during the polymerization reaction and continued after removal of the curing light. When stored in water, the greatest shrinkage was noted at one hour for both materials. This was followed by a slow uptake of water and expansion from one day to one month. The polyacid-modified composite had significantly less polymerization shrinkage than the conventional composite after one month of storage in water.
On the Propagation of Concentration Polarization from Microchannel−Nanochannel Interfaces Part II: Numerical and Experimental Study (2009)

We present results of a combined computational and experimental study of the propagation of concentration polarization (CP) zones in a microchannel-nanochannel system. Our computational model considers the combined effects of bulk flow, electromigration, and diffusion and accurately captures the dynamics of CP. Using wall charge inside the nanochannel as a single fitting parameter, we predict experimentally observed enrichment and depletion shock velocities. Our model can also be used to compute the existence of CP with propagating enrichment and depletion shocks on the basis of measured ion mobility and wall properties. We present experiments where the background electrolyte consists of only a fluorescent ion and its counterion. These results are used to validate the computational model and to confirm predicted trends from an analytical model presented in the first of this two-paper series. We show experimentally that the enrichment region concentration is effectively independent of the applied current, while the enrichment and depletion shock velocities increase in proportion to current density.
Magnetic Resonance Imaging of the Breast Prior to Biopsy (2004)

ContextBreast magnetic resonance imaging (MRI) has been shown to have high sensitivity for cancer detection and is increasingly used following mammography to evaluate suspicious breast lesions.ObjectiveTo determine the accuracy of breast MRI in conjunction with mammography for the detection of breast cancer in patients with suspicious mammographic or clinical findings.Design, Setting, and PatientsProspective multicenter investigation of the International Breast MR Consortium conducted at 14 university hospitals in North America and Europe from June 2, 1998, through October 31, 2001, of 821 patients referred for breast biopsy for American College of Radiology category 4 or 5 mammographic assessment or suspicious clinical or ultrasound finding.InterventionsMRI examinations performed prior to breast biopsy; MRI results were interpreted at each site, which were blinded to pathological results.Main Outcome MeasuresArea under the receiver operating characteristic curve (AUC), sensitivity, and specificity of breast MRI.ResultsAmong the 821 patients, there were 404 malignant index lesions, of which 63 were ductal carcinoma in situ (DCIS) and 341 were invasive carcinoma. Of the 417 nonmalignant index lesions, 366 were benign, 47 showed atypical histology, and 4 were lobular carcinoma in situ. The AUC pooled over all institutions was 0.88 (95% confidence interval [CI], 0.86-0.91). MRI correctly detected cancer in 356 of 404 cancer cases (DCIS or invasive cancer), resulting in a sensitivity of 88.1% (95% CI, 84.6%-91.1%), and correctly identified as negative for cancer 281 of 417 cases without cancer, resulting in a specificity of 67.7% (95% CI, 62.7%-71.9%). MRI performance was not significantly affected by mammographic breast density, tumor histology, or menopausal status. The positive predictive values for 356 of 492 patients was 72.4% (95% CI, 68.2%-76.3%) and of mammography for 367 of 695 patients was 52.8% (95% CI, 49.0%-56.6%) (P&lt;.005). Dynamic MRI did not improve the AUC compared with 3-dimensional MRI alone, but the specificity of a washout pattern for 123 of 136 patients without cancer was 90.4% (95% CI, 84%-95%).ConclusionsBreast MRI has high sensitivity but only moderate specificity independent of breast density, tumor type, and menopausal status. Although the positive predictive value of MRI is greater than mammography, MRI does not obviate the need for subsequent tissue sampling in this setting.
Transient reduction in myocardial free oxygen radical levels is involved in the improved cardiac function and structure after long-term allopurinol treatment initiated in established chronic heart failure (2005)

In experimental CHF, long-term allopurinol treatment, initiated in a pathological state of overt CHF, improves LV haemodynamics and function and prevents LV remodelling. These long-term effects are, at least partially, caused by a transient reduction of myocardial ROS shortly after initiation of allopurinol treatment, but whether other mechanism(s), independent of myocardial redox 'status', such as reduced inflammation, are implicated remains to be confirmed.
High speed obstacle avoidance using monocular vision and reinforcement learning (2005)

We consider the task of driving a remote control car at high speeds through unstructured outdoor environments. We present an approach in which supervised learning is first used to estimate depths from single monocular images. The learning algorithm can be trained either on real camera images labeled with ground-truth distances to the closest obstacles, or on a training set consisting of synthetic graphics images. The resulting algorithm is able to learn monocular vision cues that accurately estimate the relative depths of obstacles in a scene. Reinforcement learning/policy search is then applied within a simulator that renders synthetic scenes. This learns a control policy that selects a steering direction as a function of the vision system's output. We present results evaluating the predictive ability of the algorithm both on held out test data, and in actual autonomous driving experiments.
Pharmacokinetics of Cetuximab After Administration of Escalating Single Dosing and Weekly Fixed Dosing in Patients with Solid Tumors (2006)

Pharmacokinetic results support using body surface area or weight in calculating individual cetuximab doses. A weekly dose of 250 mg/m2 is predicted to nearly fully saturate cetuximab clearance and, by inference, epidermal growth factor receptors. The association between rash and disease stability supports further prospective studies of this relationship.
Straining Urethral Reflex: Description of a Reflex and Its Clinical Significance (1991)

The present communication describes a reflex, which I call 'straining urethral reflex', and discusses its clinical significance. The study was performed on 17 healthy volunteers with a mean age of 39.6 years. The intrarectal pressure (representative of the intra-abdominal pressure) was measured by means of a balloon-tipped catheter introduced into the rectum and connected to a pressure transducer. A concentric needle electrode was introduced into the external urethral sphincter. The subject was asked to strain, and the urethral sphincter electromyographic activity and the intrarectal pressure were recorded. Two types of straining were investigated: sudden and slow. The procedure was repeated in 10 subjects after urethral sphincter infiltration with xylocaine or saline. On sudden straining, the external urethral sphincter contracted. The anesthetized sphincter did not respond, while the saline-infiltrated sphincter responded to sudden straining. Slow sustained straining did not evoke the reflex response. The latency of the reflex was calculated. The external urethral sphincter contraction on sudden straining guards against the involuntary opening of the vesical neck and urinary leak under stress conditions of a sudden increase in the intra-abdominal pressure. The reflex may prove significant in the diagnosis of micturition control disorders. It can thus be included as an investigative tool in urologic practice.
myc protooncogene linked to retroviral promoter, but not to enhancer, transforms embryo cells. (1988)

To define conditions under which the chicken protooncogene p-myc is converted to a viral and possibly to a cellular transforming gene, we assayed transforming function of hybrid genes put together from cloned retroviral and p-myc elements and of p-myc genes isolated from spontaneous viral lymphomas. Transforming function was measured in quail embryo cells transfected with cloned myc genes. We found that only myc genes with a promoter of a retroviral long terminal repeat (LTR) located between the native p-myc promoter and the second p-myc exon have transforming function. Transforming efficiencies decreased with increasing lengths of unspliced sequences between the LTR and p-myc exon 2. p-myc DNAs with LTRs downstream of the coding region or upstream but in the opposite transcriptional orientation failed to transform embryo cells. Likewise, only those retroviral-p-myc combinations from chicken B-cell lymphomas with a LTR positioned as promoter upstream of p-myc exon 2 had transforming function. We conclude that substitution of a retroviral LTR for the promoter and for as yet poorly defined, untranscribed regulatory elements of p-myc is sufficient to convert chicken p-myc to a transforming gene. However, retroviral LTRs can only convert p-myc genes to embryo-cell-transforming genes from a limited number of positions, and not as position-independent enhancers. Further, we deduce that there are two classes of viral chicken B-cell lymphomas, those with and those without embryo-cell-transforming p-myc genes.
[Behçet disease]. (2002)

The authors show this multisystem inflammatory illness and present history, epidemiology, prevalence, symptoms, diagnostic criteria proposed by "The Behçet's Disease Research Committee of Japan" and "The International Study Group for Behçet Disease", evolution, prognosis and the most new drugs in the treatment.
Gonadotropin releasing hormone inhibitory autofeedback by subproducts antagonist at N-methyl-D-aspartate receptors: a model of autocrine regulation of peptide secretion (1994)

The secretion of Gonadotropin-releasing Hormone (GnRH) involves activation of N-methyl-D-aspartate (NMDA) receptors. Here, we show that pulsatile GnRH secretion from hypothalamic explants is suppressed by 1-5GnRH, an endogenous breakdown product of GnRH, while 2-10GnRH has no effect. GnRH secretion evoked by NMDA is selectively inhibited by 1-5GnRH and this effect is similar to that of AP-5, a competitive antagonist at NMDA receptors. In addition, 1-5GnRH accounts for a dose-related inhibition of tritiated glutamate binding to hypothalamic membrane preparations. Using GnRH secretion as a model of NMDA-receptor controlled system, the effect of different peptides has been studied. Growth Hormone Releasing Factor (GRF), Insulin-like Growth Factor-I (IGF-I) and Proinsulin result in inhibition of GnRH secretion. Bioactive subproducts of those peptides (1-29GRF, 4-701GF-I and insulin) do not show any effect, suggesting that their classical receptors are not involved. In contrast, GnRH secretion is inhibited by other subproducts (1-37GRF, 1-31GF-I and C-peptide) all terminating in a glutamate residue. These subproducts selectively suppress the NMDA-evoked secretion of GnRH. Protease inhibitors prevent the inhibitory effects of IGF-I on GnRH secretion. This, breakdown products of different peptide hormones are possible endogenous antagonists at NMDA receptors. This effect could account for an autocrine or paracrine limitation of NMDA-receptor-mediated secretion of peptides.
Comparison of Omeprazole with Ranitidine in the Treatment of Reflux Oesophagitis (1989)

The amount and concentration of acid in the refluxed gastric contents are considered to be the major factors in the development and progression of reflux oesophagitis. Omeprazole, with its pronounced inhibition of gastric acid secretion, should therefore be a most effective drug for the treatment of patients with this disease. In an international clinical programme, the effects of treatment with placebo, ranitidine, 150 mg b.d. and omeprazole in doses ranging from 20 mg to 60 mg once daily, have been compared in patients with erosive and/or ulcerative oesophagitis. One placebo-controlled study and five comparative studies with ranitidine have been performed. Similar inclusion criteria, definition of oesophagitis on endoscopic evidence of mucosal defects, and assessment of symptoms were used in all the trials. It is evident from the placebo-controlled study that spontaneous healing of erosions and/or ulcers in the oesophageal mucosa seldom occurs. After 4 weeks of treatment, 6% (2/32) of patients randomized to the placebo group had healed, compared to 81% (25/31) treated with omeprazole, 20 mg or 40 mg once daily. In the five studies comparing omeprazole and ranitidine, nearly twice as many patients healed in the omeprazole-treated groups compared with those receiving ranitidine. The overall healing rate was 76% after 4 weeks on omeprazole (range 67-85%) and 37% on ranitidine (range 28-45%), and after 8 weeks the corresponding figures were 90% (85-95%) and 56% (43-66%), respectively. Apart from choice of treatment, only severity of the oesophagitis influenced the rate of healing.(ABSTRACT TRUNCATED AT 250 WORDS)
Toolbox Approach to the Search for Effective Ligands for Catalytic Asymmetric Cr-Mediated Coupling Reactions (2009)

Chromium catalysts derived from chiral sulfonamides represented by A effect the couplings of aldehydes with vinyl, allyl, or alkyl halides. With three distinct sites for structural modification, A affords access to a structurally diverse pool of chiral sulfonamides. The Cr catalysts derived from these sulfonamides exhibit a broad range of catalyst-substrate matching profiles. A strategy is presented to search for a satisfactory chiral sulfonamide for a given substrate. In order to demonstrate the generality and effectiveness of this approach, five diverse C-C bond-forming cases have been selected from the halichondrin synthesis. For each of the cases, two ligands have been deliberately searched for, to induce the formation of (R)- and (S)-alcohols, respectively, at the arbitrarily chosen efficiency level of ">or=80% yield with >or=20:1 stereoselectivity in the presence of <or=20 mol % of a Cr catalyst". For 9 out of the 10 cases studied, a satisfactory catalyst has been found within this pool of sulfonamides. Even for the remaining case, a Cr catalyst inducing stereoselectivity up to 8:1 has been identified.
4-Alkyl-2-trichloromethyloxazolidin-5-ones: Valuable Precursors to Enantiomerically Pure C- and N-Protected α-Alkyl Prolines (1999)

An efficient, economical and enantioselective method for preparation of various mono-and diprotected a-substituted proline derivatives is described. The lithium enolate of known 2-trichlo- romethyloxazolidin-5-one 3b reacted with electrophiles to furnish the 4-alkyloxazolidinones 4a-d with high diastereoselectivity and in good yields. The oxazolidinones 4 represented versatile synthons that could be converted in a single step into useful proline peptido- mimetics. For example oxazolidinones 4a-d reacted with sodium methoxide by a novel mechanism that involved elimination of trichloromethyl anion from an intermediate tetrahedral adduct to af- ford N-formyl a-substituted proline methyl esters 5a-d. Alternative- ly acidic methanolysis of oxazolidinone 4a afforded the amino acid methyl ester hydrochloride 6. Hydrolysis of the N,O-acetal function of 4a could be effected under acidic conditions (6 N HCl, RT) to af- ford the free amino acid 1a after ion exchange chromatography. Our procedure represents a convenient and general route to a valuable class of peptidomimetics and should be welcomed by chemists pre- paring conformationally restricted peptides and other compounds.
Mutations that permit residual CFTR function delay acquisition of multiple respiratory pathogens in CF patients (2010)

Residual CFTR function correlates with later onset of respiratory tract infection by a wide spectrum of organisms frequently cultured from CF patients. The protective effect conferred by residual CFTR function is diminished in CF patients with more advanced lung disease.
Cell kinetic analysis of mixed populations using three‐color fluorescence flow cytometry (1991)

The development of antibodies to DNA-incorporated thymidine analogs has in turn led to the development of flow cytometric techniques for rapidly measuring cell kinetics parameters. More recently, these techniques have been applied to clinical tumor material. One problem with such measurements has been the difficulty of distinguishing malignant cells from coexistent normal cells in the biopsy material. In the present study, the feasibility of selecting out the desired malignant cell population for kinetic analysis from a mixture of cells was tested in vitro. An anticytokeratin antibody was used to discriminate between a mixture of tumor cells (cytokeratin positive) and normal cells (cytokeratin negative). The cell lines chosen for the study, A549 human lung carcinoma cells and Chinese hamster ovary (CHO) cells, were pulse labeled with iododeoxyuridine (IdUrd) and sampled every hour up to 16 hours. Selecting out cells from the mixture required the application of three-color fluorescence flow cytometry, which was carried out using the fluorochromes FITC (fluorescein isothionate, green fluorescence, IdUrd-DNA antibody), PE (phycoerythrin, orange fluorescence, cytokeratin antibody), and PI (propidium iodide, red fluorescence, DNA). This allowed single laser excitation. The staining procedure involved incubation with the IdUrd antibodies (specific antibody plus FITC-conjugated second antibody) followed by the cytokeratin antibodies (specific antibody plus PE-conjugated second antibody) and lastly by the DNA stain containing RNase. Two analysis methods of the IdUrd/DNA cytograms were applied: a mid-S window analysis and a relative movement (RM) analysis. Results of the analyses for cells selected out of mixtures were compared with results of cells stained and analyzed separately. A clear separation of the two cell lines could be obtained on the basis of orange fluorescence (cytokeratin content) despite a large overlap of their DNA histograms. By gating on high or low orange fluorescence, almost pure populations of the individual cell types could be selected out for further kinetic analysis. Little difference was seen, with both the mid-S and RM analyses, between cells gated from mixtures or stained separately. It is concluded that this technique is feasible for use on clinical material, provided good cell suspensions can be obtained, leading to the hope of increasing the accuracy of kinetic measurements on human tumors.