gebhart/patrepeval huggingface dataset:
Disseminated intravascular coagulation as a consequence of cerebral damage (1974)

Three cases with intracranial lesions developed evidence of disseminated intravascular coagulation which was confirmed at necropsy. The factors engendering this state, including release of potent thromboplastin from neural tissue are discussed and the danger of this intermediary mechanism of disease increasing the mortality of intracranial disease is demonstrated. Careful haematological investigation of all patients with intracranial disease is therefore advised, especially if they manifest evidence of a bleeding tendency.
Use of a flexible cassette method to generate a double unmarked Mycobacterium tuberculosis tlyA plcABC mutant by gene replacement (2000)

Progress in the field of mycobacterial research has been hindered by the inability to readily generate defined mutant strains of the slow-growing mycobacteria to investigate the function of specific genes. An efficient method is described that has been used to generate several mutants, including the first double unmarked deletion strain of Mycobacterium tuberculosis. Four mutants were constructed: a marked deletion of the plcABC cluster, which encodes three phospholipases C; separate unmarked deletions in plcABC and tlyA (encoding a haemolysin); and a double unmarked mutant tlyADelta plcABCDelta. To accomplish this, two series of vectors were designed, the first of which, named pNIL, allows manipulation of the target gene sequence at a variety of convenient restriction sites. The second series, named pGOAL, contains marker cassettes flanked by PAC:I restriction enzyme sites. The final suicide plasmid vectors were then obtained by cloning a marker cassette from a pGOAL vector into the single PAC:I site of the pNIL vector with the modified gene of interest. Finally, a two-step strategy was employed whereby single cross-over events were first selected, then screening for the second cross-over was carried out to yield the mutant strains. This technique will now allow the construction of potential vaccine strains without the inclusion of antibiotic resistance markers, the ability to make multiple defined mutations and the possibility of making more subtle defined mutations, such as point mutations.
Insulin Signaling and Action in Fat Cells: Associations with Insulin Resistance and Type 2 Diabetes (1999)

ABSTRACT: Adipose tissue only accounts for a relatively small proportion (&lt;10%) of the peripheral glucose utilization in response to insulin. However, the fat cells may still play an important role in insulin resistance and Syndrome X through, for instance, its endocrine functions (production of leptin, TNFα, PAI‐1, etc.) and involvement in lipid metabolism (FFA release and hydrolysis of triglycerides). The fat cells are also highly sensitive to insulin and may thus be used to elucidate molecular mechanisms for insulin resistance in man. Examinations of the intracellular signaling mechanisms for insulin in fat cells from individuals with Type 2 diabetes revealed markedly lower insulin‐stimulated PI3‐kinase activity. This was due to a pronounced reduction in the cellular expression of the docking protein, IRS 1, whereas expression of IRS 2 was normal. However, IRS 2‐associated PI3‐kinase activity was only approximately one‐third of that found to be associated with IRS 1 in normal cells. Downstream activation and serine phosphorylation of PKB/Akt by insulin were also markedly reduced in Type 2 diabetes. Furthermore, the dose‐response curve for this effect of insulin was similar to that for glucose transport in both normal and Type 2 diabetic cells. Thus, these data show that both PI3‐kinase and PKB activation by insulin are markedly reduced in Type 2 diabetes. We also examined whether an attenuated activation of PI3‐kinase by insulin can be seen in non‐diabetic insulin‐resistant states. Approximately 30% of healthy subjects with at least two first‐degree relatives with Type 2 diabetes exhibited perturbations in IRS‐1 expression and signaling. These individuals were characterized by insulin resistance as well as other markers of Syndrome X. Thus, impaired IRS‐1 expression and downstream signaling events in fat cells in response to insulin are associated with insulin resistance and Syndrome X.
Endogenous opioid immunoreactivity in rat spinal cord following traumatic injury (1985)

It has been postulated that endogenous opioids play a pathophysiological role in spinal cord injury, based on the therapeutic effects of the opiate receptor antagonist naloxone in certain experimental models. The high doses of naloxone required to exert a therapeutic action suggest that naloxone's effects may be mediated by non-mu opiate receptors, such as the kappa receptor. This notion is supported by recent pharmacological studies demonstrating that an opiate antagonist more active at kappa sites is effective and far more potent than naloxone in improving outcome after spinal cord injury. Moreover, dynorphin--postulated to be the endogenous ligand for the kappa receptor--is unique among opioids in producing hindlimb paralysis following intrathecal administration in the rat. In the present studies we have examined changes in endogenous opioid immunoreactivity following traumatic spinal cord injury in the rat. Dynorphin A was found to increase progressively with graded injury; changes were restricted to the injury segment and adjacent areas and were time dependent. Dynorphin A-(1-8) showed no marked changes. Methionine and leucine enkephalin were either unaltered or reduced at the injury site; changes were not well localized and were not clearly related to the injury variables. These findings provide further support for a potential pathophysiological role of prodynorphin-derived peptides in spinal cord injury.
Feedforward Tracking Controller Design Based on the Identification of Low Frequency Dynamics (1993)

Several methodologies are proposed for identifying the dynamics of a machine tool feed drive system in the low frequency region. An accurate identification is necessary for the design of a feedforward tracking controller, which achieves unity gain and zero phase shift for the overall system in the relevant frequency band. In machine tools and other mechanical systems, the spectrum of the reference trajectory is composed of low frequency signals. Standard least squares fits are shown to heavily penalize high frequency misfit. Linear models described by the output-error (OE) and Autoregressive Moving Average with eXogenous Input (ARMAX) models display better closeness-of-fit properties at low frequency. Based on the identification, a feedforward compensator is designed using the Zero Phase Error Tracking Controller (ZPETC). The feedforward compensator is experimentally shown to achieve near-perfect tracking and contouring of high-speed trajectories on a machining center X-Y bed.
Development of Electroactive and Elastic Nanofibers that contain Polyaniline and Poly(L‐lactide‐co‐ε‐caprolactone) for the Control of Cell Adhesion (2008)

In this work, electrically conductive polyaniline (PAni) doped with camphorsulfonic acid (CPSA) is blended with poly(L-lactide-co-epsilon-caprolactone) (PLCL), and then electrospun to prepare uniform nanofibers. The CPSA-PAni/PLCL nanofibers show a smooth fiber structure without coarse lumps or beads and consistent fiber diameters (which range from 100 to 700 nm) even with an increase in the amount of CPSA-PAni (from 0 to 30 wt.-%). However, the elongation at break decreases from 391.54 +/- 9.20% to 207.85 +/- 6.74% when 30% of CPSA-PAni is incorporated. Analysis of the surface of the nanofibers demonstrates the presence of homogeneously blended CPSA-PAni. Most importantly, a four-point probe analysis reveals that electrical properties are maintained in the nanofibers where the conductivity is significantly increased from 0.0015 to 0.0138 S x cm(-1) when the nanofibers are prepared with 30% CPSA-PAni. The cell adhesion tests using human dermal fibroblasts, NIH-3T3 fibroblasts, and C2C12 myoblasts demonstrate significantly higher adhesion on the CPSA-PAni/PLCL nanofibers than pure PLCL nanofibers. In addition, the growth of NIH-3T3 fibroblasts is enhanced under the stimulation of various direct current flows. The CPSA-PAni/PLCL nanofibers with electrically conductive properties may potentially be used as a platform substrate to study the effect of electrical signals on cell activities and to direct desirable cell function for tissue engineering applications.
Oxide-bypassed VDMOS (OBVDMOS): an alternative to superjunction high voltage MOS power devices (2001)

The superjunction concept has been proposed to overcome the ideal silicon MOSFET limit, but its fabrication was handicapped by the precise charge balance requirement and inter-diffusion problem. We report a novel device structure termed oxide-bypassed VDMOS (OBVDMOS) that requires the well-established oxide thickness control instead of the difficult doping control in translating the limit to a higher blocking voltage. This is done by using metal-thick-oxide (MTO) at the sidewalls of drift region. One can choose to have a higher blocking voltage or increase the background doping. A PiN structure, essentially identical to MOSFET during off state, was fabricated to demonstrate the proposed concept. Its measured BV/sub dss/ of 170 V is 2.5 times higher than measured conventional device BV/sub dss/ of 67 V on the same silicon wafer.
Analysis of numeric data streams at different granularities (2005)

A novel method for analyzing time-series data and extracting time-correlations (time-dependent relationships) among multiple time-series data streams is described. The proposed method is the first online method that can detect and report time-dependent relationships among multiple time-series data streams. Time-correlations tell us the relationships among numeric variables whose values are recorded over the course of time and transmitted using time-series data streams. Each time-correlation rule explains how the changes in the values of one set of time-series data streams influence the values in another set of time-series data streams. Those rules can be stored digitally and fed into various data analysis tools for further analysis. Performance experiments showed that the described method is 95% accurate, and has a linear running time with respect to the amount of input data.
Enantioselective Syntheses of Potent Retinoid X Receptor Ligands:  Differential Biological Activities of Individual Antipodes (2001)

The synthesis and characterization of chiral RXR selective ligands are described. The enantiomeric acids 2 and 3 were synthesized employing an enantioselective cylopropanation procedure as the key step. Compound 2, with an S,S configuration at C-9 and C-10, is a potent RXR agonist devoid of any RAR activity. The R,R enantiomer 3 is a weak RXR agonist and has demonstrable RAR activity in the receptor transactivation assays. The potent RXR activity of 2 was further confirmed in a hyperglycemic animal model (db/db mice). Compound 2 lowered glucose by 50% by day 7 at 2 mg/kg, whereas 3 had no effect at the same dosage. This further supports the contention that RXR mediated gene transcription is involved in the antidiabetic effects of RXR ligands.
Main Group Heterocycles from Lithiated Phosphinimines (2007)

Reaction of the phosphinimines (Me)tBu2PNSiMe3 (1), (Me)tBu2PNC6H2Me3 (3), and (PhCH2)tBu2PNSiMe3 (6) with nBuLi and subsequently (C6F5)2BCl affords the four-membered heterocycles [((C6F5)2BCH2)tBu2PNSiMe3] (2), [((C6F5)2BCH2)tBu2PNC6H2Me3] (5), and [((C6F5)2BCH(Ph))t-Bu2PNSiMe3] (7), respectively. The related phosphinimine (iPr)tBu2PNSiMe3 (8) reacts with tBuLi to give (LiCMe2)tBu2PNSiMe3 (9), which reacts with (C6F5)2BCl to yield the five-membered heterocycle [((C6F5)2BCH2CH(Me))tBu2PNSiMe3] (10). Similarly, the species [(Me2AlCMe2)iPr2PNSiMe3] (12) and [((Me2N)2BCMe2)iPr2PNSiMe3] (13) were prepared from lithiation of the phosphinimine iPr3PNSiMe3 (11). In exploring the chemistry of these heterocycles, compound 2 reacts with [Me3NH]Cl and MeOH to open the heterocycle, giving [(C6F5)2B(Cl)CH2PtBu2NH(SiMe3)] (14) and ((C6F5)2B(OMe)CH2)tBu2PNH2 (15), respectively. Subsequent treatment of 15 with Me3SiCl affords the species ((C6F5)2B(Cl)CH2)tBu2PNH2 (16), while treatment of 16 with nBuLi gives [((C6F5)2BCH2)tBu2PNH)] (17). Compound 17 coordinates AlMe3 to give ((C6F5)2BCH2)tBu2PNH](AlMe3) (18), while 15 reacts with AlMe3 to give the six-membered heterocycle [((C6F5)2B(OMe)CH2)tBu2PNH)(AlMe2)] (19). This chemistry is discussed and the implications are considered. X-ray crystallographic data are reported for 2, 5, 7, 9, 10, 14, and 17.
Extended-reach wells tap outlying reserves (1993)

The MAP is closely related to the development of ascites in compensated HCV-related cirrhosis. The risk of ascites development increases in 4.4 fold for subjects with MAP values <83.32 mm/Hg.
Abstract 868: HER2-targeted engineered toxin body demonstrates selective binding and cell kill of HER2-overexpressing breast cancer. (2013)

Abstract The HER2 receptor is overexpressed in 20-30% of breast cancers. HER2 overexpression in breast cancer has been successfully targeted by both antibody and antibody-drug conjugate approaches. Trastuzumab, a humanized monoclonal antibody is approved for the treatment of HER2 positive metastatic breast cancer. More recently, trastuzumab-DM1, an antibody drug conjugate (ADC), has shown promising clinical results in patients refractory to trastuzumab. Because DM1 is a chemotherapeutic and refractory breast cancer patients have typically progressed through several rounds of chemotherapy, we were interested in developing a new ADC approach with trastuzumab that utilized a novel mechanism of action. 5G2 is an engineered toxin body comprised of the trastuzumab scFv and a modified ribosome-inhibiting protein derived from Shiga-like toxin 1 A. 5G2 has exhibited high binding affinity to HER2 protein and HER2-expressing cells. 5G2 exerts a potent HER2-specific cytotoxic effect on HER2-expressing cells, but little activity on various HER2 negative cells. These results demonstrate that 5G2 is a promising HER2-targeted therapeutic agent against breast carcinomas and is currently under further development. Citation Format: Sangeetha Rajagopalan, Erin Willert, Rachel Wirth, William Null, Jen-Sing Liu, Jack P. Higgins. HER2-targeted engineered toxin body demonstrates selective binding and cell kill of HER2-overexpressing breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 868. doi:10.1158/1538-7445.AM2013-868
Classifying Colorectal Cancer by Tumor Location Rather than Sidedness Highlights a Continuum in Mutation Profiles and Consensus Molecular Subtypes (2017)

<b>Purpose:</b> Colorectal cancers are classified as right/left-sided based on whether they occur before/after the splenic flexure, with established differences in molecular subtypes and outcomes. However, it is unclear if this division is optimal and whether precise tumor location provides further information.<b>Experimental Design:</b> In 1,876 patients with colorectal cancer, we compared mutation prevalence and overall survival (OS) according to side and location. Consensus molecular subtype (CMS) was compared in a separate cohort of 608 patients.<b>Results:</b> Mutation prevalence differed by side and location for <i>TP53, KRAS, BRAFV600, PIK3CA, SMAD4, CTNNB1, GNAS</i>, and <i>PTEN</i> Within left- and right-sided tumors, there remained substantial variations in mutation rates. For example, within right-sided tumors, <i>RAS</i> mutations decreased from 70% for cecal, to 43% for hepatic flexure location (<i>P</i> = 0.0001), while <i>BRAF</i>V600 mutations increased from 10% to 22% between the same locations (<i>P</i> < 0.0001). Within left-sided tumors, the sigmoid and rectal region had more <i>TP53</i> mutations (<i>P</i> = 0.027), less <i>PIK3CA</i> (<i>P</i> = 0.0009), <i>BRAF</i> (<i>P</i> = 0.0033), or <i>CTNNB1</i> mutations (<i>P</i> < 0.0001), and less MSI (<i>P</i> < 0.0001) than other left-sided locations. Despite this, a left/right division preceding the transverse colon maximized prognostic differences by side and transverse colon tumors had K-modes mutation clustering that appeared more left than right sided. CMS profiles showed a decline in CMS1 and CMS3 and rise in CMS2 prevalence moving distally.<b>Conclusions:</b> Current right/left classifications may not fully recapitulate regional variations in tumor biology. Specifically, the sigmoid-rectal region appears unique and the transverse colon is distinct from other right-sided locations. <i>Clin Cancer Res; 24(5); 1062-72. ©2017 AACR</i><i>See related commentary by Dienstmann, p. 989</i>.
Therapeutic Approaches to Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Chronic Bronchitis. (2016)

Chronic obstructive pulmonary disease is a common cause of morbidity and a rising cause of mortality worldwide. Its rising impact indicates the ongoing unmet need for novel and effective therapies. Previous work has established a pathophysiological link between the chronic bronchitis phenotype of chronic obstructive pulmonary disease and cystic fibrosis as well as phenotypic similarities between these two airways diseases. An extensive body of evidence has established that cigarette smoke and its constituents contribute to acquired dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in the airways, pointing to a mechanistic link with smoking-related and chronic bronchitis. Recent interest surrounding new drugs that target both mutant and wild-type CFTR channels has paved the way for a new treatment opportunity addressing the mucus defect in chronic bronchitis. We review the clinical and pathologic evidence for modulating CFTR to address acquired CFTR dysfunction and pragmatic issues surrounding clinical trials as well as a discussion of other ion channels that may represent alternative therapeutic targets.
Development of the Hybrid/Battery ECU for the Toyota Hybrid System (1998)

&lt;div class="htmlview paragraph"&gt;For energy saving and global warming prevention, Toyota has developed Toyota Hybrid System (THS) for mass-produced passenger cars, which achieves drastic improvement in fuel efficiency and reduction in exhaust emissions compared to conventional gasoline engine cars.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The THS has two motive power sources which engage depending on driving conditions. It's power is supplied either from an engine (controlled by the engine ECU) or an electric motor (controlled by the motor ECU) which is powered by a high-voltage battery (monitored by the battery ECU). These ECUs are controlled by a hybrid ECU. Each ECU has been developed with a fail-safe system in mind, to ensure driver safety in case of vehicle breakdowns.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Among these ECUs, this paper reports particularly on the newly introduced ECUs: hybrid ECU and battery ECU. In the development of these ECUs, special attention was focused on fail-safe performance.&lt;/div&gt;
Characterization of Error-Tolerant Applications when Protecting Control Data (2006)

Soft errors have become a significant concern and recent studies have measured the "architectural vulnerability factor" of systems to such errors, or conversely, the potential that a soft error is masked by latches or other system behavior. We take soft-error tolerance one step further and examine when an application can tolerate errors that are not masked. For example, a video decoder or approximation algorithm can tolerate errors if the user is willing to accept degraded output. The key observation is that while the decoder can tolerate error in its data, it can not tolerate error in its control. We first present static analysis that protects most control operations. We examine several SPEC CPU2000 and MiBench benchmarks for error tolerance, develop fidelity measures for each, and quantify the effect of errors on fidelity. We show that protecting control is crucial to producing error-tolerance, for without this protection, many applications experience catastrophic errors (infinite execution time or crashing). Overall, our results indicate that with simple control protection, the error tolerance of many applications can provide designers with considerable added flexibility when considering future challenges posed by soft errors
Non‐Steroidal Antiinflammatory Agents Synthesis of Novel 2‐Pyrazolyl‐4(3H)‐Quinazolinones (1990)

Four novel series of pyrazolyl-4(3H)-quinazolinones have been prepared through the reaction of 3-aryl-2-hydrazino-4(3H)-quinazolinones with antipyrylazo-derivatives of ethyl acetoacetate, acetylacetone or diethyl malonate. These series of compounds are 3-aryl-2-[1-ethoxycarbonyl-1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H - pyrazol-4-yl)hydrazono-2-propylidene]hydrazino-4(3H)-quinazo linones; 3-aryl-2-[4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) hydrazono-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl]-4(3H)-quinaz olinones; 3-aryl-2-[4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)azo -3,5- dimethyl-1H-pyrazol-1-yl]-4(3H)-quinazolinones and 3-aryl-2-[4-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) hydrazono-3,5-dioxo-pyrazolidin-2-yl]-4(3H)-quinazolinones. The antiinflammatory activity of some representatives of the prepared compounds was studied.
Taxonomy of periodic nets and the design of materials (2007)

The concept of a natural tiling for a periodic net is introduced and used to derive a transitivity associated with the structure. It is accordingly shown that the transitivity provides a useful method of classifying polyhedra and nets. For design of materials to serve as targets for synthesis, structures with one kind of edge (edge transitive) are particularly important. Edge-transitive polyhedra, layers and 3-periodic nets are then described. Some other nets of special importance in crystal chemistry are also identified.
3,4-Dimethyl-4-(3-hydroxyphenyl)piperidines: opioid antagonists with potent anorectant activity (1993)

A series of (3R*,4R*)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists with varying substituents on the nitrogen were evaluated for their effect on food consumption in obese Zucker rats. Opioid affinity (mu, kappa, and delta for selected compounds) and opioid antagonist activity (mu and kappa) were characterized and compared to effects on food consumption. No compounds with high selectivity for either mu or kappa receptors were discovered. However, compounds in the series had exceptional potency as opioid antagonists and in reducing food consumption in the obese Zucker rat. In contrast, a few compounds with high potency as opioid antagonists had much weaker potency for inhibiting food consumption. (3R,4R)-3,4-Dimethyl-1-[(3S)-3- hydroxy-3-cyclohexyl-propyl]-4-(3-hydroxyphenyl)piperidine (11,LY255582) emerged as having the best activity profile, both in reducing food consumption and as an opioid antagonist. Compound 11 is a highly potent mu, kappa-, and delta-opioid antagonist with possible clinical utility as an appetite suppressant for weight loss.