gebhart/patrepeval huggingface dataset:
<b>C-reactive Protein and Coronary Artery Disease</b> (2002)

Evidence suggests that inflammation plays a key role in the pathogenesis of atherosclerosis. The chronic inflammatory process can develop to an acute clinical event by the induction of plaque rupture and therefore cause acute coronary syndromes. The aim of this study was to determine the serum levels of the circulating acute-phase reactant C-reactive protein (CRP), which is a sensitive indicator of inflammation, in patients with chronic stable coronary artery disease (CAD) and acute coronary syndromes (ACS). We studied 56 subjects: 1) 25 consecutive patients (18 men, 7 women; mean age, 68.5 +/- 14.3 years, range, 40-86) with unstable angina (UA) or acute myocardial infarction (AMI); 2) 31 consecutive patients (25 men, 6 women; mean age 64 +/- 12.7; range, 47-83, years) with signs and symptoms of clinically stable CAD. High-sensitivity-C-reactive protein (hs-CRP) levels were determined with a commercially available enzyme-linked immunoassay method. In patients with unstable angina and AMI before reperfusion therapy, CRP levels were not significantly different to those in patients with stable CAD (5.96 +/- 2.26 versus 4.35 +/- 2.6 mg/L; P = 0.12), but tended to be higher in patients with unstable angina and AMI. Baseline CRP levels in the subgroup of patients with AMI (6.49 +/- 2.28 mg/L) were significantly higher than levels in patients with stable CAD (4.35 +/- 2.6 mg/L; P = 0.02). CRP levels in patients with unstable angina and AMI were measured four times during a 72-hour period (0, 12, 24, and 72 hours). The lowest value was observed at baseline and differed significantly from values measured at any other time of the observation period (P < 0.001; 5.96 +/- 2.26; 9.5 +/- 9.04, 18.25 +/- 11.02; 20.25 +/- 10.61). CRP levels after 12, 24, and 72 hours were also significantly different to the initial values for patients with stable CAD (P < 0.01). There was no correlation between CRP and creatine kinase (CK), CK-MB isoenzyme, or troponin I positivity as markers for the extent of the myocardial injury during the observation period. Baseline levels of serum CRP tended to be higher in patients with unstable angina or AMI but were not significantly different from levels in patients with chronic stable CAD. In the subgroup of patients with AMI, baseline CRP levels were significantly higher than the levels in patients with stable CAD. CRP as a marker of inflammation is significantly increased in patients with AMI and unstable angina shortly after the onset of symptoms (after a period of 12 hours), supporting the hypothesis of an activation of inflammatory mechanisms in patients with an acute coronary syndrome or AMI.
The Teicoplanin-Associated Locus Regulator (TcaR) and the Intercellular Adhesin Locus Regulator (IcaR) Are Transcriptional Inhibitors of the ica Locus in Staphylococcus aureus (2004)

Infections involving Staphylococcus aureus are often more severe and difficult to treat when the organism assumes a biofilm mode of growth. The polysaccharide poly-N-acetylglucosamine (PNAG), also known as polysaccharide intercellular adhesin, is synthesized by the products of the intercellular adhesin (ica) locus and plays a key role in biofilm formation. Numerous conditions and exogenous factors influence ica transcription and PNAG synthesis, but the regulatory factors and pathways through which these environmental stimuli act have been only partially characterized. We developed a DNA affinity chromatography system to purify potential regulatory proteins that bind to the ica promoter region. Using this technique, we isolated four proteins, including the staphylococcal gene regulator SarA, a MarR family transcriptional regulator of the teicoplanin-associated locus TcaR, DNA-binding protein II, and topoisomerase IV, that bound to the ica promoter. Site-directed deletion mutagenesis of tcaR indicated that TcaR was a negative regulator of ica transcription, but deletion of tcaR alone did not induce any changes in PNAG production or in adherence to polystyrene. We also investigated the role of IcaR, encoded within the ica locus but divergently transcribed from the biosynthetic genes. As has been shown previously in Staphylococcus epidermidis, we found that IcaR was also a negative regulator of ica transcription in S. aureus. We also demonstrate that mutation of icaR augmented PNAG production and adherence to polystyrene. Transcription of the ica locus, PNAG production, and adherence to polystyrene were further increased in a tcaR icaR double mutant. In summary, TcaR appeared to be a weak negative regulator of transcription of the ica locus, whereas IcaR was a strong negative regulator, and in their absence PNAG production and biofilm formation were enhanced.
Downsizing a Gasoline Engine Using Turbocharging with Direct Injection (2003)

&lt;div class="htmlview paragraph"&gt;Nowadays, downsizing (reduction of the engine size) appears as a major way of improving fuel consumption of spark ignited engines while maintaining the advantage of the low emission capability of three ways catalytic system. The downsizing approach with turbocharged applications is now more and more oriented towards fuel economy, thanks to dedicated solutions. The use of gasoline direct injection system coupled with adapted turbochargers provides several ways of enhancing engine knock resistance especially at high load and low engine speed where existing PFI turbocharged engines are still limited.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The purpose of this paper is to highlight the combustion behaviors of the new generation of turbocharged direct injection engines and to demonstrate the potential of such a solution on a specific application. First, we explain the global system approach (injection, turbocharger, fluid motion, valve timing …) used to reach the necessary goals: high low end torque and specific power capabilities and low specific fuel consumption over the whole engine map. Then, we present all the results at part load and full load obtained on the Renault basis 1.8l IDE concept modified by IFP for a turbocharged application. This engine allows to take advantage of its high knocking limit in order to replace a 3.0 liter naturally aspirated engine and thus to have a fuel consumption benefit of more than 15% with at least the same acceleration performance. At full load, the specific fuel consumption is less than 300 g/kWh over the whole engine speed range with a BMEP of 2.0 MPa over 1500 rpm and a power density of 83 kW/l with a fixed compression ratio of 10.3:1.&lt;/div&gt;
Differential protein–protein interactions of LRRK1 and LRRK2 indicate roles in distinct cellular signaling pathways (2014)

Genetic studies show that LRRK2, and not its closest paralogue LRRK1, is linked to Parkinson's disease. To gain insight into the molecular and cellular basis of this discrepancy, we searched for LRRK1- and LRRK2-specific cellular processes by identifying their distinct interacting proteins. A protein microarray-based interaction screen was performed with recombinant 3xFlag-LRRK1 and 3xFlag-LRRK2 and, in parallel, co-immunoprecipitation followed by mass spectrometry was performed from SH-SY5Y neuroblastoma cell lines stably expressing 3xFlag-LRRK1 or 3xFlag-LRRK2. We identified a set of LRRK1- and LRRK2-specific as well as common interactors. One of our most prominent findings was that both screens pointed to epidermal growth factor receptor (EGF-R) as a LRRK1-specific interactor, while 14-3-3 proteins were LRRK2-specific. This is consistent with phosphosite mapping of LRRK1, revealing phosphosites outside of 14-3-3 consensus binding motifs. To assess the functional relevance of these interactions, SH-SY5Y-LRRK1 and -LRRK2 cell lines were treated with LRRK2 kinase inhibitors that disrupt 14-3-3 binding, or with EGF, an EGF-R agonist. Redistribution of LRRK2, not LRRK1, from diffuse cytoplasmic to filamentous aggregates was observed after inhibitor treatment. Similarly, EGF induced translocation of LRRK1, but not of LRRK2, to endosomes. Our study confirms that LRRK1 and LRRK2 can carry out distinct functions by interacting with different cellular proteins. LRRK1 and LRRK2 (leucine-rich repeat kinase) interaction partners were identified by two different protein-protein interaction screens. These confirmed epidermal growth factor receptor (EGR-R) as a LRRK1-specific interactor, while 14-3-3 proteins were LRRK2-specific. Functional analysis of these interactions and the pathways they mediate shows that LRRK1 and LRRK2 signaling do not intersect, reflective of the differential role of both LRRKs in Parkinson's disease.
Integrin activation (2004)

The ability of cells to regulate dynamically their adhesion to one another and to the extracellular matrix (ECM) that surrounds them is essential in multicellular organisms. The integrin family of transmembrane adhesion receptors mediates both cell-cell and cell-ECM adhesion. One important, rapid and reversible mechanism for regulating adhesion is by increasing the affinity of integrin receptors for their extracellular ligands (integrin activation). This is controlled by intracellular signals that, through their action on integrin cytoplasmic domains, induce conformational changes in integrin extracellular domains that result in increased affinity for ligand. Recent studies have shed light on the final intracellular steps in this process and have revealed a vital role for the cytoskeletal protein talin.
Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. (1999)

In a series of 111 patients with squamous cell carcinoma (SCC), we used immunohistochemistry to examine the expression levels of four epidermal growth factor receptor (EGFR) family members (EGFR, HER-2/neu, HER-3, and HER-4). Expression of the EGFR members was not significantly associated with tumor size. However, their expressions (except for HER-4) were significantly associated with the presence of lymph node metastasis, and all of them were significantly associated with distant metastasis. We further examined the association between the expression levels of the EGFR members and the survival rates in 47 oral SCC patients whose detailed clinical follow-ups were available. The expression of all EGFR members was significantly associated with shortened patient survival, and the association was strongest for HER-2/neu. Furthermore, the combination of HER-2, HER-3, and EGFR but not HER-4 significantly improved the predicting power. The expression level of HER-2/neu was significantly correlated with that of EGFR or HER-3. Similar coexpression patterns were also observed in three oral SCC cell lines studied, but not in four other head and neck SCC cell lines. Taken together, these results indicated that expression levels of EGFR, HER-2/ neu, and HER-3 may help predict the outcome of patients with oral SCC.
Extensive terminal and asymmetric processing of small RNAs from rRNAs, snoRNAs, snRNAs, and tRNAs (2012)

Deep sequencing studies frequently identify small RNA fragments of abundant RNAs. These fragments are thought to represent degradation products of their precursors. Using sequencing, computational analysis, and sensitive northern blot assays, we show that constitutively expressed non-coding RNAs such as tRNAs, snoRNAs, rRNAs and snRNAs preferentially produce small 5' and 3' end fragments. Similar to that of microRNA processing, these terminal fragments are generated in an asymmetric manner that predominantly favors either the 5' or 3' end. Terminal-specific and asymmetric processing of these small RNAs occurs in both mouse and human cells. In addition to the known processing of some 3' terminal tRNA-derived fragments (tRFs) by the RNase III endonuclease Dicer, we show that several RNase family members can produce tRFs, including Angiogenin that cleaves the TψC loop to generate 3' tRFs. The 3' terminal tRFs but not the 5' tRFs are highly complementary to human endogenous retroviral sequences in the genome. Despite their independence from Dicer processing, these tRFs associate with Ago2 and are capable of down regulating target genes by transcript cleavage in vitro. We suggest that endogenous 3' tRFs have a role in regulating the unwarranted expression of endogenous viruses through the RNA interference pathway.
Estrogen receptor (ER)-β isoforms: A key to understanding ER-β signaling (2006)

Estrogen receptor beta (ER-beta) regulates diverse physiological functions in the human body. Current studies are confined to ER-beta1, and the functional roles of isoforms 2, 4, and 5 remain unclear. Full-length ER-beta4 and -beta5 isoforms were obtained from a prostate cell line, and they exhibit differential expression in a wide variety of human tissues/cell lines. Through molecular modeling, we established that only ER-beta1 has a full-length helix 11 and a helix 12 that assumes an agonist-directed position. In ER-beta2, the shortened C terminus results in a disoriented helix 12 and marked shrinkage in the coactivator binding cleft. ER-beta4 and -beta5 completely lack helix 12. We further demonstrated that ER-beta1 is the only fully functional isoform, whereas ER-beta2, -beta4, and -beta5 do not form homodimers and have no innate activities of their own. However, the isoforms can heterodimerize with ER-beta1 and enhance its transactivation in a ligand-dependent manner. ER-beta1 tends to form heterodimers with other isoforms under the stimulation of estrogens but not phytoestrogens. Collectively, these data support the premise that (i) ER-beta1 is the obligatory partner of an ER-beta dimer, whereas the other isoforms function as variable dimer partners with enhancer activity, and (ii) a single functional helix 12 in a dimer is sufficient for gene transactivation. Thus, ER-beta behaves like a noncanonical type-I receptor, and its action may depend on differential amounts of ER-beta1 homo- and heterodimers formed upon stimulation by a specific ligand. Our findings have provided previously unrecognized directions for studying ER-beta signaling and design of ER-beta-based therapies.
Dual targeting of HER1/EGFR and HER2 with cetuximab and trastuzumab in patients with metastatic pancreatic cancer after gemcitabine failure: results of the “THERAPY”phase 1-2 trial (2015)

To improve treatment efficacy, we decided to simultaneously target HER1 and HER2 with trastuzumab and cetuximab. Following promising preclinical results, we conducted a phase 1-2 trial in advanced pancreatic cancer patients after first-line gemcitabine-based chemotherapy failure. In this single-arm, non-randomized, multicenter trial, patients received weekly cetuximab (400mg/m², then 250mg/m²). They were sequentially included in two trastuzumab dose levels: 3.0 or 4.0mg/kg, then 1.5 or 2.0mg/kg/weekly. Endpoints were the objective response rate, safety, progression-free (PFS) and overall survival (OS). During phase 1 (n=10 patients), toxicities were evenly distributed except for skin toxicities that frequently caused compliance issues. The higher dose level was defined as the trastuzumab recommended dose. During phase 2 (n=39 patients), toxicities were mainly cutaneous reactions and asthenia. No objective response was observed. Nine patients were stabilized but arrested treatment due to toxicity. Median PFS was 1.8 months (95%CI: 1.7-2.0 months) and median OS was 4.6 months (95%CI: 2.7-6.6 months). Both were positively correlated with skin toxicity severity (P=0.027 and P=0.001, respectively). Conventional phase 1 dose-escalation schedules are unsuitable for targeted therapies because most cutaneous toxicities are not considered dose-limiting toxicities. The compliance issues caused by skin toxicities were particularly detrimental because of the toxicity-response correlation.
Isolation of a coaggregation-inhibiting cell wall polysaccharide from Streptococcus sanguis H1 (1989)

Coaggregation between Streptococcus sanguis H1 and Capnocytophaga ochracea ATCC 33596 cells is mediated by a carbohydrate receptor on the former and an adhesin on the latter. Two methods were used to release the carbohydrate receptor from the gram-positive streptococcus, autoclaving and mutanolysin treatment. The polysaccharide released from the streptococcal cell wall by either treatment was purified by ion-exchange chromatography; this polysaccharide inhibited coaggregation when preincubated with the gram-negative capnocytophaga partner. After hydrolysis of the polysaccharide by hydrofluoric acid (HF), the major oligosaccharide of the polysaccharide was purified by high-performance liquid chromatography. By analysis of the HF hydrolysis of the polysaccharide and the purified oligosaccharide, this major oligosaccharide appeared to be the repeating unit of the polysaccharide, with minor components resulting from internal hydrolysis of the major oligosaccharide. Gas chromatography results showed that the oligomer was a hexasaccharide, consisting of rhamnose, galactose, and glucose, in the ratio of 2:3:1, respectively. By weight, the purified hexasaccharide was a fourfold-more-potent inhibitor of coaggregation than the native polysaccharide. Resistance to hydrolysis by sulfuric acid alone and susceptibility to hydrolysis by HF suggested that oligosaccharide chains of the polysaccharide are linked by phosphodiester bonds. Studies with a coaggregation-defective mutant of S. sanguis H1 revealed that the cell walls of the mutant contained neither the polysaccharide nor the hexasaccharide repeating unit. The purification of both a polysaccharide and its constituent hexasaccharide repeating unit, which both inhibited coaggregation, and the absence of this polysaccharide or hexasaccharide on a coaggregation-defective mutant strongly suggest that the hexasaccharide derived from the polysaccharide functions as the receptor for the adhesin from C. ochracea ATCC 33596.
X-ray photoelectron spectroscopy for sulfide glass electrolytes in the systems Li<sub>2</sub>S&ndash;P<sub>2</sub>S<sub>5</sub> and Li<sub>2</sub>S&ndash;P<sub>2</sub>S<sub>5</sub>&ndash;LiBr (2016)

X-ray photoelectron spectra of S 2p and P 2p were obtained for the xLi 2 S(100 x)P 2 S 5 (x = 70, 75 and 80 mol %) glasses prepared by mechanochemical treatment. A peak deconvolution technique was used to separate the S 2p spectra into three sulfur components of bridging sulfur (S 0 ), non-bridging sulfur (S ) and sulfide ion (S 2 ) with different photoelectron binding energies. The fractions of sulfurs at different electronic states were obtained from the area ratio of each peak. No apparent difference in the P 2p spectra was observed in the glasses. In the (100 y)(0.7Li 2 S0.3P 2 S 5 )yLiBr (y = 0, 5, 10 and 20 mol %) glasses, the fractions of S 0 and S were almost the same in each glass regardless of the amount of added LiBr content. The addition of LiBr did not affect the electronic state of sulfur in the Li 2 SP 2 S 5 LiBr glasses.
GARANT-a general algorithm for resonance assignment of multidimensional nuclear magnetic resonance spectra (1997)

A new program for automatic resonance assignment of nuclear magnetic resonance (NMR) spectra of proteins, GARANT (General Algorithm for Resonance AssignmeNT), is introduced. Three principal elements used in this approach are: (a) representation of resonance assignments as an optimal match of two graphs describing, respectively, peaks expected from combined knowledge of the primary structure and the magnetization transfer pathways in the spectra used, and experimentally observed peaks; (b) a scoring scheme able to distinguish between correct and incorrect resonance assignments; and (c) combination of an evolutionary algorithm with a local optimization routine. The score that evaluates the match of expected peaks to observed peaks relies on the agreement of the information available about these peaks, most prominently, but not exclusively, the chemical shifts. Tests show that the combination of an evolutionary algorithm and a local optimization routine yields results that are clearly superior to those obtained when using either of the two techniques separately in the search for the correct assignments. GARANT is laid out for assignment problems involving peaks observed in two- and three-dimensional homonuclear and heteronuclear NMR spectra of proteins. © 1997 by John Wiley & Sons, Inc.
Irrefutable evidence for the use of docetaxel in newly diagnosed metastatic prostate cancer: results from the STAMPEDE and CHAARTED trials (2015)

Androgen deprivation therapy (ADT) has been used in the treatment of metastatic prostate cancer since the first description of its hormonal dependence in 1941. In 2004, docetaxel chemotherapy became the mainstay of treatment in metastatic castration-resistant prostate cancer (mCRPC), following robust, albeit modest, survival benefit in two randomized phase 3 trials. The recently published CHAARTED trial was the first to show that combining ADT with docetaxel in men with hormone-naïve (hormone-sensitive) metastatic prostate cancer (mHSPC) yielded a remarkable overall survival benefit of 13.6 months as compared with ADT alone. In the current issue of The Lancet, James et al. report results of the STAMPEDE trial in men with high-risk locally advanced or metastatic prostate cancer initiating long-term hormone therapy. The combination of six cycles of docetaxel with ADT in men commencing long-term ADT demonstrated a similar OS benefit compared with standard of care (SOC) by a median of 10 months. Based on the consistency of the data and the firmness of the benefit provided, docetaxel in addition to ADT should be considered SOC for men with newly diagnosed mHSPC.
JNK Regulation of Depression and Anxiety (2017)

Depression and anxiety are the most common mood disorders affecting 300 million sufferers worldwide. Maladaptive changes in the neuroendocrine stress response is cited as the most common underlying cause, though how the circuits underlying this response are controlled at the molecular level, remains largely unknown. Approximately 40% of patients do not respond to current treatments, indicating that untapped mechanisms exist. Here we review recent evidence implicating JNK in the control of anxiety and depressive-like behavior with a particular focus on its action in immature granule cells of the hippocampal neurogenic niche and the potential for therapeutic targeting for affective disorders.
A simple distributed autonomous power control algorithm and its convergence (1993)

For wireless cellular communication systems, one seeks a simple effective means of power control of signals associated with randomly dispersed users that are reusing a single channel in different cells. By effecting the lowest interference environment, in meeting a required minimum signal-to-interference ratio of rho per user, channel reuse is maximized. Distributed procedures for doing this are of special interest, since the centrally administered alternative requires added infrastructure, latency, and network vulnerability. Successful distributed powering entails guiding the evolution of the transmitted power level of each of the signals, using only focal measurements, so that eventually all users meet the rho requirement. The local per channel power measurements include that of the intended signal as well as the undesired interference from other users (plus receiver noise). For a certain simple distributed type of algorithm, whenever power settings exist for which all users meet the rho requirement, the authors demonstrate exponentially fast convergence to these settings.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>