gebhart/patrepeval huggingface dataset:
CodeBreak 100: Activity of AMG 510, a novel small molecule inhibitor of KRAS<sup>G12C</sup>, in patients with advanced colorectal cancer. (2020)

4018 Background: Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation is associated with poor prognosis in colorectal cancer (CRC). AMG 510 is a first-in-class small molecule that specifically and irreversibly inhibits KRAS G12C by locking it in the inactive guanosine diphosphate-bound state. In a previous interim analysis of the phase 1, first-in-human trial of AMG 510, we observed a favorable safety profile and preliminary antitumor activity in patients (pts) with advanced solid tumors harboring KRAS p.G12C. Here, we present updated data in pts with CRC. Methods: Key inclusion criteria were KRAS p.G12C mutation identified through molecular testing, measurable disease, and progression on standard therapy. Primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), as assessed per RECIST 1.1, and overall survival (OS). Oral daily doses of 180, 360, 720, and 960mg were tested in the dose escalation phase, and 960mg dose was selected for the expansion phase. Results: As of Jan 8, 2020, 42 pts with CRC (21 female [50%], median age: 57.5 years [range: 33–82]) were enrolled and dosed (25 on 960mg). All pts received prior systemic therapies; 19 pts (45.2%) received > 3 prior lines. Median follow-up was 7.9 months (mos) (range: 4.2–15.9). 13 pts (31.0%) died, and 8 pts (19.0%) remained on treatment (tx). 22 (52.4%) and 8 (19.0%) pts had remained on tx for more than 3 and 6 months, respectively. Progressive disease was the most common reason for tx discontinuation. 20 pts (47.6%) had tx-related adverse events (TRAEs): 18 (42.9%) had grade 2 or lower TRAEs; 2 (4.8%) had grade 3 TRAEs, which were diarrhea (2.4%) and anemia (2.4%). There were no dose-limiting toxicities, fatal TRAEs, or TRAEs leading to tx discontinuation. Overall, ORR and DCR were 7.1% (3/42) and 76.2% (32/42), respectively. At 960mg, ORR and DCR were 12.0% (3/25) and 80.0% (20/25). 3 pts with PR had duration of response of 1.5, 4.2, and 4.3 months, respectively, and their responses were still ongoing at data cutoff. In all pts treated with all doses, median duration of stable disease was 4.2 mos (range: 2.5[+]–11.0). PFS/OS will be reported. Conclusions: In pts with heavily pretreated KRAS p.G12C mutant CRC, AMG 510 monotherapy was well tolerated, with the majority of pts achieving disease control. Study is ongoing. Clinical trial information: NCT03600883 .
Learning executable semantic parsers for natural language understanding (2016)

Semantic parsing is a rich fusion of the logical and the statistical worlds.
Susceptibility pattern of Campylobacter jejuni from human and animal origins to different antimicrobial agents (1982)

The in vitro antimicrobial activities of different antimicrobial agents on Campylobacter jejuni from human and animal origins were compared by using a Dynatech MIC 2000 system. In general, the minimal inhibitory concentration distributions for the human strains were very comparable with those of the animal strains. The animal strains had a bimodal distribution for ampicillin, clindamycin, and tetracycline.
Synergistic effects of low oxygen concentration, predator kairomone, and a pesticide on the cladoceran Daphnia pulex (1995)

The cladoceran Daphnia pulex was exposed to low oxygen concentration, a kairomone from the predator Chaoborus, and the pesticide carbaryl; the combined effects of these factors on Daphnia life-history characteristics were analyzed. Low oxygen reduced juvenile growth rate, mature size, clutch size, neonate body size, and neonatal neckteeth development; the effects depended on size at birth (neonate size), with a stronger influence on smaller neonates. The kairomone and carbaryl had similar effects, apart from the effect on neonatal neckteeth development, which was enhanced. In all treatments, positive relationships were found between individual body size and clutch size, mother’s body size and neonate size, and neonate size and neonatal neckteeth development. The most important effect of the environmental factors is probably reduction in juvenile growth rate. Reduced growth rate induced small size at maturation and thus smaller adult sizes, leading to smaller clutch sizes and producing smaller neonates, which had poorer neckteeth. Synergism was detected statistically for the effects of any pair of the three factors and of all together, indicating that one factor reduces tolerance to the other factors.
Mechanism of human platelet activation by endotoxic glycolipid-bearing mutant Re595 of Salmonella minnesota. (1986)

The mechanism through which human blood platelets interact with gram-negative bacteria with well-defined structural variations in endotoxic lipopolysaccharide was studied. Secretion of 14C-serotonin and aggregation of platelets separated from plasma proteins were observed on challenge with rough mutant Re595 of Salmonella minnesota possessing a glycolipid outer layer composed of Lipid A and 2-keto-3-deoxyoctonate (KDO) but lacking heptose phosphate in the core and O-polysaccharide in its outer portion. Both 14C-serotonin secretion and platelet aggregation were concentration-dependent, with a half-maximum response at the ratio of one bacterial colony-forming unit (CFU) to two platelets. The aggregation of human platelets induced by mutant Re595 was divalent cation-dependent and required secretion of ADP and fibrinogen from platelet storage granules because it was inhibited by chelators, by the ADP-splitting enzyme apyrase, and by monospecific antifibrinogen Fab fragments. The synthetic peptide analog of the platelet receptor recognition site on the gamma chain of fibrinogen, gamma 400-411, inhibited platelet aggregation induced by mutant Re595 (IC50 160 mumol/L), whereas serotonin secretion was unaffected. Tetrapeptide, RGDS, analogous to human fibrinogen alpha chain (alpha 572-575) and to the cell adhesion site of fibronectin, also inhibited aggregation induced by mutant Re595 (IC50 60 mumol/L). Secretion of 14C-serotonin was preceded by a very rapid phosphorylation of a platelet protein of mol wt 47,000, which is associated with protein kinase C activation. Myosin light chain (mol wt 20,000) was also phosphorylated. Both phosphoproteins were dephosphorylated while secretion was reaching maximum. Furthermore, release of 3H-arachidonic acid from platelet phospholipids and generation of thromboxane B2 via the cyclooxygenase pathway were observed. Inhibition of this pathway with acetylsalicylic acid (10(-4) mol/L) or indomethacin (5 X 10(-4) mol/L) reduced 14C-serotonin secretion and platelet aggregation. The role of Lipid A in the interaction of mutant Re595 with human platelets was deduced from the inhibitory effect of the Lipid A-binding protein present in Limulus amebocyte lysate. Likewise, polymyxin B, known to complex with Lipid A, was inhibitory. The reactivity of mutant Re595 toward platelets was attenuated by mild acid hydrolysis, during which KDO was dissociated from the glycolipid, and by alkaline hydrolysis, which breaks ester-linked fatty acids in Lipid A. In contrast to mutant Re595, strain S218 of S minnesota bearing "complete" endotoxic lipopolysaccharide did not induce secretion and aggregation of human platelets.(ABSTRACT TRUNCATED AT 400 WORDS)
Thick single crystal CVD diamond prepared from CH<sub>4</sub>‐rich mixtures (2006)

Abstract Recent interests in freestanding single‐crystal CVD diamond (SC‐CVD) discs for several applications in electronics led to an intense study of SC‐CVD layer growth and properties. In this work we have investigated the growth mechanism of monocrystalline CVD diamond films with surfaces smooth in nanometer scale taking into account the defect incorporation in the SC‐CVD layers. Specifically we discuss the surface structure characteristics for these conditions as studied with high‐resolution AFM mapping. The as‐grown CVD layers were removed from the substrate by laser cutting, followed by a polishing step, yielding freestanding plates. Subsequently, microscopic and colour studies as well as infrared absorption spectroscopy were performed. These investigations revealed the presence of several characteristic defects and impurities. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Idebenone increases mitochondrial complex I activity in fibroblasts from LHON patients while producing contradictory effects on respiration (2011)

These results indicate that idebenone is able to compensate the complex I deficiency in LHON patient cells with variable effects on respiration, indicating that the patients might not be equally likely to benefit from the treatment.
Unobtrusive Multimodal Biometric Authentication: The HUMABIO Project Concept (2008)

Human Monitoring and Authentication using Biodynamic Indicators and Behavioural Analysis (HUMABIO) (2007) is an EU Specific Targeted Research Project (STREP) where new types of biometrics are combined with state of the art sensorial technologies in order to enhance security in a wide spectrum of applications. The project aims to develop a modular, robust, multimodal biometrics security authentication and monitoring system which utilizes a biodynamic physiological profile, unique for each individual, and advancements of the state-of-the art in behavioural and other biometrics, such as face, speech, gait recognition, and seat-based anthropometrics. Several shortcomings in biometric authentication will be addressed in the course of HUMABIO which will provide the basis for improving existing sensors, develop new algorithms, and design applications, towards creating new, unobtrusive biometric authentication procedures in security sensitive, controlled environments. This paper presents the concept of this project, describes its unobtrusive authentication demonstrator, and reports some preliminary results.
Trends in death associated with pediatric dental sedation and general anesthesia (2013)

This series of media reports likely represent only a fraction of the overall morbidity and mortality related to dental anesthesia. These data may indicate an association between mortality and pediatric dental procedures under sedation, particularly in office settings. However, these relationships are difficult to test in the absence of a database that could provide an estimate of incidence and prevalence of morbidity and mortality. With growing numbers of children receiving anesthesia for dental procedures from providers with variable training, it is imperative to be able to track anesthesia-related adverse outcomes. Creating a national database of adverse outcomes will enable future research to advance patient safety and quality.
Observation of higher order quadrupole excitation frequencies in a linear ion trap (2000)

The resonant frequencies for quadrupole excitation of ions confined with a buffer gas in a linear quadrupole ion trap with Mathieu parameters a = 0 and q approximately 0.36 have been measured. The resonances are predicted to occur at angular frequencies omega(K)n given by omega(K)n = (omega/K)n + beta without the presence of a buffer gas where omega is the angular frequency of the trapping radio frequency, K = 1, 2, 3... is the order of the resonance calculated with perturbation theory, and n = 0, +/-1, +/-2, +/-3.... The resonances are measured through fragmentation of protonated reserpine. The observed frequencies agree closely with the theoretical values but there are small differences which vary from +0.6% at K = 2 to -2.7% at K = 6. This is believed to be the result of the dependence of the resonant frequencies upon the buffer gas density and/or the excitation amplitude. The resolution of the resonances (measured from the depletion of precursor and formation of fragment ions) increased by a factor of 2 as K increased from 1 to 6. This increase in resolution warrants further investigation into the use of higher order resonances for isolation and excitation of trapped ions.
Optically active poly(hydroxyurethane)s derived from cyclic carbonate andL-lysine derivatives (1996)

The polyaddition of L-lysine hydrochloride and bifunctional five-membered cyclic carbonate 1 was carried out in DMAc in the presence of 1 equiv of DBU or 2 equiv of sodium hydride for 24 h to afford optically active polyurethane 2 bearing hydroxy and carboxyl group. The polyaddition of L-lysinol and 1 was also carried out in NMP to afford higher molecular weight of optically active polyurethane 3 bearing hydroxy group in quantitative yield. These polyurethanes reacted with cupric acetate, sodium tetrahydroborate, and titanium tetraisopropoxide to afford the corresponding crosslinked gels immediately. © 1996 John Wiley & Sons, Inc.
Overcoming the Problem of Cytomegalovirus Infection after Organ Transplantation: Calling for Heracles? (1999)

Although diagnosis of CMV infections and treatment of CMV disease with effetive antiviral drugs have become much easier, the persistent problem of CMV infection after solid-organ transplantation still requires solid knowledge of the pathophysiology of its clinical manifestations in order to minimize the impact of CMV infections in the future. The complex symptomatology of CMV infection after solid-organ transplantation is reviewed as well as some of the new theories attempting to explain the myriad of symptoms seen after transplantation.
Proposal of backside Die-level analysis (2008)

We propose a Die-level backside analysis system, which makes it possible to apply backside emission analysis and the Optical Beam Induced Resistance Change (OBIRCH) for die chips. It is possible to analyze only failure dies without sacrificing good dies which exist on the same wafer with this system. As a result, we realize cost free wafer-level failure analysis. Furthermore, we have developed Solid Immersion Lens(SIL) plate realizing high spatial resolution observation conveniently. The die chip is ideal to apply to the SIL-plate, so that we can achieve high sensitivity and resolution efficiently.
Downstream elements of mammalian pre-mRNA polyadenylation signals: primary, secondary and higher-order structures (2003)

Primary, secondary and higher-order structures of downstream elements of mammalian pre-mRNA polyadenylation signals [poly(A) signals] are re viewed. We have carried out a detailed analysis on our database of 244 human pre-mRNA poly(A) signals in order to characterize elements in their downstream regions. We suggest that the downstream region of the mammalian pre-mRNA poly(A) signal consists of various simple elements located at different distances from each other. Thus, the downstream region is not described by any precise consensus. Searching our database, we found that approximately 80% of pre-mRNAs with the AAUAAA or AUUAAA core upstream elements contain simple downstream elements, consisting of U-rich and/or 2GU/U tracts, the former occurring approximately 2-fold more often than the latter. Approximately one-third of the pre-mRNAs analyzed here contain sequences that may form G-quadruplexes. A substantial number of these sequences are located immediately downstream of the poly(A) signal. A possible role of G-rich sequences in the polyadenylation process is discussed. A model of the secondary structure of the SV40 late pre-mRNA poly(A) signal downstream region is presented.
Studies on Fabrication and Reliability of GaN High-Resistivity-Cap-Layer HEMT (2018)

In this paper, we systematically investigate the effect of hydrogen plasma treatment radio frequency (RF) power, treatment time, and rapid thermal annealing (RTA) on the performance of high-resistivity-cap-layer high-electron-mobility-transistor (HRCL-HEMT). It is found that high RF power contributes to obtain high drain current, but induces more damage. An appropriate RTA process not only can repair the plasma damage but also improves the static characteristics of HRCL-HEMT. Subsequently, a large hydrogen plasma treatment time window of 4 min is demonstrated with an optimized RF power of 2 W and RTA at 350 °C for 5 min. Furthermore, the thermal stability of the optimized HRCL-HEMT is investigated by high temperature test and long-term thermal stress test. No obvious degradation of V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">TH</sub> , I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">G</sub> , R <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SH</sub> , and dynamic R <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ON</sub> is observed in both before and after passivation devices after 1000-h thermal stress. Finally, gate reliability of the HRCL-HEMT is also analyzed by time-to-failure test. The maximum gate voltage is determined to be 6.28 V for a ten-year lifetime with a failure rate of 1% at 25 °C.
Conservative Polarimetric Scatterers and Their Role in Incorrect Extensions of the Cameron Decomposition (2006)

The properties of conservative symmetric polarimetric scatterer scattering matrices are examined. It is shown that the unambiguous rotation angle for "conservative" symmetric polarimetric scatterers is the interval (-pi/4,+pi/4] as compared with (-pi/2,+pi/2] for nonconservative symmetric scatterers. Errors relating to the Cameron decomposition, which are recently introduced into the literature, are discussed. It is demonstrated that these errors arise from a faulty symmetric scatterer scattering matrix distance measure. This, in turn, leads to an improper mapping of the symmetric scatterer unit disk to a hemisphere. The correct mapping of the symmetric scatterer unit disk to the symmetric scatterer unit sphere is described
The BTB and CNC Homology 1 (BACH1) Target Genes Are Involved in the Oxidative Stress Response and in Control of the Cell Cycle (2011)

The regulation of gene expression in response to environmental signals and metabolic imbalances is a key step in maintaining cellular homeostasis. BTB and CNC homology 1 (BACH1) is a heme-binding transcription factor repressing the transcription from a subset of MAF recognition elements at low intracellular heme levels. Upon heme binding, BACH1 is released from the MAF recognition elements, resulting in increased expression of antioxidant response genes. To systematically address the gene regulatory networks involving BACH1, we combined chromatin immunoprecipitation sequencing analysis of BACH1 target genes in HEK 293 cells with knockdown of BACH1 using three independent types of small interfering RNAs followed by transcriptome profiling using microarrays. The 59 BACH1 target genes identified by chromatin immunoprecipitation sequencing were found highly enriched in genes showing expression changes after BACH1 knockdown, demonstrating the impact of BACH1 repression on transcription. In addition to known and new BACH1 targets involved in heme degradation (HMOX1, FTL, FTH1, ME1, and SLC48A1) and redox regulation (GCLC, GCLM, and SLC7A11), we also discovered BACH1 target genes affecting cell cycle and apoptosis pathways (ITPR2, CALM1, SQSTM1, TFE3, EWSR1, CDK6, BCL2L11, and MAFG) as well as subcellular transport processes (CLSTN1, PSAP, MAPT, and vault RNA). The newly identified impact of BACH1 on genes involved in neurodegenerative processes and proliferation provides an interesting basis for future dissection of BACH1-mediated gene repression in neurodegeneration and virus-induced cancerogenesis.
How I treat T-cell acute lymphoblastic leukemia in adults (2015)

T-cell immunophenotype of acute lymphoblastic leukemia (T-ALL) is an uncommon aggressive leukemia that can present with leukemic and/or lymphomatous manifestations. Molecular studies are enhancing our understanding of the pathogenesis of T-ALL, and the discovery of activating mutations of NOTCH1 and FBXW7 in a majority of patients has been a seminal observation. The use of pediatric intensive combination chemotherapy regimens in adolescents and young adults has significantly improved the outcome of patients with T-ALL. The use of nelarabine for relapsed and refractory T-ALL results in responses in a substantial minority of patients. Allogeneic hematopoietic cell transplantation (HCT) still plays a key role in patients with high-risk or relapsed/refractory disease. γ-Secretase inhibitors hold promise for the treatment of patients with NOTCH1 mutations, and the results of clinical trials with these agents are eagerly awaited. It is recommended that younger patients receive a pediatric-intensive regimen. Older and unfit patients can receive suitable multiagent chemotherapy and be allocated to HCT based on their response, risk factors, and comorbidities. Although advances in the treatment of T-ALL have lagged behind those of B-cell ALL, it is hoped that the molecular revolution will enhance our understanding of the pathogenesis and treatment of this aggressive lymphoid malignancy.
RADARS, a bioinformatics solution that automates proteome mass spectral analysis, optimises protein identification, and archives data in a relational database (2002)

RADARS, a rapid, automated, data archiving and retrieval software system for high-throughput proteomic mass spectral data processing and storage, is described. The majority of mass spectrometer data files are compatible with RADARS, for consistent processing. The system automatically takes unprocessed data files, identifies proteins via in silico database searching, then stores the processed data and search results in a relational database suitable for customized reporting. The system is robust, used in 24/7 operation, accessible to multiple users of an intranet through a web browser, may be monitored by Virtual Private Network, and is secure. RADARS is scalable for use on one or many computers, and is suited to multiple processor systems. It can incorporate any local database in FASTA format, and can search protein and DNA databases online. A key feature is a suite of visualisation tools (many available gratis), allowing facile manipulation of spectra, by hand annotation, reanalysis, and access to all procedures. We also described the use of Sonar MS/MS, a novel, rapid search engine requiring 40 MB RAM per process for searches against a genomic or EST database translated in all six reading frames. RADARS reduces the cost of analysis by its efficient algorithms: Sonar MS/MS can identifiy proteins without accurate knowledge of the parent ion mass and without protein tags. Statistical scoring methods provide close-to-expert accuracy and brings robust data analysis to the non-expert user.
Nitrate Therapy for Angina Pectoris (1985)

Nitrates are presently used in the therapy for angina pectoris. They have both direct coronary vascular and indirect systemic effects; each appears to contribute to their anti-anginal efficacy. The various nitrate preparations, including the newer preparations recently made clinically available, have varying utilities in the relief of acute ischemic pain or for anginal prophylaxis. Nitrate tolerance and dependence are proved phenomena, yet their impact on the clinical usage of nitrates is not clearly defined. The utility of nitrates, including intravenous nitroglycerin, in the treatment of unstable angina and vasospastic angina is well documented. Their efficacy compared with that of calcium channel blockers is still being investigated. The reported adverse effects of nitrates are few, despite their many years of usage in clinical medicine.