gebhart/patrepeval huggingface dataset:
Introduction of acis-Acting Mutation in the Capsid-Coding Gene of Moloney Murine Leukemia Virus Extends Its Leukemogenic Properties (1999)

Inoculation of newborn mice with the retrovirus Moloney murine leukemia virus (MuLV) results in the exclusive development of T lymphomas with gross thymic enlargement. The T-cell leukemogenic property of Moloney MuLV has been mapped to the U3 enhancer region of the viral promoter. However, we now describe a mutant Moloney MuLV which can induce the rapid development of a uniquely broad panel of leukemic cell types. This mutant Moloney MuLV with synonymous differences (MSD1) was obtained by introduction of nucleotide substitutions at positions 1598, 1599, and 1601 in the capsid gene which maintained the wild-type (WT) coding potential. Leukemias were observed in all MSD1-inoculated animals after a latency period that was shorter than or similar to that of WT Moloney MuLV. Importantly, though, only 56% of MSD1-induced leukemias demonstrated the characteristic thymoma phenotype observed in all WT Moloney MuLV leukemias. The remainder of MSD1-inoculated animals presented either with bona fide clonal erythroid or myelomonocytic leukemias or, alternatively, with other severe erythroid and unidentified disorders. Amplification and sequencing of U3 and capsid-coding regions showed that the inoculated parental MSD1 sequences were conserved in the leukemic spleens. This is the first report of a replication-competent MuLV lacking oncogenes which can rapidly lead to the development of such a broad range of leukemic cell types. Moreover, the ability of MSD1 to transform erythroid and myelomonocytic lineages is not due to changes in the U3 viral enhancer region but rather is the result of a cis-acting effect of the capsid-coding gag sequence.
Transition-Metal-Free One-Pot Tandem Synthesis of 3-Ketoisoquinolines from Aldehydes and Phenacyl Azides (2019)

An efficient and transition-metal-free strategy for the synthesis of 3-keto-isoquinolines in one pot has been developed from the easily accessible 2-(formylphenyl)acrylates and phenacyl azides. Various substituted aldehydes and phenacyl azides were successfully employed in this transformation to furnish a variety 3-keto-isoquinolines in very good yields. A number of controlled experiments were conducted to postulate the reaction mechanism. Secondary functionalizations of 2-keto-isoquinolins were also performed to showcase the synthetic utility.
Prognostic implication of p53 mutations in HNSCC: Results of Intragroup margin study (E4393) (2006)

5504 Background: The role of p53 as a prognostic marker in head and neck squamous cell carcinoma (HNSCC) is controversial. The intent of this study was to evaluate rigorously the prognostic value of p53 genetic status. Methods: Tumor samples from 480 HNSCC patients treated surgically with curative intent were collected in a prospective multicenter study over 5 years. 57 cases were not analyzed due to technical or administrative factors. Mutation status was determined in the 423 remaining cases, using p53 chip (GP53 GeneChip from Affymetrix, Inc., Santa Clara, CA) which identifies mutations in exons 2 through 11. Indeterminate calls were investigated using Surveyor and/or DHPLC analysis and all mutations were confirmed with an automated fluorescent system or manual sequencing. Clinical follow-up was accomplished following Eastern Cooperative Oncology Group protocol. Results: Median follow-up of the 423 evaluable subjects was 5.4 years with all patients followed at least 3 years. Mutation of p53 gene was present in 224 (53%) cases. There we significantly fewer mutations in tumors arising in the oropharynx (chi-square p = 0.02). The presence of p53 mutation was significantly associated with decreased overall survival. Median survival for patients with tumors with p53 mutation was 3.1 years compared to 5.4 years fro WT tumors (HR = 1.4, 95% CI =1.1 to 1.8, p = 0.01 log-rank test). This proved to be independent of tumor site in multivariate analysis. When mutations were segregated according to their effect on biological function through alteration of key DNA binding domains a Cox regression analysis revealed a statistically significant linear effect of the more disruptive mutations on overall survival with a HR of 1.3 for comparison of each group to the one of lower risk (more vs. less disruptive mutation v. WT (p = 0.001 Wald test). Conclusions: This large prospective series shows a strong relationship between TP53 mutation and prognosis in HNSCC patients. Furthermore, the biological impact of specific mutations has a predictable graded relation to clinical outcome. The results set the stage for use of p53 genetic status in the design of future clinical trials and support the development of targeted therapy to restore wild-type p53 function. No significant financial relationships to disclose.
Data from ABT-888 Confers Broad <i>In vivo</i> Activity in Combination with Temozolomide in Diverse Tumors (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; ABT-888, currently in phase 2 trials, is a potent oral poly(ADP-ribose) polymerase inhibitor that enhances the activity of multiple DNA-damaging agents, including temozolomide (TMZ). We investigated ABT-888+TMZ combination therapy in multiple xenograft models representing various human tumors having different responses to TMZ.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; ABT-888+TMZ efficacy in xenograft tumors implanted in subcutaneous, orthotopic, and metastatic sites was assessed by tumor burden, expression of poly(ADP-ribose) polymer, and &lt;i&gt;O&lt;/i&gt;&lt;sup&gt;6&lt;/sup&gt;-methylguanine methyltransferase (MGMT).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Varying levels of ABT-888+TMZ sensitivity were evident across a broad histologic spectrum of models (55-100% tumor growth inhibition) in B-cell lymphoma, small cell lung carcinoma, non–small cell lung carcinoma, pancreatic, ovarian, breast, and prostate xenografts, including numerous regressions. Combination efficacy in otherwise TMZ nonresponsive tumors suggests that TMZ resistance may be overcome by poly(ADP-ribose) polymerase inhibition. Profound ABT-888+TMZ efficacy was seen in experimental metastases models that acquired resistance to TMZ. Moreover, TMZ resistance was overcome in crossover treatments, indicating that combination therapy may overcome acquired TMZ resistance. Neither tumor MGMT, mismatch repair, nor poly(ADP-ribose) polymer correlated with the degree of sensitivity to ABT-888+TMZ.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Robust ABT-888+TMZ efficacy is observed across a spectrum of tumor types, including orthotopic and metastatic implantation. As many TMZ nonresponsive tumors proved sensitive to ABT-888+TMZ, this novel combination may broaden the clinical use of TMZ beyond melanoma and glioma. Although TMZ resistance may be influenced by MGMT, neither MGMT nor other mechanisms of TMZ resistance (mismatch repair) precluded sensitivity to ABT-888+TMZ. Underlying mechanisms of TMZ resistance in these models are not completely understood but likely involve mechanisms independent of MGMT.(Clin Cancer Res 2009;15(23):7277–90)&lt;/p&gt;&lt;/div&gt;
Effect of In Vitro Nitrogen Dioxide Exposure on Human Bronchial Smooth Muscle Response (1992)

The aim of this study was to develop an in vitro system in which an isolated bronchus from human lung was exposed, during 30 min, to a constant flow of either air or nitrogen dioxide (NO2), and to examine subsequently the contractile response of airway smooth muscle rings to carbachol, histamine, and substance P. Two proximal bronchi were mounted in an organ bath, perfused externally with Krebs-Henseleit solution and ventilated with clean air, 1.0 or 2.0 ppm NO2. The exposed bronchi were then cut into rings and mounted in a computerized organ bath system. Contractile responses to agonists were measured isometrically. In each ring, a cumulative concentration response curve was obtained to the desired agonist. We found that in vitro exposure of human lumen bronchus to a constant flow of air did not alter the contractility of the smooth muscle. Whereas in vitro exposure of the bronchus to 1.0 ppm NO2 did not significantly increase the efficacy or the potency of carbachol, exposure to 2.0 ppm NO2 increased airway smooth muscle contractions in response to carbachol, histamine, and substance P. These results indicate that our experimental preparation is well suited to study the respiratory toxicity of inhaled pollutants in order to understand further the mechanisms underlying toxicant-induced airway hyperresponsiveness.
A structure/function analysis of Escherichia coli RNA polymerase (1996)

Control of RNA polymerase is a common means of regulating gene expression. A detailed picture of both the structure and how the structural details of RNA polymerase encode function is a key to understanding the molecular strategies used to regulate RNA polymerase. We review here data which ascribes functions to some regions of the primary sequence of the subunits (alpha, beta beta' sigma) which make up E. coli RNA polymerase. We review both genetic and biochemical data which place regions of the primary sequence that are distant from one another in close proximity in the tertiary structure. Finally we discuss the implications of these findings on the quaternary structure of RNA polymerase.
ChemInform Abstract: THE SYNTHESIS OF ENANTIOMERIC CYCLOPHOSPHAMIDES (1976)

Abstract Ausgehend von (‐)‐S‐ oder (?‐R‐a‐Phenyläthylamin (I) werden durch Umsetzung mit γ‐Chlorpropanol (II) zum (‐)‐ bzw. (+)‐N‐Hydroxypropylamin‐Derivat (III) und deren Reaktion mit dem P‐dichlorid (IV) vier Diastereoisomere ‐ zwei (‐)‐ bzw. zwei (+)‐Formen ‐ der Oxazaphosphorinan‐Verbindung (V) dargestellt und säulenchromatographisch isoliert.
Uncooked rice consumption: Causes, implications, regulation, and interventions (2022)

Abstract Background and Objectives Uncooked rice is not classified as produce under the Food Safety Modernization Act (FSMA) of the United States Food and Drug Administration produce safety rule because it is considered a food grain that is typically processed before consumption. However, uncooked rice is eaten by members of the raw food movement, pregnant pica patients, refugees in war zones, and young women as a perceived beauty treatment. Findings The consumption of raw rice may pose serious health risks such as foodborne illness, gastrointestinal issues, exposure to lectin and heavy metals, dental problems, and poor nutrition in consumers, especially those with low immunity including children and pregnant women. This review identifies the various circumstances under which raw rice is eaten or may be eaten, the possible health risks associated with raw rice consumption, and interventions that can be made to prevent the consumption of raw rice. Conclusions Many interventions are available to curb the raw rice consumption problem, including providing alternative sources of energy for cooking, medical interventions like iron therapy and psychological counseling for pica patients, and public education on the risks associated with the consumption of raw foods, and clearly differentiating foods that can be eaten raw from those that should not be eaten raw. Significance and Novelty This review raises awareness and provides vital multifaceted interventions that may influence policy changes that lead to a reduction in risk.
Establishment and Validation of a Rabbit Model for In Vivo Pharmacodynamic Screening of Tachykinin NK2 Antagonists (2012)

We attempted to establish and validate an in vivo pharmacodynamic (PD) rabbit model to screen tachykinin NK(2) receptor (NK(2)-R) antagonists using pharmacological and pharmacokinetic (PK)/PD analyses. Under urethane anesthesia, changes in intracolonic pressure associated with intravenous (i.v.) administration of a selective NK(2)-R agonist, βAla(8)-neurokinin A(4-10) (βA-NKA), was monitored as a PD marker. The analgesic effects of NK(2)-R antagonists were evaluated by monitoring visceromotor response (VMR) to colorectal distension in a rabbit model of visceral hypersensitivity induced by intracolonic treatment of acetic acid. Intravenous administration of βA-NKA induced transient colonic contractions dose-dependently, which were inhibited by the selective NK(2)-R antagonists in dose- and/or plasma concentration-dependent manners. The correlation between PD inhibition and plasma concentration normalized with the corresponding in vitro binding affinity was relatively high (r(2) = 0.61). Furthermore, the minimum effective doses on the VMR and ID(50) values calculated in the PD model were highly correlated (r(2) = 0.74). In conclusion, we newly established and validated a rabbit model of agonist-induced colonic contractions as a screening tool for NK(2)-R antagonists. In a drug discovery process, this PD model could enhance the therapeutic candidate selection for irritable bowel syndrome, pharmacologically connecting in vitro affinity for NK(2)-R with in vivo therapeutic efficacy.
Optical Millimeter-Wave Signal Generation Using Frequency Quadrupling Technique and No Optical Filtering (2008)

This letter demonstrates a novel method to generate high-purity optical millimeter-wave signals with carrier suppression by using a frequency quadrupling technique. To the authors' knowledge, this is the first time that a frequency quadrupling system requires only a single integrated Mach-Zehnder modulator without a narrowband optical filter to remove undesired optical sidebands. Since no optical filter is needed, fast frequency tuning is straightforward and this approach will be particularly attractive for optical up-conversion in wavelength-division-multiplexing radio-over-fiber systems. This letter provides both theoretical analysis and experimental demonstration. The generated optical millimeter-wave signals have very high quality with an optical carrier and harmonic distortion suppression ratio of more than 38 and 36 dB at 40 and 72 GHz, respectively.
The Metastatic Breast Cancer Project: A national direct-to-patient initiative to accelerate genomics research. (2016)

LBA1519 Background: The challenge in studying tumors from patients (pts) with metastatic breast cancer (MBC) has been that most tumors are not available for research, largely because most pts are cared for in community settings where genomics studies are not conducted. To address this, we launched a nationwide study, The Metastatic Breast Cancer Project, which seeks to empower patients to accelerate research by sharing their samples and clinical information. Methods: In collaboration with pts and advocacy groups, we developed a website to allow MBC pts to participate across the U.S. Enrolled pts are sent a saliva kit and asked to mail back a saliva sample, which is used to extract germline DNA. We contact participants’ medical providers and obtain medical records and part of their tumor biopsy. Whole exome and transcriptome sequencing is performed on tumor and germline. Clinically annotated genomic data are used to identify mechanisms of response and resistance to therapies. The database is shared widely with researchers. Study updates and discoveries are shared with participants regularly. Results: In the first 3 months, 1227 MBC pts enrolled. 1178 (96%) completed the 16-question survey about their cancer and treatments. Median age was 54 years (yrs) (range 25-91). Median time between initial diagnosis (dx) of breast cancer and MBC was 2 yrs; 424 pts were dx’d with de novo MBC. 1022 (87%) reported having a biopsy at or following their dx of MBC. Median time since MBC dx was 3 yrs; 87 reported having MBC &gt;10 yrs. 436 (37%) reported being on a therapy for &gt;2 yrs; 672 (57%) reported an “extraordinary response” to a therapy. For example, 77 reported long and/or extraordinary responses to capecitabine ; 44 to platinums, and 20 to everolimus. Initial medical records, saliva, and tumors have been received. Conclusions: A direct-to-patient approach enabled rapid identification of large numbers of MBC pts willing to share tumors, saliva, and medical records. This includes many with rare phenotypes, a group that has been challenging to identify with traditional approaches. Genomic analysis of pts with extraordinary responses and with de novo MBC are underway. Pt reported data has also identified unanticipated research questions.
Terrain Adaptive Navigation for planetary rovers (2009)

Abstract This paper describes the design, implementation, and experimental results of a navigation system for planetary rovers called Terrain Adaptive Navigation (TANav). This system was designed to enable greater access to and more robust operations within terrains of widely varying slippage. The system achieves this goal by using onboard stereo cameras to remotely classify surrounding terrain, predict the slippage of that terrain, and use this information in the planning of a path to the goal. This navigation system consists of several integrated techniques: goodness map generation, terrain triage, terrain classification, remote slip prediction, path planning, High‐Fidelity Traversability Analysis, and slip‐compensated path following. Results from experiments with an end‐to‐end onboard implementation of the TANav system in a Mars analog environment are shown and compared to results from experiments with a more traditional navigation system that does not account for terrain properties. © 2009 Wiley Periodicals, Inc.
Off-Line Control of Time-Pressure Dispensing Processes for Electronics Packaging (2003)

A wafer-level packaging (WLP) technology is under devel- opment that provides compliant electrical leads with a density as high as 12,000 per . The leads are batch processed while the integrated circuits are still in wafer form through a series of relatively simple pho- tolithographic steps. After electrical testing, the wafers are diced and the integrated circuits (ICs) are ready for direct assembly to an interconnect substrate. Sufficient lateral and vertical compliance is provided by the leads to accommodate the nonplanarity encountered during assembly and the thermal mismatch between the IC and substrate during normal operation. The high density of compliant leads presents both challenges and opportunities for electrical testing. This paper first summarizes the process technology used to fabricate these high-density electrical contacts. Several potential test strategies are then introduced that may take advantage of these contacts. Abstract—Computational fluid dynamics is used to calculate flows in the time-pressure dispenser. The analysis of different factors such as the yield stress, the power-law constants, the needle length, etc. will be useful in un- derstanding the dispensing mechanism and thus allow for performance im- provement. The numerical solution can provide more information about the wall shear stress and the pressure drop caused by a sudden contrac- tion. The approximation error associated with the analytical method can be understood through comparison with the numerical results. Thus, an ap- proximation compensation model may be derived for the analytical method to improve modeling accuracy.
Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep (2000)

To examine the function of prostaglandin (PG) D synthase (PGDS) gene, as well as endogenously produced PGD(2) in sleep regulation in vivo, we generated transgenic (TG) mice that overexpress human PGDS gene to study their sleep behavior. Although no difference was observed in the sleep/wake patterns between wild-type and TG mice, a striking time-dependent increase in non-rapid eye movement (NREM), but not in rapid eye movement (REM), sleep was observed in two independent lines of TG mice after stimulation by tail clipping. Concomitantly, the spontaneous locomotor activity of TG animals was drastically decreased in response to the tail clip. Induction of NREM sleep in TG mice was positively correlated with the PGD(2) production in the brain. Sleep, locomotion, and PGD(2) content were essentially unchanged in wild-type mice after tail clipping. The results with TG mice demonstrate the involvement of the PGDS gene in the regulation of NREM sleep.
Untidy Data: The Unreasonable Effectiveness of Tables (2021)

Working with data in table form is usually considered a preparatory and tedious step in the sensemaking pipeline; a way of getting the data ready for more sophisticated visualization and analytical tools. But for many people, spreadsheets - the quintessential table tool - remain a critical part of their information ecosystem, allowing them to interact with their data in ways that are hidden or abstracted in more complex tools. This is particularly true for data workers [61], people who work with data as part of their job but do not identify as professional analysts or data scientists. We report on a qualitative study of how these workers interact with and reason about their data. Our findings show that data tables serve a broader purpose beyond data cleanup at the initial stage of a linear analytic flow: users want to see and "get their hands on" the underlying data throughout the analytics process, reshaping and augmenting it to support sensemaking. They reorganize, mark up, layer on levels of detail, and spawn alternatives within the context of the base data. These direct interactions and human-readable table representations form a rich and cognitively important part of building understanding of what the data mean and what they can do with it. We argue that interactive tables are an important visualization idiom in their own right; that the direct data interaction they afford offers a fertile design space for visual analytics; and that sense making can be enriched by more flexible human-data interaction than is currently supported in visual analytics tools.
Hugoniot Constraint Molecular Dynamics Study of a Transformation to a Metastable Phase in Shocked Silicon (2002)

A molecular dynamics constraint based on the Hugoniot is formulated for the study of shocked materials. The constraint allows the simulation of a small part of the system under shock conditions for longer time periods than the use of a moving piston which creates a shock wave in a large system. It also allows for the use of quantum mechanical methods for which the work scales rapidly with system size. The constraint is used as a first approximation to study dynamical effects in shocked silicon. Transformations through metastable states are found under some conditions for shocks in the [111] direction using a tight‐binding model. A new six‐fold coordinated phase of silicon is found to be metastable under hydrostatic conditions using density functional theory.
Numerical and Experimental Study of Suspensions Containing Carbon Blacks Used as Conductive Additives in Composite Electrodes for Lithium Batteries (2014)

Suspensions of carbon blacks and spherical carbon particles are studied experimentally and numerically to understand the role of the particle shape on the tendency to percolation. Two commercial carbon blacks and one lab-synthesized spherical carbon are used. The percolation thresholds in suspensions are experimentally determined by two complementary methods: impedance spectroscopy and rheology. Brownian dynamics simulations are performed to explain the experimental results taking into account the fractal shape of the aggregates in the carbon blacks. The results of Brownian dynamics simulations are in good agreement with the experimental results and allow one to explain the experimental behavior of suspensions.
A Comparison of Implants Used in Open-Door Laminoplasty (2014)

Structural rib allograft struts and metallic miniplates result in similar improvements in pain and functional outcome scores with no difference in the rate of complications in short-term follow-up. Potential benefits of using a plate include shorter procedure length and less need for postoperative immobilization. When costs of bracing and operative time are included, the difference in cost between miniplates and allograft struts is negligible.