gebhart/patrepeval huggingface dataset:
Abstract 1122: Germline mutation prevalence in young adults with cancer (2020)

Abstract The identification of germline pathogenic variants in young adult cancer patients is especially critical given risk of second primary cancers, need for appropriate long-term surveillance, potential reproductive implications, and cascade testing of at-risk family members. We sought to determine the prevalence of germline susceptibility in cancer patients, age 18-39, across diverse solid tumor phenotypes. A total of 1201 cases, diagnosed between ages 18-39 were prospectively ascertained from 2015-2019 under a human subjects-approved protocol that provided result transmission of germline analysis. A next-generation sequencing panel consisting of up to 88 genes previously implicated in cancer predisposition (MSK-IMPACT) was utilized. Based on SEER data, we refined our population of young cancer patients into those with 1) early-onset cancer (EO-CA), defined as cancer wherein age 39 is &amp;gt;1 standard deviation (STD) below the mean age of diagnosis for that cancer type and 2) young-adult cancer (YA-CA), defined as cancer wherein age 39 is &amp;lt;1 STD below the mean age at cancer diagnosis. Among EO-CA (n=877) cases, the most common cancers included colorectal, breast, kidney, pancreas, and ovarian cancer, while among YA-CAs (n=324), the most frequent diagnoses were sarcoma, brain, testicular and thyroid cancer. Germline prevalence of likely pathogenic or pathogenic variants (PV) was 21% in the EO-CA versus 13% in YA-CA patients (p=0.002), with an enrichment of high- and moderate-penetrance PVs in the EO-CA cohort (15% vs 10%; p=0.01). Among EO-CAs, the most commonly mutated genes were BRCA2, BRCA1, CHEK2 and ATM, with pancreas, breast, and kidney cancer harboring the highest rates of germline PVs. In contrast, in the YA-CA cohort, TP53 and SDHA mutations predominated. Among YA-CA patients with sarcoma, the 18.1% mutation prevalence was similar to the prevalence in EO-CAs. Matched tumor analyses assessing biallelic inactivation is on-going and will be presented. Among young adults with early-onset phenotypes of malignancies typically presenting at later ages, the increased prevalence of germline PVs supports a role for genetic testing irrespective of tumor type. Citation Format: Zsofia K. Stadler, Anna Maio, Angelika Padunan, Yelena Kemel, Erin Salo-Mullen, Margaret Sheehan, Kimeisha Belanfanti, Prince R. Tejada, Ozge Birsoy, Diana Mandelker, Liying Zhang, Jesse Galle, Darren Feldman, Laura Boucai, Julia Glade Bender, Anna Piotrowski, Carol Aghajanian, Karen A. Cadoo, Maria I. Carlo, Michael Walsh, Yelena Janjigian, Eileen O'Reilly, Lisa M. DeAngelis, David B. Solit, Barry Taylor, Andrea Cercek, William Tap, Mark E. Robson, Michael F. Berger, Kenneth Offit, Luis A. Diaz. Germline mutation prevalence in young adults with cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1122.
Calidad de vida en pacientes egresados de una unidad de cuidados intensivos de tercer nivel; estudio prospectivo de 12 meses (2016)

La calidad de vida los pacientes que son egresados de las unidades de cuidado intensivo es una preocupación frecuente por la alta incidencia de secuelas cognitivas y las complicaciones funcionales que padece esta población luego de su egreso. Este trabajo presenta el resultado de un seguimiento de 6 meses de pacientes que pasaron por cuidados intensivos y luego del alta hospitalaria. Este estudio fue parte de una investigación mayor que dio seguimiento a los pacientes por espacio total de 12 meses. Materiales y método: Se trató de un estudio observacional, descriptivo y prospectivo de un año de duración que dio seguimiento a los pacientes egresados de la UCI hasta los 6 meses del egreso hospitalario. La información recabada incluyó datos demográficos y de condición de salud que se recolectaron al ingreso a la UCI, al momento del alta hospitalaria, a los 28 días y a los 6 meses. Además, se evaluó la calidad de vida a partir de su grado de independencia y reinserción laboral o regreso a las actividades normales. Resultados: Completaron el estudio un total de 118 pacientes, 52% de ellos hombres, con una edad promedio de 50 años. La estancia promedio en la Unidad fue de 6,5 días y la estancia promedio de hospitalización posterior a la UCI fue de 6 días. La mayor parte de los pacientes ingresaron por cardiopatía isquémica. La mortalidad intrahospitalaria fuera de la unidad de cuidados intensivos fue del 3%, con una mortalidad a los 28 días de un 3%, para una mortalidad global del 14 % a los 6 meses. A los 6 meses, el 64% de los pacientes tenían una reinserción adecuada, 24% tenían problemas en un área, 10% presentaban problemas en dos áreas, y el 1% presentó problemas en 3 áreas. Las mujeres presentaron una mejor tasa de reinserción. Conclusión: A los 6 meses, los pacientes egresados de la unidad de cuidados intensivos presentan un alto porcentaje de reinserción completa a sus labores habituales. Los hombres presentaron mayores problemas de reinserción en relación a secuelas de trauma.
A High-Throughput Screen Identifies 2,9-Diazaspiro[5.5]Undecanes as Inducers of the Endoplasmic Reticulum Stress Response with Cytotoxic Activity in 3D Glioma Cell Models (2016)

The endoplasmic reticulum (ER) is involved in Ca2+ signaling and protein folding. ER Ca2+ depletion and accumulation of unfolded proteins activate the molecular chaperone GRP78 (glucose-regulated protein 78) which in turn triggers the ER stress response (ERSR) pathway aimed to restore ER homeostasis. Failure to adapt to stress, however, results in apoptosis. We and others have shown that malignant cells are more susceptible to ERSR-induced apoptosis than their normal counterparts, implicating the ERSR as a potential target for cancer therapeutics. Predicated on these findings, we developed an assay that uses a GRP78 biosensor to identify small molecule activators of ERSR in glioma cells. We performed a quantitative high-throughput screen (qHTS) against a collection of ~425,000 compounds and a comprehensive panel of orthogonal secondary assays was formulated for stringent compound validation. We identified novel activators of ERSR, including a compound with a 2,9-diazaspiro[5.5]undecane core, which depletes intracellular Ca2+ stores and induces apoptosis-mediated cell death in several cancer cell lines, including patient-derived and 3D cultures of glioma cells. This study demonstrates that our screening platform enables the identification and profiling of ERSR inducers with cytotoxic activity and advocates for characterization of these compound in in vivo models.
Abstract B28: Discovery of 2-acetylpyridine-[N-(3-hydroxy-2-naphthoyl)]hydrazone analogs as glycine N-methyltransferase (GNMT) inducers for the treatment of hepatocellular carcinoma (HCC) (2017)

Abstract Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third most common cause of cancer mortality. Because of the late diagnosis, poor treatment options and high recurrence, the incidence still nearly equals to the mortality rate. Therefore, the discovery of novel therapeutic agents and/or drug combination strategies is urgently needed. Glycine N-methyltransferase (GNMT) is a tumor suppressor gene for HCC. Literatures revealed that the expression of GNMT is significantly down-regulated in HCC patients. Therefore, discovery of small molecule compounds that are able to enhance GNMT expression will have important implications for the treatment of HCC. Recently, we have identified a small molecule, 2-acetylpyridine-[N-(3-hydroxy-2-naphthoyl)]hydrazone (1), as a hit from a collective drug library containing more than 20,000 compounds using a GNMT gene expression-oriented screen platform. Preliminary results indicated that compound 1 is capable of inducing GNMT expression strongly with 7.57 folds to control in 2.5 micromole. In order to discover novel lead compounds based on the initial hit, we have synthesized more than 100 analogs of compound 1 and evaluated for their effects on GNMT promoter activity. Results indicated certain newly synthesized compounds are more active than compound 1. A comprehensive Structure-activity relationships (SAR) study will be presented. Citation Format: Cherng-Chyi Tzeng, Chih-Hua Tseng, Yeh-Long Chen. Discovery of 2-acetylpyridine-[N-(3-hydroxy-2-naphthoyl)]hydrazone analogs as glycine N-methyltransferase (GNMT) inducers for the treatment of hepatocellular carcinoma (HCC). [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B28.
Actividad insecticida de aceite de trementina modificado en Culex quinquefasciatus y Aedes albopictus (Diptera:Culicidae) (2015)

Introduccion: el estudio de alternativas naturales para el control vectorial es de gran importancia debido a los fenomenos de resistencia a insecticidas sinteticos encontrados en diversas especies de mosquitos. Objetivo: evaluar la actividad insecticida de aceite de trementina modificado en Culex quinquefasciatus y Aedes albopictus. Metodos: se evaluo la actividad larvicida, adulticida e inhibidora del desarrollo de este aceite, segun metodologias estandarizadas. Se utilizo para el estudio una cepade Cx. quinquefasciatus (Regla 2013) y una de Ae. albopictus (Fraga 2012). Resultados: el aceite de trementina modificado mostro actividad larvicida para Cx. quinquefasciatus y Ae. albopictus lo que se evidencio por los valores bajos de concentraciones letales que causaron el 90 % de mortalidad (CL 90 = 0,0054 % y CL 90 = 0,00115 %), en orden. Al evaluar la actividad adulticida se obtuvo el 100 % de derribo a los 30 minutosde los individuos expuestos de ambas cepas a la concentracion de 60 mg/mL. Al exponer larvas a sus respectivas CL 90 del aceite de trementina modificado, se observo en Cx. quinquefasciatus una mortalidad 2 veces mayor en la fase de larva que en la fase de pupa. Durante los primeros 5 dias la mortalidad fue mayor en los estadios pupa y adulto en Ae. Albopictus .Sin embargo, los resultados difieren con Cx. quinquefasciatus en el mismo periodo. El sexo femenino fue prevaleciente en la mortalidad pupal. La mayor mortalidad en adultos se observo en machos, por lo que ocurrio una desproporcion en los sexos de los sobrevivientes. Conclusiones: los resultados encontrados avalan y permiten recomendar el aceite de trementina modificado como un insecticida de origen natural para el control de Ae. albopictus y Cx. quinquefasciatus .
Optimization and reconstruction over graphs (2007)

We study several instances of the following combinatorial optimization problem: Efficiently find a graph that satisfies, to the extent possible, a given set of constraints. 
The thesis begins with two NP-hard problems: The Minimum-Degree Minimum Spanning Tree (MBDST) problem is to find, given a graph, an MST of minimum degree. The Minimum Bounded-Degree Spanning Tree (MBDST) problem is to find, given a graph and an integer B, a minimum-cost tree in the set of spanning trees of degree at most B. 
We present the first polynomial-time constant-factor approximation algorithm for the MDMST problem, which uses the push-relabel framework developed by Goldberg [20] for the max-flow problem. It improves Fischer's local-search algorithm [14]. Via an analysis by Konemann and Ravi [34], our algorithm implies the first polynomial-time constant-factor bi-criteria approximation algorithm for the MBDST problem. It also works for a new generalization of the MDMST problem. 
Other results include the first true MBDST approximation algorithms: a polynomial-time algorithm incurring no error in cost, and a quasi-polynomial-time algorithm, based on augmenting paths, that significantly improves the error in degree by finding a spanning tree of optimal cost and degree B+ Olognloglog n . Our cost-bounding method requires finding MSTs that meet both upper and lower degree bounds. 
The second part of the thesis considers the problem of reconstructing a directed graph, given the vertices and an oracle for the reachability relation. We show this reduces to the problem of sorting a partially ordered set (poset). 
Sorting algorithms obtain information about a poset by queries that compare two elements. We give an algorithm that sorts a width-w poset of size n and has query complexity O( wn + n log n), meeting the information-theoretic lower bound. We describe a variant of Mergesort that has query complexity O(wnlogn), matching the upper bound shown by Faigle and Turan [13], and total complexity O(w 2n log n). The exact total complexity of sorting remains unresolved. 
We also give upper and lower bounds for several related problems, including biding the minimal elements in a poset, which we show has query and total complexity Θ(wn), and its generalization, k-selection.
BioClips of symmetric and asymmetric cell division (2007)

Animations have long been used as tools to illustrate complex processes in such diverse fields as mechanical engineering, astronomy, bacteriology and physics. Animations in biology hold particular educational promise for depicting complex dynamic processes, such as photosynthesis, motility, viral replication and cellular respiration, which cannot be easily explained using static two-dimensional images. However, these animations have often been restrictive in scope, having been created for a specific classroom or research audience. In recent years, a new type of animation has emerged called the BioClip (http://www.bioclips.com) that strives to present science in an interactive multimedia format, which is, at once, informative and entertaining, by combining animations, text descriptions and music in one portable cross-platform document. In the present article, we illustrate the educational value of this new electronic resource by reviewing in depth two BioClips our group has created which describe the processes of symmetric and asymmetric cell division (http://www.wormclassroom.org/cb/bioclip).
Gene expression based inference of drug resistance in cancer (2021)

Abstract Inter and intra-tumoral heterogeneity are major stumbling blocks in the treatment of cancer and are responsible for imparting differential drug responses in cancer patients. Recently, the availability of large-scale drug screening datasets has provided an opportunity for predicting appropriate patient-tailored therapies by employing machine learning approaches. In this study, we report a predictive modeling approach to infer treatment response in cancers using gene expression data. In particular, we demonstrate the benefits of considering integrated chemogenomics approach, utilizing the molecular drug descriptors and pathway activity information as opposed to gene expression levels. We performed extensive validation of our approach on tissue-derived single-cell and bulk expression data. Further, we constructed several prostate cancer cell lines and xenografts, exposed to differential treatment conditions to assess the predictability of the outcomes. Our approach was further assessed on pan-cancer RNA-sequencing data from The Cancer Genome Atlas (TCGA) archives, as well as an independent clinical trial study describing the treatment journey of three melanoma patients. To summarise, we benchmarked the proposed approach on cancer RNA-seq data, obtained from cell lines, xenografts, as well as humans. We concluded that pathway-activity patterns in cancer cells are reasonably indicative of drug resistance, and therefore can be leveraged in personalized treatment recommendations.
Dibenzo-15-crown-5 ether and its sodium thiocyanate complex. X-ray crystallographic and NMR studies in the solid phase and in solution (1991)

For the title systems, single crystal X-ray data indicate the presence of totally asymmetric structures. These features are reflected in the multiplicity of resonances in the solid phase 13 C NMR spectra. Some of the 13 C chemical shift trends are analyzed in terms of torsional angle influences. In solution, resonance assignments have been made with the aid of 2D methods. Stereochemical inferences are drawn from NOESY spectra and 1 H– 1 H couplings. Low temperature solution experiments indicate that conformational interconversions in both the free ligand and the NaNCS complex are rapid on the NMR timescale down to 163 K. Key words: crown ethers, NMR, stereochemistry.
User experience evaluation (2009)

High quality user experience (UX) has become a central competitive factor of product development in mature consumer markets. Although the term UX is widely used, the methods and tools for evaluating UX are still inadequate. This SIG session collects information and experiences about UX evaluation methods used in both academia and industry, discusses the pros and cons of each method, and ideates on how to improve the methods.
Industrial Application of Adenosine 5′-Triphosphate Regeneration to Synthesis of Sugar Phosphates (1991)

Enzyme-catalyzed reactions are attracting attention in the field of chemical synthesis, especially for the production of fine chemicals such as pharmaceuticals and agricultural chemicals. Although many studies concerning bioreactor systems employing enzymes as catalysts have been intensively investigated, most of the investigations are still at the stage of fundamental research. Consequently, there is an increasing demand for demonstrations that bioreactors can be employed for the production of fine chemicals on an industrial scale. For this purpose, we have developed purification methods for many types of thermostable enzymes and have used them to produce valuable sugar phosphates on a kilogram scale. We also have demonstrated the preparation of peptides and a fascinating nucleotide, diadenosine tetraphosphate, using aminoacyl tRNA synthetase and an ATP regeneration system.
Novel bioreductive mitosene and mitosane analogues of mitomycin C. (1987)

Mitosenes of both the pyrrolo- and pyrido[1,2-a]indole type have been prepared via a modified Madelung reaction of benzeneacetonitriles ortho-substituted with gamma- and delta-lactam moieties, respectively, followed by modification of the resulting heterotricyclic compounds. Some in vitro anti-tumour activity data of these novel compounds are rearrangement of 2-(1-pyrrolidinyl)-3-vinylquinone derivatives to 5,8-dioxo-1H-pyrrolo[1,2-a]indoles.
Characterization of physical and biochemical changes in plasma treated spinach seed during germination (2018)

Despite the accumulating data on the effect of plasma on seed germination, mechanisms of plasma action need more extensive research. In a previous study, we observed that high voltage nanosecond pulsed plasma enhanced the germination of spinach seeds and subsequent seedling growth. As a follow-up study, we investigated the physico-chemical, biochemical, and molecular changes in seed after plasma treatment, focusing on the early germination stage, to elucidate mechanism(s) for the stimulating effects of plasma on seed germination. The primary radicle protruded from seeds exposed to high voltage nanosecond pulsed plasma (one shot) slightly faster than the control seeds. The hydrophilicity of the seed surface significantly increased after treatment with high voltage nanosecond pulsed plasma (one shot). However, a very subtle increase in water uptake by plasma treated seeds was observed. Raman and FTIR spectroscopy analyses on chloroform extract of seed coats demonstrated no significant chemical etching on the surface of plasma treated seeds. This may be related to no dramatic increase in water absorption by seeds. The level of GA hormone and starch hydrolysis inside the plasma treated seeds was significantly elevated within 24 h. Taken together, our results suggest that high voltage nanosecond pulsed plasma may not only enhance hydrophilicity of the seed surface but also stimulate biochemical and molecular processes inside seed, leading to enhanced embryonic development.
Molecular dynamics simulations and functional characterization of the interactions of the PAR2 ectodomain with factor VIIa (2009)

Signaling of the tissue factor-FVIIa complex regulates angiogenesis, tumor growth, and inflammation. TF-FVIIa triggers cell signaling events by cleavage of protease activated receptor (PAR2) at the Arg36-Ser37 scissile bond. The recognition of PAR2 by the FVIIa protease domain is poorly understood. We perform molecular modeling and dynamics simulations to derive the PAR2-FVIIa interactions. Docking of the PAR2 Arg36-Ser37 scissile bond to the S1 site and subsequent molecular dynamics leads to interactions of the PAR2 ectodomain with P and P' sites of the FVIIa catalytic cleft as well as to electrostatic interactions between a stably folded region of PAR2 and a cluster of basic residues remote from the catalytic cleft of FVIIa. To address the functional significance of this interaction for PAR2 cleavage, we employed two antibodies with epitopes previously mapped to this cluster of basic residues. Although these antibodies do not block the catalytic cleft, both antibodies completely abrogated PAR2 activation by TF-FVIIa. Our simulations indicate a conformation of the PAR2 ectodomain that limits the cleavage site to no more than 33 A from its membrane proximal residue. Since the active site of FVIIa in the TF-FVIIa complex is approximately 75 A above the membrane, cleavage of the folded conformation of PAR2 would require tilting of the TF-FVIIa complex toward the membrane, indicating that additional cellular factors may be required to properly align the scissile bond of PAR2 with TF-FVIIa.
Development and Evaluation of a Novel Method for Lignocellulosic Ethanol Production : Simultaneous Saccharification Filtration and Fermentation (SSFF) (2014)

A novel method of lignocellulosic ethanol production was developed and evaluated, “Simultaneous Saccharification Filtration and Fermentation (SSFF)”. SSFF is an integrated process which combines the advantages of both Separate hydrolysis and fermentation (SHF) and Simultaneous saccharification and fermentation (SSF). The process involves simultaneous enzymatic hydrolysis of lignocellulosic biomass, filtration and fermentation of the filtrate with yeast Saccharomyces cerevisiae as fermenting organism. Different suspended solid (SS) were evaluated to determine what solid concentration can be pumped through the filtration device and the life span of a cross-flow filter module was assessed. Capacity tests were performed on the fermentation unit to determine the uptake capability of the fermenting organism. It was furthermore investigated how long the cells can be successfully reused. It was observed that up to 14% solids concentration could be pumped through the filtration unit. After enzymatic treatment, a slurry with 14.4% initial SS was filtered continuously for 28 days without clogging or fouling. A flocculating yeast strain (CCUG 53310) was able to consume the glucose from the hydrolysis through the filtration effectively and the yeast culture was reused for 5 batches of SSFF. The SSFF cultivations resulted in an ethanol yield of up to 85.0% of the theoretical yield. Our new process of SSFF could potentially be used in lignocellulosic ethanol production.
Synthesis of PEVE-<i>b</i>-P(CTFE-<i>alt</i>-EVE) block copolymers by sequential cationic and radical RAFT polymerization (2017)

Block copolymers containing chlorotrifluoroethylene (CTFE) are relatively rare.
Effects of exciton-exciton correlation on parametric scattering of cavity polaritons (2002)

Summary form only given.In a normal-mode coupling semiconductor microcavity (NMC-SMC), the cavity polariton frequencies are well separated from the exciton resonance; therefore, the populations of the excitonic states are suppressed. This reduces the contribution of the incoherent processes to the nonlinear optical response and implies that the coherent processes play a major rot in NMC-SMC four-wave mixing.