gebhart/patrepeval huggingface dataset:
Nucleotide sequence analysis of human abl and bcr-abl cDNAs. (1989)

The complete nucleotide sequence of human abl RNA containing exon Ia was determined. It spans 5598 nucleotides and codes for a protein of 1130 amino acids. The 3' untranslated region contains two short open reading frames and multiple ATTT(A) motifs characteristic of short lived mRNAs. Computer analysis of the abl protein predicts four domains distinct with regard to surface probability and chain flexibility. Nucleotide analysis of the abl segment within a bcr-abl cDNA cloned from the K562 cell line indicated no further alterations within the coding region. A bcr-abl construct containing this segment transformed, together with c-myc, RAT-1 cells and produced a highly active tyrosine kinase.
Ionic Liquids in Synthesis (2002)

Preface A Note From The Editors THE EARLY YEARS OF IONIC LIQUIDS SYNTHESIS AND PURIFICATION Synthesis Quality Aspects and other Questions Related to Commercial Ionic Liquid Production Synthesis of Task-specific Ionic Liquids PHYSICO-CHEMICAL PROPERTIES Melting Points Viscosity and Density Solubility and Solvation in Ionic Liquids Gas Solubilities Polarity Electrochemistry STRUCTURE AND DYNAMICS Order in the Liquid State and Structure Computational Modelling of Ionic Liquids Translational Diffusion Molecular Reorientational Dynamics ORGANIC SYNTHESIS Ionic Liquids in Organic Synthesis: Effects on Rate and Selectivity Stoicheiometric Organic Reactions and Acid-catalysed Reactions in Ionic Liquids Transition Metal Catalysis in Ionic Liquids Ionic Liquids in Multiphasic Reactions Task Specific Ionic Liquids (TSILs): A New Generation of Soluble Supports for Supported Organic Synthesis (SPOS) Supported Ionic Liquid Phase Catalysts Multiphasic Catalysis Using Ionic Liquids in Combination with Compressed CO2 INORGANIC SYNTHESIS Directed Inorganic and Organometallic Synthesis Making of Inorganic Materials by Electrochemical Methods Ionic Liquids in Material Synthesis: Functional Nanoparticles and Other Inorganic Nanostructures POLYMER SYNTHESIS IN IONIC LIQUIDS BIOCATALYTIC REACTIONS IN IONIC LIQUIDS INDUSTRIAL APPLICATIONS OF IONIC LIQUIDS CONLUDING REMARKS AND OUTLOOK
Combined antiangiogenic and anti–PD-L1 therapy stimulates tumor immunity through HEV formation (2017)

Inhibitors of VEGF (vascular endothelial growth factor)/VEGFR2 (vascular endothelial growth factor receptor 2) are commonly used in the clinic, but their beneficial effects are only observed in a subset of patients and limited by induction of diverse relapse mechanisms. We describe the up-regulation of an adaptive immunosuppressive pathway during antiangiogenic therapy, by which PD-L1 (programmed cell death ligand 1), the ligand of the negative immune checkpoint regulator PD-1 (programmed cell death protein 1), is enhanced by interferon-γ-expressing T cells in distinct intratumoral cell types in refractory pancreatic, breast, and brain tumor mouse models. Successful treatment with a combination of anti-VEGFR2 and anti-PD-L1 antibodies induced high endothelial venules (HEVs) in PyMT (polyoma middle T oncoprotein) breast cancer and RT2-PNET (Rip1-Tag2 pancreatic neuroendocrine tumors), but not in glioblastoma (GBM). These HEVs promoted lymphocyte infiltration and activity through activation of lymphotoxin β receptor (LTβR) signaling. Further activation of LTβR signaling in tumor vessels using an agonistic antibody enhanced HEV formation, immunity, and subsequent apoptosis and necrosis in pancreatic and mammary tumors. Finally, LTβR agonists induced HEVs in recalcitrant GBM, enhanced cytotoxic T cell (CTL) activity, and thereby sensitized tumors to antiangiogenic/anti-PD-L1 therapy. Together, our preclinical studies provide evidence that anti-PD-L1 therapy can sensitize tumors to antiangiogenic therapy and prolong its efficacy, and conversely, antiangiogenic therapy can improve anti-PD-L1 treatment specifically when it generates intratumoral HEVs that facilitate enhanced CTL infiltration, activity, and tumor cell destruction.
Titration Curves and Dissociation Constants of l-Ascorbic Acid (Vitamin C) and Diethyl Dihydroxymaleate (1935)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTitration Curves and Dissociation Constants of l-Ascorbic Acid (Vitamin C) and Diethyl DihydroxymaleateW. D. Kumler and T. C. DanielsCite this: J. Am. Chem. Soc. 1935, 57, 10, 1929–1930Publication Date (Print):October 1, 1935Publication History Published online1 May 2002Published inissue 1 October 1935https://pubs.acs.org/doi/10.1021/ja01313a053https://doi.org/10.1021/ja01313a053research-articleACS PublicationsRequest reuse permissionsArticle Views738Altmetric-Citations30LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Alterations in Mental Function and Paroxysmal Cerebral Activity (1957)

We have previously reported a study in which we found that certain kinds of "nonanswer" responses (NR's) to intelligence test items occurred to a significantly greater extent among a group of epileptics than among a group having organic brain impairment but without known seizures, and a psychiatric group, respectively.<sup>2</sup>Patients with paroxysmal electroencephalographic abnormality, regardless of diagnosis, also were found to demonstrate NR's significantly more frequently than those without such abnormality. NR's might be categorized as temporary losses of goal idea, or what would appear to be transient inattention, preoccupation, or internal distraction. The temporary loss of goal idea was indicated by a direct admission of confusion, request for repetition of the test instructions, a comment or criticism about the test item, a response to part of the question, or verbalization of merely a simple association. As a result of these findings, our belief was that NR's occur concomitantly
Inverse association of anti‐inflammatory treatments and Alzheimer's disease (1994)

We conducted a co-twin control study among 50 elderly twin pairs with onsets of Alzheimer's disease (AD) separated by 3 or more years. Twenty-three male pairs (46%) were screened from the (U.S.) National Academy of Sciences-National Research Council Registry (NAS-NRC Registry) of World War II veteran twins; others (mostly women) had responded to advertisements or were referred from AD clinics. Twenty-six pairs (52%) were monozygous. The onset of AD was inversely associated with prior use of corticosteroids or ACTH (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.06 to 0.95; p = 0.04). Similar but weaker trends were present among pairs discordant for history of arthritis or for prior daily use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin. The association was strongest when we combined use of steroids/ACTH or NSAIDs post hoc into a single variable of anti-inflammatory drugs (AIs) (OR, 0.24; CI, 0.07 to 0.74; p = 0.01). The inverse relation was strong in female (volunteer) twin pairs but was not present in the younger men from the NAS-NRC Registry. AIs had typically been taken for arthritis or related conditions, but a similar result was apparent after controlling statistically for the arthritis variable (OR, 0.08; CI, 0.01 to 0.69; p = 0.02). AIs have been proposed as a means of retarding the progression of AD symptoms, and these data suggest that AIs may also prevent or delay the initial onset of AD symptoms. Because of limitations in the case-control method, our results require corroboration with hypothesis-driven research designed to control bias and confounding.
CD163 and Inflammation: Biological, Diagnostic, and Therapeutic Aspects (2012)

The diagnostic and therapeutic properties of CD163 await further clinical studies and regulatory approval before implementation in the clinic.
Phospholipid hydroperoxide cysteine peroxidase activity of human serum albumin (1999)

Human serum albumin (HSA) reduced the phospholipid hydroperoxide, 1-palmitoyl-2-(13-hydroperoxy-cis-9,trans-11-octadecadienoyl)-l-3-phosphatidylcholine (PLPC-OOH) to the corresponding hydroxy-derivative with a high apparent affinity (Km = 9.23±0.95 µM). Removal of bound lipid during purification increased this activity. At physiological concentration, HSA reduced the phospholipid hydroperoxide in the absence of a cofactor. However, in the presence of a cofactor (reductant), the rate of the reaction was increased. All of the major aminothiols in plasma could act as reductants, the best being the most abundant, cysteine (Km = 600±80 µM). For every nanomole of PLPC-OOH reduced by HSA, 1.26 nmol of cystine was formed, indicating a reaction stoichiometry of 1 mol PLPC-OOH to 2 mol cysteine. We used chemical modification to determine which amino acid residues on HSA were responsible for the activity. Oxidation of thiol group(s) by N-ethylmaleimide led to a reduction in the rate of activity, whereas reduction of thiols by either dithiothreitol or the angiotensin-converting enzyme inhibitor, captopril, increased the activity. Both N-ethylmaleimide-modified HSA and dithiothreitol-treated HSA exhibited increased apparent affinities for PLPC-OOH. For a range of preparations of albumin with different modifications, the activity on PLPC-OOH was dependent on the amount of free thiol groups on the albumin (correlation coefficient = 0.91). Patients with lowered albumin concentrations after septic shock showed lowered total plasma thiol concentrations and decreased phospholipid hydroperoxide cysteine peroxidase (PHCPx) activities. These results therefore show for the first time that HSA exhibits PHCPx activity, and that the majority of the activity depends on the presence of reduced thiol group(s) on the albumin.
A phase Ib study of gemcitabine plus PEGPH20 (pegylated recombinant human hyaluronidase) in patients with stage IV previously untreated pancreatic cancer. (2013)

4010 Background: PEGPH20 is a PEGylated version of human recombinant hyaluronidase. In preclinical studies, PEGPH20 depleted pancreatic cancers of their high hyaluronan (HA) content. In a genetically-engineered murine model of PDA, PEGPH20 + gemcitabine (Gem) significantly prolonged survival compared to Gem alone. In Ph1 PEGPH20 monotherapy studies, the MTD was 3.0 μg/kg. The most common AEs were musculoskeletal events (MSEs). Methods: This was a dose-escalation study to find the recommended Phase 2 dose (RP2D) of PEGPH20 in combination with Gem in patients (pts) with Stage IV previously untreated pancreatic cancer. Pts received PEGPH20 at 1, 1.6, or 3 μg/kg IV twice a week for Wks 1-4, weekly for Wks 5-7, then 1 wk rest. Dose escalation was based on safety. Gem was given at 1000 mg/m 2 IV once a week for Wks 1-7, then 1 wk rest. Thereafter, PEGPH20 + Gem were given once a week for 3 wks in 4-wk cycles. Dexamethasone was given pre and post PEGPH20 doses. Results: Of the 28 pts enrolled, the majority had a Karnofsky performance status of 80%, and 85%/19%/26% of pts had liver/lung/visceral metastases. The median age was 58 yrs. Four pts received PEGPH20 at 1 μg/kg, 4 at 1.6 μg/kg, and 20 at 3 μg/kg. The RP2D was 3 μg/kg. Treatment duration ranged from 1-274 days; 5 pts remain on study. Treatment was generally well tolerated. Ten pts had 1 Gem dose reduction, 2 pts had 1 PEGPH20 dose reduction (3 to 1.6 µg/kg), but no pt had a DLT. The most common PEGPH20-related AEs were MSEs (25% Gr1; 18% Gr2) and fatigue (21% Gr1; 11% Gr2). Objective response was assessed by an independent central radiologist using RECIST 1.1. Of the 21 pts evaluable for efficacy, 7 had partial response (PR) for an overall response rate (ORR) of 33%, and 9 had stable disease for ≥ 2 mo. Tumor biopsies from 12 pts were evaluable for HA staining. HA was high in 9 and low in 3. Of the 9 with high HA staining, 5 had PR (56% ORR); HA data were not available for the other 2 PR pts. PK results show dose-dependent exposure consistent with data from PEGPH20 monotherapy studies. Conclusions: PEGPH20 in combination with Gem is generally well tolerated in advanced pancreatic cancer and shows promising efficacy, especially in pts with high intratumoral HA content. Clinical trial information: NCT01453153.
Outcome Model of Asphyxial Cardiac Arrest in Rats (1995)

An outcome model with asphyxial cardiac arrest in rats has been developed for quantifying brain damage. Twenty-two rats were randomized into three groups. Control group I was normal, was conscious, and had no asphyxia (n = 6). Sham group II had anesthesia and surgery but no asphyxia (n = 6). All 12 rats in groups I and II survived to 72 h and were functionally and histologically normal. Arrest group III (the model; n = 10) had light anesthesia and apneic asphyxia of 8 min, which led to cessation of circulation at 3-4 min of apnea, resulting in cardiac arrest (no flow) of 4-5 min. All 10 rats had spontaneous circulation restored by standard external cardiopulmonary resuscitation. Nine rats survived controlled ventilation for 1 h and observation to 72 h, while one rat died before extubation. All nine survivors were conscious at 72 h, with neurologic deficit scores (0% = best; 100% = worst) of 7 +/- 6% (2-16%). All brain regions at five coronal levels were examined for ischemic neurons. The prevalence of ischemic neurons in five regions was categorically scored. The average total brain histopathologic damage score in group III (n = 9) was 2.1 (p < 0.05 vs. group I or II). A reproducible outcome model of cardiac arrest in rats was documented. It provides a tool for investigating pathophysiological mechanisms of neuronal death caused by a transient global hypoxic-ischemic brain insult.
Probabilistic models of text and images (2004)

Managing large and growing collections of information is a central goal of modern computer science. Data repositories of texts, images, sounds, and genetic information have become widely accessible, thus necessitating good methods of retrieval, organization, and exploration. In this thesis, we describe a suite of probabilistic models of information collections for which the above problems can be cast as statistical queries. 
We use directed graphical models as a flexible, modular framework for describing appropriate modeling assumptions about the data. Fast approximate posterior inference algorithms based on variational methods free us from having to specify tractable models, and further allow us to take the Bayesian perspective, even in the face of large datasets. 
With this framework in hand, we describe latent Dirichlet allocation (LDA), a graphical model particularly suited to analyzing text collections. LDA posits a finite index of hidden topics which describe the underlying documents. New documents are situated into the collection via approximate posterior inference of their associated index terms. Extensions to LDA can index a set of images, or multimedia collections of interrelated text and images. 
Finally, we describe nonparametric Bayesian methods for relaxing the assumption of a fixed number of topics, and develop models based on the natural assumption that the size of the index can grow with the collection. This idea is extended to trees, and to models which represent the hidden structure and content of a topic hierarchy that underlies a collection.
Substitutions in the β subunits of sickle-cell hemoglobin improve oxidative stability and increase the delay time of sickle-cell fiber formation (2019)

After reacting with hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), sickle-cell hemoglobin (HbS, βE6V) remains longer in a highly oxidizing ferryl form (HbFe<sup>4+</sup>=O) and induces irreversible oxidation of "hot-spot" amino acids, including βCys-93. To control the damaging ferryl heme, here we constructed three HbS variants. The first contained a redox-active Tyr in β subunits (F41Y), a substitution present in Hb Mequon; the second contained the Asp (K82D) found in the β cleft of Hb Providence; and the third had both of these β substitutions. Both the single Tyr-41 and Asp-82 constructs lowered the oxygen affinity of HbS but had little or no effects on autoxidation or heme loss kinetics. In the presence of H<sub>2</sub>O<sub>2</sub>, both rHbS βF41Y and βF41Y/K82D enhanced ferryl Hb reduction by providing a pathway for electrons to reduce the heme via the Tyr-41 side chain. MS analysis of βCys-93 revealed moderate inhibition of thiol oxidation in the HbS single F41Y variant and dramatic 3- to 8-fold inhibition of cysteic acid formation in rHbS βK82D and βF41Y/K82D, respectively. Under hypoxia, βK82D and βF41Y/K82D HbS substitutions increased the delay time by ∼250 and 600 s before the onset of polymerization compared with the rHbS control and rHbS βF41Y, respectively. Moreover, at 60 °C, rHbS βK82D exhibited superior structural stability. Asp-82 also enhanced the function of Tyr as a redox-active amino acid in the rHbS βF41Y/K82D variant. We conclude that the βK82D and βF41Y substitutions add significant resistance to oxidative stress and anti-sickling properties to HbS and therefore could be potential genome-editing targets.
Discrimination of three types of homopolymers in single-stranded DNA with solid-state nanopores through external control of the DNA motion (2017)

Abstract To achieve DNA sequencing with solid-state nanopores, the speed of the DNA in the nanopore must be controlled to obtain sequence-specific signals. In this study, we fabricated a nanopore-sensing system equipped with a DNA motion controller. DNA strands were immobilized on a Si probe, and approach of this probe to the nanopore vicinity could be controlled using a piezo actuator and stepper motor. The area of the Si probe was larger than the area of the membrane, which meant that the immobilized DNA could enter the nanopore without the need for the probe to scan to determine the location of the nanopore in the membrane. We demonstrated that a single-stranded DNA could be inserted into and removed from a nanopore in our experimental system. The number of different ionic-current levels observed while DNA remained in the nanopore corresponded to the number of different types of homopolymers in the DNA.
Micrometastases and Survival in Stage II Colorectal Cancer (1998)

Molecular detection of micrometastases is a prognostic tool in stage II colorectal cancer.
Dynamics of translation on the ribosome: molecular mechanics of translocation (1999)

The translocation step of protein elongation entails a large-scale rearrangement of the tRNA-mRNA-ribosome complex. Recent years have seen major advances in unraveling the mechanism of the process on the molecular level. A number of intermediate states have been defined and, in part, characterized structurally. The article reviews the recent evidence that suggests a dynamic role of the ribosome and its ligands during translocation. The focus is on dynamic aspects of tRNA movement and on the role of elongation factor G and GTP hydrolysis in translocation catalysis. The significance of structural changes of the ribosome induced by elongation factor G as well the role of ribosomal RNA are addressed. A functional model of elongation factor G as a motor protein driven by GTP hydrolysis is discussed.
Ubiquitous Widgets: Designing Interactions Architecture for Adaptive Mobile Applications (2013)

Modern mobile devices spreading introduce a new way of using and designing software applications. These pervasive systems are now part of our lives. More and more connected objects provide us more and more software capabilities. In this environment we have to rethink the way we traditionally consider our interactions with this software. These interactions are now potentially spread over multiple devices with different interacting modalities. We propose, in this paper, a software container component based architecture to design such interactions and a software platform to manage their dynamic life-cycle.
Analysis of Odorants Produced from Indoor Drying Laundries and Effects of Enzyme for Preventing Malodor Generation (2005)

Abstract Recently more consumers hang and dry their laundries indoor for various reasons. Under these slow drying conditions malodor was sometimes generated. Gas chromatography analysis showed the odorants were composed of medium-chain alcohols, medium-chain aldehydes, ketones, fatty acids, N-compounds and S-compounds. Especially, medium-chain fatty acids were confirmed to make up a characteristic and striking sweaty and sour odor. The malodor is supposed to be formed from sebum and soils by oxidative degradation as well as by metabolism of microorganisms. This study shows that a laundry detergent with an enzyme possessing high protease as well as bacteriolytic activity can prevent washed clothes from malodor generation during such a prolonged drying.
Major Advances Associated with Reproduction in Dairy Cattle (2006)

The purpose of this overview is to review some of the major advances in reproductive technologies, and how they may be applied to meet the challenge of enhancing reproductive efficiency in the high-producing dairy cow of the 21st century. The current population of high-producing dairy cows is considered to be subfertile, as characterized by low pregnancy rates and high rates of embryonic mortality. Coordinated systems of reproductive management have been developed based upon a thorough understanding of the endocrine, cellular, and molecular factors controlling ovarian and uterine function. These systems will partially restore herd reproductive performance. Advances in other reproductive technologies offer possibilities for wider use of superior germplasm. Technologies such as sexed semen, cloning, transgenesis, and preimplantation genetic diagnosis offer the potential to enhance the influence of superior animals on production of food for human consumption. However, at this time, additional research is needed to counteract the higher rates of embryonic and fetal mortality associated with some of these technologies. Furthermore, use of genomics, proteomics, and bioinformatics in the study of reproduction will undoubtedly provide investigators with a greater understanding of the limitations to efficient reproductive processes in the subfertile lactating dairy cow.