gebhart/patrepeval huggingface dataset:
Absolute and Relative Organ Weight Trends in B6C3F1 Mice (2012)

Since the early 1970s, the National Cancer Institute (NCI) and National Toxicology Program (NTP) have conducted carcinogenesis and toxicology studies on several hundred chemicals using the B6C3F1 mouse. A number of publications have examined growth, survival, and tumor incidence over time, including the impact of changes in housing and diet. However, no reports have been published to date examining the variation in organ weights over time, especially in light of reported body weight effects associated with housing and diet changes. Therefore, all available absolute and relative organ weight data for untreated control B6C3F1 mice were collected from 2-wk, 3-mo, and 15-mo NCI/NTP investigations with report dates through August 2010 in order to examine organ weight changes over time and by study type. Study data were grouped into 5-yr intervals by initiation date. Body weights in males increased over time except in 2-wk studies, while body weights in females rose through 1993 and remained constant or declined thereafter. Higher body weights were noted in individually housed mice, and in drinking water studies compared to feed or inhalation studies. Elevated organ weights were typically associated with increased body weights except that lower organ weights were evident as early as 2-wk on study with the introduction of the NTP-2000 diet in 1994. Relative organ weights decreased over time in males and females. Finally, organ weight coefficients of variation (standard deviation/mean) declined over time in 2-wk, 3-mo, and 15-mo studies, which may reflect improved data collection methods or reduced interlaboratory variability.
Detection of altered membrane phospholipid asymmetry in subpopulations of human red blood cells using fluorescently labeled annexin V (1996)

The phospholipids of the human red cell are distributed asymmetrically in the bilayer of the red cell membrane. In certain pathologic states, such as sickle cell anemia, phospholipid asymmetry is altered. Although several methods can be used to measure phospholipid organization, small organizational changes have been very difficult to assess. Moreover, these methods fail to identify subpopulations of cells that have lost their normal phospholipid asymmetry. Using fluorescently labeled annexin V in flow cytometry and fluorescent microscopy, we were able to identify and quantify red cells that had lost their phospholipid asymmetry in populations as small as 1 million cells. Moreover, loss of phospholipid organization in subpopulations as small as 0.1% of the total population could be identified, and individual cells could be studied by fluorescent microscopy. An excellent correlation was found between fluorescence-activated cell sorter (FACS) analysis results using annexin V to detect red cells with phosphatidylserine (PS) on their surface and a PS-requiring prothrombinase assay using similar red cells. Cells that bound fluorescein isothiocyanate (FITC)-labeled annexin V could be isolated from the population using magnetic beads covered with an anti-FITC antibody. Evaluation of blood samples from patients with sickle cell anemia under oxygenated conditions demonstrated the presence of subpopulations of cells that had lost phospholipid asymmetry. While only a few red cells were labeled in normal control samples (0.21% +/- 0.12%, n = 8), significantly increased (P < .001) annexin V labeling was observed in samples from patients with sickle cell anemia (2.18% +/- 1.21%, n = 13). We conclude that loss of phospholipid asymmetry may occur in small subpopulations of red cells and that fluorescently labeled annexin V can be used to quantify and isolate these cells.
Chromosome engineering in Saccharomyces cerevisiae by using a site-specific recombination system of a yeast plasmid (1990)

We have developed an effective method to delete or invert a chromosomal segment and to create reciprocal recombination between two nonhomologous chromosomes in Saccharomyces cerevisiae, using the site-specific recombination system of pSR1, a circular cryptic DNA plasmid resembling 2 microns DNA of S. cerevisiae but originating from another yeast, Zygosaccharomyces rouxii. A 2.1-kilobase-pair DNA fragment bearing the specific recombination site on the inverted repeats of pSR1 was inserted at target sites on a single or two different chromosomes of S. cerevisiae by using integrative vectors. The cells were then transformed with a plasmid bearing the R gene of pSR1, which encodes the site-specific recombination enzyme and is placed downstream of the GAL1 promoter. When the transformants were cultivated in galactose medium, the recombination enzyme produced by expression of the R gene created the modified chromosome(s) by recombination between two specific recombination sites inserted on the chromosome(s).
Conceptual design of a high field ultra-compact cyclotron for nuclear physics research (2002)

We have studied the feasibility of using an existing wide-bore 8 T magnet as a component of an ultra-high-field cyclotron. Such a machine would use the highest magnetic field of any cyclotron to date, viz. 7.6 T averaged azimuthally with 8.5 T in the hills. The K95 'Eight Tesla Cyclotron' would have roughly the same magnetic rigidity (B/spl rho/) as the Oak Ridge Isochronous Cyclotron in a package of only one fourth the radius, with a corresponding reduction in cost. Such a cyclotron could accelerate particles with a charge state Q/A=1/4 to a final energy of 5 to 6 MeV/nucleon, the energy range currently being used to study superdeformed, high angular momentum nuclei that result from glancing collisions. Studies have stressed achieving sufficient vertical focusing (v/sub z/) despite the high magnetic field level, and finding a central region geometry that fits comfortably in the limited space available while providing centering and early-turn focusing properties that are similar to those of less compact machines.
Monoclonal antibodies to ligand-occupied conformers of integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) alter receptor affinity, specificity, and function. (1991)

Occupancy of integrin receptors induces conformational changes in the receptor, resulting in exposure of novel interactive sites termed ligand-induced binding sites (LIBS). We report here that Fab fragments of certain antibodies against LIBS on integrin alpha IIb beta 3 (platelet glycoprotein IIb-IIIa) block platelet aggregation. Thus, certain LIBS or the regions surrounding them may participate in events required for platelet aggregation. In addition, certain anti-alpha IIb beta 3 LIBS Fab fragments stimulated platelet aggregation. This was due to induction of fg binding to alpha IIb beta 3, apparently by shifting a conformational equilibrium between a "resting" and an "activated" state of alpha IIb beta 3. Some of the activating anti-LIBS Fab fragments also induced high affinity fibronectin binding to alpha IIb beta 3, whereas others did not. Thus, changes in the conformation of this integrin modulate both the specificity and affinity of ligand recognition.
ChemInform Abstract: Synthesis of Some New N,N′‐Linked Biheteroaryls. (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Discovery of Aminopyridine-Based Inhibitors of Bacterial Enoyl-ACP Reductase (FabI) (2002)

Bacterial enoyl-ACP reductase (FabI) catalyzes the final step in each cycle of bacterial fatty acid biosynthesis and is an attractive target for the development of new antibacterial agents. Our efforts to identify potent, selective FabI inhibitors began with screening of the GlaxoSmithKline proprietary compound collection, which identified several small-molecule inhibitors of Staphylococcus aureus FabI. Through a combination of iterative medicinal chemistry and X-ray crystal structure based design, one of these leads was developed into the novel aminopyridine derivative 9, a low micromolar inhibitor of FabI from S. aureus (IC(50) = 2.4 microM) and Haemophilus influenzae (IC(50) = 4.2 microM). Compound 9 has good in vitro antibacterial activity against several organisms, including S. aureus (MIC = 0.5 microg/mL), and is effective in vivo in a S. aureus groin abscess infection model in rats. Through FabI overexpressor and macromolecular synthesis studies, the mode of action of 9 has been confirmed to be inhibition of fatty acid biosynthesis via inhibition of FabI. Taken together, these results support FabI as a valid antibacterial target and demonstrate the potential of small-molecule FabI inhibitors for the treatment of bacterial infections.
Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node (2008)

Lymph nodes are strategically localized at the interfaces between the blood and lymphatic vascular system, delivering immune cells and antigens to the lymph node. As cellular junctions of endothelial cells actively regulate vascular permeability and cell traffic, we have investigated their molecular composition by performing an extensive immunofluorescence study for adherens and tight junction molecules, including vascular endothelium (VE)-cadherin, the vascular claudins 1, 3, 5 and 12, occludin, members of the junctional adhesion molecule family plus endothelial cell-selective adhesion molecule (ESAM)-1, platelet endothelial cell adhesion molecule-1, ZO-1 and ZO-2. We found that junctions of high endothelial venules (HEV), which serve as entry site for naive lymphocytes, are unique due to their lack of the endothelial cell-specific claudin-5. LYVE-1(+) sinus-lining endothelial cells form a diffusion barrier for soluble molecules that arrive at the afferent lymph and use claudin-5 and ESAM-1 to establish characteristic tight junctions. Analysis of the spatial relationship between the different vascular compartments revealed that HEV extend beyond the paracortex into the medullary sinuses, where they are protected from direct contact with the lymph by sinus-lining endothelial cells. The specific molecular architecture of cellular junctions present in blood and lymphatic vessel endothelium in peripheral lymph nodes establishes distinct barriers controlling the distribution of antigens and immune cells within this tissue.
Mobile Streams (1998)

We present a toolkit for building event-driven, re-configurable distributed systems. An event-driven application is driven by asynchronous inputs that cause event-handlers to be invoked. A large class of distributed collaborative, testing, monitoring and control applications fit this paradigm - for example, conferencing and conference control applications, distributed control and testing applications and many others. In each case the notion of an event varies. In a collaborative system, events are user inputs; in a distributed monitoring and control system, events are changes in transducer inputs; in a distributed testing scenario, events are test outputs, timer alarms and so on. In such systems, it may be useful to have the ability to dynamically extend and re-configure the system. For example, in a collaborative system, different users may be interested in getting notification of different events that may not be known to the system designer a-priori - necessitating dynamic extension while the system is in execution. There are also situations where system design and performance may be enhanced by dynamic re-configuration - that is dynamic re-mapping of the system functionality while the system is in execution. Our goal is to build a system that enables the scripting of such event-driven applications.
From transition paths to transition states and rate coefficients (2003)

Transition states are defined as points in configuration space with the highest probability that trajectories passing through them are reactive (i.e., form transition paths between reactants and products). In the high-friction (diffusive) limit of Langevin dynamics, the resulting ensemble of transition states is shown to coincide with the separatrix formed by points of equal commitment (or splitting) probabilities for reaching the product and reactant regions. Transition states according to the new criterion can be identified directly from equilibrium trajectories, or indirectly by calculating probability densities in the equilibrium and transition-path ensembles using umbrella and transition-path sampling, respectively. An algorithm is proposed to calculate rate coefficients from the transition-path and equilibrium ensembles by estimating the frequency of transitions between reactants and products.
Changes in the expression of NaV1.7, NaV1.8 and NaV1.9 in a distinct population of dorsal root ganglia innervating the rat knee joint in a model of chronic inflammatory joint pain (2007)

Voltage-gated sodium channels play an essential role in regulating the excitability of nociceptive primary afferent neurones. In particular the tetrodotoxin-sensitive (TTX-S) Na(V)1.7 and the tetrodotoxin-resistant (TTX-R) Na(V)1.8 and Na(V)1.9 channels have been suggested to play a role in inflammatory pain. Previous work has revealed acute administration of inflammatory mediators, such as Freund's complete adjuvant (FCA) or carrageenan caused an upregulation in the levels of Na(V)1.7 and Na(V)1.8 protein in DRG (dorsal root ganglia) tissue up to 4 days post-insult. In the present study, the expression of Na(V)1.7, Na(V)1.8 and Na(V)1.9 was examined over a 28 day timecourse during a rat model of FCA-induced chronic inflammatory joint pain. Using the retrograde tracer Fast Blue (FB) and specific Na(V)1.7, Na(V)1.8 and Na(V)1.9 sodium channel antibodies, immunohistochemical staining techniques were used to study sodium channel expression in a distinct population of L3-L5 knee joint afferent DRGs. In the ganglia, counts were made of positively labelled cells in the FB population. The results demonstrate that, following FCA injection, Na(V)1.9 expression is upregulated at days 14, 21 and 28 post-FCA, with Na(V)1.7 and Na(V)1.8 showing increased channel expression at days 14 and 28. These observations are accompanied by a unilateral joint hypersensitivity in the FCA-injected knee indicated by a behavioural shift in weight distribution measured using an incapacitance tester. The increased presence of these channels suggests that Na(V)1.7, Na(V)1.8 and Na(V)1.9 play a role, at least in part, in the maintenance of chronic inflammatory pain several weeks after the initial insult.
ZnO Nanowire UV Photodetectors with High Internal Gain (2007)

ZnO nanowire (NW) visible-blind UV photodetectors with internal photoconductive gain as high as G approximately 108 have been fabricated and characterized. The photoconduction mechanism in these devices has been elucidated by means of time-resolved measurements spanning a wide temporal domain, from 10-9 to 102 s, revealing the coexistence of fast (tau approximately 20 ns) and slow (tau approximately 10 s) components of the carrier relaxation dynamics. The extremely high photoconductive gain is attributed to the presence of oxygen-related hole-trap states at the NW surface, which prevents charge-carrier recombination and prolongs the photocarrier lifetime, as evidenced by the sensitivity of the photocurrrent to ambient conditions. Surprisingly, this mechanism appears to be effective even at the shortest time scale investigated of t < 1 ns. Despite the slow relaxation time, the extremely high internal gain of ZnO NW photodetectors results in gain-bandwidth products (GB) higher than approximately 10 GHz. The high gain and low power consumption of NW photodetectors promise a new generation of phototransistors for applications such as sensing, imaging, and intrachip optical interconnects.
A Normalized Levenshtein Distance Metric (2007)

Although a number of normalized edit distances presented so far may offer good performance in some applications, none of them can be regarded as a genuine metric between strings because they do not satisfy the triangle inequality. Given two strings X and Y over a finite alphabet, this paper defines a new normalized edit distance between X and Y as a simple function of their lengths (|X| and |Y|) and the Generalized Levenshtein Distance (GLD) between them. The new distance can be easily computed through GLD with a complexity of O(|X|.|Y|) and it is a metric valued in [0, 1] under the condition that the weight function is a metric over the set of elementary edit operations with all costs of insertions/deletions having the same weight. Experiments using the AESA algorithm in handwritten digit recognition show that the new distance can generally provide similar results to some other normalized edit distances and may perform slightly better if the triangle inequality is violated in a particular data set.
A taxonomy of visualization techniques using the data state reference model (2002)

In previous work, researchers have attempted to construct taxonomies of information visualization techniques by examining the data domains that are compatible with these techniques. This is useful because implementers can quickly identify various techniques that can be applied to their domain of interest. However, these taxonomies do not help the implementers understand how to apply and implement these techniques. The author extends and proposes a new way to taxonomize information visualization techniques by using the Data State Model (E.H. Chi and J.T. Reidl, 1998). In fact, as the taxonomic analysis in the paper will show, many of the techniques share similar operating steps that can easily be reused. The paper shows that the Data State Model not only helps researchers understand the space of design, but also helps implementers understand how information visualization techniques can be applied more broadly.
De Novo Biosynthesis of Vanillin in Fission Yeast ( Schizosaccharomyces pombe ) and Baker's Yeast ( Saccharomyces cerevisiae ) (2009)

Vanillin is one of the world's most important flavor compounds, with a global market of 180 million dollars. Natural vanillin is derived from the cured seed pods of the vanilla orchid (Vanilla planifolia), but most of the world's vanillin is synthesized from petrochemicals or wood pulp lignins. We have established a true de novo biosynthetic pathway for vanillin production from glucose in Schizosaccharomyces pombe, also known as fission yeast or African beer yeast, as well as in baker's yeast, Saccharomyces cerevisiae. Productivities were 65 and 45 mg/liter, after introduction of three and four heterologous genes, respectively. The engineered pathways involve incorporation of 3-dehydroshikimate dehydratase from the dung mold Podospora pauciseta, an aromatic carboxylic acid reductase (ACAR) from a bacterium of the Nocardia genus, and an O-methyltransferase from Homo sapiens. In S. cerevisiae, the ACAR enzyme required activation by phosphopantetheinylation, and this was achieved by coexpression of a Corynebacterium glutamicum phosphopantetheinyl transferase. Prevention of reduction of vanillin to vanillyl alcohol was achieved by knockout of the host alcohol dehydrogenase ADH6. In S. pombe, the biosynthesis was further improved by introduction of an Arabidopsis thaliana family 1 UDP-glycosyltransferase, converting vanillin into vanillin beta-D-glucoside, which is not toxic to the yeast cells and thus may be accumulated in larger amounts. These de novo pathways represent the first examples of one-cell microbial generation of these valuable compounds from glucose. S. pombe yeast has not previously been metabolically engineered to produce any valuable, industrially scalable, white biotech commodity.
Applications and Limitations of Horizontal Drilling in Oklahoma (1991)

ABSTRACT Focusing on case histories of recent horizontal wells in Oklahoma, this paper provides an overview of horizontal drilling activity in a region where, currently, horizontal drilling applications are still being defined. Consequently, the paper provides information — including successes and failures — of the various target applications, drilling and completion techniques, reservoir characteristics and production histories of these case history wells. With particular focus on one of the first proposed multiwell horizontal drilling programs in the region, the paper provides specific comparisons of two different target intervals, as well as the actual drilling applications, drilling fluid types, survey techniques, and well designs. Results of the different drilling techniques are documented, including specific drilling assemblies used and production techniques employed. In addition, specific formations are documented according to their success as horizontal drilling applications.
Subcarrier multiplexed lightwave systems for broad-band distribution (1989)

Microwave subcarrier multiplexing (SCM) is an important approach to the design of lightwave systems for broadband distribution. Recent progress in the design and performance of both analog and digital multichannel SCM systems is reviewed. The application of broadband SCM systems to both passive and optically amplified distribution networks is discussed. The discussion covers the general features of SCM systems; the electrooptic components that have been used in the system experiments described here, including laser intensity noise and noise due to intermodulation products; the carrier-to-noise ratio requirements; some multichannel FM systems experiments; and a 20-channel digital systems experiment; and a hybrid system carrying 60 FM SCM channels plus a 100-Mb/s baseband digital channel. Several approaches to broadband subscriber distribution networks are analyzed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Redefining Affective Disorders: Relevance for Drug Development (2008)

The evaluation of new drug entities with specific modes of action may be hampered by rigid diagnostic classification systems and patient selection processes that do not focus on the anticipated symptomatic, behavioral, and functional outcomes to be achieved.Patients enrolled in central nervous system (CNS) clinical trials may present with a heterogeneous group of symptoms representing several syndromes or subtypes, subsumed under the same diagnosis in the DSM-IV classification system.As a result, enrolled patients may not have the valid illness characteristics of interest to the particular study.We propose that clinical drug development needs to focus on the primary nosological entity likely to be affected by a new drug entity's mode of action.Ideally, a valid patient will have the acute primary symptoms that the novel drug is supposed to influence.In this article, we propose operational criteria to delineate a more symptom-specific and ecologically valid approach to the identification of the valid patient for clinical trials.* There may be some disease entities (e.g., social phobia, GAD) where the symptoms have been longstanding and presented early in the course of illness, but are the targets for symptomatic change of the treatment intervention.In these instances, score state vs. trait as 2 (possibly yes).* * Exceptions: Multiple domains or contexts may not be relevant for some disease entities (e.g., specific phobias) or when targeted symptoms of interest are narrow (e.g., cognition, sleep).In these instances, score pervasive symptoms as 2 (possibly yes).