gebhart/patrepeval huggingface dataset:
Evaluation of rodent-only toxicology for early clinical trials with novel cancer therapeutics (1999)

Preclinical toxicology studies are performed prior to phase I trials with novel cancer therapeutics to identify a safe clinical starting dose and potential human toxicities. The primary aim of this study was to evaluate the ability of rodent-only toxicology studies to identify a safe phase I trial starting dose. In addition, the ability of murine studies to predict the quantitative and qualitative human toxicology of cancer therapeutics was studied. Data for 25 cancer drugs were collated for which the preclinical and clinical routes and schedules of administration were either the same (22/25), or closely matched. The maximum tolerated dose/dose lethal to 10% of mice (MTD/LD10) was identified for 24 drugs, and in patients the maximum administered dose (MAD) was associated with dose-limiting toxicity (DLT) in initial clinical trials with 20 compounds. In addition, for 13 agents, the toxicity of the drug at one-tenth the mouse MTD/LD10 was also investigated in rats, following repeated administration (20 doses). A phase I trial starting dose of one-tenth the mouse MTD/LD10 (mg m(-2)) was, or would have been, safe for all 25 compounds. With the exception of nausea and vomiting, which cannot be assessed in rodents, other common DLTs were accurately predicted by the murine studies (i.e. 7/7 haematological and 3/3 neurological DLTs). For two of the 13 drugs studied in rats, repeated administration of one-tenth the mouse MTD/LD10 was toxic, leading to a reduction in the phase I trial starting dose; however, one-tenth the mouse MTD/LD10 was subsequently tolerated in patients. For the 20 drugs where clinical DLT was reached, the median ratio of the human MAD to the mouse MTD/LD10 was 2.6 (range 0.2-16) and the median ratio of the clinical starting dose to the MAD was 35 (range 2.3-160). In contrast, in 13 subsequent phase I trials with 11 of the initial 25 drugs, the median ratio of the clinical starting dose to the MAD was 2.8 (range 1.6-56), emphasizing the value of early clinical data in rapidly defining the dose range for therapeutic studies. For all 25 drugs studied, rodent-only toxicology provided a safe and rapid means of identifying the phase I trial starting dose and predicting commonly encountered DLTs. This study has shown that the routine use of a non-rodent species in preclinical toxicology studies prior to initial clinical trials with cancer therapeutics is not necessary.
Violet laser diodes in flow cytometry: An update (2006)

While 55 mW laser sources performed adequately in the stream-in-air format, increasing the power to 100 mW did give a small but detectable increase in instrument sensitivity. This sensitivity level approached that of cuvette systems.
Treatment of E. Coli and Klebsiella Bacteremia in Agranulocytic Animals with Antiserum to a UDP-GAL Epimerase-Deficient Mutant (1973)

Abstract In order to produce antiserum with broad protection against different Gramnegative bacteria we immunized rabbits with a UDP-galactose-deficient mutant (J5) of Escherichia coli O111 that is unencumbered by O antigen since it cannot incorporate galactose into core LPS. Without O side chains, core is accessible for producing antiserum to a wide range of bacteria with similar cores. Such antiserum has previously been shown to prevent unrelated endotoxins from producing dermal and generalized Shwartzman reactions, and death. The current study reports the results of treating bacteremia with this antiserum. Bacteremia was produced in rabbits made granulocytopenic with nitrogen mustard and fed either Klebsiella pneumoniae, E. coli O17 (multiply antibiotic-resistant), or E. coli O4. Since most rabbits are coliform-free, the organisms colonized the gut and overwhelming bacteremia occurred as granulocytes disappeared. When nonimmune serum was given intravenously (i.v.) at the onset of bacteremia with any of these three organisms, only 3.1% to 5.7% survived. In contrast, survival rates in animals given antiserum to the J5 mutant were 33.3% from E. coli O4, 40% from Klebsiella, and 69.2% from the multiply antibiotic-resistant E. coli O17 (combined p &lt; 0.0005). Antiserum to the parent E. coli O111, (with O antigen intact) provided no significant protection. The protection against death from E. coli O17 by J5 antiserum was greater than that obtained from gentamicin (50%), the only antibiotic to which this strain was sensitive. Rabbits given J5 antiserum cleared labeled bacteria more rapidly than those given nonimmune sera. Antiserum to the J5 mutant is thought to prevent lethal bacteremia from unrelated Gram-negative bacteria by acting as both antitoxin and opsonin.
Examination of insulator regime conduction mechanisms in epitaxial and polycrystalline SmNiO3 thin films (2011)

Correlated oxides that exhibit metal–insulator phase transitions are emerging as potential candidates for switching devices. One such material is SmNiO3, which has a transition temperature above room temperature (∼400 K in bulk crystals). In this work, we study temperature- and bias-dependent conduction mechanisms in epitaxial and polycrystalline SmNiO3 thin films. In both cases, at low electric field we observe thermally assisted hopping conduction through defect states with activation energies of ∼170 meV and ∼270 meV, respectively. At high electric field the conduction transitions to a space-charge limited regime controlled by an exponential trap distribution. The power law exponents are ∼3 in epitaxial films and ∼8–14 in polycrystalline films. The trap decay parameter in epitaxial films does not have the expected 1/T temperature dependence, which may be a signature of bandgap narrowing at high temperature because of the insulator-to-metal transition. The larger activation energy and power law dependency in polycrystalline films are consistent with additional defect density from extraneous phases. In polycrystalline films, current-voltage data measured perpendicular to the film surface are rectifying because of asymmetry in electrode work functions with a ratio of 104 at ± 1 V. We find that whereas the space-charge limited conduction for positive bias is bulk limited, the negative bias conduction is injection limited.
CNR1 gene polymorphisms in addictive disorders: a systematic review and a meta-analysis (2010)

The aim of the present work was to systematically review all association studies of cannabis receptor 1 (CNR1) polymorphisms with dependence syndrome and to perform a meta-analysis. Odds ratios (ORs) were estimated by contrasting the ratio of counts of the 'high risk' versus 'low risk' alleles in cases with dependence versus controls. Studies were analyzed by random-effects meta-analysis using pooled OR. Eleven full text articles met our eligibility criteria and nine meta-analyses were performed on three polymorphisms of CNR1: rs1049353, rs806379 and the AAT repeat. Of these, only the AAT polymorphism showed a significant association with illicit substance dependence but only in the Caucasian population samples and using a risk allele definition of ≥ 16 repeats. Our analysis showed a small effect size (OR = 1.55, P = 0.045), with strong heterogeneity (Q = 19.87, P < 0.01 with I² = 85%). In line with the polygenic model, our meta-analysis supports a minor implication for CNR1 AAT polymorphism in illicit substance dependence vulnerability. Further studies in well-phenotyped samples and using more polymorphisms are needed to conclude on the actual influence of cannabinoid receptor polymorphisms.
<i>Caenorhabditis elegans</i>Twist plays an essential role in non-striated muscle development (2000)

The basic helix-loop-helix (bHLH) transcription factor Twist plays a role in mesodermal development in both invertebrates and vertebrates. In an effort to understand the role of the unique Caenorhabditis elegans Twist homolog, hlh-8, we analyzed mesodermal development in animals with a deletion in the hlh-8 locus. This deletion was predicted to represent a null allele because the HLH domain is missing and the reading frame for the protein is disrupted. Animals lacking CeTwist function were constipated and egg-laying defective. Both of these defects were rescued in transgenic mutant animals expressing wild-type hlh-8. Observing a series of mesoderm-specific markers allowed us to characterize the loss of hlh-8 function more thoroughly. Our results demonstrate that CeTwist performs an essential role in the proper development of a subset of mesodermal tissues in C. elegans. We found that CeTwist was required for the formation of three out of the four non-striated enteric muscles born in the embryo. In contrast, CeTwist was not required for the formation of the embryonically derived striated muscles. Most of the post-embryonic mesoderm develops from a single lineage. CeTwist was necessary for appropriate patterning in this lineage and was required for expression of two downstream target genes, but was not required for the expression of myosin, a marker of differentiation. Our results suggest that mesodermal patterning by Twist is an evolutionarily conserved function.
Shape-selective and asymmetric cyclopropanation of alkenes catalyzed by rhodium porphyrins (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTShape-selective and asymmetric cyclopropanation of alkenes catalyzed by rhodium porphyrinsJana L. Maxwell, Sean O'Malley, Kathlynn C. Brown, and Thomas KodadekCite this: Organometallics 1992, 11, 2, 645–652Publication Date (Print):February 1, 1992Publication History Published online1 May 2002Published inissue 1 February 1992https://pubs.acs.org/doi/10.1021/om00038a023https://doi.org/10.1021/om00038a023research-articleACS PublicationsRequest reuse permissionsArticle Views688Altmetric-Citations101LEARN 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
Effects of Nozzle Diameter on Performance Characteristics for a Tangential Impeller-type Water Meter (1999)

In this study the effects of nozzle diameter on the performance characteristics for the tangential impeller-type water meter are studied experimentally. The nozzle is cut along the tangential direction of the inner case in the water meter. The nozzle shape is round and the number of nozzles used for the experimental study are 8. The performance characteristics are discussed for various nozzle diameters such as 3.1, 3.3, 3.5, 4.0, 4.5 and 5.0 mm. Among the tangential impeller-type water meters, the water meter with the nozzle diameter of 5.0 mm shows the least pressure loss and the instrumental error compared to the Korean Standards.
Single-aperture STED illumination using a q-plate and fiber (2015)

We demonstrate single-aperture STED nanoscopy illumination with vortex-fiber modes excited by a dispersive q=1/2 plate at visible wavelengths. The vortex-fiber-compatible bias-voltage-tunable mode conversion of q-plates enables easy switching between multiple STED-wavelength pairs.
CH Bond Arylation of Diamondoids Catalyzed by Palladium(II) Acetate (2016)

Abstract We have developed an effective approach to 1,2‐disubstituted diamondoids by palladium(II) acetate catalyzed functionalization of CH bond. Selective mono‐arylation of the adamantane framework was achieved using picolylamide as a directing group in yields up to 87 %. Kinetic studies in combination with deuterium labeling experiments, competitive experiments and mass spectrometry contribute to the mechanistic understanding of the arylation process of alkanes with number of CH bonds neighboring the directing group. Triflic anhydride promoted cyclization of the directing group generates imidazo[1,5‐ a ]pyridine derivatives. Acid‐mediated removal of the directing group provides access to 2‐aryl diamondoid carboxylic acids, which are common precursors for the synthesis of various bioactive compounds (drug candidates). magnified image
CO2 on the International Space Station: An Operations Update (2016)

PROBLEM STATEMENT: We describe CO2 symptoms that have been reported recently by crewmembers on the International Space Station and our continuing efforts to control CO2 to lower levels than historically accepted. BACKGROUND: Throughout the International Space Station (ISS) program, anecdotal reports have suggested that crewmembers develop CO2-related symptoms at lower CO2 levels than would be expected terrestrially. Since 2010, operational limits have controlled the 24-hour average CO2 to 4.0 mm Hg, or below as driven by crew symptomatology. In recent years, largely due to increasing awareness by crew and ground team, there have been increased reports of crew symptoms. The aim of this presentation is to discuss recent observations and operational impacts to lower CO2 levels on the ISS. CASE PRESENTATION: Crewmembers are routinely asked about CO2 symptoms in their weekly private medical conferences with their crew surgeons. In recent ISS expeditions, crewmembers have noted symptoms attributable to CO2 starting at 2.3 mmHg. Between 2.3 - 2.7 mm Hg, fatigue and full-headedness have been reported. Between 2.7 - 3.0 mm Hg, there have been self-reports of procedure missed steps or procedures going long. Above 3.0 - 3.4 mm Hg, headaches have been reported. A wide range of inter- and intra-individual variability in sensitivity to CO2 have been noted. OPERATIONAL / CLINICAL RELEVANCE: These preliminary data provide semi-quantitative ranges that have been used to inform a new operational limit of 3.0 mmHg as a compromise between systems capabilities and the recognition that there are human health and performance impacts at recent ISS CO2 levels. Current evidence would suggest that an operational limit between 0.5 and 2.0 mm Hg may maintain health and performance. Future work is needed to establish long-term ISS and future vehicle operational limits.
A technique for minimum/nonminimum phase identification during multipath fading (2002)

The use of an adaptive transversal equalizer at the receiver end of a digital radio receiver as a tool for identifying the phase of dispersive fading events is discussed. The identification is based on the online comparison of the equalizer precursor and postcursor taps and can be used without service disruption. It is shown that this method can be applied to dispersive fades with in-band notches and that noise in the received signal is a major cause of identification errors. The method used to compute the equalizer taps is described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Modeling projectile impact onto prestressed ceramic targets (2003)

This work presents computed results for the responses of ceramic targets, with and without prestress, subjected to projectile impact. Also presented is a computational technique to include prestress. Ceramic materials have been considered for armor applications for many years because of their high strength and low density. Many researchers have demonstrated that providing confinement enhances the ballistic performance of ceramic targets. More recently, prestressing the ceramic is being considered as an additional enhancement technique. This work investigates the effect of prestressing the ceramic for both thin and thick target configurations subjected to projectile impact. In all cases the targets with ceramic prestress provided enhanced ballistic performance. The computed results indicate that prestressed ceramic reduces and/or delays failure, resulting in improved ceramic performance and ballistic efficiency.
A hybrid P2P and master-slave architecture for intelligent multi-agent reinforcement learning in a distributed computing environment: A case study (2010)

In this paper, we propose a distributed architecture for reinforcement learning in a multi-agent environment, where agents share information learned via a distributed network. Here we propose a hybrid master/slave and peer-to-peer system architecture, where a master node effectively assigns a work load (a portion of the terrain) to each node. However, this master node also manages communications between all the other system nodes, and in that sense it is a peer-to-peer architecture. It is a loosely-coupled system in that node slaves only know about the existence of the master node, and are only concerned with their work load (portion of the terrain). As part of this architecture, we show how agents are allowed to communicate with other agents in the same or different nodes and share information that pertains to all agents, including the agent obstacle barriers. In particular, one main contribution of the paper is multi-agent reenforcement learning in a distributed system, where the agents do not have complete knowledge and information of their environment, other than what is available on the computing node, the particular agent (s) is (are) running on. We show how agents, running on same or different nodes, coordinate the sharing of their respective environment states/information to collaboratively perform their respective tasks.
Study of the transient behavior of microfluidic heat sinks (2010)

In this work the transient behavior of a microfluidic heat sink is studied. Transient response of a heat sink is important for situations where heat inputs are dynamic, especially for applications such as microprocessors that have surfaces which generate heat non-uniformly. Heat generation profile on their surface changes with time and sometimes this change is very rapid. It is the transient characteristics and behavior of the heat sink that determines the surface temperature profile in response to the dynamic heat input. Transient simulation of microfluidic heat sinks confirms that their characteristic approximately follows a simple first order RC equivalent circuit model. Simulations show that the steady state surface temperature of the copper heat sink in transient condition is lower than the surface temperature of the silicon and nickel heat sinks. Therefore, the copper heat sink is superior for long duration transient conditions. Also shown is that a larger heat sink thermal capacitance provides a delayed temperature rise on the surface of the heat sink during the transient. This indicates that using a material with higher heat conductance is not necessarily good if it possess a small heat capacitance. This is illustrated by the silicon heat sink performing poorer than the nickel heat sink, in terms of temperature rise during transient situation, even though it has a higher heat conductance.
A cost effective direct drive option for the Thirty Meter Telescope (2006)

Direct drive motors are finding their way into telescope drive designs and have many advantages over more traditionally used friction and rack/pinion drives. They are implemented as curved linear motors custom made to the actual diameter required by the telescope design. Custom design is by definition a costly process and this paper discusses the possibility to use standard straight linear segments to approximate the curvature. Detailed analysis is given concerning differences in the electro-magnetic properties compared to a custom design motor.
Cloning and Expression of Acetylcholinesterase from Venom (1996)

As deduced from cDNA clones, the catalytic domain of Bungarus fasciatus venom acetylcholinesterase (AChE) is highly homologous to those of other AChEs. It is, however, associated with a short hydrophilic carboxyl-terminal region, containing no cysteine, that bears no resemblance to the alternative COOH-terminal peptides of the GPI-anchored molecules (H) or of other homomeric or heteromeric tailed molecules (T). Expression of complete and truncated AChE in COS cells showed that active hydrophilic monomers are produced and secreted in all cases, and that cleavage of a very basic 8-residue carboxyl-terminal fragment occurs upon secretion. The COS cells produced Bungarus AChE about 30 times more efficiently than an equivalent secreted monomeric rat AChE. The recombinant Bungarus AChE, like the natural venom enzyme, showed a distinctive ladder pattern in nondenaturing electrophoresis, probably reflecting a variation in the number of sialic acids. By mutagenesis, we showed that two differences (methionine instead of tyrosine at position 70; lysine instead of aspartate or glutamate at position 285) explain the low sensitivity of Bungarus AChE to peripheral site inhibitors, compared to the Torpedo or mammalian AChEs. These results illustrate the importance of both the aromatic and the charged residues, and the fact that peripheral site ligands (propidium, gallamine, D-tubocurarine, and fasciculin 2) interact with diverse subsets of residues.
Research on CGF Entity Model Based on Factory Mechanism (2008)

The model engine development for CGF entities is designed and realized based on ldquoabstract factoryrdquo and ldquofactory methodrdquo design pattern. Firstly, the entities factory manager encapsulates the responsibility and the process of creating CGF entities, and provides an interface for creating families of related or dependent CGF entities without specifying their concrete classes; then, each created families of CGF entities is defined a corresponding parameterized factory, and it is overridden by the parameterized class identifier for each to extend or change the CGF entity product; Finally, configure and modify the created CGF entities or its components, and edit the loading information in a MTL file. The result of the engine design shows that it isolates concrete classes and makes exchanging and extending product families easy. The method also can help the client construct the CGF entity models quickly in order to reduce time and complexity.
In vivo optical imaging of cancer cell function and tumor microenvironment (2018)

In vivo optical imaging using fluorescence and bioluminescence is superior to other methods in terms of spatiotemporal resolution and specificity, and represents a new technology for comprehensively studying living organisms in a less invasive way. Nowadays, it is an indispensable technology for studying many aspects of cancer biology, including dynamic invasion and metastasis. In observations of fluorescence or bioluminescence signals in a living body, various problems were caused by optical characteristics such as absorption and scattering and, therefore, observation of deep tissue was difficult. Recent developments in techniques for observation of the deep tissues of living animals overcame this difficulty by improving bioluminescent proteins, fluorescent proteins, and fluorescent dyes, as well as detection technologies such as two-photon excitation microscopy. In the present review, we introduce these technological developments and in vivo application of bioluminescence and fluorescence imaging, and discuss future perspectives on the use of in vivo optical imaging technology in cancer research.