gebhart/patrepeval huggingface dataset:
Whitted Ray-Tracing for Dynamic Scenes using a Ray-Space Hierarchy on the GPU (2007)

In this paper, we present a new algorithm for interactive rendering of animated scenes with Whitted Ray-Tracing, running on the GPU. We focus our attention on the secondary rays (the rays generated by one or more bounces on specular objects), and use the GPU rasterizer for primary rays. Our algorithm is based on a ray-space hierarchy, allowing us to handle truly dynamic scenes without the need to rebuild or update the scene hierarchy. The rayspace hierarchy is entirely built on the GPU for every frame, using a very fast process. Traversing the ray-space hierarchy is also done on the GPU; one of the benefits of using a ray-space hierarchy is that we have a single shader, and a fixed number of passes. After traversing each level of the hierarchy, we prune empty branches using a stream reduction method. We present two different stream reduction methods, a fast one using a hierarchical algorithm, and an easy one using the Geometry shaders. Our algorithm results in interactive rendering with specular reflections and shadows for moderately complex scenes (~ 700K triangles), handles any kind of dynamic or unstructured scenes without any pre-processing, and scales well with both the scene complexity and the image resolution.
Human Bile Salt Export Pump Promoter Is Transactivated by the Farnesoid X Receptor/Bile Acid Receptor (2001)

The bile salt excretory pump (BSEP, ABCb11) is critical for ATP-dependent transport of bile acids across the hepatocyte canalicular membrane and for generation of bile acid-dependent bile secretion. Recent studies have demonstrated that the expression of this transporter is sensitive to the flux of bile acids through the hepatocyte, possibly at the level of transcription of the BSEP gene. To determine the mechanisms underlying the regulation of BSEP by bile acids, the promoter of the BSEP gene was cloned. The sequence of the promoter contained an inverted repeat (IR)-1 element (5'-GGGACA T TGATCCT-3') at base pairs -63/-50 consisting of two nuclear receptor half-sites organized as an inverted repeat and separated by a single nucleotide. This IR-1 element has been shown in several recent studies to serve as a binding site for the farnesoid X receptor (FXR), a nuclear receptor for bile acids. FXR activity requires heterodimerization with RXR alpha, and when bound by bile acids, the complex effectively regulates the transcription of several genes involved in bile acid homeostasis. Gel mobility shift assays demonstrated specific binding of FXR/RXR alpha heterodimers to the IR-1 element in the BSEP promoter. In HepG2 cells, co-transfection of FXR and RXR alpha is required to attain full transactivation of the BSEP promoter by bile acids. Two FXR transactivation-deficient mutants (an AF-2 deletion and a W469A point mutant) failed to transactivate, indicating that the effect of bile acids is FXR-dependent. Further, mutational analysis confirms that the FXR/RXR alpha heterodimer activates transcription through the IR-1 site in the human BSEP promoter. These results demonstrate a mechanism by which bile acids transcriptionally regulate the activity of the bile salt excretory pump, a critical component involved in the enterohepatic circulation of bile acids.
The Role of Chloramphenicol in the Treatment of Bloodstream Infection Due to Vancomycin‐ResistantEnterococcus (1998)

The incidence of bacteremia due to vancomycin-resistant Enterococcus (VRE) has increased markedly in recent years. We investigated the role of chloramphenicol in its treatment. All cases of VRE bacteremia occurring at our facility during a 45-month period were analyzed. The response to chloramphenicol, its effect on mortality, and the incidence of adverse effects were assessed. Fifty-one patients (65.4%) received chloramphenicol. Among patients in whom a response could be assessed, 22 (61.1%) of 36 demonstrated a clinical response, while 34 (79.1%) of 43 showed a microbiological response. Forty-two patients (53.8%) died as a result of the bacteremia. Although the mortality rate was lower for patients treated with chloramphenicol, the difference was not significant (odds ratio = 0.72; 95% confidence interval, 0.28-1.85; P = .49), nor was there an association between earlier initiation of therapy and reduced mortality (P = .45). In cases with central line-related bacteremia, there was no difference in mortality among patients treated with chloramphenicol, line removal, or both (P = .36). Although 16 patients (31.4%) had adverse effects, none could be definitely attributed to chloramphenicol. Although chloramphenicol was well-tolerated, no significant effect of its use on mortality could be demonstrated.
An inexpensive and portable microchip-based platform for integrated RT–PCR and capillary electrophoresis (2008)

We present an inexpensive, portable and integrated microfluidic instrument that is optimized to perform genetic amplification and analysis on a single sample. Biochemical reactions and analytical separations for genetic analysis are performed within tri-layered glass-PDMS microchips. The microchip itself consists of integrated pneumatically-actuated valves and pumps for fluid handling, a thin-film resistive element that acts simultaneously as a heater and a temperature sensor, and channels for capillary electrophoresis (CE). The platform is comprised of high voltage circuitry, an optical assembly consisting of a laser diode and a charged coupled device (CCD) camera, circuitry for thermal control, and mini-pumps to generate vacuum/pressure to operate the on-chip diaphragm-based pumps and valves. Using this microchip and instrument, we demonstrate an integration of reverse transcription (RT), polymerase chain reaction (PCR), and capillary electrophoresis (CE). The novelty of this system lies in the cost-effective integration of microfluidics, optics, and electronics to realize a fully portable and inexpensive system (on the order of $1000 in component costs) for performing both genetic amplification and analysis - the basis of many medical diagnostics. We believe that this combination of portability, cost-effectiveness and performance will enable more accessible healthcare.
Cyclic Ketone Inhibitors of the Cysteine Protease Cathepsin K (2001)

Cathepsin K (EC 3.4.22.38), a cysteine protease of the papain superfamily, is predominantly expressed in osteoclasts and has been postulated as a target for the treatment of osteoporosis. Crystallographic and structure--activity studies on a series of acyclic ketone-based inhibitors of cathepsin K have led to the design and identification of two series of cyclic ketone inhibitors. The mode of binding for four of these cyclic and acyclic inhibitors to cathepsin K is discussed and compared. All of the structures are consistent with addition of the active site thiol to the ketone of the inhibitors with the formation of a hemithioketal. Cocrystallization of the C-3 diastereomeric 3-amidotetrahydrofuran-4-one analogue 16 with cathepsin K showed the inhibitor to occupy the unprimed side of the active site with the 3S diastereomer preferred. This C-3 stereochemical preference is in contrast to the X-ray cocrystal structures of the 3-amidopyrrolidin-4-one inhibitors 29 and 33 which show these inhibitors to prefer binding of the 3R diastereomer. The 3-amidopyrrolidin-4-one inhibitors were bound in the active site of the enzyme in two alternate directions. Epimerization issues associated with the labile alpha-amino ketone diastereomeric center contained within these inhibitor classes has proven to limit their utility despite promising pharmacokinetics displayed in both series of compounds.
Light Propagation in Composite Two-Dimensional Arrays of Polystyrene Spherical Particles (1999)

Light propagation in composite two-dimensional spherical arrays in which mixtures of fluorescent and nonfluorescent polystyrene latex particles (3, 1, 0.5 μm) are packed in a highly dense, highly oriented manner on a solid surface was observed by use of fluorescence microscopy and phase-contrast microscopy. In addition, by means of through-focusing, we were able to determine directly the stacking mode, e.g., face-centered-cubic packing or hexagonal close packing, in up to three layers. The propagation modes can be divided into two types: one inside the particles and the other on the particle surfaces. The contribution of these two modes appears to be dependent upon the relative light frequency.
Ximelagatran versus Warfarin for the Prevention of Venous Thromboembolism after Total Knee Arthroplasty (2002)

For prophylaxis of venous thromboembolism, fixed-dose ximelagatran started the morning after total knee arthroplasty is well tolerated and at least as effective as warfarin, but it does not require coagulation monitoring or dose adjustment.
Adenosine Analogues as Inhibitors of Trypanosoma brucei Phosphoglycerate Kinase:  Elucidation of a Novel Binding Mode for a 2-Amino-N6-Substituted Adenosine (2000)

As part of a project aimed at structure-based design of adenosine analogues as drugs against African trypanosomiasis, N(6)-, 2-amino-N(6)-, and N(2)-substituted adenosine analogues were synthesized and tested to establish structure-activity relationships for inhibiting Trypanosoma brucei glycosomal phosphoglycerate kinase (PGK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and glycerol-3-phosphate dehydrogenase (GPDH). Evaluation of X-ray structures of parasite PGK, GAPDH, and GPDH complexed with their adenosyl-bearing substrates led us to generate a series of adenosine analogues which would target all three enzymes simultaneously. There was a modest preference by PGK for N(6)-substituted analogues bearing the 2-amino group. The best compound in this series, 2-amino-N(6)- [2''(p-hydroxyphenyl)ethyl]adenosine (46b), displayed a 23-fold improvement over adenosine with an IC(50) of 130 microM. 2-[[2''-(p-Hydroxyphenyl)ethyl]amino]adenosine (46c) was a weak inhibitor of T. brucei PGK with an IC(50) of 500 microM. To explore the potential of an additive effect that having the N(6) and N(2) substitutions in one molecule might provide, the best ligands from the two series were incorporated into N(6),N(2)-disubstituted adenosine analogues to yield N(6)-(2''-phenylethyl)-2-[(2'' -phenylethyl)amino]adenosine (69) as a 30 microM inhibitor of T. brucei PGK which is 100-fold more potent than the adenosine template. In contrast, these series gave no compounds that inhibited parasitic GAPDH or GPDH more than 10-20% when tested at 1.0 mM. A 3.0 A X-ray structure of a T. brucei PGK/46b complex revealed a binding mode in which the nucleoside analogue was flipped and the ribosyl moiety adopted a syn conformation as compared with the previously determined binding mode of ADP. Molecular docking experiments using QXP and SAS program suites reproduced this "flipped and rotated" binding mode.
Performance criteria for graph clustering and Markov cluster experiments (2000)

In~[1] a cluster algorithm for graphs was introduced called the Markov cluster algorithm or MCL~algorithm. The algorithm is based on simulation of (stochastic) flow in graphs by means of alternation of two operators, expansion and inflation. The results in~[2] establish an intrinsic relationship between the corresponding algebraic process (MCL~process) and cluster structure in the iterands and the limits of the process. Several kinds of experiments conducted with the MCL~algorithm are described here. Test cases with varying homogeneity characteristics are used to establish some of the particular strengths and weaknesses of the algorithm. In general the algorithm performs well, except for graphs which are very homogeneous (such as weakly connected grids) and for which the natural cluster diameter (i.e. the diameter of a subgraph induced by a natural cluster) is large. This can be understood in terms of the flow characteristics of the MCL~algorithm and the heuristic on which the algorithm is grounded. A generic performance criterion for clusterings of weighted graphs is derived, by a stepwise refinement of a simple and appealing criterion for simple graphs. The most refined criterion uses a particular Schur convex function, several properties of which are established. A metric is defined on the space of partitions, which is useful for comparing different clusterings of the same graph. The metric is compared with the metric known as the equivalence mismatch coefficient. The performance criterion and the metric are used for the quantitative measurement of experiments conducted with the MCL~algorithm on randomly generated test graphs with 10000 nodes. Scaling the MCL~algorithm requires a regime of pruning the stochastic matrices which need to be computed. The effect of pruning on the quality of the retrieved clusterings is also investigated. [1] A cluster algorithm for graphs. Technical report INS-R0010, National Research Institute for Mathematics and Computer Science in the Netherlands, Amsterdam, 2000. [2] A stochastic uncoupling process for graphs. Technical report INS-R0011, National Research Institute for Mathematics and Computer Science in the Netherlands, Amsterdam, 2000.
Reduced Diabetes in btk-Deficient Nonobese Diabetic Mice and Restoration of Diabetes with Provision of an Anti-Insulin IgH Chain Transgene (2009)

Type 1 diabetes results from T cell-mediated destruction of insulin-producing beta cells. Although elimination of B lymphocytes has proven successful at preventing disease, modulation of B cell function as a means to prevent type 1 diabetes has not been investigated. The development, fate, and function of B lymphocytes depend upon BCR signaling, which is mediated in part by Bruton's tyrosine kinase (BTK). When introduced into NOD mice, btk deficiency only modestly reduces B cell numbers, but dramatically protects against diabetes. In NOD, btk deficiency mirrors changes in B cell subsets seen in other strains, but also improves B cell-related tolerance, as indicated by failure to generate insulin autoantibodies. Introduction of an anti-insulin BCR H chain transgene restores diabetes in btk-deficient NOD mice, indicating that btk-deficient B cells are functionally capable of promoting autoimmune diabetes if they have a critical autoimmune specificity. This suggests that the disease-protective effect of btk deficiency may reflect a lack of autoreactive specificities in the B cell repertoire. Thus, signaling via BTK can be modulated to improve B cell tolerance, and prevent T cell-mediated autoimmune diabetes.
Adaptive base station antennas for mobile communication systems (2002)

There has been a rapid increase in the number of mobile communication users, resulting in an equally rapid need for increased capacity in the networks. Extensive research and development work on advanced base station antennas for mobile communication is in progress at Ericsson. This includes both active and adaptive antenna systems. With the introduction of active antenna products, it is now possible to use small-size base stations, with high levels of equivalent radiated power (ERP) and low power consumption. Array designs and measured results from the work on adaptive base station antennas are presented.
Biodegradable implants with different drug release profiles (2011)

Maximum torques during hot-melt extrusion were dependent on the inherent viscosity of PLGA, extrusion temperature, drug loading and drug properties, when keeping a constant screw rotation speed. The incorporation of ibuprofen into PLGA could reduce the maximum torque and Tg of PLGA caused by its plasticizing effect. A pulsatile drug release profile from PLGA hot-melt extruded implants was achieved, demonstrated by a lag time after an initial burst release, followed by a second burst or late rapid release phase. The plasticizing effect of ibuprofen on PLGA led to higher water uptake, faster mass loss, and thus the fastest drug release in comparison with the other model drugs. The initial burst release from PLGA implants prepared by hot-melt extrusion increased with an increase in drug loading, decrease in inherent viscosity of PLGA and higher water solubility of the drug. The change in processing parameters, PLGA inherent viscosity, drug solubility and the presence of coating played an important role on the lag times of pulsatile release from PLGA implants. The factors generating the acceleration of PLGA degradation led to shorter lag-times, except the drug solubility. The second burst release phase was influenced by the drug solubility and acid-base properties. The release after the lag time was slowed with higher diazepam drug loading because of its low solubility. The release of a basic drug (tramadol HCl) was prolonged due to a possible ionic interaction. The replacement of phosphate buffer of pH 7.4 by Lipofundin to mimic in vivo subcutaneous tissue condition resulted in less water uptake, the deformation of the PLGA implant, and faster diazepam release during the diffusion phase due to the decrease in the Tg of PLGA, which is due to the presence of glycerol in the formulation.
Manoyl-Oxide Biotransformations with Filamentous Fungi (2007)

Microbial transformations of manoyl oxides by filamentous fungi have been used to introduce hydroxyl groups, regio- and stereoselectively, into substrates at positions difficult to achieve by chemical means. The principal objective of most papers published in this field has been to produce new, highly oxygenated, bioactive manoyl-oxide compounds that present a large diversity of biological properties. The manoyl oxides most frequently studied at present are forskolin and its derivatives, the pharmacological activity of which is related to their ability to activate AC (adenylate cyclase), thus generating an increase in intracellular cAMP (cyclic adenosine monophosphate). The microbial hydroxylation of forskolin and 1,9-dideoxyforskolin has been extensively studied, using the fungi Scopuloriopsis sp., Syncephalastrum sp., Neurospora crassa, Mortierella isabellina and several Aspergillus sp.. Other biotransformation studies of natural manoyl oxides and hemi-synthetic enantio derivatives, carried out via the biomimetic cyclization of ent-8α-hydroxylabda-13(16),14- dienes, have used filamentous fungi Curvularia lunata, Cunninghamella elegans, Fusarium moniliforme, Gibberella fujikuroi, Gliocladium roseum, Mucor plumbeus, Rhizopus nigricans and Neurospora crassa. In some cases, the new hydroxylations were introduced at the same positions as in natural forskolin, yielding some noteworthy products that show biological activities. Keywords: Forskolin, Gibberella fujikuroi, ribenol, varodiol derivatives, Fusarium moniliforme
Nanotechnology-based drug delivery systems (2007)

Nanoparticles hold tremendous potential as an effective drug delivery system. In this review we discussed recent developments in nanotechnology for drug delivery. To overcome the problems of gene and drug delivery, nanotechnology has gained interest in recent years. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signalling involved in pathobiology of the disease under consideration. Several anti-cancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been successfully formulated using nanomaterials. Quantom dots, chitosan, Polylactic/glycolic acid (PLGA) and PLGA-based nanoparticles have also been used for in vitro RNAi delivery. Brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents past the blood-brain barrier and into the brain. Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have been shown to cross the intact blood-brain barrier and released at therapeutic concentrations in the brain. The use of nanomaterials including peptide-based nanotubes to target the vascular endothelial growth factor (VEGF) receptor and cell adhesion molecules like integrins, cadherins and selectins, is a new approach to control disease progression.
Keratinocyte growth factor and hepatocyte growth factor/scatter factor are heparin-binding growth factors for alveolar type II cells in fibroblast-conditioned medium. (1993)

Epithelial-mesenchymal interactions mediate aspects of normal lung growth and development and are important in the restoration of normal alveolar architecture after lung injury. To determine if fibroblasts are a source of soluble growth factors for alveolar type II cells, we investigated the effect of fibroblast-conditioned medium (CM) on alveolar type II cell DNA synthesis. Serum-free CM from confluent adult human lung fibroblasts was concentrated fivefold by lyophilization. Type II cells were isolated from adult rats by elastase dissociation and incubated with [3H]thymidine and varying dilutions of concentrated CM and serum from day 1 to 3 of culture. Stimulation of type II cell DNA synthesis by fibroblast-CM was maximal after 48 h of conditioning and required the presence of serum. The activity of the CM was eliminated by boiling and by treatment with trypsin, pepsin, or dithiothreitol and was additive with saturating concentrations of acidic fibroblast growth factor, epidermal growth factor, and insulin. The growth factor activity bound to heparin-Sepharose and was eluted with 0.6 and 1.0 M NaCl. Neutralizing antibody studies demonstrated that the primary mitogens isolated in the 0.6 and 1.0 M NaCl fractions were keratinocyte growth factor (KGF, fibroblast growth factor 7) and hepatocyte growth factor/scatter factor (HGF/SF), respectively. HGF/SF was demonstrated in the crude CM and KGF was detected in the 0.6 M NaCl eluent by immunoblotting. Northern blot analysis confirmed that the lung fibroblasts expressed both KGF and HGF/SF transcripts. Human recombinant KGF and HGF/SF induced a concentration- and serum-dependent increase in rat alveolar type II cell DNA synthesis. We conclude that adult human lung fibroblasts produce at least two soluble heparin-binding growth factors, KGF and HGF/SF, which promote DNA synthesis and proliferation of rat alveolar type II cells in primary culture. KGF and HGF/SF may be important stimuli for alveolar type II cell proliferation during lung growth and after lung injury.
Understanding the Dissemination of Sacral Neuromodulation (2013)

Rates of sacral neuromodulation have increased dramatically over the past decade. However, these rates of utilization are highly variable across regions, with some regions performing large numbers of these procedures and other regions performing few to no procedures. This range in practice patterns may reflect medical uncertainty surrounding the role of this procedure.
The facilitating role of the play specialist (2000)

Play should be viewed as a language, according to Alison Webster, who describes the wider context of play, defining play interventions and the roles of play professionals