gebhart/patrepeval huggingface dataset:
Nanomedicines: addressing the scientific and regulatory gap (2014)

Nanomedicine is the application of nanotechnology to the discipline of medicine: the use of nanoscale materials for the diagnosis, monitoring, control, prevention, and treatment of disease. Nanomedicine holds tremendous promise to revolutionize medicine across disciplines and specialties, but this promise has yet to be fully realized. Beyond the typical complications associated with drug development, the fundamentally different and novel physical and chemical properties of some nanomaterials compared to materials on a larger scale (i.e., their bulk counterparts) can create a unique set of opportunities as well as safety concerns, which have only begun to be explored. As the research community continues to investigate nanomedicines, their efficacy, and the associated safety issues, it is critical to work to close the scientific and regulatory gaps to assure that nanomedicine drives the next generation of biomedical innovation.
Monitoring Accident Blackspot Sites (1991)

The key aspects and features of the Accident Blackspot Program that involves the use of low-cost engineering improvements to reduce accidents are discussed. The goals that monitoring achieves as well as benefits that the results of the Accident Blackspot program will offer are highlighted.
Microthermoforming of flexible, not-buried hollow microstructures for chip-based life sciences applications (2004)

A new method is presented for the manufacturing of flexible, not buried and thin-walled hollow microstructures from polymer films. This low-cost method seems to be especially suited for the fabrication of plastic microstructures for fluidic one-way applications in the field of life sciences. It is based on a thermoforming process adapted to microstructure technology and is called 'microthermoforming'. Inside a hot embossing press, a heated thin thermoplastic film is formed into the evacuated microcavities of a plate-shaped metal mould using a compressed gas. The film may be heat-sealed on to a thicker plastic film substrate inside the same press without demoulding the thermoformed film. To demonstrate the performance of the new manufacturing method, flexible capillary electrophoresis and cell culture chips from polystyrene, polycarbonate and a cyclo-olefin polymer with 16 and 625 parallel microstructures each, respectively, have been fabricated.
Investigation of 1.2 kV SiC MOSFET for high frequency high power applications (2010)

SiC is among the most promising materials for next generation power electronic devices due to its superior physical properties to Si and relative mature technology. SiC MOSFET is expected to offer performance improvement over Si counterpart. This paper presents the characterization of 1.2 kV SiC MOSFET, including its static and dynamic characteristics, and its high-frequency (1 MHz), high-power (1.2 kW) zero-voltage switching (ZVS) operation in a half-bridge parallel resonant converter. In comparison with SiC JFET and Si CoolMOS, the advantages and disadvantages of the SiC MOSFET are summarized.
A systematic analysis of the AF‐2 domain of human retinoic acid receptor α reveals amino acids critical for transcriptional activation and conformational integrity (1996)

We previously identified a carboxy-terminal transactivation function termed AF-2 within the last 15 amino acids of the ligand binding domain of the human retinoic acid receptor alpha (hRAR alpha). Truncation of this region abolished transcriptional activity. Here we provide a systematic analysis using alanine scanning mutagenesis of amino acids from Ser405 to Gly419 on a truncated hRAR alpha (delta419) to identify residues within this region that are responsible for transcriptional activity. Whereas mutations in positions 405, 408, 411, and 415-419 have little or no effect on the ability of modified receptors to activate a DR5 response element, mutations in positions 406, 407, 409, 410, and 412-413 modify either the potency or efficacy of all-trans retinoic acid (tRA) -induced gene transcription. Therefore, receptors with mutations in positions 409, 410, 413, and 414 have low transcriptional activity over a wide range of tRA concentrations. Receptors with mutations in positions 406, 407, and 412 exhibit a maximum transcriptional activity similar to wild-type hRAR alpha, but require higher concentrations of tRA. Replacing residues 405-419 on delta419 with the conserved AF-2 domain from the vitamin D3 receptor or the estrogen receptor results in a receptor with wild-type or low transcriptional activity, respectively. A full-length hRAR alpha mutant with an alanine substitution at position 406 (hRAR alpha M406A) binds tRA, but unlike the truncated M406A, which lacks the "F" region, it is not transcriptionally active. Protease mapping experiments detect a consistent difference in the conformation of hRAR alpha M406A compared to wild-type hRAR alpha. These data define amino acids from Ser405 to Gly419 on delta419 that are critical for transcriptional activity and point to the importance of the conformational integrity of receptor domains in maintaining ligand-induced transcriptional activation.
Design and Analysis of Digitized RF-Over-Fiber Links (2009)

In this paper, we present a performance analysis of microwave signal transmission by deploying digitized RF transport over a standard optical fiber link. The bandpass sampling technique is used to digitize the RF signal. An analytical model, which is transparent to any modulation format, was developed to assess the transmission performance of a digitized RF signal in M-level quadrature amplitude modulation (M-QAM) format. Using this analytical model, key design parameters such as bit resolution, link bit rate, receiver sensitivity, and link signal-to-noise ratio (SNR) were analyzed for a digitized 2.475 GHz RF signal with 16-QAM data modulation format and 6 MSymbols/s baud rate over a 20-km optical link. The analytical results show that the link SNR is predominantly determined by the performance of the analog-to-digital converter (ADC). We experimentally demonstrated the digitized RF transmission over a 20-km optical link. The analytical model and experimental results show that the performance of the link SNR is governed by jitter noise beyond 7 bits of resolution of the ADC. Using an ADC with 8-bit resolution, a 2.475 GHz RF signal with 16-QAM 6 MSymbols/s data was successfully transmitted and recovered with very good error vector magnitude of 1.77.
Controlling Electron-Phonon Interactions in Graphene at Ultrahigh Carrier Densities (2010)

We report on the temperature dependent electron transport in graphene at different carrier densities n. Employing an electrolytic gate, we demonstrate that n can be adjusted up to 4 × 10(14) cm(-2) for both electrons and holes. The measured sample resistivity ρ increases linearly with temperature T in the high temperature limit, indicating that a quasiclassical phonon distribution is responsible for the electron scattering. As T decreases, the resistivity decreases more rapidly following ρ(T) ∼ T(4). This low temperature behavior can be described by a Bloch-Grüneisen model taking into account the quantum distribution of the two-dimensional acoustic phonons in graphene. We map out the density dependence of the characteristic temperature Θ(BG) defining the crossover between the two distinct regimes, and show that, for all n, ρ(T) scales as a universal function of the normalized temperature T/Θ(BG).
Rate-limiting steps for the esterase and dehydrogenase reaction catalyzed by horse liver aldehyde dehydrogenase. (1976)

Horse liver aldehyde dehydrogenase, like other aldehyde dehydrogenases, is capable of hydrolyzing esters such as nitrophenyl acetate. Pre-steady state and burst kinetics were performed using substrate levels of enzyme to determine whether the rate-limiting step occurred prior to or after the formation of an acyl enzyme intermediate. A burst was found by both techniques for the dehydrogenase reaction; but no burst was found for the esterase reaction. These data show that the rate-limiting step for the two reactions catalyzed by the enzyme differs. For dehydrogenase it occurs after the formation of the acyl intermediate, but for esterase it occurs prior to its formation.
Nitric Oxide-Loaded Antimicrobial Polymer for the Synergistic Eradication of Bacterial Biofilm (2018)

Bacterial biofilms are often difficult to treat and represent the main cause of chronic and recurrent infections. In this study, we report the synthesis of a novel antimicrobial/antibiofilm polymer that consists of biocompatible oligoethylene glycol, hydrophobic ethylhexyl, cationic primary amine, and nitric oxide (NO)-releasing functional groups. The NO-loaded polymer has dual-action capability as it can release NO which triggers the dispersion of biofilm, whereas the polymer can induce bacteria cell death via membrane wall disruption. By functionalizing the polymers with NO, we observed a synergistic effect in biofilm dispersal, planktonic and biofilm killing activities against <i>Pseudomonas aeruginosa</i>. The NO-loaded polymer results in 80% reduction in biofilm biomass and kills >99.999% of planktonic and biofilm <i>P. aeruginosa</i> cells within 1 h of treatment at a polymer concentration of 64 μg mL<sup>-1</sup>. To achieve this synergistic effect, it is imperative that the NO donors and antimicrobial polymer exist as a single chemical entity, instead of a cocktail physical mixture of two individual components. The excellent antimicrobial/antibiofilm activity of this dual-action polymer suggests the advantages of combination therapy in combating bacterial biofilms.
Advances in Spinal Interbody Cages (2016)

Since the late 1980s, spinal interbody cages (ICs) have been used to aid bone fusion in a variety of spinal disorders. Utilized to restore intervertebral height, enable bone graft containment for arthrodesis, and restore anterior column biomechanical stability, ICs have since evolved to become a highly successful means of achieving fusion, being associated with less postoperative pain, shorter hospital stay, fewer complications and higher rates of fusion when than bone graft only spinal fusion. IC design and materials have changed considerably over the past two decades. The threaded titanium-alloy cylindrical screw cages, typically filled with autologous bone graft, of the mid-1990s achieved greater fusion rates than bone grafts and non-threaded cages. Threaded screw cages, however, were soon found to be less stable in extension and flexion; additionally, they had a high incidence of cage subsidence. As of the early 2000s, non-threaded box-shaped titanium or polyether ether ketone IC designs have become increasingly more common. This modern design continues to achieve greater cage stability in flexion, axial rotation and bending. However, cage stability and subsidence, bone fusion rates and surgical complications still require optimization. Thus, this review provides an update of recent research findings relevant to ICs over the past 3 years, highlighting trends in optimization of cage design, materials, alternatives to bone grafts, and coatings that may enhance fusion.
The Involvement of Platelet Activating Factor in Ovulation (1989)

Follicle rupture during ovulation is associated with inflammation-like changes. Because platelet activating factor (PAF) participates in the inflammatory process, the effect of a PAF-specific antagonist, BN52021, on the ovulatory response was tested in rats. BN52021, administered locally, inhibited follicle rupture in rats stimulated to ovulate with human chorionic gonadotropin (hCG). In addition to suppressing rupture of the follicles, this antagonist suppressed the hCG-stimulated increase in ovarian collagenolysis and vascular permeability. The inhibition of ovulation of BN52021 could be reversed by simultaneous administration of PAF. Furthermore, PAF partially reversed the blockage of ovulation by inhibitors of eicosanoid synthesis. Collectively, these results suggest the involvement of PAF in ovulation. Its role seems to be closely related to the metabolism of arachidonic acid. Thus, modulation of PAF action may serve as an additional target for regulation of reproduction via its action on ovulation.
Development of an STS marker and SSRs suitable for marker‐assisted selection for the BaMMV resistance gene <i>rym9</i> in barley (2000)

Abstract Based on the RAPD marker OP‐C04H910 which is closely linked to the barley mild mosaic virus (BaMMV) resistance gene rym9 derived from the variety ‘Bulgarian 347’ the marker STS‐C04H910 cosegregating with OP‐C04H910 and generating a single additional band on plants carrying the recessive resistance encoding allele has been developed. Furthermore, the simple sequence repeats (SSRs) WMS6 and HVM67 have been integrated into the genetic map of the rym9 region on chromosome 4HL. Because of their close linkage to rym9 and distinct banding pattern STS‐C04H910 and HVM67 are well‐suited for marker‐ assisted selection, enhanced backcrossing procedures and pyramiding of resistance genes.
Conical diffraction: observations and theory (2006)

Conical refraction was produced by a transparent biaxial crystal of KGd(WO 4 ) 2 illuminated by a laser beam. The ring patterns at different distances from the crystal were magnified and projected onto a screen, giving rings whose diameter was 265 mm. Comparison with theory revealed all predicted geometrical and diffraction features: close to the crystal, there are two bright rings of internal conical refraction, separated by the Poggendorff dark ring; secondary diffraction rings decorate the inner bright ring; as the distance from the crystal increases, the inner bright ring condenses onto an axial spot surrounded by diffraction rings. The scales of these features were measured and agreed well with paraxial theory; this involves a single dimensionless parameter ρ 0 , defined as the radius of the rings emerging from the crystal divided by the width of the incident beam. The different features emerge clearly in the asymptotic limit ρ 0 ≫1; in these experiments, ρ 0 =60.
Characterisation of a GII-4 norovirus variant-specific surface-exposed site involved in antibody binding (2009)

As predicted by our earlier study, significant amino acid changes at site A and site B give rise to GII-4 norovirus epidemic variants that are antibody escape mutants.
Expression of Endogenous Oncogenic<i>V600EB-raf</i>Induces Proliferation and Developmental Defects in Mice and Transformation of Primary Fibroblasts (2005)

Mutations of the human B-RAF gene are detected in approximately 8% of cancer samples, primarily in cutaneous melanomas (70%). The most common mutation (90%) is a valine-to-glutamic acid mutation at residue 600 (V600E; formerly V599E according to previous nomenclature). Using a Cre/Lox approach, we have generated a conditional knock-in allele of (V600E)B-raf in mice. We show that widespread expression of (V600E)B-Raf cannot be tolerated in embryonic development, with embryos dying approximately 7.5 dpc. Directed expression of mutant (V600E)B-Raf to somatic tissues using the IFN-inducible Mx1-Cre mouse strain induces a proliferative disorder and bone marrow failure with evidence of nonlymphoid neoplasia of the histiocytic type leading to death within 4 weeks of age. However, expression of mutant B-Raf does not alter the proliferation profile of all somatic tissues. In primary mouse embryonic fibroblasts, expression of endogenous (V600E)B-Raf induces morphologic transformation, increased cell proliferation, and loss of contact inhibition. Thus, (V600E)B-Raf is able to induce several hallmarks of transformation in some primary mouse cells without evidence for the involvement of a cooperating oncogene or tumor suppressor gene.
Nitric Oxide Synthase Is the Mediator of Late Preconditioning Against Myocardial Infarction in Conscious Rabbits (1998)

Taken together, these results indicate that in the conscious rabbit, the infarct-sparing effect of the late phase of ischemic PC is mediated by the activity of NOS and suggest that the specific isoform primarily responsible for this cardioprotective phenomenon is iNOS. Thus, NO appears to be a pivotal component of the pathophysiological cascade of late PC.
ChemInform Abstract: CHEMISTRY OF COORDINATED DINITROGEN PART 2, REACTIONS OF BIS(DINITROGEN) COMPLEXES OF MOLYBDENUM (1974)

Abstract 144 bei ‐78°C zum mer‐Komplex (IVa) oder bei (I Vb) bzw. fac‐Komplex (VI).
Overcoming antigenic diversity and improving vaccines using DNA shuffling and screening technologies (2004)

Viral, bacterial and parasitic pathogens have evolved multiple strategies to evade the immune response, facilitate transmission and establish chronic infections. One of the underlying strategies that pathogens have evolved is antigenic variation of immune response targets that reduce the affinity of antigen binding to antibodies and major histocompatability complex class I and II receptors. Vaccine candidates generally target a limited number of these antigen variants or combine antigens from several variants to include in multivalent vaccine formulations. DNA shuffling and screening technologies, also known as MolecularBreeding (Maxygen, Inc.) directed molecular evolution, have been successfully used to identify and develop novel and chimaeric vaccine candidates capable of inducing immune responses that recognise and control multiple antigenic variants. DNA shuffling and screening strategies also select vaccine candidates with improved immunogenicity, increased expression as recombinant polypeptides and improved growth of whole viruses in cell culture. As DNA shuffling and screening strategies can be applied to many pathogens, there remain numerous applications of DNA shuffling to solve challenging problems in vaccine process development and manufacture.
Transition metal-catalyzed C-C/C-N bond formation (2014)

from Simple Diols 3 Although cyclic imide derivatives have numerous applications, available synthetic methods from simple substrates are very limited. Traditionally, the general approaches are the dehydrative condensation of anhydrides with amines at high temperature, or in the presence of Lewis acids, 1,8 and the dehydrative cyclization of an amic acid with help of acidic reagents. 1,9 However, neither of the methods are atom economical and they always generate stoichiometric amount of by-products (Scheme 1.1). 10 Scheme 1.1 Recently, several novel and efficient approaches have been developed for the synthesis of cyclic imides. In 2003, Murahashi and co-worker reported an iridium-catalyzed 5
Diagnosys: automatic generation of a debugging interface to the Linux kernel (2012)

The Linux kernel does not export a stable, well-defined kernel interface, complicating the development of kernel-level services, such as device drivers and file systems. While there does exist a set of functions that are exported to external modules, this set of functions frequently changes, and the functions have implicit, ill-documented preconditions. No specific debugging support is provided.
Direct Fabrication of Super -Fine Wiring and Bumping by Using Inkjet process (2007)

A super-fine inkjet technology that enables fine pattern processing by super fine droplets measuring less than 1 micro-meter are developed. Direct drawing of metal wires having a width of just a few microns have we have been achieved by using a conductive paste which is made from nano-metal particles as an ink. Furthermore, direct forming of three-dimensional structures at any point on the substrate have been demonstrated, by taking advantage of the fast drying by such fine droplets. The process is simple and it can be carried out on the desktop in the air at room temperature. This technology should be useful from the keywords of current packaging trend of miniaturization and integration.
Concerning the relative importance of enantiomorphic site vs. chain end control in the stereoselective polymerization of lactides: reactions of (R,R-salen)- and (S,S-salen)–aluminium alkoxides LAlOCH<sub>2</sub>R complexes (R = CH<sub>3</sub>and S-CHMeCl) (2004)

The preparations and structures of LAlOCH(2)C(S)HMeCl, where L = (R,R) or (S,S)-N,N'-bis(3,5-di-tert-butyl-salicylidene)-1,2-cyclohexenediamino, are reported together with the respective LAlOEt compounds, and their reactivities toward L- and rac-lactides in various solvents reveal the surprising complexity of the stereopreference for the ring-opening event.
Tailoring Intermolecular Interactions for Efficient Room‐Temperature Phosphorescence from Purely Organic Materials in Amorphous Polymer Matrices (2014)

Herein we report a rational design strategy for tailoring intermolecular interactions to enhance room-temperature phosphorescence from purely organic materials in amorphous matrices at ambient conditions. The built-in strong halogen and hydrogen bonding between the newly developed phosphor G1 and the poly(vinyl alcohol) (PVA) matrix efficiently suppresses vibrational dissipation and thus enables bright room-temperature phosphorescence (RTP) with quantum yields reaching 24%. Furthermore, we found that modulation of the strength of halogen and hydrogen bonding in the G1-PVA system by water molecules produced unique reversible phosphorescence-to-fluorescence switching behavior. This unique system can be utilized as a ratiometric water sensor.
Pyramid: An Integrated Platform for Fragment‐based Drug Discovery (2006)

This chapter contains sections titled: Introduction The Pyramid Process Introduction Fragment Libraries Overview Physico-chemical Properties of Library Members Drug Fragment Library Privileged Fragment Library Targeted Libraries and Virtual Screening Quality Control of Libraries Fragment Screening X-ray Data Collection Automation of Data Processing Hits and Diversity of Interactions Example 1: Compound 1 Binding to CDK2 Example 2: Compound 2 Binding to p38α Example 3: Compound 3 Binding to Thrombin Pyramid Evolution – Integration of Crystallography and NMR NMR Screening Using Water-LOGSY Complementarity of X-ray and NMR Screening Conclusions Acknowledgments References
Spontaneous emission and optical gain characteristics of blue InGaAlN/InGaN quantum well structures with reduced internal field (2012)

Spontaneous emission and optical gain characteristics of blue InGaAlN/InGaN quantum well (QW) structures with reduced internal field were investigated by using the non-Markovian model with many-body effects. The spontaneous emission coefficient of the InGaAlN/InGaN system with reduced internal field is shown to be increased by 30% compared to that of the conventional InGaN/GaN system. This is mainly due to the increase in the optical matrix element by the reduced internal field effect. If the threshold optical gain is assumed to be about 13000cm−1, the InGaAlN/InGaN QW structure is expected to have smaller threshold current density the InGaN/GaN QW structure. In the case of the InGaAlN/InGaN system, the transition wavelength is a weak function of the carrier density.