gebhart/patrepeval huggingface dataset:
Cinanserin Is an Inhibitor of the 3C-Like Proteinase of Severe Acute Respiratory Syndrome Coronavirus and Strongly Reduces Virus Replication In Vitro (2005)

The 3C-like proteinase (3CLpro) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for anti-SARS-CoV drugs due to its crucial role in the viral life cycle. In this study, a database containing structural information of more than 8,000 existing drugs was virtually screened by a docking approach to identify potential binding molecules of SARS-CoV 3CLpro. As a target for screening, both a homology model and the crystallographic structure of the binding pocket of the enzyme were used. Cinanserin (SQ 10,643), a well-characterized serotonin antagonist that has undergone preliminary clinical testing in humans in the 1960s, showed a high score in the screening and was chosen for further experimental evaluation. Binding of both cinanserin and its hydrochloride to bacterially expressed 3CLpro of SARS-CoV and the related human coronavirus 229E (HCoV-229E) was demonstrated by surface plasmon resonance technology. The catalytic activity of both enzymes was inhibited with 50% inhibitory concentration (IC50) values of 5 microM, as tested with a fluorogenic substrate. The antiviral activity of cinanserin was further evaluated in tissue culture assays, namely, a replicon system based on HCoV-229E and quantitative test assays with infectious SARS-CoV and HCoV-229E. All assays revealed a strong inhibition of coronavirus replication at nontoxic drug concentrations. The level of virus RNA and infectious particles was reduced by up to 4 log units, with IC50 values ranging from 19 to 34 microM. These findings demonstrate that the old drug cinanserin is an inhibitor of SARS-CoV replication, acting most likely via inhibition of the 3CL proteinase.
Ultra-sparse AC-link converters (2013)

Due to their remarkable merits, the soft-switching ac-link universal power converters have received noticeable attention during the last few years. These converters, which can appear as dc-dc, dc-ac, ac-dc, or ac-ac, are compact, reliable, and expected to offer longer life time compared to the other types of converters. However, they require more switches, which make the control process more involved. The sparse ac-link buck-boost converters were proposed to partially solve this problem. The sparse configuration reduces the number of switches from 24 to 20 in a three-phase ac-ac configuration. This paper proposes a modified configuration, which further reduces the number of switches without changing the principles of operation. This converter, which is named Ultra-Sparse ac-Link Buck-Boost converter, reduces the number of switches from 24 to 16, in a three phase ac to ac case, and from 16 to 10, in a dc to three-phase ac configuration. The proposed converter is applicable to systems with unidirectional flow of power, such as PV and wind power generation. Despite reducing the number of switches, the partial resonance time, during which no power is transferred, is as short as the original configuration. The proposed converter is expected to offer higher reliability compared to the original converter; and higher reliability and efficiency compared to the sparse configuration. Another important feature of this configuration is that it can be fabricated by IGBT modules, which are more compact and more cost-effective compared to the discrete devices. This paper presents the principles of the operation of this configuration, and compares the efficiency, the failure rate and the current rating of the switches in the ultra-sparse, sparse and original configurations. Moreover, it evaluates the performance of the proposed converter through simulation and experiment.
Valley splittings in Si/SiGe quantum dots with a germanium spike in the silicon well (2021)

Silicon-germanium heterostructures have successfully hosted quantum dot qubits, but the intrinsic near-degeneracy of the two lowest valley states poses an obstacle to high-fidelity quantum computing. We present a modification to the Si/SiGe heterostructure by the inclusion of a spike in germanium concentration within the quantum well in order to increase the valley splitting. The heterostructure is grown by chemical vapor deposition and magnetospectroscopy is performed on gate-defined quantum dots to measure the excited state spectrum. We demonstrate a large and widely tunable valley splitting as a function of applied vertical electric field and lateral dot confinement. We further investigate the role of the germanium spike by means of tight-binding simulations in single-electron dots and show a robust doubling of the valley splitting when the spike is present, as compared to a standard (spike-free) heterostructure. This doubling effect is nearly independent of the electric field, germanium content of the spike, and spike location. This experimental evidence of a stable, tunable quantum dot, despite a drastic change to the heterostructure, provides a foundation for future heterostructure modifications.
Melt processable cellulose fibres engineered for replacing oil-based thermoplastics (2023)

If cellulosic materials are to replace materials derived from non-renewable resources, it is necessary to overcome intrinsic limitations such as fragility, permeability to gases, susceptibility to water vapour and poor three-dimensional shaping. Novel properties or the enhancement of existing properties are required to expand the applications of cellulosic materials and will create new market opportunities. Here we have overcome the well-known restrictions that impede melt-processing of high cellulose content composites. Cellulose fibres, partially derivatised to dialcohol cellulose, have been used to manufacture three-dimensional high-density materials by conventional melt processing techniques, with or without the addition of a thermoplastic polymer. This work demonstrates the use of melt processable chemically modified cellulose fibres in the preparation of a new generation of highly sustainable materials with tuneable properties that can be tailored for specific applications requiring complex three-dimensional parts.
GONAD: A Novel CRISPR/Cas9 Genome Editing Method that Does Not Require Ex Vivo Handling of Embryos (2016)

Transgenic technologies used for creating a desired genomic change in animals involve three critical steps: isolation of fertilized eggs, microinjection of transgenic DNA into them and their subsequent transfer to recipient females. These ex vivo steps have been widely used for over 3 decades and they were also readily adapted for the latest genome editing technologies such as ZFNs, TALENs, and CRISPR/Cas9 systems. We recently developed a method called GONAD (Genome editing via Oviductal Nucleic Acids Delivery) that does not require all the three critical steps of transgenesis and therefore relieves the bottlenecks of widely used animal transgenic technologies. Here we provide protocols for the GONAD system.
The Effect of SHB Gene Polymorphisms on Ovarian Response and Oocyte Maturation in IVF (2014)

Infertility affects 15 % of couples, which corresponds to 60 - 80 million worldwide. The microenvironments in which the oocyte, embryo and fetus mature are vital to the establishment and development of a healthy pregnancy. Different biological systems, such as angiogenesis, the immune system and apoptosis need to be adequately regulated for pregnancy to occur and progress normally. The overall aim of this thesis was to investigate the impact of Histidine-rich glycoprotein (HRG) and Src homology 2 domain-containing adapter protein B (SHB) on human female fertility.HRG is a plasma protein that regulates angiogenesis, the immune system, coagulation/fibrinolysis and apoptosis, by building complexes with various ligands. The impact of HRG on fertility is studied here for the first time. HRG is present in follicular fluid, the Fallopian tube, endometrium, myometrium and placenta. HRG distribution within embryo nuclei depends on developmental stage. Blastocysts express and secrete HRG. The HRG C633T single nucleotide polymorphism (SNP) appears to affect the chance of pregnancy and, correspondingly, parameters associated with pregnancy in IVF. Additionally, this HRG genotype may increase the risk in IVF of only developing embryos unfit for transfer.SHB is an adaptor protein involved in intracellular signaling complexes that regulate angiogenesis, the immune system and cell proliferation/apoptosis. Shb knockout mice have altered oocyte/follicle maturation and impaired embryogenesis. The impact of three SHB polymorphisms (rs2025439, rs13298451 and rs7873102) on human fertility is studied for the first time. The SNP prevalences did not differ between infertile and fertile women. BMI, gonadotropin dosages, the percentage of immature oocytes, the number of fertilized oocytes, the percentage of good-quality embryos and the day of embryo transfer seems to be affected by SHB genotype.In conclusion, HRG and SHB appear to influence female fertility. They are potential biomarkers that might be used for predicting pregnancy chance in infertile women. Knowledge of these genotypes may improve patient counseling and individualization of treatment.
A four gene signature predicts benefit from anthracyclines: evidence from the BR9601 and MA.5 clinical trials (2015)

Chromosome instability (CIN) in solid tumours results in multiple numerical and structural chromosomal aberrations and is associated with poor prognosis in multiple tumour types. Recent evidence demonstrated CEP17 duplication, a CIN marker, is a predictive marker of anthracycline benefit. An analysis of the BR9601 and MA.5 clinical trials was performed to test the role of existing CIN gene expression signatures as predictive markers of anthracycline sensitivity in breast cancer. Univariate analysis demonstrated, high CIN25 expression score was associated with improved distant relapse free survival (DRFS) (HR: 0.74, 95% CI 0.54-0.99, p = 0.046). High tumour CIN70 and CIN25 scores were associated with aggressive clinicopathological phenotype and increased sensitivity to anthracycline therapy compared to low CIN scores. However, in a prospectively planned multivariate analysis only pathological grade, nodal status and tumour size were significant predictors of outcome for CIN25/CIN70. A limited gene signature was generated, patients with low tumour CIN4 scores benefited from anthracycline treatment significantly more than those with high CIN4 scores (HR 0.37, 95% CI 0.20-0.56, p = 0.001). In multivariate analyses the treatment by marker interaction for CIN4/anthracyclines demonstrated hazard ratio of 0.35 (95% CI 0.15-0.80, p = 0.012) for DRFS. This data shows CIN4 is independent predictor of anthracycline benefit for DRFS in breast cancer.
Studies of the Interaction between Human Protein S and Human C4b-Binding Protein Using Deletion Variants of Recombinant Human Protein S (1994)

Human protein S interacts noncovalently with human C4b-binding protein (C4BP). We have studied this interaction using deletion variants of recombinant human protein S. Two deletion variants were constructed by restriction enzyme digestion and in vitro site-specific mutagenesis of the human protein S cDNA. The variants were stably expressed in C127 cells. Recombinant proteins were purified using Fast Flow Q anion-exchange chromatography. The activated protein C (APC) cofactor activity, C4BP binding properties and reactivity to different monoclonal antibodies against human protein S were examined. The first variant (E variant), which has a deletion of the third epidermal growth factor (EGF)-like domain (deletion of exon VII, corresponding to amino acid residues ASP-160 to Asp-202) expresses normal APC cofactor activity in a plasma system. This activity was inhibited by the addition of purified C4BP. The second variant (L variant), which has a deletion of the C-terminal loop of the sex hormone binding globulin (SHBG)-like domain (deletion of exon XV, corresponding to amino acid residues Asp-583 to Ser-635) also expresses normal APC cofactor activity in plasma. This activity could only be partially inhibited by the addition of purified C4BP. Binding of the recombinant proteins to C4BP was studied in a system using purified proteins. The E variant binds to C4BP with the same affinity similar as recombinant wild type protein S (apparent Kd approximately 10(-10) M). The L variant, however, shows a markedly reduced affinity for binding to C4BP (apparent Kd approximately 10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Nonpolar Interactions of Thrombin S‘ Subsites with Its Bivalent Inhibitor:  Methyl Scan of the Inhibitor Linker (1997)

We have designed bivalent thrombin inhibitors, consisting of a nonsubstrate type active site blocking segment, a hirudin-based fibrinogen recognition exosite blocking segment, and a linker connecting these segments. The inhibition provided by the bivalent inhibitors with various linker lengths revealed that a minimum of 15 atoms was required for simultaneous binding of the two blocking segments of the inhibitor to thrombin without significant distortion. The crystal structure of the inhibitors with a 16-atom linker showed some conformational flexibility in the linker portion which still lies deep in the groove joining the active site and the fibrinogen recognition exosite. Since the thrombin S' subsites are not well characterized, we designed a new strategy to search for possible nonpolar interactions between the linker and the thrombin S' subsites. This strategy, the "methyl scan", is based on the incorporation of a methyl side chain at each atom position of the linker by using sarcosine, D,L-alanine, D,L-3-aminoisobutyric acid, or N-methyl-beta-alanine. The methyl groups on the second and the eighth atom positions of the linker, which correspond to the side chains of the P1' and the P3' residues, respectively, improved the affinity of the inhibitors significantly. Further study of the stereospecificity showed that L-Ala at the P1' residue and D-Ala at the P3' residue preferably improved the affinity of the inhibitors 20- and 25-fold, respectively. Molecular modeling calculations using a methyl probe were also carried out to identify favorable nonpolar interacting sites on the thrombin surface. Two sites were identified in the vicinity of the P1' and the P3' residues, supporting the validity of the methyl scan method. Thus, this study has improved our understanding of the interactions taking place in this groove. In particular, we have been able to show that some specific structural features, such as hydrophobic complementarity between the linker and the thrombin S' subsites, could be exploited and make these inhibitors trivalent.
A rapid optical method for the determination of stress-optical constants of optically isotropic and anisotropic materials (1976)

A novel and rapid method for the evaluation of the stress-optical constants, with high accuracy, and furthermore, of the principal stresses in plane-stress fields, is developed. A monochromatic source is used. A collimated light beam incident at the tip of a crack, which exists at the edge of a thin plate under plane-stress conditions, forms a caustic projected on a screen placed at either side of the plate. Loading of the specimen will increase the size of the constraint zone and consequently the size of the caustic until it becomes measurable with conventional tools and with high accuracy. The ratio of the size of the two caustics, one obtained with the transmitted-shadow method and the other obtained with the reflected-shadow method, will give the stress-optical constants directly, for optically isotropic and anisotropic materials, with the use of a chart which is also developed by the authors.
Heating asymmetry induced by tunneling current flow in magnetic tunnel junctions (2012)

In this work, exchange bias was used as a probe to characterise the temperature profile induced by the inelastic relaxation of electrons tunnelling across a MgO barrier. Thermally assisted magnetic random access memory (TA-MRAM) cells comprising a magnetic tunnel junction (MTJ) with a reference pinned layer and a FeMn exchange biased storage layer were used. The pinning direction of the ferromagnetic storage layer is reversed when heated above the blocking temperature of the antiferromagnetic layer (FeMn). The power density required to reach this blocking temperature in the FeMn layer depends on the current polarity, indicating that the heat source term associated with the current flowing through the barrier depends itself on the current direction in contrast to simple Joule heating. This effect is due to the mechanism of energy dissipation in tunnelling. The tunnelling itself is ballistic i.e., without dissipation. However, after tunnelling, the hot electrons very quickly relax to the Fermi energy thereby loosing their excess energy in the receiving electrode. Therefore, the heat is essentially generated on one side of the barrier so that the whole profile of temperature throughout the pillar depends on the current direction. Full 3D thermal simulations also confirmed the temperature profile asymmetry. The proper choice of heating current direction (i.e., voltage polarity applied to the MTJ) can yield a reduction of about 10% in the heating power density required to enable writing in thermally assisted MRAM cells.
Optimal receive array beamforming for non-collaborative MIMO space division multiple access (2010)

In this paper, multi-user multiple input multiple output (MIMO) beamforming techniques with reduced overhead compared to hitherto known works are examined. In previous works, the subscriber station (SS) feeds back the entire channel matrix to the base station (BS) and the BS designs its zero-forcing transmit beamformer and each user's receive beamformer, and feeds forward each user its respective receive beamformer. In this paper, each SS designs its receive beamformer using only its own channel and independent of the other user's channels and feeds back only a vector this framework is called non-collaborative. Assuming zero-forcing beamforming (ZFBF) with a single stream to each SS, we derive the optimal receive beamformer using the average SNR metric and determine the feedback vector based on this optimal receive beamformer. We show that the average receive SNR per user degrades linearly with increasing number of users assuming isotropically distributed MIMO channels and that the dominant right singular vector of the channel matrix is the optimal SS receive beamformer. This optimality holds even when the MIMO channels are correlated. Furthermore, we propose a receive beamformer design in the presence of external interference which can be caused due to aggressive time-frequency reuse in neighboring cells.
57.3: Adaptive Digital Video Format Converter IC Featuring Qdeo True Color and Natural Depth Expansion (2009)

Abstract Today's consumer has access to a wide variety of video sources, including traditional broadcast and packaged media sources as well as internet sources like YouTube, Hulu and iTunes. These video sources have a variety of resolutions and usually a lot of artifacts. Furthermore, they all have limited gray‐scales of 256 levels or less, resulting in contouring artifacts. On the other hand displays continue to increase in bit‐depth, size, and resolution, with 10‐bit and 12‐bit panels increasingly common and 4K×2K displays starting to enter the high‐end. This paper describes a new digital video format converter IC featuring proprietary Qdeo video processing that bridges this big “color‐gap” between video sources and video displays.
Complete Genome Sequence of a Channel Catfish Epidemic Isolate, Aeromonas hydrophila Strain ML09-119 (2013)

Aeromonas hydrophila is a Gram-negative, rod-shaped, mesophilic bacterium that infects both aquatic poikilothermic animals and mammals, including humans. Here, we present the complete genome sequence of Aeromonas hydrophila strain ML09-119, which represents a clonal group of A. hydrophila isolates causing outbreaks of bacterial septicemia in channel catfish since 2009.
Metabolic Engineering of <i>Corynebacterium glutamicum</i> for <scp>l</scp> -Serine Production (2005)

Although L-serine proceeds in just three steps from the glycolytic intermediate 3-phosphoglycerate, and as much as 8% of the carbon assimilated from glucose is directed via L-serine formation, previous attempts to obtain a strain producing L-serine from glucose have not been successful. We functionally identified the genes serC and serB from Corynebacterium glutamicum, coding for phosphoserine aminotransferase and phosphoserine phosphatase, respectively. The overexpression of these genes, together with the third biosynthetic serA gene, serA(delta197), encoding an L-serine-insensitive 3-phosphoglycerate dehydrogenase, yielded only traces of L-serine, as did the overexpression of these genes in a strain with the L-serine dehydratase gene sdaA deleted. However, reduced expression of the serine hydroxymethyltransferase gene glyA, in combination with the overexpression of serA(delta197), serC, and serB, resulted in a transient accumulation of up to 16 mM L-serine in the culture medium. When sdaA was also deleted, the resulting strain, C. glutamicum delta sdaA::pK18mobglyA'(pEC-T18mob2serA(delta197)CB), accumulated up to 86 mM L-serine with a maximal specific productivity of 1.2 mmol h(-1) g (dry weight)(-1). This illustrates a high rate of L-serine formation and also utilization in the C. glutamicum wild type. Therefore, metabolic engineering of L-serine production from glucose can be achieved only by addressing the apparent key position of this amino acid in the central metabolism.
Classifying prosthetic use via accelerometry in persons with transtibial amputations (2013)

Knowledge of how persons with amputation use their prostheses and how this use changes over time may facilitate effective rehabilitation practices and enhance understanding of prosthesis functionality. Perpetual monitoring and classification of prosthesis use may also increase the health and quality of life for prosthetic users. Existing monitoring and classification systems are often limited in that they require the subject to manipulate the sensor (e.g., attach, remove, or reset a sensor), record data over relatively short time periods, and/or classify a limited number of activities and body postures of interest. In this study, a commercially available three-axis accelerometer (ActiLife ActiGraph GT3X+) was used to characterize the activities and body postures of individuals with transtibial amputation. Accelerometers were mounted on prosthetic pylons of 10 persons with transtibial amputation as they performed a preset routine of actions. Accelerometer data was postprocessed using a binary decision tree to identify when the prosthesis was being worn and to classify periods of use as movement (i.e., leg motion such as walking or stair climbing), standing (i.e., standing upright with limited leg motion), or sitting (i.e., seated with limited leg motion). Classifications were compared to visual observation by study researchers. The classifier achieved a mean +/- standard deviation accuracy of 96.6% +/- 3.0%.
Irradiance rigs (2010)

When precomputed lighting is generated for static scene elements, the incident illumination on dynamic objects must be computed in a manner that is efficient and that faithfully captures the near- and far-field variation of the environment's illumination. Depending on the relative size of dynamic objects, as well as the number of lights in the scene, previous approaches fail to adequately sample the incident lighting and/or fail to scale. We present a principled, error-driven approach for dynamically transitioning between near- and far-field lighting. A more accurate model for sampling near-field lighting for disk sources is introduced, as well as far-field sampling and interpolation schemes tailored to each dynamic object. Lastly, we apply a flexible reflectance model to the computed illumination.