gebhart/patrepeval huggingface dataset:
The pharmacokinetics, tolerability and pharmacodynamics of tucaresol (589C80; 4[2‐formyl‐3‐hydroxyphenoxymethyl] benzoic acid), a potential anti‐sickling agent, following oral administration to healthy subjects. (1993)

1. Tucaresol (589C80; 4[2-formyl-3-hydroxyphenoxymethyl] benzoic acid) interacts stoichiometrically with haemoglobin to increase oxygen affinity. By decreasing the proportion of insoluble deoxy sickle haemoglobin at capillary oxygen concentrations, tucaresol may be of therapeutic benefit in sickle cell anaemia. 2. In this study, which involved the first administration to man, the pharmacokinetics and pharmacodynamics of tucaresol were studied in healthy male volunteers following oral doses of 200-3600 mg. 3. Peak drug concentrations in plasma and erythrocytes were linearly related to dose; mean (s.d.) values were 95.8 (26.1) and 1035 (67) micrograms ml-1, respectively, at the highest dose. Median tmax in plasma was 6.5 h and in erythrocytes 24.5 h, when approximately 60% of the administered dose was in the target tissue. Plasma drug concentrations fell biexponentially with commencement of the apparent terminal elimination phase at approximately 24 h. The terminal elimination half-life from plasma increased with dose (r = 0.77; P < 0.0001) from 133-190 h at 400 mg to a mean (s.d.) of 289 (30) h at 3600 mg. Erythrocyte drug concentrations declined mono-exponentially with a half-life that was always shorter than the apparent terminal half-life in plasma: overall mean (95% CI) of t1/2 erythrocyte/t1/2 plasma ratio was 0.57 (0.53, 0.61). The erythrocyte AUC/plasma AUC ratio increased with dose (r = 0.67; P < 0.001). 4. The proportion of haemoglobin modified to a form with high oxygen affinity (%MOD) increased in a dose-related manner above doses of 800 mg reaching 19-26% after the 3600 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Promiscuous Expression of H2B-GFP Transgene in Hematopoietic Stem Cells (2008)

We observed promiscuous expression of the H2B-GFP transgene in the hematopoietic stem cell compartment of the bone marrow. This leaky expression prohibits the use of this model to study hematopoietic stem cells in vivo and careful characterization for each organ must be done if this transgenic system is to be used to isolate other prospective tissue stem cells.
Broadband Transparent Optical Phase Change Materials (2017)

We report a new group of optical phase change materials Ge-Sb-Se-Te (GSST) with low loss from telecom bands to LWIR. We further demonstrated GSST-integrated SiN photonics with significantly improved switching performance over conventional GST alloys.
Using recurrent neural networks toward black-box system anomaly prediction (2016)

Component based enterprise systems are becoming extremely complex in which the availability and usability are influenced intensively by the system's anomalies. Anomaly prediction is highly important for ensuring a system's stability, which aims at preventing anomaly from occurring through pre-failure warning. However, due to the system's complex nature and the noise from monitoring, capturing pre-failure symptoms is a challenging problem. In this paper, we present a sequential and an averaged recurrent neural networks (RNN) models for distributed systems and component based systems. Specifically, we use cycle representation to capture cyclical system behaviors, which can be used to improve prediction accuracy. The anomaly data used in the experiments is collected from RUBis, IBM System S, and the component based system of enterprise T. The experimental results show that our proposed methods can achieve high prediction accuracy with satisfying lead time. Our recurrent neural networks model also demonstrates time efficiency for monitoring large-scale systems.
Effects of molecular interface modification in hybrid organic-inorganic photovoltaic cells (2007)

We have systematically investigated the effects of surface modification of titania (TiO2) in hybrid TiO2∕regioregular poly(3-hexylthiophene) (P3HT) photovoltaic cells. By employing a series of para-substituted benzoic acids with varying dipoles and a series of multiply substituted benzene carboxylic acids, the energy offset at the TiO2∕polymer interface and thus the open-circuit voltage of devices can be tuned systematically by 0.25 V. Transient photovoltage measurements showed that the recombination kinetics was dominated by charge carrier concentration in these devices and were closely associated with the dark current. The saturated photocurrent of TiO2∕P3HT devices exhibited more than a twofold enhancement when molecular modifiers with large electron affinity were employed. The ability of modifiers to accept charge from polymers, as revealed in photoluminescence quenching measurement with blends of polymers, was shown to be correlated with the enhancement in device photocurrent. A planar geometry photoluminescence quenching measurement showed that TiO2 substrates modified by these same molecules that accept charge quenched more excitons in regioregular P3HT than bare TiO2 surfaces. An exciton diffusion length in P3HT as large as 6.5−8.5 nm was extracted. By measuring the external quantum efficiency (EQE) of working devices, it was found that all of the excitons that were quenched were accountable as extracted photocurrent. EQE was effectively increased from 5% to 10%−14% with certain surface modifiers; consequently exciton harvesting was more than doubled. The use of ruthenium (II) sensitizing dyes with good exciton harvesting property coupled with suppression of the recombination kinetics improved the efficiency of optimized bilayer TiO2∕P3HT devices from 0.34% to 0.6% under AM 1.5 solar illuminations. The implication of this work is directly relevant to the design of nanostructured bulk heterojunction inorganic-organic cells, in which efficient exciton harvesting and control of the recombination kinetics are key to achieving high efficiency.
Novel Tweezers for Biological Cells Using Piezoelectric Polylactic Acid Fibers (2005)

Abstract We fabricated poly-L-lactic acid (PLLA) fiber samples using high-speed spinning in order to improve their piezoelectricity. If an electric field is applied to the PLLA fiber in the direction perpendicular to its fiber axis, the PLLA fiber must be driven by the piezoelectric effect. We developed an effective method of applying an electric field to the PLLA fiber. As a result, we could drive the PLLA fiber by the shear piezoelectric effect under the application of ac voltage, and observed the bending motion of the entire PLLA fiber. Next, we have designed tweezers using a pair of PLLA fibers controlled by applied ac voltage, and have pursued the realization of PLLA fiber tweezers; finally, this was achived. On the basis of our experimental results, we believe that there is a high possibility of realizing the PLLA fiber tweezers for the manipulation of soft and minute samples such as biological cells.
107 Gb/s Coherent Optical OFDM Reception Using Orthogonal Band Multiplexing (2008)

We show the first 107 Gb/s coherent optical OFDM (CO-OFDM) reception using multiple orthogonal bands. The demonstrated system employs 2x2 MIMO-OFDM signal processing and achieves high spectral efficiency with direct-conversion at both transmitter and receiver.
Potent and Selective Antisense Oligonucleotides Targeting Single-Nucleotide Polymorphisms in the Huntington Disease Gene / Allele-Specific Silencing of Mutant Huntingtin (2011)

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild-type HTT protein is essential for development and has critical roles in maintaining neuronal health. Therapies for HD that reduce wild-type HTT may therefore generate unintended negative consequences. We have identified single-nucleotide polymorphism (SNP) targets in the human HD population for the disease-specific targeting of the HTT gene. Using primary cells from patients with HD and the transgenic YAC18 and BACHD mouse lines, we developed antisense oligonucleotide (ASO) molecules that potently and selectively silence mHTT at both exonic and intronic SNP sites. Modification of these ASOs with S-constrained-ethyl (cET) motifs significantly improves potency while maintaining allele selectively in vitro. The developed ASO is potent and selective for mHTT in vivo after delivery to the mouse brain. We demonstrate that potent and selective allele-specific knockdown of the mHTT protein can be achieved at therapeutically relevant SNP sites using ASOs in vitro and in vivo.
Empirical Predictions of Protein Conformation (1978)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Crystal Structure of Unmodified tRNAGln Complexed with Glutaminyl-tRNA Synthetase and ATP Suggests a Possible Role for Pseudo-Uridines in Stabilization of RNA Structure (1994)

tRNA(2Gln) made in vitro by transcription with T7 RNA polymerase does not contain the pseudouridines at positions 38, 39, and 55, the 4-thiouridine at position 8, or any of the methylated bases found in the tRNA(2Gln) made in vivo. Cocrystals of unmodified tRNA(2Gln) complexed with glutaminyl-tRNA synthetase from Escherichia coli are isomorphous with those of the complex with modified tRNA(2Gln). A difference electron density map between the complexes with modified and unmodified tRNAs calculated at 2.5-A resolution shows no differences in the protein or tRNA structures, except for some very small shifts in atoms contacting the thiol at the 4 position of uridine 8 that are required to accommodate the smaller oxygen in the unmodified tRNA. Perhaps the most functionally significant change in the unmodified tRNA is the absence of the specifically bound water molecules that are observed to cross-link the N5 of the pseudo-uridines to their 5' phosphate. This suggests a possible role for pseudouridinylation in stabilization of the tRNA through water-mediated linking of these modified bases to the backbone, which is consistent with the lower thermal stability of the unmodified tRNA. An identical water-bridging structure is possible at four of the five other psuedo-uridines in known tRNA structures.
DNA vaccines for transplantation (2010)

DNA vaccination could reduce the need for systemic immunosuppressants and be applied to prevention of chronic rejection, which remains a major barrier to successful allotransplantation.
KRAS Mutations and Sensitivity to Epidermal Growth Factor Receptor Inhibitors in Colorectal Cancer: Practical Application of Patient Selection (2009)

Recent retrospective evidence from several randomized studies has established that advanced colorectal cancer patients with tumors harboring a mutation in the KRAS gene do not derive benefit from the administration of epidermal growth factor receptor-directed monoclonal antibodies, such as cetuximab or panitumumab. This represents a paradigm-changing event and will have substantial impact on current and future anticancer drug development. These results add to the economic and ethical considerations involved in the development of novel targeted therapies and should increase our scrutiny of mechanisms of resistance and predictive biomarkers while in earlier developmental stages. In this article we will review the available clinical data, discuss the potential implications for future drug development in colorectal cancer, and provide a comprehensive overview of the technical aspects of KRAS mutation testing. In particular we aimed at enumerating the available procedures for mutation detection and their main characteristics, as well as comparing them from a clinical feasibility standpoint. While the true specificity and sensitivity of these methods have yet to be fully characterized, a better understanding of the differences between tests will be critical so that clinicians and pathologists can fully integrate this testing into the routine care of patients with colorectal cancer.
Intradermal Electroporation of Naked Replicon RNA Elicits Strong Immune Responses (2012)

RNA-based vaccines represent an interesting immunization modality, but suffer from poor stability and a lack of efficient and clinically feasible delivery technologies. This study evaluates the immunogenic potential of naked in vitro transcribed Semliki Forest virus replicon RNA (RREP) delivered intradermally in combination with electroporation. Replicon-immunized mice showed a strong cellular and humoral response, contrary to mice immunized with regular mRNA. RREP-elicited induction of interferon-γ secreting CD8+ T cells and antibody responses were significantly increased by electroporation. CD8+ T cell responses remained substantial five weeks post vaccination, and antigen-specific CD8+ T cells with phenotypic characteristics of both effector and central memory cells were identified. The immune response during the contraction phase was further increased by a booster immunization, and the proportion of effector memory cells increased significantly. These results demonstrate that naked RREP delivered via intradermal electroporation constitute an immunogenic, safe and attractive alternative immunization strategy to DNA-based vaccines.
Prevalence of HIV infection in childbearing women in the United States. Surveillance using newborn blood samples. (1991)

A national, population-based survey was initiated in 1988 to measure the prevalence of human immunodeficiency virus (HIV) infection in women giving birth to infants in the United States. Following standardized procedures, residual dried-blood specimens collected on filter paper for newborn metabolic screening were tested anonymously in state public health laboratories for maternal antibody to HIV. As of September 1990, annual survey data were available from 38 states and the District of Columbia. The highest HIV seroprevalence rates were observed in New York (5.8 per 1000), the District of Columbia (5.5 per 1000), New Jersey (4.9 per 1000), and Florida (4.5 per 1000). Nationwide, an estimated 1.5 per 1000 women giving birth to infants in 1989 were infected with HIV. Assuming a perinatal transmission rate of 30%, we estimate that approximately 1800 newborns acquired HIV infection during one 12-month period. Preventing transmission of HIV infection to women and infants is an urgent public health priority.
Maximizing Non-Monotone Submodular Functions (2007)

Submodular maximization generalizes many important problems including Max Cut in directed/undirected graphs and hypergraphs, certain constraint satisfaction problems and maximum facility location problems. Unlike the problem of minimizing submodular functions, the problem of maximizing submodular functions is NP-hard.
Production of Plaques in Monolayer Tissue Cultures by Single Particles of an Animal Virus (1952)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
The solution structure of the DNA-binding domain of Skn-1 (1998)

Skn-1 is a maternally expressed transcription factor that specifies the fate of certain blastomeres early in the development of Caenorhabditis elegans. It has been reported that the DNA-binding domain is a molten globule and that the structure cannot be defined because there are no long-range nuclear Overhauser effects (NOEs). Working with short Skn domain fragments and using 13C-labeled proteins, we have been able to identify 28 long-range NOEs that establish a tertiary fold for the Skn domain. The internal region of the Skn domain consists of three stable helices and one conformationally labile helix organized into a nascent helix-turn-helix-turn-helix-turn-helix motif. The N and C termini of the Skn domain are unstructured and emerge from the same end of the folded domain. This structure is consistent with biochemical data on binding of the Skn domain to DNA, which shows that the N and C termini bind in the adjacent minor and major grooves from the same face of the DNA helix. The NMR solution structure of the Skn domain should be useful for developing a complete understanding of the DNA recognition event, including any conformational changes that take place upon binding.
Worst-case optimal hidden-surface removal (1987)

An O( n 2 ) hidden-surface removal algorithm is shown. This is an improvement over the previous best worst-case performance of O( n 2 log n ). It has been established that the hidden-line and hidden-surface problems have an Ω( n 2 ) worst-case lower bound, so the algorithm is optimal. However, the algorithm is not output-size sensitive. Two corollaries to the result are (1) hidden-lines can be removed in optimal O( n 2 ) time, and (2) the portion of a 3-D polyhedron visible from a given interior point is constructible in optimal O( n 2 ) time.
Autotune (2018)

Machine learning applications often require hyperparameter tuning. The hyperparameters usually drive both the efficiency of the model training process and the resulting model quality. For hyperparameter tuning, machine learning algorithms are complex black-boxes. This creates a class of challenging optimization problems, whose objective functions tend to be nonsmooth, discontinuous, unpredictably varying in computational expense, and include continuous, categorical, and/or integer variables. Further, function evaluations can fail for a variety of reasons including numerical difficulties or hardware failures. Additionally, not all hyperparameter value combinations are compatible, which creates so called hidden constraints. Robust and efficient optimization algorithms are needed for hyperparameter tuning. In this paper we present an automated parallel derivative-free optimization framework called Autotune , which combines a number of specialized sampling and search methods that are very effective in tuning machine learning models despite these challenges. Autotune provides significantly improved models over using default hyperparameter settings with minimal user interaction on real-world applications. Given the inherent expense of training numerous candidate models, we demonstrate the effectiveness of Autotune's search methods and the efficient distributed and parallel paradigms for training and tuning models, and also discuss the resource trade-offs associated with the ability to both distribute the training process and parallelize the tuning process.
A Mr 46,000 human milk fat globule protein that is highly expressed in human breast tumors contains factor VIII-like domains. (1991)

The human milk fat globule has proved to be a good source of antigenic material for production of antibodies against surface components of breast epithelial cells. Monoclonal antibodies against one of the major components of the human milk fat globule, which identify a glycoprotein with an apparent molecular weight of 46,000, have been found to be useful for both breast cancer diagnosis and therapy. In order to characterize this Mr 46,000 glycoprotein, specific monoclonal antibodies were used to select complementary DNAs from a lambda gt11 expression library from lactating breast. The largest complementary DNA insert (BA46-1) was 1270 base pairs and encoded 217 amino acids. A single 2.2-kilobase RNA was specifically detected in a variety of carcinoma cell lines, using this complementary DNA probe, and it was overexpressed in some carcinoma lines. The mRNA levels correlated with the level of expression of the antigen in these cell lines as detected by Western blot analysis. Sequence analysis revealed strong homology of the Mr 46,000 glycoprotein with serum factors VIII and V, in the region implicated in phospholipid binding.
Isolation and Purification of Lutein from the Microalga Chlorella vulgaris by Extraction after Saponification (2002)

A simple and efficient method for the isolation and purification of lutein from the microalga Chlorella vulgaris was developed. Crude lutein was obtained by extraction with dichloromethane from the microalga after saponification. Partition values of lutein in the two-phase system of ethanol-water-dichloromethane at different ratios were measured by HPLC so as to assist the determination of an appropriate condition for washing water-soluble impurities in the crude lutein. Partition values of lutein in another two-phase system of ethanol-water-hexane at different ratios were also measured by HPLC for determining the condition for removing fat-soluble impurities. The water-soluble impurities in the crude lutein were removed by washing with 30% aqueous ethanol, and the fat-soluble impurities were removed by extraction with hexane. The final purity of lutein obtained was 90-98%, and the yield was 85-91%.
Minor Groove Binding of a Novel Tetracationic Diviologen (2006)

Novel tetracationic diviologen compounds of the general formula CH3(CH2)nV2+(CH2)6V2+(CH2)nCH3 (where V2+ = 4,4'-bipyridinium and n = 5 or 11) were investigated as electrochemical reporters of DNA duplex formation. These compounds bind to both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) when the DNA is either present in solution or immobilized at electrode surfaces. Binding to thiolated ssDNA and dsDNA immobilized at Au electrodes was characterized using the electrochemical response for the reduction of the V2+ state to the V+ (viologen radical cation) state. An analysis of the charge for this reduction provided isotherms and binding constants for binding of these diviologens to both forms of immobilized DNA. Saturation of the binding is achieved at solution concentrations near 20 microM. For both the n = 5 and 11 diviologens, binding to ssDNA is driven by electrostatic charge neutralization. For the n = 11 case, the binding is cooperative. In the presence of dsDNA, the n = 11 diviologen exhibits a unique reduction potential for the V2+/+ redox couple that is shifted approximately 100 mV negative of that in the presence of ssDNA. This new electrochemical signature is attributed to the reduction of viologen groups bound in the minor groove of the DNA duplex. For dsDNA in solution, an increase in the thermal denaturation temperature (Tm) from 60 to 66 degrees C as a function of the n = 11 diviologen concentration confirmed its interaction with the duplex. Circular dichroism (CD) spectroscopy also was used to investigate the binding of both the V2+ and V+ redox states of the n = 11 diviologen to dsDNA in solution. For the V+ state, a CD signal was observed that is consistent with the presence of face-to-face pi dimers of the viologen groups. This unambiguously demonstrates the binding of this redox state of the diviologen in the dsDNA minor groove and the formation of such dimers in the minor groove.
Growth ripples upon strained SiGe epitaxial layers on Si and misfit dislocation interactions (1994)

Ripple arrays are formed under certain growth conditions upon the surface of epitaxial Si1−xGex on Si, and their nature is examined in detail using transmission electron microscopy, atomic force microscopy, and x-ray diffraction measurements. The driving force for ripple formation on the strained layers is the lowering of the system free energy by partial elastic strain relief due to oscillatory lattice plane distortion. We present the first direct measurement of the lattice distortion and demonstrate that this corresponds to near-complete relaxation in the ripple peaks in a direction normal to the ripple rows. The additional compressive lattice plane distortion present at ripple troughs is also estimated and is likely to promote misfit dislocation nucleation. Surface faceting can reduce the energy of the configuration, allowing troughs to deepen and minimize the dislocation nucleation barrier. The way in which the ripple strain fluctuations couple to already formed underlying misfit dislocations (often pinned bunches) is also demonstrated.