gebhart/patrepeval huggingface dataset:
[Killer Ig-like receptor gene content diversity and haplotype analysis in Chinese Han population in Shanghai]. (2003)

These findings suggest that there are distinctive frequencies of KIR gene content, haplotype as well as genotype in Chinese Han population in Shanghai area.
Clinical Relevance of Dissolution Testing in Quality by Design (2008)

Quality by design (QbD) has recently been introduced in pharmaceutical product development in a regulatory context and the process of implementing such concepts in the drug approval process is presently on-going. This has the potential to allow for a more flexible regulatory approach based on understanding and optimisation of how design of a product and its manufacturing process may affect product quality. Thus, adding restrictions to manufacturing beyond what can be motivated by clinical quality brings no benefits but only additional costs. This leads to a challenge for biopharmaceutical scientists to link clinical product performance to critical manufacturing attributes. In vitro dissolution testing is clearly a key tool for this purpose and the present bioequivalence guidelines and biopharmaceutical classification system (BCS) provides a platform for regulatory applications of in vitro dissolution as a marker for consistency in clinical outcomes. However, the application of these concepts might need to be further developed in the context of QbD to take advantage of the higher level of understanding that is implied and displayed in regulatory documentation utilising QbD concepts. Aspects that should be considered include identification of rate limiting steps in the absorption process that can be linked to pharmacokinetic variables and used for prediction of bioavailability variables, in vivo relevance of in vitro dissolution test conditions and performance/interpretation of specific bioavailability studies on critical formulation/process variables. This article will give some examples and suggestions how clinical relevance of dissolution testing can be achieved in the context of QbD derived from a specific case study for a BCS II compound.
Botulinum Neurotoxin Serotypes Detected by Electrochemical Impedance Spectroscopy (2015)

Botulinum neurotoxin is one of the deadliest biological toxins known to mankind and is able to cause the debilitating disease botulism. The rapid detection of the different serotypes of botulinum neurotoxin is essential for both diagnosis of botulism and identifying the presence of toxin in potential cases of terrorism and food contamination. The modes of action of botulinum neurotoxins are well-established in literature and differ for each serotype. The toxins are known to specifically cleave portions of the SNARE proteins SNAP-25 or VAMP; an interaction that can be monitored by electrochemical impedance spectroscopy. This study presents a SNAP-25 and a VAMP biosensors for detecting the activity of five botulinum neurotoxin serotypes (A-E) using electrochemical impedance spectroscopy. The biosensors are able to detect concentrations of toxins as low as 25 fg/mL, in a short time-frame compared with the current standard methods of detection. Both biosensors show greater specificity for their compatible serotypes compared with incompatible serotypes and denatured toxins.
Investigations on conductivity anomalies in Li2O center dot 4MnO(1+x)center dot 4B(2)O(3) glasses (2001)

Glassy material Li2O . 4MnO(1+x) . 4B(2)O(3) (0 < x < 0.5) has been prepared by quenching the melt in air, and its electrical conduction behavior has been studied. Two conductivity anomalies are observed around the glass transition temperature. One appears in the dependence of the isothermal conductivity vs, the annealing time. This anomaly is attributed to the oxidation of Mn2+ by oxygen ions penetrating into the glass matrix, leading to the increase of the charge carrier density. The other anomaly is observed in the dependence of the conductivity vs, the temperature for different times of annealing. The abnormal increase and decrease of the conductivity vs, annealing time might result from a complicated structural variation in the glass. Below 200 degreesC, the conductivity obeys an Arrhenius relation. Above 350 degreesC, the formation of crystalline MnBO3 causes a conductivity decrease by one order of magnitude. The conductivity is enhanced by the redistribution of free volume between these two temperatures. (C) 2001 Elsevier Science B.V. All rights reserved.
Radioimmunoimaging of experimental thrombi in dogs using technetium-99m-labeled monoclonal antibody fragments reactive with human platelets. (1986)

Monoclonal antibody 50H.19, which reacts with human platelets, was converted to fragments, pretinned, and made into kits for subsequent radiolabeling with 99mTc. The antibody, which cross-reacts with dog platelets, was used to evaluate in vitro binding to blood clots and in vivo in experimental thrombi in dogs. After radiolabeling, 97.4 +/- 6.4% of the 99mTc was antibody-associated. The preparations retained immunoreactivity, as determined by: binding studies using whole blood and determining the ratio of cell-to-plasma radioactivity (ratios of 57.6-61.2) and binding of the antibody to clots (clot/serum ratios were 57.2-74.6%). Approximately 50% of the radioactivity was cleared from the blood in 3-6 min and 18-24% was excreted in urine within 3 hr. Experimental thrombi in dogs could be visualized consistently within 2-3 hr postinjection in peripheral veins and arteries, pulmonary arteries, and the right ventricle. In addition, damage to blood vessel intima without visible thrombi could also be detected. This method has the following advantages: short and simple pre-imaging preparation, and rapid visualization of thrombi with no need for blood-pool subtraction or delayed imaging.
Large Volume Flow Electroporation of mRNA: Clinical Scale Process (2012)

Genetic modification for enhancing cellular function has been continuously pursued for fighting diseases. Messenger RNA (mRNA) transfection is found to be a promising solution in modifying hematopoietic and immune cells for therapeutic purpose. We have developed a flow electroporation-based system for large volume electroporation of cells with various molecules, including mRNA. This allows robust and scalable mRNA transfection of primary cells of different origin. Here we describe transfection of chimeric antigen receptor (CAR) mRNA into NK cells to modulate the ability of NK cells to target tumor cells. High levels of CAR expression in NK cells can be maintained for 3-7 days post transfection. CD19-specific CAR mRNA transfected NK cells demonstrate targeted lysis of CD19-expressing tumor cells OP-1, primary B-CLL tumor cells, and autologous CD19+ B cells in in vitro assays with enhanced potency: >80% lysis at effector-target ratio of 1:1. This allows current good manufacturing practices (cGMP) and regulatory compliant manufacture of CAR mRNA transfected NK cells for clinical delivery.
Machine-to-man communication by speech part II (1968)

For several years, research has gone on in an attempt to develop a reading machine for the blind. Such a machine must be able to scan letters on a normal printed page, then recognize the scanned letters and punctuation, and finally convert the resultant character strings into an encoded form that may be perceived by some nonvisual sensory modality. Within recent years, at the Massachusetts Institute of Technology, an opaque scanner has been developed, and an algorithm for recognizing scanned letters has been devised. The output display can take many forms, but the form that we feel is best suited for acceptably high reading speeds and intelligibility is synthesized speech. Effort has recently been focused on the conversion of orthographic letter strings to synthesized speech.
Release of the cellular prion protein from cultured cells after loss of its glycoinositol phospholipid anchor (1993)

Secreted forms of the sialoglycoprotein designated cellular prion protein (PrPC) have been identified that cannot be explained by alternative splicing. We report that secreted forms of PrPC derive from precursors that are bound to the plasma membrane by glycoinositol phospholipid (GPI) anchors. Secreted PrPC slowly appeared in the culture medium of metabolically radiolabelled cells after incubations of 8-24 h. Digestion of nascent PrPC with phosphatidylinositol-specific phospholipase C (PIPLC) prevented the appearance of secreted PrPC. Secreted PrPC partitioned into the aqueous phase of Triton X-114 like PrpC-released PrPC. While the M(r) of PIPLC-released PrPC was reduced 2-4 kDa after treatment with aqueous hydroflouric acid, which removes the entire GPI anchor modification, the M(r) of secreted PrPC was unchanged. Both PIPLC-released and secreted PrPC were recognized by antiserum raised against a synthetic C-terminal peptide corresponding to residues 220-233 (amino acid 231 is the site of GPI attachment). We conclude that GPI-anchored PrPC is post-translationally processed to remove most, if not all, of the GPI modification and then shed into culture medium. Whether PrPC is shed after proteolysis near the C-terminus remains to be established. A minority of PrPC in normal Syrian hamster brain partitioned into the aqueous phase of Triton X-114 like shed PrPC, suggesting physiological significance.
Path Vector Face Routing: Geographic Routing with Local Face Information (2006)

Existing geographic routing algorithms depend on the planarization of the network connectivity graph for correctness, and the planarization process gives rise to a well-defined notion of "faces". In this paper, we demonstrate that we can improve routing performance by storing a small amount of local face information at each node. We present a protocol, path vector exchange (PVEX), that maintains local face information at each node efficiently, and a new geographic routing algorithm, greedy path vector face routing (GPVFR), that achieves better routing performance in terms of both path stretch and hop stretch than existing geographic routing algorithms by exploiting available local face information. Our simulations demonstrate that GPVFR/PVEX achieves significantly reduced path and hop stretch than greedy perimeter stateless routing (GPSR) and somewhat better performance than greedy other adaptive face routing (GOAFR+) over a wide range of network topologies. The cost of this improved performance is a small amount of additional storage, and the bandwidth required for our algorithm is comparable to GPSR and GOAFR+ in quasi-static networks.
Demo: DEMS (2017)

We present the demonstration of DEMS, a new multipath scheduler aiming at reducing the data chunk download time. DEMS consists of three key design decisions: (1) being aware of the chunk boundary and strategically decoupling the paths for chunk delivery, (2) ensuring simultaneous subflow completion at the receiver side, and (3) allowing a path to trade a small amount of redundant data for performance. We integrate the DEMS components into a holistic system and implement it on commodity mobile devices, where unmodified mobile applications can use DEMS to transmit data over multipath. We demonstrate the simple configuration of using DEMS over multipath, visualization of multipath scheduling, download time reduction of data chunks with DEMS over both emulated and real cellular/WiFi networks compared to default MinRTT scheduler, and application QoE improvement on mobile phones from DEMS.
On Re-Reading Marion Milner (2001)

Abstract Over a period of some sixty years Marion Milner published a series of books and papers that made a distinctive and valuable contribution to understanding the mental processes operative in human creativity. Milners writing on this subject constantly emphasised the wisdom of the unconscious mind and the power of symbols to transform and integrate experience. This article emerged out of the experience of rereading Marion Milners books and collected papers following her death in 1998. It examines the important but frequently unrecognised influence Milners writing has had upon art therapy and discusses some of the implications her thinking might have for art therapists working today. The development of Milners writing on the relationship between creativity and psychotherapeutic work is outlined, paying particular attention to her thinking on the nature and function of symbols, boundaries and inhibitions in the creative process.
Precipitate morphology in MnS-AlN-inhibited high permeability grain oriented silicon steel (1976)

A transmission electron microscope study of precipitation in an MnS-AlN-inhibited 3% silicon steel is described. The effects of various hot rolled band heat treatments are related to precipitate morphologies developed by subsequent cold rolling and recrystallization in a decarburizing anneal. The hot rolled band heat treatments consisted of solutioning at 1120°C, air cooling to selected temperatures and quenching. Quenching at temperatures higher than about 650°C resulted in a uniformly distributed fine structure (approx. 100Å) imaged by strain contrast and believed to be vacancy discs stabilized by carbon diffusion. The vacancy discs did not occur in hot rolled bands quenched from temperatures below 650°C. Cold rolled and recrystallized structures derived from high quench temperatures contained clusters of very fine precipitate particles. The clusters consisted mostly of spheroidal MnS particles with some angular AlN particles. The tendency for particle clustering decreased with decreasing quench temperature, and non-uniform coarsening of the MnS particles occurred both within clusters and from cluster to cluster. Quenching from 540°C and below resulted in essentially random particle distribution and in the more frequent occurrence of angular AlN particles. The absence of particle clusters in cold rolled and recrystallized structures corresponded approximately with the disappearance of vacancy discs as quench temperature was decreased in the original heat treatments.
A distinctive DNA methylation pattern in insufficient sleep (2019)

Short sleep duration or insomnia may lead to an increased risk of various psychiatric and cardio-metabolic conditions. Since DNA methylation plays a critical role in the regulation of gene expression, studies of differentially methylated positions (DMPs) might be valuable for understanding the mechanisms underlying insomnia. We performed a cross-sectional genome-wide analysis of DNA methylation in relation to self-reported insufficient sleep in individuals from a community-based sample (79 men, aged 39.3 ± 7.3), and in relation to shift work disorder in an occupational cohort (26 men, aged 44.9 ± 9.0). The analysis of DNA methylation data revealed that genes corresponding to selected DMPs form a distinctive pathway: "Nervous System Development" (FDR P value < 0.05). We found that 78% of the DMPs were hypomethylated in cases in both cohorts, suggesting that insufficient sleep may be associated with loss of DNA methylation. A karyoplot revealed clusters of DMPs at various chromosomal regions, including 12 DMPs on chromosome 17, previously associated with Smith-Magenis syndrome, a rare condition comprising disturbed sleep and inverse circadian rhythm. Our findings give novel insights into the DNA methylation patterns associated with sleep loss, possibly modifying processes related to neuroplasticity and neurodegeneration. Future prospective studies are needed to confirm the observed associations.
Outer Membrane Protein-Specific Monoclonal Antibodies Protect SCID Mice from Fatal Infection by the Obligate Intracellular Bacterial Pathogen <i>Ehrlichia chaffeensis</i> (2001)

Previous studies of Ehrlichia chaffeensis infection in the mouse have demonstrated that passive transfer of polyclonal Abs from resistant immunocompetent mice to susceptible SCID mice ameliorated infection and disease, even when Abs were administered during established infection. To identify particular Abs that could mediate bacterial clearance in vivo, E. chaffeensis-specific mAbs were generated and administered to infected SCID mice. Bacterial infection in the livers was significantly lowered after administration of either of two Abs of different isotypes (IgG2a and IgG3). Moreover, repeated administration of one Ab (Ec56.5; IgG2a) rescued mice from an otherwise lethal infection for at least 5 wk. Both protective Abs recognized the E. chaffeensis major outer membrane protein (OMP)-1g. Further studies revealed that both Abs recognized closely related epitopes within the amino terminus of the first hypervariable region of OMP-1g. Analyses of human sera showed that E. chaffeensis-infected patients also generated serological responses to OMP-1g hypervariable region 1, indicating that humans and mice recognize identical or closely related epitopes. These studies demonstrate that OMP-specific mAbs can mediate bacterial elimination in SCID mice, and indicate that Abs, in the absence of cell-mediated immunity, can play a significant role in host defense during infection by this obligate intracellular bacterium.
Poly(<scp>L</scp>‐lactide) Nanoparticles via Ring‐Opening Polymerization in Non‐aqueous Emulsion (2012)

Abstract The preparation of poly( L ‐lactide) nanoparticles via ring‐opening polymerization (ROP) of L ‐lactide is conducted in non‐aqueous emulsion. In this process, acetonitrile is dispersed in either cyclohexane or n ‐hexane as the continuous phase and stabilized by a PI‐ b ‐PEO, respectively, a PI‐ b ‐PS copolymer as emulsifier. The air and moisture sensitive N ‐heterocyclic carbene 1,3‐bis(2,4,6‐trimethylphenyl)‐2‐ididazolidinylidene (SIMes) catalyzes the polymerization of L ‐lactide at ambient temperatures. Spherical poly( L ‐lactide) nanoparticles with an average diameter of 70 nm and a tunable molecular weight are generated. Hence, the non‐aqueous emulsion technique demonstrates its good applicability toward the generation of well‐defined poly( L ‐lactide) nanoparticles under very mild conditions.
ChemInform Abstract: SYNTHESIS OF O‐SUBSTITUTED HYDROXYLAMINES (1975)

Abstract Zur Darstellung der O‐substituierten Hydroxylamine (V), die Histidin‐decarboxylaseinhibierende Wirksamkeit besitzen, werden die aus Hydroxyphthalimid (I) und Halogeniden (II) erhältlichen Verbindungen (III) nicht wie üblich mit Hydrazin, sondern vorteilhaft mit prim. Aminen (IV) dephthaloyliert; die Vorteile dieses Verfahrens bestehen in seiner breiten Anwendbarkeit, den milden Reaktionsbedingungen, hohen Ausbeuten sowie der′ Möglichkeit, auch O‐substituierte Hydroxylamine mit Hydrazinempfindlichen Gruppen darzustellen.
Performance model for characterizing AC modules and predicting their power (2015)

PV modules and their inverting electronics are becoming increasingly more integrated. When a PV module and microinverter are completely integrated a new class of PV system, the AC module, is created. Unfortunately, existing characterization and modeling techniques require separate characterization of PV and inverting components. Thus, existing methods are incapable of modeling AC modules. We have developed an empirical performance model capable of characterizing and modeling an AC module. The model is capable of predicting the active power from an AC module in a typical application with RMSE of approximately 1% of the reference power of the AC module. This paper describes the model form and presents the validation results in terms of model residuals.
Catheter-related sepsis (1990)

We studied the infectious risk of different methods of managing vascular catheters during long-term use. Consecutive surgical ICU patients requiring triple lumen catheters, pulmonary artery catheters, or arterial catheters for greater than 7 days were prospectively randomized to one of three management groups: a) percutaneous (PERC) puncture with every 7-day catheter change at a new site, b) no weekly change (NWC) with a new site when changed, or c) guidewire exchange (GWX) with every 7-day catheter change at the same site. In all groups, a catheter change was mandatory for a positive blood culture, skin site infection, or sepsis without a likely source. Cultures were obtained when clinically indicated and at the time of every catheter change. Catheter-related sepsis (CRS) was defined as a positive blood culture and catheter culture with the same organism. A total of 112 patients met evaluation criteria. There were no intergroup differences in age, primary diagnosis, severity of injury or illness, number of study days, number of protocol violations, route of catheterization, number of catheters present/patient day, catheter sepsis rate, or bacteremia rate. The NWC group demonstrated an increased number of days/catheter, fewer catheter/subcutaneous tract segment cultures/patient, and a reduced incidence of catheter tip colonization. These results occurred in a setting where the number of CRS episodes/patient was 0.17 for GWX, 0.22 for PERC, and 0.16 for NWC. We conclude that there is no difference in infectious risk between these three methods of long-term catheter management. The method with the least complications and expense should be used.(ABSTRACT TRUNCATED AT 250 WORDS)
Tensile strengths >4 GPa for lightguide fusion splices (1981)

In previous work, the authors obtained median tensile strengths for lightguide fusion splices of ~2.5 GPa by avoiding mechanical damage to the fibre surface. In the present work, values of ~4 GPa have been obtained by using a chlorine-hydrogen torch for splicing. This results in the removal or deactivation of surface hydroxyl groups, thereby reducing corrosion during splicing.
LFQC: a lossless compression algorithm for FASTQ files (2015)

rajasek@engr.uconn.edu.
The Tutorial System in the Harvard Medical School (1940)

Associate Professor of Medicine, Harvard Medical School and Physician to the Massachusetts General Hospital, Boston, Massachusetts
Model identification and attitude control for a micromechanical flying insect including thorax and sensor models (2004)

This paper describes recent developments on the model identification and attitude control system for a micromechanical flying insect (MFI). We include recently developed dynamical models for the thorax actuators and the various sensor models. Wing kinematic parameterization scheme was designed to generate feasible wing motions to decouple the body torques under the constraints of the thorax model. A nominal state-space LTI model in hover was identified through linear estimation and a LQR controller was designed to achieve stable hovering and steering maneuvers. Simulation results show satisfactory performance comparable to that of the real insects.
2-Phenylpyrazolo[1,5-a]pyrimidin-7-ones. A new class of nonsteroidal antiinflammatory drugs devoid of ulcerogenic activity (1983)

Syntheses of some pyrazolo[1,5-a]pyrimidines were performed in order to study the relationship between structural modifications on the parent 4,7-dihydro-2-phenylpyrazolo[1,5-a]pyrimidin-7-one (1) and their antiinflammatory properties. The modifications carried out were introduction and functionalization of a longer side chain at the 4-position, substitution of the hydrogen atom at the 3-position, and replacement of the phenyl group with a 4-methylphenyl, methyl, or hydrogen substituent. 4-Ethyl-4,7-dihydro-2-phenylpyrazolo [1,5-a]pyrimidin-7-one (3) showed the highest activity and a better therapeutic index than phenylbutazone and indomethacin, used as reference drugs. All other changes at the 3-, 5-, and 6-positions, as well as the replacement of the phenyl group at position 2, caused a marked decrease of activity. Compound 3 was found devoid of ulcerogenic activity and was probably endowed with antiulcerogenic properties.