gebhart/patrepeval huggingface dataset:
Cell surface glycoproteins involved in the stimulation of interleukin 1-dependent interleukin 2 production by a subline of EL4 thymoma cells. II. Structure, biosynthesis, and maturation. (1985)

In the present study, we examined the biosynthesis and the maturation of two distinct membrane glycoproteins detected by two monoclonal antibodies (RL388 and RL119), which were selected on the basis of their ability to stimulate the production of interleukin 2 by a subline of the murine EL4 thymoma. RL388 detected a disulfide-linked heterodimer complex (Mr = 130,000) composed of a glycosylated heavy (Mr = 86,000) and a nonglycosylated light (Mr = 39,000) subunit. The unglycosylated precursor of the heavy chain was a polypeptide of Mr = 57,500, which was converted upon maturation into a Mr = 73,000 core-glycosylated intermediate, and then into the Mr = 86,000 surface-expressed molecule. Partial endo-H digestion of the core-glycosylated form suggested the presence of four N-linked glycan units. The antibody reacted with a protein determinant expressed on the mature form as well as the unglycosylated precursor of the heavy chain. Moreover, both subunits assembled rapidly during biosynthesis, and the glycosylation of the heavy chain was not required for this association. Taken together, these data suggest that the antigen detected by RL388 may be the murine homologue of the human 4F2 antigen. The antigen identified by RL119 was a surface glycoprotein of Mr = 55,000 with three to five N-linked glycan units. The unglycosylated precursor polypeptide was of Mr = 29,000. The fully core-glycosylated form of Mr = 41,000, which was detected after inhibition of glucosidase I with 1-deoxynojirimycin, was converted into a Mr = 39,000 intermediate, and upon further trimming, into a Mr = 36,000 endo-H-sensitive form. The latter could be detected for chase periods of over several hours, thus suggesting a low rate of intracellular processing. The wide cellular distribution of the molecules identified by RL388 and RL119 and their preferential expression on the surface of growing cells suggests that they may be associated with cell activation events.
The possible role of myostatin in skeletal muscle atrophy and cachexia (2005)

The presence of sufficient skeletal muscle is of paramount importance for body function. Cachexia can be defined as a wasting syndrome describing the progressive loss of both adipose and skeletal muscle tissue in concert with severe injury, chronic or end-stage malignant and infectious diseases. Generally, cachexia predisposes to poor prognosis, co-morbidities and death. One signaling pathway possibly involved in muscle atrophy and cachexia is the myostatin cascade. This transforming growth factor-beta superfamily member myostatin is a strong candidate for regulating muscle mass, and is shown to inhibit muscle growth in different in vivo mammalian models. Overall, the modulation of the myostatin pathway seems interesting from the perspective of both pathology and sports medicine. Hence, myostatin signaling components and post-translational modulators are possible targets of pharmacological and other treatments against muscle loss, thus potentially contributing to the understanding and mitigation of muscle atrophies associated with inactivity, senescence and disease.
Peripheral blood RNA gene expression profiling in patients with bacterial meningitis (2013)

This study demonstrates that there is a very strong activation of immune response at the transcriptional level during BM and that the type of pathogen influences this transcriptional activation.
The Crystal Structure of AMP-Bound PDE4 Suggests a Mechanism for Phosphodiesterase Catalysis, (2003)

Cyclic nucleotide phosphodiesterases (PDEs) regulate the intracellular concentrations of cyclic 3',5'-adenosine and guanosine monophosphates (cAMP and cGMP, respectively) by hydrolyzing them to AMP and GMP, respectively. Family-selective inhibitors of PDEs have been studied for treatment of various human diseases. However, the catalytic mechanism of cyclic nucleotide hydrolysis by PDEs has remained unclear. We determined the crystal structure of the human PDE4D2 catalytic domain in complex with AMP at 2.4 A resolution. In this structure, two divalent metal ions simultaneously interact with the phosphate group of AMP, implying a binuclear catalysis. In addition, the structure suggested that a hydroxide ion or a water bridging two metal ions may serve as the nucleophile for the hydrolysis of the cAMP phosphodiester bond.
A FRET-Based Assay for the Identification and Characterization of Cereblon Ligands (2016)

Cereblon serves as an ubiquitin ligase substrate receptor that can be tuned toward different target proteins by various cereblon-binding agents. This offers one of the most promising avenues for targeted protein degradation in cancer therapy, but cereblon binding can also mediate teratogenic effects. We present an effective assay that is suited for high-throughput screening of compound libraries for off-target cereblon interactions but also can guide lead optimization and rational design of novel cereblon effector molecules.
Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems (1993)

An N⋅log(N) method for evaluating electrostatic energies and forces of large periodic systems is presented. The method is based on interpolation of the reciprocal space Ewald sums and evaluation of the resulting convolutions using fast Fourier transforms. Timings and accuracies are presented for three large crystalline ionic systems.
Peptide Macrocycle Inhibitor of Coagulation Factor XII with Subnanomolar Affinity and High Target Selectivity (2017)

Factor XII (FXII) is a plasma protease that has emerged in recent years as a potential target to treat or prevent pathological thrombosis, to inhibit contact activation in extracorporeal circulation, and to treat the swelling disorder hereditary angioedema. While several protein based inhibitors with high affinity for activated FXII (FXIIa) were developed, the generation of small molecule inhibitors has been challenging. In this work, we have generated a potent and selective FXIIa inhibitor by optimizing a peptide macrocycle that was recently evolved by phage display (K<sub>i</sub> = 0.84 ± 0.03 nM). A fluorine atom introduced in the para-position of phenylalanine enhanced the binding affinity as much as 10-fold. Furthermore, we improved the proteolytic stability by substituting the N-terminal arginine by norarginine. The resulting inhibitor combines high inhibitory affinity and selectivity with a good stability in plasma (K<sub>i</sub> = 1.63 ± 0.18 nM, >27 000-fold selectivity, t<sub>1/2</sub>(plasma) =16 ± 4 h). The inhibitor efficiently blocked activation of the intrinsic coagulation pathway in human blood ex vivo.
PEGylation of nanoparticles improves their cytoplasmic transport. (2007)

The efficacy of nucleus-targeted drug- or gene-carrying nanoparticles may be limited by slow transport through the molecularly crowded cytoplasm following endosome escape. Cytoskeletal elements and cellular organelles may pose steric and/or adhesive obstacles to the efficient intracellular transport of nanoparticles. To potentially reduce adhesive interactions of colloids with intracellular components, the surface of model nanoparticles was coated with polyethylene glycol (PEG). Subsequently, multiple-particle tracking (MPT) was used to quantify the cytoplasmic transport rates of particles microinjected into the cytoplasm of live cells. PEGylation increased average nanoparticle diffusivities by 100% compared to unPEGylated particles (time scale of 10 s) in live cells. Faster particle transport correlated with a marked decrease in the number of particles that underwent hindered transport, from 79.2% (unmodified) to 48.8% (PEGylated). This result adds to an impressive list of positive benefits associated with PEGylation of drug and gene delivery vectors.
Differential interleukin-1 elaboration by density-defined human monocyte subpopulations (1985)

Interleukin-1 (IL-1) is an important immunoregulatory peptide produced by monocytes and macrophages. Because mononuclear phagocytes are morphologically and functionally heterogeneous, we examined whether they differ in their ability to elaborate IL-1. We used discontinuous Percoll gradients to obtain five density-defined human blood monocyte subpopulations. Unfractionated monocytes and their subsets were compared for their ability to stimulate thymocyte proliferation. Supernatants obtained from the denser monocytes consistently contained more IL-1 activity than did supernatants from the less dense cells. This difference in IL-1 activity was the result of differences in IL-1 elaboration, not the selective production of an inhibitor of IL-1-induced thymocyte proliferation. These data demonstrate that density-defined human monocyte subpopulations differ in their capacity to elaborate IL-1.
Polarity and Velocity of Sliding Filaments: Control of Direction by Actin and of Speed by Myosin (1990)

Myosin filaments, which are responsible for a large repertoire of motile activities in muscle and nonmuscle cells, can translocate actin filaments both toward and away from their central bare zone. This bidirectional movement suggests that there is enough flexibility in the head portion of the tightly packed myosin molecules in the native myosin filaments to move actin filaments not only in the expected direction, but also in the direction opposite to that predicted by the regular structure of muscle--away from the center of the myosin filament.
Elevation localization and head-related transfer function analysis at low frequencies (2001)

Monaural spectral features due to pinna diffraction are the primary cues for elevation. Because these features appear above 3 kHz where the wavelength becomes comparable to pinna size, it is generally believed that accurate elevation estimation requires wideband sources. However, psychoacoustic tests show that subjects can estimate elevation for low-frequency sources. In the experiments reported, random noise bursts low-pass filtered to 3 kHz were processed with individualized head-related transfer functions (HRTFs), and six subjects were asked to report the elevation angle around four cones of confusion. The accuracy in estimating elevation was degraded when compared to a baseline test with wideband stimuli. The reduction in performance was a function of azimuth and was highest in the median plane. However, when the source was located away from the median plane, subjects were able to estimate elevation, often with surprisingly good accuracy. Analysis of the HRTFs reveals the existence of elevation-dependent features at low frequencies. The physical origin of the low-frequency features is attributed primarily to head diffraction and torso reflections. It is shown that simple geometrical approximations and models of the head and torso explain these low-frequency features and the corresponding elevations cues.
Chromatic dispersion compensation in coherent optical communications (1990)

Chromatic dispersion compensation techniques in coherent transmission systems are reviewed and discussed for potential feasibility. The key compensation device is the wideband delay equalizer. It is shown that stripline-type delay equalizers have the potential for compensating distortion up to 10 Gb/s using a conventional 1.3- mu m zero-dispersion single-mode fiber at 1.5 mu m. Chromatic dispersion is successfully compensated with a stripline delay for CPFSK transmission at 4 and 6 Gb/s over 200 km of 1.3- mu m zero-dispersion single-mode fiber at 1.55 mu m. The bandwidth requirement of the compensation techniques for heterodyne detection is more than 10 GHz. However, it is difficult to realize such broadband receivers. Therefore, phase diversity detection with dispersion compensation is a promising scheme.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The PiezoElectronic switch: A path to low energy electronics (2013)

The information age has produced astonishing improvements in compute power, but the current highly successful CMOS technology is running into power limitations. Computing takes up of order 5% of the US electricity production, power is now the primary limiting factor on clock speed, and power limits practical development of exascale computing facilities. CMOS power depends on voltage which is now limited by fundamental physics and cannot be further lowered by an engineering fix. A fundamentally new device concept is needed in order to take computing into a new lower power regime.
Ecology‐based screen identifies new metabolites from a Cordyceps‐colonizing fungus as cancer cell proliferation inhibitors and apoptosis inducers (2009)

Gliocladicillins A (1) and B (2) are effective anti-tumour agents in vitro and in vivo and should be further evaluated for their potential in clinical use.
Nano-volume plates with excellent optical properties for fast, inexpensive crystallization screening of membrane proteins (2003)

A simple convenient and low-cost glass-based plate for high-throughput screening of membrane protein crystallization is described. The plates are robust and reduce dramatically the amount of protein and precipitant solution used per crystallization trial, while offering excellent optical properties for the detection of micro-crystals and crystals of colorless proteins. The plates were developed primarily for crystallization of membrane proteins in lipidic mesophases. They can also be used in batch crystallization of soluble and membrane proteins.
Polarizerless Nanomaterial Doped Guest-Host LCD Exhibiting High Luminance and Good Legibility (2001)

Abstract A polarizerless reflective guest-host LCD, which exhibits high luminance and good legibility has been fabricate by using NLC with Δ ε < 0 that is doped with nanomaterial molecules, fullerene C60, and dichroic dye molecules, where the NLCs are homeotroptically aligned without rubbing. It is considered that the doped C60 molecules may play a role in reducing the order parameter of the host NLC, and in turn, the contrast ratio is enhanced.
GaN: Processing, defects, and devices (1999)

The role of extended and point defects, and key impurities such as C, O, and H, on the electrical and optical properties of GaN is reviewed. Recent progress in the development of high reliability contacts, thermal processing, dry and wet etching techniques, implantation doping and isolation, and gate insulator technology is detailed. Finally, the performance of GaN-based electronic and photonic devices such as field effect transistors, UV detectors, laser diodes, and light-emitting diodes is covered, along with the influence of process-induced or grown-in defects and impurities on the device physics.
Lithographic technique using radiation‐induced grafting of acrylic acid into poly(methyl methacrylate) films (1980)

Abstract A lithographic process is described which increases the sensitivity of polymers to electron beam irradiation. The free radicals and peroxides produced in a film of polymer by irradiation are used to initiate the grafting of a monomer to form a graft copolymer, the solubility of which may be higher or lower than that of the initial polymer. Acrylic acid has been grafted into poly(methyl methacrylate) films to produce a copolymer which is insoluble in the solvents of PMMA. The sensitivity of this negative system depends on the conditions of grafting and on the conditions of development. A sensitivity of 2.8 10 −8 C.cm −2 at 20 keV has been obtained.
Progression of brain atrophy in PSP and CBS over 6 months and 1 year (2016)

Volume loss is quantifiable over a period of 6 months in CBS and PSP. Future clinical trials may be able to combine CBS and PSP to measure therapeutic effects.
WDMA/subcarrier-FDMA lightwave networks: limitations due to optical beat interference (1991)

The authors present a general model of optical beat interference, and its contribution of channel outage in a WD-SFDMA (wavelength division-subcarrier frequency division multiple access) network. The probability of channel outage due to optical beat interference is determined from analysis and computer simulation for externally and directly modulated single-mode lasers. These results are used to calculate the ultimate limitation on the throughput and capacity of the network due to beat note interference, for a simple retransmission protocol. It is shown that, as more subcarrier channels are added, network capacity increases sublinearly and eventually saturates.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthetic Shutter Speed Imaging (2007)

Abstract Hand held long exposures often result in blurred photographs due to camera shake. Long exposures are desirable both for artistic effect and in low‐light situations. We propose a novel method for digitally reducing imaging artifacts, which does not require additional hardware such as tripods or optical image stabilization lenses. A series of photographs is acquired with short shutter times, stabilized using image alignment, and then composited. Our method is capable of reducing noise and blurring due to camera shake, while simultaneously preserving the desirable effects of motion blur. The resulting images are very similar to those obtained using a tripod and a true extended exposure.
Novel Therapies Focused on the High-Density Lipoprotein Particle (2014)

Cardiovascular disease (CVD) remains a major burden for morbidity and mortality in the general population, despite current efficacious low-density lipoprotein-cholesterol-lowering therapies. Consequently, novel therapies are required to reduce this residual risk. Prospective epidemiological studies have shown that high-density lipoprotein-cholesterol (HDL-C) levels are inversely correlated with cardiovascular disease risk, and this initiated the quest for HDL-C-increasing therapies. Consequently, several different targets in HDL metabolism have been identified. Initial studies addressing the effect of cholesteryl ester transfer protein inhibition on cardiovascular disease outcome have been discontinued for reasons of futility or increased mortality. As of yet, 2 cholesteryl ester transfer protein inhibitors are still in phase III studies. Other HDL-based interventions, such as apolipoprotein A1-based compounds, ABC-transporter upregulators, selective peroxisome proliferator-activated receptor modulators and lecithin-cholesterol acyltransferase-based therapy, hold great promise for the future. The aim of this review is to provide a comprehensive overview of HDL-targeted pharmaceutical strategies in humans, both in early development as well as in late stage clinical trials.
A new quality assessment parameter for optical coherence tomography (2006)

A quality index such as QI may permit automated objective and quantitative assessment of OCT image quality that performs similarly to an expert human observer.
Encapsidated adenovirus mini-chromosome-mediated delivery of genes to the retina: application to the rescue of photoreceptor degeneration (1998)

First (DeltaE1/E3) and second (DeltaE1+DeltaE2/E3/E4) generation adenovirus (Ad) vectors have been shown previously to be of limited use in the treatment of human genetic diseases due to the induction of a host cytotoxic T-cell mediated immune response against virally expressed genes. In addition, a limited cloning capacity of approximately 8 kb does not cater for the incorporation of large upstream sequences essential for regulated tissue-specific expression or inclusion of multiple gene-expression cassettes. In this study we have exploited our recently developed Ad-based vector, the encapsidated adenovirus mini-chromosome (EAM) from which all of the viral genes have been deleted. EAMs contain only the inverted terminal repeats required for replication and five cis -acting Ad encapsidation signals necessary for packaging. We have shown previously that EAMs can efficiently transduce a variety of cell types in vitro. In this study we demonstrate that EAMs can transduce and rescue cells from the neurosensory retina in vivo. EAM-mediated delivery of the beta subunit of cyclic GMP phosphodiesterase (PDE) cDNA to mice affected with retinal degeneration (rd) allows prolonged transgene expression and rescue of rod photoreceptor cells. RT-PCR analysis from the injected retina indicates that transgene products are present for at least 18 weeks post-injection. Both the alpha and beta subunits of PDE could be detected up to 90 days postnatal in EAM-injected rd retina by western analysis. A maximal PDE activity of 150 nm/min/mg was detected at 33 days postnatal. Examination of outer nuclear thickness showed significant differences up to 12 weeks post-injection. These results demonstrate an improved level of rescue over first-generation adenoviral vectors and suggest the possibility of successful EAM-mediated treatment of some retinal diseases in humans.
Activation Function 2 in the Human Androgen Receptor Ligand Binding Domain Mediates Interdomain Communication with the NH2-terminal Domain (1999)

Activation function 2 in the ligand binding domain of nuclear receptors forms a hydrophobic cleft that binds the LXXLL motif of p160 transcriptional coactivators. Here we provide evidence that activation function 2 in the androgen receptor serves as the contact site for the androgen dependent NH(2)- and carboxyl-terminal interaction of the androgen receptor and only weakly interacts with p160 coactivators in an LXXLL-dependent manner. Mutagenesis studies indicate that it is the NH(2)-/carboxyl-terminal interaction that is required by activation function 2 to stabilize helix 12 and slow androgen dissociation critical for androgen receptor activity in vivo. The androgen receptor recruits p160 coactivators through its NH(2)-terminal and DNA binding domains in an LXXLL motif-independent manner. The results suggest a novel function for activation function 2 and a unique mechanism of nuclear receptor transactivation.
Psilocybin-Occasioned Mystical Experiences in the Treatment of Tobacco Addiction (2015)

Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior, attitudes, and values, and increases in the personality domain of openness. In an open-label pilot-study of psilocybin-facilitated smoking addiction treatment, 15 smokers received 2 or 3 doses of psilocybin in the context of cognitive behavioral therapy (CBT) for smoking cessation. Twelve of 15 participants (80%) demonstrated biologically verified smoking abstinence at 6-month follow-up. Participants who were abstinent at 6 months (n=12) were compared to participants still smoking at 6 months (n=3) on measures of subjective effects of psilocybin. Abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience. No significant differences in general intensity of drug effects were found between groups, suggesting that mystical-type subjective effects, rather than overall intensity of drug effects, were responsible for smoking cessation. Nine of 15 participants (60%) met criteria for "complete" mystical experience. Smoking cessation outcomes were significantly correlated with measures of mystical experience on session days, as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions. These results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment.