gebhart/patrepeval huggingface dataset:
Constitutively active cAMP receptor mutants dominantly inhibit receptor-mediated signaling pathways in Dictyostelium discoideum (2002)

Dictyostelium, a soil amoeba, is able to develop from free-living cells to multicellular fruiting bodies upon starvation using extracellular cAMP to mediate cell-cell communication, chemotaxis and developmental gene expression. The seven transmembrane G protein-coupled cAMP receptor-1 (cAR1) mediated responses, such as the activation of adenylyl cyclase and guanylyl cyclase, are transient, due to the existence of poorly understood adaptation mechanisms. For this dissertation, the powerful genetics of the Dictyostelium system was employed to study the adaptation mechanism of cAR1-mediated cAMP signaling as well as mechanisms intrinsic to cAR1 that regulate its activation. We proposed that constitutively active cAR1 would cause constant adaptation, thus inhibiting downstream pathways that are essential for aggregation and development. Therefore, a screen for dominant negative cAR1 mutants was undertaken to identify constitutively active receptor mutants. Three dominant negative cAR1 mutants were identified. All appear to be constitutively active receptor mutants because they are constitutively phosphorylated and possess high affinity for cAMP. Biochemical studies showed that these mutant receptors prevented the activation of downstream effectors, including adenylyl and guanylyl cyclases. In addition, these cells also were defective in cAMP chemotaxis and cAR1-mediated gene expression. These findings suggest that the mutant receptors block development by constantly activating multiple adaptation pathways. Sequence analysis revealed that these mutations (I104N, L100H) are clustered in a conserved region of the third transmembrane helix (TM3) of cAR1. To investigate the role of this region in receptor activation, one of these residues, I104, was mutated to all the other 19 possible amino acids. We found that all but the most conservative substitutions increase the receptor's affinity about 20- to 70-fold. However, only highly polar substitutions of I104, particularly basic residues, resulted in receptors that are constitutively phosphorylated and dominantly inhibit development, suggesting that highly polar substitutions not only disrupt an interaction constraining the receptor in its low-affinity, inactive state but also promote an additional conformational change that resembles the ligand-bound conformation. Our findings suggest that I104 plays a specific role in constraining the receptor in its inactive state and that substituting it with highly polar residues results in constitutive activation.
Acid-induced reversible unfolding of mitochondrial aspartate aminotransferase. (1994)

The acid-induced reversible unfolding of several forms of the mitochondrial isoenzyme of mammalian aspartate aminotransferase, including its precursor form, has been characterized under equilibrium conditions. A minimum of two transitions can be detected for the holoenzyme (pyridoxal form). One transition takes place at pH 3.6 and corresponds to the monomerization of the dimeric protein. The second transition is centered at pH 3.3 and represents the disappearance of much of the tertiary and secondary structures. The presequence peptide in the precursor protein does not affect the equilibria nor the rate of unfolding in the pH range from 7.5 to 2.0. The presence of the cofactor, pyridoxal 5'-phosphate, stabilizes the protein against acid denaturation. At pH 2.0, the protein retains significant amounts of secondary structure (26% alpha-helix, 20% beta-structure). Increasing the ionic strength at pH 2.0 results in significant changes in the secondary structure of the unfolded protein that acquires some of the characteristics ascribed to a compact molten globule. According to the circular dichroism spectra these changes are characterized by an increase in beta-structure, although Fourier transform infrared spectroscopy analysis indicates that this increase in beta-structure is due mostly to the formation of intermolecular beta-sheet as a consequence of protein aggregation. The formation of high molecular weight aggregates has been confirmed by analytical ultracentrifugation. Following neutralization of the acid-unfolded state at low ionic strength both mature and precursor proteins refold to their native active state (> 80% yield). By contrast the compact state present at pH 2.0 and high ionic strength is unable to recover its activity following neutralization. Thus, this compact state does not appear to represent an intermediate in the folding pathway of the protein, but rather a dead end product of aggregation, which may reflect the intrinsic tendencies of the unfolded protein to oligomerize at intracellular salt concentrations unless controlled by factors such as chaperones present in the cellular environment.
Testosterone Patch for Low Sexual Desire in Surgically Menopausal Women: A Randomized Trial (2005)

In surgically menopausal women with hypoactive sexual desire disorder, a 300 mug/d testosterone patch significantly increased satisfying sexual activity and sexual desire, while decreasing personal distress, and was well tolerated through up to 24 weeks of use.
: what do we know, and what do we still need to know? (2007)

Maximal oxygen uptake (.VO(2,max)) is a physiological characteristic bounded by the parametric limits of the Fick equation: (left ventricular (LV) end-diastolic volume--LV end-systolic volume) x heart rate x arterio-venous oxygen difference. 'Classical' views of .VO(2,max) emphasize its critical dependence on convective oxygen transport to working skeletal muscle, and recent data are dispositive, proving convincingly that such limits must and do exist. 'Contemporary' investigations into the mechanisms underlying peripheral muscle fatigue due to energetic supply/demand mismatch are clarifying the local mediators of fatigue at the skeletal muscle level, though the afferent signalling pathways that communicate these environmental conditions to the brain and the sites of central integration of cardiovascular and neuromotor control are still being worked out. Elite endurance athletes have a high .VO(2,max) due primarily to a high cardiac output from a large compliant cardiac chamber (including the myocardium and pericardium) which relaxes quickly and fills to a large end-diastolic volume. This large capacity for LV filling and ejection allows preservation of blood pressure during extraordinary rates of muscle blood flow and oxygen transport which support high rates of sustained oxidative metabolism. The magnitude and mechanisms of cardiac phenotype plasticity remain uncertain and probably involve underlying genetic factors, as well as the length, duration, type, intensity and age of initiation of the training stimulus.
IL-6 Mediates Macrophage Infiltration after Irradiation via Up-regulation of CCL2/CCL5 in Non-small Cell Lung Cancer (2017)

Radiotherapy is effective in reducing primary tumors, however, it may enhance macrophage infiltration to tumor sites, accelerating tumor progression in several ways. We investigated whether radiation can increase macrophage infiltration into non-small cell lung carcinoma (NSCLC) cells. Analysis of in vitro macrophage (differentiated THP-1 cells) migration to either nonirradiated or irradiated tumor cells showed increased migration to the irradiated tumor cells. Because the IL-6 levels in A549 and H157 cells were significantly increased after irradiation, we then investigated whether this increased IL-6 level contributes to radiation-induced macrophage migration. Radiation-induced macrophage infiltration was reduced when IL-6 was knocked down in tumor cells, indicating a positive IL-6 role in this process. To validate this in vitro result, an orthotopic mouse model was developed using a luciferase-tagged H157siIL-6/scramble control (sc) cell set. After tumors developed, the lungs were irradiated, and infiltration of endogenous macrophages and tail-vein injected fluorescent macrophages to tumor sites was investigated. In both groups, increased macrophage infiltration was observed in H157sc cell-derived xenografts compared to H157siIL-6 cell-derived xenografts, confirming the positive IL-6 role in the radiation-induced macrophage infiltration process. In mechanistic dissection studies, radiation-induced up-regulation of CCL2 and CCL5 by IL-6 was detected, and blocking the action of CCL2/CCL5 molecules significantly reduced the number of migrated macrophages to tumor cells after irradiation. These results demonstrate that targeting the IL-6 signaling or CCL2/CCL5 molecules in combination with conventional radiotherapy potentially blocks undesired radiation-induced macrophage infiltration.
An optical fiber network oracle for NP-complete problems (2014)

The modern information society is enabled by photonic fiber networks characterized by huge coverage and great complexity and ranging in size from transcontinental submarine telecommunication cables to fiber to the home and local segments. This world-wide network has yet to match the complexity of the human brain, which contains a hundred billion neurons, each with thousands of synaptic connections on average. However, it already exceeds the complexity of brains from primitive organisms, i.e., the honey bee, which has a brain containing approximately one million neurons. In this study, we present a discussion of the computing potential of optical networks as information carriers. Using a simple fiber network, we provide a proof-of-principle demonstration that this network can be treated as an optical oracle for the Hamiltonian path problem, the famous mathematical complexity problem of finding whether a set of towns can be travelled via a path in which each town is visited only once. Pronouncement of a Hamiltonian path is achieved by monitoring the delay of an optical pulse that interrogates the network, and this delay will be equal to the sum of the travel times needed to visit all of the nodes (towns). We argue that the optical oracle could solve this NP-complete problem hundreds of times faster than brute-force computing. Additionally, we discuss secure communication applications for the optical oracle and propose possible implementation in silicon photonics and plasmonic networks. Optical fibre networks can tackle complex mathematical calculations such as the famous Hamiltonian path problem. Kan Wu and co-workers from Nanyang Technological University, Singapore, and the University of Southampton, UK, built a fibre network comprising optical fibres of varying lengths. Because each path in the network has a different delay, timing the transit time of light pulses exiting the network makes it possible to see if any output pulse leaves with a unique delay time that matches the time needed to visit each node once and only once. If such an output pulse is found, then it is concluded that a Hamiltonian path for the network exists.
Gene delivery to mitotic and postmitotic photoreceptors Via compacted DNA nanoparticles results in improved phenotype in a mouse model of retinitis pigmentosa (2009)

The purpose of the present study was to test the therapeutic efficiency and safety of compacted-DNA nanoparticle-mediated gene delivery into the subretinal space of a juvenile mouse model of retinitis pigmentosa. Nanoparticles containing the mouse opsin promoter and wild-type mouse Rds gene were injected subretinally into mice carrying a haploinsufficiency mutation in the retinal degeneration slow (rds(+ or -)) gene at postnatal day (P)5 and 22. Control mice were either injected with saline, injected with uncompacted naked plasmid DNA carrying the Rds gene, or remained untreated. Rds mRNA levels peaked at postinjection day 2 to 7 (PI-2 to PI-7) for P5 injections, stabilized at levels 2-fold higher than in uninjected controls for both P5 and P22 injections, and remained elevated at the latest time point examined (PI-120). Rod function (measured by electroretinography) showed modest but statistically significant improvement compared with controls after both P5 and P22 injections. Cone function in nanoparticle-injected eyes reached wild-type levels for both ages of injections, indicating full prevention of cone degeneration. Ultrastructural examination at PI-120 revealed significant improvement in outer segment structures in P5 nanoparticle-injected eyes, while P22 injection had a modest structural improvement. There was no evidence of macrophage activation or induction of IL-6 or TNF-alpha mRNA in P5 or P22 nanoparticle-dosed eyes at either PI-2 or PI-30. Thus, compacted-DNA nanoparticles can efficiently and safely drive gene expression in both mitotic and postmitotic photoreceptors and retard degeneration in this model. These findings, using a clinically relevant treatment paradigm, illustrate the potential for application of nanoparticle-based gene replacement therapy for treatment of human retinal degenerations.-Cai, X., Conley, S. M., Nash, Z., Fliesler, S. J., Cooper, M. J., Naash, M. I. Gene delivery to mitotic and postmitotic photoreceptors via compacted DNA nanoparticles results in improved phenotype in a mouse model of retinitis pigmentosa.
T Cells Signaled by NF-κB− Dendritic Cells Are Sensitized Not Anergic to Subsequent Activation (2004)

Paradoxically, while peripheral self-tolerance exists for constitutively presented somatic self Ag, self-peptide recognized in the context of MHC class II has been shown to sensitize T cells for subsequent activation. We have shown that MHC class II(+)CD86(+)CD40(-) DC, which can be generated from bone marrow in the presence of an NF-kappa B inhibitor, and which constitutively populate peripheral tissues and lymphoid organs in naive animals, can induce Ag-specific tolerance. In this study, we show that CD40(-) human monocyte-derived dendritic cells (DC), generated in the presence of an NF-kappa B inhibitor, signal phosphorylation of TCR zeta, but little proliferation or IFN-gamma in vitro. Proliferation is arrested in the G(1)/G(0) phase of the cell cycle. Surprisingly, responding T cells are neither anergic nor regulatory, but are sensitized for subsequent IFN-gamma production. The data indicate that signaling through NF-kappa B determines the capacity of DC to stimulate T cell proliferation. Functionally, NF-kappa B(-)CD40(-)class II(+) DC may either tolerize or sensitize T cells. Thus, while CD40(-) DC appear to "prime" or prepare T cells, the data imply that signals derived from other cells drive the generation either of Ag-specific regulatory or effector cells in vivo.
Conserved Expression of the Arabidopsis ACT1 and ACT3 Actin Subclass in Organ Primordia and Mature Pollen (1996)

Yong-Qiang An, Shurong Huang, John M. McDowell, Elizabeth C. McKinney, Richard B. Meagher, Conserved Expression of the Arabidopsis ACT1 and ACT3 Actin Subclass in Organ Primordia and Mature Pollen, The Plant Cell, Vol. 8, No. 1 (Jan., 1996), pp. 15-30
Comparison of Two Methods for Concentrating CD34 + Cells from Patients with Acute Non-Lymphocytic Leukemia (1992)

The aim of the present study was to compare two different methods for obtaining CD34+ cells from the peripheral blood or the bone marrow of patients with acute non-lymphocytic leukemia (ANLL). Twenty-two samples, obtained from 19 patients, were density cut (Ficoll-Hypaque 1.077) and, after incubation with My10 antibody, separated by panning or by immunomagnetic beads. Immunomagnetic beads provided a significantly better separation than panning, either in terms of concentration of CD34+ cells (85.5 +/- 11.6% vs. 55.7 +/- 25.0%, p = 0.003) or in terms of depletion of CD34+ cells (3.9 +/- 8.0% vs. 30.9 +/- 26.3%, p = 0.008). This was consistent with the virtually complete depletion of colony forming cells (CFC) in the CD34 negative fraction and the recovery of virtually all the CFC in the positive fraction in the samples separated by immunomagnetic beads. In conclusion, separation by immunomagnetic beads can allow collection of nearly pure CD34+ and CD34- cell populations from patients with ANLL, thereby facilitating the study of the biological characteristics of these cell populations. Moreover the method is less time consuming than panning and is not toxic to the CFC.
Purification and biochemical characterization of dog gastric lipase (1991)

A lipase was found to be present in dog stomach which appeared to be more abundant in the fundic than in the pyloric mucosa. Dog gastric lipase was extracted by soaking the gastric tissue and further purified after cation exchange, anion exchange and gel-filtration using fast protein liquid chromatography. The amino-acid composition, N-terminal amino-acid sequence, substrate specificity, interfacial and kinetic behavior and inactivation by sulfhydryl reagents were determined and compared with those of human and rabbit gastric lipases. We report for the first time that a gastric lipase is 13 times more active on long-chain than on short-chain triacylglycerols at pH 4.0, reaching a maximal specific activity of 950 U/mg on Intralipide emulsion.
Rational Design and Synthesis of Freestanding Photoelectric Nanodevices as Highly Efficient Photocatalysts (2010)

Photocatalysts are of significant interest in solar energy harvesting and conversion into chemical energy. However, the photocatalysts available to date are limited by either poor efficiency in the visible light range or insufficient photoelectrochemical stability. Here we report the rational design of a new generation of freestanding photoelectric nanodevices as highly efficient and stable photocatalysts by integrating a nanoscale photodiode with two redox catalysts in a single nanowire heterostructure. We show that a platinum-silicon-silver nanowire heterostructure can be synthesized to integrate a nanoscale metal-semiconductor Schottky diode encased in a protective insulating shell with two exposed metal catalysts. We further demonstrated that the Schottky diodes exhibited a pronounced photovoltaic effect with nearly unity internal quantum efficiency and that the integrated nanowire heterostructures could be used as highly efficient photocatalysts for a wide range of thermodynamically downhill and uphill reactions including the photocatalytic degradation of organic dyes and the reduction of metal ions and carbon dioxide using visible light. Our studies for the first time demonstrated the integration of multiple distinct functional components into a single nanostructure to form a standalone active nanosystem and for the first time successfully realized a photoelectric nanodevice that is both highly efficient and highly stable throughout the entire solar spectrum. It thus opens a rational avenue to the design and synthesis of a new generation of photoelectric nanosystems with unprecedented efficiency and stability and will have a broad impact in areas including environmental remediation, artificial photosynthesis and solar fuel production.
QAM: the modulation scheme for future mobile radio communications? (1992)

With spectral congestion increasing, and plans announced to dramatically increase the number of mobile telephone users over the coming decade, many approaches are being considered to reduce the bandwidth requirements of each user. One approach is the use of quadrature amplitude modulation (QAM), a particular form of multilevel modulation where each symbol contains several bits of information. The use of QAM for mobile radio applications is considered and it is shown that this form of multilevel modulation can offer an attractive solution to current bandwidth restrictions in microcellular networks. An advanced variable-rate system is also considered and hardware development of a QAM modem discussed.
Random networks of carbon nanotubes as an electronic material (2003)

We report on the transport properties of random networks of single-wall carbon nanotubes fabricated into thin-film transistors. At low nanotube densities (∼1 μm−2) the networks are electrically continuous and behave like a p-type semiconductor with a field-effect mobility of ∼10 cm2/V s and a transistor on-to-off ratio ∼105. At higher densities (∼10 μm−2) the field-effect mobility can exceed 100 cm2/V s; however, in this case the network behaves like a narrow band gap semiconductor with a high off-state current. The fact that useful device properties are achieved without precision assembly of the nanotubes suggests the random carbon nanotube networks may be a viable material for thin-film transistor applications.
A Versatile Wide-Range Electrical Heart Stimulator (1980)

A versatile wide-range electrical stimulator has been built for stimulated fibrillation of the heart in animal experiments using readily available low cost IC's and general purpose instruments easily available in the laboratory or commercially. An outline of the whole system is presented along with a detailed description of the master control section which generates all the important trigger commands.
Efficient depth buffer compression (2006)

Depth buffer performance is crucial to modern graphics hardware. This has led to a large number of algorithms for reducing the depth buffer bandwidth. Unfortunately, these have mostly remained documented only in the form of patents. Therefore, we present a survey on the design space of efficient depth buffer implementations. In addition, we describe our novel depth buffer compression algorithm, which gives very high compression ratios.
Cloning of rat "prion-related protein" cDNA. (1987)

Rat prion-related protein (PrP) cDNA has been cloned and sequenced. Comparison of this cDNA with those from human, hamster, and mouse indicates extremely high conservation (about 95%). The deduced partial rat PrP possesses: (a) a highly conserved region composed of repetitive sequences in what is presumably an extracellular domain, (b) a hydrophobic transmembrane domain, (c) a highly charged region which should stop membrane transfer, (d) a substantial cytoplasmic domain (which contains all of the nonconservative substitutions and a high proportion of conservative substitutions), and (e) a hydrophobic C-terminus. Dot and Northern blot analyses suggest a limited expression of PrP in rat tissues and indicate that PrP expression is decreased in the brain during the acute phase response systemically. Our results lend support to the notion that PrP is a highly conserved, normal cellular membrane protein of essential (although unknown) biologic function, which may be deposited in fibrillar amyloid form as a result of abnormal processing.