gebhart/patrepeval huggingface dataset:
Bacillus subtilis citB gene is regulated synergistically by glucose and glutamine (1985)

The activity of aconitase in Bacillus subtilis is greatly reduced in cells cultured in media containing rapidly metabolized carbon sources (e.g., glucose). Thus, expression of this enzyme appears to be subject to a form of catabolite repression. Since the product of the citB gene of B. subtilis is required for aconitase activity, we cloned the wild-type allele of this gene and used this DNA as a probe for transcription of citB in cells grown in various media. The steady-state level of RNA that hybridized to this probe was about 10-fold higher in B. subtilis cells grown in citrate-glutamine medium than in cells grown in glucose-glutamine medium. This result correlates well with the steady-state levels of aconitase activity. Two transcripts were shown to initiate within the cloned DNA; the steady-state level of one of these transcripts varied in the same way as did aconitase activity when cells were grown in media containing different carbon sources. This is the first demonstration of regulation by the carbon source of the level of a vegatative-cell transcript in B. subtilis.
Identification of Two Serine Residues Involved in Agonist Activation of the β-Adrenergic Receptor (1989)

Pharmacophore mapping of the ligand binding domain of the beta-adrenergic receptor has revealed specific molecular interactions which are important for agonist and antagonist binding to the receptor. Previous site-directed mutagenesis experiments have demonstrated that the binding of amine agonists and antagonists to the receptor involves an interaction between the amine group of the ligand and the carboxylate side chain of Asp113 in the third hydrophobic domain of the receptor (Strader, C. D., Sigal, I. S., Candelore, M. R., Rands, E., Hill, W. S., and Dixon, R. A. F. (1988) J. Biol. Chem. 263, 10267-10271). We have now identified 2 serine residues, at positions 204 and 207 in the fifth hydrophobic domain of the beta-adrenergic receptor, which are critical for agonist binding and activation of the receptor. These serine residues are conserved with G-protein-coupled receptors which bind catecholamine agonists, but not with receptors whose endogenous ligands do not have the catechol moiety. Removal of the hydroxyl side chain from either Ser204 or Ser207 by substitution of the serine residue with an alanine attenuates the activity of catecholamine agonists at the receptor. The effects of these mutations on agonist activity are mimicked selectively by the removal of the catechol hydroxyl moieties from the aromatic ring of the agonist. The data suggest that the interaction of catecholamine agonists with the beta-adrenergic receptor involves two hydrogen bonds, one between the hydroxyl side chain of Ser204 and the meta-hydroxyl group of the ligand and a second between the hydroxyl side chain of Ser207 and the para-hydroxyl group of the ligand.
Growth of high-quality 3C-SiC epitaxial films on off-axis Si(001) substrates at 850 °C by reactive magnetron sputtering (1994)

Single crystal 3C-SiC films of thickness ∼10 μm were grown by reactive magnetron sputtering on off-axis Si(001) at 850 °C. The film quality was comparable to the best chemical vapor deposited 3C-SiC as characterized by x-ray diffraction, transmission electron microscopy, and photo- luminescence (PL). The lattice mismatch and difference in thermal contraction between SiC and Si resulted in complete arrays of misfit dislocations at the film/substrate interface and a residual in-plane strain of (−6.9±1)×10−4, respectively. The full width at half-maximum (FWHM) of the 3C-SiC(004) peak was 59 arcsec in ω-2θ direction. The structural defects in the SiC film were planar faults on {111} planes and no voids or plastic deformation in the Si substrate were observed. PL spectra of SiC films showed characteristic appearances with N bound-exciton (N-BE) lines with a FWHM value of 3.4 meV. The deposition conditions leading to low defect-density 3C-SiC films are discussed in terms of low-energy ion-surface interactions.
Transmission Power Requirements for Novel ZigBee Implants in the Gastrointestinal Tract (2008)

In this paper, a novel multinode wireless monitoring platform, based on ZigBee communication standard, is presented and tested in vivo. The transmission power levels needed to establish a reliable connection from the different gastrointestinal districts are reported and compared with safety levels from international guidelines. These findings can be useful to evaluate the effectiveness of a commercial and standardized approach to implantable and miniaturized monitoring of physiological parameters.
An IQ Domain Mediates the Interaction with Calmodulin in a Plant Cyclic Nucleotide-Gated Channel (2013)

Cyclic nucleotide-gated channels (CNGCs) form non-selective cation entry pathways regulated by calmodulin (CaM), a universal Ca(2+) sensor in eukaryotes. Although CaM binding has been shown to be important for Ca(2+)-dependent feedback regulation of CNGC activity, the CaM-binding properties of these channels have been investigated in a few cases only. We show that CNGC20 from Arabidopsis thaliana binds CaM in a Ca(2+)-dependent manner and interacts with all AtCaM isoforms but not with the CaM-like proteins CML8 and CML9. CaM interaction with the full-length channel was demonstrated in planta, using bimolecular fluorescence complementation. This interaction occurred at the plasma membrane, in accordance with our localization data of green fluorescent protein (GFP)-fused CNGC20 proteins. The CaM-binding site was mapped to an isoleucine glutamine (IQ) motif, which has not been characterized in plant CNGCs so far. Our results show that compared with the overlapping binding sites for cyclic nucleotides and CaM in CNGCs studied so far, they are sequentially organized in CNGC20. The presence of two alternative CaM-binding modes indicates that ligand regulation of plant CNGCs is more complex than previously expected. Since the IQ domain is conserved among plant CNGCs, this domain adds to the variability of Ca(2+)-dependent channel control mechanisms underlining the functional diversity within this multigene family.
Analysis, synthesis, and perception of spatial sound : binaural localization modeling and multichannel loudspeaker reproduction (2006)

In everyday audio environments, sound from several sources arrives at a listening position both directly from the sources and as reflections from the acoustical environment. This thesis deals, within some limitations, with analysis of the resulting spatial sound field, reproduction of perceptually relevant features of the sound as measured in a chosen listening position, as well as with modeling of the related auditory localization.\n\nFor the localization, the auditory system needs to independently determine the direction of each source, while ignoring the reflections and superposition effects of any possible concurrently arriving sound. A modeling mechanism with these desired properties is proposed. Interaural time difference (ITD) and interaural level difference (ILD) cues are only considered at time instants when only the direct sound of a single source has non-negligible energy within a critical band and, thus, when the evoked ITD and ILD represent the direction of that source. It is shown how to identify such time instants as a function of the interaural coherence (IC). The source directions suggested by the selected ITD and ILD cues are also shown to imply the results of a number of published psychophysical studies.\n\nAlthough the room reflections are usually suppressed in auditory localization, they contribute to the perception of the acoustical environment. The reviewed physical analysis techniques and psychoacoustical knowledge on spatial hearing are applied in development of the Spatial Impulse Response Rendering (SIRR) method. SIRR aims at recreating ITD, ILD, IC, and monaural localization cues by using a perceptually motivated analysis-synthesis method. The method is described in the context of multichannel loudspeaker reproduction of room responses with convolving reverberators. The analyzed quantities consist of the time- and frequency-dependent direction of arrival and diffuseness of sound. Based on the analysis data and a recorded omnidirectional signal, multichannel responses suitable for reproduction with any chosen surround loudspeaker setup are synthesized. In formal listening tests, it is shown that SIRR creates a more natural spatial impression than can be achieved with conventional techniques.
Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat. (1993)

As the action of aldose reductase (EC 1.1.1.21) is believed to be linked to the pathogenesis of diabetic complications affecting the nervous, renal, and visual systems, the development of therapeutic agents has attracted intense effort. We report the refined 1.8 A x-ray structure of the human holoenzyme complexed with zopolrestat, one of the most potent noncompetitive inhibitors. The zopolrestat fits snugly in the hydrophobic active site pocket and induces a hinge-flap motion of two peptide segments that closes the pocket. Excellent complementarity and affinity are achieved on inhibitor binding by the formation of 110 contacts (< or = 4 A) with 15 residues (10 hydrophobic), 13 with the NADPH coenzyme and 9 with four water molecules. The structure is key to understanding the mode of action of this class of inhibitors and for rational design of better therapeutics.
Combined OX40 ligation plus CTLA-4 blockade (2014)

It is becoming clear that combination strategies will be necessary to augment cancer immunotherapy. We report that combination anti-OX40/anti-CTLA-4 mAb immunotherapy improves survival by enhancing effector T cell expansion and function, even while inducing Th2 cytokine production. Furthermore, IL-4 blockade in addition to combination therapy significantly improved anti-tumor efficacy.
Neutrophil recognition requires a Ca(2+)-induced conformational change in the lectin domain of GMP-140. (1991)

GMP-140, a receptor for myeloid cells that is expressed on surfaces of thrombin-activated platelets and endothelial cells, is a member of the selectin family of adhesion molecules that regulate leukocyte interactions with the blood vessel wall. Each selectin contains an N-terminal domain homologous to Ca(2+)-dependent lectins and mediates cell-cell contact by binding to oligosaccharide ligands in a Ca(2+)-dependent manner. The mechanisms by which Ca2+ promotes selectin-dependent cellular interactions have not been defined. We demonstrate that purified GMP-140 contains two high affinity binding sites for Ca2+ as measured by equilibrium dialysis (Kd = 22 +/- 2 microM). Occupancy of these sites by Ca2+ alters the conformation of the protein as detected by a reduction in intrinsic fluorescence emission intensity (Kd = 4.8 +/- 0.2 microM). This Ca(2+)-dependent conformational change exposes an epitope spanning residues 19-34 of the lectin domain that is recognized by a monoclonal antibody capable of blocking neutrophil adhesion to GMP-140 (half-maximal antibody binding at approximately 20 microM Ca2+). Furthermore, a synthetic peptide encoding this epitope, CQNRYTDLVAIQNKNE, inhibits neutrophil binding to GMP-140. Mg2+ also alters the conformation of the protein, but not in a manner that will support leukocyte recognition in the absence of Ca2+. There is a strong correlation between the Ca2+ levels required for neutrophil adhesion to GMP-140, for occupancy of the two Ca(2+)-binding sites, for the fluorescence-detected conformational change, and for exposure of the antibody epitope in the lectin domain. We conclude that binding of Ca2+ to high affinity sites on GMP-140 modulates the conformation of the lectin domain in a manner that is essential for leukocyte recognition.
Improving the translational hit of experimental treatments in multiple sclerosis (2010)

EAE has proven to be a valuable model in elucidating pathogenesis as well as identifying candidate therapies for multiple sclerosis. However, there is an inconsistent application of measures to limit bias that could be addressed by adopting methodological best practice in study design. Our analysis provides an estimate of sample size required for different levels of power in future studies and suggests a number of interventions for which there are substantial animal data supporting efficacy.
Smart Homes: See Multiple Heartbeats Through Wall Using Wireless Signals (2019)

In this paper, we developed a new multiple-subject heart-rates monitoring algorithm through a wall using a wireless sensor. We proposed an adaptive heart-rate estimation algorithm to enable continuous heart-rate monitoring. Finally, we demonstrated the proposed theory through experimental demonstration.
Development and Evaluation of a Reference Measurement Procedure for the Determination of Total 3,3‘,5-Triiodothyronine in Human Serum Using Isotope-Dilution Liquid Chromatography−Tandem Mass Spectrometry (2004)

3,3',5-Triiodothyronine (T3) is an important diagnostic marker for thyroid function. A reference measurement procedure (RMP) for total T3 in serum involving isotope dilution coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS) has been developed and critically evaluated. The method uses solid-phase extraction with mixed-mode retention mechanisms of reversed phase and ion exchange prior to reversed-phase LC/MS/MS. In addition to a labeled T3 internal standard (T3-13C9), labeled thyroxine (T4-d5) is also added to serum samples in order to monitor the degradation of T4 to T3. The accuracy of the measurement was evaluated by a recovery study for added T3 and was supported by a comparison study with the other RMP. The recovery of the added T3 ranged from 98.9% to 99.4%. The results of this method and the other RMP agreed to within 1%. Samples of frozen serum pools were prepared and measured in three separate sets. Excellent reproducibility was obtained with within-set coefficients of variation (CVs) ranging from 0.8% to 1.6% and between-set CVs ranging from 1.9% to 2.6%. Excellent linearity was also obtained with correlation coefficients of all linear regression lines (measured intensity ratios vs mass ratios) ranging from 0.9995 to 0.9996. The detection limit at a signal-to-noise ratio of approximately 3 was 1 pg of T3. The T4 degradation during sample preparation was minimized to a small percentage (no more than 3% of the T3 values) by use of antioxidants (ascorbic acid, dithiothreitol, citric acid) and can be accounted for in the T3 measurement process. This well-characterized LC/MS/MS method for total serum T3, which demonstrates good accuracy and precision, low susceptibility to interferences, accountability of the conversion of T4 to T3, and comparability with the other RMP, qualifies as a reference measurement procedure and can be used to provide an accuracy base to which routine methods for T3 can be compared.
New Insights into Host Factor Requirements for Prokaryotic %-Recombinase-mediated Reactions in Mammalian Cells (2001)

The prokaryotic beta-recombinase catalyzes site-specific recombination between two directly oriented minimal six sites in mammalian cells, both on episomic and chromatin-integrated substrates. Using a specific recombination activated gene expression system, we report the site-specific recombination activity of an enhanced green fluorescent protein (EGFP) fused version of beta-recombinase (beta-EGFP). This allows expression of active beta-recombinase detectable in vivo and in fixed cells by fluorescence microscopy. In addition, cellular viability is compatible with a substantial level of expression of the beta-EGFP protein. Using fluorescence-activated cell sorting, we have been able to enrich cell populations expressing this fusion protein. Application of this strategy has allowed us to study in more depth the host factor requirements for this system. Previous work showed that eukaryotic HMG1 protein was necessary and sufficient to help beta-recombinase activity in vitro. The influence of ectopic expression of HMG1 protein in the recombination process has been analyzed, indicating that HMG1 overexpression does not lead to a significant increase on the efficiency of beta-recombinase-mediated recombination both on episomal substrates and chromatin-associated targets. In addition, beta-recombinase-mediated recombination has been demonstrated in HMG1 deficient cells at the same levels as in wild type cells. These data demonstrate the existence of cellular factors different from HMG-1 that can act as helpers for beta-recombinase activity in the eukaryotic environment.
Functional and Morphologic Characterization of Human T Cells Continuously Grown in Vitro (1977)

Long-term growth (now over 13 months) of thymus-derived lymphocytes from numerous normal human bone marrow and peripheral blood cell samples was accomplished by using a factor present in media obtained from mitogen-stimulated human peripheral blood lymphocytes. This long-term growth could neither be initiated nor maintained by mitogens alone. All cell cultures were greater than 90% E rosette-positive, whereas the tests for B cell markers, surface IgG and IgM, and EAC rosette were routinely negative. There was no evidence for the presence of granulocytes, monocytes, and their precursors in these cultures. The E rosette-positive cells were then tested to see if they had T cell functions. PHA, Con A, and pokeweed mitogens stimulated lymphproliferative responses in these cultures comparable to those of fresh peripheral blood cells. These proliferating cells were also able to release cell mediators, such as interferon and colony-stimulating activity. Further evidence for the T lymphocyte nature of these cultured cells was obtained from one-way mixed leukocyte cultures in which these cells responded to but were unable to stimulate allogeneic cells. The functional and morphologic characteristics of these cultured cells show that these cells are T cells that grow continuously in vitro.
Locating animals from their sounds and tomography of the atmosphere: Experimental demonstration (1999)

Calling animals are located using widely distributed receivers, and the sounds from the animals are used to map the sound speed and wind fields by means of tomography. In particular, two Red-Winged Blackbirds Agelaius phoeniceus are correctly located within a meter using recordings from five receivers spread over a 20 by 30 m region. The demonstration hinges on two new developments. First, a new algorithm for blindly estimating the impulse response of the channel is shown capable of estimating the differences in the time of first arrivals at two receivers. Since it is known that the first arrivals travel along nearly straight paths, the difference in time constrains the animal's location to a hyperboloid, and the animal is located by intersecting hyperboloids from many pairs of receivers. Second, in order to accurately find the intersection point and map the sound speed and wind fields using tomography, a nonlinear equation is solved. The new algorithm for blindly estimating the impulse response of a channel offers a new way for locating sounds and making tomographic maps of the environment without any requirement for a model for the propagation of sound such as is needed for focalization and matched field processing.
Interleukin-3 stimulates the tyrosine phosphorylation of the 140-kilodalton interleukin-3 receptor (1989)

Murine interleukin-3 (mIL-3) stimulates the rapid and transient tyrosine phosphorylation of a number of proteins in mIL-3-dependent B6SUtA1 cells. Two of these proteins, p68 and p140, are maximally phosphorylated at tyrosine residues within 2 min of addition of mIL-3. Because 125I-mIL-3 can be cross-linked to both 70- and 140-kDa proteins on intact B6SUtA1 cells, we investigated whether the tyrosine phosphorylated p68 and p140 were these two mIL-3 receptor proteins. Addition of antiphosphotyrosine antibodies (alpha PTyr Abs) to cell lysates from B6SUtA1 cells, to which 125I-mIL-3 had been disuccinimidyl suberate-cross-linked, resulted in the immunoprecipitation of 125I-mIL-3 complexed to both 70- and 140-kDa proteins. To determine if the observed immunoprecipitation pattern was due to the direct interaction of alpha-PTyr Abs with these two mIL-3 receptor proteins or with tyrosine-phosphorylated proteins that were associated with the receptor proteins, cell lysates were treated with 2% sodium dodecyl sulfate, 5% 2-mercaptoethanol, and boiled for 1 min. After removal of sodium dodecyl sulfate and 2-mercaptoethanol, alpha PTyr Abs immunoprecipitated 125I-mIL-3 cross-linked to only the 140-kDa protein. To confirm this finding, 32P-labeled B6SUtA1 cells were treated with biotinylated or fluoresceinated mIL-3. Addition of immobilized streptavidin or antifluorescein antibodies, respectively, to cell lysates from these cells resulted in the enrichment of only a 140-kDa tyrosine phosphorylated protein. Taken together, these results strongly suggest that only the 140-kDa receptor protein is tyrosine phosphorylated upon mIL-3 binding.
From flavors and pharmaceuticals to advanced biofuels: Production of isoprenoids in Saccharomyces cerevisiae (2013)

Isoprenoids denote the largest group of chemicals in the plant kingdom and are employed for a wide range of applications in the food and pharmaceutical industry. In recent years, isoprenoids have additionally been recognized as suitable replacements for petroleum-derived fuels and could thus promote the transition towards a more sustainable society. To realize the biofuel potential of isoprenoids, a very efficient production system is required. While complex chemical structures as well as the low abundance in nature demonstrate the shortcomings of chemical synthesis and plant extraction, isoprenoids can be produced by genetically engineered microorganisms from renewable carbon sources. In this article, we summarize the development of isoprenoid applications from flavors and pharmaceuticals to advanced biofuels and review the strategies to design microbial cell factories, focusing on Saccharomyces cerevisiae for the production of these compounds. While the high complexity of biosynthetic pathways and the toxicity of certain isoprenoids still denote challenges that need to be addressed, metabolic engineering has enabled large-scale production of several terpenoids and thus, the utilization of these compounds is likely to expand in the future.
Hepatitis B Virus Infection and Exposure Among Foreign-Born Asian Americans in the U.S. (2017)

: This study reports hepatitis B serologic test results among foreign-born Asian Americans. In 2013 - 2014, a sample of foreign-born Asian American adults, (â¥ 18 years of age) were drawn from community-based organizations in the Baltimore-Washington Metropolitan Area. Hepatitis B screening tests were administered, including tests for HBsAg, anti-HBs, and anti-HBc. Among total of 600 people who completed screening, 33 (5.5%) tested positive for HBsAg, indicating chronic hepatitis B virus (HBV) infection. About 44% (n = 263) tested positive for anti-HBc, indicating a previous exposure to HBV. Asian Americans from Vietnam (53.2%) had the highest exposure to HBV, followed by Asian Americans from Korea (43.4%) and China (34.8%) (P < 0.001). In multivariate analysis, gender, age, education, and family history of HBV infection were associated with previous exposure to HBV infection. The prevalence of anti-HBc (44%) in our study group was much higher than that of a nationally representative sample in the NHANES study (6%), indicating that there is higher incidence of HBV in foreign-born Asian Americans than the general U.S. population.