gebhart/patrepeval huggingface dataset:
Kinetic analysis of yeast TFIID-TATA box complex formation suggests a multi-step pathway. (1992)

The eukaryotic transcription factor TFIID recognizes and binds a promoter sequence element called the TATA box. We have analyzed the interaction of yeast TFIID with the consensus TATA box sequence of the adenovirus major late promoter. To facilitate this detailed characterization, we developed a method for obtaining quantitative information from a gel retardation (bandshift) assay, allowing measurement of the rate and extent of TFIID-TATA box complex formation. Using this assay and DNase I protection assays, we determined that the association rate constant for TFIID binding to the major late promoter was too low to be consistent with a simple diffusion-limited association, suggesting that the binding proceeds by a multi-step pathway. Furthermore, we found that the slow rate of TFIID binding reported by other research groups was not the consequence of a rate-limiting conformational change, as has been previously suggested. Instead, we observed that the formation of a stable TFIID-TATA box complex was relatively rapid (complete in less than 1 min) at saturating concentrations of TFIID. We have proposed a two-step pathway consistent with the observed kinetics and have considered the possible contributions of each step to the overall rate of TFIID binding. This study lays the groundwork for a systematic characterization of the interaction of TFIID with additional TATA box sequences, including an experimental test of the possibility that different steps in the binding reaction are rate-limiting for different promoters.
Micromachined capacitive silicon bulk acoustic wave gyroscopes (2008)

Micromachined gyroscopes are attractive replacements to conventional macro-mechanical and optical gyroscopes due to their small size, low power and low cost. The application domain of these devices is quickly expanding from automotive to aerospace and consumer electronics industries. As potential high volume consumer applications for micromachined gyroscopes continue to emerge, design and manufacturing techniques that improve their performance, shock survivability and reliability without driving up the cost and size become important.&#13;\nToday, state-of-the-art micromachined gyroscopes can achieve high performance with low frequency operation (3-30kHz) but at the cost of large form factor, large operating voltages and high vacuum packaging. At the same time, most consumer applications require gyroscopes with fast response time and high shock survivability, which are generally unavailable in low frequency gyroscopes. As a result, innovative designs and fabrication technologies that will offer more practical gyroscopes are desired. &#13;\nIn this dissertation, capacitive bulk acoustic wave (BAW) silicon disk gyroscopes are introduced as a new class of micromachined gyroscope to investigate the operation of Coriolis-based vibratory gyroscopes at high frequency and further meet consumer electronics market demands. Capacitive BAW gyroscopes, operating in the frequency range of 1-10MHz are stationary devices with vibration amplitudes less than 20nm, resulting in high device bandwidth and high shock tolerance. They require low operating voltages, which simplifies the interface circuit design and implementation in standard CMOS technologies. They also demonstrate appropriate thermally stable performance in air, which eliminates the need both for vacuum packaging and for temperature control. A revised high aspect ratio poly- and single crystal silicon (HARPSS) process was utilized to implement these devices in thick SOI substrates with very small capacitive gap sizes (~200 nm). The prototype devices show ultra-high quality factors (Q&gt;200,000) and large bandwidth of 15-30Hz. &#13;\nIn addition, the design and implementation of BAW disk gyroscopes are optimized for self-matched mode operation. Operating a vibratory gyroscope in matched mode is a straightforward way to improve performance parameters but, is challenging to achieve without applying large voltages. In this work, self-matched mode operation was provided by enhanced design of the perforations of the disk structure. &#13;\nFurthermore, a multi-axis BAW gyroscope, an extension of the z-axis, is developed. This novel approach avoids the issues associated with integrating multiple proof masses, permitting a very small form factor. The multi-axis gyroscopes operate in out-of plane and in-plane modes to measure the rotation rate around the x- and z-axes. These gyroscopes were also optimized to achieve self-matched mode operation in their both modes.
Observed solar near UV variability: A contribution to variations of the solar constant (1989)

Continuous Measurements of the Solar UV have been made by an instrument on the Solar Mesosphere Explorer (SME) since October 1981. The results for the wavelength interval 200 to 300 nm show an irradiance decrease to a minimum in early 1987 and a subsequent increase to mid-April 1989. The observed UV changes during part of solar cycles 21 to 22 represent approx. 35 percent (during the decreasing phase) and 25 percent (during the increasing phase) of the observed variations of the solar constant for the same time period as the SME measurements.
Isolation of Drosophila genes encoding G protein-coupled receptor kinases. (1991)

G protein-coupled receptors are regulated via phosphorylation by a variety of protein kinases. Recently, termination of the active state of two such receptors, the beta-adrenergic receptor and rhodopsin, has been shown to be mediated by agonist- or light-dependent phosphorylation of the receptor by members of a family of protein-serine/threonine kinases (here referred to as G protein-coupled receptor kinases). We now report the isolation of a family of genes encoding a set of Drosophila protein kinases that appear to code for G protein-coupled receptor kinases. These proteins share a high degree of sequence homology with the bovine beta-adrenergic receptor kinase. The presence of a conserved family of G protein-coupled receptor kinases in vertebrates and invertebrates points to the central role of these kinases in signal transduction cascades.
Common molecular mechanisms in explicit and implicit memory (2006)

Cellular and molecular studies of both implicit and explicit memory suggest that experience-dependent modulation of synaptic strength and structure is a fundamental mechanism by which these memories are encoded and stored within the brain. In this review, we focus on recent advances in our understanding of two types of memory storage: (i) sensitization in Aplysia, a simple form of implicit memory, and (ii) formation of explicit spatial memories in the mouse hippocampus. These two processes share common molecular mechanisms that have been highly conserved through evolution.
Induction of cellular immune responses to tumor cells and peptides in colorectal cancer patients by vaccination with SART3 peptides. (2001)

The tumor-rejection antigen SART3 possesses two antigenic epitopes (SART3(109-118) and SART3(315-323)) capable of inducing HLA-A24-restricted and tumor-specific CTLs. To determine its safety and ability to generate antitumor immune responses, 12 patients with advanced colorectal cancer were administered s.c. vaccinations of these peptides. No severe adverse events were associated with the vaccinations. Significant levels of increased cellular immune responses to both HLA-A24+ colon cancer cells and the vaccinated peptide were observed in the postvaccination peripheral blood mononuclear cells in 7 of 11 and 7 of 10 patients tested, respectively, and the higher responses were observed in those patients vaccinated with the highest dose (3 mg/injection) of the peptides. These results encourage further development of SART3 peptide vaccine for colorectal cancer patients.
Cloning and Functional Characterization of an Arabidopsis Nitrate Transporter Gene That Encodes a Constitutive Component of Low-Affinity Uptake (1999)

The Arabidopsis CHL1 (AtNRT1) gene encodes an inducible component of low-affinity nitrate uptake, which necessitates a "two-component" model to account for the constitutive low-affinity uptake observed in physiological studies. Here, we report the cloning and characterization of a CHL1 homolog, AtNRT1:2 (originally named NTL1), with data to indicate that this gene encodes a constitutive component of low-affinity nitrate uptake. Transgenic plants expressing antisense AtNRT1:2 exhibited reduced nitrate-induced membrane depolarization and nitrate uptake activities in assays with 10 mM nitrate. Furthermore, transgenic plants expressing antisense AtNRT1:2 in the chl1-5 background exhibited an enhanced resistance to chlorate (7 mM as opposed to 2 mM for the chl1-5 mutant). Kinetic analysis of AtNRT1:2-injected Xenopus oocytes yielded a K(m) for nitrate of approximately 5.9 mM. In contrast to CHL1, AtNRT1:2 was constitutively expressed before and after nitrate exposure (it was repressed transiently only when the level of CHL1 mRNA started to increase significantly), and its mRNA was found primarily in root hairs and the epidermis in both young (root tips) and mature regions of roots. We conclude that low-affinity systems of nitrate uptake, like high-affinity systems, are composed of inducible and constitutive components and that with their distinct functions, they are part of an elaborate nitrate uptake network in Arabidopsis.
The generation of antibody diversity through somatic hypermutation and class switch recombination (2004)

In CSR, the C region is replaced by downstream C, C, or C segments to generate IgG, IgE, and IgA antibodies, respectively. This process is mediated by an intrachromosomal recombinational event between the switch (S) region of the C region (S) and one of the downstream S regions (Fig. These S regions are located immediately upstream of each of the C regions (except for ; Fig.
Three-dimensional structures of avidin and the avidin-biotin complex. (1993)

The crystal structures of a deglycosylated form of the egg-white glycoprotein avidin and of its complex with biotin have been determined to 2.6 and 3.0 A, respectively. The structures reveal the amino acid residues critical for stabilization of the tetrameric assembly and for the exceptionally tight binding of biotin. Each monomer is an eight-stranded antiparallel beta-barrel, remarkably similar to that of the genetically distinct bacterial analog streptavidin. As in streptavidin, binding of biotin involves a highly stabilized network of polar and hydrophobic interactions. There are, however, some differences. The presence of additional hydrophobic and hydrophilic groups in the binding site of avidin (which are missing in streptavidin) may account for its higher affinity constant. Two amino acid substitutions are proposed to be responsible for its susceptibility to denaturation relative to streptavidin. Unexpectedly, a residual N-acetylglucosamine moiety was detected in the deglycosylated avidin monomer by difference Fourier synthesis.
Concise Synthesis of (±)‐Aurantioclavine through a Base‐Promoted Pictet–Spengler Reaction (2009)

Abstract A concise total synthesis of (±)‐aurantioclavine ( 1 ) was completed in three steps through the base‐promoted Pictet–Spengler reaction of N b ‐benzylserotonin with 3‐methylbut‐2‐enal. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)
Association of Cholesteryl Ester Transfer Protein– Taq IB Polymorphism With Variations in Lipoprotein Subclasses and Coronary Heart Disease Risk (2000)

Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides and cholesteryl esters between lipoprotein particles, a key step in reverse cholesterol transport in humans. Variations at the CETP locus have been shown to be determinants of the levels and activity of CETP and high density lipoprotein (HDL) plasma concentration. The associations of the common CETP polymorphism, TaqIB in intron 1, with lipoprotein levels and particle size distribution, CETP activity, and coronary heart disease (CHD) risk were examined in a population-based sample of 1411 men and 1505 women from the Framingham Offspring Study. The B2 allele frequency was 0.444 in men and 0.433 in women, and its presence was significantly (P<0.05) associated with decreased CETP activity. B1B1 men had lower HDL cholesterol (HDL-C) levels (1.07 mmol/L) compared with B1B2 (1.14 mmol/L) and B2B2 (1.18 mmol/L) men (P<0.001). Likewise, B1B1 women had lower HDL-C levels (1.40 mmol/L) compared with B1B2 (1.46 mmol/L) and B2B2 (1.53 mmol/L) women (P<0.001). In men, the B2 allele was associated with increased particle size for HDL and low density lipoprotein. In women, a similar effect was demonstrated only for HDL particle size. The odds ratio for prevalent CHD associated with the B2 allele was 0.696 (P=0.035) in men. After adjusting for age, body mass index, systolic blood pressure, diabetes, smoking, alcohol consumption, beta-blocker use, total cholesterol, and HDL-C, this odds ratio was 0.735 (P=0.187), suggesting that the protective effect of the B2 allele was due in part to its association with HDL-C levels. No significant protective effects were observed in women. These data demonstrate that variation at the CETP gene locus is a significant determinant of HDL-C levels, CETP activity, and lipoprotein size in this population. Moreover, these effects appear to translate into a lower CHD risk among those men with the B2 allele.
Activation of pineal acetyl coenzyme A hydrolase by disulfide peptides. (1982)

Incubation of pineal acetyl-CoA hydrolase preparations with disulfide peptides activates the enzyme. Activation of somatostatin, the most potent peptide tested, is enhanced at higher pH, indicating that disulfide exchange is probably involved. This interpretation is supported by the observation that activation is reversed by dithiothreitol treatment. The order of potency is somatostatin = [Tyr1]somatostatin greater than or equal to Tyr-somatostatin greater than vasopressin = pressinoic acid = [Arg8]vasotocin greater than oxytocin. Insulin, insulin A, insulin B, and [Asu1,6, Arg8]vasopressin were ineffective. This order of potency is distinctly different from that for the inactivation of pineal N-acetyltransferase (Namboodiri, M. A. A., Favilla, J., and Klein, D. C. (1981) Science 213, 571-573) by these peptides. Examination of the primary structure of the peptides reveals that the above order of potency is consistent with the predictions of the nearest neighbor model as applied to the disulfide group.
Exploiting diverse knowledge sources via maximum entropy in named entity recognition (1998)

This paper describes a novel statistical namedentity (i.e. &amp;quot;proper name&amp;quot;) recognition system built around a maximum enti W framework. By working within the framework of maximum entropy. theory and utilizing a flexible object-based architecture, the system is able to make use of an extraordinarily diverse range of knowledge sources in making its tagging decisions. These knowledge sources include capitalization features, lexical features, features in- dicating the current section of text (i.e. headline or main body), and dictionaries of single or multi-wtrd terms. The purely statistical system contains no hand-generated patterns and achieves a result comparable with the best statistical systems. However, when combined with other handcoded systems, the system achieves scores that exceed the highest comparable scores thus-far published.
Labile plasma iron in iron overload: redox activity and susceptibility to chelation (2003)

Plasma non-transferrin-bound-iron (NTBI) is believed to be responsible for catalyzing the formation of reactive radicals in the circulation of iron overloaded subjects, resulting in accumulation of oxidation products. We assessed the redox active component of NTBI in the plasma of healthy and beta-thalassemic patients. The labile plasma iron (LPI) was determined with the fluorogenic dihydrorhodamine 123 by monitoring the generation of reactive radicals prompted by ascorbate but blocked by iron chelators. The assay was LPI specific since it was generated by physiologic concentrations of ascorbate, involved no sample manipulation, and was blocked by iron chelators that bind iron selectively. LPI, essentially absent from sera of healthy individuals, was present in those of beta-thalassemia patients at levels (1-16 microM) that correlated significantly with those of NTBI measured as mobilizer-dependent chelatable iron or desferrioxamine chelatable iron. Oral treatment of patients with deferiprone (L1) raised plasma NTBI due to iron mobilization but did not lead to LPI appearance, indicating that L1-chelated iron in plasma was not redox active. Moreover, oral L1 treatment eliminated LPI in patients. The approach enabled the assessment of LPI susceptibility to in vivo or in vitro chelation and the potential of LPI to cause tissue damage, as found in iron overload conditions.
Pseudouridines in and near the branch site recognition region of U2 snRNA are required for snRNP biogenesis and pre-mRNA splicing inXenopusoocytes (2004)

Virtually all uridines in the branch site recognition region (BSRR) of vertebrate U2 are converted into pseudouridines after initial transcription. Here, we report a functional analysis of these modified nucleotides using the Xenopus oocyte reconstitution system. Using site-specific (32)P-labeling and TLC, we show that U2 pseudouridylation occurs much faster in the BSRR than in the 5'-terminal region. To functionally dissect the pseudouridines in the BSRR, we replaced each uridine with 5-fluorouridine (unmodifiable nucleotide) using site-specific RNase H cleavage directed by 2'-O-methyl-RNA-DNA chimeras followed by three-piece ligation. Whereas in vitro transcribed U2 containing no 5-fluorouridines rescued splicing in U2-depleted oocytes, no rescue was observed with U2 RNA containing 5-fluorouridines introduced into the BSRR. Additionally, U2 RNA containing 5-fluorouridines in the BSRR specifically inhibited pseudouridylation in the BSRR of in vitro transcribed U2 injected at a later time, although pseudouridylation in the 5'-end region was not affected. Our reconstitution results indicated that prior injection into U2-depleted oocytes with U2 RNA containing 5-fluorouridines in the BSRR almost completely abrogated the ability of in vitro transcribed U2 to rescue splicing, whereas full rescue was obtained with either cellular U2 or U2 containing pseudouridines in the BSRR. Further analyses using glycerol-gradient and native gel electrophoresis indicated that U2 RNAs lacking the BSRR pseudouridines do not participate in the assembly of the functionally active 17S U2 snRNP and the spliceosome. We conclude that the BSRR pseudouridines of vertebrate U2 are required for complete snRNP assembly and pre-mRNA splicing in Xenopus oocytes.
Audio coding technology of ExAC (2005)

A new low bitrate audio coding technology (called "ExAC") based on enhanced audio coding (EAC) and spectral band replication (SBR) is introduced. The major building blocks of the coding schemes are explained, in which EAC works as a core coder and SBR works as a powerful bandwidth extension module. The new coding technology provides a high quality audio compression scheme for a broad range of applications, including the high-density laser video diskette, HDTV and very low bitrate applications such as AM audio broadcasting and streaming.
Analysis of parathyroid hormone's principal receptor-binding region by site-directed mutagenesis and analog design (1993)

Previous deletion studies established that the 25-34 region of PTH is important for receptor binding. We used oligonucleotide-directed mutagenesis to generate 47 different mutations in this region of human (h) PTH-(1-84) and evaluated cAMP-stimulating activity in ROS 17/2.8 cells. The hydrophobic residues Leu24 and Leu28 stood out as mutationally intolerant sites, while neighboring polar residues were comparatively tolerant. A series of synthetic PTH analogs was designed to test these residues further. The affinity of [Tyr34]hPTH-(1-34)NH2 for ROS 17/2.8 cells [dissociation constant (Kd), approximately 5 nM)] was dramatically reduced by the substitution of either Leu24 or Leu28 with Glu (Kd, approximately 20,000 and 8,000 nM, respectively). The Val31—>Glu substitution also sharply reduced affinity (Kd, approximately 200 nM). In contrast, the nearby charge-reversing change of Asp30—>Lys had no effect on binding affinity (Kd, approximately 5 nM). Similar effects were observed in the opposum kidney cell line. The binding of [Tyr34]hPTH-(15-34)NH2 to ROS 17/2.8 and opposum kidney cells (Kd, approximately 10 microM) was abolished by Glu substitutions at position 24, 28, or 31; the Lys30 change was without effect. These results suggest that the adverse effects of the Glu substitutions on receptor binding are not due purely to the disruption of tertiary interactions with the 1-14 region. Circular dichroism spectroscopy indicated that the substitutions do not affect local helical structure. The data suggest that Leu24, Leu28, and Val31 contribute important receptor-binding interactions and are consistent with the hypothesis that an amphipathic alpha-helix in the carboxy-terminal region of PTH-(1-34) is involved in receptor binding.
Alcohol Exacerbates Murine Pulmonary Tuberculosis (2004)

Alcohol consumption has been described as a risk factor for infection with Mycobacterium tuberculosis, but its contribution to tuberculosis has been difficult to isolate from other adverse socioeconomic factors. Our objective was to evaluate the impact of alcohol consumption on pulmonary infection with M. tuberculosis in a murine model. BALB/c mice were maintained on the Lieber-DeCarli liquid ethanol diet or a liquid control diet and infected intratracheally with low-dose M. tuberculosis H37Rv. Lung organism burdens, lung and lung-associated lymph node CD4(+)- and CD8(+)- lymphocyte numbers and rates of proliferation, and CD4(+)-lymphocyte cytokine production levels were compared between the groups. The alcohol-consuming mice had significantly higher lung organism burdens than the control mice, and the CD4(+)- and CD8(+)-lymphocyte responses to pulmonary infection with M. tuberculosis were blunted in the alcohol group. Lymphocyte proliferation and production of gamma interferon were decreased in the CD4(+) lymphocytes from the alcohol-consuming mice. Additionally, lung granulomas were significantly smaller in the alcohol-consuming mice. In conclusion, murine alcohol consumption is associated with decreased control of pulmonary infection with M. tuberculosis, which is accompanied by alterations in the region-specific CD4(+)- and CD8(+)-lymphocyte responses and defective lung granuloma formation.