gebhart/patrepeval huggingface dataset:
Computational Prediction and Experimental Verification of the Gene Encoding the NAD+/NADP+-Dependent Succinate Semialdehyde Dehydrogenase inEscherichia coli (2007)

ABSTRACT Although NAD + -dependent succinate semialdehyde dehydrogenase activity was first described in Escherichia coli more than 25 years ago, the responsible gene has remained elusive so far. As an experimental proof of concept for a gap-filling algorithm for metabolic networks developed earlier, we demonstrate here that the E. coli gene yneI is responsible for this activity. Our biochemical results demonstrate that the yneI -encoded succinate semialdehyde dehydrogenase can use either NAD + or NADP + to oxidize succinate semialdehyde to succinate. The gene is induced by succinate semialdehyde, and expression data indicate that yneI plays a unique physiological role in the general nitrogen metabolism of E. coli . In particular, we demonstrate using mutant growth experiments that the yneI gene has an important, but not essential, role during growth on arginine and probably has an essential function during growth on putrescine as the nitrogen source. The NADP + -dependent succinate semialdehyde dehydrogenase activity encoded by the functional homolog gabD appears to be important for nitrogen metabolism under N limitation conditions. The yneI -encoded activity, in contrast, functions primarily as a valve to prevent toxic accumulation of succinate semialdehyde. Analysis of available genome sequences demonstrated that orthologs of both yneI and gabD are broadly distributed across phylogenetic space.
Mechanistic Investigation of the Staudinger Ligation (2005)

The Staudinger ligation of azides and phosphines has found widespread use in the field of chemical biology, but the mechanism of the transformation has not been characterized in detail. In this work, we undertook a mechanistic study of the Staudinger ligation with a focus on factors that affect reaction kinetics and on the identification of intermediates. The Staudinger ligation with alkyl azides was second-order overall and proceeded more rapidly in polar, protic solvents. Hammett analyses demonstrated that electron-donating substituents on the phosphine accelerate the overall reaction. The electronic and steric properties of the ester had no significant impact on the overall rate but did affect product ratios. Finally, the structure of an intermediate that accumulates under anhydrous conditions was identified. These findings establish a platform for optimizing the Staudinger ligation for expanded use in biological applications.
Fluidity of a retrovirus genome (1984)

Comparison of the genomic sequences of the Friend spleen focus-forming virus with other murine retroviral sequences indicated that the spleen focus-forming virus was derived from at least three retroviruses. The 5' end of the virus, from the primer binding site through most of gag, was derived from AKV. The rest of gag and all of pol were of uncertain origin, but were probably derived from the same xenotropic virus that gave rise to the 5' half of env. The remainder was derived from Friend murine leukemia virus. The positions of a 585-base deletion, a 6-base duplication, and a point insertion that leads to a frame shift and premature protein termination in the ecotropic 3' end of env were invariant between three spleen focus-forming virus strains, indicating that they had a single common ancestor. However, the point of crossover between xenotropic viral sequences and Friend murine leukemia virus was different in each strain, and two strains were much more closely related to each other than to the third in the xenotropic region, indicating that these strains had diverged by multiple recombinations. Furthermore, a different nucleotide comprised the single point insertion near the 3' end of env, suggesting that these viruses have an extremely high transition and transversion rate.
Design and Study of Piracetam-like Nootropics, Controversial Members of the Problematic Class of Cognition-Enhancing Drugs (2002)

Cognition enhancers are drugs able to facilitate attentional abilities and acquisition, storage and retrieval of information, and to attenuate the impairment of cognitive functions associated with head traumas, stroke, age and age-related pathologies. Development of cognition enhancers is still a difficult task because of complexity of the brain functions, poor predictivity of animal tests and lengthy and expensive clinical trials. After the early serendipitous discovery of first generation cognition enhancers, current research is based on a variety of working hypotheses, derived from the progress of knowledge in the neurobiopathology of cognitive processes. Among other classes of drugs, piracetam-like cognition enhancers (nootropics) have never reached general acceptance, in spite of their excellent tolerability and safety. In the present review, after a general discussion of the problems connected with the design and development of cognition enhancers, the class is examined in more detail. Reasons for the problems encountered by nootropics, compounds therapeutically available and those in development, their structure activity relationships and mechanisms of action are discussed. Recent developments which hopefully will lead to a revival of the class are reviewed.
Effects of renal denervation on postprandial sodium excretion in experimental heart failure (1994)

The hormonal, hemodynamic and renal excretory changes after an oral load of sodium were examined in renal-denervated dogs with an arteriovenous (AV) fistula and the syndrome of compensated high-output heart failure. After ingestion of a meal containing 125 meq of sodium, the total postprandial urinary sodium excretion and fractional sodium excretion were approximately twofold higher in the renal-denervated AV fistula dogs, compared with a control group with intact renal nerves (P < 0.05). The postprandial elevations in right atrial pressure, plasma atrial natriuretic factor, and filtered load of sodium were similar in the two groups (P > 0.05). Mean arterial pressure and plasma renin activity remained unchanged from baseline in the two subsets of animals (P > 0.05). In the renal-denervated AV fistula dogs, ingestion of a low-salt meal containing 2-3 meq of sodium produced elevations in creatinine clearance and filtered load of sodium of similar magnitude to the high-salt meal. However, the increases in sodium excretion and plasma atrial natriuretic factor were modest and inconsistent. These results demonstrate that the renal nerves play an important modulatory role for postprandial sodium metabolism after a high-salt meal in experimental compensated high-output heart failure. It is suggested that the renal nerves attenuate the expression of postprandial natriuretic mechanisms via a direct tubular mechanism of action.
CAN-based Synchronized Motion Control for Induction Motors (2009)

一个控制区域网络(罐头) 基于多马达有先进同步控制策略的同步运动控制系统被建议。策略是把邻近的跨 coupling 控制策略合并到滑动模式控制建筑学。是由 four-induction-motor-based 说明了试验性的结果，多马达同步经由 CAN 总线，运动控制系统成功地被实现了。与先进同步运动控制策略的雇用，同步表演能显著地被改进。
Structural analysis based on state‐space modeling (1993)

A new method has been developed to compute the probability that each amino acid in a protein sequence is in a particular secondary structural element. Each of these probabilities is computed using the entire sequence and a set of predefined structural class models. This set of structural classes is patterned after Jane Richardson's taxonomy for the domains of globular proteins. For each structural class considered, a mathematical model is constructed to represent constraints on the pattern of secondary structural elements characteristic of that class. These are stochastic models having discrete state spaces (referred to as hidden Markov models by researchers in signal processing and automatic speech recognition). Each model is a mathematical generator of amino acid sequences; the sequence under consideration is modeled as having been generated by one model in the set of candidates. The probability that each model generated the given sequence is computed using a filtering algorithm. The protein is then classified as belonging to the structural class having the most probable model. The secondary structure of the sequence is then analyzed using a "smoothing" algorithm that is optimal for that structural class model. For each residue position in the sequence, the smoother computes the probability that the residue is contained within each of the defined secondary structural elements of the model. This method has two important advantages: (1) the probability of each residue being in each of the modeled secondary structural elements is computed using the totality of the amino acid sequence, and (2) these probabilities are consistent with prior knowledge of realizable domain folds as encoded in each model. As an example of the method's utility, we present its application to flavodoxin, a prototypical alpha/beta protein having a central beta-sheet, and to thioredoxin, which belongs to a similar structural class but shares no significant sequence similarity.
Prominent oligodendrocyte genesis along the border of spinal contusion lesions (2007)

Oligodendrocyte (OL) loss and axon demyelination occur after spinal cord injury (SCI). OLs may be replaced, however, by proliferating NG2+ progenitor cells. Indeed, new OLs have been noted in ventral white matter after SCI. Since tissue adjacent to lesion cavities is exposed to different mediators compared with outlying spared tissue, the authors used a rat SCI model to compare NG2 cell proliferation and OL genesis adjacent to lesion cavities with that in spared tissue closer to meninges. NG2 cells proliferated throughout the first week postinjury and accumulated along lesion borders, especially within gray matter. By 3 days postinjury (dpi), new OLs were detected throughout the cross-sections; between 4 and 7 dpi, however, oligogenesis was restricted to lesion borders. New OLs derived from cells proliferating during 1-7 dpi increased dramatically by 14 dpi; most were located along lesion borders and in spared gray matter. Oligogenesis continued along lesion borders during the second week postinjury. Overall OL numbers were reduced at 3 dpi in spared tissue, but rebounded to normal levels by 14 dpi. Surprisingly, lesion borders maintained normal OL numbers at 3 dpi, which then rose to exceed preinjury levels at 7 and 14 dpi. These results indicate that oligogenesis is protracted after SCI and leads to increased OL numbers. Most new OLs are formed in regions of greatest NG2 cell proliferation. Thus, the adult spinal cord spontaneously develops a dynamic gliogenic zone along lesion borders.
Monoclonal antibody-induced cytokine-release syndrome (2009)

Monoclonal antibodies (mAbs) are widely used in anti-inflammatory and tumor therapy. Although effective, mAbs can cause a variety of adverse effects. An important toxicity seen with a few mAbs is cytokine-release syndrome (CRS). These mAbs include: alemtuzumab, muromonab-CD3, rituximab, tosituzumab, CP-870,893, LO-CD2a/BTI-322 and TGN1412. By contrast, over 30 mAbs used clinically are not associated with CRS. In this review, the clinical aspects of CRS, the mAbs associated with CRS, the cytokines involved and putative mechanisms mediating cytokine release will be discussed. This will be followed by a discussion of the poor predictive value of studies in animals and the prospects for creating in vitro screens. Finally, approaches to decreasing the probability of CRS, decreasing the severity or treating CRS, should it occur, will be described.
An SN2 deprotection of synthetic peptides with a low concentration of hydrofluoric acid in dimethyl sulfide: evidence and application in peptide synthesis (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn SN2 deprotection of synthetic peptides with a low concentration of hydrofluoric acid in dimethyl sulfide: evidence and application in peptide synthesisJames P. Tam, William F. Heath, and R. B. MerrifieldCite this: J. Am. Chem. Soc. 1983, 105, 21, 6442–6455Publication Date (Print):October 1, 1983Publication History Published online1 May 2002Published inissue 1 October 1983https://pubs.acs.org/doi/10.1021/ja00359a014https://doi.org/10.1021/ja00359a014research-articleACS PublicationsRequest reuse permissionsArticle Views1770Altmetric-Citations485LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Serine proteases from nematode and protozoan parasites: isolation of sequence homologs using generic molecular probes. (1989)

Serine proteases are one of the biologically most important and widely distributed families of enzymes. Isolation of serine protease genes from organisms of widely diverged phylogenetic groups would provide a basis for studying their biological function, the relationship between structure and function, and the molecular evolution of these enzymes. Serine proteases for which little structural information is known are those that are important in the pathogenesis of parasitic nematode and protozoan diseases. Identification and isolation of protease genes from these organisms is a critical first step in understanding their function for the parasite and possibly suggesting innovative approaches to arresting parasitic diseases. Serine protease gene fragments were isolated from genomic DNA of the parasitic nematode Anisakis simplex by using degenerate oligonucleotide primers and the polymerase chain reaction. Primers were designed based upon the consensus sequence of amino acids flanking the active site serine and histidine residues of eukaryotic serine proteases. Four serine protease gene fragments from this parasite were sequenced and one is 67% identical to the rat trypsin II gene. Alignment of these two genes revealed that the intron-exon junctions are conserved between nematode and rat suggesting that this Anisakis serine protease is structurally and functionally similar to rat trypsin. The generality of this approach to identify serine protease genes from genomic DNA of two very divergent species, a parasitic protozoan and a mammal, was also confirmed. Genes for other enzymes or any protein with conserved structural motifs can be identified and isolated using this technology. Using a similar strategy, a cathepsin B-like cysteine (thiol) protease gene fragment was isolated from Caenorhabditis elegans DNA.
Synthesis and antiviral activity of homologs of noformycin (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and antiviral activity of homologs of noformycinGuy D. Diana, Urano J. Salvador, Ethel S. Zalay, and Francis PancicCite this: J. Med. Chem. 1973, 16, 9, 1050–1053Publication Date (Print):September 1, 1973Publication History Published online1 May 2002Published inissue 1 September 1973https://pubs.acs.org/doi/10.1021/jm00267a022https://doi.org/10.1021/jm00267a022research-articleACS PublicationsRequest reuse permissionsArticle Views72Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Structural and Sequence-Dependent Aspects of Drug Intercalation Into Nucleic Acid (1984)

Information gained from X-ray crystallographic studies on drug-nucleic acid complexes is described, with emphasis on the intercalation process. Relevant data from NMR experiments are examined in order to highlight similarities and differences between solution and solid-state structures. Theoretical analyses of intercalation complexes are also discussed and evaluated, with respect to the structural methods, with special reference being made to nucleic acid conformation and positions of drug molecules in the binding sites.
Precision of extracting absorption profiles from weakly scattering media with spectroscopic time-domain optical coherence tomography (2004)

The feasibility of spectroscopic optical coherence tomography (SOCT) to quantify spatially localized absorption profiles of chromophores embedded in weakly scattering media with a single measurement over the full spectral bandwidth of the light source was investigated by using a state-of-the-art ultra-broad bandwidth Ti:Al(2)O(3) laser (lambdac = 800 nm, Deltalambda = 260 nm, P(out) = 120 mW ex-fiber). The precision of the method as a function of the chromophore absorption, the sample thickness, and different parameters related to the measurement procedure was evaluated both theoretically and experimentally in single and multilayered phantoms. It is demonstrated that in weakly scattering media SOCT is able to extract mua(lambda) as small as 0.5 mm-1 from 450 mum thick phantoms with a precision of ~2% in the central and ~8% at the edges of the used wavelength region. As expected, in phantoms with the same absorption properties and thickness ~180 mum the precision of SOCT decreases to >10% in the central wavelength region.
RET Mutation Screening in MEN2 Patients and Discovery of a Novel Mutation in a Sporadic Medullary Thyroid Carcinoma (1996)

RET germline mutations were found to predispose to the development of three variants of multiple endocrine neoplasia type 2, MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC). We have screened for RET mutations at exons 10, 11, 13, and 16 in leukocyte DNA extracted from 37 individuals, and have identified RET germline mutations in 12 affected individuals from 9 unrelated families. No RET germline mutation was found in 19 individuals with apparent sporadic diseases. We have also screened for RET mutations at exons 10, 11, and 16 in tumor DNA extracted from 13 freshly frozen medullary thyroid carcinomas (MTC). RET mutation was detected in every tumor, either inherited or sporadic, indicating that RET plays an important role in the development of both inherited and sporadic MTC. We initially screened for RET mutations by direct DNA sequencing of the genomic PCR products amplified from patients' leukocyte or tumor DNA. Recently, we utilized the "Cold SSCP" method, nonradioactive single-stranded conformation polymorphism analysis, to screen for RET mutations and have identified a novel mutation, a 6-bp deletion preceding the cysteine-634, in a sporadic MTC.
Adenosine Triphosphate–Induced Shedding of CD23 and L-Selectin (CD62L) From Lymphocytes Is Mediated by the Same Receptor but Different Metalloproteases (1998)

CD23 is a transmembrane protein expressed on the surface of B-lymphocytes that binds IgE, CD21, CD11b, and CD11c. High concentrations of soluble CD23 and L-selectin are found in the serum of patients with B-chronic lymphocytic leukemia (B-CLL). Because extracellular adenosine triphosphate (ATP) causes shedding of L-selectin via activation of P2Z/P2X7 receptors expressed on B-CLL lymphocytes, we studied the effect of ATP on shedding of CD23. ATP-induced shedding of CD23 at an initial rate of 12% of that for L-selectin, whereas the EC50 for ATP was identical (35 micromol/L) for shedding of both molecules. Furthermore, benzoylbenzoyl ATP also produced shedding of CD23 and L-selectin with the same agonist EC50 values for both (10 micromol/L). Inactivation of the P2Z/P2X7 receptor by preincubation with oxidized ATP abolished ATP-induced shedding of both molecules. Moreover, KN-62, the most potent inhibitor for the P2Z/P2X7 receptor, inhibited ATP-induced shedding of both CD23 and L-selectin with the same IC50 (12 nmol/L). Ro 31-9790, a membrane permeant zinc chelator that inhibits the phorbol-ester-stimulated shedding of L-selectin, also inhibited shedding of CD23 from B-CLL lymphocytes. However, the IC50 for this inhibition by Ro31-9790 was different for L-selectin and CD23 (83 v 6 micromol/L, respectively). Although L-selectin was completely shed by incubation of cells with phorbol-ester, CD23 was not lost under these conditions. The data show that extracellular ATP induces shedding of L-selectin and CD23 from B-CLL lymphocytes by an action mediated by the P2Z/P2X7 receptor. However, different membrane metalloproteases seem to mediate the shedding of L-selectin and CD23.
An 8-bit video ADC incorporating folding and interpolation techniques (1987)

A flash-type analog-to-digital converter that operates without a sample-and-hold circuit and incorporates folding and interpolation techniques is presented. It achieves an excellent performance while dissipating only 300 mW from a single 5-V power supply. The folding and interpolation system and the corresponding block diagram are explained. Implementation of folding and interpolation circuitry and the design of the reference resistor are discussed in detail. Several advantages of the system are investigated. The effective resolution of the converter is given as a function of analog input frequency. An 8-bit resolution bandwidth of 8 MHz is achieved. Up to an analog input frequency of 5 MHz, every distortion component stays below -60 dB. The maximum sample rate is 55 MHz. The circuit occupies 6 mm/SUP 2/ of silicon area, bonding pads included. It is realized in a 2.5-/spl mu/m bipolar process with an f/SUB T/ of 7.5 GHz.