gebhart/patrepeval huggingface dataset:
Tuning a Three-Component Reaction For Trapping Kinase Substrate Complexes (2008)

The upstream protein kinases responsible for thousands of phosphorylation events in the phosphoproteome remain to be discovered. We developed a three-component chemical reaction which converts the transient noncovalent substrate-kinase complex into a covalently cross-linked product by utilizing a dialdehyde-based cross-linker, 1. Unfortunately, the reaction of 1 with a lysine in the kinase active site and an engineered cysteine on the substrate to form an isoindole cross-linked product could not be performed in the presence of competing cellular proteins due to nonspecific side reactions. In order to more selectively target the cross-linker to protein kinases in cell lysates, we replaced the weak, kinase-binding adenosine moiety of 1 with a potent protein kinase inhibitor scaffold. In addition, we replaced the o-phthaldialdehyde moiety in 1 with a less-reactive thiophene-2,3-dicarboxaldehyde moiety. The combination of these two structural modifications provides for cross-linking of a cysteine-containing substrate to its corresponding kinase in the presence of competing cellular proteins.
ACIS Sub-Pixel Resolution: Improvement in Point Source Detection (2011)

We investigate how to achieve the best possible ACIS spatial resolution by binning in ACIS sub-pixel and applying an event repositioning algorithm after removing pixel-randomization from the pipeline data. We quantitatively assess the improvement in spatial resolution by (1) measuring point source sizes and (2) detecting faint point sources. The size of a bright (but no pile-up), on-axis point source can be reduced by 20–30%. With the improved resolution, we detect ∼ 20% more faint sources when embedded in the extended, diffuse emission in a crowded field. We further discuss the false source rate of ∼ 10% among the newly detected sources, using a few ultra-deep observations. 1. How to Obtain the Best Possible ACIS Resolution In order to achieve the best possible ACIS resolution, we apply the following steps to the Chandra X-ray Center (CXC) pipeline products. Then we quantitatively assess the improvement by comparing the point source sizes (§ 2) and detections (§ 3) before and after the procedure. Sub-pixel binning: Chandra coordinates contain positional accuracy finer than one ACIS pixel (0.492 arcsec) through dither and aspect correction. Imaging data binned by ACIS subpixel can already provide an improved resolution. Remove pixel randomization: The current pipeline default is to apply pixel randomization by 1/2 ACIS pixel on the chip coordinate to remove the instrumental “gridded” appearance of the data and to avoid any possible aliasing affects associated with this spatial grid. This pixel randomization has to be removed before applying a sub-pixel algorithm. ACIS sub-pixel algorithm: Positional accuracy can be improved by utilizing the positional information in 3 × 3 event islands. Several sub-pixel event repositioning algorithms have been developed during the first years of the Chandra mission. The first implementation by Tsunemi et al. (2001) applied the knowledge of charge cloud size in 3×3 event islands to corner events with ASCA grade 6 (4–16% of on-axis events). Mori et al. (2001) extended the algorithm to all split pixel events: event grades 2, 3, 4 are shifted 1/2 pixel in one direction, grade 6 events are shifted 1/2 pixel in two directions, while grade 0 events remain centered on the event island. Later Li et al. (2003, 2004) improved the algorithm to SER (subpixel event repositioning) and further to EDSER (energy dependent SER). CXC also implemented EDSER in CIAO 4.3. PSF deconvolution: We do not discuss deconvolution here. We refer the reader to CXC Announcement #64. http://space.mit.edu/CXC/docs/docs.html#subpix http://cxc.harvard.edu/ciao/releasenotes/ciao_4.3_release.html http://cxc.harvard.edu/announcements/announce_64.html
Primary structure of the monomer of the 12S subunit of transcarboxylase as deduced from DNA and characterization of the product expressed in Escherichia coli (1993)

Transcarboxylase from Propionibacterium shermanii is a complex biotin-containing enzyme composed of 30 polypeptides of three different types: a hexameric central 12S subunit to which 6 outer 5S subunits are attached through 12 1.3S biotinyl subunits. The enzyme catalyzes a two-step reaction in which methylmalonyl coenzyme A and pyruvate serve as substrates to form propionyl coenzyme A (propionyl-CoA) and oxalacetate, the 12S subunit specifically catalyzing one of the two reactions. We report here the cloning, sequencing, and expression of the 12S subunit. The gene was identified by matching amino acid sequences derived from isolated authentic 12S peptides with the deduced sequence of an open reading frame present in a cloned P. shermanii genomic fragment known to contain the gene encoding the 1.3S biotinyl subunit. The cloned 12S gene encodes a protein of 604 amino acids and of M(r) 65,545. The deduced sequence shows regions of extensive homology with the beta subunit of mammalian propionyl-CoA carboxylase as well as regions of homology with acetyl-CoA carboxylase from several species. Two genomic fragments were subcloned into pUC19 in an orientation such that the 12S open reading frame could be expressed from the lac promoter of the vector. Crude extracts prepared from these cells contained an immunoreactive band on Western blots (immunoblots) which comigrated with authentic 12S. The Escherichia coli-expressed 12S was purified to apparent homogeneity by a three-step procedure and compared with authentic 12S from P. shermanii. Their quaternary structures were identical by electron microscopy, and the E. coli 12S preparation was fully active in the reactions catalyzed by this subunit. We conclude that we have cloned, sequenced, and expressed the 12S subunit which exists in a hexameric active form in E.coli.
A simple method for extended heart-lung preservation by autoperfusion. (1984)

A modification of Robicsek's autoperfusing heart-lung preparation preserved normal structure in the canine lung for 8 hrs and in the heart for 12 hrs. Applicable to both heart and heart-lung transplantation, the system would permit a safe extension of preservation time limits.
[Two cases of side effects of a fumaric acid ester--local therapy]. (1990)

We report on two cases of adverse reactions to topical treatment with monoethyl fumarate. One patient suffering from atopic dermatitis reacted with contact dermatitis; the other, suffering from psoriasis, developed a generalized, partly pustulous exanthema as well as signs of systemic involvement, such as tachycardia and dyspnea. As the causative mechanism we suggest non-immunological contact urticaria syndrome.
Variant CCG and GGC repeats within the CTG expansion dramatically modify mutational dynamics and likely contribute toward unusual symptoms in some myotonic dystrophy type 1 patients (2010)

Myotonic dystrophy type 1 (DM1) is one of the most variable inherited human disorders. It is characterized by the involvement of multiple tissues and is caused by the expansion of a highly unstable CTG repeat. Variation in disease severity is partially accounted for by the number of CTG repeats inherited. However, the basis of the variable tissue-specific symptoms is unknown. We have determined that an unusual Dutch family co-segregating DM1, Charcot-Marie-Tooth neuropathy, encephalopathic attacks and early hearing loss, carries a complex variant repeat at the DM1 locus. The mutation comprises an expanded CTG tract at the 5'-end and a complex array of CTG repeats interspersed with multiple GGC and CCG repeats at the 3'-end. The complex variant repeat tract at the 3'-end of the array is relatively stable in both blood DNA and the maternal germ line, although the 5'-CTG tract remains genetically unstable and prone to expansion. Surprisingly though, even the pure 5'-CTG tract is more stable in blood DNA and the maternal germ line than archetypal DM1 alleles of a similar size. Complex variant repeats were also identified at the 3'-end of the CTG array of approximately 3-4% of unrelated DM1 patients. The observed polarity and the stabilizing effect of the variant repeats implicate a cis-acting modifier of mutational dynamics in the 3'-flanking DNA. The presence of such variant repeats very likely contributes toward the unusual symptoms in the Dutch family and additional symptomatic variation in DM1 via affects on both RNA toxicity and somatic instability.
Anti-Thy 1.2 monoclonal antibody linked to ricin is a potent cell-type-specific toxin. (1980)

The cell-type specificity of the toxin ricin, which ordinarily binds, enters, and kills cells through receptors containing galactose, has been altered by covalently binding it to a monoclonal antibody and by reversibly binding it to lactose. The antibody, a monoclonal rat IgG2b directed against the Thy 1.2 antigen, provides ricin with a new binding site for the murine thymus cell surface. Addition of lactose saturates the galactose-binding site on ricin and inhibits ricin from binding and killing cells via the galactose-containing receptors. The antibody-ricin hybrid protein, anti-Thy 1.2-ricin, formed with a thioether linkage, has been purified by size exclusion and affinity chromatography. When assayed by inhibition of protein synthesis of EL-4 cells, which express the Thy 1.2 antigen anti-Thy 1.2-ricin is equally as toxic as ricin on a molar basis. The hybrid protein toxicity is unchanged in the presence of 100 mM lactose, whereas unmodified ricin toxicity is reduced to 1% of its toxicity in the absence of lactose. This demonstrates the altered receptor specificity of the ricin hybrid. The cell-type specificity of the anti-Thy 1.2-ricin inhibition of protein synthesis correlates with the presence of the Thy 1.2 antigen. Anti-Thy 1.2-ricin at 4 microgram/ml in the presence of lactose inhibits protein synthesis within 3.5 hr by 60-80% in EL-4 cells but does not affect Thy 1.1 alloantigen and HeLa cells that lack the Thy 1 antigen. Anti-Thy 1.2-ricin in the presence of lactose selectively kills EL-4 cells at concentrations that do not kill AKR-K36 cells. This selectivity, expressed as the ratio of anti-Thy 1.2-ricin concentrations required to kill 40% of both cell types, is 700. Ricin-monoclonal antibody hybrids of this type combine a high degree of cell-type selectivity and toxicity and may have pharmacologic utility as antitumor reagents.
Zein Protein Interactions, Rather Than the Asymmetric Distribution of Zein mRNAs on Endoplasmic Reticulum Membranes, Influence Protein Body Formation in Maize Endosperm (2002)

Prolamin-containing protein bodies in maize endosperm are composed of four different polypeptides, the alpha-, beta-, gamma-, and delta-zeins. The spatial organization of zeins within the protein body, as well as interactions between them, suggests that the localized synthesis of gamma-zeins could initiate and target protein body formation at specific regions of the rough endoplasmic reticulum. To investigate this possibility, we analyzed the distribution of mRNAs encoding the 22-kD alpha-zein and the 27-kD gamma-zein proteins on cisternal and protein body rough endoplasmic reticulum membranes. In situ hybridization revealed similar frequencies of the mRNAs in both regions of the endoplasmic reticulum, indicating that the transcripts are distributed more or less randomly. This finding implies that zein protein interactions determine protein body assembly. To address this question, we expressed cDNAs encoding alpha-, beta-, gamma-, and delta-zeins in the yeast two-hybrid system. We found strong interactions among the 50-, 27-, and 16-kD gamma-zeins and the 15-kD beta-zein, consistent with their colocalization in developing protein bodies. Interactions between the 19- and 22-kD alpha-zeins were relatively weak, although each of them interacted strongly with the 10-kD delta-zein. Strong interactions were detected between the alpha- and delta-zeins and the 16-kD gamma-zein and the 15-kD beta-zein; however, the 50- and 27-kD gamma-zeins did not interact with the alpha- and delta-zein proteins. We identified domains within the 22-kD alpha-zein that bound preferentially the alpha- and delta-zeins and the beta- and gamma-zeins. Affinities between zeins generally were consistent with results from immunolocalization experiments, suggesting an important role for the 16-kD gamma-zein and the 15-kD beta-zein in the binding and assembly of alpha-zeins within the protein body.
Power Reduction during Scan Testing Based on Multiple Capture Technique (2008)

In this paper, we present a multiple capture approach to reducing the peak power as well as average power consumption during testing. The basic idea behind is to divide a scan chain into two sub-scan chains, and only one sub-scan chain will be enabled at a time during the scan shift or capture operations. We develop a pattern insertion technique to efficiently deal with the capture violation problem during the capture cycle. In order to alleviate the timing cost due to the insertion of redundant patterns, a scan chain partitioning method incorporated with test pattern reordering is developed to reduce the testing time. Experimental results for large ISCAS'89 benchmark circuits show that the proposed approach can efficiently reduce peak and average power with little timing overhead.
DYNAMIC O-LINKED GLYCOSYLATION OF NUCLEAR AND CYTOSKELETAL PROTEINS (1997)

Modification of Ser and Thr residues by attachment of O-linked N-acetylglucos-amine [Ser(Thr)-O-GlcNAcylation] to eukaryotic nuclear and cytosolic proteins is as dynamic and possibly as abundant as Ser(Thr) phosphorylation. Known O-GlcNAcylated proteins include cytoskeletal proteins and their regulatory proteins; viral proteins; nuclear-pore, heat-shock, tumor-suppressor, and nuclearoncogene proteins; RNA polymerase II catalytic subunit; and a multitude of transcription factors. Although functionally diverse, all of these proteins are also phosphoproteins. Most O-GlcNAcylated proteins form highly regulated multimeric associations that are dependent upon their posttranslational modifications. Evidence is mounting that O-GlcNAcylation is an important regulatory modification that may have a reciprocal relationship with O-phosphorylation and may modulate many biological processes in eukaryotes.
A prospective study of K-ras mutations in the plasma of pancreatic cancer patients. (1998)

K-ras mutations are frequently found in primary pancreatic adenocarcinomas. In this prospective study, we looked for K-ras mutations in the plasma of patients with pancreatic cancer. We isolated plasma DNA from 21 pancreatic cancer patients using a simple and rapid extraction technique and detected K-ras alterations with a PCR assay and subsequent product sequencing. Patients were followed up to determine their clinical outcome. We found K-ras mutations in the plasma of 17 patients (81%). In cases in which both plasma and pancreatic tissue were available, DNA mutations were similar in corresponding plasma and tissue samples. Plasma DNA alterations were found 5-14 months before clinical diagnosis in four patients. Mutant DNA was not found in the plasma of two patients with chronic pancreatitis or in five healthy controls. Our results indicate that K-ras mutations are often found in DNA isolated from the plasma of pancreatic cancer patients and that a noninvasive plasma-based assay may provide qualitative diagnostic information to clinicians in the future. Larger studies are required to further assess the relevance of our findings to clinical practice.
Case Studies of a Method for Predicting Speech Privacy in the Contemporary Workplace (2003)

In surveys of office environments that measure occupants’ satisfaction with their workspace, the intrusion of unwanted sound—noise—vies with temperature as the leading source of dissatisfaction (Harris, 1978, 1991, Sundstrom, 1994, Brill, 2001). Recent research by the Center for the Built Environment supports this finding, with more than 40% of employees responding to CBE’s occupant satisfaction survey reporting that workplace acoustics make it harder for them to do their job (CBE, 2001). Moreover, an elevated level of workplace noise has been shown to increase stress, decrease motivation and is associated with risk factors for musculoskeletal disorder (Evans, 2000).To improve this situation, architects, interior designers, and facilities management professionals need to be able to translate a proposed design into a specific prediction of acoustical satisfaction with the resulting workspace. Over the past 40 years, acoustical consultants have in fact developed such a method. In the late 1950’s, engineers at Bolt, Beranek &amp;amp; Newman recognized that a majority of acoustical complaints in offices were related to speech privacy—overhearing unwanted conversations or feeling that one is overheard. Building on research at Bell Labs that correlated a listener’s ability to understand words with the ratio between the loudness of a person’s voice and the loudness of the background noise, these engineers demonstrated that a listener’s inability to understand words in a workplace setting is part of this same continuum of signal to noise. They then showed that that a series of objective measurements can establish this ratio and accurately predict an occupant’s satisfaction with their speech privacy (Cavanaugh 1962). Over the past forty years, this method for predicting speech privacy satisfaction with has been simplified (Young, 1965), adapted for use in open plan environments (Pirn, 1971) and consolidated into worksheet formats for both open and closed office environments (Egan, 1972). Versions of this calculation procedure have been published in leading texts on acoustical design, including ones by Cavanaugh (1999), Egan (1988), and Salter (1998).
Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+, CD45RBhigh T cells to SCID recipients (1997)

Transfer of specific T lymphocyte subsets isolated from the spleens of healthy donor mice into immunodeficient SCID mice leads to chronic intestinal inflammation with characteristics similar to those of human inflammatory bowel disease (IBD). CD4+, CD45RBhigh cells cause disease, whereas CD4+, CD45RBlow and CD8+, CD45RBhigh cells do not. Despite this difference, we demonstrate that all three T cell populations reconstitute the intraepithelial and lamina propria compartments of both small and large intestines of SCID recipients. Therefore, infiltration of lymphocytes alone is not sufficient for disease development. CD4+ lymphocytes that have trafficked to the SCID intestine exhibit a phenotype characteristic of normal mucosal lymphocytes. This includes high expression of alpha E integrin and CD69, expression of CD8 alpha alpha homodimers in some of the intraepithelial lymphocytes, as well as low expression of CD62L and CD45RB. The phenotype of the infiltrating mucosal cells is indistinguishable, with respect to the cell surface markers tested, regardless of whether the starting donor population is CD45RBhigh or CD45RBlow. Severe inflammation is restricted primarily to the colon despite lymphocyte infiltration throughout the length of the intestine. This suggests that some property of the colon microenvironment contributes to inflammation. Consistent with this, transfer of CD4+, CD45RBhigh cells to SCID mice that have significantly reduced numbers of enteric flora results in attenuation of the wasting and colitis. Fewer numbers of donor lymphocytes are recovered from the intraepithelial and lamina propria compartments of reduced flora SCID mice. We hypothesize that the ability of pathogenic cells to traffic to the intestine and mediate colitis may be driven by T cell reactivity to bacteria or bacterial products.
Genetics of Parkinson's disease. (2005)

The past few years, mutations in 5 genes (a-synuclein, parkin, DJ-1, PINK1, and LRRK2) have been firmly implicated, and additional chromosomal loci have been mapped for inherited forms of Parkinson's disease (PD). These discoveries have profound implications for both the scientific and clinical communities. First, although some of the Mendelian forms of PD are very rare (including those caused by alfa-synuclein, DJ-1, and PINK1 mutations) they are facilitating greatly the dissection of the molecular pathways that lead to death of dopaminergic neurons; these pathways might also be implicated in the pathogenesis of the common forms of PD. Second, the discoveries of Mendelian forms are challenging the concept of PD as one disease, as well as the validity of the current clinico-pathological disease definition. Last, mutations in 2 of these genes turned out to be frequent enough to have relevance in clinical practice: parkin mutations are common in early-onset familial and sporadic PD; moreover, emerging data delineate mutations in the LRRK2 gene (encoding the dardarin protein) as a frequent cause of the familial late onset PD forms, and even of few late-onset sporadic cases. The importance of genetic testing is expected to increase in the near future in the PD field. Here, the author provides a brief update on the genetics of the monogenic forms of PD.
Effects of Th2 Cytokines on Chemokine Expression in the Lung: IL-13 Potently Induces Eotaxin Expression by Airway Epithelial Cells (1999)

Airway inflammation associated with asthma is characterized by massive infiltration of eosinophils, mediated in part by specific chemoattractant factors produced in the lung. Allergen-specific Th2 cells appear to play a central role in asthma; for example, adoptively transferred Th2 cells induced lung eosinophilia associated with induction of specific chemokines. Interestingly, Th2 supernatant alone administered intranasally to naive mice induced eotaxin, RANTES, monocyte-chemotactic protein-1, and KC expression along with lung eosinophilia. We tested the major cytokines individually and found that IL-4 and IL-5 induced higher levels of macrophage-inflammatory protein-1alpha and KC; IL-4 also increased the production of monocyte-chemotactic protein-1; IL-13 and IL-4 induced eotaxin. IL-13 was by far the most potent inducer of eotaxin; indeed, a neutralizing anti-IL-13 Ab removed most of the eotaxin-inducing activity from Th2 supernatants, although it did not entirely block the recruitment of eosinophils. While TNF-alpha did not stimulate eotaxin production by itself, it markedly augmented eotaxin induction by IL-13. IL-13 was able to induce eotaxin in the lung of JAK3-deficient mice, suggesting that JAK3 is not required for IL-13 signaling in airway epithelial cells; however, eosinophilia was not induced in this situation, suggesting that JAK3 transduces other IL-13-mediated mechanisms critical for eosinophil recruitment. Our study suggests that IL-13 is an important mediator in the pathogenesis of asthma and therefore a potential target for asthma therapy.
Clinical efficacy of the Nd:YAG laser for combination periodontitis therapy. (1997)

Recent results of a limited clinical trial suggest that mechanical root scaling and root planing therapy alone may not be the most effective mode of treatment for patients affected by moderate to severe adult periodontitis. However, scaling and planing combined with laser therapy utilizing a low-powered pulsed Nd:YAG laser have been shown to be successful in the elimination of the bacteria commonly associated with the development of this oral condition. The double-blind, split mouth design study involved 10 human subjects randomly assigned to one of three treatments: 1) scaling and root planing alone, 2) dental laser plus scaling and root planing, and 3) control only. This article presents the clinical results of the trial, which suggest that laser therapy is a viable adjunct to local, nonsurgical therapy such as scaling and planing.