gebhart/patrepeval huggingface dataset:
Inducibility of the TOL catabolic pathway in Pseudomonas putida (pWW0) growing on succinate in continuous culture: evidence of carbon catabolite repression control (1994)

The TOL catabolic genes in Pseudomonas putida (pWW0) are clustered in the upper operon, encoding enzymes for the conversion of toluene and xylenes to benzoate and toluates, and the meta-cleavage operon, encoding enzymes for the conversion of the benzoate and toluates to tricarboxylic acid cycle intermediates. In this study, it was shown that cells growing in a chemostat under succinate growth-limiting conditions express both the upper and meta-cleavage pathways in response to o-xylene, a nonmetabolizable effector of the XylR regulatory protein. The dilution rate maintained in the succinate-limited chemostat cultures influenced the synthesis levels of TOL pathway enzymes, their steady-state levels, and their turnover rates. Cells growing in the presence of nonlimiting concentrations of succinate in continuous culture did not express pathway enzymes in response to the addition of o-xylene, which was due to a blockage at the transcriptional level. Expression of the meta-cleavage pathway in response to 2,3-dimethylbenzoate, a nonmetabolizable effector of the XylS regulatory protein, was 93% lower in cultures exposed to succinate at nonlimiting concentrations than in the succinate-limited chemostats. The mRNA level of xylS during nonlimited growth on succinate was very low compared with that in succinate-limited cultures, suggesting that suppression of expression of the meta-cleavage pathway is regulated mainly by the level of the XylS regulator.
High‐affinity glutamate transporters in chronic pain: an emerging therapeutic target (2014)

Neurons responsible for sensing noxious stimuli and conducting pain signals from periphery to the spinal cord are predominantly glutamatergic. Members of the SLC1A family of high-affinity glutamate transporters (GluTs) are differentially expressed in sensory neurons and surrounding glial cells. These plasma membrane proteins along with glutamate/cystine exchanger, light chain of cystine/glutamate exchanger, are responsible for fine tuning of extracellular glutamate concentrations and, thus, for modulation of excitatory signalling in the spinal cord. Emerging data point at key roles of GluTs in molecular mechanisms of chronic pain and analgesia, incl. development of opioid tolerance. Pharmacological inhibition or antisense down-regulation of spinal GluTs can induce/aggravate pain behaviours, whereas increasing of expression of GluTs by viral gene transfer or positive pharmacological modulators can mitigate chronic pain. Furthermore, some drugs, originally introduced for targeting different pathological conditions, but in parallel exhibiting analgesic properties (e.g. anti-convulsants valproate and riluzole, β-lactam- and tetracycline antibiotics, tricyclic anti-depressants), can enhance glutamate transport in the spinal cord. Thus, molecular modulation of GluTs may turn into prospective therapeutic approach for the management of chronic pain. However, precise pharmacological targeting of this transport system requires in-depth elucidation of molecular factors and signalling pathways underlying expression and activity of individual GluT subtypes, including their splice variants. Neurons conducting pain signals from periphery to the spinal cord are predominantly glutamatergic. High-affinity glutamate transporters (GluTs) regulate extracellular glutamate concentrations and, thus, modulate excitatory signalling in pain circuits. The present review critically analyses accumulated data on the roles of GluTs in molecular mechanisms of chronic pain, as well as perspectives for targeting this transport system in pain therapies.
Optical interconnects to electronic chips (2010)

Optical interconnects are progressively replacing wires at shorter and shorter distances in information processing machines. This paper summarizes the progress toward and prospects for the penetration of optics all the way to the silicon chip.
Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses (2016)

C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.
A Critical Role for Murine Complement Regulator Crry in Fetomaternal Tolerance (2000)

Complement is a component of natural immunity. Its regulation is needed to protect tissues from inflammation, but mice with a disrupted gene for the complement regulator decay accelerating factor were normal. Mice that were deficient in another murine complement regulator, Crry, were generated to investigate its role in vivo. Survival of Crry-/- embryos was compromised because of complement deposition and concomitant placenta inflammation. Complement activation at the fetomaternal interface caused the fetal loss because breeding to C3-/- mice rescued Crry-/- mice from lethality. Thus, the regulation of complement is critical in fetal control of maternal processes that mediate tissue damage.
The Challenges of FIB Chip Repair and Debug Assistance in the 0.25μm Copper Interconnect Millennium (1998)

Abstract Copper will probably replace aluminum alloys as the interconnect metallurgy of choice for high performance semiconductor devices. This transition will challenge the suitability of established practices in focused ion beam (FIB) chip repair. A fundamental rethink in methodology, techniques, and process gases will be required to deal with the new metal films. This paper discusses the results of recent experiments in the areas of FIB exposure, cuts and connections to buried copper lines. While copper tends to mill faster than aluminum, etch rate variations due to grain structure tend to make reliable isolation cuts more difficult. The films also have been shown to suffer regrowth and surface reactions during long term storage following FIB exposure. Attempts at halogen gas assisted etch (GAE) mills result in undesirable removal characteristics, and in the case of bromine, the spontaneous destruction of all exposed copper in the immediate area. Resistance measurements and reliability of deposited tungsten connections to copper lines are also presented. In addition, the latest techniques developed for aluminum wiring isolation and device characterization are shown. These include 'cleanup' methods for achieving good circuit isolation without the extensive use of local oxide deposition, and the latest multilevel version of the FIB ‘wagon wheel’ for SRAM cell characterization. Also included is preliminary data from a custom built FIB chamber four manipulator prober module.
JOHN CALDWELL COLT: A NOTORIOUS ACCOUNTANT (1985)

John C. Colt was the author of a successful bookkeeping text which had many school adoptions and at least 46 editions. During an argument with Samuel Adams, his publisher, over the cost of his 5th edition, Colt killed Adams with a hatchet. Convicted of murder and condemned to execution by hanging, Colt committed suicide in prison in 1842. His text, The Science of Double Entry Bookkeeping, first published in 1838, continued in print until 1856.
Dual modulation of cell survival and cell death by β 2 -adrenergic signaling in adult mouse cardiac myocytes (2001)

The goal of this study was to determine whether beta(1)-adrenergic receptor (AR) and beta(2)-AR differ in regulating cardiomyocyte survival and apoptosis and, if so, to explore underlying mechanisms. One potential mechanism is that cardiac beta(2)-AR can activate both G(s) and G(i) proteins, whereas cardiac beta(1)-AR couples only to G(s). To avoid complicated crosstalk between beta-AR subtypes, we expressed beta(1)-AR or beta(2)-AR individually in adult beta(1)/beta(2)-AR double knockout mouse cardiac myocytes by using adenoviral gene transfer. Stimulation of beta(1)-AR, but not beta(2)-AR, markedly induced myocyte apoptosis, as indicated by increased terminal deoxynucleotidyltransferase-mediated UTP end labeling or Hoechst staining positive cells and DNA fragmentation. In contrast, beta(2)-AR (but not beta(1)-AR) stimulation elevated the activity of Akt, a powerful survival signal; this effect was fully abolished by inhibiting G(i), G(beta gamma), or phosphoinositide 3 kinase (PI3K) with pertussis toxin, beta ARK-ct (a peptide inhibitor of G(beta gamma)), or LY294002, respectively. This indicates that beta(2)-AR activates Akt via a G(i)-G(beta gamma)-PI3K pathway. More importantly, inhibition of the G(i)-G(beta gamma)-PI3K-Akt pathway converts beta(2)-AR signaling from survival to apoptotic. Thus, stimulation of a single class of receptors, beta(2)-ARs, elicits concurrent apoptotic and survival signals in cardiac myocytes. The survival effect appears to predominate and is mediated by the G(i)-G(beta gamma)-PI3K-Akt signaling pathway.
Human Homologs of Schizosaccharomyces pombe Rad1, Hus1, and Rad9 Form a DNA Damage-responsive Protein Complex (1999)

DNA damage activates cell cycle checkpoints in yeast and human cells. In the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe checkpoint-deficient mutants have been characterized, and the corresponding genes have been cloned. Searches for human homologs of S. pombe rad1, rad9, and hus1 genes identified the potential human homologs hRad1, hRad9, and hHus1; however, little is known about the roles of these proteins in human cells. The present studies demonstrate that hRad1 and hHus1 associate in a complex that interacts with a highly modified form of hRad9, but hHus1 and hRad1 do not associate with hRad17. In addition to being a key participant in complex formation, hRad9 is phosphorylated in response to DNA damage. Together, these results suggest that hRad9, hRad1, and hHus1 are central components of a DNA damage-responsive protein complex in human cells.
Synthetic peracetate tea polyphenols as potent proteasome inhibitors and apoptosis inducers in human cancer cells (2005)

It has been suggested that proteasome activity is essential for tumor cell proliferation and drug resistance development. We have previously shown that natural and synthetic ester bond-containing tea polyphenols are selective inhibitors of the chymotrypsin-like activity of the proteasome. The most abundant catechin in green tea is (-)-epigallocatechin-3-gallate [(-)-EGCG], which has been found by many laboratories to exhibit the most potent anticancer activity. We have reported that (-)-EGCG is also the most effective proteasome inhibitor among all the natural green tea catechins tested. Unfortunately, (-)-EGCG is very unstable in neutral and alkaline conditions. In an attempt to increase the stability and thus the efficacy, we synthesized several (-)-EGCG analogs with acetyl protected -OH groups as prodrugs. Here we report, for the first time, that these acetylated synthetic tea analogs are much more potent than natural (-)-EGCG in inhibiting the proteasome in cultured tumor cells. Consistently, these protected analogs showed much higher potency than (-)-EGCG to inhibit proliferation and transforming activity and to induce apoptosis in human leukemic, prostate, breast, and simian virus 40-transformed cells. Additionally, these protected analogs had greatly reduced effects on human normal and non-transformed cells. Therefore, these peracetate protected tea polyphenols are more efficacious than (-)-EGCG and possess great potential to be developed into novel anticancer drugs. Identification of the cytosolic metabolite(s) of peracetate-protected polyphenols in cultured tumor cells and examination of their in vivo tumor growth-inhibitory activity are currently underway in our laboratory.
Chronic lymphocytic leukemia: 2013 update on diagnosis, risk stratification and treatment (2013)

Several new agents (e.g., ibrutinib, obinutuzumab) hold the potential to change standard of CLL treatment in the next 6-12 months. Therefore, CLL patients should be included into current clinical trials whenever possible.
Functional complementarity between the HMG1-like yeast mitochondrial histone HM and the bacterial histone-like protein HU (1993)

The mitochondrial histone HM is the major DNA-binding protein in mitochondria and is necessary for maintenance of the mitochondrial genome in the yeast Saccharomyces cerevisiae during growth on fermentable sugars. HM and the Escherichia coli histone-like protein HU have similar activities in vitro, including DNA supercoiling, but share no sequence similarity. We show that HU can functionally complement the respiration deficiency associated with yeast strains lacking HM. Conversely, phenotypes of E. coli cells lacking HU protein, including nucleoid loss and a filamentous cell morphology, were alleviated by expression of HM in these cells. The HU protein of bacteria and the HM protein of mitochondria are therefore functionally complementary in vivo. Functional similarities among HM, HU, and the nuclear HMG1 proteins are implicated and discussed.
A Phase I, pharmacokinetic (PK) and pharmacodynamic (PD) study of a novel histone deacetylase inhibitor LAQ824 in patients with hematologic malignancies (2004)

3024 Background: LAQ824 is a novel cinnamic acid hydroxamate that inhibits HDAC activity, IC50 of 0.03 μM, and acetylates hsp90 thereby inducing proteosomal degradation of Bcr-Abl and her-2. Methods: LAQ824 is administered by a 3 hr IV infusion on days 1–3 of a 21 day cycle to pts with ALL, AML, CLL, CML in blast crisis or advanced MDS. Modified continuous reassessment method (MCRM) was utilized for dose escalation. Results: 21 pts (median age: 68 yrs; 14 M, 7 F) with AML (15 pts), MDS (4 pts) and CLL (2 pts) have been treated at dose levels (mg/m2): 6 (2 pts); 12 (3 pts); 24 (3 pts); 36 (4 pts); 54 (4 pts); 80 (5 pts). One patient experienced DLT, at the 54 mg/m2 dose level, (cerebral bleed secondary to thrombocytopenia in a CLL patient with rapid disease progression). Grade 2 hyperbilirubinemia was seen in 6 pts. but was rapidly reversible (generally in < 1 week). Monitoring with > 400 ECGs, demonstrates no QTc prolongation. One patient with de novo M1 AML achieved a CR after 2 cycles, and remains in CR after 6 cycles. Six patients had stable disease (5 pts, 4 AML, 1 MDS) or hematologic improvement (1 pt, MDS). PD study for increased histone acetylation (HA) in peripheral lymphocytes was seen on days of dosing ≥ 12 mg/m2, and at ≥ 36 mg/m2 was present for 24 hours after the last dose. PK in 15 pts receiving LAQ824 over a dose range of 6–54 mg/m2 were evaluated by noncompartmental analysis. Plasma LAQ824 concentrations were determined using HPLC/MS/MS assay. Exposure (AUC) increased proportionally with increasing dose. The mean AUCs(0–24) were 165.4 and 1816.8 ng.h/mL, respectively, for 6 and 54 mg/m2 on Day 1. The mean terminal half-lives ranged from 9 to 18 hr. Comparison of AUC between Day 3 and Day 1 indicated a 1.5 fold drug accumulation. Maximum plasma concentrations (Cmax) were observed at 1.5 h after the beginning of infusion, not at the end of infusion, in more than 50% of patients, indicating a non-linear PK. Conclusions: LAQ824 is a novel HDAC inhibitor which is well tolerated, exhibits dose dependent PD effects, and has shown evidence of clinical activity in hematologic malignancies. Further dose escalation is in progress. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceutics Novartis Novartis Novartis
Biomechanical Properties of Bone Allografts (1983)

The biomechanical properties of allograft bone can be altered by the methods chosen for its preservation and storage. These effects are minimal with deep-freezing or low-level radiation. Freeze-drying, however, markedly diminishes the torsional and bending strength of bone allografts but does not deleteriously affect the compressive or tensile strength. Irradiation of bone with more than 3.0 megarad or irradiation combined with freeze-drying appears to cause a significant reduction in breaking strength. These factors should be considered when choosing freeze-dried or irradiated allogeneic bone that will be subjected to significant loads following implantation.
Protein–protein binding is often associated with changes in protonation state (2007)

pK(a) values of ionizable residues have been calculated using the PROPKA method and structures of 75 protein-protein complexes and their corresponding free forms. These pK(a) values were used to compute changes in protonation state of individual residues, net changes in protonation state of the complex relative to the uncomplexed proteins, and the correction to a binding energy calculated assuming standard protonation states at pH 7. For each complex, two different structures for the uncomplexed form of the proteins were used: the X-ray structures determined for the proteins in the absence of the other protein and the individual protein structures taken from the structure of the complex (referred to as unbound and bound structures, respectively). In 28 and 77% of the cases considered here, protein-protein binding is accompanied by a complete (>95%) or significant (>50%) change in protonation state of at least one residue using unbound structures. Furthermore, in 36 and 61% of the cases, protein-protein binding is accompanied by a complete or significant net change in protonation state of the complex relative to the separated monomers. Using bound structures, the corresponding values are 12, 51, 20, and 48%. Comparison to experimental data suggest that using unbound and bound structures lead to over- and underestimation of binding-induced protonation state changes, respectively. Thus, we conclude that protein-protein binding is often associated with changes in protonation state of amino acid residues and with changes in the net protonation state of the proteins. The pH-dependent correction to the binding energy contributes at least one order of magnitude to the binding constant in 45 and 23%, using unbound and bound structures, respectively.
RNA's as catalysts: A new class on enzymes (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRNA's as catalysts: A new class on enzymesGeorge M. McCorkle and Sidney Altman Cite this: J. Chem. Educ. 1987, 64, 3, 221Publication Date (Print):March 1, 1987Publication History Received3 August 2009Published online1 March 1987Published inissue 1 March 1987https://doi.org/10.1021/ed064p221RIGHTS & PERMISSIONSArticle Views126Altmetric-Citations9LEARN 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 InReddit PDF (4 MB) Get e-Alerts Get e-Alerts
Deficiency of the Humoral Immune Response to Measles Vaccine in Infants Immunized at Age 6 Months (1998)

Humoral immunity was deficient in 6-month-old infants given measles vaccine, even in the absence of detectable passively acquired neutralizing antibodies. Comparison of their responses with those of 9- and 12-month-old infants indicates that a developmental maturation of the immune response to measles may occur during the first year of life, which affects the immunogenicity of measles vaccine.
Stable Gastric Pentadecapeptide BPC 157: Novel Therapy in Gastrointestinal Tract (2011)

Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent, safe in inflammatory bowel disease clinical trials (GEPPPGKPADDAGLV, M.W. 1419, PL 14736) and wound healing, stable in human gastric juice and has no reported toxicity. We focused on BPC 157 as a therapy in peridontitis, esophagus, stomach, duodenum, intestine, liver and pancreas lesions. Particularly, it has a prominent effect on alcohol-lesions (i.e., acute, chronic) and NSAIDs-lesions (interestingly, BPC 157 both prevents and reverses adjuvant arthritis). In rat esophagitis and failed function of both lower esophageal sphincter (LES) and pyloric sphincters (PS), BPC 157 increased pressure in both sphincters till normal and reduced esophagitis. However, in healthy rats, it may decrease (PS) or increase (LES) the pressure in sphincters. It has strong angiogenic potential, it acts protectively on endothelium, prevents and reverses thrombus formation after abdominal aorta anastomosis, affects many central disturbances (i.e., dopamine and 5-HT system), the NO-system (either L-arginine and L-NAME effects), endothelin, acts as a free radical scavenger (counteracting CCl4-, paracetamol-, diclofenac-injuries) and exhibits neuroprotective properties. BPC 157 successfully heals the intestinal anastomosis, gastrocutaneous, duodenocutaneous and colocutaneous fistulas in rats, as well as interacting with the NO-system. Interestingly, the fistula closure was achieved even when the BPC 157 therapy was postponed for one month. In short-bowel syndrome escalating throughout 4 weeks, the constant weight gain above preoperative values started immediately with peroral and parental BPC 157 therapy and the villus height, crypth depth and muscle thickness (inner (circular) muscular layer) additionally increased. Thus, BPC 157 may improve gastrointestinal tract therapy.
Sugar‐Responsive Fluorescent Nanospheres (2007)

Sugar-responsive polymer fluorescent nanospheres based on N-isopropylacrylamide and phenylboronic acid were prepared by precipitation polymerization with an average size of 380 nm. The particles swell in the presence of sugar, and the rate and extent of this swelling was measured with distance-dependent fluorescence resonance energy transfer. We present a direct link between the ratio of the intensities of the fluorophores and the particle size. Depending on the kind of sugar and the sugar concentration, different swelling kinetics and equilibrium sizes are observed. With this approach we can obtain insight into complex structure changes with simple fluorescent measurements.