gebhart/patrepeval huggingface dataset:
The Transcriptional Program in the Response of Human Fibroblasts to Serum (1999)

The temporal program of gene expression during a model physiological response of human cells, the response of fibroblasts to serum, was explored with a complementary DNA microarray representing about 8600 different human genes. Genes could be clustered into groups on the basis of their temporal patterns of expression in this program. Many features of the transcriptional program appeared to be related to the physiology of wound repair, suggesting that fibroblasts play a larger and richer role in this complex multicellular response than had previously been appreciated.
Mutational analysis of the trans-activation-responsive region of the human immunodeficiency virus type I long terminal repeat (1988)

We used site-directed mutagenesis to delineate sequences within the human immunodeficiency virus type I (HIV-I) long terminal repeat (LTR) required for trans-activation by the viral tat gene product. We demonstrated that sequences 3' to LTR position +44 are dispensable for trans-activation but that almost all of the mutations tested located between positions -17 and +44 greatly reduced trans-activation at both the transcriptional and posttranscriptional levels. However, displacement of the HIV-I LTR trans-activation-responsive region (TAR) 3' by insertion of up to 32 base pairs between the LTR TATA box and cap site had little effect on trans-activation. An analysis of the DNase I hypersensitivity profile of the HIV-I LTR in transfected cultures suggested the presence of at least two DNase I-hypersensitive sites, including one which extends into the viral TAR element; however, neither of these sites appeared to be significantly affected by tat coexpression. These results allow more precise delineation of the sequences important for TAR function and suggest that the TAR may be recognized by a host-specific DNA-binding protein rather than by the tat protein directly.
CO 2 signaling in guard cells: Calcium sensitivity response modulation, a Ca 2+ -independent phase, and CO 2 insensitivity of the gca2 mutant (2006)

Leaf stomata close in response to high carbon dioxide levels and open at low CO(2). CO(2) concentrations in leaves are altered by daily dark/light cycles, as well as the continuing rise in atmospheric CO(2). Relative to abscisic acid and blue light signaling, little is known about the molecular, cellular, and genetic mechanisms of CO(2) signaling in guard cells. Interestingly, we report that repetitive Ca(2+) transients were observed during the stomatal opening stimulus, low [CO(2)]. Furthermore, low/high [CO(2)] transitions modulated the cytosolic Ca(2+) transient pattern in Arabidopsis guard cells (Landsberg erecta). Inhibition of cytosolic Ca(2+) transients, achieved by loading guard cells with the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and not adding external Ca(2+), attenuated both high CO(2)-induced stomatal closing and low CO(2)-induced stomatal opening, and also revealed a Ca(2+)-independent phase of the CO(2) response. Furthermore, the mutant, growth controlled by abscisic acid (gca2) shows impairment in [CO(2)] modulation of the cytosolic Ca(2+) transient rate and strong impairment in high CO(2)-induced stomatal closing. Our findings provide insights into guard cell CO(2) signaling mechanisms, reveal Ca(2+)-independent events, and demonstrate that calcium elevations can participate in opposed signaling events during stomatal opening and closing. A model is proposed in which CO(2) concentrations prime Ca(2+) sensors, which could mediate specificity in Ca(2+) signaling.
Hormonal Control of Androgen Receptor Function through SIRT1 (2006)

The NAD-dependent histone deacetylase Sir2 plays a key role in connecting cellular metabolism with gene silencing and aging. The androgen receptor (AR) is a ligand-regulated modular nuclear receptor governing prostate cancer cellular proliferation, differentiation, and apoptosis in response to androgens, including dihydrotestosterone (DHT). Here, SIRT1 antagonists induce endogenous AR expression and enhance DHT-mediated AR expression. SIRT1 binds and deacetylates the AR at a conserved lysine motif. Human SIRT1 (hSIRT1) repression of DHT-induced AR signaling requires the NAD-dependent catalytic function of hSIRT1 and the AR lysine residues deacetylated by SIRT1. SIRT1 inhibited coactivator-induced interactions between the AR amino and carboxyl termini. DHT-induced prostate cancer cellular contact-independent growth is also blocked by SIRT1, providing a direct functional link between the AR, which is a critical determinant of progression of human prostate cancer, and the sirtuins.
Trivalent copper, superoxide, and galactose oxidase (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTrivalent copper, superoxide, and galactose oxidaseGordon A. Hamilton, Paul K. Adolf, John De Jersey, Garrett C. DuBois, Gary R. Dyrkacz, and R. Daniel LibbyCite this: J. Am. Chem. Soc. 1978, 100, 6, 1899–1912Publication Date (Print):March 1, 1978Publication History Published online1 May 2002Published inissue 1 March 1978https://doi.org/10.1021/ja00474a042RIGHTS & PERMISSIONSArticle Views584Altmetric-Citations128LEARN 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 (2 MB) Get e-Alertsclose Get e-Alerts
Phase 1 study of CPX-1, a fixed ratio formulation of irinotecan (IRI) and floxuridine (FLOX), in patients with advanced solid tumors (2006)

2014 Background: In vitro studies have shown that varying the ratio of individual agents in drug combinations can result in synergistic, additive or antagonistic activity against tumor cells. CPX-1 is a liposomal formulation of IRI and FLOX in a fixed 1:1 molar ratio which was selected as optimal in vitro and confirmed to be synergistic in vivo in preclinical tumor models. CPX-1 overcomes the dissimilar pharmacokinetics (PK) of the individual drugs, enables sustained maintenance of this ratio after IV administration, and was evaluated in a Phase I open-label, dose-escalation study. Methods: Starting dose was 30 U/m 2 (1 Unit of CPX-1 contains 1 mg IRI + 0.36 mg FLOX) given on day 1 and 15 of each 28-day cycle. Dose escalation was by modified Fibonacci with 4 subjects/cohort. Eligibility included: ≥ 18 yo; advanced solid tumor; ECOG PS ≤ 2; adequate bone marrow/liver/renal function. PK analysis was done on day 1 and 15 of the first cycle. Results: 26 subjects (16M:10F), median age 54.5 y (21–72), all with prior therapy, enrolled in 6 cohorts with the 5th cohort expanded to 6 subjects. Diagnoses: 8 colorectal, 3 pancreatic, 3 ovarian, 2 breast, 2 gastric, 2 esophageal, 2 sarcomas, 1 renal cell, 1 prostate, 1 NSCLC and 1 sphenoid sinus. Response: 20 subjects evaluable: 2 confirmed PRs (NSCLC 8+ wks; Colon 13+ wks, in a patient with prior IRI exposure) and 13 with SD (8–24+wks). Safety: DLTs were observed at the 6 th dose level: 4 subjects with DLTs: 3 diarrhea (one resulting in death due to dehydration/ARF) and one neutropenia. Other possibly related grade 3 and 4 events included one each of: grade 3 diarrhea, grade 3 vomiting, grade 3 neutropenia, grade 3 fatigue, grade 3 compression fracture and arthralgia and pulmonary embolism grade 4. PK: In all 14 subjects analyzed to date the 1:1 molar ratio of IRI to FLOX was maintained for 24 hours and metabolites 5-FU and SN-38 were present in the plasma. Conclusions: CPX-1 represents a new approach to developing drug combinations in which drug ratios are pre-selected in vitro based on optimal antitumor activity and maintained systemically through pharmacokinetic control. Phase 2 studies are planned with a recommended dose of 210U/m 2 of CPX-1. [Table: see text]
A Substituted Imidazolium Chloroaluminate Molten Salt Possessing an Increased Electrochemical Window (1987)

The preparation and characterization of a new molten salt system prepared from aluminum chloride and a trialkylimidazolium halide is described, particularly those molten salts prepared with 1,2‐dimethyl‐3‐propylimidazolium chloride. Molten salts prepared with this salt are liquid over the composition range of ca. 0.65:1 to 2.2:1 at 25°C. A value for the acid‐base equilibrium constant of was determined by potentiometric titration. Cyclic voltammetry results are presented comparing reduction potentials for MEICl and DMPrICl and the electrochemical windows of the respective molten salts. For a 1:1 molten salt, an electrochemical window of nearly 5V is obtained at glassy carbon.
Stabilization of Triple-Stranded Oligonucleotide Complexes: Use of Probes Containing Alternating Phosphodiester and Stereo-Uniform Cationic Phosphoramidate Linkages (1996)

Pyrimidine oligonucleotides containing alternating anionic and stereo-uniform cationic N-(dimethylamino-propyl)phosphoramidate linkages [e.g. d(T+T-)7T, d(T+T-)2(T+C-)5T and (U'+U'-)7dT, where U' is 2'-O-methyluridine)] are shown to bind to complementary double-stranded DNA segments in 0.1 M NaCl at pH 7 to form triple-stranded complexes with the pyrimidine.purine.pyrimidine motif. For each of the sequences investigated, one stereoisomer bound with higher affinity, and the other stereoisomer with lower affinity, than the corresponding all-phosphodiester oligonucleotide. The stereoisomer of d(T+T-)7T that interacted weakly with a dT.dA target in 0.1 M NaCl formed a novel dA.dA.dT triple-stranded complex with poly(dA) or d(Al5C4A15) in 1 M NaCl; in contrast, the stereoisomer that bound strongly to the dT.dA target failed to form a dA.dA.dT triple-stranded complex.
Non-A, Non-B Hepatitis in Chimpanzees and Marmosets (1981)

Nine of 15 specimens of human origin thought to contain non-A, non-B hepatitis agents caused hepatitis in recipient chimpanzees. Two have been further characterized. One inoculum, designated strain F, has been reported to produce unique cytoplasmic changes detected by electron microscopy in liver biopsy specimens; the other, strain H, produced distinctive nuclear changes. It is not yet clear whether these two changes result from infection by different agents; they have been useful markers of non-A, non-B hepatitis in chimpanzees. Strain F was serially passaged six times in chimpanzees, and the infectivity titer of the strain F plasma was estimated to be less than 10(2)/ml. Strain H had an infectivity titer in chimpanzees of at least 10(6)/ml. Both the strain F and strain H agents have been successfully transmitted and serially passaged in marmosets. Although hepatitis was detected in a lower percentage of marmosets than chimpanzees given either the strain F or H inoculum, the infectivity titer of the strain H agent appeared to be greater than or equal to 10(8) marmoset infectious doses/ml.
The role of PARP in DNA repair and its therapeutic exploitation (2011)

Historically, PARP inhibitors (PARPi) were developed to potentiate the cytotoxic effect of certain chemotherapeutic agents and are currently being investigated in combination with chemotherapy in diverse cancer types. These agents are also radiosensitisers and clinical trials of PARPi with concurrent radiation are required. It has long been recognised that defective DNA repair pathways lead to tumour susceptibility. Recent studies indicate that tumour cells with defective homologous recombination (HR) repair pathways, the classic example being BRCA mutations, are exquisitely sensitive to PARPi. Defects in HR are not restricted to BRCA-associated tumours and other cancer types may be enriched for HR defects and hence susceptible to PARP inhibition. The identification of predictive markers for sensitivity to PARP inhibition is a priority area for research.
Penicillin V for group A streptococcal pharyngotonsillitis. A randomized trial of seven vs ten days' therapy (1981)

The effect of duration of orally administered penicillin V potassium on the bacteriologic and clinical cure of group A streptococcal pharyngitis was evaluated. One hundred ninety-one middle-class patients received either seven days (96 patients) or ten days (95 patients) of therapy. Compliance with taking penicillin was assessed by multiple methods, including penicillinuria. Throat cultures were obtained during therapy and three times in the three weeks after therapy. M-precipitin and T-agglutinin typing were done on paired isolates of group A streptococci from patients who had recurrences. Patients treated for seven days had a significantly greater failure rate (30/96 [31%]) compared with patients receiving ten days of penicillin (17/95 [18%]). Compliance rates were high; 66% to 81% of patients showed penicillinuria throughout the study period. Treatment failure was not a function of poor compliance in either treatment group. The data support the current recommendation for ten full days of penicillin therapy and suggest that persistence of streptococci in the throat after adequate therapy may be common.
Cytokine-mediated Transcriptional Induction of the Human Inducible Nitric Oxide Synthase Gene Requires Both Activator Protein 1 and Nuclear Factor κB-binding Sites (1998)

The involvement of AP-1 and NF-kappaB transcription factors in cytokine-mediated induction of human inducible nitric oxide synthase (hiNOS) promoter activity was examined. Luciferase reporter plasmids, containing mutations in AP-1 and NF-kappaB sites, in a hiNOS promoter extending from -8.3 kilobase pairs (kb) to +168, were transiently expressed in A549 cells, and promoter activity was determined after treatment with a cytokine mixture (CM) containing interleukin 1-beta, interferon-gamma, and tumor necrosis factor-alpha. Mutation of the AP-1 heptad located -5301 base pairs upstream decreased gene activation by 90% in a -8.3-kb promoter and a shorter -5.574-kb promoter. Disruption of AP-1 (at -5115) or NF-kappaB (at -115 and -8283) sites reduced promoter activity by 45, 67, and 52%, respectively. Responsiveness to CM was decreased by 85% in constructs mutated in both NF-kappaB sites. By gel retardation analyses, CM increased AP-1- and NF-kappaB binding. Supershift analysis identified Jun D and Fra-2 as components of AP-1 complexes. Each kappaB site bound different complements of NF-kappaB/Rel family members (downstream site, Rel A/p50; upstream site, Rel A/Rel A). Rel A was maximally, whereas IkappaB-alpha was minimally, expressed in nuclei after 1 h of CM treatment, corresponding with the peak in NF-kappaB inding activity. Thus, AP-1 and NF-kappaB are important cis-elements for induction of hiNOS gene transcription.
Variation-aware thermal characterization and management of multi-core architectures (2008)

The accuracy and efficiency of dynamic power and thermal management are both affected by the increased levels of on-chip variation, mainly because dynamic thermal management schemes are oblivious to the variation characteristics of the underlying hardware. We propose a technique that utilizes the existing on-chip sensor infrastructure to improve the inherent thermal imbalances among different cores in a multi-core architecture. Thermal sensor readings are compiled to generate an on-chip variation map, which is provided to the system power/thermal management to effectively manage the existing on-chip variation. Experimental analysis based on live measurements on a special test-chip shows reduced on-chip heating with no performance loss, which improves the power/thermal efficiency of the chip at no cost.
Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma. (1991)

A novel plasminogen-binding protein has been isolated from human plasma utilizing plasminogen-Sepharose affinity chromatography. This protein copurified with alpha 2 antiplasmin when the plasminogen affinity column was eluted with high concentrations of epsilon-aminocaproic acid (greater than 20 mM). Analysis by sodium dodecyl sulfate suggests this protein has an apparent Mr of 60,000. The amino-terminal amino acid sequence showed no similarity to other protein sequences. Based on the amino-terminal amino acid sequence, oligonucleotide probes were designed for polymerase chain reaction primers, and an approximately 1,800 base pair cDNA was isolated that encodes this Mr 60,000 protein. The deduced amino acid sequence reveals a primary translation product of 423 amino acids that is very similar to carboxypeptidase A and B and consists of a 22-amino acid signal peptide, a 92-amino acid activation peptide, and a 309-amino acid catalytic domain. This protein shows 44 and 40% similarity to rat procarboxypeptidase B and human mast cell procarboxypeptidase A, respectively. The residues critical for catalysis and zinc and substrate binding of carboxypeptidase A and B are conserved in the Mr 60,000 plasminogen-binding protein. The presence of aspartic acid at position 257 of the catalytic domain suggests that this protein is a basic carboxypeptidase. When activated by trypsin, it hydrolyzes carboxypeptidase B substrates, hippuryl-Arg and hippuryl-Lys, but not carboxypeptidase A substrates, and it is inhibited by the specific carboxypeptidase B inhibitor (DL-5-guanidinoethyl)mercaptosuccinic acid. We propose that the Mr 60,000 plasminogen-binding protein isolated here is a novel human plasma carboxypeptidase B and that it be designated pCPB.
Using Stop-Flow Lithography To Produce Opaque Microparticles: Synthesis and Modeling (2011)

We report on modeling and experimental studies of the synthesis of opaque microparticles made via stop-flow lithography. Opaque magnetic beads and UV-absorbing dyes incorporated into hydrogel microparticles during synthesis changed the height and the degree of cross-linking of the polymer matrices formed. The effect of the concentration of these opaque materials on the particle height was determined experimentally and agreed well with model predictions based on the photopolymerization process over a wide range of UV absorbance. We also created particles with two independent anisotropies, magnetic and geometric, by applying magnetic fields during particle synthesis. Our work provides a platform for rational design of lithographic patterned opaque particles and also a new class of structured magnetic microparticles.
Mechanistic coupling of protease signaling and initiation of coagulation by tissue factor (2001)

The crucial role of cell signaling in hemostasis is clearly established by the action of the downstream coagulation protease thrombin that cleaves platelet-expressed G-protein-coupled protease activated receptors (PARs). Certain PARs are cleaved by the upstream coagulation proteases factor Xa (Xa) and the tissue factor (TF)--factor VIIa (VIIa) complex, but these enzymes are required at high nonphysiological concentrations and show limited recognition specificity for the scissile bond of target PARs. However, defining a physiological mechanism of PAR activation by upstream proteases is highly relevant because of the potent anti-inflammatory in vivo effects of inhibitors of the TF initiation complex. Activation of substrate factor X (X) by the TF--VIIa complex is here shown to produce enhanced cell signaling in comparison to the TF--VIIa complex alone, free Xa, or Xa that is generated in situ by the intrinsic activation complex. Macromolecular assembly of X into a ternary complex of TF--VIIa--X is required for proteolytic conversion to Xa, and product Xa remains transiently associated in a TF--VIIa--Xa complex. By trapping this complex with a unique inhibitor that preserves Xa activity, we directly show that Xa in this ternary complex efficiently activates PAR-1 and -2. These experiments support the concept that proinflammatory upstream coagulation protease signaling is mechanistically coupled and thus an integrated part of the TF--VIIa-initiated coagulation pathway, rather than a late event during excessive activation of coagulation and systemic generation of proteolytic activity.
Expression of Recombinant Human Pregnancy-associated Plasma Protein-A and Identification of the Proform of Eosinophil Major Basic Protein as Its Physiological Inhibitor (2000)

Pregnancy-associated plasma protein-A (PAPP-A), originally known from human pregnancy serum, has recently been demonstrated to be a metzincin superfamily metalloproteinase involved in normal and pathological insulin-like growth factor (IGF) physiology. PAPP-A specifically cleaves IGF-binding protein (IGFBP)-4, one of six antagonists of IGF action, which results in release of IGF bound to IGFBP-4. IGFBP-4 is the only known PAPP-A substrate. Its cleavage by PAPP-A uniquely depends on the presence of IGF. We here report mammalian expression and purification of recombinant 1547-residue PAPP-A (rPAPP-A). The recombinant protein is secreted as a homodimer of about 400 kDa composed of two 200-kDa disulfide-bound subunits. Antigenically and functionally, rPAPP-A behaves like the native protein. In human pregnancy, PAPP-A is known to circulate as a 500-kDa disulfide-bound 2:2 complex with the proform of eosinophil major basic protein (proMBP), PAPP-A/proMBP. A comparison between rPAPP-A and pregnancy serum PAPP-A/proMBP complex surprisingly reveals a difference greater than 100-fold in proteolytic activity, showing that proMBP functions as a proteinase inhibitor in vivo. We find that polyclonal antibodies against PAPP-A abrogate all detectable IGFBP-4 proteolytic activity in pregnancy serum, pointing at PAPP-A as the dominating, if not the only, IGFBP-4 proteinase present in the circulation. We further show that pregnancy serum and plasma contain traces (<1%) of uncomplexed PAPP-A with a much higher specific activity than the PAPP-A/proMBP complex. The measurable activity of the PAPP-A/proMBP complex probably results from the presence of a minor subpopulation of partly inhibited PAPP-A that exists in a 2:1 complex with proMBP. Inhibition of PAPP-A by proMBP represents a novel inhibitory mechanism with the enzyme irreversibly bound to its inhibitor by disulfide bonds.
Expression and significance of LRIG3 in human cervical squamous cell carcinoma. (2015)

LRIG3 plays an important role in Hela229 cell proliferation, apoptosis, and invasiveness.
Carbohydrate-binding protein 35 (Mac-2), a laminin-binding lectin, forms functional dimers using cysteine 186. (1991)

Carbohydrate-binding protein 35 (CBP35), also known as the macrophage surface antigen Mac-2, is a lactosamine-specific lectin whose extracellular properties include the ability to agglutinate cells and to bind avidly to the basement membrane glycoprotein laminin. Although these and other properties would be facilitated by dimerization of this lectin, previous studies have argued against multimeric forms of this protein. We report here that macrophage CBP35, purified by laminin affinity chromatography, exists as several distinct species (Mr 35,000, 67,000, and 80,000) when analyzed under non-reducing conditions. This unexpected finding prompted us to study the biochemistry of multimerization using recombinant CBP35 (rCBP35). rCBP35 expressed in Escherichia coli forms disulfide-linked homodimers (Mr 67,000). The dimeric form of CBP35 binds to laminin with higher affinity than does monomer and by a lactosamine-dependent mechanism. Site-directed mutagenesis indicated that cysteine 186, the single cysteine residue in CBP35, is required for dimerization. These results raise the possibility that homo- and heterodimeric forms of CBP35 contribute to its postulated functions in cell-matrix interactions and growth regulation.