gebhart/patrepeval huggingface dataset:
Transforming growth factor β‐activated kinase 1 inhibitor suppresses the proliferation in triple‐negative breast cancer through TGF‐β/TGFR pathway (2017)

Breast cancer is one of the most invasive cancer types in female population. The functional activity of Transforming growth factor β-activated kinase 1 (TAK1) in breast cancer progression increasingly attracts attention as it provides a potential target for antibreast cancer drug development. However, the fundamental role of TAK1 for triple-negative breast cancer (TNBC) progression and the effect of potential anti-TAK1 drug candidate needs to be further evaluated. Herein, we focused on the role of TAK1 in human breast cancer cells, and we hypothesized that the inhibition of TAK1 activation can repress the growth of human TNBC cells. We found that the TAK1 is robustly activated within cancer cell population of clinic-derived TNBC samples and the human breast cancer cell lines in culture. Furthermore, we determined the effect of 5Z-7-oxozeaenol (5Z-O), a TAK1-specific small molecule inhibitor, on proliferation of human TNBC cell line. 5Z-O treatment significantly suppressed the proliferation of human TNBC cells. Collectively, these demonstrate the role of TAK1 in human breast cancer and the antiproliferate effect of TAK1 inhibitor. Our study sets the stage for further research on TAK1 as a promising target for development of anti-TNBC drugs and therapeutic strategies.
Semenogelin, the Predominant Protein in Human Semen (1989)

The predominant protein in human semen, semenogelin, was characterized by lambda gt11 clones isolated from a seminal vesicular cDNA library. One clone, carrying a cDNA insert of 1606 nucleotides and a polyadenylated tail, coded for the entire semenogelin precursor. An open reading frame of 1386 nucleotides encodes a signal peptide and the mature protein of 439 amino acid residues, in which residues 85-136 are identical with a previously characterized semenogelin fragment. The polypeptide chain displays a most conspicuous region of internal sequence homology where 46 of the 58 amino acid residues at positions 259-316 are repeated at positions 319-376. An abundant seminal vesicular transcript of 1.8 kilobases (kb) codes for semenogelin. Two additional transcripts, one seminal vesicular 2.2-kb species and one epididymal 2.0-kb species, code for related proteins that have a close structural relationship as well as antigenic epitopes in common with semenogelin. Semenogelin and the semenogelin-related proteins are the major proteins involved in the gelatinous entrapment of ejaculated spermatozoa. Antigenic epitopes common to these proteins are localized to the parts of the spermatozoa involved in locomotion. The spermatozoa become progressively motile as the gel-forming proteins are fragmented by the kallikrein-like protease, prostate-specific antigen, and the gel dissolves.
Bioactivity of anti-angiogenic ribozymes targeting Flt-1 and KDR mRNA (1999)

Vascular endothelial growth factor (VEGF) and its receptors Flt-1 and KDR play important roles in physiological and pathological angiogenesis. Ribozymes that target the VEGF receptor mRNAs were developed and their biological activities in cell culture and an animal model were assessed. Ribozymes targeting Flt-1 or KDR mRNA sites reduced VEGF-induced proliferation of cultured human vascular endothelial cells and specifically lowered the level of Flt-1 or KDR mRNA present in the cells. Anti- Flt-1 and KDR ribozymes also exhibited anti-angiogenic activity in a rat corneal pocket assay of VEGF-induced angiogenesis. This report illustrates the anti-angiogenic potential of these ribozymes as well as their value in studying VEGF receptor function in normal and pathophysiologic states.
A -1 ribosomal frameshift in a double-stranded RNA virus of yeast forms a gag-pol fusion protein. (1991)

The L-A double-stranded RNA (dsRNA) virus of Saccharomyces cerevisiae has two open reading frames (ORFs). ORF1 encodes the 80-kDa major coat protein (gag). ORF2, which is expressed only as a 180-kDa fusion protein with ORF1, encodes a single-stranded RNA-binding domain and has the consensus sequence for RNA-dependent RNA polymerases of (+)-strand and double-stranded RNA viruses (pol). We show that the 180-kDa protein is formed by -1 ribosomal frame-shifting by a mechanism indistinguishable from that of retro-viruses. Analysis of the "slippery site" suggests that a low probability of unpairing of the aminoacyl-tRNA from the 0-frame codon at the ribosomal A site reduces the efficiency of frameshifting more than the reluctance of a given tRNA to have its wobble base mispaired. Frameshifting of L-A requires a pseudoknot structure just downstream of the shift site. The efficiency of the L-A frameshift site is 1.8%, similar to the observed molar ratio in viral particles of the 180-kDa fusion protein to the major coat protein.
Anti-TNF Therapy, from Rationale to Standard of Care: What Lessons Has It Taught Us? (2010)

In the mid-1980s, new molecular tools enabled the biology of cytokine expression and regulation to be studied. Our group uncovered a TNF-dependent cascade in active rheumatoid synovium, suggesting that TNF might be a therapeutic target; this concept was supported in an animal model of the disease. The proof of concept was a series of clinical trials, which have led to marked changes in the therapy of human rheumatoid arthritis and subsequently of other diseases. The work with TNF clearly demonstrated the importance of cytokines in medicine as well as the capacity of mAbs (or receptor fusion proteins) to be used long-term in large populations, thus changing the therapeutic landscape.
Positive selection of CD56+ lymphocytes by magnetic cell sorting. (1998)

A new method for the isolation of CD56+ lymphocytes from peripheral mononuclear blood cells is described. Magnetic microbeads conjugated to goat antimouse antiserum in combination with a murine monoclonal anti-CD56 antibody were coated to the CD56+ target cells. CD56+ cells were then isolated with the use of a magnetic cell sorter. The purity of the CD56+ cells was 98.4 +/- 1% (n = 12) with a recovery of the CD56+ lymphocytes of 57.2 +/- 9% (range 48-77%). The natural killer, activity of the CD56+ lymphocytes as well as the interleukin-2-induced proliferative response were not affected by the isolation procedure or the presence of the magnetic microbeads on the CD56+ cells. The described method might be a useful tool for the further characterization of CD56+ cells and their subsets and can easily be upgraded for clinical use in adoptive immunotherapy with CD56+ lymphocytes.
Polymorphisms in DNA Double-Strand Break Repair Genes and Skin Cancer Risk (2004)

UV can cause a wide range of DNA lesions. UVA-induced oxidative DNA damage and blocked DNA replication by UVB-induced photoproducts can lead to double-strand breaks (DSBs). We selected 11 haplotype-tagging single nucleotide polymorphisms in three DSB repair genes XRCC2, XRCC3, and LigaseIV and evaluated their associations with skin cancer risk in a nested case-control study within the Nurses' Health Study [219 melanoma, 286 squamous cell carcinoma (SCC), 300 basal cell carcinoma (BCC), and 873 controls]. We observed that the XRCC3 18085T (241Met) allele and its associated haplotype were significantly inversely associated with the risks of SCC and BCC, whereas the XRCC3 4552C allele along with its associated haplotype and the XRCC2 30833A allele were significantly associated with increased BCC risk. The LigaseIV 4044T and 4062T alleles were associated with decreased BCC risk; two of four haplotypes were significantly associated with altered BCC risk. A trend toward decreased risk of nonmelanoma skin cancer was found in those harboring a greater number of putative low risk alleles (P for trend, 0.05 for SCC, <0.0001 for BCC). The main effects of these genotypes were essentially null for melanoma risk. This study provides evidence to suggest the role of the DSB repair pathway in skin cancer development, especially for BCC.
Fabrication of 3D InGaN/GaN structures providing semipolar GaN planes for efficient green light emission (2009)

Abstract A fabrication method for the formation of 3D GaN structures with reduced piezoelectric field is presented. Via optimized selective epitaxy the surface is just composed of hexagonally patterned semipolar {1 $ \bar 1 $ 01} or {11 $ \bar 2 $ 2} planes. GaN growth with less NH 3 at a higher growth speed, a doubled effective area and good light outcoupling properties compared to c‐plane growth are additional advantages of this effective technique. The high material quality is confirmed via PL measurements. No defect related optical transitions, often observed in non‐ and semipolar GaN, were found. An In‐GaN QW grown on these semipolar planes showed efficient green (522 nm) light emission in spite of a reduced influence of the quantum confined stark effect (QCSE) (© 2009 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Hybrid heptafocal intraocular lenses (2015)

Optica Applicata, Vol. 45, 2015, nr 3, s. 285-298
Cloning and expression of a complementary DNA encoding a high affinity human neurotensin receptor (1993)

A human neurotensin receptor (hNTR) cDNA was cloned from the colonic adenocarcinoma cell line HT29. The cloned cDNA encodes a putative peptide of 418 amino acids with 7 transmembrane domains. The amino acid sequence of the hNTR is 84% identical to the rat NTR [Neuron, 4 (1990) 847-854]. Transfection of this cDNA into COS cells results in the expression of receptors with pharmacological properties similar to those found with HT29 cells. Northern blot analysis using the hNTR cDNA probe indicated a single transcript of 4 kb in the brain, the small intestine and blood mononuclear cells.
Cerebrospinal Fluid Tissue Factor and Thrombin-Antithrombin III Complex as Indicators of Tissue Injury After Subarachnoid Hemorrhage (1997)

Both mTF and TAT reflected brain injury from SAH and predicted vasospasm, though mTF was more sensitive and a better predictor of outcome. Unlike mTF, TAT did not correlate with vasospasm during the interval when it most commonly occurs, which raised doubt about thrombin activation as a cause.
Site-specific antibodies as probes of the topology and function of the human erythrocyte glucose transporter. (1990)

Antibodies were raised against synthetic peptides corresponding to most of the regions of the human erythrocyte glucose transporter predicted to be extramembranous in the model of Mueckler, Caruso, Baldwin, Panico, Blench, Morris, Lienhard, Allard & Lodish [(1985) Science 229, 941-945]. Most of the antibodies (17 out of a total of 19) recognized the intact denatured protein on Western blots. However, only seven of the antibodies recognized the native membrane-bound protein, even after its deglycosylation. These antibodies, against peptides encompassing residues 217-272 and 450-492 in the hydrophilic central and C-terminal regions of the transporter, bound to the cytoplasmic surface of the erythrocyte membrane. This finding is in agreement with the prediction of the model that these regions of the sequence are cytoplasmic. Antibodies against peptides from the central cytoplasmic loop of the transporter were found to inhibit the binding of cytochalasin B to the membrane-bound protein, whereas antibodies against the C-terminal region had no effect. The anti-peptide antibodies were then used to map the sequence locations of fragments of the transporter arising from tryptic digestion of the membrane-bound protein. This in turn enabled the epitopes for a number of anti-transporter monoclonal antibodies to be located within either the central cytoplasmic loop or the C-terminal region of the protein. Of those monoclonal antibodies which inhibited cytochalasin B binding to the protein, all but one were found to have epitopes within the central region of the sequence. In conjunction with the results of the anti-peptide antibody studies, these findings indicate the importance of this part of the protein for transporter function.
Antibody Recognition of the Pandemic H1N1 Influenza Virus Hemagglutinin Receptor Binding Site (2013)

Influenza virus is a global health concern due to its unpredictable pandemic potential. This potential threat was realized in 2009 when an H1N1 virus emerged that resembled the 1918 virus in antigenicity but fortunately was not nearly as deadly. 5J8 is a human antibody that potently neutralizes a broad spectrum of H1N1 viruses, including the 1918 and 2009 pandemic viruses. Here, we present the crystal structure of 5J8 Fab in complex with a bacterially expressed and refolded globular head domain from the hemagglutinin (HA) of the A/California/07/2009 (H1N1) pandemic virus. 5J8 recognizes a conserved epitope in and around the receptor binding site (RBS), and its HCDR3 closely mimics interactions of the sialic acid receptor. Electron microscopy (EM) reconstructions of 5J8 Fab in complex with an HA trimer from a 1986 H1 strain and with an engineered stabilized HA trimer from the 2009 H1 pandemic virus showed a similar mode of binding. As for other characterized RBS-targeted antibodies, 5J8 uses avidity to extend its breadth and affinity against divergent H1 strains. 5J8 selectively interacts with HA insertion residue 133a, which is conserved in pandemic H1 strains and has precluded binding of other RBS-targeted antibodies. Thus, the RBS of divergent HAs is targeted by 5J8 and adds to the growing arsenal of common recognition motifs for design of therapeutics and vaccines. Moreover, consistent with previous studies, the bacterially expressed H1 HA properly refolds, retaining its antigenic structure, and presents a low-cost and rapid alternative for engineering and manufacturing candidate flu vaccines.
A Phase I Evaluation of the Safety and Immunogenicity of Vaccination with Recombinant gp160 in Patients with Early Human Immunodeficiency Virus Infection (1991)

This gp160 vaccine is safe and immunogenic in volunteer patients with early HIV infection. Although it is too early to know whether this approach will be clinically useful, further scientific and therapeutic evaluation of HIV-specific vaccine therapy is warranted. Similar vaccines may prove to be effective for other chronic infections.
D-Glucose Dehydrogenase from Bacillus megaterium M 1286: Purification, Properties and Structure (1975)

1) Glucose dehydrogenase from Bacillus megaterium has been purified to a specific activity of 550 U per mg protein. The homogeneity of the purified enzyme was demonstrated by gel electrophoresis and isoelectric focusing. 2) The amino acid composition has been determined. 3) The molecular weight of the native enzyme was found to be 116000 by gel permeation chromatography, in good agreement with the values of 120000 and 118000, which were ascertained electrophoretically according to the method of Hedrick and Smith and by density gradient centrifugation, respectively. 4) In the presence of 0.1% sodium dodecylsulfate and 8M urea, the enzyme dissociates into subunits with a molecular weight of 30000 as determined by dodecylsulfate gel electrophoresis. These values indicate that the native enzyme is composed of four polypeptide chains, each probably possessing one coenzyme binding site, which can be concluded from fluorescent titration of the NADH binding sites. 5) In polyacrylamide disc electrophoresis, samples of the purified enzyme exhibit three bands of activity, which present the native (tetrameric) form of glucose dehydrogenase and two monomeric forms (molecular weight 30000), arising under the conditions of pH and ionic strength of this method. 6) The enzyme shows a sharp pH optimum at pH 8.0 in Tris/HCl buffer, and a shift of the pH optimum to pH 9.0 in acetate/borate buffer. The limiting Michaelis constant at pH 9.0 for NAD is 4.5 mM and 47.5 mM for glucose. The dissociation constant for NAD is 0.69 mM. 7) D-Glucose dehydrogenase is highly specific for beta-D-glucose and is capable of using either NAD or NADP. The enzyme is insensitive to sulfhydryl group inhibitors, heavy metal ions and chelating agents.
Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response (2005)

Although aminoacyl-tRNA synthetases (ARSs) are essential for protein synthesis, they also function as regulators and signaling molecules in diverse biological processes. Here, we screened 11 different human ARSs to identify the enzyme that is secreted as a signaling molecule. Among them, we found that lysyl-tRNA synthetase (KRS) was secreted from intact human cells, and its secretion was induced by TNF-alpha. The secreted KRS bound to macrophages and peripheral blood mononuclear cells to enhance the TNF-alpha production and their migration. The mitogen-activated protein kinases, extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, and Galphai were determined to be involved in the signal transduction triggered by KRS. All of these activities demonstrate that human KRS may work as a previously uncharacterized signaling molecule, inducing immune response through the activation of monocyte/macrophages.
A 0.5 V Sub-Microwatt CMOS Image Sensor With Pulse-Width Modulation Read-Out (2010)

Energy minimization is a critical goal in size-constrained wireless sensors. Sensing elements are traditionally power hungry and require special attention in low energy systems. In this work, we study ultra-low power image sensors. In particular, we explore the use of aggressive voltage scaling in CMOS image sensors for applications ranging from retinal prostheses to battlefield monitoring and surveillance. We begin with a discussion of the challenges faced by a traditional 3T active pixel sensor as the supply voltage scales to 0.5 V and below. We then discuss an image sensor with pulse-width modulation read-out that is optimized for 0.5 V operation. A 0.13 ¿m test-chip with a 128 × 128 pixel array is shown to be functional with V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dd</sub> as low as 0.45 V with energy consumption of 140 nJ/frame at V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dd</sub> = 0.5 V (8.5 frames per second) and power consumption of only 700 nW at V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dd</sub> = 0.5 V (0.5 frames per second). A focus is also placed on quantifying the noise implications of low voltage operation on the test-chip, which has a measured signal-to-noise ratio of 23.4 dB in saturation at V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dd</sub> = 0.5 V.
Three-dimensional position and orientation measurements using magneto-quasistatic fields and complex image theory [measurements corner] (2014)

Traditional wireless position-location systems, operating using propagating waves, suffer reduced performance in non-line-of-sight (NLoS) applications. Traditional systems that use quasistatic fields have instead been limited to short ranges, progressive direction-finding applications, require RF fingerprinting, or do not provide complete immunity to dielectric obstacles (use of electric fields). These limitations impose severe restrictions in applications such as tracking an American football during game play, where position and orientation tracking may be required over long ranges, and when the line-of-sight (LoS) is blocked by groups of people. A technique using magneto-quasistatic fields and complex image theory was recently shown to circumvent these problems, and to enable accurate long-range one-dimensional and two-dimensional measurements. In this work, we present three-dimensional position and orientation measurements using the magneto-quasistatic system and complex image theory over an area of 27.43 m × 27.43 m. Inverting the theoretical expression for the voltage measured at the terminals of the receiving loops to determine three-dimensional position and orientation resulted in mean and median geometric position errors of 0.77 m and 0.71 m, respectively; inclination orientation mean and median errors of 9.67° and 8.24°, respectively; and azimuthal orientation mean and median errors of 2.84° and 2.25°, respectively.
Thrombotic complications during L-asparaginase treatment for acute lymphocytic leukemia. (1991)

We report 2 new cases of thrombosis occurring in a cohort of 21 consecutive patients with acute lymphocytic leukemia treated with L-asparaginase (L-ase), 6,000 U/die s.c. or i.m. days 15-21 from start of chemotherapy, according to the GIMEMA LAL 0288 protocol. The first patient died of massive diffuse thromboembolism (thrombosis of sagittal sinus and of suprahepatic veins and pulmonary arteries; multiple hepatic and splenic infarctions) associated with markedly reduced levels of protein C, antithrombin III and plasminogen. In the second patient, portal vein thrombosis developed soon after the completion of L-ase. Antithrombin III was reduced, whereas protein C level was normal. Therapy with fresh frozen plasma and subcutaneous calcium heparin (12,500 U twice daily) proved successful, and 8 days later abdominal echotomography revealed the complete disappearance of the thrombus. The incidence of thrombosis is similar to that previously found in a cohort of consecutive patients treated at our Department with a different schedule and dosage of L-ase administration, and similar to that reported in previous series.
A Flat High-Frequency Scanning Micromirror (2000)

We present the Staggered Torsional Electrostatic Combdrive (STEC) fabrication process that creates thick mirrors with hightorque actuators, thereby allowing high-speed optical scanning with large angular deflections.
Development of a Wide Range pH Sensor based on Electrolyte-Insulator-Semiconductor Structure with Corrosion-Resistant Al[sub 2]O[sub 3]-Ta[sub 2]O[sub 5] and Al[sub 2]O[sub 3]-ZrO[sub 2] Double-Oxide Thin Films (2004)

In order to develop a pH sensor having a wide pH response range from strong acid to strong alkali, electrolyte-insulator-semiconductor capacitors using corrosion-resistant and double-oxide films as the insulator were fabricated and their response characteristics to and alkali metal ions were examined. The sensors with and films having an cationic fraction of about 0.4 showed a wide linear pH response range of −1.5 to 13.0 and a small alkali metal ion sensitivity. The use of the film is suitable for increasing pH sensitivity and that of the film is promising for increasing corrosion resistance against strong alkali solutions. © 2004 The Electrochemical Society. All rights reserved.
Introduction (1993)

This book focuses on late medieval sermons and considers some of the requirements of preaching in general. The present study surveys in some detail the dissemination of the texts in the medieval period. It concentrates upon manuscripts produced in c.1370–c.1500, which appear to have been disseminated in consequence of a number of interrelated developments which had their origins in the later fourteenth century. Notable among these are the enhanced prestige of English, the interests of an increasingly literate laity in more advanced matters of theology than the rudiments of Christian behaviour, and dissatisfaction with the Church, expressed by orthodox and heterodox alike, for what they saw as its failure as a social institution to exhibit the highest spiritual ideals.
Cerebrospinal fluid biogenic amine metabolites, plasma‐rich platelet serotonin and [3H]imipramine reuptake in the primary fibromyalgia syndrome (2001)

Changes in metabolites of CSF biogenic amines appear to be partially correlated to age but remained diagnosis-dependent. High levels of PRP 5-HT in PFS patients were associated with low CSF 5-HIAA levels in female patients but were not accompanied by any change in serotonergic uptake as assessed by platelet [(3)H]imipramine binding sites. These findings do not allow us to confirm that serotonin metabolism is deregulated in PFS patients.