gebhart/patrepeval huggingface dataset:
The GA-binding Protein Can Serve as Both an Activator and Repressor of ribosomal protein Gene Transcription (1996)

The GA-binding protein (GABP), a heterodimeric transcription factor with widespread tissue distribution, has been found to be a strong positive regulator of several ribosomal protein (rp)-encoding genes. In such genes, e.g. the mouse rpL30 gene, the GABP-binding sites are located 40-80 base pairs upstream of the transcriptional start point. Potential GABP-binding sites are present in the promoters of numerous other rp genes, not only in upstream regions, but also in the immediate vicinity of the transcriptional start point. The mouse rpS16 gene is an example of the latter type. We demonstrate here that GABP binds to the rpS16 initiation region, and in so doing down-regulates rpS16 transcription both in vivo and in vitro. Supplementation of cell-free extracts with GABP inhibits transcription on rpS16 templates while concomitantly stimulating transcription on rpL30 templates. The repressive and stimulatory effects, which were proportional to the amount of GABP added, required both the GABP alpha subunit and either a beta1 or beta2 subunit. Mutations of the rpS16 GABP-binding sites that abolish binding increased rpS16 promoter activity in vivo and in vitro, whereas mutations that strengthen GABP binding caused a reduction in promoter activity. The binding of GABP to the rpS16 initiation region does not significantly affect the positioning of the transcriptional start points. Taken together with earlier studies, these new findings indicate that GABP can have a dual role as repressor or activator of rp gene transcription.
Novel Actions of Next-Generation Taxanes Benefit Advanced Stages of Prostate Cancer (2015)

Cabazitaxel not only induces improved cytostatic and cytotoxic effects, but also affects distinct molecular pathways, compared with docetaxel, which could underlie its efficacy after docetaxel treatment has failed in patients with CRPC. Finally, RB is identified as the first potential biomarker that could define the therapeutic response to taxanes in metastatic CRPC. This would suggest that loss of RB function induces sensitization to taxanes, which could benefit up to 50% of CRPC cases.
Fluctuations and Instability in Sedimentation (2011)

This review concentrates on the fluctuations of the velocities of sedimenting spheres, and on the structural instability of a suspension of settling fibers. For many years, theoretical estimates and numerical simulations predicted the fluctuations of the velocities of spheres to increase with the size of the container, whereas experiments found no such variation. Two ideas have increased our understanding. First, the correlation length of the velocity fluctuations was found experimentally to be 20 interparticle separations. Second, in dilute suspensions, a vertical variation in the concentration due to the spreading of the front with the clear fluid can inhibit the velocity fluctuations. In a very dilute regime, a homogeneous suspension of fibers suffers a spontaneous instability in which fast descending fiber-rich columns are separated by rising fiber-sparse columns. In a semidilute regime, the settling is hindered, more so than for spheres.
The Role of Genetic factors in Susceptibility to Esophageal Squamous Cell Carcinoma (ESCC) (2011)

Esophageal squamous cell carcinoma (ESCC) is a common cancer in the northeast of Iran. In a series of studies we explored the genetic basis for this. First we showed the risk to age 75 of esophageal cancer in the first-degree relatives of patients with esophageal cancer was 34%, versus 14% for the first-degree relatives of the controls (hazard ratio = 2.3, 95%CI = 1.7-3.1; P = 3 x 10 – 8). Second, in a candidate-gene association approach, we showed that the ADH1B p.Arg48His mutation was associated with a significantly decreased risk of ESCC (OR = 0.41, 95%CI = 0.29-0.76; P = 4x10-4) under a recessive mode of inheritance, although our study subjects were not alcohol drinkers. Third, we showed the BRCA2 p.Lys3326X variant to be associated with increased risk of ESCC (OR = 3.38, 95%CI = 1.97-6.91; P = 2x10-4). Then, we hypothesized that the genes for Fanconi anemia may be candidate genes for ESCC and sequenced the entire coding regions of 12 Fanconi anemia genes in the germline DNA of 190 ESCC cases. We identified three heterozygous insertion/deletions in FANCD2, FANCE and FANCL. All three patients had a strong family history of ESCC. In addition, we found two homozygous patients for the deleterious FANCA p.Ser858Arg mutation. We found two more homozygotes in 556 more ESCC patients, but in none of 1373 matched controls (OR = 16.7, 95%CI = 6.2-44.2; P = 0.01). Finally, we implemented a pilot genome-wide association study in ESCC using 182 cases and 177 matched controls. None of the 1.2 M observed and imputed SNPs showed an association with ESCC at a genome-wide significance level. This showed that an ESCC susceptibility allele with OR&gt;3 estimated from our familial risk study, is unlikely to be identified among common variants of the human genome and we should look for it among rare variants.
Introduction to Combinatorial Solid-Phase Assays for Enzyme Activity and Inhibition (2003)

Proteolytic enzymes are often present as major factors in viral, bacterial, and parasitic infections Therefore, an interest in inhibitors of proteolytic enzymes has been expressed by the pharmaceutical industry, and the investment in the development of specific enzyme mhlbltors remains an important challenge. This chapter describes combinatorial approaches to the characterization of enzyme specificity and identification of enzyme inhibitors or lead compounds by direct visual inspection of resin beads containing both a good substrate and a portion mixing librari of inhibitors (1).
Number and Stoichiometry of Subunits in the Native Atrial G-protein-gated K+ Channel, IKACh (1998)

The G-protein-regulated, inwardly rectifying K+ (GIRK) channels are critical for functions as diverse as heart rate modulation and neuronal post-synaptic inhibition. GIRK channels are distributed predominantly throughout the heart, brain, and pancreas. In recent years, GIRK channels have received a great deal of attention for their direct G-protein betagamma (Gbetagamma) regulation. Native cardiac IKACh is composed of GIRK1 and GIRK4 subunits (Krapivinsky, G., Gordon, E. A., Wickman, K. A., Velimirovic, B., Krapivinsky, L., and Clapham, D. E. (1995) Nature 374, 135-141). Here, we examine the quaternary structure of IKACh using a variety of complementary approaches. Complete cross-linking of purified atrial IKACh protein formed a single adduct with a total molecular weight that was most consistent with a tetramer. In addition, partial cross-linking of purified IKACh produced subsets of molecular weights consistent with monomers, dimers, trimers, and tetramers. Within the presumed protein dimers, GIRK1-GIRK1 and GIRK4-GIRK4 adducts were formed, indicating that the tetramer was composed of two GIRK1 and two GIRK4 subunits. This 1:1 GIRK1 to GIRK4 stoichiometry was confirmed by two independent means, including densitometry of both silver-stained and Western-blotted native atrial IKACh. Similar experimental results could potentially be obtained if GIRK1 and GIRK4 subunits assembled randomly as 2:2 and equally sized populations of 3:1 and 1:3 tetramers. We also show that GIRK subunits may form homotetramers in expression systems, although the evidence to date suggests that GIRK1 homotetramers are not functional. We conclude that the inwardly rectifying atrial K+ channel, IKACh, a prototypical GIRK channel, is a heterotetramer and is most likely composed of two GIRK1 subunits and two GIRK4 subunits.
Transcriptional analysis of the region of the herpes simplex virus type 1 genome containing the UL8, UL9, and UL10 genes and identification of a novel delayed-early gene product, OBPC (1994)

The region of the UL component of the herpes simplex virus type 1 genome between nucleotides 17,793 and 25,150 includes three open reading frames that code for the protein products of the UL8, UL9, and UL10 genes (D.J. McGeogh, M.A. Dalrymple, A.J. Davison, A. Dolan, M.C. Frame, D. McNab, L.J. Perry, J.E. Scott, and P. Taylor, J. Gen. Virol. 69:1531-1574, 1988). We have mapped and characterized the overlapping transcripts in this region and have found that, in addition to the low-abundance UL8 and UL9 transcripts and the abundant UL10 transcript, at least two additional transcription units, designated UL8.5 and UL9.5, are specified by this region of the genome. The 5' ends of the UL8, UL8.5, and UL9 transcripts were mapped to nucleotides 20,682, 22,351, and 23,381, respectively. The 5' terminus of the UL9.5 transcript has not yet been mapped. The 3' ends of the UL8, UL8.5, UL9, and UL9.5 transcripts are coterminal at nucleotide 18,197. The 5' end of the UL10 mRNA, which is transcribed from the strand opposite that specifying the UL8, UL8.5, UL9, and UL9.5 transcripts, lies within the UL9 open reading frame at nucleotide 22,944, while the 3' terminus was mapped to nucleotide 24,666. Time course studies demonstrated that the UL8 and UL9 transcripts are members of the early kinetic class, the UL8.5 mRNA is a delayed-early transcript, and the UL9.5 and UL10 transcripts belong to the true-late kinetic class. Examination of the nucleotide sequence of the UL8.5 transcript revealed a potential open reading frame that overlaps and is in frame with the C-terminal half of the open reading frame encoding the origin-binding protein (OBP), the product of the UL9 gene. In vitro translation of the UL8.5 transcript demonstrated that it encodes a protein with an apparent molecular mass of 53 kDa. This protein was recognized by antibody directed against the C-terminal region of OBP and has thus been designated OBPC. A protein with an identical apparent molecular mass was also recognized by this antibody in infected-cell lysates, indicating that OBPC is synthesized during viral infection.
MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A/PRMT5/RIOK1 Axis (2016)

Homozygous deletions of p16/CDKN2A are prevalent in cancer, and these mutations commonly involve co-deletion of adjacent genes, including methylthioadenosine phosphorylase (MTAP). Here, we used shRNA screening and identified the metabolic enzyme, methionine adenosyltransferase II alpha (MAT2A), and the arginine methyltransferase, PRMT5, as vulnerable enzymes in cells with MTAP deletion. Metabolomic and biochemical studies revealed a mechanistic basis for this synthetic lethality. The MTAP substrate methylthioadenosine (MTA) accumulates upon MTAP loss. Biochemical profiling of a methyltransferase enzyme panel revealed that MTA is a potent and selective inhibitor of PRMT5. MTAP-deleted cells have reduced PRMT5 methylation activity and increased sensitivity to PRMT5 depletion. MAT2A produces the PRMT5 substrate S-adenosylmethionine (SAM), and MAT2A depletion reduces growth and PRMT5 methylation activity selectively in MTAP-deleted cells. Furthermore, this vulnerability extends to PRMT5 co-complex proteins such as RIOK1. Thus, the unique biochemical features of PRMT5 create an axis of targets vulnerable in CDKN2A/MTAP-deleted cancers.
Galactosyltransferase‐dependent sialylation of complex and endo‐N‐acetylglucosaminidase H‐treated core N‐glycans in vitro (1986)

Purified beta-N-acetylglucosaminide beta(1-4)galactosyltransferase and partially purified beta-galactoside alpha(2-6)-sialyltransferase were used to elongate and terminate glycan chains of agalacto-ovalbumin and endo-beta-N-acetylglucosaminidase H-treated yeast invertase in vitro. In the presence of both transferases, 0.1 mol sialic acid was incorporated per mol agalacto-ovalbumin within 24 h. Evidence is presented to show that purification of the galactosylated intermediate increases the efficiency of sialylation. Incorporation of sialic acid into endo-beta-N-acetylglucosaminidase H-treated oligomannose glycoproteins may be useful for in vivo stabilization of these glycoproteins by preventing uptake in liver or reticuloendothelial cells.
Improve the Performance of Soy Protein-Based Adhesives by a Polyurethane Elastomer (2018)

The purpose of this study was to improve the performance of soy protein isolate (SPI) adhesives using a polyurethane elastomer. Triglycidylamine (TGA), SPI, thermoplastic polyurethane elastomer (TPU), and γ-(2,3-epoxypropoxy) propyltrimethoxysilane (KH-560) were used to develop a novel SPI-based adhesive. The residual rate, functional groups, thermal stability, and fracture surface micrographs of the cured adhesives were characterized. Three-ply plywood was fabricated, and the dry/wet shear strength was determined. The experimental results suggested that introducing 2% TGA improved the residual rate of the SPI/TGA adhesive by 4.1% because of the chemical cross-linking reaction between epoxy groups and protein molecules. Incorporating 7% TPU into the SPI/TGA adhesive, the residual rate of the adhesive increased by 5.2% and the dry/wet shear strength of plywood bonded by SPI/TGA/TPU adhesive increased by 10.7%/67.7%, respectively, compared with that of SPI/TGA adhesive. When using KH-560 and TPU together, the residual rate of the adhesive improved by 0.9% compared with that of SPI/TGA/TPU adhesive. The dry and wet shear strength of the plywood bonded by the SPI/TGA/TPU/KG-560 adhesive further increased by 23.2% and 23.6% respectively when compared with that of SPI/TGA/TPU adhesive. TPU physically combined with the SPI/TGA adhesive to form a interpenetration network and KH-560 acted as a bridge to connect TPU and SPI/TGA to form a joined crosslinking network, which improved the thermo stability/toughness of the adhesive and created a uniform ductile fracture section of the adhesive.
Lymphaticovenous Bypass Decreases Pathologic Skin Changes in Upper Extremity Breast Cancer-Related Lymphedema (2014)

We have shown, for the first time, that microsurgical LVB not only improves symptomatology of lymphedema but also helps to improve pathologic changes in the skin. These findings suggest that the some of the pathologic changes of lymphedema are reversible and may be related to lymphatic fluid stasis.
PU.1 Is Essential for p47 Promoter Activity in Myeloid Cells (1997)

Expression of the phagocyte cytosolic protein p47(phox), a component of NADPH oxidase, is restricted mainly to myeloid cells. To study the cis-elements and trans-acting factors responsible for its gene expression, we have cloned and characterized the p47(phox) promoter. A predominant transcriptional start site was identified 21 nucleotides upstream of the translation initiation codon. To identify the gene promoter sequences, transient transfections of HL-60 human myeloid cells were performed with a series of 5'-deletion p47(phox)-luciferase reporter constructs that extended as far upstream as -3050 bp relative to the transcriptional start site. The -224 and -86 constructs had the strongest p47(phox) promoter activity, whereas the -46 construct showed a major reduction in activity and the -36 construct a complete loss of activity. DNase I footprint analysis identified a protected region from -37 to -53. This region containing a consensus PU.1 site bound specifically both PU.1 present in nuclear extracts from myeloid cells and PU.1 synthesized in vitro. Mutations of this site eliminated PU.1 binding and abolished the ability of the p47(phox) promoter to direct expression of the reporter gene. The p47(phox) promoter was active in all myeloid cell lines tested (HL-60, THP-1, U937, PLB-985), but not in non-myeloid cells (HeLa, HEK293). Finally, PU.1 trans-activated the p47(phox)-luciferase constructs in HeLa cells. We conclude that, similar to certain other myeloid-specific genes, p47(phox) promoter activity in myeloid cells requires PU.1.
Five human genes encoding F-box proteins: chromosome mapping and analysis in human tumors (2000)

Members of the F-box protein (Fbp) family are characterized by an approximately 40 amino acid F-box motif. SCF complexes (formed by Skp1, cullin, and one of many Fbps) act as protein-ubiquitin ligases that control the G(1)/S transition of the eukaryotic cell cycle. The substrate specificity of SCF complexes is determined by the presence of different Fbp subunits that recruit specific substrates for ubiquitination. Unchecked degradation of cellular regulatory proteins has been observed in certain tumors and it is possible that deregulated ubiquitin ligases play a role in the altered degradation of cell cycle regulators. We have recently identified a family of human Fbps. As a first step aimed at determining if FBP genes could be involved in human neoplasia, we have mapped the chromosome positions of 5 FBP genes by fluorescence in situ hybridization (FISH) to 10q24 (BTRC alias beta-TRCP/FBW1a), 9q34 (FBXW2 alias FBW2), 13q22 (FBXL3A alias FBL3a), 5p12 (FBXO4 alias FBX4) and 6q25-->q26 (FBXO5 alias FBX5). Since most of these are chromosomal loci frequently altered in tumors, we have screened 42 human tumor cell lines and 48 human tumor samples by Southern hybridization and FISH. While no gross alterations of the genes encoding beta-Trcp/Fbw1a, Fbw2, Fbx4 and Fbx5 were found, heterozygous deletion of the FBXL3A gene was found in four of 13 small cell carcinoma cell lines. This is the first evaluation of genes encoding Fbps in human tumors.
Identification, cloning, and expression of bolA, an ftsZ-dependent morphogene of Escherichia coli (1988)

A newly found morphogene of Escherichia coli, bolA, mapping at min 10 of the genetic map, was cloned in a 7.2-kilobase BamHI fragment and identified by its ability to produce osmotically stable spherical cells when overexpressed. This gene codes for a polypeptide of 13 kilodaltons. Overexpression of bolA+ was achieved in low-copy-number vectors with operon fusions to the tet and lac promoters, indicating a clockwise direction of transcription. While no modification of any of the penicillin-binding proteins was observed, morphological effects due to overexpression of bolA+ were shown to be dependent on the presence of an active ftsZ gene product. Our results suggest the existence of a mechanism mediated by FtsZ for modifying the conformation of nascent murein in the early steps of septum formation.
Optical diffraction gratings from polymer-dispersed liquid crystals switched by interdigitated electrodes (2004)

A spatial dependence of the refractive index perturbation induced in a 5-μm-thick polymer-dispersed liquid-crystal layer, by the use of a periodic electric field from the system of 50μm separated interdigitated electrodes, was investigated by measuring the induced in-plane birefringence of the sample. The efficiency of various diffraction orders was measured as a function of the applied voltage amplitude, and the dependence achieved for the 1st diffraction order was compared to the values calculated on the basis of the refractive index profile. The switching properties in response to the amplitude modulation of the driving voltage of various modulation depths were investigated. Our results demonstrate that a very effective phase modulation with response times considerably below 10ms can be achieved at the expense of slightly higher driving fields than needed for the bulk nematic liquid-crystal gratings.
A fully scalable 3D subband video codec (2002)

Multimedia transmissions over heterogeneous networks require a high degree of flexibility from video compression systems. They are expected to be fully scalable, that is to say to be able to partly decode a video bitstream and to get a reconstruction quality proportional to the received amount of information. To achieve this functionality, we propose a video codec based on 2D+t subband decomposition. Groups of frames are first temporally filtered using motion compensation and then spatially decomposed with wavelets. The spatiotemporal coefficients are further scanned and compressed using a new SPIHT-like strategy, namely fully scalable zerotree coding, together with arithmetic encoding, which provides a combination of temporal, spatial and SNR scalability. In addition, scalable motion vector coding ensures a fully progressive bitstream.
Frequency-domain maximum likelihood estimation for automatic speech recognition in additive and convolutive noises (2000)

A feature estimation technique is proposed for speech signals that are degraded by both additive and convolutive noises. An EM algorithm is formulated in the frequency-domain for identification of the magnitude response of the distortion channel and power spectrum of additive noise, and posterior estimates of short-time power spectra of speech are obtained based on the identified channel and noise. The estimated posterior power spectra are used to calculate perceptually-based linear prediction cepstral coefficients, and the estimated cepstral features and their temporal regression coefficients are used for automatic speech recognition using acoustic models trained from clean speech. Experiments were performed on speaker independent continuous speech recognition, where the speech data were taken from the TIMIT database and were degraded by a distortion channel and simulated additive noises with white or colored spectral characteristics at various SNR levels. Experimental results indicate that the proposed technique leads to convergent identification of channel and noise and significantly improved recognition accuracy for speaker-independent continuous speech.
Mucin Glycosylation Is Altered by Pro-Inflammatory Signaling in Pancreatic-Cancer Cells (2009)

Altered glycosylation on the surfaces or secreted proteins of tumor cells is common in pancreatic cancer and is thought to promote cancer progression, but the factors leading to the changes in carbohydrate structures are incompletely understood. We hypothesized that pro-inflammatory conditions can lead to alterations in cancer-associated glycans on mucins produced by pancreatic-cancer cells. With the use of a novel antibody-glycan microarray method, we measured the effects of pro-inflammatory stimuli (oxidative stress and treatment with the cytokines IFNgamma, IL-1alpha, and TNFalpha) on the expression and glycosylation of the mucins MUC1, MUC5AC, and MUC16 in multiple pancreatic cancer cell lines. Mucin glycosylation was significantly affected in specific cell lines, particularly in structures involving terminal galactose or N-acetylgalactosamine. In addition, the responses of the cell lines grouped according to the expression of cell-surface markers that are associated with tumorigenicity, as cell lines bearing minimal surface markers, showed evidence of increased O-glycan extension and decreased presentation of terminal beta1,4-linked galactose, opposite to cell lines bearing multiple markers. These results suggest mechanisms whereby inflammation might influence tumor behavior in a cell-type specific manner through modulating the presentation of cancer-associated glycans.
The Enzymatic Hydrolysis of Methotrexate and Folic Acid (1967)

Abstract A pseudomonad has been isolated from soil which can utilize glutamate derived from the hydrolysis of folate or methotrexate (4-amino-N10-methylpteroylglutamic acid) as a source of carbon and nitrogen. During growth of the organism on folate, large quantities of pteroic acid accumulate in the growth medium. The enzyme responsible for the deamidation has been partially purified. It has a pH optimum of 7.3 and a Km toward methotrexate of 2.4 x 10-4 m. The reactivity of the enzyme toward a number of folate analogues has been studied.
The management of severe Crohn’s disease (2001)

The treatment of severe and active Crohn's disease is currently based on immunosuppression, but also involves the management of nutrition, appropriate selection of patients for surgery, and maintenance of remission in the long term. Corticosteroids remain the drug of the first choice, particularly in the acute setting. However, there is evolving understanding of the role of other immunosuppressants and immune modifiers, as major concerns regarding side-effects and efficacy of steroids in the medium to long-term drive the search for alternatives.