gebhart/patrepeval huggingface dataset:
HDAC1,2 inhibition impairs EZH2- and BBAP- mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma (2014)

Gain-of-function mutations in the catalytic site of EZH2 (Enhancer of Zeste Homologue 2), is observed in about 22% of diffuse large B-cell lymphoma (DLBCL) cases. Here we show that selective inhibition of histone deacetylase 1,2 (HDAC1,2) activity using a small molecule inhibitor causes cytotoxic or cytostatic effects in EZH2 gain-of-function mutant (EZH2GOF) DLBCL cells. Our results show that blocking the activity of HDAC1,2 increases global H3K27ac without causing a concomitant global decrease in H3K27me3 levels. Our data shows that inhibition of HDAC1,2 is sufficient to decrease H3K27me3 present at DSBs, decrease DSB repair and activate the DNA damage response in these cells. In addition to increased H3K27me3, we found that the EZH2GOF DLBCL cells overexpress another chemotherapy resistance factor - B-lymphoma and BAL-associated protein (BBAP). BBAP monoubiquitinates histone H4K91, a residue that is also subjected to acetylation. Our results show that selective inhibition of HDAC1,2 increases H4K91ac, decreases BBAP-mediated H4K91 monoubiquitination, impairs BBAP-dependent DSB repair and sensitizes the refractory EZH2GOF DLBCL cells to treatment with doxorubicin, a chemotherapy agent. Hence, selective HDAC1,2 inhibition provides a novel DNA repair mechanism-based therapeutic approach as it can overcome both EZH2- and BBAP-mediated DSB repair in the EZH2GOF DLBCL cells.
Increased Cytokine Production by Gastric Mucosa in Patients with Helicobacter pylori Infection (1997)

To determine the mechanisms of gastric mucosal injury associated with Helicobacter pylori infection, we investigated the contents of cytokines and inflammatory cell infiltration in the gastric mucosa. Ninety-six patients with dyspepsia were studied (58 gastric ulcer, 38 nonulcer dyspepsia). Of the 96 patients, 63 were infected with H. pylori as determined by microscopic examination with HE staining, culture of H. pylori, or the rapid urease test. Endoscopic biopsy specimens were obtained from both the antrum and the body to examine interleukin (IL)-8, IL-6, IL-1 beta, and tumor necrosis factor-alpha contents in the gastric mucosa by enzyme-linked immunosorbent assay. Inflammatory cell infiltration was assessed according to the Sydney system. IL-8 content was enhanced in both the antral and body mucosa of the H. pylori-positive patients compared with the H. pylori-negative patients. Furthermore, IL-8 content correlated well with the infiltration of both mononuclear cells and polymorphonuclear cells. These results suggest that IL-8 plays important roles in the pathogenesis of gastric mucosal injury associated with H. pylori infection.
The Canine Factor VIII cDNA and 5’ Flanking Sequence (1998)

Factor VIII is a trace plasma glycoprotein involved as a cofactor in the activation of factor X by factor IXa. Inherited deficiency of factor VIII results in the X-linked bleeding disorder hemophilia A which has been documented in humans, horses, sheep and dogs. In this report, the putative proximal promoter, 5' untranslated region, complete coding sequence and 3' untranslated region of the canine factor VIII gene have been characterized. When compared to the human gene, the 5' flanking region shows conservation of transcription factor binding sites in the 5' untranslated region. Alignment of the amino acid sequence with that of the previously reported human, mouse and pig proteins demonstrates sequence identity of between 77 and 92% for the A1, A2, A3, C1 and C2 domains but an identity of only between 44 and 62% for the central B domain. The three thrombin cleavage sites are conserved in the canine sequence as are the protein C cleavage sites and the von Willebrand factor binding region. In addition, all six tyrosine residues that are known to undergo sulfation in the human protein are conserved in the dog. The 3' untranslated region of the canine gene extends 1.5 kilobases. The initial 700 basepairs of this sequence are highly GC rich and the sequence terminates with 2 alternative potential polyadenylation sites. The knowledge of this sequence, in combination with a well described canine model of hemophilia A, provides the necessary starting point for studies addressing the long-term evaluation of factor VIII gene therapy using a homologous transgene.
Different Peptide Binding Specificities of hsp70 Family Members (1994)

A set of heptapeptides was used to compare the relative peptide affinities of three proteins of the hsp70 family: bacterial DnaK, mammalian cytosolic hsc70, and BiP from mammalian ER. Each hsp displays a characteristic pattern of relative affinities. DnaK and hsc70 are more similar to each other than to BiP. A difference in peptide binding specificity may be an important determinant in adjusting an hsp70 family member to its particular cellular function.
P,N ligands in asymmetric catalysis (2013)

P,N ligands are an important class of ligands for asymmetric catalysis. In this tutorial review an up to date account of recent applications of these ligands in asymmetric catalysis is presented. A special focus is given to newer classes of ligands and the application of more established P,N ligands in novel reactions.
Data representation for subsequent image interpretation (1991)

Radiological scans acquired using either the X-ray CT or the NMR imaging techniques provide a wealth of information about tissue behaviour under that imaging modality and contrast agent. To reason about the image in an interpretation stage the scans have to be converted from a pixel by pixel representation to a symbolic form. The technique used by us to generate such a description is region-based segmentation. Each region refers to a pixel or group of pixels having a common attribute. This work has provided a quantitative measure for the partial evaluation of the segmentation which can be applied independent of attribute or combination of attributes. From our initial studies of the behaviour of CT scans a precept for segmentation was developed. The segmentation employs a one-to-one map as an adaptive mechanism. The segmentation criterion at each point in the image therefore depends on the value at the corresponding point in the map. Any process can be used to generate this map, and so easily utilizes new operators as they are developed.
Cytogenetic analysis of plants regenerated from tissue explants and mesophyll protoplasts of winter rape, Brassica napus L. (1984)

Plants were regenerated from seedling tissue explants of four lines of winter rape (Brassica napus L.) including a cytoplasmic male sterile line carrying Raphanus sativus L. cytoplasm, and from leaf mesophyll protoplasts of the cytoplasmic male sterile line. Chromosome number variability was investigated in 102 regenerated plants. Mitotic root-tip cells were scored initially; those plants exhibiting mixoploidy or an altered chromosome number were reexamined at meiosis to confirm the presence of alterations in germ line cells. Plants regenerated from seedling explants included 2n = 38 diploids (87.0%) similar to the parental line, monosomics (7.8%), trisomics (2.6%), and 2n = 76 tetraploids (1.3%). The germ line number was not resolved in one mixoploid (1.3%). Protoplast-derived regenerated plants were diploid (44%), hypodiploid (20%), and tetraploid or hypotetraploid (36%). Meiotic analysis of regenerated plants showed a range of multiple chromosome associations with no plants consistently exhibiting bivalent formation only. Chromosomal alterations other than number may have been induced by culture, but could not be substantiated since multiple chromosome associations were also frequent in control plants grown from seed.Key words: plant regeneration, protoplast regeneration, Brassica napus, cytogenetics.
Dressings and ajunctive therapies: AHCPR guidelines revisited. (1999)

The Agency for Health Care Policy and Research Pressure Ulcer Treatment Guidelines released in 1994 offered 11 recommendations relating to the use of dressings and adjunctive therapies. These recommendations were based on evidence gleaned from the medical literature from 1966 to mid-1993 as well as the accumulated expertise of a multidisciplinary advisory panel. As the recommendations are now 5 years old, a review of the literature published since 1993 was undertaken in order to determine additional evidence for their continued validity or disapproval. The review focused on evidence at the level of controlled clinical trials of dressings and adjunctive therapies in the treatment of pressure ulcers.
TORTİKOLLİS İLE BAŞVURAN İKİ PARAFARENGEAL ABSE VAKASI. CERRAHİ TEDAVİ Mİ? MEDİKAL TEDAVİ Mİ? (2010)

Bu yazida tortikollis ile basvuran iki parafarengeal abse olgusu sunuyoruz. Cocuklarda parafarengeal abselere yonelik tedavi seceneklerini tartisacagiz. VAKA 1: Yirmibes aylik erkek cocuk, boynunu hareket ettirmek istememe sikayetiyle getirildi. Laboratuar incelemesinde WBC:20400 / mm3 ve CRP:76,8 mg/L bulundu. Boyun BT incelemelerinde parafarengeal abse ile uyumlu gorunum saptandi. intravenoz ampisilin-sulbaktam ve metronidazol tedavileri baslandi. Tedavi altindayken abse boyutunda buyume ve enflamasyon gostergelerinde yukselme saptandi. Abse drene edildi ve kulture gonderildi. Kulturde MRSA uremesi oldu. intravenoz vankomisin ve rifampisin tedavisi baslandi. Tedavinin birinci haftasi bittiginde kontrol BT incelemesinde absenin kayboldugu gozlendi. VAKA 2: Sekiz yasinda erkek hasta, boyunda sislik ve egrilik sikayetiyle getirildi. Anterior servikal lenf nodu palpe edilmekteydi. Enflamasyon gostergelerinde yukselme saptandi. Boyun BT incelemesinde parafarengeal abse ile uyumlu gorunum saptandi. Hastaya intravenoz ampisilin-sulbaktam ve metronidazol kombinasyonu baĢlandi. Medikal tedavi ile hasta komplikasyonsuz iyilesti. Sonuc olarak, parafarengeal abselerde tedavi sekli hastalarin klinik bulgularina gore secilmeli ve klinik izlemdeki bulgulara gore yonlendirilmelidir. Anahtar kelimeler: Parafarengeal abse; derin boyun enfeksiyonu; tortikollis; cocuk; tedavi
Observing the Multiexciton State in Singlet Fission and Ensuing Ultrafast Multielectron Transfer (2011)

Multiple exciton generation (MEG) refers to the creation of two or more electron-hole pairs from the absorption of one photon. Although MEG holds great promise, it has proven challenging to implement, and questions remain about the underlying photo-physical dynamics in nanocrystalline as well as molecular media. Using the model system of pentacene/fullerene bilayers and femtosecond nonlinear spectroscopies, we directly observed the multiexciton (ME) state ensuing from singlet fission (a molecular manifestation of MEG) in pentacene. The data suggest that the state exists in coherent superposition with the singlet populated by optical excitation. We also found that multiple electron transfer from the ME state to the fullerene occurs on a subpicosecond time scale, which is one order of magnitude faster than that from the triplet exciton state.
Field Evaluation of a Prototype Paper-Based Point-of-Care Fingerstick Transaminase Test (2013)

Monitoring for drug-induced liver injury (DILI) via serial transaminase measurements in patients on potentially hepatotoxic medications (e.g., for HIV and tuberculosis) is routine in resource-rich nations, but often unavailable in resource-limited settings. Towards enabling universal access to affordable point-of-care (POC) screening for DILI, we have performed the first field evaluation of a paper-based, microfluidic fingerstick test for rapid, semi-quantitative, visual measurement of blood alanine aminotransferase (ALT). Our objectives were to assess operational feasibility, inter-operator variability, lot variability, device failure rate, and accuracy, to inform device modification for further field testing. The paper-based ALT test was performed at POC on fingerstick samples from 600 outpatients receiving HIV treatment in Vietnam. Results, read independently by two clinic nurses, were compared with gold-standard automated (Roche Cobas) results from venipuncture samples obtained in parallel. Two device lots were used sequentially. We demonstrated high inter-operator agreement, with 96.3% (95% C.I., 94.3-97.7%) agreement in placing visual results into clinically-defined "bins" (<3x, 3-5x, and >5x upper limit of normal), >90% agreement in validity determination, and intraclass correlation coefficient of 0.89 (95% C.I., 0.87-0.91). Lot variability was observed in % invalids due to hemolysis (21.1% for Lot 1, 1.6% for Lot 2) and correlated with lots of incorporated plasma separation membranes. Invalid rates <1% were observed for all other device controls. Overall bin placement accuracy for the two readers was 84% (84.3%/83.6%). Our findings of extremely high inter-operator agreement for visual reading-obtained in a target clinical environment, as performed by local practitioners-indicate that the device operation and reading process is feasible and reproducible. Bin placement accuracy and lot-to-lot variability data identified specific targets for device optimization and material quality control. This is the first field study performed with a patterned paper-based microfluidic device and opens the door to development of similar assays for other important analytes.
Encoded combinatorial chemistry. (1992)

The diversity of chemical synthesis and the power of genetics are linked to provide a powerful, versatile method for drug screening. A process of alternating parallel combinatorial synthesis is used to encode individual members of a large library of chemicals with unique nucleotide sequences. After the chemical entity is bound to a target, the genetic tag can be amplified by replication and utilized for enrichment of the bound molecules by serial hybridization to a subset of the library. The nature of the chemical structure bound to the receptor is decoded by sequencing the nucleotide tag.
Insights into Long-Lasting Protection Induced by RTS,S/AS02A Malaria Vaccine: Further Results from a Phase IIb Trial in Mozambican Children (2009)

ClinicalTrials.gov NCT00197041.
ChemInform Abstract: Self‐Consistent Spectrophotometric Basicity Scale in Acetonitrile Covering the Range Between Pyridine and DBU. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Thermostable NAD-linked secondary alcohol dehydrogenase from propane-grown Pseudomonas fluorescens NRRL B-1244 (1983)

NAD-linked alcohol dehydrogenase activity was detected in cell-free crude extracts from various propane-grown bacteria. Two NAD-linked alcohol dehydrogenases, one which preferred primary alcohols (alcohol dehydrogenase I) and another which preferred secondary alcohols (alcohol dehydrogenase II), were found in propane-grown Pseudomonas fluorescens NRRL B-1244 and were separated from each other by DEAE-cellulose column chromatography. The properties of alcohol dehydrogenase I resembled those of well-known primary alcohol dehydrogenases. Alcohol dehydrogenase II was purified 46-fold; it was homogeneous as judged by acrylamide gel electrophoresis. The molecular weight of this secondary alcohol dehydrogenase is 144,500; it consisted of four subunits per molecule of enzyme protein. It oxidized secondary alcohols, notably, 2-propanol, 2-butanol, and 2-pentanol. Primary alcohols and diols were also oxidized, but at a lower rate. Alcohols with more than six carbon atoms were not oxidized. The pH and temperature optima for secondary alcohol dehydrogenase activity were 8 to 9 and 60 to 70 degrees C, respectively. The activation energy calculated from an Arrhenius plot was 8.2 kcal (ca. 34 kJ). The Km values at 25 degrees C, pH 7.0, were 8.2 X 10(-6) M for NAD and 8.5 X 10(-5) M for 2-propanol. The secondary alcohol dehydrogenase activity was inhibited by strong thiol reagents and strong metal-chelating agents such as 4-hydroxymercuribenzoate, 5,5'-dithiobis(2-nitrobenzoic acid), 5-nitro-8-hydroxyquinoline, and 1,10-phenanthroline. The enzyme oxidized the stereoisomers of 2-butanol at an equal rate. Alcohol dehydrogenase II had good thermal stability and the ability to catalyze reactions at high temperature (85 degrees C). It appears to have properties distinct from those of previously described primary and secondary alcohol dehydrogenases.
New topical antifungal drugs. (1983)

The new antifungal drugs used for topical treatment of superficial, skin and mucosal mycoses are reviewed. Amorolfine and allylamines (naftifine and terbinafine) are promising original molecules with new and different modes of action against fungi. Rilopirox is a new pyridone derivative under study. A great number of azole derivatives, such as oxiconazole, isoconazole, sulconazole, and terconazole, are used as topical antifungals. Three of them are synthesized in Barcelona by pharmaceutical laboratories: sertaconazole, flutrimazole and eberconazole. All of them are now in the register process for commercialization. The combination of antifungals with active products, such as keratoplastics, is used mainly for the treatment of onychomycoses; 40% urea associated with 1% bifonazole has shown high efficacy for this indication.
Classical Trial Design (2008)

This chapter contains sections titled: Introduction How to Calculate Sample Size Using ExpDesign Mathematical Notes on Classical Design
Nuclear casein kinase 2 (CK‐2) activity in human normal, benign hyperplastic, and cancerous prostate (1994)

In previous work, we had observed that chromatin-associated nonhistone protein phosphorylation, catalyzed by intrinsic protein kinase reaction in chromatin preparations from human benign prostatic hyperplasia (BPH) prostate samples was markedly elevated, compared with the normal prostate chromatin samples [Rayan et al: Cancer Res 45:2277-2282, 1985]. The properties of this protein kinase reaction were suggestive of the involvement of casein kinase(s). By employing the specific synthetic substrate for casein kinase 2 (CK-2) for assays in cellular fractions, we have shown that this protein kinase is present in human prostate chromatin. Its activity is increased in BPH chromatin by about 25-fold, as compared with its activity in the normal prostate chromatin. This suggests that CK-2 is a possible mediator of the enhanced phosphorylation of chromosomal proteins in BPH chromatin. By comparison, CK-2 activity in chromatin preparations from prostatic carcinoma samples was markedly less elevated than that of the BPH chromatin. Immunohistochemical analysis of the enzyme in human frozen sections of prostate tissue samples showed that the enzyme immunostaining was diffuse in the cytoplasm, but more intense in the nucleus, especially in the nucleoli. In general, the staining corresponded with the enzymic data. However, sections from prostatic carcinoma samples appeared to show differential staining, depending on the Gleason's grade of the sample. The samples with higher Gleason's grade showed less intense immunostain in the nucleus, compared with samples of lower Gleason's grade. Further, regions of sections in samples with higher Gleason's grade did not show any immunostaining. These differences in the characteristics of CK-2 expression in prostatic carcinoma samples may be potentially significant, but need to be evaluated further for their significance to the pathobiology of prostatic neoplasia.
Structure and expression of a cloned cDNA for mouse interferon-beta. (1983)

A unique sequence in the mouse genome which cross-hybridized to a cloned human interferon-beta 1 gene was detected by DNA blot analysis. Taking advantage of this, a cDNA library prepared from partially purified mRNA for mouse interferon-beta was screened using human interferon-beta 1 DNA as a probe. One of the positive clones, pM beta-3, contained a 680-base pair cDNA insert, whose base sequence contained a single large open reading frame for 182 amino acids. The coding sequences of the cDNA showed homologies of 63% at the nucleotide and 48% at the amino acid level with respect to human interferon-beta 1 cDNA (Taniguchi, T., Ohno, S., Fujii-Kuriyama, Y., and Muramatsu, M. (1980) Gene 10, 11-15). The first 21 amino acids, considered to be the signal peptide, were followed by 24 amino acids, whose sequence was identical with the NH2-terminal sequence that had been reported for mouse interferon-beta from Ehrlich ascites tumor cells (Taira, H., Broeze, R. J., Jayaram, B. M., Lengyel, P., Hunkapiller, M. W., and Hood, L. E. (1980) Science (Wash. D.C.) 207, 528-530). The complete primary sequence of mature interferon-beta polypeptide consisting of 161 amino acids (Mr = 19,700) was deduced. There are three N-glycosylation sites, and this offers an explanation for the larger molecular size (Mr = 26,000-40,000) of natural mouse interferon-beta in comparison to the deduced interferon polypeptide. The cDNA, when fused to a SV40 promoter sequence and then introduced into COS-7 cells, directed the synthesis and secretion of a protein product indistinguishable from the authentic mouse interferon-beta.
HLA-G Expression in Cancers: Potential Role in Diagnosis, Prognosis and Therapy (2011)

Human leukocyte antigen G (HLA-G) is a non-classic major histocompatibility complex (MHC) class I molecule that functions as an immune suppressive molecule. HLA-G has direct inhibitory effects on natural killer cells(NK), dendritic cells (DC), T cells and has long-term tolerogenic indirect effects by inducing regulator T cells (Treg). HLA-G has been reported to be involved in various physio-pathological conditions such as reproduction, transplantation, autoimmunity, infectious and malignant diseases. In this context, aberrant expression of HLA-G in malignant diseases including hematological and solid tumors has been extensively investigated and its relevance to clinicoparameters and potential significance in diagnosis, prognosis and immune target therapy has been postulated. We here summarized the HLA-G expression in malignancies and emphasis its clinical relevance to malignant disease diagnosis, prognosis, and its potential in target-based immunotherapy was also discussed.
MR Imaging with Ultrasmall Superparamagnetic Iron Oxide Particles in Experimental Soft-Tissue Infections in Rats (2002)

Activated macrophages in acute soft-tissue infection can be labeled with USPIOs and detected with MR imaging because of susceptibility effects.
Polyol accumulation by Aspergillus oryzae at low water activity in solid-state fermentation (2004)

Polyol accumulation and metabolism were examined in Aspergillus oryzae cultured on whole wheat grains or on wheat dough as a model for solid-state culture. In solid-state fermentation (SSF), water activity (a(w)) is typically low resulting in osmotic stress. In addition to a high level of mannitol, which is always present in the cells, A. oryzae accumulated high concentrations of glycerol, erythritol and arabitol at relatively low a(w) (0.96-0.97) in SSF. Accumulation of such a mixture of polyols is rather unusual and might be typical for SSF. A. oryzae mycelium accumulating various polyols at low a(w) contained at least four distinct polyol dehydrogenases with highest activities toward glycerol, erythritol, D-arabitol and mannitol. NADP(+)-dependent glycerol dehydrogenase activity correlated very well with glycerol accumulation. A similar correlation was observed for erythritol and NADP(+)-erythritol dehydrogenase suggesting that NADP(+)-dependent glycerol and erythritol dehydrogenases are involved in biosynthesis of glycerol and erythritol, respectively, and that these enzymes are induced by osmotic stress.