gebhart/patrepeval huggingface dataset:
La memoria recuperada (2002)

Choroidal neovascularization secondary to age-related macular degeneration is a leading cause of vision loss in adults. Although most patients present with occult CNV, treatment has focused on the small percentage of eyes with well-delineated, classic CNV. Transpupillary thermotherapy is a recent advancement in the management of occult CNV. Transpupillary thermotherapy acts in a subthreshold manner by slightly raising the choroidal temperature. A recent pilot study demonstrated that 56% of treated eyes remained stable one year after treatment with only 25% losing two lines of visual acuity. The TTT4CNV study will further evaluate the effectiveness of transpupillary thermotherapy in a randomized, double-blind trial.
Oncogene and growth factor expression in ovarian cancer (1992)

The varying tumor-biological behavior of ovarian carcinomas probably influences both their operability and response to chemotherapy, which are the most relevant prognostic factors. The phenotype of different ovarian carcinomas is obviously associated with an activation of the EGF/TGF-alpha signal pathway, including c-myc and c-jun expression. Analysis of EGF-R, TGF-alpha, c-myc and c-jun expression in 33 stage III/IV, and 2 stage I/II ovarian carcinomas with biochemical, molecular-chemical and immunohistochemical methods showed a correlation between the mRNA and protein levels of EGF-R and TGF-alpha for tumors with low or high expressing rates. However, the concentration of measurable free EGF-Rs seems to depend on the amount of TGF-alpha expression by the tumors. The EGF-R binding ligand TGF-alpha is produced by epithelial tumor cells; stromal cells are usually TGF-alpha-negative, as shown by immunohistochemistry. High expression rates of EGF-R. TGF-alpha and c-myc were detected in 6, 7, and 10 out of 35 ovarian carcinomas, respectively. C-jun mRNA was detected in 18/19 cases studied. Non-malignant tissues originating from myometrium or ovary expressed no (or only small amounts of) EGF-R or TGF-alpha mRNA, whereas a high c-myc expression was found in 1/7 normal myometria, and in 2/5 normal ovaries. There was no strong correlation between EGF-R/TGF-alpha and c-myc/c-jun expression.(ABSTRACT TRUNCATED AT 250 WORDS)
A testis-specific promoter in the rat vasopressin gene. (1994)

In the rat testis, the vasopressin gene is transcribed into precursor RNAs that are processed into a number of mature transcripts. One of these transcripts has a structure identical to that of the hypothalamic RNA that encodes the vasopressin prepropeptide, but is present at such low levels that it can only be detected by the polymerase chain reaction. Other vasopressin-like RNAs are derived from differential splicing events that join transcribed sequences between 3 and 9 kilobases upstream of the hypothalamic transcription start site to exons corresponding to II and III of the hypothalamic-type RNA. Here we describe the sequence of a testis-specific promoter and the exon structure of its transcription unit. We show that an in vitro synthesized RNA corresponding to the longer testicular vasopressin gene-derived transcript is not able to act as a template for protein synthesis in two different cell-free lysates. As attempts to localize the vasopressin-gene derived RNAs to particular cell types in the testis by in situ hybridization have consistently failed, we have used indirect methods. Three different procedures were used to effect germ cell depletion in adult male rats. Acute heat treatment of the testis, chronic ingestion of hydroxyurea, and chronic vitamin A deficiency all reduced the level of the aberrant testicular vasopressin-gene derived RNAs, indicating that their expression is closely associated with the integrity of germ cells and ongoing spermatogenesis.
The intrauterine and early postnatal origins of cardiovascular disease and chronic bronchitis. (1989)

Geographical differences in mortality from cardiovascular disease and chronic bronchitis within England and Wales are closely related to past differences in infant mortality. This paper examines the separate relations of mortality during 1968-78 with neonatal and post-neonatal mortality during 1911-25. These divisions of infant mortality are indicators of the intrauterine and early postnatal environments respectively. Stroke is related to neonatal mortality and therefore to the intrauterine environment. Prenatal determinants of blood pressure levels may be one mechanism underlying this. Bronchitis is related to postnatal mortality and therefore to the postnatal environment. This may reflect the long term effects of lower respiratory tract infection in early childhood. Ischaemic heart disease is related to both neonatal and post-neonatal mortality and therefore to the intrauterine and postnatal environments. The links may include blood pressure and as yet unknown processes established in early postnatal life.
A novel member of the thyroid/steroid hormone receptor family is encoded by the opposite strand of the rat c-erbA alpha transcriptional unit. (1989)

A cDNA encoding a novel member of the thyroid/steroid hormone receptor superfamily, called Rev-ErbA alpha, has been isolated from a rat GH3 cell library. Rev-ErbA alpha is an approximately 56-kilodalton protein most similar in structure to the thyroid hormone receptor (c-erbA) and the retinoic acid receptor, but it does not bind either thyroid hormone or retinoic acid. The mRNA encoding Rev-ErbA alpha is present in many tissues and is particularly abundant in skeletal muscle and brown fat. A genomic DNA fragment containing the entire Rev-ErbA alpha cDNA sequence was isolated and characterized. Remarkably, this DNA fragment also contained a portion of the c-erbA alpha gene. r-erbA alpha-1 and r-erbA alpha-2 are alternative splice products of the c-erbA alpha gene and are members of the receptor superfamily. The genes encoding Rev-ErbA alpha and r-erbA alpha-2 overlap, with their coding strands oriented opposite one another. A 269-base-pair segment of the bidirectionally transcribed region is exonic in both the Rev-ErbA alpha and r-erbA alpha-2 genes, resulting in complementary mRNAs. Thus, through alternative splicing and opposite-strand transcription, a single genomic locus codes for three different members of the thyroid/steroid hormone receptor superfamily. Potential implications of this unusual genomic arrangement are discussed.
Expression of EphA2 is Prognostic of Disease-Free Interval and Overall Survival in Surgically Treated Patients with Renal Cell Carcinoma (2005)

Whereas normally expressed at sites of cell-to-cell contact in adult epithelial tissues, recent studies have shown that the receptor tyrosine kinase EphA2 is overexpressed in numerous epithelial-type carcinomas, with the greatest level of EphA2 expression observed in metastatic lesions. In the current study, we have assessed EphA2 expression in archived renal cell carcinoma (RCC) tissues as it relates to patient disease course. Using specific anti-EphA2 monoclonal antibody 208 and immunohistochemistry, we evaluated EphA2 protein expression levels in RCC specimens surgically resected from 34 patients (including 30 conventional clear-cell RCC, 3 papillary, and 1 chromophobic RCC cases) resulting in clinical cures. Regardless of histopathologic subtype, RCC lesions expressing higher levels of EphA2 tended to be of a higher grade (P < 0.05) and larger (P = 0.093), more-highly-vascularized tumors (P = 0.005). Perhaps most notable, the degree of EphA2 overexpression (versus normal matched autologous kidney tissue) seemed predictive of short-term (<1 year) versus longer-term (> or =1 year) disease-free interval (P < 0.001) and of overall survival (P < 0.001) among the RCC patients evaluated. These data suggest that EphA2 expression level may serve as a useful prognostic tool in the clinical management of patients who have been successfully treated with surgery, but who are at greater risk for accelerated disease recurrence and who have a poorer prognosis.
Genomic and Nongenomic Mechanisms of Nitric Oxide Synthesis Induction in Human Endothelial Cells by a Fourth-Generation Selective Estrogen Receptor Modulator (2002)

Cardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women. EM-652 (acolbifene) is a fourth-generation selective ER modulator (SERM) exerting complete antiestrogenic effects on the breast and uterus. EM-652 potently inhibits bone resorption and induces positive lipid modifications in estrogen-deficient animals. As most of the cardioprotective actions of estrogen are exerted directly at the vascular level, we studied the effects of EM-652 on endothelial production of nitric oxide (NO) in vitro and in vivo. EM-652 triggers NO release by human umbilical vein endothelial cells through nongenomic mechanisms, rapidly activating endothelial nitric oxide synthase (eNOS) via an ER-dependent sequential activation of MAPKs and PI3K/Akt pathways independently from gene transcription or protein synthesis. Moreover, EM-652 increases eNOS protein levels during prolonged treatments. Upon pharmacological comparison, EM-652 is markedly more potent than the SERMs raloxifene and tamoxifen in increasing NO synthesis from endothelial cells. In ovariectomized and fertile rats, EM-652 increases aortic eNOS expression and enzymatic activity at low, but not at higher, dosages. The present data show that EM-652 (acolbifene) has estrogen-like activity on the vascular wall, directly increasing NO production through genomic and nongenomic mechanisms in vitro and in vivo.
A Microfluidic DNA Library Preparation Platform for Next-Generation Sequencing (2013)

Next-generation sequencing (NGS) is emerging as a powerful tool for elucidating genetic information for a wide range of applications. Unfortunately, the surging popularity of NGS has not yet been accompanied by an improvement in automated techniques for preparing formatted sequencing libraries. To address this challenge, we have developed a prototype microfluidic system for preparing sequencer-ready DNA libraries for analysis by Illumina sequencing. Our system combines droplet-based digital microfluidic (DMF) sample handling with peripheral modules to create a fully-integrated, sample-in library-out platform. In this report, we use our automated system to prepare NGS libraries from samples of human and bacterial genomic DNA. E. coli libraries prepared on-device from 5 ng of total DNA yielded excellent sequence coverage over the entire bacterial genome, with >99% alignment to the reference genome, even genome coverage, and good quality scores. Furthermore, we produced a de novo assembly on a previously unsequenced multi-drug resistant Klebsiella pneumoniae strain BAA-2146 (KpnNDM). The new method described here is fast, robust, scalable, and automated. Our device for library preparation will assist in the integration of NGS technology into a wide variety of laboratories, including small research laboratories and clinical laboratories.
Quantitation of biological tumor markers (p53, c‐myc, Ki‐67 and DNA ploidy) by multiparameter flow cytometry in non‐small‐cell lung cancer (1992)

Fifteen primary non-small-cell lung carcinomas (8 adenocarcinomas and 7 squamous-cell carcinomas) were analyzed by multiparameter flow cytometry for their expression of p53 and c-myc proteins. In addition, the fraction of cells staining with the proliferation-associated antibody Ki-67 and DNA ploidy was determined. These 4 biological markers were analyzed in parallel samples from a single-cell suspension made from fresh, frozen biopsies. Thus, the internal relationship between these markers within each tumor-cell population was established. Three different anti-p53 antibodies were used: PAb 421, PAb 1801 and PAb 240. All 15 tumors were p53-positive with the antibodies PAb 1801 and PAb 240, whereas only 9 were positive as judged by the antibody PAb 421. This indicates that the choice of p53 antibody is not irrelevant. Ten tumors were c-myc-positive; 7 of these were adenocarcinomas. The c-myc-positive tumors had a significantly higher level of p53 expression, judged by PAb 1801 and PAb 240, than c-myc-negative tumors. For PAb 421, there was no difference. We did not find any correlation between Ki-67 staining and expression of p53 and c-myc proteins, either with DNA ploidy, S-phase fraction or histological type. Our study indicates that there might be an association between accumulation of p53 protein and c-myc over-expression in non-small-cell lung cancer, and that this in particular might apply to adenocarcinomas. Furthermore, we show that multiparameter flow cytometry is a powerful tool in the study of the relationship between different markers in a cell population.
Improved Multi-Stage Training of Online Attention-Based Encoder-Decoder Models (2019)

In this paper, we propose a refined multi-stage multi-task training strategy to improve the performance of onli <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ne</sup> attention-based encoder-decoder (AED) models. A three-stage training based on three levels of architectural granularity namely, character encoder, byte pair encoding (BPE) based encoder, and attention decoder, is proposed. Also, multi-task learning based on two-levels of linguistic granularity namely, character and BPE, is used. We explore different pre-training strategies for the encoders including transfer learning from a bidirectional encoder. Our encoder-decoder models with online attention show ~35% and ~10% relative improvement over their baselines for smaller and bigger models, respectively. Our models achieve a word error rate (WER) of 5.04% and 4.48% on the Librispeech test-clean data for the smaller and bigger models respectively after fusion with long short-term memory (LSTM) based external language model (LM).
Helper-Inducer T-Lymphocytes Mediate Diabetes in EMC-Infected BALB/c By J Mice (1987)

Diabetes mellitus developing in BALB/c ByJ mice infected with the M variant of encephalomyocarditis (EMC) virus is dependent on thymic immune mechanisms. We treated mice with the anti-T-lymphocyte monoclonal anti-L3T4 and anti-Lyt2.2 antibodies before virus inoculation and monitored the infection and occurrence of diabetes thereafter. Mice depleted of L3T4+ cells exhibited a reduced incidence and severity of diabetes compared with both untreated and anti-Lyt2.2-treated animals. All mice sustained pancreatic infections, but islet lesions with beta-cell degranulation only occurred in control infected and anti-Lyt2.2-treated animals. These data support the conclusion that the induction of diabetes in EMC-infected BALB/c mice is immune mediated and controlled by the L3T4 T-lymphocyte subpopulation.
A review of aquatic weed biology and management research conducted by the United States Department of Agriculture—Agricultural Research Service (2003)

Ever-increasing demand for water to irrigate crops, support aquaculture, provide domestic water needs and to protect natural aquatic and riparian habitats has necessitated research to reduce impacts from a parallel increase in invasive aquatic weeds. This paper reviews the past 4-5 years of research by USDA-ARS covering such areas as weed biology, ecology, physiology and management strategies, including herbicides, biological control and potential for use of natural products. Research approaches range from field-level studies to highly specific molecular and biochemical work, spanning several disciplines and encompassing the most problematic weeds in these systems. This research has led to new insights into plant competition, host-specificity, and the fate of aquatic herbicides, their modes of action and effects on the environment. Another hallmark of USDA-ARS research has been its many collaborations with other federal, state action and regulatory agencies and private industry to develop new solutions to aquatic weed problems that affect our public natural resources and commercial enterprises.
Immune Control of HSV-1 Latency (2005)

A hallmark of the herpes family of viruses is their ability to cause recurrent disease. Upon primary infection, Herpes Simplex virus (HSV) establishes a latent infection in sensory neurons that persists for the life of the individual. Reactivation of these latent viral genomes with virion formation is the source of virus for most HSV recurrent disease. This review details recent exciting findings supporting a role for the host immune system, particularly CD8+ T cells in maintaining HSV-1 in a latent state.
Adeno-Associated Virus Serotype 4 (AAV4) and AAV5 Both Require Sialic Acid Binding for Hemagglutination and Efficient Transduction but Differ in Sialic Acid Linkage Specificity (2001)

Adeno-associated virus serotype 4 (AAV4) and AAV5 have different tropisms compared to AAV2 and to each other. We recently reported that alpha 2--3 sialic acid is required for AAV5 binding and transduction. In this study, we characterized AAV4 binding and transduction and found it also binds sialic acid, but the specificity is significantly different from AAV5. AAV4 can hemagglutinate red blood cells from several species, whereas AAV5 hemagglutinates only rhesus monkey red blood cells. Treatment of red blood cells with trypsin inhibited hemagglutination for both AAV4 and AAV5, suggesting that the agglutinin is a protein. Treatment of Cos and red blood cells with neuraminidases also indicated that AAV4 bound alpha 2--3 sialic acid. However, resialylation experiments with neuraminidase-treated red blood cells demonstrated that AAV4 binding required alpha 2--3 O-linked sialic acid, whereas AAV5 required N-linked sialic acid. Similarly, resialylation of sialic acid-deficient CHO cells supported this same conclusion. The difference in linkage specificity for AAV4 and AAV5 was confirmed by binding and transduction experiments with cells incubated with either N-linked or O-linked inhibitors of glycosylation. Furthermore, AAV4 transduction was only blocked with soluble alpha 2-3 sialic acid, whereas AAV5 could be blocked with either alpha 2--3 or alpha 2-6 sialic acid. These results suggest that AAV4 and AAV5 require different sialic acid-containing glycoproteins for binding and transduction of target cells and they further explain the different tropism of AAV4 and AAV5.
The remarkable effect of titanium tetraisopropoxide in diastereoselective reaction of carbaldehydes with chiral benzenesulfonamide lithium complexes. (1991)

Chiral benzenesulfonamide titanium ate-complexes (4 and 8) were prepared from the lithium complexes (2 and 6) by treatment with titanium tetraisopropoxide. The diastereoselective reactions of aromatic carbaldehydes with 4 and 8 were performed, and the chiral o-(1-aryl-1-hydroxymethyl)benzenesulfonamides (3a-d and 7a-e) were obtained in 80-87% yields. The diastereomeric excesses (d.e.) of these products were evaluated as 62-82%. These compounds were also prepared from the lithium complexes (2 and 6), but the d.e. values were only 6-14% in this case.
Roll Press Briquetting and Pelleting of Corn Stover and Switchgrass (2009)

Corn stover and switchgrass, potential biomass feedstocks for bioenergy and bioproducts industries, are often harvested during a limited harvest season and stored as bales with bulk densities of about 100 to 200 kg m-3. Because of low bulk density, corn stover and switchgrass are difficult to handle, transport, store, and use in their natural forms. One of the solutions to reduce these problems and the associated costs is to densify these biomass feedstocks into pellets or briquettes. In this study, roll press briquetting characteristics of corn stover and switchgrass were studied using a pilot-scale roll press briquetting machine. Almond-shaped briquettes 28.7 to 31.3 mm in length were made. Results showed that high-durability corn stover and switchgrass briquettes with bulk densities of 480 to 530 kg m-3 could be produced. This corresponds to about a three- to five-fold increase in bulk densities compared to those of bales. Briquettes produced with the roll press briquetting machine had bulk densities (351 to 527 kg m-3), durabilities (39% to 90%), and crushing strengths (28 to 277 N) that were somewhat less than, but in a range comparable to, the pellets (9.6 to 9.8 mm diameter) produced with a conventional ring-die pelleting machine. The bulk density, durability, and hardness of the pellets ranged from 528 to 610 kg m-3, 75% to 95%, and 148 to 224 N, respectively. Micro-structural studies (chemical composition analyses, scanning electron microscopy imaging, and UV auto-fluorescence imaging) on grinds, briquettes, and pellets confirmed that highly dense, strong, and durable briquettes and pellets from corn stover and switchgrass could be produced without adding chemical binders (i.e., additives) by activating (softening) the natural binders such as water-soluble carbohydrates, lignin, protein, starch, and fat in the biomass materials by providing moisture and temperature in the range of glass transition of the biomass materials. No steam conditioning was necessary to produce good-quality corn stover briquettes. For switchgrass, a grind temperature of about 75C obtained by steam conditioning was necessary to produce good-quality briquettes. Roll press briquetting appears to be a promising low-cost, low-energy, high-capacity densification approach for commercial production of biomass briquettes.
Emergency room dermatology. (1999)

Dermatologic problems are seen very often in the urgent care setting. Common acute problems such as urticaria, pruritus, and less common but potentially devastating dermatologic diseases will be discussed in this review. Emphasis will be placed on an efficient and cost-effective initial approach to diagnosis and treatment.
Inhibition of SCF ubiquitin ligases by engineered ubiquitin variants that target the Cul1 binding site on the Skp1–F-box interface (2016)

Skp1-Cul1-F-box (SCF) E3 ligases play key roles in multiple cellular processes through ubiquitination and subsequent degradation of substrate proteins. Although Skp1 and Cul1 are invariant components of all SCF complexes, the 69 different human F-box proteins are variable substrate binding modules that determine specificity. SCF E3 ligases are activated in many cancers and inhibitors could have therapeutic potential. Here, we used phage display to develop specific ubiquitin-based inhibitors against two F-box proteins, Fbw7 and Fbw11. Unexpectedly, the ubiquitin variants bind at the interface of Skp1 and F-box proteins and inhibit ligase activity by preventing Cul1 binding to the same surface. Using structure-based design and phage display, we modified the initial inhibitors to generate broad-spectrum inhibitors that targeted many SCF ligases, or conversely, a highly specific inhibitor that discriminated between even the close homologs Fbw11 and Fbw1. We propose that most F-box proteins can be targeted by this approach for basic research and for potential cancer therapies.
Electronic Trading Systems: Strategic Implications of Market Design Choices (2002)

Modern financial markets compete aggressively for trading activity and investor interest. Information technology, once a crucial element in streamlining paper flows and operations, is now a strategic resource used in attracting or retaining market liquidity. Established exchanges introduce technology to enhance their markets. New market venues challenge the status quo and rely on technology to offer diverse services to increasingly sophisticated investors. In this paper, we examine the strategic design decisions embedded in these new electronic trading systems. Design decisions are critical, as they determine the market microstructure which influences investing strategies, patterns of trade, liquidity and volatility. We propose a taxonomy of design alternatives based on six major dimensions: market structure, type of orders, order execution priority rules, price discovery rules, time stamping, and transparency. Using examples of existing systems, we discuss the potential impact of the various alternatives on the eventual attractiveness of the market to the investors.