gebhart/patrepeval huggingface dataset:
Egg fortification with n-3 polyunsaturated fatty acids (PUFA): nutritional benefits versus high n-6 PUFA western diets, and consumer acceptance. (2008)

Effective concentration and transformation of supplemental n-3 PUFA/LCPUFA from feed to egg substantially enhanced egg n-3 PUFA %DRI, particularly of DHA, critical for health but often deficient. Such land-based n-3 PUFA/LCPUFA fortification may be applicable to high n-6 PUFA diets, fitting within cholesterol limitations and market criteria. It may contribute to general health and specific requirements (i.e., pregnancy and lactation), with possibilities of wide accessibility and standardization.
Toll-quality 16 kb/s CELP speech coding with very low complexity (2002)

We present a 16 kb/s CELP coder with a complexity as low as 3 MIPS. The main thrust is to reduce the complexity as much as possible while maintaining toll-quality. This low-complexity CELP (LC-CELP) coder has the following features: (1) fast LPC quantization, (2) 3-tap pitch prediction with efficient open-loop pitch search and predictor tap quantization, (3) backward-adaptive excitation gain, and (4) a trained excitation codebook with a small vector dimension and a small codebook size. Most CELP coders require one full DSP or even two DSP chips to implement in real-time. In contrast, 3 to 6 full-duplex LC-CELP coders can fit into a single DSP chip, since each takes only around 3 MIPS to implement. This coder achieved slightly higher mean opinion stores (MOS) than the CCITT 32 kb/s ADPCM. It also exhibits good performance when tandemed with itself or transcoded with other coders.
ISOTRETINOIN THERAPY IN ACNE VULGARIS: A 10‐YEAR RETROSPECTIVE STUDY IN SINGAPORE (1994)

This study confirms that isotretinoin is very effective for severe acne, and complete remission can be induced in more than 90% of cases even with lower dosage regimens. Significant clinical improvement can be achieved with the use of lower doses (mean 0.5 mg/kg/day) for an average of 4 months of treatment with lower risk of adverse effects.
4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity. (1980)

alpha-Melanocyte-stimulating hormone (alpha-MSH) reversibly darkens frog skins by stimulating melanosome movement (dispersion) within melanophores. Heat-alkali treatment of alpha-MSH results in prolonged biological activity of the hormone. Quantitative gas chromatographic analysis of the hydrolyzed heat-alkali-treated peptide revealed partial racemization particularly at the 4(methionine) and 7(phenylalanine) positions. [Nle4]-alpha-MSH, a synthetic analogue of alpha-MSH, reversibly darkens frog skins and also exhibits prolonged activity after heat-alkali treatment. Synthesis of [Nle4, D-Phe7]-alpha-MSH provided an analogue with prolonged biological activity identical to that observed with heat-alkali-treated alpha-MSH or [Nle4]-alpha-MSH. [Nle4, D-Phe7]-alpha-MSH was resistant to enzymatic degradation by serum enzymes. In addition, this peptide exhibited dramatically increased biological activity as determined by frog skin bioassay, activation of mouse melanoma adenylate cyclase, and stimulation of mouse melanoma cell tyrosinase activity. This Nle4, D-Phe7 synthetic analogue of alpha-MSH is a very porent melanotropin, 26 times as potent as alpha-MSH in the adenylate cyclase assay. The resistance of the peptide to enzymatic degradation and its extraordinarily potent and prolonged biological activity should make this analogue of alpha-MSH an important molecular probe for studying the melanotropin receptors of both normal and abnormal (melanoma) melanocytes.
Synthesis, Properties and Microbiological Activity of Hydrophobic Derivatives of Vitamin B12. (1995)

Long chain alkylcobalamins and long chain acyl-cyanocobalamins, two types of hydrophobic derivatives of vitamin B12, were synthesized. It was shown by TLC and determination of the partition coefficient between organic and aqueous phases that the hydrophobicity of alkylcobalamins and acyl-cyanocobalamins increased with the chain length of the alkyl or acyl group introduced into cobalamin. Long chain alkylcobalamins were easily converted to aquacobalamin by photoirradiation, but the first-order rate constant of photolysis decreased with the length of an alkyl group. Long chain acyl-cyanocobalamins were gradually hydrolyzed to cyanocobalamin in neutral or alkaline solution with the pseudo-first order rate constant increasing with the pH of the solution. Stabilization of acyl-cyanocobalamins toward hydrolysis was achieved by introducing a methyl group into the alpha-position of an acyl group. All the long chain alkylcobalamins tested supported the growth of Escherichia coli 215, a cobalamin- or L-methionine-auxotroph, and Lactobacillus leichmannii, although their activity as cobalamin was at most 28% and 15% that of cyanocobalamin for E. coli 215 and L. leichmannii, respectively.
MEMS resonators that are robust to process-induced feature width variations (2002)

In this paper, a frequency stability analysis and design method for MEMS resonators is presented. The frequency characteristics of a laterally vibrating resonator are analyzed. With the fabrication error on the sidewall of the structure being considered, the first and second order frequency sensitivities to the fabrication error are derived. A simple relationship between the proof mass area and perimeter, and the beam width, is developed for single material structures, which expresses that the proof mass perimeter times the beam width should equal six times the area of the proof mass. Design examples are given for the single material and multi-layer structures. The results and principles presented in the paper can be used to analyze and design other MEMS resonators.
Advances in gene therapy of liver cirrhosis: a review (2001)

Liver fibrosis or cirrhosis is a common progressively pathological lesion of chronic liver diseases in response to various liver-damaging factors. The main mechanisms of fibrotic or cirrhotic initiation and progression at the level of cellular and molecular events have been elucidated in the past two decades[1,2]. Various causes, including hepatitis virus infections, toxification, ischemia, congestion, parasites infection, abnormal cooper or iron load, etc, result in chronic inflammation and/or wound healing responses, of which the main characteristics manifest in the absolute increase of the excessive extracellular martrix (ECM) synthesis and the relative decrease of them, leading to ECM deposit. With the stimulation of inflammation or toxins, activated hepatic stellate cells(Ito cells), injuried or regenerated hepatocytes, Kupffer cells, sinusoidal cells and natural killer (NK) cells produce certain cytokines or immunoreactive factors, which exert various biological effects on their respective target cells or organs in an autocrine or paracrine manner. These consist of the cellular basis of hepatic fibrosis advances[3,4]. It is the vital molecular event in fibrosis progression that activated hepatic stellate cell exocrine ECM components and fibrosis-implementing factors, for example, the transforming growth factor β (TGF-β), which is considered the key cytokine to accelerate cirrhotic procession[5,6]. Various factors participate in fibrosis or cirrhosis formation. They could be simply divided into the fibrosis-implementing factors, such as TGF-β, platelet-derived growth factor (PDGF), epithelial growth factor (EGF), and antifibrotic factors, such as interferon γ and interleukin-10. These cytokines play important and unique roles in the interactive complicated network. Excessive ECM deposit, disappearance of sinusoidal endothelial fenestra and subsequent capillary vascularization cause the dysfunction of hepatocytes. The unblocked progressively pathological lesions with inevitably result in, lobular reconstruction, pseudolobule formation and nodular regeneration. With the elucidation of vital cellular and molecular events, gene delivery strategies for treatment of liver fibrosis or cirrhosis emerge on the basis of gene manipulations. Our interest focuses on the recent advances of gene therapy for liver fibrosis or cirrhosis.

Effective antifibrotic treatments, including medicinal or gene therapy, should satisfy several essential criteria. First, any therapy should have a sound biological basis. Additionally, the pharmacologically active drugs or compounds should reach or reside in the liver at a high concentration and have little side effect outside the liver. Specific targeting to hepatic stellate cells were preferentially chosen. Finally, in the ideal case, a therapeutic agent should keep the regional target environment for a relatively long period[7].
Generation and characterization of murine antiflagellum monoclonal antibodies that are protective against lethal challenge with Pseudomonas aeruginosa (1990)

Two murine monoclonal antibodies, IIG5 (IgG3) and IVE8 (IgG2a), that bind to Pseudomonas aeruginosa type a flagella and type b flagella, respectively, were prepared by conventional hybridoma methodology. Specificity of each monoclonal antibody for type a or type b flagella was demonstrated by enzyme-linked immunosorbent assay, indirect immunofluorescence, and immunoblotting. The percentage of P. aeruginosa isolates recognized by each monoclonal antibody was analyzed by enzyme-linked immunosorbent assay. Among a panel of 257 flagellated P. aeruginosa clinical isolates, IIG5 bound to 67.7% of the isolates and IVE8 bound to another 30.7%, for a combined coverage of 98.4%. Inhibition of motility of P. aeruginosa by the monoclonal antibodies was observed in vitro in a soft agar assay and was dose dependent. The protective efficacy of IIG5 and IVE8 was examined in a mouse burn wound sepsis model. The antiflagellum monoclonal antibodies provided specific and significant prophylactic and therapeutic protection against lethal challenge with P. aeruginosa strains.
Endostatin: yeast production, mutants, and antitumor effect in renal cell carcinoma. (1999)

Endostatin is a Mr 20,000 COOH-terminal fragment of collagen XVIII that inhibits the growth of several primary tumors. We report here the cloning and expression of mouse endostatin in both prokaryotic and eukaryotic expression systems. Soluble recombinant protein expressed in yeast (15-20 mg/L) inhibited the proliferation and migration of endothelial cells in response to stimulation by basic fibroblast growth factor. A rabbit polyclonal antibody was raised that showed positive immunoreactivity to the recombinant protein expressed from both systems. Importantly, the biological activity of the mouse recombinant protein could be neutralized by this antiserum in both endothelial proliferation and chorioallantoic membrane assays. Systemic administration of endostatin at 10 mg/kg suppressed the growth of renal cell cancer in a nude mouse model. The inhibition of tumor growth with soluble yeast-produced protein was comparable to that obtained with non-refolded precipitated protein expressed from bacteria. In addition, two closely related COOH-terminal deletion mutants of endostatin were also tested and showed strikingly differing activity. Collectively, these findings demonstrate the expression of a biologically active form of mouse endostatin in yeast, define a role for the molecule in inhibiting endothelial cell migration, extend its antitumor effects to renal cell carcinoma, and provide a formal proof (via the neutralizing antiserum experiments and the mutant data) that endostatin (and not a possible contaminant) acts as an antiangiogenic agent. Finally, the high level expression of mouse endostatin in yeast serves as an endotoxin free, soluble source of protein for fundamental studies on the mechanisms of tumor growth suppression by angiogenesis inhibitors.
SIRT1 Modulation as a Novel Approach to the Treatment of Diseases of Aging (2010)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTSIRT1 Modulation as a Novel Approach to the Treatment of Diseases of AgingCharles A. Blum*, James L. Ellis, Christine Loh, Pui Yee Ng, Robert B. Perni, and Ross L. SteinView Author Information Sirtris, A GSK Company, 200 Technology Square, Cambridge, Massachusetts 02139, United States*To whom correspondence should be addressed. Phone: 617-252-6920, extension 2102. Fax: 617-252-6924. E-mail: [email protected]Cite this: J. Med. Chem. 2011, 54, 2, 417–432Publication Date (Web):November 16, 2010Publication History Received10 July 2010Published online16 November 2010Published inissue 27 January 2011https://pubs.acs.org/doi/10.1021/jm100861phttps://doi.org/10.1021/jm100861preview-articleACS PublicationsCopyright © 2010 American Chemical SocietyRequest reuse permissionsArticle Views4196Altmetric-Citations66LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Inhibition,Inhibitors,Peptides and proteins,Phytochemistry,Rodent models Get e-Alerts
Synthesis of 7-Substituted 5,6-Dimethyl-2,4-dioxo-1,2,4,7-tetrahydropyrrolo[2,3-d][1,3]oxazines (1985)

The title compounds 2 are prepared by the cyclization of substituted pyrroles 3 with phosgene in refluxing tetrahydrofuran. In the case of 3a, it is shown that the cyclization can also be achieved after alkylation to give 8.
Evanescent-Coupled Ge p-i-n Photodetectors on Si-Waveguide With SEG-Ge and Comparative Study of Lateral and Vertical p-i-n Configurations (2008)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> Si-waveguide-integrated lateral Ge p-i-n photodetectors using novel Si/SiGe buffer and two-step Ge-process are demonstrated for the first time. Comparative analysis between lateral Ge p-i-n and vertical p-Si/i-Ge/n-Ge p-i-n is made. Light is evanescently coupled from Si waveguide to the overlaying Ge-detector, achieving high responsivity of 1.16 A/W at 1550 nm with <formula formulatype="inline"><tex>$f_{3\,{\rm dB}}$</tex></formula> bandwidth of 3.4 GHz for lateral Ge p-i-n detector at 5 V reverse bias. In contrast, vertical p-Si/i-Ge/n-Ge p-i-n has lower responsivity of 0.29 A/W but higher bandwidth of 5.5 GHz at <formula formulatype="inline"><tex>$-$</tex></formula>5 V bias. The higher responsivity of lateral p-i-n detectors is attributed to smaller optical mode overlap with highly doped Ge region as in vertical p-i-n configuration. </para>
Chimeric anti-angiogenin antibody cAb 26–2F inhibits the formation of human breast cancer xenografts in athymic mice (1998)

Angiogenin (Ang), an inducer of neovascularization, is secreted by several types of human tumor cells and appears critical for their growth. The murine anti-Ang monoclonal antibody (mAb) 26-2F neutralizes the activities of Ang and dramatically prevents the establishment and metastatic dissemination of human tumor cell xenografts in athymic mice. However, for use clinically, the well-documented problem of the human anti-globulin antibody response known to occur with murine antibodies requires resolution. As a result, chimeric as well as totally humanized antibodies are currently being evaluated as therapeutic agents for the treatment of several pathological conditions, including malignancy. Therefore, we have constructed a chimeric mouse/human antibody based on the structure of mAb 26-2F. Complementary DNAs from the light and heavy chain variable regions of mAb 26-2F were cloned, sequenced, and genetically engineered by PCR for subcloning into expression vectors that contain human constant region sequences. Transfection of these vectors into nonproducing mouse myeloma cells resulted in the secretion of fully assembled tetrameric molecules. The chimeric antibody (cAb 26-2F) binds to Ang and inhibits its ribonucleolytic and angiogenic activities as potently as mAb 26-2F. Furthermore, the capacities of cAb 26-2F and its murine counterpart to suppress the formation of human breast cancer tumors in athymic mice are indistinguishable. Thus cAb 26-2F, with its retained neutralization capability and likely decreased immunogenicity, may be of use clinically for the treatment of human cancer and related disorders where pathological angiogenesis is a component.
Salient features of Haemophilus vaginalis (1979)

A total of 78 strains of Haemophilus vaginalis were examined for 104 features. All strains fermented dextrin, maltose, and starch. Additionally, more than 90% of the strains fermented galactose, glucose, and ribose. Arbutin, cellobiose, melibiose, rhamnose, and salicin were not fermented by any of these strains. None of the strains acidified any of 14 alcohols or alkalinized any of 25 organic salts and amides. More than 90% of the strains hemolyzed human blood agar and hydrolyzed hippurate. No strain hemolyzed sheep blood agar. A recommendation is included for those minimal features that best differentiate H. vaginalis from other oxidase- and catalase-negative, gram-negative organisms.
Evidence on the Benefits and Harms of Screening and Treating Pregnant Women Who Are Asymptomatic for Bacterial Vaginosis: An Update Review for the U.S. Preventive Services Task Force (2008)

No benefit was found in treating women with low- or average-risk pregnancies for asymptomatic bacterial vaginosis. More research is needed to better understand these groups and the conditions under which treatment can be harmful or helpful, and to explore the relevance of bacterial vaginosis to other adverse pregnancy outcomes, such as delivery before 34 weeks.
Detection of Mycoplasma pneumoniae in Spiked Clinical Samples by Nucleic Acid Sequence-Based Amplification (2002)

Isothermal nucleic acid sequence-based amplification (NASBA) was applied to the detection of Mycoplasma pneumoniae. M. pneumoniae RNA prepared from a plasmid construct was used to assess the sensitivity of the assay, and an internal control for the detection of inhibitors was constructed. The sensitivity of the NASBA assay was 10 molecules of wild-type M. pneumoniae RNA generated in vitro and 5 color-changing units (CCU) of M. pneumoniae. An appropriate specimen preparation procedure was developed: after protease treatment of the respiratory specimens, guanidine thiocyanate lysis solution (4.7 M guanidine thiocyanate [Sigma-Aldrich NV], 46 mM Tris-HCl [Merck, Darmstadt, Germany], 20 mM EDTA [Sigma-Aldrich NV], 1.2% [wt/vol] Triton X-100 [Sigma-Aldrich NV], pH 6.2.) was added. With spiked throats, nasopharyngeal aspirates, bronchoalveolar lavage specimens, and sputum specimens, the sensitivity of the NASBA assay in the presence of the internal control was 2 x 10(4) molecules of in vitro-generated RNA or 5 CCU of M. pneumoniae. The sensitivity of the NASBA assay was comparable to that of a PCR targeted to the P1 adhesin gene. Fifteen clinical specimens positive for M. pneumoniae by PCR were also positive by NASBA. These results indicate that the sensitivity of detection of M. pneumoniae in spiked respiratory samples by NASBA is high. Together with the use of the internal control, the assay merits evaluation as a diagnostic tool.
Immune escape of cancer cells with beta2‐microglobulin loss over the course of metastatic melanoma (2013)

Cancer cells escape T-cell-mediated destruction by losing human leukocyte antigen (HLA) class I expression via various mechanisms, including loss of beta2-microglobulin (β2m). Our study illustrates the immune escape of HLA class I-negative tumor cells and chronological sequence of appearance of tumor β2m gene mutation in successive lesions obtained from a patient with metastatic melanoma. We observed a gradual decrease in HLA expression in consecutive lesions with few HLA-negative nodules in the primary tumor and the emergence of a totally negative lesion at later stages of the disease. We detected loss of β2m in β2m-negative nests of the primary tumor caused by a combination of two alterations: (i) a mutation (G to T substitution) in codon 67 in exon 2 of β2m gene, producing a stop codon and (ii) loss of the second gene copy by loss of heterozygosity (LOH) in chromosome 15. The same β2m mutation was found in a homogeneously β2m-negative metastasis 10 months later and in a cell line established from a biopsy of a postvaccination lymph node. Microsatellite analysis revealed the presence of LOH in chromosomes 6 and 15 in tumor samples, showing an accumulation of chromosomal loss at specific short tandem repeats in successive metastases during disease progression. HLA loss correlated with decreased tumor CD8+ T-cell infiltration. Early incidence of β2m defects can cause an immune selection and expansion of highly aggressive melanoma clones with irreversible genetic defects causing total loss of HLA class I expression and should be taken into consideration as a therapeutic target in the development of cancer immunotherapy protocols.
Glycosylation of human protein C affects its secretion, processing, functional activities, and activation by thrombin (1991)

Human protein C (HPC) is an antithrombotic serine protease that circulates in the plasma as several glycoforms. To examine the role of glycosylation in the function of this protein, we singly eliminated each of the four potential N-linked glycosylation sites by site-directed mutagenesis of Asn to Gln at amino acid positions 97, 248, and 313 (HPC derivatives Q097, Q248, and Q313) or at the unusual consensus sequence Asn-X-Cys at 329 (HPC derivative Q329). The cDNAs for wild type and each derivative were inserted into expression vectors and expressed both transiently and stably in human 293 and hamster AV12-664 cells. We demonstrate that N-linked glycosylation at position 97 in the light chain of HPC is critical for efficient secretion and affects the degree of core glycosylation at Asn-329. Glycosylation at position 248 affects the intracellular processing of the internal Lys-Arg (KR) KR cleavage site, and partial glycosylation at the sequence Asn-329-X-Cys is responsible for the natural alpha-glycoform. Altering the glycosylation pattern of the protein had no significant effect on the level of fully gamma-carboxylated HPC secreted from the 293 cell line. However, elimination of glycosylation sites in the heavy chain resulted in a 2- to 3-fold increase in anticoagulant activity. Utilizing synthetic substrate, both the Km and kcat were affected, depending on the specific glycosylation site eliminated. However, there were no significant differences in the inhibition kinetics by alpha-1-antitrypsin (association rate constants of 10-11 M-1s-1 and t1/2 of 27-29 min at 40 microM alpha-1-antitrypsin) or t1/2 in human plasma (17-18 min). A comparison of the rate of activation of each derivative by thrombin alone or in complex with thrombomodulin revealed that Q313 was activated approximately 2.5-fold faster than wt HPC, independent of calcium concentration. This increase in rate was due to an enhanced affinity of thrombin-thrombomodulin for Q313, as indicated by a 3-fold reduction in Km. Overall, our studies demonstrate that glycosylation at different sites in HPC affects distinct properties of this complex protein. Furthermore, we demonstrate the ability to improve the catalytic efficiency of this enzyme through carbohydrate modifications.