gebhart/patrepeval huggingface dataset:
Dietary protein and lactose increase translation initiation factor activation and tissue protein synthesis in neonatal pigs (2005)

Protein synthesis and eukaryotic initiation factor (eIF) activation are increased in muscle and liver of pigs parenterally infused with amino acids and insulin. To examine the effects of enteral protein and carbohydrate on protein synthesis, pigs (n = 42, 1.7 kg body wt) were fed isocaloric milk diets containing three levels of protein (5, 15, and 25 g x kg body wt(-1) x day(-1)) and two levels of lactose (low = 11 and high = 23 g x kg body wt(-1) x day(-1)) from 1 to 6 days of age. On day 7, pigs were gavage fed after 4-h food deprivation, and tissue protein synthesis rates and biomarkers of mRNA translation were assessed. Piglet growth and protein synthesis rates in muscle and liver increased with dietary protein and plateaued at 15 g x kg body wt(-1) x day(-1) (P < 0.001). Growth tended to be greater in high-lactose-fed pigs (P = 0.07). Plasma insulin was lowest in pigs fed 5 g x kg body wt(-1) x day(-1) protein (P < 0.0001). Plasma branched-chain amino acids increased as protein intake increased (P < 0.0001). Muscle (P < 0.001) and liver (P < or = 0.001) ribosomal protein S6 kinase-1 and eIF4E-binding protein phosphorylation increased with protein intake and plateaued at 15 g x kg body wt(-1) x day(-1). The results indicate that growth and protein synthesis rates in neonatal pigs are influenced by dietary protein and lactose intake and might be mediated by plasma amino acids and insulin levels. However, feeding protein well above the piglet's requirement does not further stimulate the activation of translation initiation or protein synthesis in skeletal muscle and liver.
法律科学的诺贝尔奖——理论、经验工作与法学研究中的科学方法 (2014)

法律科学会有诺贝尔奖吗？托马斯·S.尤伦教授的论文从这个问题出发,阐述了法学学术研究的当前状态和其发展趋势.文章认为,在法学研究中存在一些科学方法的基本素,但一些重的、定义性的基本素被遗漏了：一个被广泛认同的理论核心或范式和普遍公认的经验或实验证实的标准与方法,这些体现科学之特性的素是作为科学的法学所应该具有的.尽管如此,法学研究已经长期存在对经验工作的关注,而且不久之前,法学研究中的理论和经验方面的工作已经增加.新近的法学理论化涉及法律的后果,其价值会通过经验和实验工作而被人们所认识.法学学术研究正在发生着清晰的变革,这种变革使得法学研究更像科学.此文是美国新时期经验主义法学的代表作,对今天中国的法学研究不无裨益.尤伦教授1946年生于美国印第安纳州,分别获得美国达特茅斯学院文学士学位、英国牛津大学文科硕士学位、美国斯坦福大学经济学博士学位,为美国伊利诺伊大学Swanlund教席教授、法学教授.尤伦教授是美国法经济学领域的领军人物,有“法经济学的祖父”之称,是美国法经济学研究的最早倡导者、推动者和积极参加者之一.其声名远播英国、法国、德国、比利时、中国等国家,是一位享誉国际学术界的著名法学家.尤伦教授著述丰厚,其著述在法经济学学科的引证率位居英文文献前十名,代表作有《法和经济学》、《认知、理性与法律》和《环境政策的基础》,其中,《法和经济学》一书已被翻译成中文、日文、西班牙文、韩文、法文和俄文.
The importance of plasma protein binding in drug discovery (2007)

Plasma protein binding of drugs is a well-recognised phenomena, but it is only recently that the implications for drug action in vivo have been fully appreciated. Plasma proteins, by virtue of their high concentration, control the free drug concentration in plasma and in compartments in equilibrium with plasma, thereby, effectively attenuating drug potency in vivo. The historical background and thermodynamic basis for the 'Free Drug Principle' is presented, along with special considerations for intracellular targets, deep compartments and α1-acid glycoprotein binding. Real and apparent exceptions to the principle are discussed along with a survey of citations from the recent medicinal chemistry literature.
High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria (2013)

Fecal microbiota transplantation (FMT) is becoming a more widely used technology for treatment of recurrent Clostridum difficile infection (CDI). While previous treatments used fresh fecal slurries as a source of microbiota for FMT, we recently reported the successful use of standardized, partially purified and frozen fecal microbiota to treat CDI. Here we report that high-throughput 16S rRNA gene sequencing showed stable engraftment of gut microbiota following FMT using frozen fecal bacteria from a healthy donor. Similar bacterial taxa were found in post-transplantation samples obtained from the recipients and donor samples, but the relative abundance varied considerably between patients and time points. Post FMT samples from patients showed an increase in the abundance of Firmicutes and Bacteroidetes, representing 75-80% of the total sequence reads. Proteobacteria and Actinobacteria were less abundant (< 5%) than that found in patients prior to FMT. Post FMT samples from two patients were very similar to donor samples, with the Bacteroidetes phylum represented by a great abundance of members of the families Bacteroidaceae, Rikenellaceae and Porphyromonadaceae, and were largely comprised of Bacteroides, Alistipes and Parabacteroides genera. Members of the phylum Firmicutes were represented by Ruminococcaceae, Lachnospiraceae, Verrucomicrobiaceae and unclassified Clostridiales and members of the Firmicutes. One patient subsequently received antibiotics for an unrelated infection, resulting in an increase in the number of intestinal Proteobacteria, primarily Enterobacteriaceae. Our results demonstrate that frozen fecal microbiota from a healthy donor can be used to effectively treat recurrent CDI resulting in restoration of the structure of gut microbiota and clearing of Clostridum difficile.
The Drosophila melanogaster actin 5C gene uses two transcription initiation sites and three polyadenylation sites to express multiple mRNA species. (1986)

At least six mRNAs are made from the Drosophila melanogaster act5C gene. We investigated the structures of these RNAs in detail and determined that they are heterogeneous at both their 5' and 3' ends. At the 5' end there were two nonhomologous leader exons which were alternately spliced to the remainder of the gene. These leader exons mapped to 1.7 and 0.7 kilobases, respectively, upstream of a common splice acceptor site which was eight base pairs 5' to the translation initiator AUG. Exon 1 is 147 bases in length, while exon 2 is 111 bases. A consensus TATA sequence was found roughly 30 base pairs upstream from exon 1, but none was found in the analogous position upstream of exon 2. The transcript length diversity arose principally from the use of three polyadenylation sites. This gave rise to RNA molecules with 3'-untranslated regions of roughly 375, 655, and 945 base pairs. With two start sites and three termination sites, this gene has the potential to produce six different transcripts. All six possible transcripts were present in whole fly mRNA. Transcripts containing the two different leader exons were found in roughly the same relative quantities through development. In contrast, the various 3' ends were differentially represented through development.
Bone Tissue Engineering: State of the Art and Future Trends (2004)

Although several major progresses have been introduced in the field of bone regenerative medicine during the years, current therapies, such as bone grafts, still have many limitations. Moreover, and in spite of the fact that material science technology has resulted in clear improvements in the field of bone substitution medicine, no adequate bone substitute has been developed and hence large bone defects/injuries still represent a major challenge for orthopaedic and reconstructive surgeons. It is in this context that TE has been emerging as a valid approach to the current therapies for bone regeneration/substitution. In contrast to classic biomaterial approach, TE is based on the understanding of tissue formation and regeneration, and aims to induce new functional tissues, rather than just to implant new spare parts. The present review pretends to give an exhaustive overview on all components needed for making bone tissue engineering a successful therapy. It begins by giving the reader a brief background on bone biology, followed by an exhaustive description of all the relevant components on bone TE, going from materials to scaffolds and from cells to tissue engineering strategies, that will lead to "engineered" bone. Scaffolds processed by using a methodology based on extrusion with blowing agents.
Adaptive texture space shading for stochastic rendering (2014)

Abstract When rendering effects such as motion blur and defocus blur, shading can become very expensive if done in a naïve way, i.e. shading each visibility sample. To improve performance, previous work often decouple shading from visibility sampling using shader caching algorithms. We present a novel technique for reusing shading in a stochastic rasterizer. Shading is computed hierarchically and sparsely in an object‐space texture, and by selecting an appropriate mipmap level for each triangle, we ensure that the shading rate is sufficiently high so that no noticeable blurring is introduced in the rendered image. Furthermore, with a two‐pass algorithm, we separate shading from reuse and thus avoid GPU thread synchronization. Our method runs at real‐time frame rates and is up to 3 × faster than previous methods. This is an important step forward for stochastic rasterization in real time.
Forgetting Falls (1988)

To determine how accurately elderly subjects recall recent falls, we studied 304 ambulatory men and women over the age of 60 years who completed a 12-month prospective study of risk factors for falling. We developed a system of weekly follow-up and home visits to record and confirm all falls. During the study, 179 participants suffered at least one fall that was confirmed by home visit. At the end of the study, all subjects were interviewed by telephone about whether they had suffered a fall during the preceding 3, 6, or 12 months. Depending on the time period of recall, 13% to 32% of those with confirmed falls did not recall falling during the specific period of time. Recall was better for the preceding 12 months than for 3 or 6 months. There were only weak correlations (r = 0.28 to 0.59) between the number of falls that were documented and the number that the subjects recalled during each of these periods. Those with lower scores on the Mini-Mental State Examination were more likely to forget falls. We conclude that elderly subjects often do not recall falls that occurred during specific periods of time over the preceding 3 to 12 months. Researchers and clinicians should consider using methods besides long-term recall for ascertaining and counting falls over specific periods of time.
Mode of binding of pyrroloquinoline quinone to apo-glucose dehydrogenase. (1985)

Whilst in acetic acid bacteria glucose dehydrogenase (EC 1.1.99.a) is abundantly formed in the cytoplasmic membrane, the enzyme was also found more or less in various other microorganisms in which its existence had not been reported previously. Glucose dehydrogenase from Escherichia coli occurred almost completely as the apoenzyme, being freed from pyrroloquinoline quinone (PQQ), a unique prosthetic group of the enzyme. Treatment of the E. coli membrane with EDTA caused a complete loss of the enzyme activity and subsequent addition of exogenous PQQ gave rise to no reactivation of the enzyme unless some magnesium ions were added. The magnesium ions could function by anchoring the PQQ to the apoenzyme.
Malignant transformation of the human endometrium is associated with overexpression of lactoferrin messenger RNA and protein. (1995)

In the mouse uterus, lactoferrin is a major estrogen-inducible uterine secretory protein, and its expression correlates directly with the period of peak epithelial cell proliferation. In this study, we examine the expression of lactoferrin mRNA and protein in human endometrium, endometrial hyperplasias, and adenocarcinomas using immunohistochemistry, Western immunoblotting, and Northern and in situ RNA hybridization techniques. Our results reveal that lactoferrin is expressed in normal cycling endometrium by a restricted number of glandular epithelial cells located deep in the zona basalis. Two thirds (8 of 12) of the endometrial adenocarcinomas examined overexpress lactoferrin. This tumor-associated increase in lactoferrin expression includes an elevation in the mRNA and protein of individual cells and an increase in the number of cells expressing the protein. In comparison, only 1 of the 10 endometrial hyperplasia specimens examined demonstrates an increase in lactoferrin. We also observe distinct cytoplasmic and nuclear immunostaining patterns under different fixation conditions in both normal and malignant epithelial cells, similar to those previously reported in the mouse reproductive tract. Serial sections of malignant specimens show a good correlation between the localization of lactoferrin mRNA and protein in individual epithelial cells by in situ RNA hybridization and immunohistochemistry. Although the degree of lactoferrin expression in the adenocarcinomas did not correlate with the tumor stage, grade, or depth of invasion in these 12 patients, there was a striking inverse correlation between the presence of progesterone receptors and lactoferrin in all 8 lactoferrin-positive adenocarcinomas. In summary, lactoferrin is expressed in a region of normal endometrium known as the zona basalis which is not shed with menstruation and is frequently overexpressed by progesterone receptor-negative cells in endometrial adenocarcinomas.
Why Particle Size Should Affect Clinical Response to Inhaled Therapy (2001)

Studies with beta2-adrenergic agonists have shown that particle size and total dose are important determinants of optimum bronchodilation. Drug deposition in the airways is probably the most important factor for bronchodilation, since beta2-adrenoceptors and muscarinic M3 receptors are present mainly in the peripheral and central airways, respectively. Furthermore, clinical efficacy can be maintained while minimizing systemic exposure by selecting an appropriate particle size. Changes in lung function provide a means of monitoring the relationship between delivery of the bronchodilator and its efficacy, whereas there is no such immediate means of assessing antiinflammatory preventative therapy such as inhaled corticosteroids. Asthma is primarily an inflammatory disease but there are no simple tests to detect the accumulation of inflammatory cells and mediators. Data are presented to demonstrate the reduction of certain inflammatory markers in bronchial biopsy tissue taken from asthmatic patients after corticosteroid therapy. Measurement of inflammatory markers in both bronchial biopsy tissue and bronchoalveolar lavage samples may provide a way of monitoring the site of action and efficacy of inhaled corticosteroids in the future. Furthermore, it is envisaged that the effect of corticosteroid particle size on efficacy and systemic bioavailability may be investigated by exploiting these methods.
Toward Defining the Human Parotid Gland Salivary Proteome and Peptidome:  Identification and Characterization Using 2D SDS−PAGE, Ultrafiltration, HPLC, and Mass Spectrometry (2005)

Saliva plays many biological roles, from lubrication and digestion to regulating bacterial and leukocyte adhesion. To understand the functions of individual components and families of molecules, it is important to identify as many salivary proteins as possible. Toward this goal, we used a proteomic approach as the first step in a global analysis of this important body fluid. We collected parotid saliva as the ductal secretion from three human donors and separated the protein components by two-dimensional SDS-polyacrylamide gel electrophoresis (2D SDS-PAGE). Proteins in gel spots were identified by peptide mass fingerprinting, and the results were confirmed by tandem mass spectrometry of selected peptides. Complementing this approach we used ultrafiltration to prepare a low-molecular-weight fraction of parotid saliva, which was analyzed directly or after reversed phase high-performance liquid chromatography separation by using mass spectrometric approaches. MS analyses of 2D SDS-PAGE spots revealed known components of saliva, including cystatins, histatins, lysozyme, and isoforms and/or fragments of alpha-amylase, albumin, and proline-rich proteins. We also discovered novel proteins, such as several isoforms of Zn-alpha-2-glycoprotein and secretory actin-binding protein. MS analyses of the ultrafiltrate showed that the low-molecular-weight fraction of parotid saliva was peptide-rich, with novel fragments of proline-rich proteins and histatins in abundance. Experiments using Candida albicans as the test organism showed that at least one of the novel peptides had antifungal activity. Our results show that saliva is a rich source of proteins and peptides that are potential diagnostic and therapeutic targets.
Distinct optical and kinetic responses from E/Z isomers of caspase probes with aggregation-induced emission characteristics (2014)

A dual-labeled probe for monitoring caspase activity was designed and synthesized based on a tetraphenylethene (TPE) fluorogen with aggregation-induced emission characteristics and a caspase-specific Asp-Glu-Val-Asp (DEVD) peptide. Two stereoisomers were furnished and successfully separated by HPLC. We demonstrated for the first time the effect of isomerization on the reaction kinetics between the probes and caspase. It was revealed that caspase can produce a much higher light-up ratio for the Z-TPE-2DEVD probe, while its kinetics favor E-TPE-2DEVD due to enhanced probability of optimal binding between the two. Understanding the stereoisomers and their biological functions will open new opportunities for bioprobe design with optimized performance.
DETERMINATION OF BASE SEQUENCE IN NUCLEIC ACIDS WIT THE ELECTRON MICROSCOPE: VISIBILITY OF A MARKER (1962)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
A Light Source Smaller Than the Optical Wavelength (1990)

A method has been developed for the efficient emission of light from subwavelength dimensions. It is based on packaging photons as molecular excitons, effectively reducing the volume of the light beam by 10(9) and making possible propagation through dimensions of 1 nanometer. Molecular microcrystals are grown in the tips of micropipettes that have inner diameters of 100 nanometers or less. Measurements are presented that demonstrate this improvement in transmission for pipettes of various diameters. The ultrasmall dimensions of these light sources, the wavelength range (ultraviolet to red) of their emission, their ease of production, and their expected unique abilities for high efficiency excitation-imaging of surfaces portend significant applications for this methodology.
A role for nonspecific (cyclosporin A) or specific (monoclonal antibodies to ICAM-1, LFA-1, and IL-10) immunomodulation in the prolongation of skin allografts after antigen-specific pretransplant immunization or transfusion. (1994)

C3H/HEJ mice given pretransplant immunization via the portal vein with irradiated B10.BR spleen cells or non-irradiated B10.BR peripheral blood leukocytes showed delayed rejection of B10.BR but not BALB.K skin grafts. No increased graft survival was seen if pretransplant immunization was given by the lateral tail vein. Addition of a single treatment with cyclosporin A after pretransplant immunization via the portal vein led to indefinite graft survival in over 70% of recipients. As reported earlier, increased graft survival in vivo was correlated with preferential production of IL-4 (from Th2 type cells) rather than IL-2 from lymphocytes stimulated in vitro. When mice were given pretransplant transfusion via the lateral tail vein and a combination of anti-LFA-1 and anti-ICAM-1 mAbs, increased graft survival was again seen. In addition, in vivo injection of anti-IL-10 mAbs (but not anti-IFN-gamma or anti-IL-4 mAbs) abolished the delayed rejection seen when mice received pretransplant immunization via the portal vein. In all cases, delayed graft rejection in vivo was correlated with preferential activation of Th2-type cells, as assessed by lymphokine production from cells harvested from treated mice and activated in vitro.
Three-step sequential solution deposition of PbI2-free CH3NH3PbI3perovskite (2014)

We demonstrate a facile approach for preparing PbI<sub>2</sub>-free CH<sub>3</sub>NH<sub>3</sub>PbI<sub>3</sub>perovskite films<italic>via</italic>a three-step sequential solution process.
Lipopolysaccharide-stimulated human monocytes secrete, apart from neutrophil-activating peptide 1/interleukin 8, a second neutrophil-activating protein. NH2-terminal amino acid sequence identity with melanoma growth stimulatory activity. (1990)

Purification of monocyte-derived NAP-1/IL-8 by preparative reversed-phase (RP)-HPLC led to the detection of a second peak with polymorphonuclear leukocyte (PMNL)-activating (degranulation, chemotaxis) properties. The monokine responsible for this biological activity, which we tentatively termed NAP-3, could be purified to homogeneity by three different RP-HPLC steps. Tricine-SDS-PAGE analysis gave a single line at Mr 5.3 kD (NAP-1/IL-8 = 5.8 kD). NH2-terminal amino acid sequence analysis read as a major sequence (ASVATELRXCXLQT. .), which shows greater than 40% homology to that of NAP-1/IL-8. The sequence is identical to that found for the 13-kD moiety of melanoma growth stimulating activity (MGSA) and the product of the oncogene gro. Determination of neutrophil chemotactic activity of NAP-3 revealed a typical bell-shaped dose-response curve (ED50 = 2 ng/ml) with no significant neutrophil chemotactic activity at doses greater than 200 ng/ml. Also, in cytochalasin B-pretreated PMNL, NAP-3 elicited release of myeloperoxidase and beta-glucuronidase. Crossdesensitization studies in PMNL enzyme release revealed crossreactivities with the NAP-1/IL-8-R on PMNL. NAP-3 (MGSA/gro) appears to represent the first member of the novel supergene family of beta-thromboglobulin-like host defense cytokines, which expresses both mitogenic as well as proinflammatory properties at the nanogram level.
Enhancement of verticillium wilt resistance in tomato transplants by in vitro co-culture of seedlings with a plant growth promoting rhizobacterium (Pseudomonas sp. strain PsJN) (1998)

The potential utilization of a plant growth promoting rhizobacterium, Pseudomonas sp. strain PsJN, to enhance the resistance of tomato transplants to verticillium wilt was investigated. Plant growth and disease development were tested on the disease-susceptible cultivar Bonny Best after Verticillium dahliae infection of tissue culture plantlets bacterized in vitro (by co-culturing with the bacterium) and seedlings bacterized in vivo (after 3 weeks growth in the greenhouse). Significant differences in both disease suppression and plant growth were obtained between in vitro bacterized and nonbacterized (control) plants. The degree of protection afforded by in vitro bacterization depended on the inoculum density of V. dahliae; the best and worst protection occurred at the lowest (10 3 conidia ·mL -1 ) and highest (10 6 conidia ·mL -1 ) levels, respectively. In contrast, the in vivo bacterized tomatoes did not show plant growth promotion when compared to the nonbacterized control plants. When challenged with Verticillium, significant growth differences between in vivo bacterized plants (26.8% for shoot height) and nonbacterized controls were only seen at the 3rd week after inoculation. Compared with the in vitro inoculation, there was no delay in the verticillium wilt symptom expression, even at the lowest concentration of V. dahliae, by in vivo PsJN inoculation. These results suggest that endophytic colonization of tomato tissues is required for the Verticillium-resistance responses. Plant growth promotion preceeds the disease-resistance responses and may depend on the colonization thresholds and subsequent sensitization of hosts.Key words: Pseudomonas sp., plant growth promoting rhizobacterium, Verticillium dahliae, tomato, colonization, plant growth promotion, disease suppression.