gebhart/patrepeval huggingface dataset:
Glucose uptake and catabolite repression in dominant HTR1 mutants of Saccharomyces cerevisiae (1993)

Growth and carbon metabolism in triosephosphate isomerase (delta tpi1) mutants of Saccharomyces cerevisiae are severely inhibited by glucose. By using this feature, we selected for secondary site revertants on glucose. We defined five complementation groups, some of which have previously been identified as glucose repression mutants. The predominant mutant type, HTR1 (hexose transport regulation), is dominant and causes various glucose-specific metabolic and regulatory defects in TPI1 wild-type cells. HTR1 mutants are deficient in high-affinity glucose uptake and have reduced low-affinity transport. Transcription of various known glucose transporter genes (HXT1, HXT3, and HXT4) was defective in HTR1 mutants, leading us to suggest that HTR mutations affect a negative factor of HXT gene expression. By contrast, transcript levels for SNF3, which encodes a component of high-affinity glucose uptake, were unaffected. We presume that HTR1 mutations affect a negative factor of HXT gene expression. Multicopy expression of HXT genes or parts of their regulatory sequences suppresses the metabolic defects of HTR1 mutants but not their derepressed phenotype at high glucose concentrations. This suggests that the glucose repression defect is not a direct result of the metabolically relevant defect in glucose transport. Alternatively, some unidentified regulatory components of the glucose transport system may be involved in the generation or transmission of signals for glucose repression.
Spinal Cord Stimulation in Treatment of Chronic Benign Pain: Challenges in Treatment Planning and Present Status, a 22-Year Experience (2006)

Spinal cord stimulation can provide significant long-term pain relief with improved quality of life and employment. Results of this study will be effective in better defining prognostic factors and reducing complications leading to higher success rates with spinal cord stimulation.
Fetal Vibroacoustic Stimulation in Computerized Cardiotocographic Analysis: The Role of Short-Term Variability and Approximate Entropy (2012)

The aim of this study was to evaluate the impact of vibroacoustic stimulation (VAS) on computerized cardiotocography short-term variability (STV) and approximate entropy (ApEn) in both low- and high-risk pregnancies. VAS was performed on 121 high- and 95 low-risk pregnancies after 10 minutes of continuous quiet, while their FHR parameters were monitored and recorded by cCTG analysis. Fetal heart rate was recorded using a computer-assisted equipment. Baseline FHR, accelerations, decelerations, STV, long-term irregularity (LTI), ApEn, and fetal movements (FMs) were calculated for defined observational periods before VAS and after 10 minutes. Data were also investigated in relationship with the perinatal outcome. In each group of patients, FHR after VAS remained almost unmodified. Fetal movements significantly increased after VAS in both groups. Results show that only in the high-risk pregnancies, the increase of STV and the decrease of ApEn after VAS were significantly associated with favorable perinatal outcomes.
Akt Maintains Cell Size and Survival by Increasing mTOR-dependent Nutrient Uptake (2002)

In multicellular organisms, constituent cells depend on extracellular signals for growth, proliferation, and survival. When cells are withdrawn from growth factors, they undergo apoptosis. Expression of constitutively active forms of the serine/threonine kinase Akt/PKB can prevent apoptosis upon growth factor withdrawal. Akt-mediated survival depends in part on the maintenance of glucose metabolism, suggesting that reduced glucose utilization contributes to growth factor withdrawal-induced death. However, it is unclear how restricting access to extracellular glucose alone would lead to the metabolic collapse observed after growth factor withdrawal. We report herein that growth factor withdrawal results in the loss of surface transporters for not only glucose but also amino acids, low-density lipoprotein, and iron. This coordinated decline in transporters and receptors for extracellular molecules creates a catabolic state characterized by atrophy and a decline in the mitochondrial membrane potential. Activated forms of Akt maintained these transporters on the cell surface in the absence of growth factor through an mTOR-dependent mechanism. The mTOR inhibitor rapamycin diminished Akt-mediated increases in cell size, mitochondrial membrane potential, and cell survival. These results suggest that growth factors control cellular growth and survival by regulating cellular access to extracellular nutrients in part by modulating the activity of Akt and mTOR.
Real-time MR Imaging With Gadoteridol Predicts Distribution of Transgenes After Convection-enhanced Delivery of AAV2 Vectors (2010)

Gene therapies that utilize convention-enhanced delivery (CED) will require close monitoring of vector infusion in real time and accurate prediction of drug distribution. The magnetic resonance imaging (MRI) contrast agent, Gadoteridol (Gd), was used to monitor CED infusion and to predict the expression pattern of glial cell line-derived neurotrophic factor (GDNF) protein after administration of adeno-associated virus type 2 (AAV2) vector encoding human pre-pro-GDNF complementary DNA. The nonhuman primate (NHP) thalamus was utilized for modeling infusion to allow delivery of volumes more relevant to planned human studies. AAV2 encoding human aromatic L-amino acid decarboxylase (AADC) was coinfused with AAV2-GDNF/Gd to confirm regions of AAV2 transduction versus extracellular GDNF diffusion. There was a close correlation between Gd distribution and GDNF or AADC expression, and the ratios of expression areas of GDNF or AADC versus Gd were both close to 1. Our data support the use of Gd and MRI to monitor AAV2 infusion via CED and to predict the distribution of GDNF protein after AAV2-GDNF administration.
A comparative study of vacuum‐assisted resin transfer molding (VARTM) for sandwich panels (2003)

Abstract Vacuum‐assisted resin transfer molding (VARTM) of sandwich panels can be facilitated by using high permeability layers (HPL) over the skins or adding channels in the surfaces of the core (CIC). The present paper investigates the advantages and disadvantages of both methods in terms of manufacturing cost and time through simulations and experimental observations. A cost model is developed, and the resin infusion time for each method was minimized through simulations. The design parameters are the number of high‐permeability layers and the number and size of channels. A penalty function with equal weight on cost and time is used to find the optimum values of the design parameters. Under the conditions studied, the optimal HPL method is found to be better than the optimal CIC method. While the conclusion is limited to the present study, the proposed approach can be used to optimize manufacturing processes for larger sandwich panels under different conditions.
Acetyl‐coenzyme A carboxylases: Versatile targets for drug discovery (2006)

Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism in humans and most other living organisms. They are attractive targets for drug discovery against a variety of human diseases, including diabetes, obesity, cancer, and microbial infections. In addition, ACCs from grasses are the targets of herbicides that have been in commercial use for more than 20 years. Significant progresses in both basic research and in drug discovery have been made over the past few years in the studies on these enzymes. At the basic research level, the crystal structures of the biotin carboxylase (BC) and the carboxyltransferase (CT) components of ACC have been determined, and the molecular basis for ACC inhibition by small molecules are beginning to be understood. At the drug discovery level, a large number of nanomolar inhibitors of mammalian ACCs have been reported and the extent of their therapeutic potential is being aggressively explored. This review summarizes these new progresses and also offers some prospects in terms of the future directions for the studies on these important enzymes.
Foamed Cement — Solving Old Problems with a New Technique (1982)

ABSTRACT A new method of combining nitrogen with an intermediate-weight cement slurry (13 to 15 1 b/gal) to generate a stable foam has solved many of the problems associated with the use of conventional lightweight cements in oil-field operations. Foaming permits placing relatively high-strength, lightweight (6 to 11 lb/gal) cement slurries into the casing-formation annulus economically. Lightweight filler cement is often needed to provide a complete cement sheath along the length of the casing, where lost circulation is encountered or long lifts of cements are required. Various methods have been used in the past to obtain this lightweight slurry. These include the use of natural and chemical extenders, glass bubbles, ceramic bubbles and the combination of intermediate-weight cement slurries with gases. While the process of foaming cement to make lightweight slurries is not new, the technology for applying this process to oil and gas well cementing has been lacking. The new method requires special treatment and slurry design to obtain a hydrostatically balanced slurry along the entire length of the casing, but can be performed with current equipment and field personnel. Laboratory data and case histories have been used to describe these designs. The added safety requirements which must be in effect to successfully complete this type of cementing operation are discussed.
Hyaluronic Acid in the Treatment and Prevention of Skin Diseases: Molecular Biological, Pharmaceutical and Clinical Aspects (2004)

The glycosaminoglycan hyaluronic acid (HA), or hyaluronan, is a major component of the extracellular matrix of skin, joints, eye and many other tissues and organs. In spite of its simple structure, HA demonstrates remarkable rheological, viscoelastic and hygroscopic properties which are relevant for dermal tissue function. Biological activities in skin, however, are also due to its interaction with various binding proteins (hyaladherins). Due to an influence on signaling pathways, HA is involved in the wound-healing process and scarless fetal healing. Increased HA concentrations have been associated with inflammatory skin diseases. In clinical trials, topical application of HA improved wound healing; in particular, acute radioepithelitis, venous leg ulcers or diabetic foot lesions responded to HA treatment. Moreover, as a topical drug delivery system for diclofenac, an HA gel has recently been approved for the treatment of actinic keratoses. Finally, chemical modifications led to new HA derivates and biomaterials, which may be introduced into therapy in the future. Therefore, ongoing research offers new horizons for the therapeutic use of this glycosaminoglycan which has been regarded as an inert structural component until recently.
Technological application of an extracellular cell lytic enzyme in xanthan gum clarification (2005)

An extracellular cell lytic enzyme from Pseudomonas sp. was active on heat killed cells of Xanthomonas campestris. The lytic activity caused enzymatic digestion of X.campestris xanthan gum. Digestion was effective for highly viscous native xanthan 2.0% (w/v) and 2.5% (w/v) commercial Sigma xanthan. Scanning electron microscopy and SDS-PAGE observations confirmed the cell lytic action on X.campestris cells.
Emergence of Grounded Compositional Language in Multi-Agent Populations (2018)

By capturing statistical patterns in large corpora, machine learning has enabled significant advances in natural language processing, including in machine translation, question answering, and sentiment analysis. However, for agents to intelligently interact with humans, simply capturing the statistical patterns is insufficient. In this paper we investigate if, and how, grounded compositional language can emerge as a means to achieve goals in multi-agent populations. Towards this end, we propose a multi-agent learning environment and learning methods that bring about emergence of a basic compositional language. This language is represented as streams of abstract discrete symbols uttered by agents over time, but nonetheless has a coherent structure that possesses a defined vocabulary and syntax. We also observe emergence of non-verbal communication such as pointing and guiding when language communication is unavailable.
T4 ribonucleic acid ligase joins single-strand oligo(deoxyribonucleotides) (1980)

T4 RNA ligase joins a 3'-hydroxyl-terminated acceptor oligoribonucleotide to a 5'-phosphate-terminated donor oligoribonucleotide. An analogous reaction with single-strand DNA oligonucleotides would be useful for the synthesis of defined sequences of DNA because it would eliminate the need to synthesize complementary sequences to form the duplex substrates required by DNA ligase. We have studied the model reaction dA(pdA)5 + [5'-32P] (pdT)4pdCp leads to dA(pdA)5 [3' leads to 5'-32P]pdT(pdT)3pdCp and have obtained 40-60% yields at equimolar concentrations (100 microM to 1 mM) of the two substrates. Higher yields have been obtained when acceptor concentrations in excess of those of the donor are used. The use of a 5'-hydroxyl, 3'-hydroxyl terminated acceptor and a 5'-phosphate, 3'-phosphate terminated donor limits the reaction to a unique product. The 3'-phosphate-terminated donor was prepared by using RNA ligase to add a single deoxyribonucleoside 3',5'-bisphosphate donor to an oligo(deoxyribonucleotide) acceptor [Hinton, D.M., Baez, J.A., & Gumport, R.I. (1978) Biochemistry 17, 5091]. The DNA oligomer joining reaction requires low concentrations of ATP and an ATP regenerating system, Mn2+, high levels of nuclease-free RNA ligase (30 microM), and incubation for several days at 17 degrees C. The product of the reaction was characterized by its resistance to alkaline phosphatase, degradation by micrococcal nuclease to the expected product [3'-32P]dAMP, and mobility during high-pressure liquid chromatography on RPC-5. The joining of several other deoxyoligomers was also demonstrated. We anticipate that this reaction of RNA ligase will contribute to its usefulness as a reagent for the synthesis of DNA of defined sequence.
“天皇制法西斯主义”重探——日本现代史的割裂与继承 (1983)

五十多年前,由于世界性的经济大萧条和中国、朝鲜的民族解放运动,仅仅3年时间,就动摇了日本政治制度的基础,促使政治改革成为当时的首要问题。在1929—1931年间的危机时期,日本的外交政策进一步军事化,各级当政者变得越来越专横,以致使社会上各个阶层都对议会制度不再抱有任何幻想。到了三十年代末,盛行于罗马与柏林的法西斯主义不仅在东京有所表现,而且在整个日本都能看到一种“天皇制法西斯主义”的专制制度。军事集团、高级文官以及企业老板、金融寡头和财阀之间的紧密勾结形成了当时的基本特征。
Finding shortest path on land surface (2011)

Finding shortest paths is a fundamental operator in spatial databases. Recently, terrain datasets have attracted a lot of attention from both industry and academia. There are some interesting issues to be studied in terrain datasets which cannot be found in a traditional two-dimensional space. In this paper, we study one of the issues called a slope constraint which exists in terrain datasets. In this paper, we propose a problem of finding shortest paths with the slope constraint. Then, we show that this new problem is more general than the traditional problem of finding shortest paths without considering the slope constraint. Since finding shortest paths with the slope constraint is costly, we propose a new framework called surface simplification so that we can compute shortest paths with the slope constraint efficiently. Under this framework, the surface is "simplified" such that the complexity of finding shortest paths on this simplified surface is lower. We conducted experiments to show that the surface simplification is very efficient and effective not only for the new problem with the slope constraint but also the traditional problem without the slope constraint.
Efficient Construction of a Large Collection of Phage-Displayed Combinatorial Peptide Libraries (2005)

Selections from phage-displayed combinatorial peptide libraries are an effective strategy for identifying peptide ligands to target proteins. Existing protocols for constructing phage-displayed libraries utilize either ligation into double-stranded phage DNA or Kunkel mutagenesis with single-stranded phagemid DNA. Although the Kunkel approach rapidly provides library sizes of up to 10(11), as many as 20% of the phagemids may be non-recombinant. With several modifications to current Kunkel protocols, we have generated peptide libraries with sizes of up to 10(11) clones and recombination frequencies approaching 100%. The production of phage libraries, as opposed to phagemid libraries, simplifies selection experiments by eliminating the need for helper phage. Our approach relies upon the presence of an amber stop codon in the coding region of gene III of bacteriophage M13. Oligonucleotides containing randomized stretches of DNA are annealed to the phage genome such that the randomized region forms a heteroduplex with the stop codon. The oligonucleotide is then enzymatically extended to generate covalently-closed, circular DNA, which is electroporated into a non-suppressor strain of Escherichia coli. If the amber stop codon is present in the DNA molecule, protein III is not synthesized and the phage cannot propagate itself. This method is customizable for the display of either random or focused peptide libraries. To date, we have constructed 22 different libraries ranging from 8-20 amino acids in length, utilizing complete or reduced codon sets.
The Molecular Basis of X‐Linked Severe Combined Immunodeficiency: The Role of the Interleukin‐2 Receptor γ Chain as a Common γ Chain, γc (1994)

X-linked severe combined immunodeficiency is characterized by severe and persistent infections from early life resulting from profound impairment of both cellular and humoral immune function. XSCID is characterized by an absence or diminished number of T cells and histologic evidence of hypoplastic and abnormal differention of the thymic epithelium. The discovery that this disease results from the mutations of the IL-2R gamma chain was surprising since IL-2-deficient mice and human SCID patients had milder phenotypes. This led to the speculation that IL-2R gamma would prove to be a common gamma chain, gamma c, which would play important roles in other cytokine receptors in addition to the IL-2 receptor. There is now compelling evidence to support a role in at least two other cytokine receptors, namely the IL-4 and IL-7 receptors. Thus, with inactivation of gamma c, multiple cytokine systems are simultaneously affected, resulting in the profoundly impaired phenotype of XSCID. It is possible and even likely that gamma c will be found to be a functional component of additional receptors as well. These findings have resulted in a significant improvement in our understanding of the pathophysiologic development of the defects in XSCID and also have important ramifications for prenatal and postnatal diagnosis, carrier female identification, and gene therapy for XSCID.
Antioxidant Redox Sensors Based on DNA Modified Carbon Screen-Printed Electrodes (2006)

Antioxidant redox sensors based on DNA modified carbon screen-printed electrodes were developed. The carbon ink was doped with TiO2 nanoparticles, onto which double-strand DNA was adsorbed. A redox mediator, namely, tris-2,2'-bipyridine ruthenium(II) [Ru(bpy)3(2+)] was electrooxidized on the electrode surface to subsequently oxidize both the adsorbed ds-DNA and the antioxidants in solution. The resulting oxidation damage of the adsorbed ds-DNA was then detected by square wave voltammetry in a second solution containing only Ru(bpy)3Cl2 at a low concentration (microM). A kinetic model was developed to study the protecting role of antioxidants in aqueous solutions. The electrochemical sensor has been applied to evaluate the redox antioxidant capacity of different molecules.
Coloring heuristics for register allocation (2004)

We describe an improvement to a heuristic introduced by Chaitin for use in graph coloring register allocation. Our modified heuristic produces better colorings, with less spill code. It has similar compile-time and implementation requirements. We present experimental data to compare the two methods.
Integrated GPS/Inertial Fault Detection Availability (1996)

Different techniques have been proposed for combining GPS and inertial sensor information, and recent published findings seem to indicate that primary-means integrity availability is achievable with standard 2 nmi/h (95 percent) inertial sensor performance. This paper investigates and quantifies the different inertial effects that contribute to enhanced integrity of the integrated GPS/inertial system, such as coasting or Schuler feedback. A Kalman filter-based integration scheme that preserves the integrity information in an optimal fashion is presented and used to quantify integrity performance. This paper also proposes an approximate model, incorporating the main inertial effects contributing to integrity, that can be used to calculate the achievable horizontal protection level (HPL) at any geographical location and time. This model is used to estimate the availability of fault detection for an integrated GPS/inertial system. In addition, the paper compares the availability of fault detection for the GPS/inertial system with that for other augmentations to provide trade-off information.
Histone-Deacetylase Inhibitors for the Treatment of Cancer (2004)

Histone deacetylase inhibitors (HDACi) are a promising new class of chemotherapeutic drug currently in early phase clinical trials. A large number of structurally diverse HDACi have been purified or synthesised that mostly inhibit the activity of all eleven class I and II HDACs. While these agents demonstrate many features required for anti-cancer activity such as low toxicity against normal cells and an ability to inhibit tumor cell growth and survival at nanomolar concentrations, their mechanisms of action are largely unknown. Initially, a model was proposed whereby HDACi-mediated transactivation of a specific gene or set of genes was responsible for the inhibition of cell cycle progression or induction of apoptosis. Given that HDACs can regulate the activity of a number of nonhistone proteins and that histone acetylation is important for events such as DNA replication and mitosis that do not directly involve gene transcription, it appears that the initial mechanistic model for HDACi may have been too simple. Herein, we provide an update on the transcription-dependent and -independent events that may be important for the anti-tumor activities of HDACi and discuss the use of these compounds in combination with other chemotherapeutic drugs.