gebhart/patrepeval huggingface dataset:
Pseudohypoxic Pathways in Renal Cell Carcinoma (2007)

Mutations of the von Hippel-Lindau (VHL) or fumarate hydratase (FH) genes lead to morphologically different renal cell carcinomas with distinct clinical courses and outcomes. The VHL protein is a part of an ubiquitin ligase complex that targets proteins for proteosomal degradation. FH is one of the mitochondrial enzymes of the Kreb's cycle. Despite two different functionalities and cellular locations, loss of either VHL or FH products has been shown to alter expression levels of hypoxia-inducible factors (HIF-1alpha and HIF-2alpha) and their downstream targets. HIF proteins are key regulators of oxygen homeostasis. Tight regulation of HIF allows for cell survival and growth at the time of hypoxic stress. HIF acts via transcriptional regulation of vascular endothelial growth factor, platelet derived growth factor, endothelial growth factor receptor, glucose transporter protein 1, erythropoietin, and transforming growth factor-alpha. Loss of VHL or FH is thought to result in a pseudohypoxic state so that cellular response pathways mediated by HIF are activated despite normal oxygen conditions. Understanding of these pseudohypoxic pathways has provided a better appreciation of the molecular mechanisms of carcinogenesis in addition to providing a rationale for targeted therapeutic approaches.
A web contents sharing system with contents delivery control functions (2003)

In this paper, we propose a web contents sharing system which allows a user to save web contents presented on internet and share them on P2P (peer to peer) network. In this system, a user can use the URL, the last update date and time, the size or some other information in order to search web pages. In addition, a user can get web pages that have existed and do not currently exist if they are stored in other systems. Furthermore, we realized a mechanism for authors to control contents delivery, such as the prohibited of forwarding the contents and notification to the authors on forwarding contents. Keyword Peer-to Peer, Web, Date Sharing, Contents Delivery, Delivery Control
The story of a new insecticidal chemistry class: the diamides (2012)

This paper describes the story of the invention of the diamides, a novel chemical class of insecticides. It starts with the pioneering work by Nihon Nohyaku researchers, who developed a herbicide lead with weak insecticidal activity to flubendiamide, a highly potent lepidoptericide. The journey continues with Nissan's isoxazolines and the invention of the anthranilamides by DuPont, culminating in the discovery of the blockbuster chlorantraniliprole and its analogue cyantraniliprole. The next steps are Syngenta's sulfoximines and bicyclic anthranilamides, Ishihara Sangyo Kaisha's cyclopropylamides, Sumitomo's hydrazides, Bayer's pyrazoles and tetrazoles, BASF's sulfoximines and more recent contributions from Chinese agrochemical companies and academic institutions. The diamides affect calcium homeostasis by binding to ryanodine receptors and releasing calcium from the intracellular stores. Investigations at Nihon Nohyaku, DuPont and Bayer on the action of the diamides on ryanodine receptors will be briefly reported.
The efficiency and equity of livestock rating systems and the accuracy of data obtained from them. (1982)

When graziers are required to pay a rate in proportion to the number of livestock they declare, some tend to reduce the number declared. In western New South Wales discrepancies exist between livestock numbers reported to local Pastures Protection Boards for rating purposes and those collected by the Australian Bureau of Statistics. The size of the discrepancy is considerable. Other systems of collecting revenue may be more efficient and more equitable. Data obtained from livestock rating systems provide an accurate indication of trends in livestock numbers but do not give an accurate assessment of the total number of livestock within an area
Thumb Site 2 Inhibitors of Hepatitis C Viral RNA-dependent RNA Polymerase Allosterically Block the Transition from Initiation to Elongation (2016)

Replication of the hepatitis C viral genome is catalyzed by the NS5B (nonstructural protein 5B) RNA-dependent RNA polymerase, which is a major target of antiviral drugs currently in the clinic. Prior studies established that initiation of RNA replication could be facilitated by starting with a dinucleotide (pGG). Here we establish conditions for efficient initiation from GTP to form the dinucleotide and subsequent intermediates leading to highly processive elongation, and we examined the effects of four classes of nonnucleoside inhibitors on each step of the reaction. We show that palm site inhibitors block initiation starting from GTP but not when starting from pGG. In addition we show that nonnucleoside inhibitors binding to thumb site-2 (NNI2) lead to the accumulation of abortive intermediates three-five nucleotides in length. Our kinetic analysis shows that NNI2 do not significantly block initiation or elongation of RNA synthesis; rather, they block the transition from initiation to elongation, which is thought to proceed with significant structural rearrangement of the enzyme-RNA complex including displacement of the β-loop from the active site. Direct measurement in single turnover kinetic studies show that pyrophosphate release is faster than the chemistry step, which appears to be rate-limiting during processive synthesis. These results reveal important new details to define the steps involved in initiation and elongation during viral RNA replication, establish the allosteric mechanisms by which NNI2 inhibitors act, and point the way to the design of more effective allosteric inhibitors that exploit this new information.
ASTOR, Concept of a Combined Acceleration and Storage Ring for the Production of Intense Pulsed or Continuous Beams of Neutrinos, Pions, Muons, Kaons and Neutrons (1983)

A new concept for a high intensity accelerator for 2 GeV protons using the continuous 590 MeV beam from the present ring cyclotron has been worked out at SIN. To suppress the cosmic background in neutrino experiments a pulsed beam with high peak current and low duty cycle is required. Using the so called phase expansion effect one can combine the acceleration and storage effect in a single isochronous cyclotron ASTOR. With the help of several RF cavities, positioned at different radii it is possible to operate ASTOR either in a pulsed mode at 1500 Hz or in a continuous mode. The anticipated beam powers are .8 MW and 4 MW respectively. The ASTOR concept is also applicable in a possible kaon factory design, acting as an interface between the SIN ring cyclotron and a 50 Hz synchrotron for 15 to 20 GeV protons.
Parallel bidirectional heuristic search on the EM-4 multiprocessor (2002)

Solving search problems takes a large amount of computational resources both in terms of execution time and memory usage. This report presents experimental results of Parallel Bidirectional Heuristic Search (PBiHS) on the 80-processor EM-4 multithreaded data-flow multiprocessor. The PBiHS searches from two directions in parallel while search in each direction is also performed in parallel. Important data structures are distributed to all processors to help reduce the execution time of realistic problem sizes down to a few seconds or less. We implement two search problems, the Eight Puzzle and the Tower of Hanoi, and execute on the target multiprocessor. Execution results demonstrate that the Parallel Bidirectional Heuristic Search can solve the tree depth 20-40 of the Eight-Puzzle and the 3-9 disks of the Tower of Hanoi in an optimal or near optimal number of iterations in less than two seconds, is highly scalable as it gives over 40-fold speedup on 80 processors, and yields on the average 10-fold improvement over unidirectional search for the 8-Puzzle while generating a far less number of nodes.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
<i>In Vivo</i> Evaluation of 1-Benzyl-4-aminoindole-Based Thyroid Hormone Receptor β Agonists: Importance of Liver Selectivity in Drug Discovery (2014)

We recently reported that the novel thyroid hormone receptor β (TRβ) selective agonists SKL-12846 and SKL-13784 reduce blood cholesterol levels without affecting thyroid-stimulating hormone (TSH) in cholesterol-fed rats. Our aim in this study was to elucidate what sets apart these SKL-compounds as TRβ agonists with no effect on TSH. To this end, we determined SKL-compounds pharmacokinetics and tissue distribution in normal rats and compared them to those of GC-1, a liver-selective TRβ agonist with concomitant effect on TSH. The present study explains why SKL-12846 and SKL-13784 have beneficial effects on lowering lipids without affecting heart rate and TSH production at the therapeutic dose in cholesterol-fed rats. In addition, we found that SKL-13784 shows no sign of escape phenomenon in fructose-fed rats. These results demonstrate the advantages of extremely high liver specificity to TRβ agonists. However, SKL-13784 has been found significantly to reduce endogenous T4 levels at doses lower than its lipid-lowering dose, which may raise concerns over this compound's ability to alter thyroid hormone metabolism in the liver. While the mechanism by which SKL-13784 reduces endogenous T4 levels is still unclear, our results would help design better liver-selective TRβ modulators.
Two-way transmission experiments over a single optical fibre at the same wavelength using micro-optic 3 dB couplers (1978)

Two-way transmission of 10 Mb/s pulse signals at the same optical wavelength over a single 600 m optical fibre cable has been realise by employing newly developed small size and low loss micro-optic 3 dB couplers, GeAlAS l.e.d.s, a SELFOC® fibre cable, and conventional Si p.d.s and compact electronic circuits with TTL level interface.
Dosing of rapamycin is critical to achieve an optimal antiangiogenic effect against cancer (2004)

Rapamycin has antiangiogenic activity against tumors. This has been discussed while addressing the problem of cancer in organ transplantation. Here we investigated effective dosing schedules against tumors and angiogenesis. Growth of established CT-26 colon adenocarcinoma tumors was measured in Balb/c mice treated with total equivalent rapamycin doses (1.5 mg/kg/day) given once a day, once every 3 days, or by continuous infusion. Tumors were most inhibited with continuous rapamycin infusion, and less by bolus dosing. Interestingly, however, continuous dosing produced the lowest rapamycin blood levels (15 ng/ml). As rapamycin-sensitive p70S6-kinase intracellular signaling is critical for angiogenesis, p70S6-kinase activation was measured in endothelial cells by Western blotting. Maximal p70S6-kinase inhibition occurred from 1-5 ng/ml rapamycin. These same rapamycin concentrations optimally blocked vessel-sprouting from cultured aortic rings. Therefore, low-level rapamycin dosing most effectively controls tumors in mice. Importantly, antiangiogenic rapamycin levels are compatible with immunosuppressive doses, supporting its potential use in transplant patients with cancer.
Dielectric Properties of Ice and Solid D2O (1952)

Complex dielectric constants have been measured for ice from the melting point to −65°C, and for solid D2O to −35°C, by a combination of bridge and transient methods. For both, the dispersion is described by the simple Debye formula, and the relaxation times τ by the simple rate expression τ = A exp(B/RT). For ice, A = 5.3×10−16 sec, B = 13.2 kcal/mole; and for solid D2O, A = 7.7×10−16 sec, B = 13.4 kcal/mole. The equilibrium dielectric constant for ice is 91.5 at 0°C and increases at lower temperatures; the values for solid D2O are only slightly smaller. Measures taken to minimize errors from voids in the sample and direct current conductance are discussed.
The Critical Zn <sup>2+</sup> Concentration for Corn and the Nonabsorption of Chelated Zinc (1977)

Abstract Corn ( Zea mays ) was grown in nutrient solutions of pH 5.2 and 7.5 with EDTA (ethylenediaminetetraacetic acid) and DTPA (diethylenetriaminepentaacetic acid) as chelating agents. At pH 5.2, corn plants were healthy and fully green, but at pH 7.5, the nutrient solutions with DTPA produced severely stunted, Zn‐deficient plants. Spraying the foliage with Zn or increasing the level of ZnSO 4 added to the nutrient solution prevented Zn deficiency. A concentration of 10 −10.6 M Zn 2+ was sufficient to prevent Zn deficiency with corn. Even at 10 5 times this concentration, chelated Zn was not absorbed by the roots. Equilibrium relationships of chelating agents in hydroponic solutions were extremely helpful in interpreting the results of this study. The findings reported herein support the hypothesis that Zn 2+ is the form of Zn absorbed by plant roots. Furthermore, plants can obtain adequate Zn from a nutrient media when Zn 2+ is maintained at approximately 10 −10.6 M . This concentration is nearly 4,000 times lower than the 10 −7 M reported by Carroll and Loneragan. The hypothesis proposed herein is that chelation aids in the transport and movement of metal ions to plant roots, but only Zn 2+ is absorbed.
Heterogeneity in Alzheimer's disease: progression rate segregated by distinct neuropsychological and cerebral metabolic profiles. (1992)

In an attempt to define possible subgroups of Alzheimer's disease, 21 patients satisfying current clinical diagnostic criteria for this disorder were divided on the basis of progression rates of symptoms. Thirteen patients with relatively rapid intellectual deterioration did not differ from eight patients showing slow progression with respect to global intellectual performance, sex, or age at onset of symptoms. Neuropsychological testing revealed that although the two groups were indistinguishable in verbal or visuospatial functions associated with the parietotemporal cortex, the more rapidly deteriorating group had significantly greater impairment in executive functions attributed to the frontal lobe. PET scans showed equivalent reductions in glucose metabolism in the parietotemporal cortex, but patients with relatively fast progression had significantly greater hypometabolism frontally. These results suggest an association between relatively severe frontal lobe involvement and a rapid clinical course that might have important implications for the development of treatment strategies for patients with Alzheimer's disease.
Adaptive Evolution of the Insulin Two-Gene System in Mouse (2008)

Insulin genes in mouse and rat compose a two-gene system in which Ins1 was retroposed from the partially processed mRNA of Ins2. When Ins1 originated and how it was retained in genomes still remain interesting problems. In this study, we used genomic approaches to detect insulin gene copy number variation in rodent species and investigated evolutionary forces acting on both Ins1 and Ins2. We characterized the phylogenetic distribution of the new insulin gene (Ins1) by Southern analyses and confirmed by sequencing insulin genes in the rodent genomes. The results demonstrate that Ins1 originated right before the mouse-rat split ( approximately 20 MYA), and both Ins1 and Ins2 are under strong functional constraints in these murine species. Interestingly, by examining a range of nucleotide polymorphisms, we detected positive selection acting on both Ins2 and Ins1 gene regions in the Mus musculus domesticus populations. Furthermore, three amino acid sites were also identified as having evolved under positive selection in two insulin peptides: two are in the signal peptide and one is in the C-peptide. Our data suggest an adaptive divergence in the mouse insulin two-gene system, which may result from the response to environmental change caused by the rise of agricultural civilization, as proposed by the thrifty-genotype hypothesis.
All-Optical Micromirrors From Nanotube MOMS With Wavelength Selectivity (2007)

The photomechanical properties of carbon nano-tubes (CNTs) enable the construction of CNT-based optical actuators. Employing a microelectromechanical systems-compatible nanotube-patterning process by plasma etching, CNT ensembles are integrated into microsystems to realize microoptomechanical systems (MOMS) (CNT-MOMS), where nanotubes behave as both the structural materials and the actuation mechanism. In this paper, following the CNT-MOMS principle, we report on all-optical micromirrors from the CNTs. Photomechanical actuation of single-wall CNTs from polymer-/nanotube-fllm bimorph structures is designed to actuate the micromirrors. A large mirror angular displacement of 19deg is obtained under laser illumination. Bidirectional rotation of the micromirrors is realized by the incorporation of two symmetrical serpentine bimorph actuators with the mirror surface. Furthermore, to add controllability to the micromirror rotations, absorptive-type optical filters are combined with the mirror structure in a "suspended" filter assembly. With green and red optical filters incorporated in the micromirrors, they show rotational selectivities of 10:1 and 20:1 for the 532-and 658-nm lasers, respectively. Depending on the wavelength of the incoming light, it could be selectively modulated into opposite directions by the micromirror.
An oral sorbent reduces overload of indoxyl sulphate and gene expression of TGF‐β1 in uraemic rat kidneys (2000)

AST-120 reduces the gene expression of TGF-beta1, TIMP-1 and pro-alpha1(I)collagen in the kidneys, and delays the progression of CRF, at least in part, by alleviating the overload of indoxyl sulphate on remnant proximal tubular epithelial cells.
Novel opportunities for CFTR-targeting drug development using organoids (2013)

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR mutations lead to production of non-functional CFTR, reduced amounts of normal functioning CFTR or misfolded CFTR with defects in trafficking or function. For decades, CF treatment has been focused on the symptoms of CF, but pharmacotherapy using small molecules that target the basic defect of CF, the mutant CFTR protein, is now possible for a limited amount of subjects with CF. This raises the exciting possibility that the majority of people with CF may receive effective treatment targeting the different CFTR mutants in the future. We recently described a functional CFTR assay using rectal biopsies from subjects with CF that were cultured in vitro into self-organizing mini-guts or organoids. We here describe how this model may assist in the discovery of new CFTR-targeting drugs, the subjects that may benefit from these drugs, and the mechanisms underlying variability in CFTR genotype-phenotype relations.
Extracellular Volume Fraction and Diffusion Characteristics during Progressive Ischemia and Terminal Anoxia in the Spinal Cord of the Rat (1994)

Extracellular space (ECS) volume fraction (alpha), ECS tortuosity (lambda), and nonspecific uptake (k'), three parameters affecting the diffusion of substances in nervous tissue, were studied during ischemia and anoxia in the rat spinal cord gray matter in vivo. Progressive ischemia evoked by exsanguination, as well as anoxia evoked by respiratory or cardiac arrest, produced prominent extracellular K+ and pH changes closely related to a decrease in blood pressure and amplitude of field potentials. With use of ion-selective microelectrodes, the changes in the diffusion parameters were measured by quantitative analysis of concentration-time profiles of tetramethylammonium (TMA+) applied by iontophoresis concomitantly with ionic shifts. Under normoxic conditions (in rats with blood pressure of 80-110 mm Hg) diffusion parameters in the dorsal horn gray matter at depth 500-900 microns were as follows: alpha = 0.20 +/- 0.019, lambda = 1.62 +/- 0.12, k' = 4.6 +/- 2.5 x 10(-3) s-1 (mean +/- SD, n = 39). Extracellular K+, pH, and diffusion properties gradually changed during progressive ischemia. As the blood pressure fell to 50-60 mm Hg and field potential amplitude to 20-60%, K+ rose to 6-12 mM, pHe fell by approximately 0.05-0.1 pH unit, and volume fraction of the ECS significantly decreased, to alpha = 0.16 +/- 0.019 (n = 22). Even though the tortuosity remained virtually constant, the nonspecific uptake significantly decreased to k' = 3.4 +/- 1.8 x 10(-3) s-1. As the blood pressure fell to 20-30 mm Hg and field potential amplitude to 0-6%, K+ rose to 60-70 mM, pHe fell by approximately 0.6-0.8 pH unit, and all three diffusion parameters significantly changed. The ECS volume fraction decreased to alpha = 0.05 +/- 0.021, tortuosity increased to lambda = 2.00 +/- 0.24, and TMA+ uptake decreased to k' = 1.5 +/- 1.6 x 10(-3) s-1 (n = 12). No further increase in extracellular K+ or changes in the alpha were found during and up to 120 min after the death of the animal. However, there was a further significant increase in lambda = 2.20 +/- 0.14 and decrease in k' = 0.4 +/- 0.3 x 10(-3) s-1 (n = 24). The acid shift reached its maximum level at approximately 5-10 min after respiratory arrest and then the pHe gradually increased by approximately 0.2 unit. Full recovery to "normoxic" diffusion parameters was achieved after reinjection of the blood or after an injection of noradrenaline during severe ischemia, if this resulted in a rise in blood pressure above 80 mm Hg and a decrease in extracellular K+ below 12 mM.(ABSTRACT TRUNCATED AT 400 WORDS)
Potassium<i>t</i>-Butoxide-Dimethyl Sulfoxide (2001)

(t-BuOK) [865-47-4] C4H9KO (MW 112.23) InChI = 1S/C4H9O.K/c1-4(2,3)5;/h1-3H3;/q-1;+1 InChIKey = LPNYRYFBWFDTMA-UHFFFAOYSA-N (DMSO) [67-68-5] C2H6OS (MW 78.15) InChI = 1S/C2H6OS/c1-4(2)3/h1-2H3 InChIKey = IAZDPXIOMUYVGZ-UHFFFAOYSA-N (highly basic reagent; useful for β-elimination and alkene isomerization reactions1) Preparative Methods: prepared in situ from anhydrous t-BuOK and anhydrous DMSO.2a Anhydrous DMSO is prepared by distillation from Calcium Hydride or Sodium Hydride under reduced pressure at 60 °C. Handling, Storage, and Precautions: see Potassium tert‐Butoxide and Dimethyl Sulfoxide. Store over 4 molecular sieves.2b Use in a fume hood.
Cancer's sweet tooth for serine (2011)

Exemplified by the cancer cell's preference for glycolysis (the Warburg effect), altered metabolism has taken centerstage as an emerging hallmark of cancer. Charting the landscape of cancer metabolic addictions should reveal new avenues for therapeutic attack. Two recent studies found subsets of human melanoma and breast cancers to have high levels of phosphoglycerate dehydrogenase (PHGDH), a key enzyme for serine biosynthesis, and these cancer cells are dependent on PHGDH for their growth and survival. Tumors may thus harbor distinct metabolic alterations to support their malignancy, and targeting enzymes such as PHGDH might prove a viable therapeutic strategy in this scenario.
Memory-Side Prefetching for Linked Data Structures (2001)

This work studies a memory-side prefetching technique to hide latency incurred by inherently serial accesses to linked data structures (LDS). A programmable prefetch engine sits close to memory and traverses LDS independently from the processor. The prefetch engine can run ahead of the processor because of its low latency, high bandwidth path to memory. This allows the prefetch engine to initiate data transfers earlier than the processor and pipeline multiple such transfers over the network. We evaluate