gebhart/patrepeval huggingface dataset:
The Sestrins Interact with GATOR2 to Negatively Regulate the Amino-Acid-Sensing Pathway Upstream of mTORC1 (2014)

The mechanistic target of rapamycin complex 1 (mTORC1) kinase is a major regulator of cell growth that responds to numerous environmental cues. A key input is amino acids, which act through the heterodimeric Rag GTPases (RagA or RagB bound to RagC or RagD) in order to promote the translocation of mTORC1 to the lysosomal surface, its site of activation. GATOR2 is a complex of unknown function that positively regulates mTORC1 signaling by acting upstream of or in parallel to GATOR1, which is a GTPase-activating protein (GAP) for RagA or RagB and an inhibitor of the amino-acid-sensing pathway. Here, we find that the Sestrins, a family of poorly understood growth regulators (Sestrin1-Sestrin3), interact with GATOR2 in an amino-acid-sensitive fashion. Sestrin2-mediated inhibition of mTORC1 signaling requires GATOR1 and the Rag GTPases, and the Sestrins regulate the localization of mTORC1 in response to amino acids. Thus, we identify the Sestrins as GATOR2-interacting proteins that regulate the amino-acid-sensing branch of the mTORC1 pathway.
Vitamin E analogues as anticancer agents: Lessons from studies with α-tocopheryl succinate (2006)

The new millennium has witnessed considerable decrease in a number of previously fatal pathologies, largely due to the advancement in molecular medicine and modern approaches to treatment. In spite of this success, neoplastic disease remains a serious problem due to several reasons. These include an exceedingly high variability of cancer cells even within the same type of tumour. Cancer cells, albeit of clonal origin, mutate so that they escape established treatments, resulting in the fatal outcome of current therapies. Moreover, there are types of cancer, such as mesotheliomas, that cannot be treated at present. A novel group of clinically interesting anticancer drugs has been a recent focus in the literature that hold substantial promise as selective anticancer drugs. These compounds, epitomised by alpha-tocopheryl succinate, comprise redox-silent analogues of vitamin E that have been shown to suppress several types of cancer in animal models, including breast, colon and lung cancer as well as mesotheliomas and melanomas, while being nontoxic to normal cells and tissues. It is now proven that the strong anticancer effect of vitamin E analogues stems from their propensity to induce selective apoptosis in malignant cells. The results point to the novel group of vitamin E analogues as promising agents applicable to different types of tumours.
New performance driven routing techniques with explicit area/delay tradeoff and simultaneous wire sizing (1996)

We present new algorithms for construction of performance driven Rectilinear Steiner Trees under the Elmore delay model. Our algorithms represent a departure f r om previous approaches in that we derive an explicit area/delay tradeo curve. We achieve this goal by limiting the solution space to the set of topologies induced b y a p ermutation on the sinks of the net. This constraint allows ecient identication of optimal solutions while still providing a rich solution space. We also incorporate simultaneous wire sizing. Our technique consistently p r o duces topologies equalling the performance o f previous approaches with substantially less area overhead.
Permeability, Relative Permeability, Microscopic Displacement Efficiency and Pore Geometry of M_1 Bimodal Pore Systems in Arab D Limestone (2009)

Summary Pore geometrical parameters for the M_1 petrophysical rock type of the Arab D limestone in Ghawar field have been related to static and dynamic reservoir properties and geological facies (Clerke et al. 2008). The M_1 bimodal pore system is the most common and important member of a new set of ultimate recovery petrophysical rock types (URPRT), which uses a new pore system classification for the Arab D limestone. The dynamic reservoir property results for the bimodal M_1 are reviewed here. The roles played by the pore system parameters describing the macropores (M) and micropores (Type 1) within the M_1 in permeability, imbibition oil relative permeability, and microscopic displacement efficiency are examined in detail. All pore systems are analyzed by the Thomeer method using an extensive mercury injection capillary pressure (MICP) data set in conjunction with dynamic experiments performed on samples prepared using the same wettability restoration. Effects commonly ascribed to wettability changes are observed by changes in the distribution of porosity between the M and Type 1 subsystems. An extensive study of the pore systems of the Ghawar Arab D limestone gathered a large and comprehensive MICP data set (484 samples) (Clerke et al. 2008; Cantrell and Hagerty 1999, 2003; Clerke 2003, 2004; Ahr et al. 2005). All MICP data were type-curve matched by Thomeer functions (Clerke et al. 2008; Thomeer 1960). The study of this carefully prepared MICP data is the foundation for a new pore system classification. The new classification is built upon intrinsic, fundamental, and separate maximum pore-throat diameter modal elements named "porositons" (Clerke 2008; Ahr et al. 2005). Porositons are stable and recurring modes in the statistics of the Thomeer maximum pore-throat diameter of these carbonate pore systems. Porositon combinations are used to construct meaningful petrophysical rock types. Petrophysical rock types (PRTs) are defined by Clerke et al. (2008) as objects or combinations of objects that are present in the 3D space of the Thomeer pore-system parameters. Porositons are a new PRT object type; other PRT objects are clusters, trends, and surfaces. By constructing PRTs from porositons, strong relationships are found connecting the geological facies, PRTs, and reservoir-flow properties of these complex multimodal carbonate rocks (Clerke et al. 2008). These relationships demonstrate that these PRTs are important for defining ultimate recovery.
Gene expression analyses of neurons, astrocytes, and oligodendrocytes isolated by laser capture microdissection from human brain: Detrimental effects of laboratory humidity (2009)

Laser capture microdissection (LCM) is a versatile computer-assisted dissection method that permits collection of tissue samples with a remarkable level of anatomical resolution. LCM's application to the study of human brain pathology is growing, although it is still relatively underutilized, compared with other areas of research. The present study examined factors that affect the utility of LCM, as performed with an Arcturus Veritas, in the study of gene expression in the human brain using frozen tissue sections. LCM performance was ascertained by determining cell capture efficiency and the quality of RNA extracted from human brain tissue under varying conditions. Among these, the relative humidity of the laboratory where tissue sections are stained, handled, and submitted to LCM had a profound effect on the performance of the instrument and on the quality of RNA extracted from tissue sections. Low relative humidity in the laboratory, i.e., 6-23%, was conducive to little or no degradation of RNA extracted from tissue following staining and fixation and to high capture efficiency by the LCM instrument. LCM settings were optimized as described herein to permit the selective capture of astrocytes, oligodendrocytes, and noradrenergic neurons from tissue sections containing the human locus coeruleus, as determined by the gene expression of cell-specific markers. With due regard for specific limitations, LCM can be used to evaluate the molecular pathology of individual cell types in post-mortem human brain.
New cyclopenta[b]-pyrroles and -pyridines by reaction of 2-azido- and 2-phosphoranylideneaminocyclopent-1-ene-1-carbaldehydes with aliphatic esters (1989)

A new cyclopenta [b]pyrrole has been synthesized by reaction of 2-azidocyclopent-1-ene-1-carbaldehyde with ethyl acetate and subsequent thermal cyclisation. Dicyclopenta [b,e] pyrazines have been isolated from a similar reaction with ethyl propionate or t-butyl propionate. Condensation of the corresponding iminophosphorane from 2-azidocyclopent-1-ene-1-carbaldehyde with ethyl acetate and cyclisation of the dienic iminophosphorane so obtained gave a cyclopenta[b]pyridine. The products were characterized on the basis of 1H n.m.r., i.r., and mass spectrometric results.
The human beta-globin gene and a functional viral thymidine kinase gene in developing mice. (1981)

Two foreign cloned genes--one encoding a tissue-specific protein and one encoding a constitutive enzyme--were introduced into mouse eggs by microinjection into a pronucleus shortly after fertilization. They were the adult human genomic beta-globin gene and the thymidine kinase (TK; ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) gene of herpes simplex virus (HSV), ligated in the pBR322 plasmid. Thirty-three developing mice were autopsied in late fetal life; all appeared normal. Blot hybridization tests revealed that the DNA of as many as five (15%) of the fetuses (from separate litters), and of their corresponding placentas, contained copies of the human beta-globin gene and of the HSV tk gene that had been retained and replicated without significant loss or rearrangement. The estimated total numbers of copies per cell were 3-50 for the donor globin gene and 3-20 for the donor tk. In some of the fetuses, these totals included some copies of molecular weight higher than that of the intact sequence; the additional segments may have arisen through changes such as deletions or duplications. The foreign genes in the five positive fetuses appear to be present in high molecular weight DNA. Assays capable of distinguishing between foreign and native TK indicated that at least one of the fetuses with the HSV tk gene had some TK enzyme of the HSV type and, therefore, at least one gene copy that was being accurately transcribed and translated to produce a functional protein, despite the absence of selective pressure. Thus, pure recombinant genes introduced into mice at the onset of their development can remain intact and be stably incorporated and even expressed. These experiments provide a practical basis for novel investigations of the developmental control of normal gene expression in vivo of the causes and possible cures of genetic diseases.
In vitro culture of isolated primary hepatocytes and stem cell-derived hepatocyte-like cells for liver regeneration (2015)

Various liver diseases result in terminal hepatic failure, and liver transplantation, cell transplantation and artificial liver support systems are emerging as effective therapies for severe hepatic disease. However, all of these treatments are limited by organ or cell resources, so developing a sufficient number of functional hepatocytes for liver regeneration is a priority. Liver regeneration is a complex process regulated by growth factors (GFs), cytokines, transcription factors (TFs), hormones, oxidative stress products, metabolic networks, and microRNA. It is well-known that the function of isolated primary hepatocytes is hard to maintain; when cultured in vitro, these cells readily undergo dedifferentiation, causing them to lose hepatocyte function. For this reason, most studies focus on inducing stem cells, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), hepatic progenitor cells (HPCs), and mesenchymal stem cells (MSCs), to differentiate into hepatocyte-like cells (HLCs) in vitro. In this review, we mainly focus on the nature of the liver regeneration process and discuss how to maintain and enhance in vitro hepatic function of isolated primary hepatocytes or stem cell-derived HLCs for liver regeneration. In this way, hepatocytes or HLCs may be applied for clinical use for the treatment of terminal liver diseases and may prolong the survival time of patients in the near future.
Altered Lipid Composition and Enhanced Nutritional Value of Arabidopsis Leaves following Introduction of an Algal Diacylglycerol Acyltransferase 2 (2013)

Enhancement of acyl-CoA-dependent triacylglycerol (TAG) synthesis in vegetative tissues is widely discussed as a potential avenue to increase the energy density of crops. Here, we report the identification and characterization of Chlamydomonas reinhardtii diacylglycerol acyltransferase type two (DGTT) enzymes and use DGTT2 to alter acyl carbon partitioning in plant vegetative tissues. This enzyme can accept a broad range of acyl-CoA substrates, allowing us to interrogate different acyl pools in transgenic plants. Expression of DGTT2 in Arabidopsis thaliana increased leaf TAG content, with some molecular species containing very-long-chain fatty acids. The acyl compositions of sphingolipids and surface waxes were altered, and cutin was decreased. The increased carbon partitioning into TAGs in the leaves of DGTT2-expressing lines had little effect on transcripts of the sphingolipid/wax/cutin pathway, suggesting that the supply of acyl groups for the assembly of these lipids is not transcriptionally adjusted. Caterpillars of the generalist herbivore Spodoptera exigua reared on transgenic plants gained more weight. Thus, the nutritional value and/or energy density of the transgenic lines was increased by ectopic expression of DGTT2 and acyl groups were diverted from different pools into TAGs, demonstrating the interconnectivity of acyl metabolism in leaves.
Ion Channels and Vascular Tone (2000)

Abstract —Ion channels in the plasma membrane of vascular muscle cells that form the walls of resistance arteries and arterioles play a central role in the regulation of vascular tone. Current evidence indicates that vascular smooth muscle cells express at least 4 different types of K + channels, 1 to 2 types of voltage-gated Ca 2+ channels, ≥2 types of Cl − channels, store-operated Ca + (SOC) channels, and stretch-activated cation (SAC) channels in their plasma membranes, all of which may be involved in the regulation of vascular tone. Calcium influx through voltage-gated Ca 2+ , SOC, and SAC channels provides a major source of activator Ca 2+ used by resistance arteries and arterioles. In addition, K + and Cl − channels and the Ca 2+ channels mentioned previously all are involved in the determination of the membrane potential of these cells. Membrane potential is a key variable that not only regulates Ca +2 influx through voltage-gated Ca 2+ channels, but also influences release of Ca 2+ from internal stores and Ca 2+ - sensitivity of the contractile apparatus. By controlling Ca 2+ delivery and membrane potential, ion channels are involved in all aspects of the generation and regulation of vascular tone.
Strain-independent temperature measurement by use of a fluorescence intensity ratio technique in optical fiber (2000)

The strain sensitivity of the fluorescence intensity ratio temperature-sensing technique has been measured to be (2 +/- 3) x 10(-4)%/muepsilon in Yb3+-doped fiber, implying a temperature-to-strain cross sensitivity of (2 +/- 3) x 10(-4) degrees C/muepsilon. The near-zero strain sensitivity means that this optical-fiber sensor technique is well suited for temperature measurement in strain-affected environments.
17-ALPHA-HYDROXYPROGESTERONE-CAPROATE: A NEW SUBSTANCE WITH PROLONGED PROGESTATIONAL ACTIVITY. A COMPARISON WITH CHEMICALLY PURE PROGESTERONE* (1955)

IT IS the purpose of this paper to compare the progestational activity of a new substance, 17-alpha-hydroxyprogesterone-17-caproate, with the activity of chemically pure progesterone. 17-Alpha-hydroxyprogesterone-caproate is of interest because of the following factors: 17-Alpha-hydroxyprogesterone, without esterification, has no progestational activity (1, 2). The 17-ester (caproate or acetate), however, shows marked progestational activity in animal experiments (1). The 17-ester (caproate or acetate), however, shows marked progestational activity in animal experiments (1). Esterification of sex hormones generally causes a prolongation and, to some extent, an increase of their effects. The character of these effects (inert to highly active), however, is not changed by esterification (3, 4). 17-Alpha-hydroxyprogesterone seems to be an exception to this general rule. 17-Alpha-hydroxyprogesterone is not metabolized to pregnanediol in the human (5). The metabolism of 17-alpha-hydroxyprogesterone and the metabolism of 17-alpha-hydroxyprogesterone-caproate in the human female are not yet fully established. There is only one report by Langecker and Prescher (6), who found that in a male patient the excretion of pregnanediol was decreased after the administration of 17-alpha-hydroxyprogesterbne.
TOP: a new method for protein structure comparisons and similarity searches (2000)

In order to facilitate the three-dimensional structure comparison of proteins, software for making comparisons and searching for similarities to protein structures in databases has been developed. The program identifies the residues that share similar positions of both main-chain and side-chain atoms between two proteins. The unique functions of the software also include database processing via Internet- and Web-based servers for different types of users. The developed method and its friendly user interface copes with many of the problems that frequently occur in protein structure comparisons, such as detecting structurally equivalent residues, misalignment caused by coincident match of C α atoms, circular sequence permutations, tedious repetition of access, maintenance of the most recent database, and inconvenience of user interface. The program is also designed to cooperate with other tools in structural bioinformatics, such as the 3DB Browser software [Prilusky (1998). Protein Data Bank Q. Newslett. 84 , 3–4] and the SCOP database [Murzin, Brenner, Hubbard &amp; Chothia (1995). J. Mol. Biol. 247 , 536–540], for convenient molecular modelling and protein structure analysis. A similarity ranking score of `structure diversity' is proposed in order to estimate the evolutionary distance between proteins based on the comparisons of their three-dimensional structures. The function of the program has been utilized as a part of an automated program for multiple protein structure alignment. In this paper, the algorithm of the program and results of systematic tests are presented and discussed.
Holdsworth, Deryck W. The Parking Authority of Toronto, 1952–1987. (1989)

Holdsworth, Deryck W. The Parking Authority of Toronto, 1952–1987. Toronto: University of Toronto Press, 1987. Pp xii, 122. Illustrations, maps, bibliography, index. An article from journal Urban History Review / Revue d'histoire urbaine (Volume 17, Number 3, February 1989, pp. 143-229), on Érudit.
Strength-Duration Curve for an Electrically Excitable Tissue Extended Down to Near 1 Nanosecond (2004)

As part of a health and safety assessment of ultrawideband sources, it was useful to determine stimulation thresholds for an electrically excitable tissue down into the low nanosecond range. Stimulation thresholds were measured using gastrocnemius muscles isolated from 16 frogs (Rana sp.). Single pulses were delivered with a pair of surface electrodes, and muscle twitch was measured with an isotonic transducer. Pulse durations of 100, 10, and 1 ms; 100, 10 and 1 /spl mu/s; and 100 and /spl ap/1 ns were used. Tissue voltage and current strength-duration (S-D) curves on log-log plots had a classic appearance, with thresholds for ultrashort pulses being linear. For a pulse of /spl ap/1 ns, the mean threshold voltage in the muscle was 4.5 kV and the mean threshold peak current was 35 A. When delivered by direct contact, a single ultrawideband pulse of /spl ap/1 ns could reliably produce a biological effect, stimulation of an electrically excitable tissue. The observation that the S-D curves extended downward to /spl ap/1 ns in a linear manner suggested that classical ion channel mechanisms regulated excitation and that other processes, such as electroporation, did not occur. Although a single nanosecond pulse delivered by direct contact can elicit a biological response, such a stimulus in air is unlikely to produce an effect.
Calibration of Permeability Derived from NMR Logs in Carbonate Reservoirs (2001)

Abstract This paper discusses the calibration of nuclear magnetic resonance (NMR) logs to determine permeability distribution in carbonate reservoirs. The examples presented indicate the need for rigorous and integrated calibration to succeed in permeability estimation. The promise of the NMR logging tool to deliver, among others, mineralogy independent total porosity and permeability makes it a tool of choice in formation evaluation. Significant savings in coring costs, particularly in horizontal wells, are possible with the NMR tool. In sandstone reservoirs, NMR has worked remarkably well in the estimation of porosity, irreducible water saturation, producible fluids, and permeability. But the success rate is low in carbonate reservoirs, with respect to permeability. This can be attributed to the complexity of carbonate reservoirs and the lack of proper calibration of the logs with laboratory data or some measured reference. The paper discusses calibration of NMR logs for permeability estimation, using laboratory NMR measurements, routine core permeability data, and formation test data. The calibrated models are then used to re-compute permeabilities in the logged intervals. The examples illustrate that reliable field-specific permeability modeling is possible when all relevant data are integrated into the calibration effort. The calibration effort also shows that it is not sufficient to adjust only the pre-factors in the SDR and Timur-Coates’ permeability models in order to make the NMR log data match the core data. The porosity exponent (m) and T2LM (or FFI/BVI) exponent (n) also require adjustments. The default values of m=4 and n=2 did not apply in most of the cases examined in this paper.
In vitro V(D)J recombination: Signal joint formation (1996)

The first step of V(D)J recombination, specific cleavage at the recombination signal sequence (RSS), can be carried out by the recombination activating proteins RAG1 and RAG2. In vivo, the cleaved coding and signal ends must be rejoined to generate functional antigen receptors and maintain chromosomal integrity. We have investigated signal joint formation using deletion and inversion substrates in a cell free system. RAG1 and RAG2 alone or in combination were unable to generate signal joints. However, RAG1 and RAG2 complemented with nuclear extracts were able to recombine an extrachromosomal substrate and form precise signal joints. The in vitro reaction resembled authentic V(D)J recombination in being Ku-antigen-dependent.
TANDEM: matching proteins with tandem mass spectra (2004)

The source code and binaries for this software are available at http://www.proteome.ca/opensource.html, for Windows, Linux and Macintosh OSX. The source code is made available under the Artistic License, from the authors.