gebhart/patrepeval huggingface dataset:
Glutathione Transport Is a Unique Function of the ATP-binding Cassette Protein ABCG2 (2010)

Glutathione (GSH) transport is vital for maintenance of intracellular and extracellular redox balance. Only a few human proteins have been identified as transporters of GSH, glutathione disulfide (GSSG) and/or GSH conjugates (GS-X). Human epithelial MDA1586, A549, H1975, H460, HN4, and H157 cell lines were exposed to 2',5'-dihydroxychalcone, which induces a GSH efflux response. A real-time gene superarray for 84 proteins found in families that have a known role in GSH, GSSG, and/or GS-X transport was employed to help identify potential GSH transporters. ABCG2 was identified as the only gene in the array that closely corresponded with the magnitude of 2',5'-dihydroxychalcone (2',5'-DHC)-induced GSH efflux. The role of human ABCG2 as a novel GSH transporter was verified in a Saccharomyces cerevisiae galactose-inducible gene expression system. Yeast expressing human ABCG2 had 2.5-fold more extracellular GSH compared with those not expressing ABCG2. GSH efflux in ABCG2-expressing yeast was abolished by the ABCG2 substrate methotrexate (10 microM), indicating competitive inhibition. In contrast, 2',5'-DHC treatment of ABCG2-expressing yeast increased extracellular GSH levels in a dose-dependent manner with a maximum 3.5-fold increase in GSH after 24 h. In addition, suppression of ABCG2 with short hairpin RNA or ABCG2 overexpression in human epithelial cells decreased or increased extracellular GSH levels, respectively. Our data indicate that ABCG2 is a novel GSH transporter.
Multiblock Polymers: Panacea or Pandora’s Box? (2012)

Advances in synthetic polymer chemistry have unleashed seemingly unlimited strategies for producing block polymers with arbitrary numbers (n) and types (k) of unique sequences of repeating units. Increasing (k,n) leads to a geometric expansion of possible molecular architectures, beyond conventional ABA-type triblock copolymers (k = 2, n = 3), offering alluring opportunities to generate exquisitely tailored materials with unparalleled control over nanoscale-domain geometry, packing symmetry, and chemical composition. Transforming this potential into targeted structures endowed with useful properties hinges on imaginative molecular designs guided by predictive theory and computer simulation. Here, we review recent developments in the field of block polymers.
Wall mannoproteins in cells from colonial phenotypic variants of Candida albicans (1990)

Candida albicans ATCC 26555 switched at high frequency (10(-1) to 10(-3)) between several phenotypes identified by colony morphology on a defined mineral amino-acid-containing agar medium supplemented with arginine and zinc (LAZ medium). When cells taken from colonies exhibiting distinct morphologies were plated directly onto LAZ agar, spontaneous conversion to all the variant phenotypes occurred at combined frequencies of 2.1 x 10(-1) to 9.5 x 10(-3). However, when cells taken from the different colonial phenotypes were plated directly onto an undefined medium (yeast extract/peptone/dextrose; YPD medium), or first incubated in liquid YPD medium and then cloned on YPD agar, all colonies observed exhibited the same phenotype (smooth-white). When cells from the smooth-white colonies were plated as clones on LAZ agar, the original switch phenotype reappeared. These results suggest that environmental conditions such as the growth medium (and possibly the temperature) influence switching by suppressing phenotype expression, but have no effect on genotype. The variant colony morphologies also appeared to be associated with differences in the relative proportions of yeast and mycelial cells. Zymolyase digests of wall preparations obtained from cells belonging to different colonial phenotypes were analysed by SDS-PAGE. After blotting to nitrocellulose paper, the mannoproteins were stained with Concanavalin A, with a polyclonal antiserum enriched in antibodies against mycelium-specific wall components, and with a monoclonal antibody raised against a high-molecular-mass mannoprotein band (260 kDa) specific to the walls of mycelial cells. The results suggest that phenotypic switching might be associated with changes in the degree of glycosylation in high-molecular-mass mannoproteins, or in the way these mannoproteins are bound to other cell wall components.
Steady-State of an Enzymatic Reaction is Dependent on the Density of Reactant (2012)

The post-translational modification of proteins is controlled by the relative activities of two opposing enzymes. For example, the extent of phosphorylation of tyrosine residues reflects the balance of a kinase and a phosphatase enzyme. The present article uses as a model system a self-assembled monolayer that presents a peptide that can be phosphorylated by Abl kinase and subsequently dephosphorylated by Lambda phosphatase. Treatment of monolayers with a reaction mixture containing both enzymes reveals that the steady-state level of peptide phosphorylation is dependent on the density of the peptide. Using identical reaction mixtures, surfaces that presented the substrate at high density led to a phosphorylated peptide at steady-state, whereas surfaces that presented the substrate at low density led to unphosphorylated peptide at steady-state. This dependence owes to an autocatalytic phosphorylation reaction that operates at high densities of substrate. This work provides an example of an interfacial reaction that has properties that have no analogue in the corresponding solution phase reaction. It also provides a model system that is relevant to understanding mechanisms that regulate signaling at the cellular membrane.
Hope (2005)

Figure: Donna C. White is an oncology patient care technician at Campbell Health System in Weatherford, Texas. She wrote this poem in memory of Amy Lynn Parker, who died of soft cell sarcoma last year at the age of 34.There is hope while there is life While my heart still beats inside my chest: Though I'm in pain my eyes still see And my mind is busy not at rest: I still love and feel, My life goes on if only for today, While I live, I'm hoping, And praying this medicine will be the one, To take the cancer away: Scientists are finding new miracle Drugs daily and another cancer is brought under control; As I lay here with chemo running in my veins, I pray This will be the one to make me whole: But if it isn't and my life is over, I hope it won't be in vain, I pray The future will hold a cure for this deadly disease that is to blame.
Theory of decoherence-free fault-tolerant universal quantum computation (2001)

Universal quantum computation on decoherence-free subspaces and subsystems (DFSs) is examined with particular emphasis on using only physically relevant interactions. A necessary and sufficient condition for the existence of decoherence-free (noiseless) subsystems in the Markovian regime is derived here for the first time. A stabilizer formalism for DFSs is then developed which allows for the explicit understanding of these in their dual role as quantum error correcting codes. Conditions for the existence of Hamiltonians whose induced evolution always preserves a DFS are derived within this stabilizer formalism. Two possible collective decoherence mechanisms arising from permutation symmetries of the system-bath coupling are examined within this framework. It is shown that in both cases universal quantum computation which always preserves the DFS (natural fault-tolerant computation) can be performed using only two-body interactions. This is in marked contrast to standard error correcting codes, where all known constructions using one- or two-body interactions must leave the code space during the on-time of the fault-tolerant gates. A further consequence of our universality construction is that a single exchange Hamiltonian can be used to perform universal quantum computation on an encoded space whose asymptotic coding efficiency is unity. The exchange Hamiltonian, which is naturally present in many quantum systems, is thus asymptotically universal.
Real-time tracking system for assisted surgical operations (2003)

This paper presents a tracking algorithm for automatic instrument localization in robotically assisted laparoscopic surgery. We present a simple and robust system that does not need the presence of artificial marks, or special colours to distinguish the instruments. So, the system enables the robot to track the usual instruments used in laparoscopic operations. Since the instruments are normally the most structured objects in laparoscopic scenes, the algorithm uses the Hough transform to detect straight lines in the scene. In order to distinguish among different instruments or other structured elements present in the scene, motion information is also used. We present a detailed description of all the stages of the vision system: noise filter, edge orientation extraction, Hough transform computation, segment extraction, heuristic filter, position prediction, and finally, the selection of the tool to be tracked.
Viral assembly of oriented quantum dot nanowires (2003)

The highly organized structure of M13 bacteriophage was used as an evolved biological template for the nucleation and orientation of semiconductor nanowires. To create this organized template, peptides were selected by using a pIII phage display library for their ability to nucleate ZnS or CdS nanocrystals. The successful peptides were expressed as pVIII fusion proteins into the crystalline capsid of the virus. The engineered viruses were exposed to semiconductor precursor solutions, and the resultant nanocrystals that were templated along the viruses to form nanowires were extensively characterized by using high-resolution analytical electron microscopy and photoluminescence. ZnS nanocrystals were well crystallized on the viral capsid in a hexagonal wurtzite or a cubic zinc blende structure, depending on the peptide expressed on the viral capsid. Electron diffraction patterns showed single-crystal type behavior from a polynanocrystalline area of the nanowire formed, suggesting that the nanocrystals on the virus were preferentially oriented with their [001] perpendicular to the viral surface. Peptides that specifically directed CdS nanocrystal growth were also engineered into the viral capsid to create wurtzite CdS virus-based nanowires. Lastly, heterostructured nucleation was achieved with a dual-peptide virus engineered to express two distinct peptides within the same viral capsid. This work represents a genetically controlled biological synthesis route to a semiconductor nanoscale heterostructure.
The importance of forest protected areas to drinking water: running pure (2003)

This report focuses on one specific interaction: the role of forests, and particularly protected forests, in maintaining quality of drinking water for large cities. There are many reasons for this focus: many city dwellers already face a crisis of water quality, and contaminated water spreads a vast and largely unnecessary burden in terms of short and long-term health impacts including infant mortality, with knock-on effects on ability to work, industrial productivity and on already over-stretched health services. The poorest members of society, unable to afford sterilized or bottled water, suffer the greatest impacts. Similar problems affect the rural poor as well of course, and sometimes these can be even more severe. However, in a rapidly urbanizing world the scale of the problem facing cities is particularly acute.
Nitrergic Neurodegeneration in Cerebral Arteries of Streptozotocin-Induced Diabetic Rats (2005)

Although autonomic neuropathy is recognized as an independent risk factor for stroke in diabetes, the mechanism by which autonomic nerves are involved in this pathology is unknown. Parasympathetic (cholinergic) nerves of the autonomic nervous system are known to innervate and to cause relaxation of cerebral arteries by releasing nitric oxide (NO); hence, they are called nitrergic nerves. However, the effect of diabetes on nitrergic nerves is unknown. Here, we show that perivascular nitrergic nerves around the cerebral arteries degenerate in two phases in streptozotocin-induced diabetic rats. In the first phase, perivascular nitrergic nerve fibers remain intact while they lose their neuronal NO synthase content. This phase is reversible with insulin treatment. In the second phase, nitrergic cell bodies in the ganglia are lost via apoptosis in an irreversible manner. Throughout the two phases, irreversible thickening of the smooth muscle layer of cerebral arteries is observed. This is the first demonstration of nitrergic degeneration in diabetic cerebral arteries, which could elucidate the link between diabetic autonomic neuropathy and stroke.
Composites for bone replacement (1988)

The application of synthetic materials for bone replacement is now well established, but it is recognized that mechanical compatibility, as well as biocompatibility, of the tissue and implant is required if stress shielding and consequent bone resorption is to be avoided at areas of fixation. The development of materials analogous to the natural tissue for longer term implantation is discussed, with particular reference to hydroxyapatite reinforced polymers.
Adenovirus Endocytosis Requires Actin Cytoskeleton Reorganization Mediated by Rho Family GTPases (1998)

Adenovirus (Ad) endocytosis via alphav integrins requires activation of the lipid kinase phosphatidylinositol-3-OH kinase (PI3K). Previous studies have linked PI3K activity to both the Ras and Rho signaling cascades, each of which has the capacity to alter the host cell actin cytoskeleton. Ad interaction with cells also stimulates reorganization of cortical actin filaments and the formation of membrane ruffles (lamellipodia). We demonstrate here that members of the Rho family of small GTP binding proteins, Rac and CDC42, act downstream of PI3K to promote Ad endocytosis. Ad internalization was significantly reduced in cells treated with Clostridium difficile toxin B and in cells expressing a dominant-negative Rac or CDC42 but not a H-Ras protein. Viral endocytosis was also inhibited by cytochalasin D as well as by expression of effector domain mutants of Rac or CDC42 that impair cytoskeletal function but not JNK/MAP kinase pathway activation. Thus, Ad endocytosis requires assembly of the actin cytoskeleton, an event initiated by activation of PI3K and, subsequently, Rac and CDC42.
Calcium-calmodulin regulated effectors of microtubule stability in bovine brain (1992)

Stable microtubules (as defined by resistance to Ca2+, drug or cold temperature induced disassembly) form in abundance during tubulin assembly in brain crude extracts. We have previously shown that, in rat brain crude extracts, all microtubule stabilizing activity could be ascribed to a single Ca(2+)-calmodulin binding and Ca(2+)-calmodulin regulated protein, called "stable tubule only polypeptide", STOP145 [Pirollet, F., Rauch, C. T., Job, D., & Margolis, R. L. (1989) Biochemistry 28, 835-842]. We have now performed an exhaustive study of STOP-like effectors in bovine brain high-speed supernatants. All activity binds to cation exchangers and to Ca(2+)-calmodulin affinity columns. The activity can be resolved into two peaks on sizing columns. The first eluted peak contains a prominent 220-kDa protein. The second peak contains an apparently homogeneous 20-kDa polypeptide. A monoclonal antibody specific to rat brain STOP145 recognizes the 220-kDa protein, but not the 20-kDa species. The 220-kDa protein can be purified on a STOP antibody column and accounts for the bulk of stabilizing activity in the first peak. The 20-kDa protein does not bind to STOP antibody affinity columns. Sequence analysis of oligopeptide fragments of the 20-kDa protein shows 100% homology with bovine myelin basic protein (MBP). Anti-MBP antibodies recognize the 20-kDa, but not the 220-kDa species. We conclude that the 220-kDa protein is the bovine equivalent to rat brain STOP145 and that the 20-kDa species is MBP. Microtubule stabilization by MBP and STOP220 is abolished in the presence of Ca(2+)-calmodulin, and inhibition curves are similar for both proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Temporal Analytics on Big Data for Web Advertising (2012)

"Big Data" in map-reduce (M-R) clusters is often fundamentally temporal in nature, as are many analytics tasks over such data. For instance, display advertising uses Behavioral Targeting (BT) to select ads for users based on prior searches, page views, etc. Previous work on BT has focused on techniques that scale well for offline data using M-R. However, this approach has limitations for BT-style applications that deal with temporal data: (1) many queries are temporal and not easily expressible in M-R, and moreover, the set-oriented nature of M-R front-ends such as SCOPE is not suitable for temporal processing, (2) as commercial systems mature, they may need to also directly analyze and react to real-time data feeds since a high turnaround time can result in missed opportunities, but it is difficult for current solutions to naturally also operate over real-time streams. Our contributions are twofold. First, we propose a novel framework called TiMR (pronounced timer), that combines a time-oriented data processing system with a M-R framework. Users write and submit analysis algorithms as temporal queries - these queries are succinct, scale-out-agnostic, and easy to write. They scale well on large-scale offline data using TiMR, and can work unmodified over real-time streams. We also propose new cost-based query fragmentation and temporal partitioning schemes for improving efficiency with TiMR. Second, we show the feasibility of this approach for BT, with new temporal algorithms that exploit new targeting opportunities. Experiments using real data from a commercial ad platform show that TiMR is very efficient and incurs orders-of-magnitude lower development effort. Our BT solution is easy and succinct, and performs up to several times better than current schemes in terms of memory, learning time, and click-through-rate/coverage.
A Chimeric Protein Induces Tumor Cell Apoptosis by Delivering the Human Bcl-2 Family BH3-Only Protein Bad (2005)

Deregulation of PI3K/Akt and Raf/Mek/Erk signal transduction cascades is one of the principal causes of neoplastic transformation. The inactivation of the proapoptotic protein Bad, upon phosphorylation by different kinases of these two pathways, may play an important role in different human malignancies. Therefore, we have expressed and purified a new chimeric protein, hGM-CSF-Bad, linking the human granulocyte-macrophage colony-stimulating factor to the N-terminus of the proapoptotic protein human Bad, to deliver Bad into tumor cells and induce apoptosis. Indeed, the human GM-CSF receptor is a good target because it is overexpressed on many leukemias and solid tumors and is not detectable on stem cells. We found that the chimeric protein binds the human GM-CSF receptor, is endocytosed, and appears to reach the cytosol via retrograde ER transport. After entering cells, the protein is able to induce apoptosis of human leukemia cells and human colon and gastric carcinoma cell lines (IC(50) values as low as 1 muM). We conclude that GM-CSF-Bad can overcome the inappropriate survival stimuli in transformed cells and restore the apoptotic pathway. The completely human sequence and the elevated selectivity for cancer cells could prevent immunogenicity and the nonspecific toxicity of targeted toxins in future clinical application of this fusion protein.
Concordance of Gastrointestinal Tract Colonization and Subsequent Bloodstream Infections With Gram-negative Bacilli in Very Low Birth Weight Infants in the Neonatal Intensive Care Unit (2010)

These data support the use of empiric gentamicin to treat late-onset sepsis in infants colonized with gentamicin-susceptible GNB. Targeted GI tract surveillance cultures of infants with specific risk factors during weeks 2 to 6 of life could be used to guide empiric therapy for late-onset sepsis.
Effect of Captopril on Progressive Ventricular Dilatation after Anterior Myocardial Infarction (1988)

We conducted a double-blind, placebo-controlled trial to determine whether ventricular dilatation continues during the late convalescent phase after myocardial infarction and whether therapy with captopril alters this process. Fifty-nine patients with a first anterior myocardial infarction and a radionuclide ejection fraction of 45 percent or less underwent cardiac catheterization 11 to 31 days after infarction, when they were not in overt congestive heart failure. They were randomly assigned to placebo or captopril and were followed for one year. A repeat catheterization was performed to evaluate interval changes in hemodynamic function and left ventricular volume. Thirty-eight male patients were evaluated with maximal-exercise treadmill tests every three months. No differences were detected at base line in clinical, hemodynamic, or quantitative ventriculographic variables. During one year of follow-up, the end-diastolic volume of the left ventricle increased by a mean [+/- SEM] of 21 +/- 8 ml (P less than 0.02) in the placebo group, but by only 10 +/- 6 ml (P not significant) in the captopril group. The left ventricular filling pressure remained elevated with placebo but decreased (P less than 0.01) with captopril. In a subset of 36 patients who were at high risk for ventricular enlargement because they had persistent occlusion of the left anterior descending coronary artery, captopril prevented further ventricular dilatation (P less than 0.05). Patients given captopril also had increased exercise capacity (P less than 0.05). This preliminary study indicates that after anterior myocardial infarction, ventricular enlargement is progressive and that captopril may attenuate this process, reduce filling pressures, and improve exercise tolerance.
Enhancement in the Orientation of the Microdomain in Block Copolymer Thin Films upon the Addition of Homopolymer (2004)

Cylindrical microdomains in thin films of mixtures of polystyrene‐ block ‐ poly(methyl methacrylate) and poly(methyl methacrylate) (PMMA) homopolymer are oriented normal to the film surface (see Figure). Confining the PMMA homopolymer to the microdomains increases the persistence of microdomain orientation over large distances; thus, aspect ratios up to ∼10 are achievable without the use of an external field.
IRF-7, a New Interferon Regulatory Factor Associated with Epstein-Barr Virus Latency (1997)

The Epstein-Barr virus (EBV) BamHI Q promoter (Qp) is the only promoter used for the transcription of Epstein-Barr virus nuclear antigen 1 (EBNA-1) mRNA in cells in the most restricted (type I) latent infection state. However, Qp is inactive in type III latency. With the use of the yeast one-hybrid system, a new cellular gene has been identified that encodes proteins which bind to sequence in Qp. The deduced amino acid sequence of the gene has significant homology to the interferon regulatory factors (IRFs). This new gene and products including two splicing variants are designated IRF-7A, IRF-7B, and IRF-7C. The expression of IRF-7 is predominantly in spleen, thymus, and peripheral blood leukocytes (PBL). IRF-7 proteins were identified in primary PBL with specific antiserum against IRF-7B protein. IRF-7s can bind to interferon-stimulated response element (ISRE) sequence and repress transcriptional activation by both interferon and IRF-1. Additionally, a functional viral ISRE sequence, 5'-GCGAAAACGAAAGT-3', has been identified in Qp. Finally, the expression of IRF-7 is consistently high in type III latency cells and almost undetectable in type I latency, corresponding to the activity of endogenous Qp in these latency states and the ability of the IRF-7 proteins to repress Qp-reporter constructs. The identification of a functional viral ISRE and association of IRF-7 with type III latency may be relevant to the mechanism of regulation of Qp.