gebhart/patrepeval huggingface dataset:
Influence of flow and diffusion on protein separation in a continuous flow electrophoresis cell: Computation procedure (1988)

Continuous flow zone electrophoresis is an efficient method for the non-destructive separation of biological materials in a flowing film of buffer solution in which the constituents of a sample are separated according to their electrophoretic mobilities, under the influence of an electric field. This paper deals with modeling of flow structure of the buffer solution taking into account the effect of electroosmosis, Joule heating and thermal free convection and the forced convection of axial flow. Modeling of diffusion is examined in a second part. The modeling equations and the corresponding boundary conditions are solved by finite difference methods. The various parameters affecting the quality of the fractionation are analyzed.
Differential Effects of Changes in the Length of a Signal/Anchor Domain on Membrane Insertion, Subunit Assembly, and Intracellular Transport of a Type II Integral Membrane Protein (1996)

The length requirement for a functional uncleaved signal/anchor (S/A) domain of the paramyxovirus hemagglutinin-neuraminidase (HN) type II glycoprotein was analyzed. HN mutants with progressive NH2-terminal S/A deletions or insertions were expressed in HeLa cells, and the membrane targeting, folding, tetramer assembly, and intracellular transport of the proteins were examined. Changing the length of the S/A by two residues resulted in HN mutants that displayed aberrant endoplasmic reticulum (ER) membrane targeting or translocation. This phenotype did not simply reflect upper or lower limitations on the size of a functional S/A, because normal signaling was restored by further alterations involving three or four residues. Likewise, ER-to-Golgi transport of mutants containing deletions of one or two S/A residues was delayed (approximately 30% of WT) or blocked, but transport was restored for a mutant with a total of three deleted residues. HN mutants with S/A insertions of three or four Leu residues differed from wild-type HN by having heterogeneous Golgi-specific carbohydrate modifications. Differences in ER-to-Golgi transport of the mutants did not strictly correlate with defects in either native folding of the ectodomain or the assembly of two dimers into a tetramer. Together, these data suggest that efficient entry into and exit from the ER are sensitive to changes in the HN S/A that may reflect alterations to a structural requirement along one side of an alpha-helix.
A Systematic Review of Nicotine by Inhalation: Is There a Role for the Inhaled Route? (2012)

Pulmonary nicotine delivery might be maximized by use of nicotine salts, which have a more physiological pH than pure nicotine, by ensuring the mass of the particles is optimal for alveolar absorption, and by adding flavoring agents. Metered-dose inhalers potentially can deliver nicotine more efficiently than other nicotine products, facilitating smoking cessation and improving smokers' lives.
A comparison of next-generation IP-centric transport architectures (2002)

The popularity of the Internet and Internet protocol (IP)-based intranets is promising enormous growth in data traffic originating from IP endpoints, prompting network operators to reconsider network architectures so that they can most effectively absorb the projected growth. At the same time, new technologies are being introduced at a phenomenal pace, providing network operators with numerous and complex choices involving dense wavelength division multiplexing (DWDM), synchronous optical networks (SONETs), packet over SONET (POS), packet over wavelength (POW), and asynchronous transfer mode (ATM). In this paper, we evaluate alternative transport architectures for carrying IP-based traffic using the projected traffic data, nodal configuration, and optical fiber connectivity of a realistic, national-scale IP backbone. We compare the option of carrying IP directly versus IP over ATM for three types of transport architecture: SONET bidirectional line-switched rings (BLSRs); mesh networks of optical (or electrical) cross connects; and DWDMs without underlying optical cross connects (OXCs) - that is, with one or more wavelength links between each pair of IP switches. These options also include restoration choices. SONET BLSRs provide fast restoration based on self-healing ring technology. OXCs provide fast restoration for underlying mesh at the wavelength level. For point-to-point wavelength links, we consider service-level (IP and ATM) restoration. We compare these options in terms of many network characteristics - port counts, circuit miles, wavelength miles, fiber miles, and overall cost - and consider all the critical constraints and flexibilities for each choice.
Mitoriboscins: Mitochondrial-based therapeutics targeting cancer stem cells (CSCs), bacteria and pathogenic yeast (2017)

The "endo-symbiotic theory of mitochondrial evolution" states that mitochondrial organelles evolved from engulfed aerobic bacteria, after millions of years of symbiosis and adaptation. Here, we have exploited this premise to design new antibiotics and novel anti-cancer therapies, using a convergent approach. First, virtual high-throughput screening (vHTS) and computational chemistry were used to identify novel compounds binding to the 3D structure of the mammalian mitochondrial ribosome. The resulting library of ∼880 compounds was then subjected to phenotypic drug screening on human cancer cells, to identify which compounds functionally induce ATP-depletion, which is characteristic of mitochondrial inhibition. Notably, the top ten "hit" compounds define four new classes of mitochondrial inhibitors. Next, we further validated that these novel mitochondrial inhibitors metabolically target mitochondrial respiration in cancer cells and effectively inhibit the propagation of cancer stem-like cells <i>in vitro</i>. Finally, we show that these mitochondrial inhibitors possess broad-spectrum antibiotic activity, preventing the growth of both gram-positive and gram-negative bacteria, as well as <i>C. albicans</i> - a pathogenic yeast. Remarkably, these novel antibiotics also were effective against methicillin-resistant Staphylococcus aureus (MRSA). Thus, this simple, yet systematic, approach to the discovery of mitochondrial ribosome inhibitors could provide a plethora of anti-microbials and anti-cancer therapies, to target drug-resistance that is characteristic of both i) tumor recurrence and ii) infectious disease. In summary, we have successfully used vHTS combined with phenotypic drug screening of human cancer cells to identify several new classes of broad-spectrum antibiotics that target both bacteria and pathogenic yeast. We propose the new term "mitoriboscins" to describe these novel mitochondrial-related antibiotics. Thus far, we have identified four different classes of mitoriboscins, such as: <i>1) mitoribocyclines, 2) mitoribomycins, 3) mitoribosporins and 4) mitoribofloxins</i>. However, we broadly define mitoriboscins as any small molecule(s) or peptide(s) that bind to the mitoribosome (large or small subunits) and, as a consequence, inhibit mitochondrial function, i.e., mitoribosome inhibitors.
Economic Utilization of Crop Residues for Value Addition: A Futuristic Approach (2000)

The ag ri cul tural pro ducts (ce llul osic and li gno-cellul osic, in clu din g soft- and hard -wood) havin g bein g pro duced by the photosyn­ thet ic processes, are virtu all y in ex haustibl e, and co ul d be co nverted into hi ghl y attrac ti ve subs tr ate for bi oco nve rsion pro cesses. The stru ctu re of li gno-cellul os ic mate ri al is based on th ree main co mpone nt s: cellul ose, hem ice llul ose and li gn in . Th ese th ree compo nents offe r tre mendo us biotec hn ologica l potentia l to be used as substr ate in bi oco nve rsion processes and can be effec ti ve ly exp loited for the prod ucti on of bul k chemi ca ls and va lue-added products. It is poin ted ou t th ere is an urge nt need to develop processes fo r eco nomic util izat ion of th ese resid ues th ro ugh th e advances in bio techn ology. Some maj or produ cts whi ch could be produ ced from these sources incl ude eth ano l, enzymes (e .g. ce llul ases (endoglu ca nases, exo-ce ll ob iohydrolase and ~-glucosidase), li gni nases (laccase, Mn- peroxi . dase and Li- pe roxi dase) , xy lanase, pectin ase, amylases, a- and ~-ga l actos i dases , caffei nase, tann ase), foo d and fee d (probi otc is), etc. Some majo r res idue s whic h need spec ial emph as is in cl ud e sugar ca ne bagasse, cassava bagasse and coffee pu lp. It is mentioned that ad diti onal research on the pre- tr ea tmen t of feeds tock is re quired to improve the com ponen ts yield and th e ce llul ose diges tibilit y to the level, whi ch would make usage of such res idues economi ca ll y viab le. Sim ilarly, although much effo rt s have been made in the past on the ce ll ulose hydrolysis , its effective conversion int o fermentab le sugars is an area whic h needs furth er inputs in te rm s of R&D. It is arg ued th at mu ch need be do ne on the hydro lysis of hem ice ll ulose (a nd so ft -wood). An in-depth analys is is presented on th e scenari o of appl icat ions of crops resi du es in develop ing co untri es, part ic ularly in Indi a, with specia l reference to sugar ca ne bagasse, cassava bagasse and coffee pulp.
Permissible amino acid substitutions within the putative nucleoside binding site of herpes simplex virus type 1 encoded thymidine kinase established by random sequence mutagenesis [corrected] (1992)

We determined the essentiality of all amino acid replacements within an 11-codon sequence in the putative nucleoside-binding site of thymidine kinase encoded by herpes simplex virus type 1. This involved partial randomization of 11 codons in the gene to create a degenerate library, followed by genetic complementation using a tk- Escherichia coli strain and selection of unnatural active enzymes. We produced and tested 53,000 variants; of which 190 were found to be biologically active. Sequence analyses of functional variants revealed a high degree of flexibility in accommodating different types of amino acid substitutions in this region. However, no replacement was tolerated at proline-173, whereas tyrosine-172 could be replaced by only phenylalanine. To further define permissible substitutions at specified positions, we constructed a library with randomization at only four test codons. We produced and tested 600,000 variants; of which only 5 were active. Again proline-173 was conserved, and only tyrosine and phenylalanine were found at position 172. The identification of these conserved amino acids should provide important insights into the understanding of the structural basis of catalysis by this enzyme.
Vector Precoding for Gaussian MIMO Broadcast Channels: Impact of Replica Symmetry Breaking (2012)

The “replica method” of statistical physics is employed for the large-system analysis of vector precoding for the Gaussian multiple-input multiple-output broadcast channel. The transmitter comprises a linear front-end combined with nonlinear precoding, minimizing transmit energy by means of input alphabet relaxation. For the common discrete lattice-based relaxation, the problem violates replica symmetry and a replica symmetry breaking (RSB) ansatz is taken. The limiting empirical distribution of the precoder's output and the limiting transmit energy are derived for one-step RSB. Particularizing to a “zero-forcing” (ZF) linear front-end, a decoupling result is derived. For discrete lattice-based relaxations, the impact of RSB is demonstrated for the transmit energy. The spectral efficiencies of the aforementioned precoding methods are compared to linear ZF and Tomlinson-Harashima precoding (THP). Focusing on quaternary phase shift-keying (QPSK), significant performance gains of both lattice and convex relaxations are revealed for medium to high signal-to-noise ratios (SNRs) when compared to linear ZF precoding. THP is shown to be outperformed as well. Comparing certain lattice-based relaxations for QPSK against a convex counterpart, the latter is found to be superior for low and high SNRs but slightly inferior for medium SNRs in terms of spectral efficiency.
Wnt-5A augments repopulating capacity and primitive hematopoietic development of human blood stem cellsinvivo (2003)

Human hematopoietic stem cells are defined by their ability to repopulate multiple hematopoietic lineages in the bone marrow of transplanted recipients and therefore are functionally distinct from hematopoietic progenitors detected in vitro. Although factors capable of regulating progenitors are well established, in vivo regulators of hematopoietic repopulating function are unknown. By using a member of the vertebrate Wnt family, Wnt-5A, the proliferation and differentiation of progenitors cocultured on stromal cells transduced with Wnt-5A or treated with Wnt-5A conditioned medium (CM) was unaffected. However, i.p. injection of Wnt-5A CM into mice engrafted with human repopulating cells increased multilineage reconstitution by >3-fold compared with controls. Furthermore, in vivo treatment of human repopulating cells with Wnt-5A CM produced a greater proportion of phenotypically primitive hematopoietic progeny that could be isolated and shown to possess enhanced progenitor function independent of continued Wnt-5A treatment. Our study demonstrates that Wnt-5A augments primitive hematopoietic development in vivo and represents an in vivo regulator of hematopoietic stem cell function in the human. Based on these findings, we suggest a potential role for activation of Wnt signaling in managing patients exhibiting poor hematopoietic recovery shortly after stem cell transplantation.
Metabolic Regulation by Leucine of Translation Initiation Through the mTOR-Signaling Pathway by Pancreatic β-Cells (2001)

Recent findings have demonstrated that the branched-chain amino acid leucine can activate the translational regulators, phosphorylated heat- and acid-stable protein regulated by insulin (PHAS-I) and p70 S6 kinase (p70S6k), in an insulin-independent and rapamycin-sensitive manner through mammalian target of rapamycin (mTOR), although the mechanism for this activation is undefined. It has been previously established that leucine-induced insulin secretion by beta-cells involves increased mitochondrial metabolism by oxidative decarboxylation and allosteric activation of glutamate dehydrogenase (GDH). We now show that these same intramitochondrial events that generate signals for leucine-induced insulin exocytosis are required to activate the mTOR mitogenic signaling pathway by beta-cells. Thus, a minimal model consisting of leucine and glutamine as substrates for oxidative decarboxylation and an activator of GDH, respectively, confirmed the requirement for these two metabolic components and mimicked closely the synergistic interactions achieved by a complete complement of amino acids to activate p70s6k in a rapamycin-sensitive manner. Studies using various leucine analogs also confirmed the close association of mitochondrial metabolism and the ability of leucine analogs to activate p70s6k. Furthermore, selective inhibitors of mitochondrial function blocked this activation in a reversible manner, which was not associated with a global reduction in ATP levels. These findings indicate that leucine at physiological concentrations stimulates p70s6k phosphorylation via the mTOR pathway, in part, by serving both as a mitochondrial fuel and an allosteric activator of GDH. Leucine-mediated activation of protein translation through mTOR may contribute to enhanced beta-cell function by stimulating growth-related protein synthesis and proliferation associated with the maintenance of beta-cell mass.
Notch Signaling Is Required to Maintain All Neural Stem Cell Populations – Irrespective of Spatial or Temporal Niche (2006)

Recently, Notch signaling has been reported to underscore the ability of neural stem cells (NSCs) to self-renew. Utilizing mice deficient in presenilin-1(PS1), we asked whether the function of Notch signaling in NSC maintenance was conserved. At embryonic day 14.5, all NSCs--both similar (cortex-, ganglionic eminence- and hindbrain-derived) and distinct (retinal stem cell)--require Notch signaling in a gene-dosage-sensitive manner to undergo expansionary symmetric divisions, as assessed by the clonal, in vitro neurosphere assay. Within the adult, however, Notch signaling modulates cell cycle time in order to ensure brain-derived NSCs retain their self-renewal property. At face value, the effects in the embryo and adult appear different. We propose potential hypotheses, including the ability of cell cycle to modify the mode of division, in order to resolve this discrepancy. Regardless, these findings demonstrate that PS1, and presumably Notch signaling, is required to maintain all NSCs.
Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats (1992)

The administration of insulin-like growth factor-I (IGF-I) via subcutaneously implanted osmotic pumps partially reversed a catabolic state produced by the co-administration of 20 micrograms of dexamethasone/day to 150 g male rats. Marked dose-dependent effects on body weight and nitrogen retention were produced, with the highest IGF-I dose, 695 micrograms/day, giving a 6 g increase in body weight over 7 days, compared with a 19 g loss in the dexamethasone-only group and an 18 g gain in pair-fed controls. Two IGF-I analogues that bind poorly to IGF-binding proteins, the truncated form, des(1-3)IGF-I, and a variant with an N-terminal extension as well as arginine at residue 3, LR3IGF-I, were approx. 2.5-fold more potent than IGF-I. The response with LR3IGF-I was particularly striking because this peptide binds 3-fold less well than IGF-I to the type 1 IGF receptor. The increased potencies of the IGF-I variants may relate to the substantially increased plasma levels of IGF-binding proteins, particularly IGFBP-3, produced by the combined treatment of dexamethasone with IGF-I or the variants. These binding proteins would be expected to decrease the transfer of IGF-I, but not that of the variants, from blood to tissue sites of action. Measurements of muscle protein synthesis at the end of the treatment period and muscle protein breakdown by 3-methylhistidine (3MH) excretion throughout the experiment indicated coordinate anabolic effects of the IGF peptides on both processes. Thus 3MH excretion was decreased at the highest IGF-I dose from 83.5 +/- 4.2 (S.E.M.) mumol/kg per 7 days to 65.1 +/- 2.2, compared with 54.9 +/- 1.2 in the pair-fed controls. Part of this response in 3MH excretion may have reflected a decrease in gut protein breakdown, because IGF-I and especially the IGF analogues increased the gut weight by up to 45%. Notwithstanding the effects on protein synthesis and breakdown, the fractional carcass weights remained low in the IGF-treated groups, although the increase in total carcass weight reflected nitrogen rather than fat gain. The dexamethasone-induced changes in liver, spleen and heart weight were restored towards normal by the IGF treatment. The experiment demonstrates the potential of IGF-I treatment of catabolic states and especially the value of modified forms of growth factors that bind weakly to IGF-binding proteins.
Downstream DNA Sequences Are Required to Activate a Gene Expressed in the Root Cortex of Embryos and Seedlings (1992)

Robert A. Dietrich, Sharon E. Radke, John J. Harada, Downstream DNA Sequences Are Required to Activate a Gene Expressed in the Root Cortex of Embryos and Seedlings, The Plant Cell, Vol. 4, No. 11 (Nov., 1992), pp. 1371-1382
Isolation, Characterization, and Nuclear Reprogramming of Cell Lines Derived from Porcine Adult Liver and Fat (2010)

Genetic manipulation of porcine genome to produce genetically modified pigs with high efficiency has been hampered by the unavailability of an ideal cell type. The cell type currently used for various genetic manipulations is fetal fibroblasts. These cells have very limited life span in culture, and efficiency of gene targeting is very low. In this study, we developed a simple but novel strategy to derive cell lines from adult porcine liver and adipose tissues with long life span. Small colonies with few cells became visible as early as 2 to 3 days on collagen-coated plates, and a full-grown colony took 10 to 14 days to form. These cells maintained a steady growth up to 80 population doublings with normal karyotype. Transfection of these cells with a plasmid containing a neomycin resistance gene and selected under G418 yielded clones with stable genetic modifications and extended expression of the transgene. Further, these cells were used as nuclear donors to produce somatic cell nuclear transfer (SCNT) embryos. The average fusion rates were 86.8, 80.5, and 90.4% for liver-derived cell lines (LDCs), fat-derived cell lines (FDCs), and fetal fibroblasts (FFs), respectively. We achieved a pregnancy rate of 50% with both LDCs and FDCs at day 30 and the efficiencies of generating fetuses from cloned embryos were 3.5, 2.1, and 4.0% for LDCs, FDCs and FFs, respectively.
Error resilient macroblock rate control for H.264/AVC video coding (2008)

In this paper, an error resilient rate control scheme for the H.264/AVC standard is proposed. This scheme differs from traditional rate control schemes in that macroblock mode decisions are not made only to minimize their rate-distortion cost, but also take into account that the bitstream will have to be transmitted through an error-prone network. Since channel errors will probably occur, error propagation due to predictive coding should be mitigated by adequate Intra coding refreshes. The proposed scheme works by comparing the rate-distortion cost of coding a macroblock in Intra and Inter modes: if the cost of Intra coding is only slightly larger than the cost of Inter coding, the coding mode is changed to Intra, thus reducing error propagation. Additionally, cyclic Intra refresh is also applied to guarantee that all macroblocks are eventually refreshed. The proposed scheme outperforms the H.264/AVC reference software, for typical test sequences, for error-free transmission and several packet loss rates.