gebhart/patrepeval huggingface dataset:
New Approaches in the Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells toward Hepatocytes (2011)

Orthotropic liver transplantation is the only established treatment for end-stage liver diseases. Utilization of hepatocyte transplantation and bio-artificial liver devices as alternative therapeutic approaches requires an unlimited source of hepatocytes. Stem cells, especially embryonic stem cells, possessing the ability to produce functional hepatocytes for clinical applications and drug development, may provide the answer to this problem. New discoveries in the mechanisms of liver development and the emergence of induced pluripotent stem cells in 2006 have provided novel insights into hepatocyte differentiation and the use of stem cells for therapeutic applications. This review is aimed towards providing scientists and physicians with the latest advancements in this rapidly progressing field.
A preliminary result on development of analog broadband tapped delay line for L-band applications (2016)

This paper presents a brief comparison of delay line elements to develop a tapped delay line system. The comparative study includes surface integrated waveguide (SIW)-based delay line elements and coaxial cables. For SIW-based delay line elements, we divide the analysis into two scenarios based on the used transition line configuration, namely microstrip-to-SIW transition and grounded coplanar waveguide (GCPW)-to-SIW transition. This transition line is required to ensure impedance matching between transmission line and SIW component. Based on numerical analysis, it can be seen that the return loss of a SIW-based delay line with microstrip-to-SIW transition is better than the one with GCPW-to-SIW transition. Furthermore, the time delay of SIW-based delay line with microstrip-to-SIW transition is longer than the one with GCPW-to-SIW transition. In addition, for the whole design of 6-taps delay line system, a flat time delay of around 1 ns is achieved which reasonable insertion loss and isolation between two neighboring taps.
Effective Protective Immunity toYersinia pestisInfection Conferred by DNA Vaccine Coding for Derivatives of the F1 Capsular Antigen (2002)

Three plasmids expressing derivatives of the Yersinia pestis capsular F1 antigen were evaluated for their potential as DNA vaccines. These included plasmids expressing the full-length F1, F1 devoid of its putative signal peptide (deF1), and F1 fused to the signal-bearing E3 polypeptide of Semliki Forest virus (E3/F1). Expression of these derivatives in transfected HEK293 cells revealed that deF1 is expressed in the cytosol, E3/F1 is targeted to the secretory cisternae, and the nonmodified F1 is rapidly eliminated from the cell. Intramuscular vaccination of mice with these plasmids revealed that the vector expressing deF1 was the most effective in eliciting anti-F1 antibodies. This response was not limited to specific mouse strains or to the mode of DNA administration, though gene gun-mediated vaccination was by far more effective than intramuscular needle injection. Vaccination of mice with deF1 DNA conferred protection against subcutaneous infection with the virulent Y. pestis Kimberley53 strain, even at challenge amounts as high as 4,000 50% lethal doses. Antibodies appear to play a major role in mediating this protection, as demonstrated by passive transfer of anti-deF1 DNA antiserum. Taken together, these observations indicate that a tailored genetic vaccine based on a bacterial protein can be used to confer protection against plague in mice without resorting to regimens involving the use of purified proteins.
Primary structure of the human laminin A chain. Limited expression in human tissues (1991)

cDNA clones for the human laminin A chain were isolated from libraries prepared from human gestational choriocarcinoma cell line (JAR) RNA. They cover approx. 8 kb from the 5'-end of the 9.5 kb mRNA coding for this protein. Our clones contain 94 nucleotide residues for the 5'-end untranslated region and 7885 nucleotide residues of coding sequence. The complete human laminin A chain contains a 17-amino acid-residue signal peptide and a 3058-residue A chain proper. The human laminin A chain has a distinct domain structure with numerous internal cysteine-rich repeats. The large globular domain G has five repeats, which have several conserved glycine and cysteine residues. Furthermore the A chain contains 20 internal cysteine-rich repeats present in tandem arrays in three separate clusters (domains IIIa, IIIb and V). Domain I + II has a predicted continuous alpha-helical structure characterized by heptad repeats and three domains (IVa, IVb and VI) are predicted to contain a number of beta-sheets and coiled-coil structures. Northern-blot analysis was used to study the laminin A chain expression in the JAR cell line, full-term placenta and newborn-human tissues (kidney, spleen, lung, heart muscle, psoas muscle and diaphragm muscle). The expression was detectable in newborn-human kidney and JAR cell line only. The overall amino acid sequence identity between human and mouse is 76%. The human chain has only one Arg-Gly-Asp (RGD) sequence, which is located in the long arm within domain G, whereas the single RGD sequence in the mouse chain is located in the short arm in domain IIIb. The degree of identity between the human laminin A chain sequence and the sequence available for merosin [Ehrig, Leivo, Argraves, Ruoslahti & Engvall (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3264-3268] is about 41% and when conservative substitutions are included the degree of similarity is 54%.
Efficient Serum Clearance of Botulinum Neurotoxin Achieved Using a Pool of Small Antitoxin Binding Agents (2009)

Antitoxins for botulinum neurotoxins (BoNTs) and other toxins are needed that can be produced economically with improved safety and shelf-life properties compared to conventional therapeutics with large-animal antisera. Here we show that protection from BoNT lethality and rapid BoNT clearance through the liver can be elicited in mice by administration of a pool of epitope-tagged small protein binding agents together with a single anti-tag monoclonal antibody (MAb). The protein binding agents used in this study were single-chain Fv domains (scFvs) with high affinity for BoNT serotype A (BoNT/A). The addition of increasing numbers of differently tagged scFvs synergistically increased the level of protection against BoNT/A. It was not necessary that any of the BoNT/A binding agents possess toxin-neutralizing activity. Mice were protected from a dose equivalent to 1,000 to 10,000 50% lethal doses (LD(50)) of BoNT/A when given three or four different anti-BoNT scFvs, each fused to an E-tag peptide, and an anti-E-tag IgG1 MAb. Toxin protection was enhanced when an scFv contained two copies of the E tag. Pharmacokinetic studies demonstrated that BoNT/A was rapidly cleared from the sera of mice given a pool of anti-BoNT/A scFvs and an anti-tag MAb but not from the sera of mice given scFvs alone or anti-tag MAb alone. The scFv pool and anti-tag MAb protected mice from lethality when administered up to 2 h following exposure of mice to a dose equivalent to 10 LD(50) of BoNT/A. These results suggest that it will be possible to rapidly and economically develop and produce therapeutic antitoxins consisting of pools of tagged binding agents that are administered with a single, stockpiled anti-tag MAb.
The DNA methyltransferases of mammals (2000)

The biological significance of 5-methylcytosine was in doubt for many years, but is no longer. Through targeted mutagenesis in mice it has been learnt that every protein shown by biochemical tests to be involved in the establishment, maintenance or interpretation of genomic methylation patterns is encoded by an essential gene. A human genetic disorder (ICF syndrome) has recently been shown to be caused by mutations in the DNA methyltransferase 3B (DNMT3B) gene. A second human disorder (Rett syndrome) has been found to result from mutations in the MECP2 gene, which encodes a protein that binds to methylated DNA. Global genome demethylation caused by targeted mutations in the DNA methyltransferase-1 (Dnmt1) gene has shown that cytosine methylation plays essential roles in X-inactivation, genomic imprinting and genome stabilization. The majority of genomic 5-methylcytosine is now known to enforce the transcriptional silence of the enormous burden of transposons and retroviruses that have accumulated in the mammalian genome. It has also become clear that programmed changes in methylation patterns are less important in the regulation of mammalian development than was previously believed. Although a number of outstanding questions have yet to be answered (one of these questions involves the nature of the cues that designate sites for methylation at particular stages of gametogenesis and early development), studies of DNA methyltransferases are likely to provide further insights into the biological functions of genomic methylation patterns.
Charge Transport in Nanostructured PS–PEO–PS Triblock Copolymer Electrolytes (2014)

Nanostructured block copolymer electrolytes (BCE) are currently attracting widespread interest for applications in rechargeable lithium batteries. In order to investigate the influence of the composition, and therefore that of confinement, on the conductivity, a series of triblock PS–PEO–PS copolymers, with three linear PEO blocks of molecular weights 9, 10, or 35 kg mol–1 and with PEO weight fractions varying from 36% to 75%, were synthesized and doped with LiTFSI. Measurements by impedance spectroscopy of the conductivity show that it increases with PEO molecular weight, which is quite counterintuitive. To explain this phenomenon, the conductivity of the BCE has been modeled using three factors: (1) the conductivity of bulk PEO, (2) the topology of the PEO percolating network, described by the tortuosity parameter, and (3) the influence on the tortuosity of the effective volume fraction of the PEO phase useful for the conduction, taking into account a “dead zone” excluded from ionic transport, at the PS/PEO interface. In this approach, by analogy with porous materials and in contrast with previous work, the tortuosity is not kept constant but depends on the PEO volume fraction effectively useful for charge transport. The thickness of the dead zone, 4–5 EO units (∼1.6 nm), is the same as that of the exclusion zone for crystallization previously reported. This value does not depend either on the PEO molecular weight (from 9 to 35 kg mol–1) or on the EO/Li ratio (from 20 to 30). The absence of both conduction and crystallization in the excluded region could be due to the low mobility of the PEO chains in this zone. Consequently, the conductivity of BCE increases with PEO molecular weight because the proportion of the excluded zone becomes smaller as the PEO molecular weight increases. This model therefore provides a fairly precise description of the ionic conductivity of BCE used in lithium battery applications.
Hexon Specific T-Cells for Adoptive T-Cell Transfer as a Treatment of Adenovirus Infection after Allogeneic Stem Cell Transplantation. (2006)

Abstract Adenovirus infection (ADV) after allogeneic hematopoietic stem cell transplantation (HSCT) is an emerging pathogen causing relevant morbidity and mortality, with preponderance in children. Since a sufficient host T-cell response has been shown essential to clear the virus, diagnostic procedures for detection of virus-specific T-cells have recently developed to asses the specific cellular immune response. Furthermore adoptive immunotherapy is a new treatment option for patients with absent specific T-cell response and present systemic adenoviral infection. The possibility of an adoptive T-cell transfer depends on the availability of GMP compatible protocols and reagents. The adenoviral hexon protein was shown a immunodominant T-cell target within the viral capsid. In the present study we investigate the presence of Hexon-specific T-cell responses in HSCT donors, i.e. the availability of donors for an adoptive T-cell transfer. Secondly, the emergence of Hexon-specific T-cells in recipients post HSCT was analyzed. Thirdly, a protocol was established under GMP-conditions for adoptive T-cell immunotherapy through isolation of IFN-γ secreting T-cells after ex-vivo stimulation with the adenoviral Hexon protein. This procedure resulted in a mixed population of CD4 and CD8 positive T-cells with an effector memory phenotype and Th1 cytokine pattern (n=8). Isolated Hexon-specific T-cells show a strong expansion potential in vitro as well as specific cytotoxic activity. The availability of a donor was evaluated in 76 HSCT donors. Only 17.1% of donors had no ADV-specific T-cell response and 72.4% of donors were eligible for an adoptive T-cell transfer using the presented approach. The Hexon protein was responsible for almost the complete response to ADV, since no significant difference was seen against ADV lysate and the Hexon protein. In 76% HSCT recipients Hexon directed T-cell responses were evaluated and were shown to be responsible for clearance of the viral infection. In conclusion feasibility of an adoptive T-cell transfer for the treatment of ADV infection post HSCT is shown in accordance to current GMP regulations.
Control of lipolysis in intra-abdominal fat cells of nonhuman primates: comparison with humans. (1995)

The mechanisms that control lipolysis in intra-abdominal fat cells from various primate species, the marmoset (Callithrix jacchus), the baboon (Papio papio), and the macaque (Macaca fascicularis), were compared to those of human intraabdominal fat cells. Selective beta 1- or beta 2-adrenoceptor agonists induced lipolysis in all species. Selective beta 3-agonists (BRL 37344, CL 316243, and SR 58611) acted as partial agonists in marmoset but were inefficient in other primates, including humans. alpha 2-Adrenoceptor number ([3H]RX 8210002 binding) equalized (baboon) or exceeded (other primates) beta 1/beta 2-adrenoceptors ([3H]CGP 12177 binding). Baboon fat cell membranes expressed similar amounts of coupled beta- and alpha 2-adrenoceptors. In all species, norepinephrine- or epinephrine-induced lipolysis did not reach the lipolytic effect of isoproterenol but their effects were enhanced after alpha 2-adrenoceptor blockade. N6-phenylisopropyladenosine (PIA) induced a full antilipolytic effect in baboon, macaque, and human adipocytes through adenosine receptors ([3H]DPCPX binding). Peptide YY (PYY) weakly inhibited lipolysis in baboon. Adrenocorticotropic hormone (ACTH) was inactive whereas parathyroid hormone (PTH) partially stimulated lipolysis in primates. Histamine was partially lipolytic in marmoset only. This study emphasizes the similarities of the mechanisms controlling the lipolysis in nonhuman primate and in human adipocytes and suggests that the baboon and the macaque should provide unique models for the study of the regulation of lipolysis.
A human monoclonal antibody blocking SARS-CoV-2 infection (2020)

Abstract The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV). This cross-neutralizing antibody targets a communal epitope on these viruses and offers potential for prevention and treatment of COVID-19.
The oxygen sensor that controls EPO production: facts and fancies (1995)

Oxygen deficit is not simply a pathophysiological incident but is at the same time a physiological event. Adaptations to high altitude or physical endurance exercise are examples of "physiological oxygen deficit". Pathophysiological conditions, on the other hand, are associated with reduced cerebral or cardiac circulation or blood loss. One of the cardinal issues of crucial importance, in this context, is relating to the nature of the "oxygen deficit sensor" which, for example, leads to increased expression of hematopoietic hormones (erythropoietin) or angiogenesis factors (Vascular Endothelial Growth Factors, VEGF). Molecular principles of such oxygen sensors are accurately defined only for certain systems: In the case of erythropoietin, only one fully known section in the 3'-region of the erythropoietin gene is necessary and is sufficient to "transfer" O2-sensitivity to that particular gene. Nuclear proteins (transcription factors), controlled by O2-deficit, are of decisive importance to that process. Additional findings are likely to suggest that a DNA section closely similar to the one regulating the VEGF gene is encoding for hypoxia dependence. In other systems, above all in the central nervous system, there are ATP-dependent Na+ or K+ flows protecting the neurons against oxygen deficit. Drop in intracellular ATP-concentration is followed by hyperpolarization of neurons due to increases in K(+)-conductivity or due to decreases in stress-dependent Na(+)-channels, with both of them apparently ATP-controlled.(ABSTRACT TRUNCATED AT 250 WORDS)
Simplified DSP-Based Signal–Signal Beat Interference Mitigation Technique for Direct Detection OFDM (2015)

Short- and medium-haul links in interdata center, access, and metro networks require cost-effective direct-detection wavelength-division multiplexing transceivers offering energy efficiency, high information spectral density (ISD), and dispersion tolerance. Single-sideband orthogonal frequency-division multiplexing (SSB-OFDM) with direct detection is a potential solution; however, it suffers a penalty from signal-signal beat interference (SSBI) caused by the square-law photodetection. In this paper, a novel DSP-based SSBI mitigation technique, with lower complexity than previously proposed methods, is proposed and assessed through numerical simulations for the first time. The performance improvement is quantified by simulations of 9 × 112 Gb/s 16-QAM SSB-OFDM signal with a net optical ISD of 2.1 (b/s)/Hz. The performance is shown to be similar to that of the more complex receiver-based iterative SSBI compensation technique. Simulations predict an 8.7 dB reduction in the required OSNR at the 7% overhead HD-FEC threshold, and increases up to 100% in maximum reach over uncompensated standard single-mode fibre using the proposed simplified SSBI compensation technique.
Effects of Self-Complementarity, Codon Optimization, Transgene, and Dose on Liver Transduction with AAV8 (2016)

Numerous methods of vector design and delivery have been employed in an attempt to increase transgene expression following AAV-based gene therapy. Here, a gene transfer study was conducted in mice to compare the effects of vector self-complementarity (double- or single-stranded DNA), codon optimization of the transgene, and vector dose on transgene expression levels in the liver. Two different reporter genes were used: human ornithine transcarbamylase (hOTC) detected by immunofluorescence, and enhanced green fluorescent protein (EGFP) detected by direct fluorescence. The AAV8 capsid was chosen for all experiments due to its strong liver tropism. While EGFP is already a codon-optimized version of the original gene, both wild-type (WT) and codon-optimized (co) versions of the hOTC transgene were compared in this study. In addition, the study evaluated which of the two hOTC modifications-codon optimization or self-complementarity-would confer the highest increase in expression levels at a given dose. Interestingly, based on morphometric image analysis, it was observed that the difference in detectable expression levels between self-complementary (sc) and single-stranded (ss) hOTCco vectors was dose dependent, with a sevenfold increase in OTC-positive area using sc vectors at a dose of 3 × 10<sup>9</sup> genome copies (GC) per mouse, but no significant difference at a dose of 1 × 10<sup>10</sup> GC/mouse. In contrast, with EGFP as a transgene, the increases in expression levels when using the sc vector were observed at both the 3 × 10<sup>9</sup> GC/mouse and 1 × 10<sup>10</sup> GC/mouse doses. Furthermore, codon optimization of the hOTC transgene generated a more significant improvement in expression than the use of self-complementarity did. Overall, the results demonstrate that increases in expression levels gained by using sc vectors instead of ss vectors can vary between different transgenes, and that codon optimization of the transgene can have an even more powerful effect on the resulting expression levels.
The Use of Plenoptic Cameras in Astronomy (2017)

Since light-field imaging cameras are starting to become more in the world today, the question that arises is, “Could these cameras help advance the science when they are used in conjunction with telescopes and microscopes?” With their use in microscopy having been partially settled and no information about their use with telescopes, this experiment was setup to start the ascertainment of the use of light-field imaging cameras with telescopes. With the use of an older plenoptic camera, it was ascertained that a new light-field imaging camera might compare with the conventional digital camera of today.
Isolation of glucagon‐37 (bioactive enteroglucagon/oxyntomodulin) from porcine jejuno‐ileum (1982)

A 37 amino acid-peptide has been isolated from porcine jejuno-ileum on the basis of its glucagon-like activity in liver (interaction with glucagon-binding sites and activation of adenylate cyclase) using gel filtration, ion-exchange and high-performance liquid chromatography. Depending on the criteria chosen, this peptide is referred to as either 'bioactive enteroglucagon' (activity in liver), 'oxyntomodulin' (specific action in gastric oxyntic glands) or 'glucagon-37' (chemical structure).
Tripartite Motif Ligases Catalyze Polyubiquitin Chain Formation through a Cooperative Allosteric Mechanism (2013)

Ligation of polyubiquitin chains to proteins is a fundamental post-translational modification, often resulting in targeted degradation of conjugated proteins. Attachment of polyubiquitin chains requires the activities of an E1 activating enzyme, an E2 carrier protein, and an E3 ligase. The mechanism by which polyubiquitin chains are formed remains largely speculative, especially for RING-based ligases. The tripartite motif (TRIM) superfamily of ligases functions in many cellular processes including innate immunity, cellular localization, development and differentiation, signaling, and cancer progression. The present results show that TRIM ligases catalyze polyubiquitin chain formation in the absence of substrate, the rates of which can be used as a functional readout of enzyme function. Initial rate studies under biochemically defined conditions show that TRIM32 and TRIM25 are specific for the Ubc5 family of E2-conjugating proteins and, along with TRIM5α, exhibit cooperative kinetics with respect to Ubc5 concentration, with submicromolar [S]0.5 and Hill coefficients of 3-5, suggesting they possess multiple binding sites for their cognate E2-ubiquitin thioester. Mutation studies reveal a second, non-canonical binding site encompassing the C-terminal Ubc5α-helix. Polyubiquitin chain formation requires TRIM subunit oligomerization through the conserved coiled-coil domain, but can be partially replaced by fusing the catalytic domain to GST to promote dimerization. Other results suggest that TRIM32 assembles polyubiquitin chains as a Ubc5-linked thioester intermediate. These results represent the first detailed mechanistic study of TRIM ligase activity and provide a functional context for oligomerization observed in the superfamily.