gebhart/patrepeval huggingface dataset:
Expression of a Recombinant Human Glycosyltransferase from a Synthetic Gene and its Utilization for Synthesis of the Human Blood Group B Trisaccharide (1995)

A 1034-bp synthetic gene encoding the human blood group B glycosyltransferase, which catalyzes the transfer of galactose from UDP-Gal to Fuc alpha(1-2)Gal beta-OR to give the blood group B determinant Gal alpha(1-3)[Fuc alpha(1-2)]Gal beta-OR (where R is a glycoprotein or glycolipid), has been expressed in Escherichia coli by replacing its membrane-anchoring domain with an ompA bacterial secretory signal. The active enzyme was purified from the periplasm using UDP-hexanolamine affinity chromatography and used in the synthesis of preparative amounts of the human blood group B trisaccharide antigen. The substrate specificity and kinetics of the recombinant enzyme were comparable to the enzyme from human sera. Thus we have achieved the construction of a completely synthetic glycosyltransferase gene and its successful expression.
Glassy materials as a hydrogen storage medium: Density functional calculations (2005)

The adsorption of molecular hydrogen on a glassy material and its relatives is studied with a use of pseudopotential density-functional method. The binding energy and distance of adsorbed hydrogen is particularly calculated. It is found that the desorption temperature of hydrogen in layered boron oxide is significantly higher than that in carbon nanotubes as much as twice, which is attributed to heteropolar bonding in boron oxide. The effect of water addition to boron oxide on hydrogen adsorption is also investigated. Our results indicate that water may reduce the surface area of boron oxide but has little effect on the hydrogen adsorption energy. We also calculated an optimum pore size for hydrogen diffusion into boron oxide. The current study demonstrates a pathway to the finding of a class of materials for hydrogen storage media that can hold hydrogen at ambient conditions through physisorption.
IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2–dependent mechanisms with implications for psoriasis pathogenesis (2006)

Aberrant cytokine expression has been proposed as an underlying cause of psoriasis, although it is unclear which cytokines play critical roles. Interleukin (IL)-23 is expressed in human psoriasis and may be a master regulator cytokine. Direct intradermal administration of IL-23 in mouse skin, but not IL-12, initiates a tumor necrosis factor-dependent, but IL-17A-independent, cascade of events resulting in erythema, mixed dermal infiltrate, and epidermal hyperplasia associated with parakeratosis. IL-23 induced IL-19 and IL-24 expression in mouse skin, and both genes were also elevated in human psoriasis. IL-23-dependent epidermal hyperplasia was observed in IL-19-/- and IL-24-/- mice, but was inhibited in IL-20R2-/- mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target.
“Blood failure” time to view blood as an organ: how oxygen debt contributes to blood failure and its implications for remote damage control resuscitation (2016)

Hemorrhagic shock is both a local and systemic disorder. In the context of systemic effects, blood loss may lead to levels of reduced oxygen delivery (DO2 ) sufficient to cause tissue ischemia. Similar to other physiologic debts such as sleep, it is not possible to incur a significant oxygen debt and suffer no consequences for lack of timely repayment. While the linkage between oxygen debt and traditional organ failure (renal, hepatic, lung, and circulation) has been long recognized, we should consider failure in two additional linked and very dynamic organ systems, the endothelium and blood. These systems are very sensitive to oxygen debt and at risk for failing, having further implications on all other organ systems. The degree of damage to the endothelium is largely modulated by the degree of oxygen debt. Thus hypoperfusion is believed to begin a cascade of events leading to acute traumatic coagulopathy (ATC). This combination of oxygen debt driven endothelial damage and ATC might be considered collectively as "blood failure" due to the highly connected networks between these drivers. This article presents the implications of oxygen debt for remote damage control resuscitation strategies, such as permissive hypotension and hemostatic resuscitation. We review the impact of whole blood resuscitation and red blood cell efficacy in mitigation of oxygen debt. At last, this article recognizes the need for simple and durable, lightweight equipment that can detect the adequacy of tissue DO2 and thus patient needs for resuscitative care. Point-of-care lactate measuring may be a predictive tool for identifying high-risk trauma patients and occult shock because it provides information beyond that of vital signs and mechanism of injury as it may help predict the level of oxygen debt accumulation and need for resuscitation. Serial measurements may also be valuable as a tool in guiding resuscitative efforts.
mRNA Vaccine Delivery Using Lipid Nanoparticles (2016)

mRNA vaccines elicit a potent immune response including antibodies and cytotoxic T cells. mRNA vaccines are currently evaluated in clinical trials for cancer immunotherapy applications, but also have great potential as prophylactic vaccines. Efficient delivery of mRNA vaccines will be key for their success and translation to the clinic. Among potential nonviral vectors, lipid nanoparticles are particularly promising. Indeed, lipid nanoparticles can be synthesized with relative ease in a scalable manner, protect the mRNA against degradation, facilitate endosomal escape, can be targeted to the desired cell type by surface decoration with ligands, and as needed, can be codelivered with adjuvants.
System-Wide Associations between DNA-Methylation, Gene Expression, and Humoral Immune Response to Influenza Vaccination (2016)

Failure to achieve a protected state after influenza vaccination is poorly understood but occurs commonly among aged populations experiencing greater immunosenescence. In order to better understand immune response in the elderly, we studied epigenetic and transcriptomic profiles and humoral immune response outcomes in 50-74 year old healthy participants. Associations between DNA methylation and gene expression reveal a system-wide regulation of immune-relevant functions, likely playing a role in regulating a participant's propensity to respond to vaccination. Our findings show that sites of methylation regulation associated with humoral response to vaccination impact known cellular differentiation signaling and antigen presentation pathways. We performed our analysis using per-site and regionally average methylation levels, in addition to continuous or dichotomized outcome measures. The genes and molecular functions implicated by each analysis were compared, highlighting different aspects of the biologic mechanisms of immune response affected by differential methylation. Both cis-acting (within the gene or promoter) and trans-acting (enhancers and transcription factor binding sites) sites show significant associations with measures of humoral immunity. Specifically, we identified a group of CpGs that, when coordinately hypo-methylated, are associated with lower humoral immune response, and methylated with higher response. Additionally, CpGs that individually predict humoral immune responses are enriched for polycomb-group and FOXP2 transcription factor binding sites. The most robust associations implicate differential methylation affecting gene expression levels of genes with known roles in immunity (e.g. HLA-B and HLA-DQB2) and immunosenescence. We believe our data and analysis strategy highlight new and interesting epigenetic trends affecting humoral response to vaccination against influenza; one of the most common and impactful viral pathogens.
The anti‐immunity system of phage‐plasmid N15: identification of the antirepressor gene and its control by a small processed RNA (1999)

N15 is a temperate virus of Escherichia coli related to lambdoid phages. However, unlike all other known phages, the N15 prophage is maintained as a low copy number linear DNA molecule with covalently closed ends. The primary immunity system at the immB locus is structurally and functionally comparable to that of lambdoid phages, and encodes the immunity repressor CB. We have characterized a second locus, immA, in which clear plaque mutations were mapped, and found that it encodes an anti-immunity system involved in the choice between the lytic and the lysogenic cycle. Three open reading frames at the immA locus encode an inhibitor of cell division (icd ), an antirepressor (antA) and a gene that may play an ancillary role in anti-immunity (antB ). These genes may be transcribed from two promoters: the upstream promoter Pa is repressed by the immunity repressor CB, whereas the downstream promoter Pb is constitutive. Full repression of the anti-immunity system is achieved by premature transcription termination elicited by a small RNA (CA RNA) produced by processing of the leader transcript of the anti-immunity operon. The N15 anti-immunity system is structurally and functionally similar to the anti-immunity system of bacteriophage P1 and to the immunity system of satellite phage P4.
ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage (2001)

The p53 tumor suppressor protein, a key regulator of cellular responses to genotoxic stress, is stabilized and activated after DNA damage. The rapid activation of p53 by ionizing radiation and radiomimetic agents is largely dependent on the ATM kinase. p53 is phosphorylated by ATM shortly after DNA damage, resulting in enhanced stability and activity of p53. The Mdm2 oncoprotein is a pivotal negative regulator of p53. In response to ionizing radiation and radiomimetic drugs, Mdm2 undergoes rapid ATM-dependent phosphorylation prior to p53 accumulation. This results in a decrease in its reactivity with the 2A10 monoclonal antibody. Phage display analysis identified a consensus 2A10 recognition sequence, possessing the core motif DYS. Unexpectedly, this motif appears twice within the human Mdm2 molecule, at positions corresponding to residues 258-260 and 393-395. Both putative 2A10 epitopes are highly conserved and encompass potential phosphorylation sites. Serine 395, residing within the carboxy-terminal 2A10 epitope, is the major target on Mdm2 for phosphorylation by ATM in vitro. Mutational analysis supports the conclusion that Mdm2 undergoes ATM-dependent phosphorylation on serine 395 in vivo in response to DNA damage. The data further suggests that phosphorylated Mdm2 may be less capable of promoting the nucleo-cytoplasmic shuttling of p53 and its subsequent degradation, thereby enabling p53 accumulation. Our findings imply that activation of p53 by DNA damage is achieved, in part, through attenuation of the p53-inhibitory potential of Mdm2.
Catumaxomab (2010)

Catumaxomab, a monoclonal bispecific trifunctional antibody, was approved in the European Union in April 2009 for the intraperitoneal treatment of patients with malignant ascites. The marketing authorization holder Fresenius Biotech GmbH developed catumaxomab (Removab(®)) together with its partner TRION Pharma GmbH, Germany. It is the first substance worldwide with a regulatory label for the treatment of malignant ascites due to epithelial carcinomas. Since the peritoneum is of mesothelial origin and therefore lacks EpCAM expression, the intraperitoneal administration of catumaxomab is an attractive targeted immunotherapeutic approach. Catumaxomab is able to destroy EpCAM positive tumor cells in the peritoneal cavity known as the main cause of malignant ascites. In addition, catumaxomab is a potential therapeutic option for several primary tumors since the EpCAM molecule is expressed on the majority of epithelial carcinomas. This review focuses on the clinical development of catumaxomab and indicates future directions.
High Doses of a Helper-Dependent Adenoviral Vector Yield Supraphysiological Levels of α 1 -Antitrypsin with Negligible Toxicity (1998)

Optimal gene therapy for many disorders will require efficient transfer to cells in vivo, high-level and long-term expression, and tissue-specific regulation, all in the absence of significant toxicity or inflammatory responses. While recombinant adenoviral vectors are efficient for gene transfer to hepatocytes, their usefulness is limited by short duration of expression related, at least in part, to immune responses to viral proteins and by a low capacity for foreign DNA. A number of systems have been developed for producing adenoviral vectors devoid of all viral coding sequences. Using AdSTK109, a vector lacking all viral coding sequences and carrying the complete human alpha1-antitrypsin (hAAT) genomic DNA locus, we have demonstrated sustained expression for longer than 10 months in mice. Utilizing high doses of this vector for hepatic gene transfer in mice, we find that supraphysiological levels of hAAT can be achieved without hepatotoxicity.
Suppression of SV40 tumors after immunization with group A Streptococcus pyogenes and Bordetella pertussis. (1974)

Tumors produced by a line of SV40-transformed cells in golden Syrian hamsters were suppressed in 60% of animals immunized with a mixed vaccine of Group A Streptococcus pyogenes and Bordetella pertussis . There was a suppression of tumor growth in 50% of animals immunized with S. pyogenes vaccine alone. Polysaccharides were extracted from S. pyogenes and tumor cells by an identical procedure. Antibody titers to these polysaccharides were measured and were found to be depressed in both tumor-bearing and suppressed animals during the period when tumors were rapidly growing in tumor-bearing animals. Antibody to tumor polysaccharide reacted with tumor and S. pyogenes polysaccharides. Such antibody was found in sera and also could be eluted from tumors. The ligands, N -acetyl-d-glucosamine and l-rhamnose, which are the major constituents of the cell wall of S. pyogenes , did not bind with any serum. There was a significantly lower level of sialoglycoprotein in the sera of tumor-bearing animals than was found in that of control animals.
An Overview of Video Encryption Techniques (2009)

With the rapid development of various multimedia technologies, more and more multimedia data are generated and transmitted in the medical, commercial, and military fields, which may include some sensitive information which should not be accessed by or can only be partially exposed to the general users. Therefore, security and privacy has become an important. Over the last few years several encryption algorithms have applied to secure video transmission. While a large number of multimedia encryption schemes have been proposed in the literature and some have been used in real products, cryptanalytic work has shown the existence of security problems and other weaknesses in most of the proposed multimedia encryption schemes. In this paper, a description and comparison between encryption methods and representative video algorithms were presented. With respect not only to their encryption speed but also their security level and stream size. A trade-off between quality of video streaming and choice of encryption algorithm were shown. Achieving an efficiency, flexibility and security is a challenge of researchers.
Specification of CNS glia from neural stem cells in the embryonic neuroepithelium (2007)

All the neurons and glial cells of the central nervous system are generated from the neuroepithelial cells in the walls of the embryonic neural tube, the 'embryonic neural stem cells'. The stem cells seem to be equivalent to the so-called 'radial glial cells', which for many years had been regarded as a specialized type of glial cell. These radial cells generate different classes of neurons in a position-dependent manner. They then switch to producing glial cells (oligodendrocytes and astrocytes). It is not known what drives the neuron-glial switch, although downregulation of pro-neural basic helix-loop-helix transcription factors is one important step. This drives the stem cells from a neurogenic towards a gliogenic mode. The stem cells then choose between developing as oligodendrocytes or astrocytes, of which there might be intrinsically different subclasses. This review focuses on the different extracellular signals and intracellular responses that influence glial generation and the choice between oligodendrocyte and astrocyte fates.
Fabrication and characterization of hydrogel-based microvalves (2002)

Several microvalves utilizing stimuli-responsive hydrogel materials have been developed. The hydrogel components are fabricated inside microchannels using a liquid phase polymerization process. In-channel processing greatly simplifies device construction, assembly, and operation since the functional components are fabricated in situ and can perform both sensing and actuation functions. Two in situ photopolymerization techniques, "laminar stream mode" and "mask mode," have been explored. Three two-dimensional (2-D) valves were fabricated and tested (response time, pressure drop, maximum differential pressure). In addition, a hydrogel/PDMS three-dimensional (3-D) hybrid valve that physically separates the sensing and regulated streams was demonstrated. Analytical modeling was performed on the 3-D valve. Hydrogel-based microvalves have a number of advantages over conventional microvalves, including relatively simple fabrication, no external power requirement, no integrated electronics, large displacement (185 /spl mu/m), and large force generation (22 mN).
Rapid Quantification of Mutant Fitness in Diverse Bacteria by Sequencing Randomly Bar-Coded Transposons (2015)

A large challenge in microbiology is the functional assessment of the millions of uncharacterized genes identified by genome sequencing. Transposon mutagenesis coupled to next-generation sequencing (TnSeq) is a powerful approach to assign phenotypes and functions to genes. However, the current strategies for TnSeq are too laborious to be applied to hundreds of experimental conditions across multiple bacteria. Here, we describe an approach, random bar code transposon-site sequencing (RB-TnSeq), which greatly simplifies the measurement of gene fitness by using bar code sequencing (BarSeq) to monitor the abundance of mutants. We performed 387 genome-wide fitness assays across five bacteria and identified phenotypes for over 5,000 genes. RB-TnSeq can be applied to diverse bacteria and is a powerful tool to annotate uncharacterized genes using phenotype data.
Rapid separation of bacteria from blood—review and outlook (2016)

The high morbidity and mortality rate of bloodstream infections involving antibiotic-resistant bacteria necessitate a rapid identification of the infectious organism and its resistance profile. Traditional methods based on culturing the blood typically require at least 24 h, and genetic amplification by PCR in the presence of blood components has been problematic. The rapid separation of bacteria from blood would facilitate their genetic identification by PCR or other methods so that the proper antibiotic regimen can quickly be selected for the septic patient. Microfluidic systems that separate bacteria from whole blood have been developed, but these are designed to process only microliter quantities of whole blood or only highly diluted blood. However, symptoms of clinical blood infections can be manifest with bacterial burdens perhaps as low as 10 CFU/mL, and thus milliliter quantities of blood must be processed to collect enough bacteria for reliable genetic analysis. This review considers the advantages and shortcomings of various methods to separate bacteria from blood, with emphasis on techniques that can be done in less than 10 min on milliliter-quantities of whole blood. These techniques include filtration, screening, centrifugation, sedimentation, hydrodynamic focusing, chemical capture on surfaces or beads, field-flow fractionation, and dielectrophoresis. Techniques with the most promise include screening, sedimentation, and magnetic bead capture, as they allow large quantities of blood to be processed quickly. Some microfluidic techniques can be scaled up. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:823-839, 2016.
The development and initial validation of the systemic lupus international collaborating clinics/American college of rheumatology damage index for systemic lupus erythematosus (1996)

This damage index for SLE records damage occurring in patients with SLE regardless of its cause. The index was demonstrated to have content, face, criterion, and discriminant validity.
Disruption of Src function potentiates Chk1-inhibitor–induced apoptosis in human multiple myeloma cells in vitro and in vivo (2010)

Ras/MEK/ERK pathway activation represents an important compensatory response of human multiple myeloma (MM) cells to checkpoint kinase 1 (Chk1) inhibitors. To investigate the functional roles of Src in this event and potential therapeutic significance, interactions between Src and Chk1 inhibitors (eg, UCN-01 or Chk1i) were examined in vitro and in vivo. The dual Src/Abl inhibitors BMS354825 and SKI-606 blocked Chk1-inhibitor-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, markedly increasing apoptosis in association with BimEL up-regulation, p34(cdc2) activation, and DNA damage in MM cell lines and primary CD138(+) MM samples. Loss-of-function Src mutants (K297R, K296R/Y528F) or shRNA knock-down of Src prevented the ERK1/2 activation induced by Chk1 inhibitors and increased apoptosis. Conversely, constitutively active Ras or mitogen-activated protein kinase/ERK kinase 1 (MEK1) significantly diminished the ability of Src inhibitors to potentiate Chk1-inhibitor lethality. Moreover, Src/Chk1-inhibitor cotreatment attenuated MM-cell production of vascular endothelial growth factor and other angiogenic factors (eg, ANG [angiogenin], TIMP1/2 [tissue inhibitor of metalloproteinases 1/2], and RANTES [regulated on activation normal T-cell expressed and secreted]), and inhibited in vitro angiogenesis. Finally, coadministration of BMS354825 and UCN-01 suppressed human MM tumor growth in a murine xenograft model, increased apoptosis, and diminished angiogenesis. These findings suggest that Src kinase is required for Chk1-inhibitor-mediated Ras → ERK1/2 signaling activation, and that disruption of this event sharply potentiates the anti-MM activity of Chk1 inhi-bitors in vitro and in vivo.
Metal Reduction and Iron Biomineralization by a Psychrotolerant Fe(III)-Reducing Bacterium, Shewanella sp. Strain PV-4 (2006)

A marine psychrotolerant, dissimilatory Fe(III)-reducing bacterium, Shewanella sp. strain PV-4, from the microbial mat at a hydrothermal vent of Loihi Seamount in the Pacific Ocean has been further characterized, with emphases on metal reduction and iron biomineralization. The strain is able to reduce metals such as Fe(III), Co(III), Cr(VI), Mn(IV), and U(VI) as electron acceptors while using lactate, formate, pyruvate, or hydrogen as an electron donor. Growth during iron reduction occurred over the pH range of 7.0 to 8.9, a sodium chloride range of 0.05 to 5%, and a temperature range of 0 to 37 degrees C, with an optimum growth temperature of 18 degrees C. Unlike mesophilic dissimilatory Fe(III)-reducing bacteria, which produce mostly superparamagnetic magnetite (<35 nm), this psychrotolerant bacterium produces well-formed single-domain magnetite (>35 nm) at temperatures from 18 to 37 degrees C. The genome size of this strain is about 4.5 Mb. Strain PV-4 is sensitive to a variety of commonly used antibiotics except ampicillin and can acquire exogenous DNA (plasmid pCM157) through conjugation.