gebhart/patrepeval huggingface dataset:
Building early-larval sexing systems for genetic control of the Australian sheep blow fly Lucilia cuprina using two constitutive promoters (2017)

Transgenic sexing strains (TSS) that carry conditional female lethal genes are advantageous for genetic control programs based on the sterile insect technique (SIT). It is desirable if females die early in development as larval diet is a major cost for mass production facilities. This can be achieved by using a gene promoter that is only active in embryos to drive expression of the tetracycline transactivator (tTA), the transcription factor commonly used in two-component TSS. While an embryo-specific promoter is ideal it may not be essential for assembling an effective TSS as tTA can be repressed by addition of tetracycline to the diet at larval and/or adult stages. Here we have investigated this idea by isolating and employing the promoters from the Lucilia spitting image and actin 5C genes to drive tTA expression in embryos and later stages. L. cuprina TSS with the tTA drivers and tTA-regulated tetO-Lshid effectors produced only females when raised on a limited tetracycline diet. The Lshid transgene contains a sex-specific intron and as a consequence only females produce LsHID protein. TSS females died at early larval stages, which makes the lines advantageous for an SIT program.
ChemInform Abstract: Structure of PLi4 and Its Comparison with SiLi4, CLi4, and Li4: The Importance of Li‐Li Interactions. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Regulator of G-protein signaling-5 induction in pericytes coincides with active vessel remodeling during neovascularization (2005)

We identified regulator of G-protein signaling-5 (RGS-5) as an angiogenic pericyte marker at sites of physiologic and pathologic angiogenesis. In a mouse model of pancreatic islet cell carcinogenesis, RGS-5 is specifically induced in the vasculature of premalignant lesions during the "angiogenic switch" and further elevated in tumor vessels. Similarly, RGS-5 is overexpressed in highly angiogenic astrocytomas but not in hypoxia-inducible factor-1alpha (HIF-1alpha)-deficient tumors, which grow along preexisting brain capillaries without inducing neovessels. Elevated levels of RGS-5 in pericytes are also observed during wound healing and ovulation indicating a strong correlation between RGS-5 expression and active vessel remodeling beyond tumor angiogenesis. Moreover, antitumor therapy, which reverses tumor vasculature to an almost normal morphology, results in down-regulation of RGS-5 transcription. Taken together, these data demonstrate for the first time a factor that is specific for "activated" pericytes. This further supports the notion that pericytes, like endothelial cells, undergo molecular changes during neovascularization that makes them a novel target for antiangiogenic therapy.
An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression (2004)

Accumulating reports demonstrate that apoptosis does not explain all the forms of programmed cell death (PCD), particularly in individual development and neurodegenerative disease. Recently, a novel type of PCD, designated 'paraptosis', was described. Here, we show that overexpression of TAJ/TROY, a member of the tumor necrosis factor receptor superfamily, induces non-apoptotic cell death with paraptosis-like morphology in 293T cells. Transmission electron microscopy studies reveal extensive cytoplasmic vacuolation and mitochondrial swelling in some dying cells and no condensation or fragmentation of the nuclei. Characteristically, cell death triggered by TAJ/TROY was accompanied by phosphatidylserine externalization, loss of the mitochondrial transmembrane potential and independent of caspase activation. In addition, TAJ/TROY suppressed clonogenic growth of HEK293 and HeLa cells. Interestingly, overexpression of Programmed cell death 5 (PDCD5), an apoptosis-promoting protein, enhanced TAJ/TROY-induced paraptotic cell death. Moreover, cellular endogenous PDCD5 protein was significantly upregulated in response to TAJ/TROY overexpression. These results provide novel evidence that TAJ/TROY activates a death pathway distinct from apoptosis and that PDCD5 is an important regulator in both apoptotic and non-apoptotic PCD.
Detailed genetic linkage map of human chromosome 21: patterns of recombination according to age and sex. (1990)

A detailed genetic linkage map of human chromosome 21 will allow the rapid regional assignment of future genes and DNA markers to this autosome. It will also facilitate the precise mapping of the genes responsible for the DS phenotype and the defect causing FAD. This map can also be used to implicate genes involved with specific features of the DS phenotype by permitting the delineation of finite regions of chromosome 21 which are duplicated in patients with partial trisomy 21, and who manifest select symptoms of the DS phenotype. In the case of FAD, most pedigrees are not ideally structured for genetic linkage analysis since affected individuals die relatively soon (6-8 years) after the onset of symptoms. By first establishing the genetic relationships of DNA markers in the vicinity of the FAD defect, multipoint analyses of these markers can then be performed in FAD families. Multipoint analysis carries a greater probability of identifying markers flanking the FAD locus thereby providing landmarks for cloning attempts aimed at isolating and characterizing the FAD gene defect. We have confirmed our initial findings of a dramatically increased rate of recombination at the telomere in both females and males, and significantly higher recombination in females in the pericentromeric region between D21S1/S11 and D21S13/S16. By comparing patterns of recombination in specific regions of chromosome 21 with regard to both parental sex and age, we have identified a statistically significant downward trend in in the frequency of crossovers in the most telomeric portion chromosome 21 with increasing maternal age. A less significant decrease in recombination with increasing maternal age was observed in the sub-centromeric region of the chromosome where recombination in females is overall higher than in males. Future confirmation of these results in combination with investigations aimed at deciphering the role played by recombination in promoting normal segregation during meiosis should help to elucidate the potential relevance of these findings to the etiological basis of nondisjunction.
Epilepsy and Exacerbation of Brain Injury in Mice Lacking the Glutamate Transporter GLT-1 (1997)

Extracellular levels of the excitatory neurotransmitter glutamate in the nervous system are maintained by transporters that actively remove glutamate from the extracellular space. Homozygous mice deficient in GLT-1, a widely distributed astrocytic glutamate transporter, show lethal spontaneous seizures and increased susceptibility to acute cortical injury. These effects can be attributed to elevated levels of residual glutamate in the brains of these mice.
Evaluation of Kinetic Light Scattering as an Approach to the Measurement of Specific Proteins with the Centrifugal Analyzer. I. Methodology (1975)

A laser-modified centrifugal analyzer was used to develop kinetic light scattering methods for the measurement of human immunoglobulins IgG, IgA, and IgM. Comparison of equilibrium light scattering methods with kinetic procedures for IgG and IgA demonstrate equivalent precision and relative accuracy. However, quantitative results obtained by equilibrium and kinetics methods for IgM were found to differ significantly. Recovery studies performed with purified IgM have shown that both methods can yield quantitative results in the normal range. Our observations demonstrate that the technique offers a viable and in some respects a superior alternative to other methods currently used in the clinical laboratory.
Human Immune Proteome in Experimental Colonization with Staphylococcus aureus (2009)

More than 20% of adults are persistently colonized with Staphylococcus aureus. When hospitalized, these carriers have increased risks of infection with their own strains. However, a recent study demonstrated a lower incidence of bacteremia-related death among carriers than among noncarriers, raising the question whether the adaptive immune system plays a protective role. In fact, S. aureus carriers mount a highly specific neutralizing antibody response against superantigens of their colonizing strains. We now used 2-dimensional immunoblotting to investigate the profiles of antibodies from healthy individuals against S. aureus extracellular proteins. Moreover, we tested whether symptom-free experimental colonization of these individuals with an S. aureus strain of low virulence, 8325-4, is sufficient to induce an antibody response. Sera obtained before and 4 weeks after colonization were screened for immunoglobulin G (IgG) antibody binding to extracellular staphylococcal proteins. At baseline, most volunteers harbored IgG directed against conserved virulence factors, including alpha-hemolysin (Hla), beta-hemolysin (Hlb), phospholipase C (Plc), staphylococcal serine protease (SspA), and cysteine protease (SspB). However, the variability of spot patterns and intensities was striking and could be important in case of infection. Experimental nasal colonization with S. aureus 8325-4 did not elicit new antibodies or boost the humoral response. Thus, the high antibody prevalence in humans is likely not induced by short-term nasal colonization, and presumably minor infections are required to trigger anti-S. aureus antibody responses.
Induction of human beta-interferon synthesis with poly(rI . rC) in mouse cells transfected with cloned cDNA plasmids. (1982)

Human genomic DNA and plasmids carrying portions of the cDNA gene for human beta-interferon have been introduced into mouse Ltk- cells by cotransfection with a herpes simplex virus thymidine kinase (TK) gene. One plasmid contains 840 base pairs of human DNA complementary to pre-beta-interferon mRNA inserted into pBR322, whereas the other plasmids have hybrid genes containing only the 560-base pair coding region inserted under the transcriptional control of the TK promoter. Constitutive interferon production could not be detected in any of the mouse TK+ cell lines tested. Nevertheless, synthesis of interferon could be induced by poly(rI . rC) treatment in at least 16 of these cell lines, including clones transfected with genomic DNA, the beta-interferon cDNA, and the TK-beta-interferon cDNA hybrid gene. The interferon produced was specific for human cells and could be neutralized by antiserum against human beta-interferon. In contrast to human fibroblast cells, in which the synthesis of induced beta-interferon is transient, the poly(rI . rC)-induced TK+ lines continued to produce beta-interferon for prolonged periods of time and did not respond to superinduction conditions. Therefore, in transfected mouse cells, the coding DNA sequence from the human beta-interferon gene, without any of the adjacent 3' or 5' flanking human DNA sequences, was sufficient both to direct synthesis of biologically active product and to respond to the specific induction system that operates in human cells. However, the mechanism that switches off the synthesis of induced interferon in human cells appears not to operate in mouse cells transfected with beta-interferon cDNA.
Down-Regulation of Metallothionein, a Reactive Oxygen Scavenger, by the Small GTPase OsRac1 in Rice (2004)

Metallothioneins are small, ubiquitous Cys-rich proteins known to be involved in reactive oxygen species (ROS) scavenging and metal homeostasis. We found that the expression of a metallothionein gene (OsMT2b) was synergically down-regulated by OsRac1 and rice (Oryza sativa) blast-derived elicitors. Transgenic plants overexpressing OsMT2b showed increased susceptibility to bacterial blight and blast fungus. OsMT2b-overexpressing cells showed reduced elicitor-induced hydrogen peroxide production. In contrast, homozygous OsMT2b::Tos17-inserted mutant and OsMT2b-RNAi-silenced transgenic cells showed significantly higher elicitor-induced hydrogen peroxide production than the wild-type cells. In vitro assay showed that recombinant OsMT2b protein possessed superoxide- and hydroxyl radical-scavenging activities. Taken together, these results showed that OsMT2b is an ROS scavenger and its expression is down-regulated by OsRac1, thus potentiating ROS, which function as signals in resistance response. The results suggest that OsRac1 plays a dual role as an inducer of ROS production and a suppressor of ROS scavenging.
Expression of immune regulatory molecules in Epstein-Barr virus-associated nasopharyngeal carcinomas with prominent lymphoid stroma. Evidence for a functional interaction between epithelial tumor cells and infiltrating lymphoid cells. (1995)

Undifferentiated nasopharyngeal carcinomas (UNPC) are characterized by an association with Epstein-Barr virus and an abundant lymphoid stroma. The role of this lymphoid stroma is uncertain but is mostly thought to represent an immune response against viral or tumor antigens. We have analyzed the expression of immune regulatory receptor/ligand pairs in snap-frozen biopsies of 20 UNPCs. All cases were Epstein-Barr virus positive and the virus-encoded latent membrane protein, LMP1, was expressed in 6 cases. By immunohistochemistry, we have demonstrated the expression of CD70 and CD40 in the tumor cells of 16 and 18 cases, respectively. Infiltrating lymphoid cells expressing CD27, the CD70 receptor, and the CD40 ligand were present in all cases. The Bcl-2 protein was detected in 17 cases. Unexpectedly, tumor cells of 5 cases expressed at least one member of the B7 family (CD80, CD86, and B7-3) and many lymphoid cells expressing the corresponding counter-receptor, CD28, were detected in all cases. Interestingly, 5 of 6 LMP1-positive cases also expressed B7, whereas all 14 LMP1-negative cases were also B7 negative. Our results indicate that T cells and carcinoma cells communicate in the microenvironment of UNPCs and suggest that the presence of a lymphoid stroma may be a requirement for UNPC growth at least in certain stages of tumor development.
Antimicrobial Peptides as Infection Imaging Agents: Better Than Radiolabeled Antibiotics (2012)

Nuclear medicine imaging techniques offer whole body imaging for localization of number and site of infective foci inspite of limitation of spatial resolution. The innate human immune system contains a large member of important elements including antimicrobial peptides to combat any form of infection. However, development of antibiotics against bacteria progressed rapidly and gained popularity over antimicrobial peptides but even powerful antimicrobials failed to reduce morbidity and mortality due to emergence of mutant strains of bacteria resulting in antimicrobial resistance. Differentiation between infection and inflammation using radiolabeled compounds with nuclear medicine techniques has always been a dilemma which is still to be resolved. Starting from nonspecific tracers to specific radiolabeled tracers, the question is still unanswered. Specific radiolabeled tracers included antibiotics and antimicrobial peptides which bind directly to the bacteria for efficient localization with advanced nuclear medicine equipments. However, there are merits and demerits attributed to each. In the current paper, radiolabeled antibiotics and radiolabeled peptides for infection localization have been discussed starting with the background of primitive nonspecific tracers. Radiolabeled antimicrobial peptides have certain merits compared with labeled antibiotics which make them superior agents for localization of infective focus.
Inhibition of Hepatitis B Virus Dna Replication by Imino Sugars Without the Inhibition of the Dna Polymerase: Therapeutic Implications (2001)

Previously we have shown that the imino sugar inhibitor of N-linked glycan processing, N-nonyl-deoxynojirimycin (N-nonyl-DNJ), had antiviral activity in the woodchuck model of chronic hepatitis B virus (HBV) infection. In studying the mechanism of action of this compound, it was discovered that imino sugars could inhibit HBV secretion without inhibiting N-linked glycoprocessing. Although N-nonyl-DNJ is an inhibitor of the endoplasmic reticulum (ER) glucosidase, here it is shown that N-nonyl-DNJ retained antiviral activity at concentrations that had no significant impact on ER glucosidase function. Taken together, these results suggested that N-nonyl-DNJ possessed an antiviral activity attributable to a function other than an impact on glycoprocessing. This hypothesis was confirmed by experiments showing that N-nonyl-deoxygalactojirimycin (N-nonyl-DGJ), an alkyl derivative of galactose with no impact on glycoprocessing, retains anti-HBV activity. The data suggest that N-nonyl-DGJ exerts its antiviral action at a point before viral envelopment and may prevent the proper encapsidation of the HBV pregenomic RNA.
Synthesis of 4′‐C‐Acylated Thymidines (1996)

Abstract Two synthetic pathways towards 4′‐ C ‐acylthymidines are presented. These modified mononucleosides are precursors of the 2′‐deoxyribonucleotide 4′‐ C ‐radical. They were converted into their corresponding 3′‐ O ‐[(2‐cyanoethyl) N,N ‐diisopropylphosphoramidites] 3a–c and incorporated in oligonucleotides by solid‐phase synthesis. The structure of some modified nucleosides was revealed by X‐ray crystal‐structure analysis.
Microvascular effects of complement blockade with soluble recombinant CR1 on ischemia/reperfusion injury of skeletal muscle (1993)

Reperfusion of ischemic tissue is associated with tissue injury greater than that resulting from ischemia alone. C activation has been hypothesized to mediate the so-called ischemia/reperfusion injury through both membrane attack and C5a-dependent recruitment of neutrophils to sites of C3 fixation on the endothelium via C3 receptors. Adherence of neutrophils is preconditional to expression of their deleterious effects, which are central to the pathophysiology of ischemia/reperfusion injury. This study was designed to evaluate the effect of inhibition of C activation on ischemia/reperfusion injury using a soluble and truncated recombinant human CR1 (sCR1) molecule, a "tail-less" form of the membrane C3b/C4b receptor (CD35) that functions as a regulator of C activation. Capillary perfusion and leukocyte adherence to venular endothelium were measured after reperfusion in a mouse cremaster muscle model that allowed microscopic video observation of microcirculatory changes. Infusion i.v. with sCR1 before a 4-h period of ischemia and during a 3-h subsequent period of reperfusion prevented the increase in leukocyte adherence to venular endothelium seen in controls, and enhanced the number of reperfusing capillaries by 55%. Trypan blue staining showed an increase in muscle cell viability from 11 to 50% in mice receiving sCR1 as compared to controls. Tests of blood samples from mice infused with sCR1 demonstrated nearly complete inhibition of the mouse alternative pathway of C activation, but no detectable loss of the mouse classical pathway of C activation. It was concluded that C activation in this model of skeletal muscle injury is likely to be due to the alternative pathway, and that inhibition of C activation during reperfusion inhibits leukocyte adherence to blood vessel walls and protects the capillary microcirculation.
Eponemycin exerts its antitumor effect through the inhibition of proteasome function. (1999)

Cell cycle progression requires the proteasome-mediated degradation of key regulatory proteins such as cyclins, cyclin-dependent kinase inhibitors, and anaphase-inhibitory proteins. Given the central role of the proteasome in the destruction of these proteins, proteasome inhibition has been proposed as a possible cancer therapy. We report here that dihydroeponemycin, an analogue of the antitumor and antiangiogenic natural product eponemycin, selectively targets the 20S proteasome. Dihydroeponemycin covalently modifies a subset of catalytic proteasomal subunits, binding preferentially to the IFN-gamma-inducible subunits LMP2 and LMP7. Moreover, the three major peptidolytic activities of the proteasome are inhibited by dihydroeponemycin at different rates. In addition, dihydroeponemycin-mediated proteasome inhibition induces a spindle-like cellular morphological change and apoptosis. These results validate the proteasome as a target for antitumor pharmacological intervention and are relevant for the design of novel chemotherapeutic strategies.
The use of lyophilized plasma in a severe multi‐injury pig model (2013)

By minimizing the volume of reconstituted LP and optimizing its anti-inflammatory properties, an LP resuscitation fluid may be created to provide effective hemostatic resuscitation with superior logistical properties.
Identification of markers of prostate cancer progression using candidate gene expression (2011)

This proof of principle study demonstrates a novel association of carcinogenic and tumourigenic gene expression with PCa stage and prognosis.
Synthesis and Properties of 4,4,9,9‐Tetramethyl‐1‐oxa‐cycloundecane‐5,6,7,8‐tetrone and 5,5,10,10‐Tetramethyl‐1‐oxa‐cyclotridecane‐6,7,8,9‐tetrone (1996)

Abstract The synthesis of 4,4,9,9‐tetramethyl‐1‐oxa‐cycloundecane‐5,6,7,8‐tetrone ( 9 ) and 5,5,10,10‐tetramethyl‐1‐oxa‐cyclotridecane‐6,7,8,9‐tetrone ( 10 ) has been achieved in a multistep procedure. The key steps in this synthesis were the ring closure of 23 and 24 to 25 and 26 , respectively, and the oxidation of the triple bond with RuO 2 /NaIO 4 to the dihydroxydiketones 31 and 32 . Compound 9 is the first cyclic tetraketone for which an intramolecular donor‐acceptor stabilization has been found. A strong transannular interaction between the ether oxygen and the C 4 O 4 unit in 9 was detected by X‐ray studies on single crystals of 9 . The transannular distance is 2.7–2.8 Å. Further evidence for a strong transannular interaction was obtained from the comparison of the reduction potential and the first band in the UV/Vis spectrum with the corresponding values from other openchain tetraketones. These findings were substantiated by PE investigations on 9 . The crystal structures of the dihydroxy‐diketones 31 a and 32 a showed that, in the case of the eleven‐membered ring ( 31 a ), there are also short transannular distances between the ether oxygen and the C 2 O 2 moiety (2.5 Å and 2.9 Å). In the case of the thirteen‐membered ring ( 32 a ), no transannular interactions were found in the solid state.
A two-layered fuzzy logic controller for systems with deadzones (1994)

Existing fuzzy control methods do not perform well when applied to systems containing nonlinearities arising from unknown deadzones. In particular, we show that a usual "fuzzy PD" controller applied to a system with a deadzone suffers from poor transient performance and a large steady-state error. In this paper, we propose a novel two-layered fuzzy logic controller for controlling systems with deadzones. The two-layered control structure consists of a fuzzy logic-based precompensator followed by a usual fuzzy PD controller. Our proposed controller exhibits superior transient and steady-state performance compared to usual fuzzy PD controllers. In addition, the controller is robust to variations in deadzone nonlinearities. We illustrate the effectiveness of our scheme using computer simulation examples.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>