gebhart/patrepeval huggingface dataset:
Protein Transduction: Cell Penetrating Peptides and Their Therapeutic Applications (2006)

Cell penetrating proteins or peptides (CPPs) have the ability to cross the plasma membranes of mammalian cells in an apparently energy- and receptor-independent fashion. Although there is much debate over the mechanism by which this "protein transduction" occurs, the ability of CPPs to translocate rapidly into cells is being exploited to deliver a broad range of therapeutics including proteins, DNA, antibodies, oligonucleotides, imaging agents and liposomes in a variety of situations and biological systems. The current review looks at the delivery of many such molecules by various CPPs, and their potential therapeutic application in a wide range of areas. CPP ability to deliver different cargoes in a relatively efficient and non-invasive manner has implications as far reaching as drug delivery, gene transfer, DNA vaccination and beyond. Although many questions remain to be answered and limitations on the use of CPPs exist, it is clear that this emerging technology has much to offer in a clinical setting.
Extracellular plasma RNA from colon cancer patients is confined in a vesicle-like structure and is mRNA-enriched (2008)

Little is yet known about the origin and protective mechanism of free nucleic acids in plasma. We investigated the possibility of these free nucleic acids being particle associated. Plasma samples from colon cancer patients and cell culture media were subjected to various antibody incubations, ultracentrifugation, and RNA extraction protocols for total RNA, epithelial RNA, and mRNA. Flow cytometry using a Ber-EP4 antibody and confocal laser microscopy after staining with propidium iodide were also performed. mRNA levels of the LISCH7 and SDHA genes were determined in cells and in culture media. Ber-EP4 antibody and polystyrene beads coated with oligo dT sequences were employed. We observed that, after incubation, total RNA and mRNA were always detected after membrane digestion, and that epithelial RNA was detected before this procedure. In ultracentrifugation, mRNA was caught in the supernatant only if a former lysis mediated or in the pellet if there was no previous digestion. Flow cytometry determinations showed that antibody-coated microbeads keep acellular structures bearing epithelial antigens apart. Confocal laser microscopy made 1- to 2-microm-diameter particles perceptible in the vicinity of magnetic polystyrene beads. Relevant differences were observed between mRNA of cells and culture media, as there was a considerable difference in LISCH7 mRNA levels between HT29 and IMR90 cell co-cultures and their culture media. Our results support the view that extracellular RNA found in plasma from cancer patients circulates in association with or is protected in a multiparticle complex, and that an active release mechanism by tumor cells may be a possible origin.
Neural transplantation (1986)

Neural transplantation, once deemed impossible, is being studied in many laboratories. Embryonic CNS from a variety of sites can be grafted into an adult host. The foreign cells differentiate and then produce neurotransmitters or neurohormones. Physical connection can be seen between graft and host. Grafting of fetal tissue may be followed by improved function of animals with experimental forms of neurologic disease or physical injury. Grafted segments of peripheral nerve become innervated by central axons that can conduct physiologic impulses. Grafted glial cells can form myelin within the CNS. Therapeutic grafting into the human nervous system may be feasible, but many scientific and ethical questions remain to be addressed.
Evolution's cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes (2003)

This study examines genomic duplications, deletions, and rearrangements that have happened at scales ranging from a single base to complete chromosomes by comparing the mouse and human genomes. From whole-genome sequence alignments, 344 large (>100-kb) blocks of conserved synteny are evident, but these are further fragmented by smaller-scale evolutionary events. Excluding transposon insertions, on average in each megabase of genomic alignment we observe two inversions, 17 duplications (five tandem or nearly tandem), seven transpositions, and 200 deletions of 100 bases or more. This includes 160 inversions and 75 duplications or transpositions of length >100 kb. The frequencies of these smaller events are not substantially higher in finished portions in the assembly. Many of the smaller transpositions are processed pseudogenes; we define a "syntenic" subset of the alignments that excludes these and other small-scale transpositions. These alignments provide evidence that approximately 2% of the genes in the human/mouse common ancestor have been deleted or partially deleted in the mouse. There also appears to be slightly less nontransposon-induced genome duplication in the mouse than in the human lineage. Although some of the events we detect are possibly due to misassemblies or missing data in the current genome sequence or to the limitations of our methods, most are likely to represent genuine evolutionary events. To make these observations, we developed new alignment techniques that can handle large gaps in a robust fashion and discriminate between orthologous and paralogous alignments.
Respiratory Infections by HMPV and RSV Are Clinically Indistinguishable but Induce Different Host Response in Aged Individuals (2011)

Contrary to other studies, no weight loss or change in activity despite productive lung infection with the different viruses were observed. This may be due to the weaker anaesthesia or the lesser volume of virus solution used, leading to less stress in the animals. The observed differences in TNF-α and NF-κB elevation lead to the assumption that young and old individuals have different mechanisms to react against the viruses.
Morphological studies of the neutralization of influenza virus by IgM (1990)

Quantitative relationships between neutralization, aggregation and attachment to monolayers of chick embryo fibroblast (CEF) cells have been studied using a constant amount of influenza A/fowl plague virus/Rostock/34 (H7N1) and varying amounts of purified mouse polyclonal IgM directed against the haemagglutinin, the major viral neutralization antigen. There are two major types of interaction. (i) At low concentrations of IgM there is aggregation of virus, but no neutralization provided that the aggregates are dispersed by vortexing and dilution. Maximum aggregation occurs at less than seven molecules of IgM per virion and the IgM is probably bound in the 'staple' or 'crab' conformation at these concentrations. (ii) At higher concentrations there is neutralization and this coincides with inhibition of attachment of virus to CEF cells. Neutralization of 50% infectivity requires about 35 molecules of IgM per virion. The maximum neutralization observed was only 87%. Quantitative data and electron microscopy observations suggest that molecules of IgM at the higher concentrations adopt a planar stance approximately perpendicular to the viral surface. It appears that IgM neutralizes fowl plague virus in vitro primarily by interfering with its attachment to cells; the fraction of neutralized virus that does attach is known not be internalized.
Macrophages and angiogenesis (1994)

Macrophages are supposed to play a key role in inflammatory and tumor angiogenesis. Their importance derives from (1) their ubiquitous presence in normal and especially inflamed tissues, (2) their potential to become activated in response to appropriate stimuli, and (3) their repertoire of secretory products. By release of proteases, growth factors (bFGF, GM-CSF, TGF-alpha, IGF-I, PDGF, VEGF/VPF, TGF-beta), and other monokines (IL-1, IL-6, IL-8, TNF-alpha, substance P, prostaglandins, interferons, thrombospondin 1), activated macrophages have the capability to influence each phase of the angiogenic process, such as alterations of the local extracellular matrix, induction of endothelial cells to migrate or proliferate, and inhibition of vascular growth with formation of differentiated capillaries. This review describes macrophage physiology and the influence of macrophage secretory products on the different phases of angiogenesis in vitro and in vivo.
Selective increase of cyclooxygenase-2 expression in a model of renal ablation (1998)

Previous studies have suggested a possible role for prostaglandins (PGs) in mediating alterations in nephron structure and function ensuing after renal ablation. Two isoforms of cyclooxygenase (COX) have been described: constitutive (COX-1) and inducible (COX-2). We examined expression of these isoforms following subtotal renal ablation (5/6 ablation, RA) in rats. In renal cortex, COX-2 mRNA and immunoreactive protein (IP) increased progressively compared with sham-operated littermates. In contrast, there were no significant changes in COX-1 mRNA expression. In normal kidney, cortical COX-1 IP was immunolocalized predominantly to mesangial cells and collecting tubules, whereas COX-2 IP was found in a subset of cortical thick ascending limb of Henle's loop (CTAL) cells in the region of the macula densa (MD). Following RA, significantly increased COX-2 IP was detected in the MD and surrounding CTAL cells. In addition, fainter immunoreactive COX-2 was detected in scattered visceral epithelial cells and mesangial cells of the glomerulus. Immunoblotting of isolated glomeruli demonstrated a selective increase of glomerular immunoreactive COX-2 expression following RA. No change of COX-1 expression was seen. To determine COX activity, isolated glomeruli were incubated with arachidonic acid and PGE2 measured by enzyme immunoassay (EIA). Compared with sham, glomeruli from 2 wk RA produced significantly more PGs. SC-58560, a selective COX-1 inhibitor, did not inhibit PG production in the remnant glomeruli at concentrations up to 10(-4) M, whereas SC-58236, a relatively selective COX-2 inhibitor, significantly inhibited PG production by RA glomeruli. In preliminary studies, to define mechanisms of altered expression of glomerular COX-2, rat mesangial cells were incubated with serum from sham or 2 wk RA. There were significant increases in COX-2 expression in response to 2 wk RA serum. In summary, these results indicate selective increases in renal cortical COX-2 expression following renal ablation.
Double-Helical Dinuclear Bis(dipyrromethene) Complexes Formed by Self-Assembly (2000)

Bis(dipyrromethene) ligands linked by an alkyl spacer between beta and beta' positions are shown to give helical dimers or monomers, dependent upon the length of the alkyl linker, upon complexation. Ligands consisting of methylene, ethylene, and propylene linkers -(CH(2))(n)()- (n = 1, 2, and 3) give helical dimers, while longer linking chains (n = 4, 5, or 6) give monomers or mixtures of dimers and monomers. X-ray crystal structures of the dimeric zinc complexes (n = 1, 2, and 3) reveal that the angles between dipyrromethene planes and the extent of helicity in the complexes differ as the length of the linker varies. The extent of helicity was assessed and found to be dependent upon the length and, specifically, the conformational preferences of the alkyl spacer unit. The presence of an ethylene linker gave complexes of greatest helicity. The use of a methylene spacer gave less helical structures upon complexation, while propylene spacers gave only slightly helical complexes. Our studies identify the crucial importance that the conformational preferences of the beta-beta' alkyl spacer group plays in the coordination algorithm of self-assembly to form dipyrromethene based complexes.
Liquid fuel developments (1983)

This book concerns the biosynthesis of ethanol fuels from biomass. Topics considered include anaerobic thermophilic bacteria, screening for cellulolytic mutants, the enzymatic hydrolysis of cellulose to fermentable sugars, process biotechnology for the conversion of biomass into liquid fuels, a flow reactor for acid hydrolysis or pretreatment of cellulosic biomass, the production of ethanol and chemicals from wood by the Georgia Tech process, liquid fuels and chemicals from cellulosic residues by acid hydrolysis, alkane fuels production from biomass, and the integration of production of corn-derived fuels with animal feed production.
Purification and Characterization of a Pregastric Esterase From a Hygienized Kid Rennet Paste (2004)

Rennet pastes obtained by maceration of gastric tissues from suckling kids are used traditionally to produce some artisanal cheeses in Spain. Besides milk-clotting function, rennet pastes provide proteolytic activity and lipolytic system, essentially pregastric, necessary in the development of piquant flavor typical of these cheeses. A simple and reproducible procedure allows us to obtain a standardized rennet paste that posses the desired activity and is of good microbiological quality. Concomitantly, a kid pregastric esterase (KPGE) was purified to homogeneity. The purification procedure was based on an aqueous extract of hygienized rennet paste (HRP), which was chromatographed on DEAE-Sepharose Fast Flow then adsorbed on phenyl superose followed by a re-chromatography on the same column. The final enzymatic preparation, where the overall activity recovery was 3%, showed a molecular mass of 53 kDa. The highest activity was determined on p-nitrophenyl butyrate, but marked hydrolysis was also detected on beta-naphthyl caprylate. In contrast, low activity on tributyrin (substrate under emulsion form) was detected, thus confirming the esterase character of purified enzyme.
Sensitive method for detecting low numbers of verotoxin-producing Escherichia coli in mixed cultures by use of colony sweeps and polymyxin extraction of verotoxin (1985)

High titers of Verotoxin (VT) were released from cell pellets of VT-producing Escherichia coli (VTEC; corresponding to E. coli strains producing "high" levels of Shiga-like toxin) after incubation in polymyxin B (0.1 mg/ml) for 30 min at 37 degrees C. Maximal titers of polymyxin-releasable VT occurred in cells obtained from 5-h Penassay broth cultures and were up to eightfold higher than the peak culture supernatant VT titers which occurred in 8-h cultures. Polymyxin-releasable cell extracts of 5-h broth cultures inoculated with mixtures of VT-positive (VT+) and VT-negative strains had easily detectable VT titers when the proportion of VT+ cells in the mixture was about 1.0%, but culture supernatants were negative for VT even when this proportion was 20%. The results were the same whether the initial inoculum consisted of broth culture mixtures of VT+ and VT-negative strains or colony sweeps (loopfuls of confluent bacterial growth) taken from solid plate media previously inoculated with the broth mixtures. In a clinical study, 80 stool cultures from patients with hemolytic uremic syndrome and family contacts with diarrhea were tested for free fecal VT, VT in polymyxin extracts of colony sweeps (VT/PECS), and VTEC (examination of 20 separate E. coli colonies from primary media for VT production). Of the 80 samples, 40 were positive for at least one of these three tests; all 40 were positive for free fecal VT, and 20 of these were positive for VT/PECS. VTEC (as few as 1 colony out of 20) were only isolated from 14 of the 20 cultures that were positive for VT/PECS. In six cases, the VT/PECS was positive even when none of 20 colonies tested were VT+, suggesting that the procedure was able to detect a proportion of VTEC that was less than one in 20(5%). We conclude that the VT/PECS method is highly sensitive for detecting low concentrations of VTEC in stools and provides a rapid method for screening out stools that are negative for VTEC. The technique should also be of value in epidemiological studies for detecting low numbers of VTEC in animal feces, foods, and environmental samples.
An improved strategy and a useful housekeeping gene for RNA analysis from formalin-fixed, paraffin-embedded tissues by PCR. (1993)

Specific amplification of nucleic acid sequences by PCR has been extensively used for the detection of gene rearrangements and gene expression. Although successful amplification of DNA sequences has been carried out with DNA prepared from formalin-fixed, paraffin-embedded (FFPE) tissues, there are only a few reports regarding RNA analysis in this kind of material. We describe a procedure for RNA extraction from different types of FFPE tissues, involving digestion with proteinase K followed by guanidinium-thiocyanate acid phenol extraction and DNase I digestion. These RNA preparations are suitable for PCR analysis of mRNA and even of intronless genes. Furthermore, the universally expressed porphobilinogen deaminase mRNA proved to be useful as a positive control because of the lack of pseudogenes.
Clock schedule verification under process variations (2005)

With aggressive scaling down of feature sizes in VLSI fabrication, process variations have become a critical issue in designs, especially for high-performance ICs. Usually having level-sensitive latches for their speed, high-performance IC designs need to verify the clock schedules. With process variations, the verification needs to compute the probability of correct clocking. Because of complex statistical correlations, traditional iterative approaches are difficult to get accurate results. Instead, a statistical checking of the structural conditions for correct clocking is proposed, where the central problem is to compute the probability of having a positive cycle in a graph with random edge weights. The proposed method only traverses the graph once to avoid the correlations among iterations, and it considers not only data delay variations but also clock skew variations. Experimental results showed that the proposed approach has an error of 0.14% on average in comparisons with the Monte Carlo simulations.
Simultaneous pO2 and HbO2 measurement to determine absolute HbO2 concentration for in vivo near infrared spectroscopy (2003)

Purpose : Near infrared spectroscopy (NIRS) monitors absolute changes in concentration of chromophores from an unquantified baseline. A change in oxygenation is required to obtain information. Clinically, knowing initial chromophore concentration is desirable. We sought absolute initial concentrations by combining NIRS measurements with simultaneous Eppendorf histograph measurement (absolute values of tissue partial pressure of oxygen (pO 2 )). Methods : There were 22 trials on 9 occasions in 2 adult volunteers. Following local anaesthetic, the histograph probe was inserted into the forearm muscle and NIRS optodes applied. A sphygmomanometer cuff was inflated over the upper arm to produce ischaemia and hypoxia. Change in pO 2 was determined as a percentage of the initial pO 2 . Change in HbO 2 was measured, and the initial HbO 2 calculated by assuming the percentage change in HbO 2 equaled the percentage change in pO 2 . Results : Mean percentage change in pO 2 was 20.7 ± 9.6. Mean change in HbO 2 was 22.4 ± 3.4 µ mol/l(tissue). Calculated initial HbO 2 was 146.4 ± 108.7 µ mol/l(tissue), range 51 to 508 µ mol/l(tissue). Correlation ( r 2 ) between pO 2 and HbO 2 was 0.97 ± 0.03. Conclusion : Although changes in pO 2 and HbO 2 were highly correlated, calculation of initial absolute concentration of HbO 2 was not achieved by this method. A reliable method of obtaining absolute concentrations of HbO 2 in vivo remains to be found.
A limited number of B cell lineages generates the heterogeneity of a secondary immune response. (1987)

We have studied the cellular basis for heterogeneity in the secondary immune response by creating a large set of B cell hybridomas from a single C57BL/6 mouse immunized with the hapten (4-hydroxy-3-nitrophenyl)acetyl coupled to chicken gamma-globulin, and searching among the cells for all possible sets of clonally related lines. Among 28 independent cell lines from a single animal we find that 21 of them fall into seven small families of from two to five members; only seven lines have no matches among the set. A statistical analysis determines that the number of genetically distinct B cell precursors whose progeny were isolated during this secondary response is 18, with 95% confidence limits of 14 and 26. The distribution of family sizes implies that each activated clone has proliferated to approximately the same extent. Complete sequencing of the variable region of immunoglobulin heavy chain mRNA from 19 of the cell lines reveals many shared somatic mutations among related lines, implying a pronounced founder effect has occurred to eliminate most of the progeny of each precursor B cell. This may be the result either of a high frequency of debilitating somatic mutation or from selection against cells still expressing the idiotype of primary anti-(4-hydroxy-3-nitrophenyl)acetyl antibodies.
The HS:19 serostrain ofCampylobacter jejunihas a hyaluronic acid‐type capsular polysaccharide with a nonstoichiometric sorbose branch andO‐methyl phosphoramidate group (2006)

A recent study that examined multiple strains of Campylobacter jejuni reported that HS:19, a serostrain that has been associated with the onset of Guillain-Barré syndrome, had unidentified labile, capsular polysaccharide (CPS) structures. In this study, we expand on this observation by using current glyco-analytical technologies to characterize these unknown groups. Capillary electrophoresis electrospray ionization MS and NMR analysis with a cryogenically cooled probe (cold probe) of CPS purified using a gentle enzymatic method revealed a hyaluronic acid-type [-4)-beta-D-GlcA6NGro-(1-3)-beta-D-GlcNAc-(1-]n repeating unit, where NGro is 2-aminoglycerol. A labile alpha-sorbofuranose branch located at C2 of GlcA was determined to have the L configuration using a novel pyranose oxidase assay and is the first report of this sugar in a bacterial glycan. A labile O-methyl phosphoramidate group, CH3OP(O)(NH2)(OR) (MeOPN), was found at C4 of GlcNAc. Structural heterogeneity of the CPS was due to nonstoichiometric glycosylation with sorbose at C2 of GlcA and the nonstoichiometric, variably methylated phosphoramidate group. Examination of whole bacterial cells using high-resolution magic angle spinning NMR revealed that the MeOPN group is a prominent feature on the cell surface for this serostrain. These results are reminiscent of those in the 11168 and HS:1 strains and suggest that decoration of CPS with nonstoichiometric elements such as keto sugars and the phosphoramidate is a common mechanism used by this bacterium to produce a structurally complex surface glycan from a limited number of genes. The findings of this work with the HS:19 serostrain now present a means to explore the role of CPS as a virulence factor in C. jejuni.
Personal communications (1989)

Abstract Death has had a lot of bad press. Many living hours are spent in great concern and fear of this great mystery. In fact, fear of death is probably the deepest fear I've experienced in my patients. This is very interesting because it is one of the few things everyone has to do yet, by definition, it is something that we cannot be conscious of. It seems our society is so uncomfortable with death that, in spite of the incredible concern for it, few are willing to discuss it openly as a stimulating topic of conversation. On the contrary, if it is spoken of at all, it is often done so in whispering, even secretive tones with people declaring that the subject is morbid. Is this deathism? Is there something in the way we are raised, reinforced in our educamtion, in the arts, yes even in the medical profession that is perpetuating a perspective (myth) that death is not simply part of nature's great design but some horrible trick (punishment) being forced on us? Do we have to buy into this grim reaper routine? Are we not free to choose the way we can look at death?