gebhart/patrepeval huggingface dataset:
Induction of a Polarized Th1 Response by Insertion of Multiple Copies of a Viral T-Cell Epitope into Adenylate Cyclase ofBordetella pertussis (2000)

The adenylate cyclase (CyaA) of Bordetella pertussis delivers the N-terminal catalytic domain into the cytosol of a large number of eukaryotic cells, in particular, professional antigen-presenting cells. This allows the delivery of CD8(+) T-cell epitopes to the major histocompatibility complex class I presentation pathway. We have previously shown that immunization of mice with CyaA carrying a single CD8(+) T-cell epitope leads to antiviral protection as well as to protective and therapeutic antitumor immunity associated with the induction of specific cytotoxic T-lymphocyte (CTL) responses. Here, we evaluated the capacity of CyaA carrying one to four copies of the CD8(+) CD4(+) T-cell epitope from the nucleoprotein of the lymphocytic choriomeningitis virus to induce T-cell responses. Both CTL and Th1-like specific responses were detected in mice immunized with recombinant CyaA with or without adjuvant. Although the insertion of the larger peptides resulted in partial loss of the invasive capacity of recombinant CyaA, insertion of several copies of the same epitope led to a strong enhancement of Th1 responses and, to a lesser degree, CTL responses. These results underscore the potency of CyaA for vaccine design with a new impact on diseases in which the Th1 response has been described to have a beneficial effect.
The Peripheral Deletion of Autoreactive CD8+ T Cells Induced by Cross-presentation of Self-antigens Involves Signaling through CD95 (Fas, Apo-1) (1998)

Recently, we demonstrated that major histocompatibility complex class I-restricted cross-presentation of exogenous self-antigens can induce peripheral T cell tolerance by deletion of autoreactive CD8+ T cells. In these studies, naive ovalbumin (OVA)-specific CD8+ T cells from the transgenic line OT-I were injected into transgenic mice expressing membrane-bound OVA (mOVA) under the control of the rat insulin promoter (RIP) in pancreatic islets, kidney proximal tubules, and the thymus. Cross-presentation of tissue-derived OVA in the renal and pancreatic lymph nodes resulted in activation, proliferation, and then the deletion of OT-I cells. In this report, we investigated the molecular mechanisms underlying this form of T cell deletion. OT-I mice were crossed to tumor necrosis factor receptor 2 (TNFR2) knockout mice and to CD95 (Fas, Apo-1) deficient mutant lpr mice. Wild-type and TNFR2-deficient OT-I cells were activated and then deleted when transferred into RIP-mOVA mice, whereas CD95-deficient OT-I cells were not susceptible to deletion by cross-presentation. Furthermore, cross-presentation led to upregulation of the CD95 molecule on the surface of wild-type OT-I cells in vivo, consistent with the idea that this is linked to rendering autoreactive T cells susceptible to CD95-mediated signaling. This study represents the first evidence that CD95 is involved in the deletion of autoreactive CD8+ T cells in the whole animal.
Temporal Denoising of High Resolution Video (2009)

This thesis is concerned with the removal or reduction of noises in high resolution<br />video sequences. Many video denoising techniques have been published in the past<br />two decades) with or without motion compensation. They vary in a wide range of<br />complexity) performance, and implementation cost. Also) many existing video denoisers make simplistic assumptions on noise statistics and motion type, and hence<br />their performance depends on the validity of the assumed noise and motion models.<br />To improve the performance and robustness of existing methods) we propose a new<br />joint spatial-temporal video denoising algorithm that combines multihypothesis interframe motion compensation and directional intra-frame filtering. The algorithm takes into account general compound motions, including both global camera motion and<br />individual object motion(s). An affine motion model is used to characterize the global<br />camera movement, whereas a blockwise translational motion model is used to approximate local object motions. Quadtree data structure is used to organize and speed up the computations of block-based motion estimation. Quadtree-structured diamond search is conducted so that a large area can be examined in motion estimation at a low computational cost.<br />In order to achieve the best possible visual quality we augment motion-compensated<br />temporal interframe denoising operation by an intra-frame denoising operation of<br />adaptive directional filtering. The directional filter is designed for the local signal<br />waveform and noise level, and it has the advantage of effectively suppressing noises<br />without blurring edges.<br />The proposed video denoising algorithm is implemented and tested extensively on<br />high-resolution digital cinema contents. The experimental results demonstrate the<br />competitive advantages of the new algorithm in both visual quality and processing<br />throughput.
Folding and self-assembly of aromatic and aliphatic urea oligomers: Towards connecting structure and function (2010)

Folding and self-assembly of biomacromolecules has inspired the development of discrete, non-natural oligomers that fold and/or self-assemble in a controlled manner. Though aromatic and aliphatic oligoamides remain unmatched for structural diversity and synthetic versatility, oligomers based on amide bond surrogates, such as urea backbones, also demonstrated a propensity for folding and self-assembly. In this Perspective, we review the advances in the design of oligomeric aromatic and aliphatic urea sequences (essentially N,N'-linked) that fold and/or self-assemble. Whenever applicable, the relationship between structure and function will be highlighted.
High performance liquid chromatography as a tool in the definition of abnormalities in monoamine and tryptophan metabolites in cerebrospinal fluid from patients with neurological disorders (1991)

In this study we report the levels of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid, homovallinic acid, tryptophan, 5-hydroxyindole-3-acetic acid and serotonin in lumbar cerebrospinal fluid (CSF) from patients with multiple sclerosis, cerebrovascular disease and muscular tension headache the later, as healthy controls. The separation of these substances was performed on a reversed phase column by ion pair high performance liquid chromatography and detection was made by a glassy carbon electrode set at +900 mV vs Ag+/AgCl. The whole separation was achieved within 25 min. Concentrations of all substances (10-1000 pmole/L) were linearly proportional to areas obtained. The system is sensitive, stable and reproducible. The significance of CSF levels of these metabolites from patients groups compared with healthy controls are discussed.
Comparative Serial Virologic and Serologic Studies of Symptomatic and Subclinical Congenitally and Natally Acquired Cytomegalovirus Infections (1975)

Infants with congenitally (38) and natally (17) acquired cytomegalovirus infection were prospectively studied by means of virologic and multiple serologic assays. These infections were characterized by chronic viral excretion (measured in years). The quantity of virus excreted in the urine during early infancy was significantly greater in infants who acquired infection in utero, particularly amon those born with overt disease; thereafter, all three groups (congenital symptomatic, congenital asymptomatic, and natal) excreted similar amounts of virus. The patterns of antibody responses, particularly the fluorescent antibody response to the early antigen and the complement-fixing antibody response, further indicated that congenitally infected infants (especially symptomatic ones) bear a greater antigenic burden than do natally infected infants. From a diagnostic standpoint, the test for fluorescent antibody to the late antigen was the most sensitive assay, whereas the test for complement-fixing antibody proved to be the least useful, The indirect hemagglutination assay, although performed only in infants with natal infection, was only slightly less sensitive than the fluorescent antibody procedure; by the former technique, diagnostic rises were detected in all but one infant after the onset of viruria.
Water management and pricing in the urban areas of Rwanda : the case of Kigali city (2012)

In this paper, we study the current water pricing system practised in Kigali, Rwanda, and evaluate the potential for efficiency gains by moving to other alternatives. Notably, our numerical examples indicate that a change in the system for connection fees could make it easier for households to gain access to the piped water network, which should be beneficial both for household welfare and for health. Moreover, all households currently pay less than the cost recovery price for their water, suggesting that a change in the tariff block structure could lead to more efficient water use and improved funding for maintenance of the water network.
Therapy for Early COVID-19 (2020)

James M. Sanders, PhD, PharmD; Marguerite L. Monogue, PharmD; Tomasz Z. Jodlowski, PharmD; James B. Cutrell, MD
The dhp1+ gene, encoding a putative nuclear 5'->3' exoribonuclease, is required for proper chromosome segregation in fission yeast (2001)

The Schizosaccharomyces pombe dhp1(+) gene is an ortholog of the Saccharomyces cerevisiae RAT1 gene, which encodes a nuclear 5'-->3' exoribonuclease, and is essential for cell viability. To clarify the cellular functions of the nuclear 5'-->3' exoribonuclease, we isolated and characterized a temperature-sensitive mutant of dhp1 (dhp1-1 mutant). The dhp1-1 mutant showed nuclear accumulation of poly(A)(+) RNA at the restrictive temperature, as was already reported for the rat1 mutant. Interestingly, the dhp1-1 mutant exhibited aberrant chromosome segregation at the restrictive temperature. The dhp1-1 cells frequently contained condensed chromosomes, most of whose sister chromatids failed to separate during mitosis despite normal mitotic spindle elongation. Finally, chromosomes were displaced or unequally segregated. As similar mitotic defects were also observed in Dhp1p-depleted cells, we concluded that dhp1(+) is required for proper chromosome segregation as well as for poly(A)(+) RNA metabolism in fission yeast. Furthermore, we isolated a multicopy suppressor of the dhp1-1 mutant, referred to as din1(+). We found that the gene product of dhp1-1 was unstable at high temperatures, but that reduced levels of Dhp1-1p could be suppressed by overexpressing Din1p at the restrictive temperature. Thus, Din1p may physically interact with Dhp1p and stabilize Dhp1p and/or restore its activity.
Decellularized Dermal Grafting in Cleft Palate Repair (2003)

Decellularized dermal graft is safe and effective for use in primary closure of wide clefts involving the hard and soft palates. Its application to wide clefts otherwise at risk of fistula is justified. Its use in repair of an existing fistula is also promising.
Bone marrow angiogenesis and progression in multiple myeloma (1994)

Tumour growth is angiogenesis-dependent. We found a high correlation between the extent of bone marrow angiogenesis, evaluated as microvessel area, and the proliferating (S-phase) fraction of marrow plasma cells, evaluated as labelling index (LI), in patients with multiple myeloma (MM) and in those with monoclonal gammopathies of undetermined significance (MGUS). Angiogenesis itself was significantly associated with active as opposed to non-active MM and MGUS. The highest microvessel area accompanied rapidly progressive MM with the highest LI. When a cut-off value of 2% or greater of the microvessel area was used, most patients with active MM were classified correctly. The risk of active disease in patients with MM increased in parallel with the microvessel area. A causal relationship between plasma cell growth, activity phase in MM and marrow angiogenesis is suggested. Since angiogenesis proceeds in step with the enlargement of plasma cell tumours and the activity phase in MM, its measurement could be a useful prognostic marker in patients with plasma cell proliferative disorders.
Metabolism of Bile Salts in Mice Influences Spore Germination in Clostridium difficile (2010)

Clostridium difficile, a spore-forming bacterium, causes antibiotic-associated diarrhea. In order to produce toxins and cause disease, C. difficile spores must germinate and grow out as vegetative cells in the host. Although a few compounds capable of germinating C. difficile spores in vitro have been identified, the in vivo signal(s) to which the spores respond were not previously known. Examination of intestinal and cecal extracts from untreated and antibiotic-treated mice revealed that extracts from the antibiotic-treated mice can stimulate colony formation from spores to greater levels. Treatment of these extracts with cholestyramine, a bile salt binding resin, severely decreased the ability of the extracts to stimulate colony formation from spores. This result, along with the facts that the germination factor is small, heat-stable, and water-soluble, support the idea that bile salts stimulate germination of C. difficile spores in vivo. All extracts able to stimulate high level of colony formation from spores had a higher proportion of primary to secondary bile salts than extracts that could not. In addition, cecal flora from antibiotic-treated mice was less able to modify the germinant taurocholate relative to flora from untreated mice, indicating that the population of bile salt modifying bacteria differed between the two groups. Taken together, these data suggest that an in vivo-produced compound, likely bile salts, stimulates colony formation from C. difficile spores and that levels of this compound are influenced by the commensal gastrointestinal flora.
Oxidative damage and mitochondrial decay in aging. (1994)

We argue for the critical role of oxidative damage in causing the mitochondrial dysfunction of aging. Oxidants generated by mitochondria appear to be the major source of the oxidative lesions that accumulate with age. Several mitochondrial functions decline with age. The contributing factors include the intrinsic rate of proton leakage across the inner mitochondrial membrane (a correlate of oxidant formation), decreased membrane fluidity, and decreased levels and function of cardiolipin, which supports the function of many of the proteins of the inner mitochondrial membrane. Acetyl-L-carnitine, a high-energy mitochondrial substrate, appears to reverse many age-associated deficits in cellular function, in part by increasing cellular ATP production. Such evidence supports the suggestion that age-associated accumulation of mitochondrial deficits due to oxidative damage is likely to be a major contributor to cellular, tissue, and organismal aging.
The genetic basis of colony opacity in Streptococcus pneumoniae: evidence for the effect of box elements on the frequency of phenotypic variation (1995)

Streptococcus pneumoniae undergoes spontaneous phase variation in colony morphology. Differences in colony opacity have previously been shown to correlate with differences in the ability of organisms to colonize the mucosal surface of the nasopharynx in an animal model. The genetic basis of opacity variation was identified in transformation experiments. A DNA library, from a strain that varies at high frequency, was screened to identify a single clone capable of transforming a transparent recipient strain which varies at low frequency to an opaque phenotype. Analysis of this opacity locus revealed two genes, glpD and glpF, with similarity to genes required for glycerol metabolism in other bacteria. Following the pneumococcal glpF, repetitive intergenic elements, boxes A and C, were identified. These stem-loop-forming elements were not present in the same locus of the recipient strain. Although not required for phase variation in colony opacity, the box element was necessary for expression of phase variation at high frequency. Introduction of the box elements during transformation affected colony morphology, possibly by altering expression of a putative regulatory gene downstream from the box element. Mutagenesis within this region confirmed the contribution of the putative regulatory gene to the expression of colony opacity. Growth characteristics of strains generated in this study provide additional evidence for an association of differences in cell wall autolysis and variation in colony opacity.
Multicarrier modulation for data transmission: an idea whose time has come (1990)

The general technique of parallel transmission on many carriers, called multicarrier modulation (MCM), is explained. The performance that can be achieved on an undistorted channel and algorithms for achieving that performance are discussed. Ways of dealing with channel impairments and of improving the performance through coding are described, and implementation methods are considered. Duplex operation of MCM and the possible use of this on the general switched telephone network are examined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Escherichia coli Di-iron YtfE Protein Is Necessary for the Repair of Stress-damaged Iron-Sulfur Clusters (2007)

DNA microarray experiments showed that the expression of the Escherichia coli ytfE gene is highly increased upon exposure to nitric oxide. We also reported that deletion of ytfE significantly alters the phenotype of E. coli, generating a strain with enhanced susceptibility to nitrosative stress and defective in the activity of several iron-sulfur-containing proteins. In this work, it is shown that the E. coli ytfE confers protection against oxidative stress. Furthermore, we found that the damage of the [4Fe-4S](2+) clusters of aconitase B and fumarase A caused by exposure to hydrogen peroxide and nitric oxide stress occurs at higher rates in the absence of ytfE. The ytfE null mutation also abolished the recovery of aconitase and fumarase activities, which is observed in wild type E. coli once the stress is scavenged. Notably, upon the addition of purified holo-YtfE protein to the mutant cell extracts, the enzymatic activities of fumarase and aconitase are fully recovered and at rates similar to the wild type strain. We concluded that YtfE is critical for the repair of iron-sulfur clusters damaged by oxidative and nitrosative stress conditions.
Biotin and fluorescent labeling of RNA using T4 RNA ligase (1983)

Biotin, fluorescein, and tetramethylrhodamine derivatives of P1-(6-aminohex-1-yl)-P2-(5'-adenosine) pyrophosphate were synthesized and used as substrates with T4 RNA ligase. In the absence of ATP, the non-adenylyl portion of these substrates is transferred to the 3'-hydroxyl of an RNA acceptor to form a phosphodiester bond and the AMP portion is released. E. coli and D. melanogaster 5S RNA, yeast tRNAPhe, (Ap)3C, and (Ap)3A serve as acceptors with yields of products varying from 50 to 100%. Biotin-labeled oligonucleotides are bound selectively and quantitatively to avidin-agarose and may be eluted with 6 M guanidine hydrochloride, pH 2.5. Fluorescein and tetramethylrhodamine-labeled oligonucleotides are highly fluorescent and show no quenching due to attachment to the acceptor. The diverse structures of the appended groups and of the chain lengths and compositions of the acceptor RNAs show that T4 RNA ligase will be a useful modification reagent for the addition of various functional groups to the 3'-terminus of RNA molecules.
Adenoviral-mediated retinoblastoma 94 produces rapid telomere erosion, chromosomal crisis, and caspase-dependent apoptosis in bladder cancer and immortalized human urothelial cells but not in normal urothelial cells. (2003)

Retinoblastoma (RB)94, which lacks the NH(2)-terminal 112 amino acid residues of the full-length RB protein (RB110), is a more potent tumor and growth suppressor than RB110. In this study, Ad-RB94, but not Ad-RB110, produced marked growth inhibition, cytotoxicity, caspase-dependent apoptosis, and G(2)-M block in the human RB-negative, telomerase-positive bladder cancer cell line UM-UC14. This effect was completely inhibited by pretreatment with caspase inhibitors (P < 0.0001). Similar results were seen in RB-positive and other RB-negative bladder cancer cell lines. Ad-RB94 produced rapid telomere length shortening and loss of telomere signal, which was associated with polyploidy and chromosomal aberrations (P < 0.001). Ad-RB94, however, showed no cytotoxicity to telomerase-negative human normal urothelium cells but was highly cytotoxic to telomerase-positive human E6 and E7 immortalized urothelial cells (P < 0.0001). In addition, telomerase-negative cells, which maintain their telomere length through an alternative lengthening of telomeres DNA recombination pathway, showed no cytotoxicity to RB94. These results suggest that the induction of rapid telomere erosion and chromosomal crisis by RB94 in telomerase-positive cancer and in telomerase-expressing immortalized human cells is a major factor in its selective and potent tumor suppression and cytotoxic activity. The lack of cytotoxicity to normal cells should also provide a high therapeutic index when used in gene therapy protocols for the treatment of bladder and other cancers.
Alteration of Gene Expression Profile in Niemann-Pick Type C Mice Correlates with Tissue Damage and Oxidative Stress (2011)

In NPC mice, liver disease is characterized by an increase in fibrosis and in markers associated with oxidative stress. NPC is also correlated with altered gene expression, mainly of genes involved in oxidative stress and fibrosis. These findings correlate with similar parameters in cerebellum, as has been previously reported in the NPC mice model.
Enzymic Unwinding of DNA (1976)

Evidence from various sources in the literature suggests that, in connection with DNA, ATP dephosphorylation can be used to provide energy for mechanical effects. Starting from this concept we have studied a novel DNA-dependent ATPase purified to 90% homogeneity from Escherichia coli. The enzyme has a peptide weight near 180 000 and, in high salt, is a monomeric, probably highly anisometric molecule. In salt-free buffer, where the ATPase activity is highest, the enzyme forms aggregates. ATP is the preferred substrate (Km 0.27 mM) and dephosphorylated at the gamma-position at a maximal rate near 10(4) molecules per enzyme monomer per min at 35 degrees C. A requirement for divalent cation is best satisfied by Mg2+ or Ca2+ and the requirement for DNA best by the single-stranded, circular DNA of phages phiX174 (Km 62 nM nucleotide) and fd indicating that the enzyme recognizes internal DNA regions. When saturated with E. coli DNA unwinding protein phiX DNA is not accepted but, once in contact with the DNA, the enzyme is little inhibited by unwinding protein. Apparently the unwinding protein interferes preferentially with the recognition of DNA. The enzyme does not detectably cleave DNA, and for this and genetic reasons is not identical with the recBC ATPase or the K12 restriction ATPase of the extracted cells. The enzyme is probably not identical either with the dnaB-product-associated ATPase or the ATPase activity found in DNA polymerase III holoenzyme under appropriate conditions, and it is certainly not identical with a DNA-dependent ATPase of molecular weight 69 000 from E. coli which has recently been purified. Attempts to ascribe the enzyme to other genes, including recA, lex and rep, have failed.