gebhart/patrepeval huggingface dataset:
Cross‐protection in mice infected with influenza A virus by the respiratory route is correlated with local IgA antibody rather than serum antibody or cytotoxic T cell reactivity (1984)

Mice previously infected with an aerosol of A/Rec 31 influenza virus were strongly protected against an aerosol challenge with A/Vic influenza as judged by lung virus titers recovered 2 days after the challenge infection. Such complete homotypic immunity was not achieved by priming with live Rec 31 virus injected i.v. or UV-inactivated Rec 31 virus administered s.c. together with Al(OH)3 and saponin. The reason for the superior protective effect of the natural infection was investigated. The protection induced by respiratory infection with Rec 31 virus was specific for influenza A viruses. It was not correlated with specific serum hemagglutination inhibition antibody titer or cross-reactive cytotoxic T (Tc) cell reactivity. Moreover, the transfer of splenic and lymphoid T cell populations with strong secondary Tc activity did not significantly reduce lung virus titers in recipient mice 3 days after infection. The protection however occurred in parallel with the presence of cross-reactive IgA antibody in the lung washings. It thus appears that local secretory IgA plays a causal role in the prevention of cross-infection by influenza A virus. Serum antibody and Tc cells, on the other hand, may be crucial for recovery from such infection. All mice primed with live Rec 31 virus, administered i.v. or by aerosol and expressing equally high levels of Tc reactivity, survived a lethal challenge with A/PR8 virus. The same challenge, however, killed half of the mice immunized s.c. with inactivated Rec 31 virus which induced only a low level of Tc reactivity.
Genetic variation in DNMT3B and increased global DNA methylation is associated with suicide attempts in psychiatric patients (2012)

Recently, a significant epigenetic component in the pathology of suicide has been realized. Here we investigate candidate functional SNPs in epigenetic-regulatory genes, DNMT1 and DNMT3B, for association with suicide attempt (SA) among patients with co-existing psychiatric illness. In addition, global DNA methylation levels [5-methyl cytosine (5-mC%)] between SA and psychiatric controls were quantified using the Methylflash Methylated DNA Quantification Kit. DNA was obtained from blood of 79 suicide attempters and 80 non-attempters, assessed for DSM-IV Axis I disorders. Functional SNPs were selected for each gene (DNMT1; n = 7, DNMT3B; n = 10), and genotyped. A SNP (rs2424932) residing in the 3' UTR of the DNMT3B gene was associated with SA compared with a non-attempter control group (P = 0.001; Chi-squared test, Bonferroni adjusted P value = 0.02). Moreover, haplotype analysis identified a DNMT3B haplotype which differed between cases and controls, however this association did not hold after Bonferroni correction (P = 0.01, Bonferroni adjusted P value = 0.56). Global methylation analysis showed that psychiatric patients with a history of SA had significantly higher levels of global DNA methylation compared with controls (P = 0.018, Student's t-test). In conclusion, this is the first report investigating polymorphisms in DNMT genes and global DNA methylation quantification in SA risk. Preliminary findings suggest that allelic variability in DNMT3B may be relevant to the underlying diathesis for suicidal acts and our findings support the hypothesis that aberrant DNA methylation profiles may contribute to the biology of suicidal acts. Thus, analysis of global DNA hypermethylation in blood may represent a biomarker for increased SA risk in psychiatric patients.
Muscle-specific calpain, p94, is degraded by autolysis immediately after translation, resulting in disappearance from muscle (1993)

We previously identified a third type of the calpain large subunit named p94 as a cDNA whose mRNA is expressed exclusively in skeletal muscle at levels approximately 10-fold more abundant than those of the conventional calpain subunit. Rat skeletal muscle fractions were screened by two anti-peptide antibodies raised against two specific sequences in p94, but the p94 protein could not be found. To examine this apparent discrepancy between the amounts of mRNA and protein, wild-type p94 was expressed in COS cells. Although p94 mRNA was expressed normally in COS cells, only very small amounts of the protein and its presumed degradation products were detected by the antibodies described above. A series of COOH-terminal deletion mutants was constructed and expressed in COS cells and L8 cells, a rat myoblast cell line. When IS2, one of the specific regions of p94, was completely eliminated, the truncated p94 proteins were expressed normally, and the amount of the expressed proteins was at least 100-fold higher than with wild-type p94. Moreover, when site-directed mutagenesis was introduced to change the presumed active-site cysteine of p94 to serine or alanine, the mutated p94 proteins were highly expressed like the IS2-deleted mutants. These results indicate the following. 1) The mRNA for p94 is normally transcribed in COS, L8, and muscle cells; 2) the p94 protein becomes active in the cytosol immediately after translation; 3) the p94 protein virtually disappears from cells by autocatalytic degradation; and 4) the p94-specific IS2 region plays an important role in this degradation. In vitro translation experiments support this idea. Furthermore, p94 shows nuclear localization when expressed in COS cells. The physiological function of p94 in muscle is discussed on the basis of the analysis of these transfectants.
Biopharmaceutical Properties of Uricase Conjugated to Neutral and Amphiphilic Polymers (1999)

A comparative pharmacokinetic and biodistribution investigation of polymer-protein conjugates prepared with various amphiphilic polymers was carried out using uricase as a model. Four polymer-uricase derivatives have been obtained by covalent binding of a similar number of polymer chains of (a) linear poly(ethylene glycol) (Mw 5000 Da); (b) branched poly(ethylene glycol) (Mw 10 000 Da); (c) poly(N-vinylpyrrolidone) (Mw 6000 Da); (d) poly(N-acryloilmorpholine) (Mw 6000 Da). By intravenous administration to Balb/c mice, the conjugates displayed different pharmacokinetic and organ distribution behaviors. (1) The unmodified enzyme and the poly(N-vinylpyrrolidone) conjugate were the enzyme forms with the shortest and the longest permanence in blood respectively (mean residence time 45 and 4378 min). (2) Native uricase was found to localize soon after administration significantly in heart, lungs, and liver from where it was also rapidly cleared. (3) The poly(N-acryloilmorpholine) derivative showed the highest concentration levels in liver (up to 25.5% of the dose) and considerable accumulation took also place in the other considered organs. (4) Poly(N-vinylpyrrolidone)-uricase displayed a relevant tropism for liver but low uptake indexes were found for the other organs. (5) The branched poly(ethylene glycol) derivative accumulated preferentially in liver and spleen. (6) The linear poly(ethylene glycol) conjugate was, among the various uricase forms, the species with the lowest distribution levels in all the examined organs. (7) Finally, all the enzyme forms slowly disposed in kidneys with higher levels for the poly(N-acryloilmorpholine) derivative (15% after 2880 min) and unmodified uricase (14% after 1440 min).
Opioid-induced androgen deficiency (2006)

Purpose of review Opioid-induced androgen deficiency has become one of the most common causes of testosterone deficiency among men in many communities. Its increase parallels the large increase in opioid use. This form of hypogonadotrophic hypogonadism is present in most men chronically consuming sustained-action opioids, including those receiving methadone for heroin addiction and those consuming opioids for control of either malignant or non-malignant chronic pain. A similar, but less well defined illness occurs in women. Opioid-induced androgen deficiency is not widely recognized. This review examines its pathophysiology, some of its signs and symptoms, and indicates some areas where current observations suggest additional investigations would be fruitful. Recent findings Recognition of opioid-induced androgen deficiency in men not receiving methadone for heroin addiction is a new observation, and in these men contributes to fatigue, depression, vasomotor phenomena, anemia, diminished libido, erectile dysfunction and osteoporosis. These signs and symptoms improved during testosterone replacement therapy in several small non-placebo-controlled trials. Summary A large majority of men consuming sustained-action opioids have symptomatic androgen deficiency which apparently responds to replacement therapy. Opioid-induced androgen deficiency is frequently overlooked, with its symptoms attributed to underlying disease states including malignant disease, chronic back disorders, HIV disease, and psychosocial illnesses contributing to opioid habituation.
Praziquantel-induced tegumental damage in vitro is diminished in schistosomes derived from praziquantel-resistant infections (2001)

The aggressive use of praziquantel to combat schistosomiasis in Egpyt raises concern about the possible emergence of resistance. Eggs from Egyptian patients with praziquantel-resistant infections (not cured by 3 doses of praziquantel) have been used to establish infection-specific schistosome isolates in mice. The response of these worms to the drug was observed in vitro, in order to determine if the isolates obtained from these resistant infections were, in fact, less responsive to praziquantel. One of the hallmark effects of praziquantel on schistosomes in vitro is a disruption of the worm's outer surface, the tegument. Here, praziquantel-induced tegumental damage is observed in 3 distinct isolates, 2 derived from resistant infections and 1 from an infection cured by a single dose. The isolates from the resistant infections were less susceptible to praziquantel-induced tegumental damage in vitro, suggesting that the worms are in some way less responsive to the drug.
Relative defect radioactivity and perceived defect severity are proportional with flurpiridaz F18 PET myocardial perfusion imaging (2011)

1115 Objectives To identify the minimum rest dose for flurpiridaz F18 PET, it is necessary to find the minimum perfusion-related change in relative myocardial radioactivity (RMR) that would alter a reader’s perceived segmental score, which could be used to find the maximum tolerable count-related inhomogeneity. To find the minimum perceived defect change, a comparison was made between reader scores from a blinded read and the corresponding normalized segmental radioactivity concentration. Methods 20 pts, enrolled in BMS747158-201 at two centers and selected for reversible defects on SPECT, were studied with the Siemens Biograph TrueV (same-day, 2 mCi rest/6 mCi stress flurpiridaz F18, 7-10min acq time). Rest and stress images prepared and presented using QPS (CSMC) were read by 3 blinded readers using a linear black and white, with optional “cool”, scale. Using a 17-segment model, readers’ scores by segment from rest data only were compared with the corresponding mean segmental %decreases in RMR from global maximum (GM) calculated by QPS. Values were plotted and a linear regression calculated separately for each reader. Results Despite a marked range in RMR %decrease at each reader score (%SD ~20% GM), the data was well modeled resulting in R2 values of 1.0, 0.98 and 0.98 for readers 1, 2 and 3 respectively. The intercept values were 84%, 82% and 85% respectively while the slopes were -14%, -10% and -8.5% respectively. Based on a mean slope of -11%, it was estimated that a 50% probability of a change of 1 in reader score corresponded to a localized change in RMR of 5.4%. Conclusions Even with a 2mCi dose, it was possible to find a simple and consistent model for reader perception of intra-image defect severity that allows identification of the maximum tolerable count-related inhomogeneity and, ultimately, minimum injected dose
Differential signal transduction via T-cell receptor CD3 zeta 2, CD3 zeta-eta, and CD3 eta 2 isoforms. (1991)

The T-cell antigen receptor (TCR) consists of an antigen-binding heterodimer, termed Ti, which is noncovalently associated with the invariant CD3 subunits (gamma, delta, epsilon, zeta, and eta). The CD3 zeta and -eta subunits form either homodimeric or heterodimeric structures in turn associated with the other components of the TCR complex. This feature increases the structural complexity of TCRs by creating "isoforms." Both CD3 zeta and -eta are thought to play an important role in signal transduction triggered by antigen/major histocompatibility complex. To compare signaling functions of TCR isoforms, MA5.8, a CD3 zeta-eta- variant of the cytochrome c-specific, I-Ek-restricted T-cell hybridoma 2B4.11, was stably transfected with cDNAs encoding CD3 zeta and/or CD3 eta, and resulting clones were characterized. The findings indicate that signals inducing Ca2+ mobilization, phosphatidylinositol turnover, and interleukin 2 production are each transmitted by the above TCR isoforms. In contrast, tyrosine phosphorylation of the CD3 zeta subunit but not the CD3 eta subunit follows TCR stimulation. Given the general importance of tyrosine phosphorylation for receptor signaling, it is likely that this difference between TCR isoforms plays a regulatory role in T-lineage function by qualitatively or quantitatively altering signaling events.
Interaction of 5-aza-2'-deoxycytidine with amsacrine or 1,25-dihydroxyvitamin D3 on HL-60 myeloid leukemic cells and inhibitors of cytidine deaminase. (1993)

5-aza-2'-deoxycytidine (5-Aza-CdR) is an experimental anti-leukemic agent that can induce the differentiation of myeloid leukemic cells and is currently under investigation in clinical trials in patients with leukemia. The objective of this study was to investigate the in vitro interaction of 5-Aza-CdR with different agents which may increase its clinical efficacy. Since 5-Aza-CdR has been used in combination with amsacrine in patients with relapsed leukemia, we have investigated the in vitro antileukemic activity of these agents in combination on human HL-60 myeloid leukemic cells. For a 24-hour drug exposure, we observed that the interaction of 5-Aza-CdR with amsacrine was subadditive to was synergistic with respect to the loss of clonogenicity of the HL-60 leukemic cells as demonstrated by a colony assay. We have also investigated the interaction of 5-Aza-CdR with 1,25-dihydroxyvitamin D3, an agent that can induce in vitro differentiation of myeloid leukemic cells. The combination of 5-Aza-CdR with 1,25-dihydroxyvitamin D3 produced a synergistic reduction in the clonogenicity of the HL-60 leukemic cells. These results indicate that 5-Aza-CdR can interact synergistically with both cytotoxic agents and agents that induce differentiation, and can provide some rationale for clinical investigations on these combinations in patients with acute leukemia. We have also explored other approaches to increase the clinical effectiveness of 5-Aza-CdR by investigating the in vitro effect of different inhibitors of human cytidine deaminase, the enzyme responsible for the rapid in vivo inactivation of this analogue.
Roles of IL-4 and IL-12 in the development of lupus in NZB/W F1 mice (1997)

Development of either Th1 or Th2 cell subsets has profound immunologic consequences, either pathogenic or protective, in several autoimmune diseases. However, it remains unclear which subset of Th cells plays a more critical role in lupus. In this study, we examined IL-4 and IL-12, which play decisive roles in the development of Th2 and Th1, respectively, in the IgG autoantibody production and development of lupus nephritis in NZB/W (B/W) F1 mice. Transfer of either IL-4- or IL-12-stimulated splenocytes from 5-mo-old B/W F1 mice into B/W F1 mice of the same age enhanced the production of IgG anti-dsDNA Ab. Consistently, administration of mAb against either IL-4 or IL-12 before the onset of lupus could inhibit the production of IgG anti-dsDNA Ab. However, only anti-IL-4 mAb was effective in preventing the onset of lupus nephritis. This discrepancy appeared to be explained by the differential effect on the production of IgG3-type autoantibody and TNF production. Interestingly, when combined, anti-IL-12 mAb abrogated the beneficial effect of anti-IL-4 mAb. These results indicate that both Th2 and Th1 contribute to the IgG autoantibody production, and IL-4 and IL-12 play key roles in the complexity of cytokine regulation in the pathogenesis of autoimmunity in lupus, but the former is more critical.
Inactivation of CMP- N -acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution (2002)

Humans are genetically deficient in the common mammalian sialic acid N-glycolylneuraminic acid (Neu5Gc) because of an Alu-mediated inactivating mutation of the gene encoding the enzyme CMP-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase (CMAH). This mutation occurred after our last common ancestor with bonobos and chimpanzees, and before the origin of present-day humans. Here, we take multiple approaches to estimate the timing of this mutation in relationship to human evolutionary history. First, we have developed a method to extract and identify sialic acids from bones and bony fossils. Two Neanderthal fossils studied had clearly detectable Neu5Ac but no Neu5Gc, indicating that the CMAH mutation predated the common ancestor of humans and the Neanderthal, approximately 0.5-0.6 million years ago (mya). Second, we date the insertion event of the inactivating human-specific sahAluY element that replaced the ancestral AluSq element found adjacent to exon 6 of the CMAH gene in the chimpanzee genome. Assuming Alu source genes based on a phylogenetic tree of human-specific Alu elements, we estimate the sahAluY insertion time at approximately 2.7 mya. Third, we apply molecular clock analysis to chimpanzee and other great ape CMAH genes and the corresponding human pseudogene to estimate an inactivation time of approximately 2.8 mya. Taken together, these studies indicate that the CMAH gene was inactivated shortly before the time when brain expansion began in humankind's ancestry, approximately 2.1-2.2 mya. In this regard, it is of interest that although Neu5Gc is the major sialic acid in most organs of the chimpanzee, its expression is selectively down-regulated in the brain, for as yet unknown reasons.
Stability of broad host range cloning vectors in the phototrophic bacterium Rhodospirillum rubrum (1992)

The suitability of the broad-host range vectors pRK290, pVK100 and pLAFRI respectively for use with the photosynthetic purple non-sulphur bacterium, Rhodospirillum rubrum has been examined. All vectors are RK2 (RP4) derivatives (incompatibility group P-1) and contain the mob region of RK2. The three vectors could each be transferred from Escherichia coli by triparental mating in the presence of a second E. coli donor containing the helper plasmid pRK2013. The conjugation frequency was approx. 10−1 in all cases. Selection of transconjugants was performed in the presence of tetracycline (pRK290, pLAFRI, pVK100) or kanamycin (pVK100). Southern-blotting experiments after many generations showed no rearrangements to have occurred. In the absence of antibiotic selection all three vectors were maintained for at least 15 generations under aerobic chemotrophic conditions but were rapidly lost when the culture was grown phototrophically (anaerobic).
Garnet-Type Li7La3Zr2O12Solid Electrolyte Thin Films Grown by CO2-Laser Assisted CVD for All-Solid-State Batteries (2016)

The detailed characterization of garnet-type Li-ion conducting Li₇La₃Zr₂O₁₂ (LLZO) solid electrolyte thin films grown by novel CO₂-laser assisted chemical vapor deposition (LA-CVD) is reported. A deposition process parameter study reveals that an optimal combination of deposition temperature and oxygen partial pressure is essential to obtain high quality tetragonal LLZO thin films. The polycrystalline tetragonal LLZO films grown on platinum have a dense and homogeneous microstructure and are free of cracks. A total lithium ion conductivity of 4.2·10⁻⁶ S·cm⁻¹ at room temperature, with an activation energy of 0.50 eV, is achieved. This is the highest total lithium ion conductivity value reported for tetragonal LLZO thin films so far, being about one order of magnitude higher than previously reported values for tetragonal LLZO thin films prepared by sputtering and pulsed laser deposition. The results of this study suggest that the tetragonal LLZO thin films grown by LA-CVD are applicable for the use in all-solid-state thin film lithium ion batteries.
Imaging &#946;-Amyloid Plaques and Neurofibrillary Tangles in the Aging Human Brain (2004)

The development of radioligands to image beta-amyloid (A beta) plaques and neurofibrillary tangles (NFTs) in vivo in the aging human brain is an important and active area of radiopharmaceutical design. When used in combination with positron emission tomography (Pet) or single photon emission computed tomography (spect), amyloid-imaging tracers could facilitate the evaluation of the efficacy of anti-amyloid therapies currently under intense development by many major pharmaceutical companies throughout the world. Amyloid-imaging agents could also serve as surrogate markers in early diagnosis and neuropathogenesis studies of Alzheimer's disease and other aging-related neurodegenerative disorders. In this review article, the design and biological evaluation of amyloid-imaging agents are discussed. The structures of these agents vary from large proteins and peptides such as radiolabeled A beta peptides and monoclonal antibodies to small molecules derived from Congo red, Chrysamine-G, thioflavin-T, and Acridine Orange. In vitro studies indicate that amyloid plaques contain multiple binding sites that can accommodate structurally diverse compounds, providing flexibility for radiopharmaceutical design of amyloid imaging agents. Compared to large biomolecules, small molecule radiotracers are often readily accessible through chemical synthesis and can display superior brain permeability. Several small molecule amyloid-imaging radioligands display high binding affinities to A beta and sufficient brain penetration for imaging studies. Recent studies demonstrate the feasibility of imaging amyloid plaques in vivo in human subjects with PET. Imaging NFTs, separately or in concert with A beta plaques, is not as far advanced as imaging A beta plaques and remains to be fully characterized and demonstrated.
Content-based retrieval and real time detection from video sequences acquired by surveillance systems (2002)

A surveillance system devoted to detect abandoned objects in unattended environments is presented; image processing content based retrieval capabilities have been added to make the inspection task of operators easier. Video based surveillance systems generally employ one or more cameras connected to a set of monitors. This kind of system needs the presence of a human operator, who interprets the acquired information and controls the evolution of the events in a surveyed environment. During the last years, efforts have been made to develop systems supporting human operators in their surveillance task, in order to focus the attention of operators when unusual situations are detected. Image sequence databases are also managed by the proposed surveillance system in order to provide operators with the possibility of retrieving in a second time the interesting sequences that may contain useful information for discovering causes of an alarm. Experimental results are shown in terms of the probability of correct detection of abandoned objects and examples concerning retrieval sequences.