gebhart/patrepeval huggingface dataset:
Positron emission tomography in Alzheimer's disease (1986)

Twenty-one patients with a clinical diagnosis of dementia of the Alzheimer's type (DAT) and 29 healthy, age-matched controls were studied using positron emission tomography (PET) and [18F]2-fluoro-2-deoxy-D-glucose to measure regional cerebral glucose consumption in the resting state. Reductions in ratio measures of relative metabolism in some parietal, temporal, and frontal regions were found in mild, moderate, and severe DAT groups. A significant increase in right/left metabolic asymmetry, particularly in parietal regions, also was seen in mild and moderate groups. Only in the severely demented patients was the absolute cerebral metabolic rate reduced significantly from control values. Fourteen patients had repeated PET studies, but only those patients with moderate to severe dementia showed a decline in IQ over 6 to 15 months. There were no significant changes in metabolic measures over time. PET is useful in quantifying regional cerebral dysfunction in DAT, even in the early stages of the disease.
Influenza Virus-Like Particles Containing M2 Induce Broadly Cross Protective Immunity (2011)

These results suggest that presenting M2 on VLPs in a membrane-anchored form is a promising approach for developing broadly cross protective influenza vaccines.
[Antioxidant therapeutic efficiency after the use of carnitine in infertile patients with bacterial or non bacterial prostato-vesiculo-epididymitis]. (2001)

These results indicate that in PVE patients antimicrobials and/or antiphlogistic drugs get a full positive antimicrobial response but a partial antioxidative response, which seems to be potentiated by the addition of antioxidative agents (Carnitines). Furthermore, it is important to underline that the antioxidative treatment with Carnitines administered in the meantime with antiinfectious agents is less effective, and finally this treatment is unsuccessful without the eradication of the pro-oxidant (germs and WBC) agents.
Sweet Pregnane Glycosides from Telosma procumbens. (2001)

An intensely sweet polyoxypregnane glycoside, telosmoside A15 (15), was isolated from an Asian Asclepiadaceae plant, Telosma procumbens, collected in Vietnam. This is the first time a sweet pregnane glycoside has been found, and its sweetness intensity is 1000 times greater than that of sucrose. From the same plant, 17 other new glycosides were isolated, having the same aglycone; they are named telosmosides A1-A14 (1-14) and A16-A18 (16-18). Some of these glycosides are also sweet, but others are tasteless or bitter. Chemical structures of the 18 glycosides were determined, and the structure-taste relationship was discussed.
Clinical significance of autoantibodies recognizing Sjögren's syndrome A (SSA), SSB, calpastatin and alpha-fodrin in primary Sjögren's syndrome (2007)

The aim of our study was (i) to compare the clinical and biological characteristics of 148 (137 women, 11 men) primary Sjögren's syndrome (pSS) patients at diagnosis as a function of their sex and (ii) to assess the prognostic value of anti-calpastatin and anti-alpha-fodrin autoantibodies. In addition, the presence of anti-nuclear antibodies (ANA), anti-52- and 60-kDa Sjögren's syndrome A (SSA), anti-Sjögren's syndrome B (SSB), anti-cyclic citrullinated peptide (CCP) antibodies and rheumatoid factors (RF) of IgA, IgG and IgM isotypes was sought in sera collected at pSS onset. Raynaud's syndrome, significantly more frequent in women, was the only systemic manifestation of pSS whose frequency differed significantly as a function of the patient's sex (P = 0.02). ANA (P = 0.001) and anti-60-kDa SSA autoantibodies (P = 0.03) were significantly more common in women, while men never synthesized detectable levels of anti-SSB, anti-calpastatin or IgG anti-alpha-fodrin autoantibodies. In addition, anti-CCP autoantibodies were found in low percentages of pSS patients (4% F/18% M). The absence of autoantibodies does not exclude the diagnosis of pSS in men that will be based mainly on the anatomopathological findings of a minor salivary gland biopsy. Positivity of anti-60-kDa SSA, anti-SSB, anti-calpastatin, IgA and IgG anti-alpha-fodrin antibodies is not associated with pSS clinical and biological severity.
Mouse Mutants Lacking the Type 2 IGF Receptor (IGF2R) Are Rescued from Perinatal Lethality inIgf2andIgf1rNull Backgrounds (1996)

The cation-dependent and cation-independent mannose 6-phosphate receptors (CD- and CI-MPRs) bind the phosphomannosyl recognition marker of lysosomal hydrolases, but in mammals the latter also interacts with insulin-like growth factor II (IGF-II). While IGF signaling is mediated by the type 1 IGF receptor (IGF1R), the type 2 receptor (IGF2R/CI-MPR) serves IGF-II turnover. Mouse mutants inheriting maternally a targeted disruption of the imprinted Igf2r gene, which is normally expressed only from the maternal allele, have increased serum and tissue levels of IGF-II and exhibit overgrowth (135% of normal birthweight) and generalized organomegaly, kinky tail, postaxial polydactyly, heart abnormalities, and edema. These mutants usually die perinatally, but a small minority can survive depending on genetic background and can occasionally reproduce, except for some females characterized by an imperforate vagina and hydrometrocolpos. Consistent with the hypothesis that lethality in the absence of IGF2R-mediated turnover is caused by excess of IGF-II overstimulating IGF1R, Igf2r mutants are completely rescued when they carry a second mutation eliminating either IGF-II or IGF1R. Normal embryonic development of the Igf1r/Igf2r double mutants, which differ from wild-type siblings only in the pattern of postnatal growth, appears to occur by signaling of IGF-II, being in excess, through a genetically identified unknown receptor, since triple mutants lacking IGF1R, IGF2R, and IGF-II are nonviable dwarfs (30% of normal size). In contrast with the Igf2r/Igf2 double mutants, mice lacking IGF2R/CI-MPR and CD-MPR survive in an IGF-II null background at a very low frequency and only for a few postnatal weeks, indicating that the mannose 6-phosphate-mediated lysosomal enzyme trafficking is essential for viability.
A non-line-of-sight error mitigation algorithm in location estimation (2003)

The location estimation of mobile telephones is of great current interest. The two sources of range measurement errors in geolocation techniques are measuring error and non-line-of-sight (NLOS) error. The NLOS errors, derived from the blocking of direct paths, have been considered as a killer issue in the location estimation. In this paper we develop an algorithm to mitigate the NLOS errors in location estimation when the range measurements corrupted by NLOS errors are not identifiable. This algorithm, referred to as the residual weighting algorithm (Rwgh), assumes that the number of range measurements is greater than the minimum number required. The Rwgh algorithm is compared with two other generic algorithms and tested under various scenarios and NLOS error models, which includes deterministic and random NLOS error models. In both cases, Rwgh has shown the effectiveness of NLOS error mitigation in location estimation.
Bringing low-level languages to the JVM: efficient execution of LLVM IR on Truffle (2016)

Although the Java platform has been used as a multi-language platform, most of the low-level languages (such as C, Fortran, and C++) cannot be executed efficiently on the JVM. We propose Sulong, a system that can execute LLVM-based languages on the JVM. By targeting LLVM IR, Sulong is able to execute C, Fortran, and other languages that can be compiled to LLVM IR. Sulong combines LLVM’s static optimizations with dynamic compilation to reach a peak performance that is near to the performance achievable with static compilers. For C benchmarks, Sulong’s peak runtime performance is on average 1.39× slower (0.79× to 2.45×) compared to the performance of executables compiled by Clang O3. For Fortran benchmarks, Sulong is 2.63× slower (1.43× to 4.96×) than the performance of executables compiled by GCC O3. This low overhead makes Sulong an alternative to Java’s native function interfaces. More importantly, it also allows other JVM language implementations to use Sulong for implementing their native interfaces.
Transfer and Expression of Immunoglobulin Genes (1984)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Enhancing the Specificity of Recombinase-Mediated Genome Engineering through Dimer Interface Redesign (2014)

Despite recent advances in genome engineering made possible by the emergence of site-specific endonucleases, there remains a need for tools capable of specifically delivering genetic payloads into the human genome. Hybrid recombinases based on activated catalytic domains derived from the resolvase/invertase family of serine recombinases fused to Cys2-His2 zinc-finger or TAL effector DNA-binding domains are a class of reagents capable of achieving this. The utility of these enzymes, however, has been constrained by their low overall targeting specificity, largely due to the formation of side-product homodimers capable of inducing off-target modifications. Here, we combine rational design and directed evolution to re-engineer the serine recombinase dimerization interface and generate a recombinase architecture that reduces formation of these undesirable homodimers by >500-fold. We show that these enhanced recombinases demonstrate substantially improved targeting specificity in mammalian cells and achieve rates of site-specific integration similar to those previously reported for site-specific nucleases. Additionally, we show that enhanced recombinases exhibit low toxicity and promote the delivery of the human coagulation factor IX and α-galactosidase genes into endogenous genomic loci with high specificity. These results provide a general means for improving hybrid recombinase specificity by protein engineering and illustrate the potential of these enzymes for basic research and therapeutic applications.
Role of the Omp25/Omp31 Family in Outer Membrane Properties and Virulence ofBrucella ovis (2007)

The genes coding for the five outer membrane proteins (OMPs) of the Omp25/Omp31 family expected to be located in the outer membrane (OM) of rough virulent Brucella ovis PA were inactivated to evaluate their role in virulence and OM properties. The OM properties of the mutant strains and of the mutants complemented with the corresponding wild-type genes were analyzed, in comparison with the parental strain and rough B. abortus RB51, in several tests: (i) binding of anti-Omp25 and anti-Omp31 monoclonal antibodies, (ii) autoagglutination of bacterial suspensions, and (iii) assessment of susceptibility to polymyxin B, sodium deoxycholate, hydrogen peroxide, and nonimmune ram serum. A tight balance of the members of the Omp25/Omp31 family was seen to be essential for the stability of the B. ovis OM, and important differences between the OMs of B. ovis PA and B. abortus RB51 rough strains were observed. Regarding virulence, the absence of Omp25d and Omp22 from the OM of B. ovis PA led to a drastic reduction in spleen colonization in mice. While the greater susceptibility of the Deltaomp22 mutant to nonimmune serum and its difficulty in surviving in the stationary phase might be on the basis of its dramatic attenuation, no defects in the OM able to explain the attenuation of the Deltaomp25d mutant were found, especially considering that the fully virulent Deltaomp25c mutant displayed more important OM defects. Accordingly, Omp25d, and perhaps Omp22, could be directly involved in the penetration and/or survival of B. ovis inside host cells. This aspect, together with the role of Omp25d and Omp22 in the virulence both of B. ovis in rams and of other Brucella species, should be thoroughly evaluated in future studies.
Preparation and Characterization of Soluble Recombinant Heterotrimeric Complexes of Human Lymphotoxins and (1996)

The lymphotoxin (LT) protein complex is a heteromer of alpha (LT-alpha, also called tumor necrosis factor (TNF)-beta) and beta (LT-beta) chains anchored to the membrane surface by the transmembrane domain of the LT-beta portion. Both proteins belong to the TNF family of ligands and receptors that regulate aspects of the immune and inflammatory systems. The LT complex is found on activated lymphocytes and binds to the lymphotoxin-beta receptor, which is generally present on nonlymphoid cells. The signaling function of this receptor-ligand pair is not precisely known but is believed to be involved in the development of the peripheral lymphoid organs. To analyze the properties of this complex, a soluble, biologically active form of the surface complex was desired. The LT-beta molecule was engineered into a secreted form and co-expressed with LT-alpha using baculovirus/insect cell technology. By exploiting receptor affinity columns, the LT-alpha3, LT-alpha2/beta1, and LT-alpha1/beta2 forms were purified. All three molecules were trimers, and their biochemical properties are described. The level of LT-alpha3-like components in the LT-alpha1/beta2 preparation was found to be 0.02% by following the activity of the preparation in a WEHI 164 cytotoxicity assay. LT-alpha3 with an asparagine 50 mutation (D50N) cannot bind the TNF receptors. Heteromeric LT complexes were prepared with this mutant LT- alpha form, allowing a precise delineation of the extent of biological activity mediated by the TNF receptors. A LT-alpha3 based cytotoxic activity was used to show that the LT-alpha1/beta2 form cannot readily scramble into a mixture of forms following various treatments and storage periods. This biochemical characterization of the LT heteromeric ligands and the demonstration of their stability provides a solid foundation for both biological studies and an analysis of the specificity of the LT-bet a and TNF receptors for the various LT forms.
ChemInform Abstract: Zn2(Zn1‐xFex)FeIII(PO4)3×2 H2O: Preparation, Crystal Structure and Moessbauer Investigation. (1991)

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.
Small CyclenImidazolium‐Containing Molecules and Their Interactions with DNA (2014)

Three small organic molecules containing different numbers of cyclen and imidazolium units were synthesized. Their interactions with plasmid DNA and their potential for gene delivery vectors were investigated. Agarose gel retardation and ethidium bromide exclusion assays revealed that these molecules can effectively condense DNA, and compounds with higher molecular weights are needed to lower w/w ratio for full condensation. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) indicated that these compounds may form nanosized spherical particles with DNA. Furthermore, the complex formed from 10, i.e., 10/DNA, can partially release DNA from compact state at a relatively higher concentration of NaCl (200 mM). In the presence of the lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 10 could transfer plasmid DNA into BEL-7402 cells. In addition, these compounds exhibited much lower cytotoxicity than PEI 25 kDa.
Axitinib (AG-013736), an Oral Specific VEGFR TKI, Shows Potential Therapeutic Utility Against Cholangiocarcinoma (2014)

Our results suggest that axitinib should be a promising therapy for vascular endothelial growth factor-expressing cholangiocarcinoma, irrespective of tumor origin and gemcitabine sensitivity.
Alternative-NHEJ Is a Mechanistically Distinct Pathway of Mammalian Chromosome Break Repair (2008)

Characterizing the functional overlap and mutagenic potential of different pathways of chromosomal double-strand break (DSB) repair is important to understand how mutations arise during cancer development and treatment. To this end, we have compared the role of individual factors in three different pathways of mammalian DSB repair: alternative-nonhomologous end joining (alt-NHEJ), single-strand annealing (SSA), and homology directed repair (HDR/GC). Considering early steps of repair, we found that the DSB end-processing factors KU and CtIP affect all three pathways similarly, in that repair is suppressed by KU and promoted by CtIP. In contrast, both KU and CtIP appear dispensable for the absolute level of total-NHEJ between two tandem I-SceI-induced DSBs. During later steps of repair, we find that while the annealing and processing factors RAD52 and ERCC1 are important to promote SSA, both HDR/GC and alt-NHEJ are significantly less dependent upon these factors. As well, while disruption of RAD51 causes a decrease in HDR/GC and an increase in SSA, inhibition of this factor did not affect alt-NHEJ. These results suggest that the regulation of DSB end-processing via KU/CtIP is a common step during alt-NHEJ, SSA, and HDR/GC. However, at later steps of repair, alt-NHEJ is a mechanistically distinct pathway of DSB repair, and thus may play a unique role in mutagenesis during cancer development and therapy.
Patterns of occult bleeding in asymptomatic colorectal cancer (1990)

The assumption that asymptomatic colorectal cancers bleed provides the rationale for widespread stool screening. The authors studied 12 patients with unoperated colorectal cancer but without colorectal symptoms and six healthy volunteers as laboratory controls. All stools were collected for 2 weeks and analyzed by the HemoQuant and Hemoccult tests. In controls, the mean HemoQuant value was 0.7 mg hemoglobin (Hb)/g stool (range, 0.1-1.8) and all stools were Hemoccult-negative. In cancer patients, the mean HemoQuant was 3.3 mg Hb/g (range, 0.3-13.2); stools were within the normal HemoQuant range (less than 2 mg Hb/g) in 38% and negative by Hemoccult in 70%. The mean cancer detection rate testing a single stool per patient was 57% for HemoQuant and 25% for Hemoccult (P less than 0.001). The detection rate rose testing multiple stools and was maximal with five stools at 83% for HemoQuant compared to 31% for Hemoccult (P less than 0.001). The authors conclude that fecal blood levels are commonly normal with asymptomatic colorectal cancer. Although higher with HemoQuant than Hemoccult, cancer detection rates by fecal blood testing appear to be lower than previously reported.
Allogeneic T cell responses are regulated by a specific miRNA-mRNA network (2013)

Donor T cells that respond to host alloantigens following allogeneic bone marrow transplantation (BMT) induce graft-versus-host (GVH) responses, but their molecular landscape is not well understood. MicroRNAs (miRNAs) regulate gene (mRNA) expression and fine-tune the molecular responses of T cells. We stimulated naive T cells with either allogeneic or nonspecific stimuli and used argonaute cross-linked immunoprecipitation (CLIP) with subsequent ChIP microarray analyses to profile miR responses and their direct mRNA targets. We identified a unique expression pattern of miRs and mRNAs following the allostimulation of T cells and a high correlation between the expression of the identified miRs and a reduction of their mRNA targets. miRs and mRNAs that were predicted to be differentially regulated in allogeneic T cells compared with nonspecifically stimulated T cells were validated in vitro. These analyses identified wings apart-like homolog (Wapal) and synaptojanin 1 (Synj1) as potential regulators of allogeneic T cell responses. The expression of these molecular targets in vivo was confirmed in MHC-mismatched experimental BMT. Targeted silencing of either Wapal or Synj1 prevented the development of GVH response, confirming a role for these regulators in allogeneic T cell responses. Thus, this genome-wide analysis of miRNA-mRNA interactions identifies previously unrecognized molecular regulators of T cell responses.
Design of Phosphorodiamidate Morpholino Oligomers (PMOs) for the Induction of Exon Skipping of the Human DMD Gene (2009)

Duchenne muscular dystrophy (DMD) is caused by out-of-frame mutations of the human DMD gene. Antisense oligonucleotides (AOs) have previously been used to skip additional exons that border the deletions such that the reading frame is restored and internally truncated, but functional, dystrophin expressed. We have designed phosphorodiamidate morpholino oligomer (PMO) AOs to various exons of the human dystrophin gene. PMOs were designed to have their target sites overlapping areas of open RNA structure, as defined by hybridization-array analysis, and likely exonic splicing enhancer (ESE)/silencer sites on the target RNA. The ability of each PMO to produce exon skipping was tested in vitro in normal human skeletal muscle cells. Retrospective analysis of design parameters used and PMO variables revealed that active PMOs were longer, bound to their targets more strongly, had their target sites closer to the acceptor splice site of the exon, overlapped areas of open conformation (as defined by the hybridization or the RNA secondary structure prediction software), and could interfere with the binding of certain SR proteins. No other parameter appeared to show significant association to PMO-skipping efficacy. No design tool is strong enough in isolation; however, if used in conjunction with other significant parameters it can aid AO design.
Amended structure of side chains in a cell wall mannan from Candida albicans serotype A strain grown in yeast extract-Sabouraud liquid medium under acidic conditions: detection of the branched side chains corresponding to antigenic factor 4 (1997)

In a previous study, we reported the excess production of α-1,3-linked mannose residues with the complete disappearance of β-1,2-linked mannose residues in cell wall mannans of Candida albicans serotype A strain cells, which were grown in yeast extract-Sabouraud liquid medium at pH 2.0. In the present study, we examined the immunochemical reactivity of the same mannan of NIH A-207 with an enzyme-linked immunosorbent assay (ELISA) using several antisera to antigenic factors of the genus Candida (FAbs) and the structure of the mannan by two-dimensional homonuclear Hartmann-Hahn analysis. The ELISA showed that the mannan reacts to FAb 4 but not to FAbs 13b and 34, which are reported to be antibody factors against linear side chains containing an α-1,3-linked mannose residue. In the Hartmann-Hahn analysis, we found two branched side chains, Manα1–2Manα1–3[Manα1–6]Manα1-(2Manα1-)22Man and Manα1–3[Manα1–6]Manα1-(2Manα1-)22Man, instead of the previously reported linear side chains. The branched side chains are oversynthesized under acidic conditions.