gebhart/patrepeval huggingface dataset:
Evaluation of Risks Related to the Use of Adeno-Associated Virus-Based Vectors (2003)

Recombinant AAV efficacy has been demonstrated in numerous gene therapy preclinical studies. As this vector is increasingly applied to human clinical trials, it is a priority to evaluate the risks of its use for workers involved in research and clinical trials as well as for the patients and their descendants. At high multiplicity of infection, wild-type AAV integrates into human chromosome 19 in approximately 60% of latently infected cell lines. However, it has been recently demonstrated that only approximately 1 out of 1000 infectious units can integrate. The mechanism of this site-specific integration involves AAV Rep proteins which are absent in vectors. Accordingly, recombinant AAV (rAAV) do not integrate site-specifically. Random integration of vector sequences has been demonstrated in established cell lines but only in some cases and at low frequency in primary cultures and in vivo. In contrast, episomal concatemers predominate.Therefore, the risks of insertional mutagenesis and activation of oncogenes are considered low. Biodistribution studies in non-human primates after intramuscular, intrabronchial, hepatic artery and subretinal administration showed low and transient levels of vector DNA in body fluids and distal organs. Analysis of patients body fluids revealed rAAV sequences in urine, saliva and serum at short-term. Transient shedding into the semen has been observed after delivery to the hepatic artery. However, motile germ cells seemed refractory to rAAV infection even when directly exposed to the viral particles, suggesting that the risk of insertion of new genetic material into the germ line is absent or extremely low. Risks related to viral capsid-induced inflammation also seem to be absent since immune response is restricted to generation of antibodies. In contrast, transgene products can elicit both cellular and humoral immune responses, depending on the nature of the expressed protein and of the route of vector administration. Finally, a correlation between early abortion as well as male infertility and the presence of wt AAV DNA in the genital tract has been suggested. Although no causal relationship has been established, this issue stresses the importance of using rAAV stocks devoid of contaminating replication-competent AAV. This review comprehensively examines virus integration, biodistribution, immune interactions, and other safety concerns regarding the wild-type AAV and recombinant AAV vectors.
Monoclonal antibody against a Burkitt lymphoma-associated antigen. (1981)

A monoclonal antibody, referred to as 38.13, was obtained by fusing murine myeloma cells with Lewis rat splenocytes sensitized with Daudi cells (human Burkitt lymphoma containing Epstein--Barr virus genome but lacking HLA-A, -B, and -C and beta 2-microglobulin molecules at the cell surface). 38.13 antibody was demonstrated to be a rat IgM. By complement-dependent microcytotoxicity and indirect immunofluorescence assays, 38.13 antibody was shown to react specifically with cells derived from Burkitt tumors, including both Epstein--Barr virus genome-carrying and Epstein--Barr virus-negative Burkitt lymphoma. By contrast, Epstein--Barr virus-containing lymphoblastoid cell lines derived from normal B lymphocytes were not recognized by 38.13 antibody. Fresh malignant cells from patients affected with various lymphoproliferative disorders were negative, except 4/8 having abdominal Burkitt-like lymphomas. Normal lymphocytes from peripheral blood, spleen, lymph node, tonsil, and bone marrow and mitogen (phytohemagglutinin, pokeweed mitogen, and concanavalin A)-activated blasts were also negative. Thus, 38.13 antibody apparently recognized a Burkitt-associated antigen that is not related to Epstein--Barr virus. The pattern of reactivity of 38.13 antibody with various Burkitt lymphoma cells appeared quite heterogenous and some Burkitt cells were consistently negative. 38.13 antibody thus defines a subset of Burkitt lymphomas.
Mycoplasma spermatophilum, a New Species Isolated from Human Spermatozoa and Cervix (1991)

A mycoplasma isolated from human spermatozoa and a human cervix was shown to be serologically distinct from 98 previously recognized Mycoplasma and Acholeplasma spp. Six mycoplasma colonies were cloned and examined in detail for morphology, growth, and biochemical characteristics; five of these were from sperm samples and one was from a cervix. These strains were closely related and had the following properties: guanine-plus-cytosine content of 32 mol%, requirement for sterol, and anaerobic growth. Glucose was not metabolized, and arginine and urea were not hydrolyzed. Strain AH159 (= NCTC 11720) is the type strain of a new species, Mycoplasma spermatophilum.
Rapid genotyping of single nucleotide polymorphisms using novel minor groove binding DNA oligonucleotides (MGB probes) (2002)

Novel fluorescent oligonucleotides that contain a 3' minor groove binding group (MGB) hybridize to single-stranded targets with increased sequence-specificity compared to ordinary DNA probes. This reduces non-specific probe hybridization and results in low background fluorescence during the 5' nuclease PCR assay (TaqMan, Applied Biosystems, Foster City, CA). We developed a method for closed-tube genotyping using two allele-specific MGB probes labeled with different fluorophores in one reaction. After PCR, tubes were transported to a fluorescence plate-reader for analysis of fluorescence. Common spreadsheet software was used for automated genotype assignment. As an example, DNA samples from 172 hemochromatosis patients were selected and tested for molecular defects in the HFE gene, i.e., mutations in codon 63 and 282. Tight genotype clusters were observed for both codons and results with MGB probes were identical to conventional genotyping (PCR + restriction-fragment-length-polymorphism). We show that this fast and easy method can be used for large-scale (high-throughput) genetic studies but also for routine molecular diagnostics without post-PCR manipulation of amplicons or the need for real-time quantitative PCR machines. Hum Mutat 19:554-559, 2002.
A study of dogs with kennel cough (1978)

A detailed study of a population of dogs with kennel cough was undertaken. Twenty-seven (77 per cent) of a total of 35 dogs had pathological evidence of respiratory disease in the form of tracheobronchitis with, in some animals, exudative pneumonia. A variety of viral and bacterial agents were isolated from the respiratory tract of diseased dogs but Bordetella bronchiseptica and canine parainfluenza virus SV-5 appeared to be the most significant organisms recovered.
Purification and characterization of a new xylanase (APX-II) from the fungus Aureobasidium pullulans Y-2311-1 (1993)

Aureobasidium pullulans Y-2311-1 produced four major xylanases (EC 3.2.1.8) with pI values of 4.0, 7.3, 7.9, and 9.4 as revealed by isoelectric focusing and zymogram analysis when grown for 4 days on 1.0% oat spelt xylan. The enzyme with a pI of 9.4 was purified by ammonium sulfate precipitation, chromatography on a DEAE-Sephadex A-50 column, and gel filtration with a Sephadex G-75 column. The enzyme had a mass of about 25 kDa as determined by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration chromatography. The purified enzyme had a Km of 7.6 mg . ml(-1) and Vmax of 2,650 micromol . min(-1) . mg(-1) for birchwood xylan at 28 degrees C and pH 4.5. It lacked activity towards carboxymethylcellulose, cellobiose, starch, mannan, p-nitrophenyl (pNP)-beta-D-xylopyranoside, pNP-beta-D-glucopyranoside, pNP-alpha-D-glucopyranoside, pNP-beta-D-cellobioside, pNP-beta-D-fucopyranoside, or pNP-alpha-D-galactopyranoside. The predominant end products of birchwood xylan or xylohexaose hydrolysis were xylobiose and xylose. The enzyme had the highest activity of pH 4.8 and 54 degrees C. Sixty percent of the activity remained after the enzyme had been incubated at 55 degrees C and pH 4.5 for 30 min. The sequence of the first 68 amino acid residues at the amino terminus showed homology to those of several other xylonases. Immunoblot analysis with antiserum raised against the purified xylanase revealed that two immunologically related polypeptides of 25 and 22 kDa were produced in A. pullulans cultures containing oat spelt xylan or xylose as carbon sources but not in cultures containing glycerol or glucose.
Effects of IL-3 gene expression on tumor response to irradiation in vitro and in vivo. (1997)

Expression of a murine interleukin 3 gene in murine fibrosarcoma cells (FSA-JmIL-3) did not alter their survival after in vitro irradiation. However, FSA-JmIL-3 tumors established in vivo were much more sensitive to irradiation than was the parental tumor. Following 25 Gy of irradiation, parental fibrosarcoma tumors regrew after a growth delay of 10 days, but FSA-JmIL-3 tumors continued to regress. Examination of the cellular composition of tumors following irradiation revealed that, instead of tumor cell repopulation, the FSA-JmIL-3 tumors became heavily infiltrated with lymphocytes, indicating that the effect of irradiation was to allow the IL-3-elicited cellular immune response to infiltrate the tumors and mediate rejection. This study indicates that combining gene immunotherapy approaches with radiotherapy might increase the effectiveness of both, and it seems logical to pursue such treatment options.
Nuclear microenvironments modulate transcription from low-affinity enhancers (2017)

Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, low-affinity interactions can drive efficient transcription. Here, we report that the transcription factor Ultrabithorax (Ubx) utilizes low-affinity binding sites in the <i>Drosophila melanogaster shavenbaby</i> (<i>svb</i>) locus and related enhancers in nuclear microenvironments of high Ubx concentrations. Related enhancers colocalize to the same microenvironments independently of their chromosomal location, suggesting that microenvironments are highly differentiated transcription domains. Manipulating the affinity of <i>svb</i> enhancers revealed an inverse relationship between enhancer affinity and Ubx concentration required for transcriptional activation. The Ubx cofactor, Homothorax (Hth), was co-enriched with Ubx near enhancers that require Hth, even though Ubx and Hth did not co-localize throughout the nucleus. Thus, microenvironments of high local transcription factor and cofactor concentrations could help low-affinity sites overcome their kinetic inefficiency. Mechanisms that generate these microenvironments could be a general feature of eukaryotic transcriptional regulation.
Hyaluronan‐based polymer scaffold modulates the expression of inflammatory and degradative factors in mesenchymal stem cells: Involvement of Cd44 and Cd54 (2005)

Hyaluronan (HA), in the bone marrow stroma, is the major non-protein glycosaminoglycan component of extracellular matrix (ECM) involved in cell positioning, proliferation, differentiation as well as in receptor-mediated changes in gene expression. Repair of bone and regeneration of bone marrow is dependent on ECM, inflammatory factors, like chemokines and degradative factors, like metalloproteinases. We analyzed the interaction between human mesenchymal stem cells (h-MSCs) and a three-dimensional (3-D) HA-based scaffold in vitro. The expression of CXC chemokines/receptors, CXCL8 (IL-8)/CXCR1-2, CXCL10 (IP-10)/CXCR3, CXCL12 (SDF-1)/CXCR4, and CXCL13 (BCA-1)/CXCR5, and metalloproteinases/inhibitors MMP-1, MMP-3, MMP-13/TIMP-1 were evaluated in h-MSCs grown on plastic or on HA-based scaffold by Real-time PCR, ELISA, and immunocytochemical techniques. Moreover, the expression of two HA receptors, CD44 and CD54, was analyzed. We found both at mRNA and protein levels that HA-based scaffold induced the expression of CXCR4, CXCL13, and MMP-3 and downmodulated the expression of CXCL12, CXCR5, MMP-13, and TIMP-1 while HA-based scaffold induced CD54 expression but not CD44. We found that these two HA receptors were directly involved in the modulation of CXCL12, CXCL13, and CXCR5. This study demonstrates a direct action of a 3-D HA-based scaffold, widely used for cartilage and bone repair, in modulating both h-MSCs inflammatory and degradative factors directly involved in the engraftment of specific cell types in a damaged area. Our data clearly demonstrate that HA in this 3-D conformation acts as a signaling molecule for h-MSCs.
Effect of teriparatide on bone mineral density and fracture in postmenopausal osteoporosis: meta-analysis of randomised controlled trials (2012)

To determine the efficacy of teriparatide supplementation for improving bone mineral density (BMD) and fracture risk in postmenopausal osteoporosis and if effects vary with factors. We identified eight randomised controlled trials (n = 2388) using electronic databases, supplemented by a hand-search of the reference lists. All trials aimed to evaluate the efficacy of daily subcutaneous teriparatide injection in postmenopausal osteoporosis. The main outcomes were fracture risk and percentage change of BMD from baseline. Data were pooled by employing a random-effect model. In trials that reported BMD as an outcome, treatment was associated with an increase of bone mass of 8.14% [95% confidence interval (CI): 6.72-9.55%; eight trials, n = 2206] in spine and 2.48% (95% CI: 1.67-3.29%; seven trials, n = 1303) at the hip. In trials that reported fracture as an outcome, treatment was associated with a 70% risk reduction in vertebral fractures (risk ratio 0.30, 95% CI: 0.21-0.44; three trials, n = 1452) and 38% risk reduction in non-vertebral fractures (risk ratio 0.62, 95% CI: 0.44-0.87; three trials, n = 1842). The PTH treatment with total calcium intake more than 1500 mg was related to a significant increase in BMD gains at total hip (1.40% vs. 3.72%; p = 0.004). However, long-term duration did not appear to contribute to differences in responsiveness to teriparatide. Evidence supports the use of teriparatide in treatment of women with postmenopausal osteoporosis who are at risk for fracture. Further studies directly comparing concurrent therapy and calcium supplement with long-term duration are warranted.
Synthesis of Bilayer-Coated Nanogels by Selective Cross-Linking of Monomers inside Liposomes (2006)

In this study, bilayer-coated polyacrylamide hydrogel nanoparticles were prepared by photoinitiated polymerization of acrylamide (AA) and bis(acrylamide) (BA) in the inner compartment of liposomes. The liposomes were formed in AA/BA solutions from lipid/Triton X-100 (TX100) mixed micelles by adsorption of TX100 to Bio-Beads SM2 and were studied by dynamic light scattering and transmission electron microscopy. The hydrodynamic diameters of the liposomes were ∼100 nm with low polydispersity. Addition of ascorbic acid before photopolymerization prevented macroscopic hydrogel formation by inhibition of free-radical polymerization of nonencapsulated monomers. Bare nanogel particles were finally obtained by removal of the lipid bilayer. As opposed to the commonly used dilution method, this convenient and versatile method of nanogel synthesis will allow incorporation of membrane proteins in the bilayer and the use of monomers that readily pass the lipid membrane.
A Two-Coordinate Nickel Imido Complex That Effects C−H Amination (2010)

An exceptionally low coordinate nickel imido complex, (IPr*)Ni═N(dmp) (2) (dmp = 2,6-dimesitylphenyl), has been prepared by the elimination of N2 from a bulky aryl azide in its reaction with (IPr*)Ni(η6-C7H8) (1). The solid-state structure of 2 features two-coordinate nickel with a linear C−Ni−N core and a short Ni−N distance, both indicative of multiple-bond character. Computational studies using density functional theory showed a Ni═N bond dominated by Ni(dπ)−N(pπ) interactions, resulting in two nearly degenerate singly occupied molecular orbitals (SOMOs) that are Ni−N π* in character. Reaction of 2 with CO resulted in nitrene-group transfer to form (dmp)NCO and (IPr*)Ni(CO)3 (3). Net C−H insertion was observed in the reaction of 2 with ethene, forming the vinylamine (dmp)NH(CH═CH2) (5) via an azanickelacyclobutane intermediate, (IPr*)Ni{N,C:κ2-N(dmp)CH2CH2} (4).
Modeling of direct wafer bonding: Effect of wafer bow and etch patterns (2002)

Direct wafer bonding is an important technology for the manufacture of silicon-on-insulator substrates and microelectromechanical systems. As devices become more complex and require the bonding of multiple patterned wafers, there is a need to understand the mechanics of the bonding process. A general bonding criterion based on the competition between the strain energy accumulated in the wafers and the surface energy that is dissipated as the bond front advances is developed. The bonding criterion is used to examine the case of bonding bowed wafers. An analytical expression for the strain energy accumulation rate, which is the quantity that controls bonding, and the final curvature of a bonded stack is developed. It is demonstrated that the thickness of the wafers plays a large role and bonding success is independent of wafer diameter. The analytical results are verified through a finite element model and a general method for implementing the bonding criterion numerically is presented. The bonding criterion developed permits the effect of etched features to be assessed. Shallow etched patterns are shown to make bonding more difficult, while it is demonstrated that deep etched features can facilitate bonding. Model results and their process design implications are discussed in detail.
Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value (2010)

Mutations in the TET2 gene are frequent in myeloid disease, although their biologic and prognostic significance remains unclear. We analyzed 355 patients with myelodysplastic syndromes using "next-generation" sequencing for TET2 aberrations, 91 of whom were also subjected to single-nucleotide polymorphism 6.0 array karyotyping. Seventy-one TET2 mutations, with a relative mutation abundance (RMA) ≥ 10%, were identified in 39 of 320 (12%) myelodysplastic syndrome and 16 of 35 (46%) chronic myelomonocytic leukemia patients (P < .001). Interestingly, 4 patients had multiple mutations likely to exist as independent clones or on alternate alleles, suggestive of clonal evolution. "Deeper" sequencing of 96 patient samples identified 4 additional mutations (RMA, 3%-6.3%). Importantly, TET2 mutant clones were also found in T cells, in addition to CD34(+) and total bone marrow cells (23.5%, 38.5%, and 43% RMA, respectively). Only 20% of the TET2-mutated patients showed loss of heterozygosity at the TET2 locus. There was no difference in the frequency of genome-wide aberrations, TET2 expression, or the JAK2V617F 46/1 haplotype between TET2-mutated and nonmutated patients. There was no significant prognostic association between TET2 mutations and World Health Organization subtypes, International Prognostic Scoring System score, cytogenetic status, or transformation to acute myeloid leukemia. On multivariate analysis, age (> 50 years) was associated with a higher incidence of TET2 mutation (P = .02).
Stretched cavity soliton in dispersion-managed Kerr resonators (2015)

Stretched cavity soliton (SCS) in dispersion-managed nonlinear resonators is numerically investigated. SCS is found to stretch and compress twice during a round-trip propagation inside the dispersion-managed resonator, exhibiting a pulse dynamics similar to dispersion-managed mode-locked femtosecond lasers. Even though the breathing ratio is relatively small, the characteristics of SCS are significantly modified by the pulse stretching dynamics in the resonator. The output pulse will have a flatter spectrum around the center frequency. However, the power for the comb lines at the wing of the spectrum decays faster than the conventional sech-shaped CS, making dispersion wave emission harder to be excited in dispersion-managed resonators. Furthermore, stretching of the pulse lowers the nonlinear phase shift and makes it more resistant towards breather soliton instability. When shortening the cavity length to the microresonator scale, we find that ultrashort pulses can be generated through dispersion management, even in a low $Q$-factor cavity.
An experimental model for studying the effect of anisotropy on percolative conduction (1980)

We present preliminary measurements of the electrical conductivity of a composite made of small conducting rods in an insulating matrix. It constitutes a model material for studying the effect of anisotropy on percolation as a function of particle length to diameter ratio. We can interpret our results, especially the lowering of threshold respective to isotropic systems, by means of a geometrical argument when the ratio is high as in our experiments.
Degradation of Relaxin Family Peptides by Insulin‐Degrading Enzyme (2009)

Insulin-degrading enzyme (IDE) is a ubiquitously expressed metalloproteinase responsible for the intracellular degradation of insulin. IDE also interacts with other members of the insulin superfamily, including relaxin, but no studies have been reported regarding the interaction of other relaxin-like peptides with IDE. In this study, we determined that relaxin, relaxin-3, and InsL3 all competitively inhibited the degradation of insulin by IDE to different degrees, and all inhibited covalent cross-linking of insulin to IDE. Each of the peptides was degraded by IDE to various degrees (insulin > relaxin > InsL3 = relaxin-3). In summary, relaxin, InsL3, and relaxin-3 all bound to IDE, competed for the binding and degradation of insulin, and were all substrates for the proteolytic activity of IDE. Therefore, it is possible that in addition to insulin, IDE may be important for the cellular proteolysis of relaxin, InsL3, and relaxin-3.
Divergent Nitric Oxide Bioavailability in Men and Women With Sickle Cell Disease (2003)

NO bioavailability and NO responsiveness are greater in women than in men with sickle cell disease and determines adhesion molecule expression. Endothelium-dependent blood flows are largely non-NO mediated in male patients. These results provide a possible mechanism for reported sex differences in sickle cell disease morbidity and mortality and provide a basis for novel pharmacological interventions.
Complement Activation by Bisretinoid Constituents of RPE Lipofuscin (2009)

The authors suggest that bisretinoid pigments of retinal pigment epithelial lipofuscin, subsequent to photoactivation and cleavage, serve to activate complement. Complement activation by this mechanism is dependent on the alternative pathway and can be modulated by an inhibitor of C3 cleavage. These events in the setting of complement dysregulation could contribute to the chronic inflammation that underlies AMD pathogenesis.
A one transistor cell on bulk substrate (1T-Bulk) for low-cost and high density eDRAM (2004)

A 1T cell for high-density eDRAM has been successfully developed on bulk silicon substrate for the first time. The device architecture is fully compatible with CMOS logic process integration, allowing very low chip cost for SoC applications. Experimental results show a retention time over 1s at 25/spl deg/C and 100ms at 85/spl deg/C, which is compatible with eDRAM requirements. Non-destructive readout is experimentally demonstrated at 85/spl deg/C. The integration of the memory cell in a matrix arrangement is evaluated. Gate and drain disturb are characterized, showing enough disturb margins for memory operations.