Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms of nonhomologous recombination in mammalian cells

The primary mechanism of nonhomologous recombination in transfected DNA involves breakage followed by end joining. To probe the joining step in more detail, linear simian virus 40 genomes with mismatched ends were transfected into cultured monkey cells, and individual viable recombinants were analyzed. The transfected genomes carried mismatched ends as a result of cleavage with two restriction enzymes, the recognition sites of which are located in the intron of the gene encoding the T antigen. Because the T antigen gene was split by this cleavage, the transfected genomes were inert until activated by cell-mediated end joining. Clonal descendants of the original recombinants were isolated from 122 plaques and were grouped into four classes based on the electrophoretic mobility of the junction fragment. The structures of representative junctions were determined by nucleotide sequencing. The spectrum of nonhomologous junctions analyzed here along with a large number of previously reported junctions suggest that there are two mechanisms for the linkage of DNA molecules: (i) direct ligation of ends and (ii) repair synthesis primed by terminal homologies of a few nucleotides. A paired-priming model of nonhomologous recombination is discussed.
Zentrum für Technomathematik Fachbereich 3 – Mathematik und Informatik Review of some results of well-posedness for models of thermo-elasto-plasticity with phase transitions in steel

This work deals with mathematical modeling of processes involved in the quenching process of steel. Some comprehensive models which integrate the complex behavior of steel materials in general models with phase transitions in steel for small deformations and deal with the modeling of the mathematical problem of linear thermo-elasto-plasticity, taking into account phase transitions and transformation-induced plasticity are described. The main objective is to give a short review on existence and uniqueness results for the corresponding mathematical problems. Kurzfassung Diese Arbeit befasst sich mit der mathematischen Modellierung von Abschreckprozessen bei Stahlbauteilen. Es werden einige Gesamtmodelle für kleine Deformationen diskutiert, welche das komplexe physikalische Materialverhalten von Stahl in allgemeinere Modelle der ThermoElasto-Plastizität integrieren und sich mit der Modellierung des mathematischen Problems der linearen Thermo-Elasto-Plastizität unter Berücksichtigung von Phasentransformationen und Umwandlungsplastizität befassen. Das Hauptziel ist es, einen kurzen Überblick über Existenzund Eindeutigkeitsresultate für die entsprechenden mathematische Probleme zu geben.
Three-dimensional analysis of macular diseases with a scanning retinal thickness analyzer and a confocal scanning laser ophthalmoscope.

OBJECTIVE To compare three-dimensional analysis of macular diseases obtained using the scanning retinal thickness analyzer (RTA) with that obtained using the confocal scanning laser ophthalmoscope, Heidelberg Retina Tomograph (HRT). PATIENTS AND METHODS Both the RTA and the HRT were used to examine 50 eyes of 36 patients with diabetic macular edema, macular edema following branch retinal vein occlusion, age-related macular degeneration, and idiopathic macular holes. RESULTS In most macular diseases, the retinal thickness map constructed using the RTA agreed with the image obtained with the HRT. The two maps were not consistent with each other, however, in patients with dense retinal hemorrhages and with extrafoveal fixation. CONCLUSIONS Although both the RTA and the HRT give additional information to clinically evaluate macular diseases, they do have limitations. The discrepancy between these two analyses in some specific macular pathologies might be caused by the different wavelengths of the laser beam and the different methodologies used to scan the retina.
Selection of human antibody fragments directed against tumor T‐cell epitopes for adoptive T‐cell therapy

Adoptive transfer of antigen‐specific T‐cells has shown therapeutic successes in the treatment of tumors in patients with metastatic melanoma. Tumor antigen‐specific T‐lymphocytes, however, occur only at low frequencies in a small proportion of patients. This low T‐lymphocyte frequency together with the difficulties associated with in vitro generation of T‐lymphocytes specific for cancers other than melanoma hampers adoptive T cell therapy. To make adoptive T‐cell therapy more uniformly applicable, strategies were developed at transferring tumor‐specificity to primary human T‐lymphocytes via antibody (Ig) or T‐cell receptor (TCR) molecules. We exploited the selection power of phage display that allows for the testing of tens of billions of individual clones with a high‐throughput selection of Fabs with peptide/MHC complex binding capacity. Following in vitro selection, human “TCR‐like” Fab fragments have been functionally expressed on human T‐lymphocytes, resulting in MHC‐restricted, tumor‐specific lysis and cytokine production. Currently, we have extended our selections to a panel of class I and II MHC‐restricted MAGE and other tumor‐specific epitopes, and would like to propose that phage display represents a technology able to expand T‐cell therapy to numerous tumor types. © 2008 International Society for Advancement of Cytometry
Small‐world network approach to identify key residues in protein–protein interaction

We show that protein complexes can be represented as small‐world networks, exhibiting a relatively small number of highly central amino‐acid residues occurring frequently at protein–protein interfaces. We further base our analysis on a set of different biological examples of protein–protein interactions with experimentally validated hot spots, and show that 83% of these predicted highly central residues, which are conserved in sequence alignments and nonexposed to the solvent in the protein complex, correspond to or are in direct contact with an experimentally annotated hot spot. The remaining 17% show a general tendency to be close to an annotated hot spot. On the other hand, although there is no available experimental information on their contribution to the binding free energy, detailed analysis of their properties shows that they are good candidates for being hot spots. Thus, highly central residues have a clear tendency to be located in regions that include hot spots. We also show that some of the central residues in the protein complex interfaces are central in the monomeric structures before dimerization and that possible information relating to hot spots of binding free energy could be obtained from the unbound structures. Proteins 2005. © 2004 Wiley‐Liss, Inc.
A LDO Regulator With Weighted Current Feedback Technique for 0.47 nF–10 nF Capacitive Load

A Weighted Current Feedback (WCF) technique for output capacitorless low-dropout (OCL-LDO) regulator is presented in this paper. Through feedback of a weighted current, the WCF permits smart management of the output impedance as well as the gain from the inter-gain stage. Based on the Routh-Hurwitz stability criterion, the WCF can avoid the right-half plane (RHP) pole and push the left-half plane (LHP) non-dominant complex pole pair to a higher frequency. Besides, it provides good regulator loop gain and fast transient response. Validated by UMC 65 nm CMOS process, the simulation and measurement results have shown that the WCF LDO regulator can operate at a load capacitance (CL) range from 470 pF to 10 nF with only 3.8 pF compensation capacitor. At a supply of 0.75 V and a quiescent current of 15.9 μA, the proposed circuit can support a maximum load current (IL) of 50 mA. When IL switches from 0 to 50 mA in 100 ns, the output can settle within 400 ns for the whole CL range. For a case of single capacitor (CL 470 pF), the settling time is only 250 ns. The comparison results have shown that the WCF LDO regulator offers a comparable or better transient figure-of-merit (FOM) and additional merit to drive wide load capacitance range.
Different eigenproblem models for field line resonances in cold plasma : Effect on magnetospheric density estimates

Magnetospheric plasma density can be remotely sensed through ground-based magnetometer data using a suitable model for field line resonances (FLRs) formed by standing shear Alfvén wave on closed geomagnetic field lines. The simplest type of FLR model, which is also the most relevant for magnetometer data inversion purposes, is based on solving a certain eigenvalue problem. Over the years a number of such models have been developed [Singer, H.J., Southwood, D.J., Walker, R.J., Kivelson, M.G. , 1981. Alfvén wave resonances in a realistic magnetospheric magnetic field geometry. J. Geophys. Res. 86, 4589–4596; Rankin, R. , Fenrich, F. , Tikhonchuk, V.T. , 2000. Shear Alfvén waves on stretched magnetic field lines near midnight in Earth’s magnetosphere. Geophys. Res. Lett. 27, 3265–3268; Rankin, R. , Kabin, K. , Marchand, R. , 2006. Alfvénic field line resonances in arbitrary magnetic field topology. Adv. Space Res. 38, 1720–1729]. In this paper we summarize the properties of these models and investigate the effect of using these different models on the magnetospheric density inferred from the ground-based magnetometer measurements. We also formulate a simple criterion which can be used to determine which one of these models should be used for a particular field line. r 2006 Elsevier Ltd. All rights reserved. PACS: 94.30. Ms; 94.30. Ch
Efficacy and Safety of Direct-acting Antivirals in Hepatitis C Virus-infected Patients Taking Proton Pump Inhibitors

Abstract Background and Aims: Direct-acting antiviral (DAA) therapy is the cornerstone of the treatment of chronic hepatitis C virus (HCV) infection. Eradication of HCV, predicted by the attainment of a sustained virologic response (SVR) 12 weeks following DAA therapy, is the goal of this treatment. Interestingly, recent studies have reported the possible association between HCV-infected patients with DAA therapy concomitant use of proton pump inhibitors (PPIs) and lower odds of achieving SVR. This meta-analysis was conducted to summarize all available data and to estimate this potential association. Methods: Comprehensive literature review was conducted by first searching the Medline and Embase databases through March 2017 to identify all studies that investigated the safety and efficacy of DAAs in patients with HCV infection taking PPIs versus those without PPIs. Adjusted point estimates from each study were combined by the generic inverse variance method of DerSimonian and Laird. Results: Nine cohort studies with 32,684 participants met the eligibility criteria and were included in the meta-analysis. The use of PPIs concomitant with DAAs among HCV-infected patients was associated with lower odds of achieving SVR compared with non-PPI users (pooled odds ratio (OR): 0.74, 95% confidence interval (CI): 0.63–0.88, I2 = 24%). Subgroup analysis addressed the association between PPIs use and SVR12 demonstrated the association of PPI users showing lower odds of achieving SVR12 compared with those with no use of PPIs (pooled OR: 0.68, 95% CI: 0.51–0.9, I2 = 33%). Conclusions: This study demonstrated a significantly increased risk of failure to achieve SVR in HCV-infected patients taking DAA with PPIs compared to non-PPI users. Providers should consider whether PPI therapy is indicated for patients and withdraw of PPI therapy in the absence of indications, especially while on DAA therapy.
Objective measures of sleep duration and continuity in major depressive disorder with comorbid hypersomnolence: a primary investigation with contiguous systematic review and meta‐analysis

Hypersomnolence plays an important role in the presentation, treatment and course of mood disorders. However, there has been relatively little research that examines objective measures of sleep duration and continuity in patients with depression and hypersomnolence, despite the use of these factors in sleep medicine nosological systems. This study compared total sleep time and efficiency measured by naturalistic actigraphic recordings followed by ad libitum polysomnography (PSG; without prescribed wake time) in 22 patients with major depressive disorder and co‐occurring hypersomnolence against age‐ and sex‐matched healthy sleeper controls. The major depressive disorder and co‐occurring hypersomnolence group demonstrated significantly longer sleep duration compared with healthy sleeper controls quantified by sleep diaries, actigraphy and ad libitum PSG. No between‐group differences in sleep efficiency (SE), latency to sleep or wake after sleep onset were observed when assessed using objective measures. To further contextualize these findings within the broader scientific literature, a systematic review was performed to identify other comparable investigations. A meta‐analysis of pooled data demonstrated patients with mood disorders and co‐occurring hypersomnolence have significantly greater sleep duration and similar SE compared with healthy controls when assessed using ad libitum PSG. These results suggest current sleep medicine nosology that distinguishes hypersomnia associated with psychiatric disorders primarily as a construct characterized by low SE and increased time in bed may not be accurate. Future studies that establish the biological bases hypersomnolence in mood disorders, as well as clarify the accuracy of nosological thresholds to define excessive sleep duration, are needed to refine the diagnosis and treatment of these disorders.
Human Macrophage Regulation Via Interaction With Cardiac Adipose Tissue-Derived Mesenchymal Stromal Cells

Background: Mesenchymal stromal cells (MSCs) improve tissue repair but their mechanism of action is not fully understood. We aimed to test the hypothesis that MSCs may act via macrophages, and that specifically, human cardiac adipose tissue-derived mesenchymal stromal cells (AT-MSCs) can polarize human macrophages into a reparative, anti-inflammatory (M2) phenotype. Methods and Results: We isolated and grew AT-MSCs from human cardiac adipose tissue obtained during cardiac surgery. Macrophages were grown from CD14+ monocytes from healthy donor blood and then cocultured with AT-MSCs, with and without transwell membrane, for 1 to 14 days. In response to AT-MSCs, macrophages acquired a star-shaped morphology, typical of alternatively activated phenotype (M2), and increased the expression of M2 markers CD206+, CD163+, and CD16+ by 1.5- and 9-fold. Significantly, AT-MSCs modified macrophage cytokine secretion and increased the secretion of anti-inflammatory and angiogenic cytokines: interleukin (IL)-10 (9-fold) and vascular endothelial growth factors (3-fold). Moreover, AT-MSCs decreased macrophage secretion of inflammatory cytokines such as IL-1α (2-fold), tumor necrosis factor α (1.5-fold), IL-17 (3-fold), and interferon gamma (2-fold). Remarkably, the interaction between AT-MSCs and macrophages was bidirectional and macrophages enhanced AT-MSC secretion of typical M2 inducers IL-4 and IL-13. Notably, AT-MSCs decreased macrophage phagocytic capacity. Finally, IL-6 mediates the M2 polarization effect of AT-MSCs on macrophages, by increasing M2-associated cytokines, IL-10 and IL-13. Conclusions: Human cardiac AT-MSCs can polarize human macrophages into anti-inflammatory phenotype. Our findings suggest a new mechanism of action of AT-MSCs that could be relevant to the pathogenesis and treatment of myocardial infarction, atherosclerosis, and various cardiovascular diseases.
Surrogate light chain is required for central and peripheral B‐cell tolerance and inhibits anti‐DNA antibody production by marginal zone B cells

Selection of the primary antibody repertoire takes place in pro‐/pre‐B cells, and subsequently in immature and transitional B cells. At the first checkpoint, μ heavy (μH) chains assemble with surrogate light (SL) chain into a precursor B‐cell receptor. In mice lacking SL chain, μH chain selection is impaired, and serum autoantibody levels are elevated. However, whether the development of autoantibody‐producing cells is due to an inability of the resultant B‐cell receptors to induce central and/or peripheral B‐cell tolerance or other factors is unknown. Here, we show that receptor editing is defective, and that a higher proportion of BM immature B cells are prone to undergoing apoptosis. Furthermore, transitional B cells are also more prone to undergoing apoptosis, with a stronger selection pressure to enter the follicular B‐cell pool. Those that enter the marginal zone (MZ) B‐cell pool escape selection and survive, possibly due to the B‐lymphopenia and elevated levels of B‐cell activating factor. Moreover, the MZ B cells are responsible for the elevated IgM anti‐dsDNA antibody levels detected in these mice. Thus, the SL chain is required for central and peripheral B‐cell tolerance and inhibits anti‐DNA antibody production by MZ B cells.
Urinary polyphenols, glutathione S‐transferases copy number variation, and breast cancer risk: Results from the Shanghai women's health study

In vitro studies have found that flavanol epigallocatechin (EGC) and flavonols, but not flavanol epicatechin (EC), activate glutathione S‐transferases (GSTs), a family of phase II enzymes that detoxify reactive oxygen species, such as catechol estrogen metabolites. This study was designed to investigate prospectively whether urinary excretion of tea polyphenols interacts with GST polymorphisms to influence breast cancer risk. We conducted a study of 352 incident breast cancer cases and 701 individually matched controls nested within the Shanghai Women's Health Study cohort of women aged 40–70 yr at baseline. Liquid chromatography tandem mass spectrometry was used to measure urinary excretion of flavanols and flavonols. Real‐time multiplex PCR was used to quantify the copy number variation in the GSTM1 and GSTT1 genes. Urinary excretion of flavonols and flavanols, particularly EGC (P = 0.02), was significantly higher among women null for GSTM1 than those positive for GSTM1. Flavonols and flavanols (EGC in particular) were associated with a reduced risk of breast cancer among those null for GSTM1 and GSTT1, with a P‐value of 0.04 for the interaction between EGC and GSTM1 polymorphism. In contrast, among women possessing both GSTM1 and GSTT1, breast cancer risk increased with levels of flavonols, particularly kaempferol. The differential associations between polyphenols and breast cancer risk by GST polymorphisms, if confirmed, may provide a new avenue for the personalized prevention of breast cancer. Mol. Carcinog. © 2011 Wiley Periodicals, Inc.
Consequences of Bullying in Schools

For the most part, studies of the consequences of bullying in schools have concentrated upon health outcomes for children persistently bullied by their peers. Conclusions have been influenced by how bullying has been conceptualized and assessed, the specific health outcomes investigated, and the research method and data analysis employed. Results from cross-sectional surveys suggest that being victimized by peers is significantly related to comparatively low levels of psychological well-being and social adjustment and to high levels of psychological distress and adverse physical health symptoms. Retrospective reports and studies suggest that peer victimization may contribute to later difficulties with health and well-being. Longitudinal studies provide stronger support for the view that peer victimization is a significant causal factor in schoolchildren's lowered health and well-being and that the effects can be long-lasting. Further evidence from longitudinal studies indicates that the tendency to bully others at school significantly predicts subsequent antisocial and violent behaviour.
A glycoprotein antigen detected with new monoclonal antibodies on the surface of human lymphocytes infected with human T‐cell leukemia virus type‐I (HTLV‐I)

We have prepared two new mouse monoclonal antibodies (MAbs) named TARM‐34 (IgM) and TAG‐34 (IgG I), that react with surface antigens of lines of human lymphocytes bearing a human T‐cell leukemia virus type‐I (HTLV‐I.) The characters of these antibodies are compared with those of anti‐HTLV‐I gp21 MAb (TA‐21, IgGI), anti‐HTLV‐I p19 MAb (GIN‐14, IgGI) and human antibodies from patients with adult T‐cell leukemia (ATL). An indirect membrane immunofluorescence assay showed that TARM‐34, TAG‐34 and TA‐21 all reacted specifically with cell‐surface antigens of HTLV‐I‐positive T‐ and B‐cell lines and cultured peripheral blood lymphocytes from HTLV‐I‐infected adults, Radioimmunoassay showed that serum antibodies from the ATL patients interfered with the binding of TA‐21 antibody to cells of the HTLV‐I‐positive T‐cell line MT‐2, but not with the bindings of TARM‐34 and TAG‐34 antibodies. TARM‐34 and TAG34 both precipitated a 34‐kd glycoprotein (gP34), while TA‐21 precipitated gp21 from a lysate of 3Hmine‐labelled MT‐2 cells. TARM.34 and TAG‐34 also precipitated the 34‐kd protein from Iysates of MT‐2 and HUT 102 cells labelled with 125l‐ or 35S‐cysteine. Interestingly, TARM‐34 and TAG‐34 also precipitated 35‐kd protein from a lysate of other HTLV‐I‐positive cells (F‐Taj cell line) derived from an ATL patient. TA21 precipitated the 21‐kd protein from the Iysates of 35S‐cysteine‐labelled HTLV‐IMT‐2 virions, but TARM‐34 and TAG‐34 did not precipitate any protein from this lysate. TARM‐34 lysed HTLV‐I‐bearing cells in the presence of rabbit complement. These results indicate that TARM‐34 and TAG‐34 both recognize a glycoprotein antigen that is expressed on the surface of HTLVI‐infected cells.
Human E2F5 gene is oncogenic in primary rodent cells and is amplified in human breast tumors

E2F transcription factors (E2F1 to 6) are central players in the control of animal cell proliferation as regulators of genes involved in cell cycle progression and in transformation. In this report, we have investigated the potential involvement of the E2F5 gene in tumorigenesis. We show that E2F5 can promote the formation of morphologically transformed foci in primary baby rat kidney cells (BRK) when it is overexpressed in the presence of its heterodimeric partner DP1 and activated RAS. This suggests that E2F5 behaves like a MYC‐type cooperating oncogene in functional assays, prompting us to monitor potential amplifications of the E2F5 gene in primary human tumors. We mapped the human E2F5 gene to 8q21.1–21.3 equidistant from the MOS (8q12) and MYC (8q24) oncogenes. Since the long arm of chromosome 8 is frequently the site of increased gene copy number (ICN) in breast cancer, we screened 442 breast tumor DNAs for gains of E2F5, MOS, and MYC genes. The three genes showed ICN, albeit at variable incidence and levels of amplification, with the ICN of E2F5 occurring concomitantly with those of MOS and/or MYC in almost half of the cases. Moreover, a marked increase of the 2.5‐kb E2F5 transcript was also detected in some tumors and tumor cell lines. In conclusion, the evidence that sustained unregulated expression of E2F5 can cooperate with other oncogenes to promote cell transformation in functional assays, together with the detection of chromosomal amplifications and overexpressions of the E2F5 gene in breast tumors, provides the first indications that E2F5 deregulation may have a role in human tumor development. Genes Chromosomes Cancer 28:126–130, 2000. © 2000 Wiley‐Liss, Inc.