gebhart/patrepeval huggingface dataset:
Diversity in the serine recombinases (2002)

Most site-specific recombinases fall into one of two families, based on evolutionary and mechanistic relatedness. These are the tyrosine recombinases or lambda integrase family and the serine recombinases or resolvase/invertase family. The tyrosine recombinases are structurally diverse and functionally versatile and include integrases, resolvases, invertases and transposases. Recent studies have revealed that the serine recombinase family is equally versatile and members have a variety of structural forms. The archetypal resolvase/invertases are highly regulated, only affect resolution or inversion and they have an N-terminal catalytic domain and a C-terminal DNA binding domain. Phage-encoded serine recombinases (e.g. phiC31 integrase) cause integration and excision with strictly controlled directionality, and have an N-terminal catalytic domain but much longer C-terminal domains compared with the resolvase/invertases. This high molecular weight group also contains transposases (e.g. TnpX from Tn4451). Other transposases, which belong to a third structurally different group, are similar in size to the resolvase/invertases but have the DNA binding domain N-terminal to the catalytic domain (e.g. IS607 transposase). These three structural groups represented by the resolvase/invertases, the large serine recombinases and relatives of IS607 transposase correlate with three major groupings seen in a phylogeny of the catalytic domains. These observations indicate that the serine recombinases are modular and that fusion of the catalytic domain to unrelated sequences has generated structural and functional diversity.
Immunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization (1996)

Vaccination with naked DNA elicits cellular and humoral immune responses that have a T helper cell type 1 bias. However, plasmid vectors expressing large amounts of gene product do not necessarily induce immune responses to the encoded antigens. Instead, the immunogenicity of plasmid DNA (pDNA) requires short immunostimulatory DNA sequences (ISS) that contain a CpG dinucleotide in a particular base context. Human monocytes transfected with pDNA or double-stranded oligonucleotides containing the ISS, but not those transfected with ISS-deficient pDNA or oligonucleotides, transcribed large amounts of interferon-alpha, interferon-beta, and interleukin-12. Although ISS are necessary for gene vaccination, they down-regulate gene expression and thus may interfere with gene replacement therapy by inducing proinflammatory cytokines.
Endometrial carcinoma in the cancer family syndrome (1991)

The study group consisted of 26 women with endometrial adenocarcinoma belonging to 19 cancer families. Age at the onset of cancer, the stage and histologic differentiation of the tumor, initial symptoms, other malignancies, 5-year survival, and transmission of cancer to descendants were studied. The focus was on the importance of endometrial carcinoma in the tumor spectrum. The diagnosis of cancer family was delayed in 14 of the 19 families because endometrial carcinoma was not included in the primary diagnostic carcinoma. This delay may have been harmful to 16 family members who had carcinomas later in life. In ten of the 14 women with multiple malignancies, endometrial adenocarcinoma was the primary malignancy diagnosed, thus enabling the suspicion of a gene carrier and screening for subsequent malignancies. The authors concluded that endometrial carcinoma is a significant component of cancer family syndrome and should be included in the main criteria of Lynch syndrome II.
Pathological Mechanisms of Acne with Special Emphasis on Propionibacterium acnes and Related Therapy (2003)

Acne is a common disease that in cases of extreme disfiguration can have severe consequences for the personality development of young people and is associated with a relatively high prevalence of depression and suicide. Spontaneous regression is common, but acne can extend into the fourth and fifth decades of life. The pathogenesis is still not fully understood. Factors promoting the development of acne are: increased sebum production, ductal cornification, bacterial colonization of the pilosebaceus ducts and inflammation. However, there is evidence that inflammation is not a factor but rather a consequence of the interaction of the other three factors. Propionibacterium acnes releases pro-inflammatory cytokines as well as antigens and mitogen(s), with cellular and non-cellular responses to these products triggering inflammation. Treatment is often frustran. Therapeutical strategies are needed based on new understandings of the pathomechanisms involved in acne. The aim of this review is to summarize the data on aetiopathological factors in acne and their contribution to acne pathology and therapy.
High-frequency modulation characteristics of hybriddielectric/AlGaAs mirrorsinglemode VCSELs (1995)

The authors have measured the small-signal frequency response characteristics of a GaAs VCSEL (λ = 835 nm) implementing a novel MOVPE-grown AlOaAs/AlAs-TiO2/SiO2 hybrid distributed Bragg reflector used to control emission to a single mode. A small-signal 3 dB bandwidth of 12.1 GHz was recorded at a bias level of only 2.8 mA. A very high modulation efficiency of 9.5 GHz/√(mA) was measured which is the highest reported for VCSELs or any semiconductor laser of any variety. In addition, large signal measurements were conducted which showed open eye patterns with pre-bias currents of ~0 mA demonstrating the possibility of direct logic-level drive.
Laparoscopic Nissen Fundoplication (2001)

The long-term outcome of laparoscopic Nissen fundoplication is similar to that following open fundoplication. Good results are obtained in most patients.
β-Amyloid-Mediated Inhibition of NMDA Receptor-Dependent Long-Term Potentiation Induction Involves Activation of Microglia and Stimulation of Inducible Nitric Oxide Synthase and Superoxide (2004)

The mechanisms underlying the inhibition of long-term potentiation (LTP) induction by amyloidbeta-peptide (Abeta) were investigated in the medial perforant path of the rat and mouse dentate gyrus in vitro. Evidence is presented in this study that the Abeta-mediated inhibition of LTP induction involves activation of microglia and production of reactive oxygen and nitrogen species. In control slices, Abeta strongly inhibited induction of NMDA receptor-dependent (NMDAR-dependent) LTP, although not induction of NMDAR-independent LTP or long-term depression (LTD). The inhibition of NMDAR-dependent LTP was prevented by minocycline, an agent that prevents activation of microglia. The involvement of inducible nitric oxide synthase (iNOS) was shown by the inability of Abeta to inhibit LTP induction in iNOS knock-out mice and also by the ability of two iNOS inhibitors, aminoguanidine and 1400W, to prevent the Abeta-mediated inhibition of LTP induction. The Abeta-mediated inhibition of LTP induction also was prevented by the superoxide scavenger superoxide dismutase applied together with catalase. Evidence for involvement of superoxide in the action of Abeta on LTP induction was shown by the ability of an inhibitor of NADPH oxidase to prevent the Abeta-mediated inhibition of LTP induction. The study thus provides evidence that the Abeta-mediated inhibition of LTP induction involves an inflammatory-type reaction in which activation of microglia results in the production of nitric oxide and superoxide and thence possibly peroxynitrite, a highly reactive oxidant.
Death Receptor-Induced Activation of the Chk2- and Histone H2AX-Associated DNA Damage Response Pathways (2008)

TRAIL is an endogenous death receptor ligand also used therapeutically because of its selective proapoptotic activity in cancer cells. In the present study, we examined chromatin alterations induced by TRAIL and show that TRAIL induces a rapid activation of DNA damage response (DDR) pathways with histone H2AX, Chk2, ATM, and DNA-PK phosphorylations. Within 1 h of TRAIL exposure, immunofluorescence confocal microscopy revealed gamma-H2AX peripheral nuclear staining (gamma-H2AX ring) colocalizing with phosphorylated/activated Chk2, ATM, and DNA-PK inside heterochromatin regions. The marginal distribution of DDR proteins in early apoptotic cells is remarkably different from the focal staining seen after DNA damage. TRAIL-induced DDR was suppressed upon caspase inhibition or Bax inactivation, demonstrating that the DDR activated by TRAIL is downstream from the mitochondrial death pathway. H2AX phosphorylation was dependent on DNA-PK, while Chk2 phosphorylation was dependent on both ATM and DNA-PK. Downregulation of Chk2 decreased TRAIL-induced cell detachment; delayed the activation of caspases 2, 3, 8, and 9; and reduced TRAIL-induced cell killing. Together, our findings suggest that nuclear activation of Chk2 by TRAIL acts as a positive feedback loop involving the mitochondrion-dependent activation of caspases, independently of p53.
α-fetoprotein variants in a case of pancreatoblastoma (2000)

We describe a 6-year-old boy with histologically confirmed pancreatoblastoma and a markedly elevated serum alpha-fetoprotein (AFP) concentration. Due to local tumour invasion, cytotoxic chemotherapy was given to debulk the tumour before attempting surgical resection. Serial serum AFP concentrations were measured on this patient. During chemotherapy there was a > 95% fall in total AFP. Tumour-specific variants of AFP, detected by isoelectric focusing, also disappeared during chemotherapy but recurred when chemotherapy was withdrawn. It is suggested that although there was no change in overall size of the tumour, as assessed by various imaging techniques, the changes in serological markers may indicate that the treatment did in fact cause considerable tumour necrosis, AFP and its variants may be useful markers of tumour response in patients with pancreatoblastoma. The expression of AFP and its variants in pancreatoblastoma may be related to the embryonic origin of the pancreas.
General Approach to the Synthesis of Sarpagine and Ajmaline Alkaloids. Enantiospecific Total Synthesis of (+)-Ajmaline and Alkaloid G via the Asymmetric Pictet−Spengler Reaction (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTGeneral Approach to the Synthesis of Sarpagine and Ajmaline Alkaloids. Enantiospecific Total Synthesis of (+)-Ajmaline and Alkaloid G via the Asymmetric Pictet−Spengler ReactionJin Li and James M. CookView Author Information Department of Chemistry, University of WisconsinMilwaukee, Milwaukee, Wisconsin 53201 Cite this: J. Org. Chem. 1998, 63, 13, 4166–4167Publication Date (Web):June 6, 1998Publication History Received12 March 1998Published online6 June 1998Published inissue 1 June 1998https://pubs.acs.org/doi/10.1021/jo980476phttps://doi.org/10.1021/jo980476prapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views835Altmetric-Citations30LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Aldehydes,Chemical synthesis,Molecular structure,Organic compounds,Organic synthesis Get e-Alerts
Can HIV be Cured? Mechanisms of HIV Persistence and Strategies to Combat It (2004)

Stable remission is the ultimate goal of HIV therapy. A review of recent studies on the ability of HIV to persist despite highly active antiretroviral therapy (HAART) and immune stimulation suggests that achieving this goal will require four developments in basic and clinical science. First, more effective antiretroviral therapies, targeted at proteins other than reverse transcriptase and protease, in order to eliminate the cryptic replication that continues despite best available HAART. Second, agents that activate latent HIV gene expression in quiescent CD4 memory T cells, thereby exposing this viral reservoir to therapeutic intervention by a "shock and kill" strategy. Third, molecules such as immunotoxins that specifically recognize HIV-encoded membrane proteins and thereby potentiate the destruction of infected cells. Fourth, and still most distant, novel approaches such as genetically engineered cytotoxic T lymphocytes or anti-HIV microbes to suppress rekindling of infection by residual virus sequestered in anatomical and cellular reservoirs. Although each of these steps will be difficult to achieve, the many benefits of a cure for HIV make this a worthwhile pursuit.
Prognostic factors for survival in 676 consecutive patients with newly diagnosed primary glioblastoma (2007)

Reliable data on large cohorts of patients with glioblastoma are needed because such studies differ importantly from trials that have a strong bias toward the recruitment of younger patients with a higher performance status. We analyzed the outcome of 676 patients with histologically confirmed newly diagnosed glioblastoma who were treated consecutively at a single institution over a 7-year period (1997-2003) with follow-up to April 30, 2006. Survival probabilities were 57% at 1 year, 16% at 2 years, and 7% at 3 years. Progression-free survival was 15% at 1 year. Prolongation of survival was significantly associated with surgery in patients with a good performance status, whatever the patient's age, with an adjusted hazard ratio of 0.55 (p < 0.001) or a 45% relative decrease in the risk of death. Radiotherapy and chemotherapy improved survival, with adjusted hazard ratios of 0.61 (p = 0.001) and 0.89 (p = 0.04), respectively, regardless of age, performance status, or residual tumor volume. Recurrence occurred in 99% of patients throughout the follow-up. Reoperation was performed in one-fourth of these patients but was not effective, whether performed within 9 months (hazard ratio, 0.86; p = 0.256) or after 9 months (hazard ratio, 0.98; p = 0.860) of initial surgery, whereas second-line chemotherapy with procarbazine, lomustine, and vincristine (PCV) or with temozolomide improved survival (hazard ratio, 0.77; p = 0.008). Surgery followed by radiotherapy and chemotherapy should be considered in all patients with glioblastoma, and these treatments should not be withheld because of increasing age alone. The benefit of second surgery at recurrence is uncertain, and new trials are needed to assess its effectiveness. Chemotherapy with PCV or temozolomide seems to be a reasonable option at tumor recurrence.
Trans activation by the bovine papillomavirus E2 protein in Saccharomyces cerevisiae (1989)

The papillomavirus E2 protein functions as an enhancer-binding factor to promote transcription in mammalian cells. We found that one copy of the E2 binding site acted as an E2 protein-dependent upstream activating sequence in Saccharomyces cerevisiae. Additional copies of the binding motif further augmented transcription. These results imply that the E2 protein functionally interacts with highly conserved transcriptional elements.
A novel tungsten light-shield structure for high-density CCD image sensors (1991)

A novel tungsten light-shield structure has been developed. Tungsten film properties, the device configuration with the tungsten light-shield structure, and experimentally achieved results regarding device characteristics are described. Optical measurement clarified that tungsten film has a sufficiently low transmittance value for practical use for more than 200-nm-thick film and is stable up to 1000 degrees C. The good step coverage and low reflectance, such as 20-40% for aluminum, required for light-shield film were also obtained. A tungsten light-shield structure was applied to a 1/2-in format 668(H)-pixel*575(V)-pixel charge coupled-device (CCD) image sensor. An extremely low smear value, less than 0.001%, was obtained for a 300-nm film thickness.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hardware is the new Software (2017)

Moore's Law may be slowing, but, perhaps as a result, other measures of processor complexity are only accelerating. In recent years, Intel's architects have turned to an alphabet soup of instruction set extensions such as MPX, SGX, MPK, and CET as a way to sell CPUs through new security features. Unlike prior extensions, which mostly focused on accelerating user-mode data processing, these new features exhibit complex interactions and give system designers plenty to think about.
Semiconducting Single‐Walled Carbon Nanotubes on Demand by Polymer Wrapping (2013)

Efficient selection of semiconducting SWCNTs of large diameter range (0.8-1.6 nm) on demand is demonstrated. Different diameters of SWCNT are systematically selected by tuning the alkyl side-chain lengths of the wrapping polymers of similar backbone. The exceptional quality and high concentration of the SWCNTs is validated by the outstanding optical properties and the highly performing random network ambipolar field-effect transistors.
Characterization of DNA Oligonucleotides by Coupling of Capillary Zone Electrophoresis to Electrospray Ionization Q-TOF Mass Spectrometry (1998)

A procedure for fast and precise molecular weight, purity, and base composition determination of oligonucleotides (in the size range of 20−120 bases) using capillary zone electrophoresis (CZE) coupled by an electrospray interface (ES) on-line to a quadrupole-inlet time-of-flight mass spectrometer (Q-TOFMS) is described. The detection limit for the 5‘-monophosphate nucleotides dAMP and TMP was 30 fmol injected for single MS and 400 fmol for a collision-induced daughter ion spectrum (CID-MS/MS). Injection of 1 pmol was the detection limit for the oligonucleotides. The use of the CZE as an injection interface for oligonucleotides successfully removed metal ion adducts, greatly enhancing the sensitivity and the precision of the mass detection without the need for sample preparation steps. Using electrophoretic separation in an ammonium carbonate buffer system (0.1 M, pH 9.68), these metal adducts were removed and exchanged for volatile ammonium ions. A simple sample stacking technique was developed in order to be able to inject sufficient amounts of sample on the capillary prior to electrophoresis. Using this sample stacking technique, the oligonucleotides could be concentrated up to a factor of 100 on the capillary. Given the high mass precision (±50 ppm) and the high mass resolution (peak widths at half-height of 4 Da), CZE−Q-TOFMS proves to be very useful not only for determination of the purity and the length of oligonucleotides (up to 120 bases) but also for confirmation of the expected base composition, making this technique an extremely useful tool for quality control in the field of oligonucleotides.
Immobilization of single‐stranded DNA by self‐assembled polymer on gold substrate for a DNA chip (2005)

We developed a self-assembling polymer based on polyallylamine (PAH) for use in DNA chips. Thioctic acid (TA) was covalently attached to PAH in sidechains to immobilize the polymer on a gold surface by self-assembly. N-hydroxysuccinimide-ester terminated probe single-stranded (ss) DNA is easily covalently immobilized onto a TA-PAH-coated gold surface. Finally, the surface was covered with polyacrylic acid, which formed ion complexes with the TA-PAH, to reduce the cationic charge. This ssDNA on a polymer-coated surface recognized a fully matched DNA sequence and restrained nonspecific adsorption of target DNA. The selectivity and efficiency of hybridization was affected by adjusting the ionic strength of sodium chloride.
Tumor markers CA19-9, CA242 and CEA in the diagnosis of pancreatic cancer: a meta-analysis. (2015)

Our meta-analysis showed that CA242 and CA19-9 have better performance in the diagnosis of pancreatic cancer than CEA. Furthermore, parallel combination test of CA19-9+CA242 could be of better diagnostic value than individual CA242 or CA19-9 test.
Pretargeted Radioimmunotherapy for B-Cell Lymphomas (2007)

Relapsed or treatment refractory B-cell lymphomas are currently incurable with conventional chemotherapy and radiation treatments. High-dose chemoradiotherapy and stem cell transplantation can cure some patients with relapsed or refractory lymphoma, but the majority of such patients die of progressive disease. We have investigated the potential utility of pretargeted radioimmunotherapy using monoclonal antibody-streptavidin, immunoconjugates, and fusion proteins in combination with N-acetylgalactosamine dendrimeric clearing agent and radiometal-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid biotin for treatment of lymphomas using mouse and primate models. We have targeted a variety of cell surface antigens, including CD20, CD22, CD45, and HLA-DR, using conventional and pretargeted radioimmunotherapy. These studies showed the marked superiority of pretargeted radioimmunotherapy for each of the antigenic targets in terms of superior biodistributions, more complete tumor regressions, and longer survival. We are optimistic that this novel approach will provide a meaningful prolongation of survival for patients with relapsed or refractory lymphomas.
Activation of the Complement Pathway: Comparison of Normal Pregnancy, Preeclampsia, and Systemic Lupus Erythematosus During Pregnancy (1992)

To evaluate a flare of systemic lupus erythematosus (SLE) during pregnancy and to differentiate it from diseases of pregnancy, serological parameters are often utilized. However, there are conflicting reports regarding the merit of conventional measurements of complement and activation products. While in normal pregnancy the levels of serum C3, C4, and CH50 gradually rise, a decline in these levels occurs during the course of pregnancy in selected SLE patients. There is controversy regarding whether such falls represent decreases in the overall synthesis of complement or activation, the former theory being supported by a report of normal levels of the C1s-C1 inhibitor complex. During normal pregnancies, increases of complement split products, such as plasma C3a, may occur, and these correlate positively with elevations of C3. In pregnancies complicated by lupus, increases of C3a are often accompanied by a decline in total C3 and CH50. In a minority of non-SLE patients, preeclampsia has been associated with elevations of a variety of complement split products. Ba, C3a, C4d, SC5b-9, indicating activation of both the classical and alternative pathways. The CH50 levels tend to remain normal in these patients. In contrast, elevations of complement split products frequently accompany disease flares in patients with SLE. A high ratio of CH50/Ba may differentiate patients with preeclampsia from those with active SLE. A decline in conventional measures of C3, C4, or CH50 which is accompanied by elevations of complement split products appears to differentiate a lupus flare from non-SLE diseases of pregnancy.