gebhart/patrepeval huggingface dataset:
Human immunodeficiency virus type 1 DNA integration: fine structure target analysis using synthetic oligonucleotides (1993)

The target specificity of DNA strand transfer mediated by human immunodeficiency virus type 1 integrase was examined in vitro with synthetic oligonucleotides. Although insertion occurred at most locations in the target, some sites were preferred over others by at least 15-fold. Changing the nucleotide sequence of the target changed the distribution of preferred sites in complex ways, some of which included changes in target preference distant from the sequence alteration. Alignment of target sequences revealed that adenosine is preferred adjacent to the insertion site. Strand transfer occurred to within 2 nucleotides of the 3' end and to within 3 nucleotides of the 5' end of the target. This suggests that only 2 or 3 nucleotides flanking the target site are required for integration; such restricted contact with target DNA would allow integrase to insert the two ends of viral DNA into two closely spaced sites in host DNA, consistent with the concerted in vivo integration reaction that generates a 5-bp target duplication.
Purification of CD34+ Cells Is Essential for Optimal Ex Vivo Expansion of Umbilical Cord Blood Cells (1997)

Allogeneic umbilical cord blood (UCB) cells have recently been used for transplantation following high-dose chemotherapy. However, the numbers of total cells, including progenitor cells, harvested are low compared with bone marrow or peripheral blood progenitor cell harvests. Therefore, we evaluated the potential of UCB cells for their ability to expand granulocyte-macrophage colony-forming cells (GM-CFC) and burst-forming unit-erythroid (BFU-E) cells over 10 days. We used an ammonium chloride lysing buffer to eliminate the majority of contaminating red blood cells. An average recovery of 61% of the starting number of white blood cells was obtained, while retaining 100% of the CD34+ cells. Ex vivo expansion cultures were established in Teflon cell culture bags (American Fluoroseal Corp, Columbia, MD) in 25 ml defined medium (Amgen Inc, Thousand Oaks, CA) containing 100 ng/ml each of stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), and megakaryocyte growth and development factor. Either unselected UCB cells or CD34+ UCB cells, selected with Magnetic Activation Cell Sorting technology (Miltenyi Biotech GmbH, Bergisch Gladbach, Germany), were incubated for 10 days at 37 degrees C without refeeding. Unselected UCB cells seeded at 1 X 10(6)/ml produced an average expansion of 1.4-fold in total cells, 0.8-fold in GM-CFC, and 0.3-fold in BFU-E cells. By contrast, CD34+ selected UCB cells seeded at 1.0 X 10(4)/ml produced an average expansion of 113-fold in total cells, 72.6-fold in GM-CFC, and 49-fold in BFU-E cells. These data demonstrate that CD34+ cell selection is necessary for optimal expansion of both GM-CFC and BFU-E cells. The cell numbers thus obtained postexpansion may be sufficient for transplantation in adults.
mTOR and HIF-1α-mediated tumor metabolism in an LKB1 mouse model of Peutz-Jeghers syndrome (2009)

Peutz-Jeghers syndrome (PJS) is a familial cancer disorder due to inherited loss of function mutations in the LKB1/ STK11 serine/threonine kinase. PJS patients develop gastrointestinal hamartomas with 100% penetrance often in the second decade of life, and demonstrate an increased predisposition toward the development of a number of additional malignancies. Among mitogenic signaling pathways, the mammalian-target of rapamycin complex 1 (mTORC1) pathway is hyperactivated in tissues and tumors derived from LKB1-deficient mice. Consistent with a central role for mTORC1 in these tumors, rapamycin as a single agent results in a dramatic suppression of preexisting GI polyps in LKB1+/- mice. However, the key targets of mTORC1 in LKB1-deficient tumors remain unknown. We demonstrate here that these polyps, and LKB1- and AMPK-deficient mouse embryonic fibroblasts, show dramatic up-regulation of the HIF-1alpha transcription factor and its downstream transcriptional targets in an rapamycin-suppressible manner. The HIF-1alpha targets hexokinase II and Glut1 are up-regulated in these polyps, and using FDG-PET, we demonstrate that LKB1+/- mice show increased glucose utilization in focal regions of their GI tract corresponding to these gastrointestinal hamartomas. Importantly, we demonstrate that polyps from human Peutz-Jeghers patients similarly exhibit up-regulated mTORC1 signaling, HIF-1alpha, and GLUT1 levels. Furthermore, like HIF-1alpha and its target genes, the FDG-PET signal in the GI tract of these mice is abolished by rapamycin treatment. These findings suggest a number of therapeutic modalities for the treatment and detection of hamartomas in PJS patients, and potential for the screening and treatment of the 30% of sporadic human lung cancers bearing LKB1 mutations.
The Use of Blood and Derived Products as Food Additives (2012)

Blood is a rich source of iron and proteins of high nutritional and functional quality. Because of the high protein content of blood, generally about 18% [1], it is sometimes referred to as “liquid protein” [2]. It has been estimated that the approximately 1,500,000 tons of porcine blood produced yearly in China has a protein content equivalent to that of 2,000,000 tons of meat or 2,500,000 tons of eggs [3]. Thus, a valuable protein source is lost if animal blood is discarded as waste and this is compounded by the resulting serious environmental pollution problems. Many countries require that animal blood be disposed off in an environmentally friendly manner, which is a capital intensive process. Accordingly, to eliminate a sizeable pollution hazard and prevent the loss of a valuable protein source, efforts have been made to ensure the utilization of animal blood on a massive scale. A further incentive is the increased profits to be made through adding value to the blood.
A new synthesis of 4‐cyano‐1,3‐dihydro‐2‐oxo‐2H‐imidazole‐5‐(N1‐tosy1)carboxamide : reactive precursor for thiopurine analogues (2001)

Abstract N ‐[(5‐Cyano‐2‐oxoimidazolidin‐4‐yl)‐iminomethyl]‐ p ‐toluensulfonamide 3 was prepared in fairly good yield by the base catalyzed cyclisation of N ‐[(Z)‐2‐amino‐1,2‐dicycanovinylcarbamoyl]‐ p ‐toluenesulfon‐amide 2 . The N ‐[(Z)‐2‐amino‐1,2‐dicycanovinyl carbamoyl]‐ p ‐toluenesulfonamide 2 was reacted readily with two molar amount of p ‐nitrobenzaldehyde at room temperature in the presence of base to give 7,8‐dihy‐dro‐2‐(4‐nitrophenyl)‐8‐oxo‐9‐tosylpurine‐6‐carboxamide 8 . Thiation of compounds 3 and 8 using Lawesson's reagent in tetrahydrofuran gave novel thioimidazoles 4, 5 , and 6 and thiopurines 9, 10 , and 11 , which have been characterized spectroscopically.
Endometrial cancer and antidepressants (2016)

To our knowledge, the association between antidepressant exposure and endometrial cancer has not been previously explored. Herein, we aim to investigate the association between antidepressant prescription, including novel antidepressants, and the risk for endometrial cancer in a population-based study.Data for the analysis were derived from National Health Insurance Research Database. We identified 8392 cases with a diagnosis of endometrial cancer and 82,432 matched controls. A conditional logistic regression model was used, with adjusting for potentially confounding variables (e.g., comorbid psychiatric diseases, comorbid physical diseases, and other medications). Risk for endometrial cancer in the population-based study sample was categorized by, and assessed as a function of, antidepressant prescription and cumulative dosage.We report no association between endometrial cancer incidence and antidepressant prescription, including those prescribed either selective serotonin reuptake inhibitors (adjusted odds ratio [OR] = 0.98; 95% confidence interval [CI], 0.84-1.15) or serotonin norepinephrine reuptake inhibitors (adjusted OR = 1.14; 95% CI, 0.76-1.71). We also did not identify an association between higher cumulative doses of antidepressant prescription and endometrial cancer.There was no association between antidepressant prescription and endometrial cancer.
A cheap and easy method for 3D C-arm reconstruction using elliptic curves (2007)

For quantitative C-arm fluoroscopy, we had earlier proposed a unified mathematical framework to tackle the issues of pose estimation, correspondence and reconstruction, without the use of external trackers. The method used randomly distributed unknown points in the imaging volume, either naturally present or induced by placing beads on the patient. These points were then inputted to an algorithm that computed the 3D reconstruction. The algorithm had an 8° region of convergence, which in general could be considered sufficient for most applications. Here, we extend the earlier algorithm to make it more robust and clinically acceptable. We propose the use of a circle/ellipse, naturally found in many images. We show that the projection of elliptic curves constrain 5 out of the 6 degrees of freedom of the C-arm pose. To completely recover the true C-arm pose, we use constraints in the form of point correspondences between the images. We provide an algorithm to easily obtain a virtual correspondence across all the images and show that two correspondences can recover the true pose 95% of the time when the seeds employed are separated by a distance of 40 mm. or greater. Phantom experiments across three images indicate a pose estimation accuracy of 1.7° using an ellipse and two sufficiently separated point correspondences. Average execution time in this case is 130 seconds. The method appears to be suffciently accurate for clinical applications and does not require any significant modification of clinical protocol.
Fabrication of Patterned Conducting Polymers on Insulating Polymeric Substrates by Electric‐Field‐Assisted Assembly and Pattern Transfer (2006)

Abstract Summary: The use of electrostatically addressable templates for the directed assembly of conducting polymers and pattern transfer to another polymer substrate is demonstrated. Doped conducting polyaniline was selectively assembled on the patterned template assisted by a DC electric field. Adding an insulated silicon dioxide layer onto the surface of the silicon wafer is critical to the formation of patterned PANi rather than a PANi film. After deposition, it was demonstrated that by compression molding or solution casting methods, patterned PANi can be completely transferred to a secondary polymer substrate, such as an NBR sheet or a polyurethane film. The conductivity of PANi lines on the PU film was found to be as high as 0.87 S · cm −1 . The simple one‐step assembly process for patterning conductive polymers and transfer provides a promising nanomanufacturing approach for cost‐effective and high performance flexible nanoelectronics and biosensors. Optical image of PANi‐assembled templates with patterned gold lines connected to negative electrodes at 10 V for 1 min. magnified image Optical image of PANi‐assembled templates with patterned gold lines connected to negative electrodes at 10 V for 1 min.
Therapeutic antibodies against viral hepatitis. (2003)

Antibodies have the potential to be immunotherapeutic agents, used either as stand-alone therapy or as an adjunct for managing chronic viral infection. In addition, antibodies may be used prophylactically in individuals who have been accidentally exposed to hepatitis B virus (HBV) or hepatitis C virus (HCV), or to prevent re-infection of the liver in patients who have undergone liver transplantation. Human monoclonal antibodies to HBV and HCV were generated and their ability to reduce viral load was tested in different animal model systems, the Trimera mouse model and HBV-carrier chimpanzees. These antibodies were further developed and are currently being studied in clinical trials for chronic HBV or HCV and in liver transplant patients. The antibodies were shown to be safe, tolerable and could significantly reduce viral load. Their ability to inhibit HCV re-infection in the transplanted liver is being evaluated.
LGR5‐Positive Colon Cancer Stem Cells Interconvert with Drug‐Resistant LGR5‐Negative cells and are Capable of Tumor Reconstitution (2012)

The cancer stem cell (CSC) concept has been proposed as an attractive theory to explain cancer development, and CSCs themselves have been considered as targets for the development of diagnostics and therapeutics. However, many unanswered questions concerning the existence of slow cycling/quiescent, drug-resistant CSCs remain. Here we report the establishment of colon cancer CSC lines, interconversion of the CSCs between a proliferating and a drug-resistant state, and reconstitution of tumor hierarchy from the CSCs. Stable cell lines having CSC properties were established from human colon cancer after serial passages in NOD/Shi-scid, IL-2Rγ(null) (NOG) mice and subsequent adherent cell culture of these tumors. By generating specific antibodies against LGR5, we demonstrated that these cells expressed LGR5 and underwent self-renewal using symmetrical divisions. Upon exposure to irinotecan, the LGR5(+) cells transitioned into an LGR5(-) drug-resistant state. The LGR5(-) cells converted to an LGR5(+) state in the absence of the drug. DNA microarray analysis and immunohistochemistry demonstrated that HLA-DMA was specifically expressed in drug-resistant LGR5(-) cells, and epiregulin was expressed in both LGR5(+) and drug-resistant LGR5(-) cells. Both cells sustained tumor initiating activity in NOG mice, giving rise to a tumor tissue hierarchy. In addition, anti-epiregulin antibody was found to be efficacious in a metastatic model. Both LGR5(+) and LGR5(-) cells were detected in the tumor tissues of colon cancer patients. The results provide new biological insights into drug resistance of CSCs and new therapeutic options for cancer treatment.
A sensitive magnetic bead method for the detection and identification of tyrosine phosphorylation in proteins by MALDI‐TOF/TOF MS (2009)

Phosphorylation is one of the most important PTMs and is estimated to occur on 30% of the mammalian proteome. Its perturbed regulation has been implicated in many pathologies. The rarity of phosphotyrosine compared with phosphoserine or phosphothreonine is prompting the development of more sensitive approaches because proteomic technologies that are currently used to assess tyrosine phosphorylation in proteins are inadequate, identifying only a fraction of the predicted tyrosine phosphoproteome. Here we describe the development of a reproducible, high-sensitivity methodology for the detection and mapping of phosphotyrosine residues by MS. The anti-phosphotyrosine antibody 4G10 was coupled covalently to super para-magnetic beads or by affinity to super para-magnetic beads with protein G covalently attached. Using this approach, we successfully enriched phosphotyrosine peptides mixed with non-phosphorylated peptides at a ratio of up to 1:200, enabling detection at a level representing the highest sensitivity reported for tyrosine phosphorylation. The beads were subsequently used to enrich tyrosine phosphopeptides from a digest of the in vitro-phosphorylated recombinant beta-intracellular region of the granulocyte-macrophage colony-stimulating factor receptor, which was subsequently analysed by MALDI-TOF/TOF MS. Our results define this methodology as a sensitive approach for tyrosine phosphoproteome analysis.
The Search for New-Generation Olefin Polymerization Catalysts: Life beyond Metallocenes (1999)

Even late transition metal complexes function as active and selective catalysts for α-olefin polymerization. The discovery of a highly active family of catalysts 1 based on iron, a metal that had no previous track record in this field, has highlighted the possibilities for further new catalyst discoveries. As a result, an intense search has developed for new-generation catalysts, in both academic and industrial research laboratories. R<sup>1</sup> =H, Me; R<sup>2</sup> =Me, iPr; R<sup>3</sup> =H, Me, iPr; R<sup>4</sup> =H, Me; X=halide.
Activin A and Follistatin-Like 3 Determine the Susceptibility of Heart to Ischemic Injury (2009)

Activin A and Fstl3 are induced in heart by myocardial stress. Activin A protects myocytes from death, and this activity is antagonized by Fstl3. Thus, the relative expression levels of these factors after injury is a determinant of cell survival in the heart.
Neutralization of HIV-1 subtypes: Implications for vaccine formulations (1998)

More than 20.8 million people are infected with HIV in sub-Saharan Africa, with South Africa having one of the fastest growing HIV-1 epidemics, where an estimated 2.4 million people were infected. Thirty-two sera from 25 patients were tested for their ability to neutralize HTLV-IIIB (IIIB) and four primary isolates representing subtypes B, C, D, and a recombinant gag C/env B type. A CEM-SS cell line-based assay was used and the neutralizing titer was defined as the reciprocal of the highest dilution giving a 50% reduction in p24 antigen production. All isolates were neutralized better by subtype-specific sera, except for the C4714 strain, which was neutralized by both subtype B and C sera. C4714 was neutralized by 18/25 (72%) sera, IIIB by 19/32 (59%) sera, D482 by 7/31(23%) sera, B3245 by 6/29 (21%) sera, and the recombinant B/C1491 isolate by 4/25 (16%) sera. Five sera were unable to neutralize any of the isolates. The V3 region of the isolates used in the neutralization assay was amplified by PCR, directly sequenced, and analyzed to reveal variability between the consensus HIV-1 sequences and the isolates. HIV-1 strain C4714 was neutralized more effectively with the sera tested than the IIIIB laboratory strain. Variability in the amino acid sequence of the V3 region, which can alter the conformation of the V3 loop secondary structure, can influence the neutralization of a particular viral isolate. Vaccine formulations should be broadened to include multiple subtypes, especially C subtypes, which is rapidly spreading worldwide.
Functional Changes in Pulmonary Arterial Endothelial Cells Associated with BMPR2 Mutations (2014)

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by abnormal remodeling of small, peripheral pulmonary arteries. Germline mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene are a major risk factor for developing PAH. At present, the correlation between the BMPR2 mutation and the patient's prognosis remains controversial despite several investigations. In this study, we explored the functional effects of four BMPR2 mutations to dissect the functional significance of the BMPR2 gene defect. Cellular immunofluorescence assay of four mutants (Tyr67Cys, Thr268fs, Ser863Asn, and Gln433X) revealed that the BMPR2 protein containing Thr268fs, Ser863Asn, or Gln433X exhibited abnormal subcellular localization. The BrdU incorporation and TUNEL assay suggested that any of the BMPR2 mutations Thr268fs, Ser863Asn, or Gln433X could improve endothelial cell apoptosis and decrease cell proliferation. All of the four mutants could inhibit nitric oxide (NO) synthesis in HLMVE cells, and ET-1 levels increased in the cells transfected with mutant Ser863Asn. Our results will improve the understanding of the genotype-phenotype correlations and mechanisms associated with BMPR2 mutations.
Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer (2004)

We report on the identification of autoantigens commonly recognized by sera from patients with breast cancer. We selected ten sera from patients with invasive ductal carcinoma (IDC) of the breast with high titer IgG autoantibodies for biopanning of a T7 phage breast cancer cDNA display library. A high throughput method involved the assembly of 938 T7 phages encoding potential breast cancer autoantigens. Microarrays of positive phages were probed with sera from 90 patients with breast cancer [15 patients with ductal carcinoma in situ (DCIS) and 75 patients with IDC of the breast], with 51 non-cancer control sera and with sera from 21 patients with systemic autoimmune diseases. A 12-phage breast cancer predictor group was constructed with phage inserts recognized by sera from patients with breast cancer and not by non-cancer or autoimmune control sera (P < 0.0001). Several autoantigens including annexin XI-A, the p80 subunit of the Ku antigen, ribosomal protein S6, and other unknown autoantigens could significantly discriminate between breast cancer and non-cancer control sera. Biopanning with three different sera led to the cloning of partial cDNA sequences identical to annexin XI-A. IgG autoantibodies reacting with the amino acid 41-74 sequence of annexin XI-A were found in 19% of all women with breast cancer but in 60% of sera from women with DCIS of the breast. In addition, partial sequences identical to annexin XI-A, nucleolar protein interacting with the forkhead-associated (FHA) domain of pKi-67, the KIAA1671 gene product, ribosomal protein S6, cyclin K, elongation factor-2, Grb2-associated protein 2, and other unknown proteins could distinguish DCIS from IDC of the breast and appear to be potential biomarkers for the diagnosis of breast cancer.
Stability of Haptic Rendering: Discretization, Quantization, Time Delay, and Coulomb Effects (2006)

Rendering stiff virtual objects remains a core challenge in the field of haptics. A study of this problem is presented, which relates the maximum achievable object stiffness to the elements of the control loop. In particular, we examine how the sampling rate, quantization, computational delay, and amplifier dynamics interact with the inertia, natural viscous, and Coulomb damping of the haptic device. Nonlinear effects create distinct stability regions, and many common devices operate stably, yet in violation of passivity criteria. An energy-based approach provides theoretical insights, supported by simulations, experimental data, and a describing function analysis. The presented results subsume previously known stability conditions
Leukemic phase of mantle cell lymphoma two case reports and review of the literature. (1996)

Two cases of mantle cell lymphoma are presented. Both patients were women, aged 68 and 56 years, who presented with lymph node enlargement. Each case was initially interpreted as a follicular small cleaved cell lymphoma. Both patients later presented with splenomegaly and recurrent lymphadenopathy. Morphologic and immunologic studies on a parotid swelling in one case and a splenectomy specimen in the other indicated a diagnosis of mantle cell lymphoma. Both women subsequently presented in leukemic phase associated with a poor prognosis, and both patients succumbed soon after. The characteristics, differential diagnosis, and leukemic phase of mantle cell lymphoma are discussed. The importance of appropriate immunohistochemical and flow cytometry analysis in distinguishing mantle cell lymphoma from morphologically similar follicular center cell lymphomas is demonstrated.