gebhart/patrepeval huggingface dataset:
Conservative homologous recombination preferentially repairs DNA double-strand breaks in the S phase of the cell cycle in human cells (2004)

DNA double-strand breaks (DSBs) are repaired by either homologous recombination (HR) or non-homologous end joining (NHEJ) in mammalian cells. Repair with NHEJ or HR using single-strand annealing (SSA) often results in deletions and is generally referred to as non-conservative recombination. Error-free, conservative HR involves strand invasion and requires a homologous DNA template, and therefore it is generally believed that this type of repair occurs preferentially in the late S, G2 and M phases of the cell cycle, when the sister chromatid is available. There are several observations supporting this hypothesis, although it has not been tested directly. Here, we synchronize human SW480SN.3 cells in the G1/G0 (with serum starvation), S (with thymidine block) and M (with nocodazole) phases of the cell cycle and investigate the efficiency of conservative HR repair of an I-SceI-induced DSB. The frequency of HR repair of DSBs was 39 times higher in S-phase cells than in M-phase cells and 24-fold higher than in G1/G0 cells. This low level of conservative HR occurs even though a homologous template is present within the recombination substrate. We propose that this can be explained by an absence of recombination proteins outside the S phase or alternatively that there maybe factors that suppress HR in G1/G0 and M. Furthermore, we found that HR repair of DSBs involves short tract gene conversion in all the phases of the cell cycle. This indicates that the same pathway for conservative HR is employed in the repair of DSBs regardless of phase of the cell cycle and that only the frequency is affected.
Human mitochondrial tRNAMet is exported to the cytoplasm and associates with the Argonaute 2 protein (2005)

Argonaute (Ago) proteins are the effector proteins of RNA interference (RNAi) and related silencing mechanisms that are mediated by small RNAs. Ago proteins bind directly to microRNAs (miRNAs) and to short interfering RNAs and are the core protein components of RNA induced silencing complexes (RISCs) and microRNPs (miRNPs). Here we report that an ~70-nt RNA associates specifically with immunopurified Ago2 expressed in human 293 cells. By directional cloning we identified this RNA as the mitochondrial tRNA(Met) (mt tRNA(Met)). Various exported (mt) tRNAs were detected in the cytosol of 293 cells, but Ago2 was found selectively bound to (mt) tRNA(Met). The association in the cytosol of exported (mt) tRNA(Met) with Ago2 complements genetic and microscopic data that link mitochondria with RNAi-related components and events.
Semi-supervised learning using label mean (2009)

Semi-Supervised Support Vector Machines (S3VMs) typically directly estimate the label assignments for the unlabeled instances. This is often inefficient even with recent advances in the efficient training of the (supervised) SVM. In this paper, we show that S3VMs, with knowledge of the means of the class labels of the unlabeled data, is closely related to the supervised SVM with known labels on all the unlabeled data. This motivates us to first estimate the label means of the unlabeled data. Two versions of the meanS3VM, which work by maximizing the margin between the label means, are proposed. The first one is based on multiple kernel learning, while the second one is based on alternating optimization. Experiments show that both of the proposed algorithms achieve highly competitive and sometimes even the best performance as compared to the state-of-the-art semi-supervised learners. Moreover, they are more efficient than existing S3VMs.
Mac OS X Disaster Relief (2002)

From the Publisher:
Ted Landau, founder of the MacFixIt Web site, has made a career of helping others keep their Mac OS machines running happily. In Mac OS X Disaster Relief, the author of the bestselling Sad Macs, Bombs, and Other Disasters trains his diagnostician's eye on Apple's new-from-the-ground-up operating system. Full of tips, tools, and preventative measures, this easy-to-follow guide not only gives you specific solutions to a raft of Mac OS glitches, it also helps you prevent disasters and sharpen your own diagnostic skills. 
The same philosophy that underlies Sad Macs operates here: You can fix most Mac problems yourself. What you get are smart, common sense solutions and sound maintenance advice, delivered in plain English. But just because Mac OS X Disaster Relief eschews jargon doesn't mean it lacks depth: the book covers OS X's new features, the pros and cons of updating system software, Library directories and folders, files and font maintenance, crash prevention and recovery, printing and networking problems, Unix commands for OS X, and more.
Global Screening of Human Cord Blood Proteomes for Biomarkers of Toxic Exposure and Effect (2008)

This validation study provides an initial view of the proteome of human cord blood sera; it demonstrates the feasibility of identifying therein by use of proteomics, biomarkers of environmental, toxic exposures.
PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling (2010)

The periosteal and endocortical surfaces of cortical bone dictate the geometry and overall mechanical properties of bone. Yet the cellular and molecular mechanisms that regulate activity on these surfaces are far from being understood. Parathyroid hormone (PTH) has profound effects in cortical bone, stimulating periosteal expansion and at the same time accelerating intracortical bone remodeling. We report herein that transgenic mice expressing a constitutive active PTH receptor in osteocytes (DMP1-caPTHR1 mice) exhibit increased cortical bone area and an elevated rate of periosteal and endocortical bone formation. In addition, DMP1-caPTHR1 mice display a marked increase in intracortical remodeling and cortical porosity. Crossing DMP1-caPTHR1 mice with mice lacking the Wnt coreceptor, LDL-related receptor 5 (LRP5), or with mice overexpressing the Wnt antagonist Sost in osteocytes (DMP1-Sost mice) reduced or abolished, respectively, the increased cortical bone area, periosteal bone formation rate, and expression of osteoblast markers and Wnt target genes exhibited by the DMP1-caPTHR1 mice. In addition, DMP1-caPTHR1 lacking LRP5 or double transgenic DMP1-caPTHR1;DMP1-Sost mice exhibit exacerbated intracortical remodeling and increased osteoclast numbers, and markedly decreased expression of the RANK decoy receptor osteoprotegerin. Thus, whereas Sost downregulation and the consequent Wnt activation is required for the stimulatory effect of PTH receptor signaling on periosteal bone formation, the Wnt-independent increase in osteoclastogenesis induced by PTH receptor activation in osteocytes overrides the effect on Sost. These findings demonstrate that PTH receptor signaling influences cortical bone through actions on osteocytes and defines the role of Wnt signaling in PTH receptor action.
Characterization of MarR Superrepressor Mutants (1999)

MarR negatively regulates expression of the multiple antibiotic resistance (mar) locus in Escherichia coli. Superrepressor mutants, generated in order to study regions of MarR required for function, exhibited altered inducer recognition properties in whole cells and increased DNA binding to marO in vitro. Mutations occurred in three areas of the relatively small MarR protein (144 amino acids). It is surmised that superrepression results from increased DNA binding activities of these mutant proteins.
Surfactant Protein-A Binds Group B Streptococcus Enhancing Phagocytosis and Clearance from Lungs of Surfactant Protein-A–Deficient Mice (1999)

Abstract Surfactant protein-A (SP-A) gene–targeted mice clear group B streptococcus (GBS) from the lungs at a slower rate than wild-type mice. To determine mechanisms by which SP-A enhances pulmonary clearance of GBS, the role of SP-A in binding and phagocytosis of GBS was assessed in SP-A (−/−) mice infected with GBS in the presence and absence of exogenous SP-A. Coadministration of GBS with exogenous SP-A decreased GBS colony counts in lung homogenates of SP-A (−/−) mice. SP-A bound to GBS in a calcium-dependent manner. Although pulmonary infiltration with macrophages was not altered in SP-A (−/−) versus wild-type mice after GBS infection, the number of alveolar macrophages with phagocytosed bacteria was lower in the SP-A (−/−) mice than in the wild-type mice. When SP-A was coadministered with GBS, phagocytosis was significantly increased. Oxygen radical production by alveolar macrophages from SP-A (−/−) mice infected with GBS was decreased compared with wild-type controls and was increased when SP-A (−/−) mice were infected in the presence of exogenous SP-A. Superoxide (SO) radical generation was deficient in macrophages from SP-A (−/−) mice. SP-A plays an important role in GBS clearance in vivo, mediated in part by binding to and enhancing GBS phagocytosis and by increasing SO production by alveolar macrophages.
Self‐processing of ribozyme‐flanked RNAs into guide RNAs in vitro and in vivo for CRISPR‐mediated genome editing (2013)

CRISPR/Cas9 uses a guide RNA (gRNA) molecule to execute sequence-specific DNA cleavage and it has been widely used for genome editing in many organisms. Modifications at either end of the gRNAs often render Cas9/gRNA inactive. So far, production of gRNA in vivo has only been achieved by using the U6 and U3 snRNA promoters. However, the U6 and U3 promoters have major limitations such as a lack of cell specificity and unsuitability for in vitro transcription. Here, we present a versatile method for efficiently producing gRNAs both in vitro and in vivo. We design an artificial gene named RGR that, once transcribed, generates an RNA molecule with ribozyme sequences at both ends of the designed gRNA. We show that the primary transcripts of RGR undergo self-catalyzed cleavage to generate the desired gRNA, which can efficiently guide sequence-specific cleavage of DNA targets both in vitro and in yeast. RGR can be transcribed from any promoters and thus allows for cell- and tissue-specific genome editing if appropriate promoters are chosen. Detecting mutations generated by CRISPR is often achieved by enzyme digestions, which are not very compatible with high-throughput analysis. Our system allows for the use of universal primers to produce any gRNAs in vitro, which can then be used with Cas9 protein to detect mutations caused by the gRNAs/CRISPR. In conclusion, we provide a versatile method for generating targeted mutations in specific cells and tissues, and for efficiently detecting the mutations generated.
Photonic crystal enhanced fluorescence immunoassay on diatom biosilica (2018)

Fluorescence biosensing is one of the most established biosensing methods, particularly fluorescence spectroscopy and microscopy. These are two highly sensitive techniques but require high-grade electronics and optics to achieve the desired sensitivity. Efforts have been made to implement these methods using consumer grade electronics and simple optical setups for applications such as point-of-care diagnostics, but the sensitivity inherently suffers. Sensing substrates, capable of enhancing fluorescence are thus needed to achieve high sensitivity for such applications. In this paper, we demonstrate a photonic crystal-enhanced fluorescence immunoassay biosensor using diatom biosilica, which consists of silica frustules with sub-100 nm periodic pores. Utilizing the enhanced local optical field, the Purcell effect and increased surface area from the diatom photonic crystals, we create ultrasensitive immunoassay biosensors that can significantly enhance fluorescence spectroscopy as well as fluorescence imaging. Using standard antibody-antigen-labeled antibody immunoassay protocol, we experimentally achieved 100× and 10× better detection limit with fluorescence spectroscopy and fluorescence imaging respectively. The limit of detection of the mouse IgG goes down to 10<sup>-16</sup> M (14 fg/mL) and 10<sup>-15</sup> M (140 fg/mL) for the two respective detection modalities, virtually sensing a single mouse IgG molecule on each diatom frustule. The effectively enhanced fluorescence imaging in conjunction with the simple hot-spot counting analysis method used in this paper proves the great potential of diatom fluorescence immunoassay for point-of-care biosensing.
[Ulcerative colitis]. (2014)

Ulcerative colitis (UC) is a prevalent inflammatory bowel disease of the colonic mucosa affecting approximately 20,000-25,000 Danes. Apart from subgroups with early onset, extensive and long-standing inflammation, or primary sclerosing cholangitis the risk of developing colorectal cancer is of the same magnitude as in the background population. The symptoms are usually diarrhoea including bloody stools, rectal tenesmi, anaemia, and fatigue. This review is an update on diagnostics and treatment strategies of relevance for clinicians, and as UC often affects patients during their peak reproductive years, emphasis is additionally put on the management of pregnant patients with UC.
Phase I Trial of Overlapping Long Peptides from a Tumor Self-Antigen and Poly-ICLC Shows Rapid Induction of Integrated Immune Response in Ovarian Cancer Patients (2012)

The current study shows that NY-ESO-1 OLP vaccine is safe and rapidly induces consistent integrated immune responses (antibody, CD8(+) and CD4(+)) in nearly all vaccinated patients when given with appropriate adjuvants.
Antigen-Antibody Analyses in Neurocysticercosis (1985)

In this report we show that there are 37 polypeptides of larval Taenia solium which react with antibodies from humans with neurocysticercosis. Six of these 37 polypeptides are recognized by antibodies present in the sera of both patients and control individuals. Thus, a minimum of 31 antigens are specific for cysticerci. We describe herein the antigens more frequently recognized by the patients, and the immunoglobulin classes favored in antibody production against each of the cysticercal antigens. It was found that there are 10 major polypeptides with molecular weights of 200,000, 64,000, 62,000-61,000, 53,000, 45,000, 41,000, 36,000-35,000, 30,000 and 16,000 daltons. About 65% of the larval components found to be antigenic are glycoproteins with oligosaccharide chains containing N-acetyl-D-glycosamine and alpha-D-galactose. These results suggest that the sugar moieties of glycoproteins may play a role in the antigenicity of larval T. solium. Based on these observations polypeptides with molecular weights of 64,000, 53,000, and 32,000-30,000 daltons are probably the best choice as sources of antigen to develop an optimal immunological test for the serological diagnosis of neurocysticercosis.
Dynamic tuning of an infrared hybrid-metamaterial resonance using vanadium dioxide (2008)

We demonstrate a metamaterial device whose far-infrared resonance frequency can be dynamically tuned. Dynamic tuning should alleviate many bandwidth-related roadblocks to metamaterial application by granting a wide matrix of selectable electromagnetic properties. This tuning effect is achieved via a hybrid-metamaterial architecture; intertwining split ring resonator metamaterial elements with vanadium dioxide (VO2)-a material whose optical properties can be strongly and quickly changed via external stimulus. This hybrid structure concept opens a fresh dimension in both exploring and exploiting the intriguing electromagnetic behavior of metamaterials.
Microwave‐Assisted Solution‐Phase Synthesis of 1,4,5‐Trisubstituted Pyrazoles (2003)

Abstract A small parallel library of 1,4,5‐trisubstituted pyrazoles was prepared in solution using a three‐step procedure starting from Meldrum acid. The Meldrum acid was acylated with different acyl chlorides and the products opened with different alcohols and amines to give substituted β‐keto esters and β‐keto amines. Further reaction with N , N ‐dimethylformamide dimethylacetal and the final cyclisation were effectively carried out under microwave irradiation. Scavenger resins were employed exclusively in the first step, whereas use of microwaves allowed complete conversion of the starting materials in the other two steps. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)
New drugs for the treatment of cancer, 1990-2001. (2002)

Between 1990 and 2001, altogether 28 new anticancer drugs were approved for use in Israel. The new agents include cytotoxic drugs, biologic compounds, and hormone therapies. Among the cytotoxic agents introduced, the taxanes, vinorelbine, gemcitabine, irinotecan, topotecan and temozolomide, represent important new drugs active in a range of solid malignancies including lung, breast, ovarian, bladder, pancreatic, and colon cancer as well as brain tumors. Epirubicin, idarubicin, and liposomal doxorubicin offer less toxic and in some instances more effective alternatives to older anthracylines for leukemia, breast cancer, ovarian cancer and other diseases. New oral agents are offering a chance for disease palliation without the need for burdensome intravenous access. Rituximab and trastuzumab have introduced monoclonal antibody therapy to the clinic, substantially improving the treatment of patients with lymphoma and breast cancer, respectively. The first tyrosine kinase inhibitor, a molecularly targeted therapy, imatinib, was approved for use in chronic myeloid leukemia and has also shown remarkable activity in gastrointestinal stromal tumors. A variety of aromatase inhibitors have provided less toxic and more effective hormone therapy for the treatment of breast cancer. The challenge for clinicians is to optimize the use of the new available agents for their patients' benefit, and the challenge for health policy-makers in Israel is to integrate the new anticancer pharmaceuticals into the basic health benefits package mandated for all citizens.
9-Aminoacridine peptide derivatives as versatile reporter systems for use in fluorescence lifetime assays (2010)

A novel long lifetime fluorescence reporter based on 9-aminoacridine was designed, the lifetime of which can be modulated in a defined manner when in proximity to a tryptophan residue enabling fluorescence lifetime based biochemical assays to be configured.
A New Strategy for the Synthesis of Glycoproteins (2004)

Posttranslational modifications of proteins regulate many biological processes, including metabolism, signal transduction, and gene expression. The synthetic challenges associated with generating homogeneous populations of selectively modified proteins, however, have hindered detailed studies of the effects of these modifications on protein structure and function. Here, we report an approach to the cotranslational synthesis of selectively glycosylated proteins in which the modified amino acid is genetically encoded. We show that myoglobin containing beta-N-acetylglucosamine (GlcNAc)-serine at a defined position can be expressed in Escherichia coli in good yield and with high fidelity. The beta-GlcNAc moiety can be recognized by a saccharide-binding protein, or subsequently modified with a galactosyltransferase to build more complex carbohydrates. This approach should be generally applicable to other posttranslational modifications such as protein phosphorylation, acetylation, and methylation.
The BB1 Monoclonal Antibody Recognizes Both Cell Surface CD74 (MHC Class II-Associated Invariant Chain) as Well as B7-1 (CD80), Resolving the Question Regarding a Third CD28/CTLA-4 Counterreceptor (1998)

The identification of all CD28/CTLA-4 counterreceptors is critical to our understanding of this pivotal pathway of T cell activation. Clouding our understanding has been the reported discrepancies in expression and function of the B7-1 (CD80) molecule based upon the use of the BB1 vs other anti-B7-1 mAbs. To resolve this issue, we have cloned a BB1-binding molecule from the BB1+B7-1(-) NALM-6 pre-B cell line. Here, we demonstrate that this BB1-binding molecule is identical to the cell surface form of CD74 (MHC class II-associated invariant chain). CD74-transfected cells bound the BB1 mAb but not other anti-CD80 mAbs, CD28-Ig, or CTLA4Ig. Absorption and blocking experiments confirmed the reactivity of BB1 mAb with CD74. A region of weak homology was identified between CD74 and the region of B7-1 encoding the BB1 epitope. Therefore, the BB1 mAb binds to a protein distinct from B7-1, and this epitope is also present on the B7-1 protein. Many of the puzzling observations in the literature concerning the expression of human B7-1 are resolved by an understanding that BB1 staining is the summation of CD74 plus B7-1 expression. This observation requires the field to reconsider studies using BB1 mAb in the analysis of CD80 expression and function.
Probing Immunosuppressant Action with a Nonnatural Immunophilin Ligand (1990)

The immunosuppressants FK506 and rapamycin bind to the same immunophilin, FK506 binding protein (FKBP), and inhibit distinct signal transduction pathways in T lymphocytes. A nonnatural immunophilin ligand, 506BD, which contains only the common structural elements of FK506 and rapamycin, was synthesized and found to be a high-affinity ligand of FKBP and a potent inhibitor of FKBP rotamase activity. Whereas 506BD does not interfere with T cell activation, it does block the immunosuppressive effects of both FK506 and rapamycin. Thus, the common immunophilin binding element of these immunosuppressants, which is responsible for rotamase inhibition, is fused to different effector elements, resulting in the inhibition of different signaling pathways. Inhibition of rotamase activity is an insufficient requirement for mediating these effects.
Interferon‐γ secretion by peripheral blood T‐cell subsets in multiple sclerosis: Correlation with disease phase and interferon‐β therapy (1999)

Interferon-γ (IFN-γ) is implicated as a participant in the immune effector and regulatory mechanisms considered to mediate the pathogenesis of multiple sclerosis (MS). We have used an intracellular cytokine staining technique to demonstrate that the proportion of ex vivo peripheral blood CD4 and CD8 T-cell subsets expressing IFN-γ is increased in secondary progressing (SP) MS patients, whereas the values in untreated relapsing-remitting (RR) MS patients are reduced compared with those of controls. Patients treated with interferon-β (IFN-β) have an even more significant reduction in the percentage of IFN-γ–secreting cells. The finding that the number of IFN-γ–expressing CD8 cells is increased in SPMS patients, a group with reduced functional suppressor activity, and is most significantly reduced by IFN-β therapy, which increases suppressor activity, indicates that IFN-γ secretion by CD8 T cells and functional suppressor defects attributed to this cell subset in MS can be dissociated. Ann Neurol 1999;45:247–250
Building Natural-Language Generation Systems (1996)

This is a very short paper that briefly discusses some of the tasks that NLG systems perform. It is of no research interest, but I have occasionally found it useful as a way of introducing NLG to potential project collaborators who know nothing about the field.