gebhart/patrepeval huggingface dataset:
Differential Roles of Viral RNA and cRNA in Functional Modulation of the Influenza Virus RNA Polymerase (2001)

The RNA-dependent RNA polymerase of influenza virus is composed of three viral P proteins (PB1, PB2, and PA) and involved in both transcription and replication of the RNA genome. For the molecular anatomy of this multifunctional enzyme, we have established a simultaneous expression of three P proteins in cultured insect cells using recombinant baculoviruses. For purification of P protein complexes, the PA protein was expressed as a fusion with a histidine tag added at its N terminus. By using affinity chromatography, a complex consisting of the three P proteins was isolated from nuclear extracts of virus-infected cells. The affinity-purified 3P complex showed the activities of capped RNA binding, capped RNA cleavage, viral model RNA binding, model RNA-directed RNA synthesis, and polyadenylation of newly synthesized RNA. We conclude that a functional form of the viral RNA polymerase with the catalytic specificity of transcriptase is formed in recombinant baculovirus-infected insect cells. Using the viral RNA-free 3P complex, we found that the capped RNA cleavage takes place in the presence of vRNA but not of cRNA, indicating that the vRNA functions as a regulatory factor for the specificity control of viral RNA polymerase as well as a template for transcription. The structural elements of RNA directing the expression of RNA polymerase functions were analyzed using variant forms of the model RNA templates.
Update on the risk of lymphoma following immunosuppressive therapy for inflammatory bowel disease (2010)

The care of inflammatory bowel disease has changed considerably with the introduction of a number of immunosuppressants including anti-metabolite and anti-TNF therapies. While efficacious, these medications also carry important risks, notably the potential risk of lymphoma. This risk is one of the most worrisome for both patients and physicians. Our current knowledge is still evolving; however, our understanding of what risks these drugs carry, both individually and synergistically, is critical in allowing informed decision making. In this article, we will describe the known lymphoma risks of commonly used immunosuppressant medications in inflammatory bowel disease, with an emphasis on non-Hodgkin's lymphoma and hepatosplenic T-cell lymphoma.
Vertical wrap-gated nanowire transistors (2006)

We present a process for fabricating a field-effect transistor based on vertically standing InAs nanowires and demonstrate initial device characteristics. The wires are grown by chemical beam epitaxy at lithographically defined locations. Wrap gates are formed around the base of the wires through a number of deposition and etch steps. The fabrication is based on standard III - V processing and includes no random elements or single nanowire manipulation.
High-Cooperativity Coupling of Electron-Spin Ensembles to Superconducting Cavities (2010)

Electron spins in solids are promising candidates for quantum memories for superconducting qubits because they can have long coherence times, large collective couplings, and many qubits could be encoded into spin waves of a single ensemble. We demonstrate the coupling of electron-spin ensembles to a superconducting transmission-line cavity at strengths greatly exceeding the cavity decay rates and comparable to the spin linewidths. We also perform broadband spectroscopy of ruby (Al₂O₃:Cr(3+)) at millikelvin temperatures and low powers, using an on-chip feedline. In addition, we observe hyperfine structure in diamond P1 centers.
Allospecific human T cell lines and clones which mediate HLA-DR restricted helper activity. (1982)

In order to analyze the immunoregulatory activity of allospecific human T cells, we have combined the techniques of limiting dilution culture and IL-2 dependent T cell growth to generate cloned alloreactive T cell lines (TCL). These TCL have been expanded in continuous culture for greater than 8 mo with retention of stable phenotypic and functional characteristics. For example, phenotypic analysis of alloproliferative TCL, utilizing a panel of monoclonal antibodies, demonstrate that these cultures are comprised of T cells belonging exclusively to the T3+ T4+ T8- "helper" or "inducer" T cell subset. Coculture of cloned alloproliferative TCL cells with a panel of allogeneic stimulators reveals that these clones are specifically reactive against the HLA-DRw1 determinant. Of greater interest, coculture of selected alloproliferative TCL cells with DRw1+ but not DRw1- B cells results in a vigorous polyclonal response as measured by the reverse hemolytic plaque assay. Although major histocompatibility complex restriction of this T-B interaction operates at the inductive level, help is at least partially unrestricted at the effector level as alloantigen-activated TCL cells provide demonstrable, although not maximal, help for DRw1- B cells.
Processing and metabolism of peptide-YY: pivotal roles of dipeptidylpeptidase-IV, aminopeptidase-P, and endopeptidase-24.11. (1994)

The processing of peptide-YY (PYY) by purified membrane peptidases and brush border membrane preparations from human kidney and jejunum has been compared. Dipeptidyl peptidase-IV hydrolyzes PYY at the Pro2-Ile3 bond, producing PYY-(3-36), which is a Y2 receptor-selective ligand. Aminopeptidase-P removes the N-terminal tyrosine from PYY, but the intact peptide is not a substrate for aminopeptidase-N. Endopeptidase-24.11 (neutral endopeptidase; enkephalinase) metabolizes PYY efficiently, with a major site of hydrolysis at the Asn29-Leu30 bond, an inactivating cleavage. Angiotensin-converting enzyme does not hydrolyze PYY. In renal brush border membranes, hydrolysis of PYY is substantially (> 75%) inhibited by phosphoramidon, suggesting that endopeptidase-24.11 initiates hydrolysis of PYY in this preparation. In jejunal brush border membranes, phosphoramidon has a much smaller effect (15% inhibition), and contributions due to the actions of aminopeptidase-P and dipeptidyl peptidase-IV were evident. Few physiological substrates have yet been identified for aminopeptidase-P and dipeptidyl peptidase-IV; the pancreatic polypeptide fold family, of which PYY is a member, may well represent endogenous substrates for those cell surface ectoenzymes. Dipeptidyl peptidase-IV converts PYY to a metabolite PYY-(3-36), a highly selective agonist for the Y2 receptor type. Thus, the relative levels of the three membrane peptidases at different tissue locations and on different cell types may play a pivotal role in postsecretory processing and metabolism of PYY to receptor-selective agonists or inactive metabolites.
Positive matrix factorization: A non‐negative factor model with optimal utilization of error estimates of data values (1994)

Abstract A new variant ‘PMF’ of factor analysis is described. It is assumed that X is a matrix of observed data and σ is the known matrix of standard deviations of elements of X . Both X and σ are of dimensions n × m . The method solves the bilinear matrix problem X = GF + E where G is the unknown left hand factor matrix (scores) of dimensions n × p , F is the unknown right hand factor matrix (loadings) of dimensions p × m , and E is the matrix of residuals. The problem is solved in the weighted least squares sense: G and F are determined so that the Frobenius norm of E divided (element‐by‐element) by σ is minimized. Furthermore, the solution is constrained so that all the elements of G and F are required to be non‐negative. It is shown that the solutions by PMF are usually different from any solutions produced by the customary factor analysis (FA, i.e. principal component analysis (PCA) followed by rotations). Usually PMF produces a better fit to the data than FA. Also, the result of PF is guaranteed to be non‐negative, while the result of FA often cannot be rotated so that all negative entries would be eliminated. Different possible application areas of the new method are briefly discussed. In environmental data, the error estimates of data can be widely varying and non‐negativity is often an essential feature of the underlying models. Thus it is concluded that PMF is better suited than FA or PCA in many environmental applications. Examples of successful applications of PMF are shown in companion papers.
Creatine kinase brain overexpression protects colorectal cells from various metabolic and non‐metabolic stresses (2011)

Creatine kinase brain (CKB) is one of three cytosolic isoforms of creatine kinase that is predominantly expressed in the brain. The enzyme is overexpressed in a wide variety of cancers, with the exception of colon cancer, where it is downregulated. The significance of this downregulation remains poorly understood. Here, we demonstrate that overexpression of CKB-C283S, a dominant-negative construct that lacks the kinase function but retains its ability to dimerize, causes remarkable changes in cell shape, adhesion, and invasion. Furthermore, it results in increased expression of stromal cell markers such as PAGE4 and SNAIL, suggesting an epithelial-to-mesenchymal transition (EMT) in these cells. In cells transfected with a CKB-expressing construct, CKB localizes not only to the cytosol but also to the nucleus, indicating a structural or kinase role unrelated to ATP storage. Furthermore, overexpression of CFP-tagged wild-type (WT) CKB in Caco-2 colon cancer cells dramatically increased the number of cells in G2/M but had little effect on cell proliferation. Taken together, these data demonstrate that the downregulation of CKB may play an important role in colon cancer progression by promoting EMT.
Aluminum Content of Neonatal Parenteral Nutrition Solutions (2016)

The study indicates that solutions containing CaCl<sub>2</sub> or CaGluc-Pl and NaPhos or NaGP are low in Al content. Using these options for calcium and phosphate additives can limit aluminum intake from neonatal PN to levels within the Food and Drug Administration guideline of ≤5 mcg/kg/d.
Panoptic Segmentation with a Joint Semantic and Instance Segmentation Network (2018)

We present a single network method for panoptic segmentation. This method combines the predictions from a jointly trained semantic and instance segmentation network using heuristics. Joint training is the first step towards an end-to-end panoptic segmentation network and is faster and more memory efficient than training and predicting with two networks, as done in previous work. The architecture consists of a ResNet-50 feature extractor shared by the semantic segmentation and instance segmentation branch. For instance segmentation, a Mask R-CNN type of architecture is used, while the semantic segmentation branch is augmented with a Pyramid Pooling Module. Results for this method are submitted to the COCO and Mapillary Joint Recognition Challenge 2018. Our approach achieves a PQ score of 17.6 on the Mapillary Vistas validation set and 27.2 on the COCO test-dev set.
Blood group-related antigens in human germ cell tumors. (1988)

With the use of immunohistochemical techniques, seven mouse monoclonal antibodies and the lectin from Ulex europaeus, detecting blood group antigens of the ABH and Lewis systems, have been used to define the distribution of these antigenic structures in germ cell tumors. The reagents used recognize the following blood group antigens: A, B, H, Lewisa, Lewisb, X (Lewisx), Y (Lewisy), and type I precursor antigen. Tumors from 29 patients were studied. Tumors studied consisted of pure embryonal carcinoma for eight patients, pure yolk sac tumor for two patients, embryonal carcinoma plus yolk sac tumor in one patient, and yolk sac tumor plus seminoma in one patient. Also studied were nine classic seminomas and a group of six patients with tumors classified as seminomas that exhibited atypical histological features. One patient had an anaplastic carcinoma arising from the mediastinum which could not be conclusively identified as a germ cell tumor morphologically and was analyzed separately. All embryonal carcinomas and yolk sac tumors exhibited strong positivity for type I precursor structure as detected by the K-21 monoclonal antibody. In marked contrast, there was non staining in classic seminomas but heterogeneous staining in five of six atypical seminomas. The majority of embryonal carcinomas and all yolk sac tumors studied demonstrated strong positivity for blood group antigen H. For seminoma, however, only one of the atypical cases and two of the classic cases (occasional cells) stained for H. Focal expression of the Y antigen was identified in 5 of 17 seminomas and in the majority of embryonal carcinomas and yolk sac tumors. Two yolk sac tumors and two classic seminomas expressed blood group X. The remaining blood group antigens were not expressed by seminomas while they were variably expressed by embryonal carcinoma and yolk sac tumors. These data suggest that K-21 and blood group antigen H may be distinguishing markers of nonseminomatous germ cell tumor versus seminoma. If so, it is possible that the heterogeneous expression of blood group substances in seminomas with atypical histologies is an indication of differentiation towards nonseminomatous germ cell tumor.
The evolving biology and treatment of prostate cancer (2007)

Since the effectiveness of androgen deprivation for treatment of advanced prostate cancer was first demonstrated, prevention strategies and medical therapies for prostate cancer have been based on understanding the biologic underpinnings of the disease. Prostate cancer treatment is one of the best examples of a systematic therapeutic approach to target not only the cancer cells themselves, but the microenvironment in which they are proliferating. As the population ages and prostate cancer prevalence increases, challenges remain in the diagnosis of clinically relevant prostate cancer as well as the management of the metastatic and androgen-independent metastatic disease states.
Managing stored voice in the Etherphone system (1988)

The voice manager in the Etherphone system provides facilities for recording, editing, and playing stored voice in a distributed personal-computing environment. It provides the basis for applications such as voice mail, annotation of multimedia documents, and voice editing using standard text-editing techniques. To facilitate sharing, the voice manager stores voice on a special voice file server that is accessible via the local internet. Operations for editing a passage of recorded voice simply build persistent data structures to represent the edited voice. These data structures, implementing an abstraction called voice ropes , are stored in a server database and consist of lists of intervals within voice files. Clients refer to voice ropes solely by reference. Interests , additional persistent data structures maintained by the server, serve two purposes: First, they provide a sort of directory service for managing the voice ropes that have been created. More importantly, they provide a reliable reference-counting mechanism, permitting the garbage collection of voice ropes that are no longer needed. These interests are grouped into classes; for some important classes, obsolete interests can be detected and deleted by a class-specific algorithm that runs periodically.
Beyond Greater Efficiency: The Concept of Water Soft Path (2005)

Even in "water-rich" Canada, many jurisdictions are having trouble providing adequate, clean fresh water as their populations not only grow but exhibit higher expectations for water availability and water safety. The conventional approach to such problems accepted the history of constantly growing demand for water and responded by extending pipelines, constructing more dams and drilling deeper. The alternative to this engineering approach is to put greater emphasis in demand-side policies promoting water efficiency and conservation. Full-cost pricing along with better information and education programs can help a great deal, but will not likely be sufficient to meet future water problems. Fortunately, there is a stronger, albeit normative, demand-side alternative called the water soft path, which is modelled on the highly successful approach known as the soft energy path. Soft paths can be described as approaches to natural resources management that rely on a multitude of relatively small-scale and renewable sources of supply coupled with ultra-efficient ways of meeting end-use demands. This paper will contrast water soft paths with the conventional (hard path) approaches, and then review the methodology and feasibility of soft path analysis.
The Narrow Proton Beam Therapy Unit at the Svedberg Laboratory in Uppsala (1991)

The synchrocyclotron at the The Svedberg Laboratory (TSL) in Uppsala is now reconstructed and can presently operate with fixed frequency and proton energies up to 100 MeV. A first treatment room with a narrow proton beam unit for therapy of eye tumours is now in operation. Therapy of eye melanomas started in April, 1989 and during 1989 and 1990, 19 patients were treated with 72 MeV protons. The narrow beam unit provides a fixed horizontal beam and the patient is treated in a seated position. The present paper describes mainly the technical aspects of the unit which so far has been used only for eye melanomas. In the future, modifications of the unit will allow therapy of intracranial targets when higher proton energies are available. In its final form, the proton therapy facility at TSL will harbour a second treatment unit. Here a rotating gantry for 200 MeV protons will provide a broad beam, which will enable treatment of tumours located anywhere in the body.
MULTIPROSPECTOR: An algorithm for the prediction of protein–protein interactions by multimeric threading (2002)

In this postgenomic era, the ability to identify protein-protein interactions on a genomic scale is very important to assist in the assignment of physiological function. Because of the increasing number of solved structures involving protein complexes, the time is ripe to extend threading to the prediction of quaternary structure. In this spirit, a multimeric threading approach has been developed. The approach is comprised of two phases. In the first phase, traditional threading on a single chain is applied to generate a set of potential structures for the query sequences. In particular, we use our recently developed threading algorithm, PROSPECTOR. Then, for those proteins whose template structures are part of a known complex, we rethread on both partners in the complex and now include a protein-protein interfacial energy. To perform this analysis, a database of multimeric protein structures has been constructed, the necessary interfacial pairwise potentials have been derived, and a set of empirical indicators to identify true multimers based on the threading Z-score and the magnitude of the interfacial energy have been established. The algorithm has been tested on a benchmark set comprised of 40 homodimers, 15 heterodimers, and 69 monomers that were scanned against a protein library of 2478 structures that comprise a representative set of structures in the Protein Data Bank. Of these, the method correctly recognized and assigned 36 homodimers, 15 heterodimers, and 65 monomers. This protocol was applied to identify partners and assign quaternary structures of proteins found in the yeast database of interacting proteins. Our multimeric threading algorithm correctly predicts 144 interacting proteins, compared to the 56 (26) cases assigned by PSI-BLAST using a (less) permissive E-value of 1 (0.01). Next, all possible pairs of yeast proteins have been examined. Predictions (n = 2865) of protein-protein interactions are made; 1138 of these 2865 interactions have counterparts in the Database of Interacting Proteins. In contrast, PSI-BLAST made 1781 predictions, and 1215 have counterparts in DIP. An estimation of the false-negative rate for yeast-predicted interactions has also been provided. Thus, a promising approach to help assist in the assignment of protein-protein interactions on a genomic scale has been developed.
Hepatitis B Virus X Protein Colocalizes to Mitochondria with a Human Voltage-Dependent Anion Channel, HVDAC3, and Alters Its Transmembrane Potential (2000)

Understanding the mechanism(s) of action of the hepatitis B virus (HBV)-encoded protein HBx is fundamental to elucidating the underlying mechanisms of chronic liver disease and hepatocellular carcinoma caused by HBV infection. In our continued attempts to identify cellular targets of HBx, we have previously reported the identification of a novel cellular protein with the aid of a yeast two-hybrid assay. This cellular gene was identified as a third member of the family of human genes that encode the voltage-dependent anion channel (HVDAC3). In the present study, physical interaction between HBx and HVDAC3 was established by standard in vitro and in vivo methods. Confocal laser microscopy of transfected cells with respective expression vectors colocalized HVDAC3 and HBx to mitochondria. This novel, heretofore unreported subcellular distribution of HBx in mitochondria implies a functional role of HBx in functions associated with mitochondria. Using a stable cationic fluorophore dye, CMXRos, we show that HBx expression in cultured human hepatoma cells leads to alteration of mitochondrial transmembrane potential. Such functional roles of HBx in affecting mitochondrial physiology have implications for HBV-induced liver injury and the development of hepatocellular carcinoma.
Regulation of Cellular Plasticity Cascades in the Pathophysiology and Treatment of Mood Disorders (2003)

There is increasing evidence from a variety of sources that mood disorders are associated with regional reductions in brain volume, as well as reductions in the number, size, and density of glia and neurons in discrete brain areas. Although the precise pathophysiology underlying these morphometric changes remains to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. In this context, it is noteworthy that a growing body of data suggests that the glutamatergic system--which is known to play a major role in neuronal plasticity and cellular resilience--may be involved in the pathophysiology and treatment of mood disorders. Preclinical studies have shown that the glutamatergic system represents targets (often indirect) for the actions of antidepressants and mood stabilizers. There are a number of glutamatergic "plasticity enhancing" strategies that may be of considerable utility in the treatment of mood disorders. Among the most immediate ones are NMDA antagonists, inhibitors of glutamate-release agents, and AMPA potentiators; this research progress holds much promise for the development of novel therapeutics for the treatment of severe, refractory mood disorders.
A linkage map of the Atlantic salmon (Salmo salar) based on EST-derived SNP markers (2008)

The linkage map presented here is an important resource for genetic, comparative, and physical mapping of the Atlantic salmon. The female map is likely to have a map coverage that is not far from complete, whereas the male map length is likely to be significantly shorter than the true map, due to suboptimal marker coverage in the apparently small physical regions where male crossovers occur. 'Useful LD' was found at inter-marker distances less than 5 cM.