gebhart/patrepeval huggingface dataset:
Directing phage selections towards specific epitopes (1996)

It is possible to direct selections from antibody repertoires displayed on filamentous phage towards unique epitopes on protein antigens by competing with related molecules. A phage display repertoire of human single chain Fvs (scFvs) was panned three times against foetal haemoglobin (HbF). The selection was dominated by one clone with a Kd of 10 nM but yielded at least 17 others, all of which bound HbF but crossreacted with adult haemoglobin (HbA). To direct selection towards HbF-specific epitopes, the repertoire was preincubated with HbA in solution before each panning. Crossreactive scFvs can form complexes with the soluble HbA and thereby be prevented from binding the immobilized HbF. Four clones with preferential binding to HbF emerged under these conditions. One of these (Hb-1), with a Kd of 6 microM, had exquisite specificity for HbF and could distinguish cells expressing HbF from those expressing HbA by immunocytochemistry and flow cytometry. This antibody has an affinity that is 600-fold lower than the dominant crossreactive clone, and so only emerged under conditions of 'competitive deselection'. Thus, competitive deselection is a viable means for directing selections towards useful epitopes. It permits a more effective 'search' of phage display repertoires and allows the emergence of lower affinity clones with useful specificities. These clones may be useful in themselves or may serve as leads for in vitro affinity maturation.
The role of transforming growth factor‐β in PEG‐rHuMGDF‐induced reversible myelofibrosis in rats (1997)

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) injected at a suprapharmacologic dose (100 microg/kg) daily for 5 d in normal rats caused marked increases in marrow megakaryocytes and platelet counts at 6-8 d followed by gradual decreases to control levels at 10-20 d. Interestingly, in addition to the expected thrombopoiesis, PEG-rHuMGDF was associated with myelofibrosis with a predominance of reticulin fibres at day 10 followed by complete normalization by day 20. At 6-8 d, the levels of transforming growth factor-beta1 (TGF-beta1) in the extracellular fluid of the marrow, the platelet poor plasma, and the platelet extract were increased 23-, 7- and 2-fold, respectively. The elevated levels of TGF-beta1 were gradually reduced to baseline levels at 13-20 d in accordance with the normalization of myelofibrosis and thrombopoiesis. An ultrastructural analysis showed that large fragments of megakaryocytes were deposited in the marrow parenchyma of PEG-rHuMGDF-treated rats at day 6. PEG-rHuMGDF administration at pharmacologic doses (1 and 10 microg/kg) did not induce the deposition of reticulin fibres in the marrow. These findings suggest that TGF-beta1 leaked from megakaryocytes is involved in the development of the PEG-rHuMGDF-induced myelofibrosis and that this is a reversible process related to the regulation of the excess production of platelets.
Ideal Ohmic contact to n-type 6H-SiC by reduction of Schottky barrier height (1997)

We formed ideal Ti Ohmic contacts on an n-type 6H-SiC epitaxial layer by reducing Schottky barrier heights. The ideal contacts were realized by utilizing ideal SiC surfaces formed under processes that intend to lower the density of surface states. As the first process to form the ideal surfaces, SiC surfaces were flattened by oxidation followed by HF etching. Further, the ideal SiC surfaces in terms of passivation of surface states were formed by immersing the flat SiC surfaces in boiling water. Ti electrodes thus formed had Ohmic properties with excellent I–V characteristic linearity without the use of heavy doping and high-temperature annealing.
How-to guide on biomarkers: biomarker definitions, validation and applications with examples from cardiovascular disease (2009)

A biomarker is a characteristic that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention. Many commonly used tests in clinical practice can serve as biomarkers. The majority have been identified on the basis of insight or underlying physiology or biological mechanisms. With increasing knowledge and practical experience, some of these tests have evolved into a measurable end point in clinical research, applied as an indicator of change, for the better or worse. The traditional identification of biomarkers as an observational side product of clinical practice is increasingly turning into an industrialised process of biomarker discovery, supported by standardised paradigms of biomarker validation and translation from bench to bedside. The potential utility of biomarkers in clinical studies, investigating either new treatments or new strategies of clinical management, is capitalizing on recent advances in technology, from molecular sciences to powerful imaging, bearing the promise of expediting the discovery of new treatments. In the active search for new biomarkers, many potential candidates can be considered side by side, allowing many failures but a few great winners. Biomarker discovery is an ongoing process, with translation being tested de novo in every single study, providing us with the opportunity to revise our knowledge of the complex scheme of human physiology and pathophysiology. In predicting what Nature has set in place, advances in technology may be only the first step. This review provides an introduction to the field of biomarker discovery and translation. It deals with evolving nomenclature, basic principles of the validation process, and, drawing on examples in cardiovascular medicine, their significance for clinical application.
Amplicon Sequencing and Improved Detection of Human Rhinovirus in Respiratory Samples (2004)

Improved knowledge of the genotypic characteristics of human rhinovirus (HRV) is required, as are nucleic detection assays with the capacity to overcome both the similarities between members of the family Picornaviridae and the wide diversity of different HRV serotypes. The goal of the present study was to investigate the variability and the genotypic diversity of clinical strains circulating in the community. Since most reverse transcription (RT)-PCR assays available cannot differentiate HRV from other members of the family Picornaviridae, we also validated an assay specific for HRV detection. The 5' noncoding regions of 87 different HRV serotypes and clinical isolates were sequenced. On the basis of sequence analysis and phylogenetic determination, we first confirmed that all clinical isolates were HRV. We then validated a real-time RT-PCR assay that was able not only to detect all HRV serotypes and all clinical isolates tested but also to accurately discriminate between rhinovirus and other viruses from the family Picornaviridae. This assay was negative with isolates of coxsackievirus (types A and B), echovirus, enterovirus, parechovirus, and poliovirus, as well as nonpicornaviruses. Among a series of bronchoalveolar lavage specimens, 4% (7 of 161) were positive by culture, whereas 13% (21 of 161) were positive by RT-PCR. In the present study we showed that to specifically identify HRV in clinical specimens, diagnostic assays need to overcome both the diversities and the similarities of picornaviruses. By sequencing the 5' noncoding regions of rhinoviruses recovered from clinical specimens, we designed probes that could specifically detect rhinovirus.
Cognitive and limbic circuits that are affected by deep brain stimulation (2009)

Several lines of evidence indicate that the neural network that underlies the pathophysiology of obsessive-compulsive disorder and depression centers on the prefronto-basal ganglia system. Particularly involved are anterior cingulate cortex, the orbital prefrontal cortex, the ventral striatum, and parts of the thalamus. Additional integral parts of the network include, the amygdala, the midbrain dopamine cells and the serotonergic neurons. Collectively, these brain regions are involved in various aspects of reward-based learning and good decision-making skills. They are also associated with sadness and depression, pathological risk-taking, addictive behaviors, and obsessive-compulsive disorder. Two of the most successful deep brain stimulation targets for obsessive-compulsive disorder and depression are centered in white matter tracts. These targets were chosen for their central location and ability to capture specific ascending and descending connections, with a particular focus on fibers connecting the subgenual anterior cingulate and orbital cortex with the basal ganglia, thalamus, and amygdala. As more knowledge is obtained concerning the details of these connections, more precise targets may be possible.
The Reduction of 2-Indanone Oxime to 2-Aminoindane. Methods and Mechanisms (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Reduction of 2-Indanone Oxime to 2-Aminoindane. Methods and MechanismsWilliam E. Rosen and Michael J. GreenCite this: J. Org. Chem. 1963, 28, 10, 2797–2804Publication Date (Print):October 1, 1963Publication History Published online1 May 2002Published inissue 1 October 1963https://pubs.acs.org/doi/10.1021/jo01045a074https://doi.org/10.1021/jo01045a074research-articleACS PublicationsRequest reuse permissionsArticle Views815Altmetric-Citations26LEARN 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-Alertsclose Get e-Alerts
TLR3 Increases Disease Morbidity and Mortality from Vaccinia Infection (2008)

Innate immunity is required for effective control of poxvirus infections, but cellular receptors that initiate the host response to these DNA viruses remain poorly defined. Given this information and the fact that functions of TLRs in immunity to DNA viruses remain controversial, we investigated effects of TLR3 on pathogenesis of vaccinia virus, a prototype poxvirus. We used a recombinant strain Western Reserve vaccinia virus that expresses firefly luciferase to infect wild-type C57BL/6 and TLR3-/- mice through intranasal inoculation. Bioluminescence imaging showed that TLR3-/- mice had substantially lower viral replication in the respiratory tract and diminished dissemination of virus to abdominal organs. Mice lacking TLR3 had reduced disease morbidity, as measured by decreased weight loss and hypothermia after infection. Importantly, TLR3-/- mice also had improved survival relative to wild-type mice. Infected TLR3-/- mice had significantly reduced lung inflammation and recruitment of leukocytes to the lung. Mice lacking TLR3 also had lower levels of inflammatory cytokines, including IL-6, MCP-1, and TNF-alpha in serum and/or bronchoalveolar lavage fluid, but levels of IFN-beta did not differ between genotypes of mice. To our knowledge, our findings show for the first time that interactions between TLR3 and vaccinia increase viral replication and contribute to detrimental effects of the host immune response to poxviruses.
Adaptive fuzzy logic compensation of actuator deadzones (1997)

A deadzone compensator is designed for nonlinear systems using a fuzzy logic (FL) controller. The classification property of FL systems makes them a natural candidate for the rejection of errors induced by the deadzone, which has regions in which it behaves differently. A tuning algorithm is given for the FL parameters so that the deadzone compensation scheme becomes adaptive, guaranteeing small tracking errors and bounded parameter estimates. A rigorous proof of stability and performance is given and a simulation example verifies excellent performance. It is seen that the extra signal produced by the adaptive FL deadzone compensator can be considered as an adaptive dithering term. ©1997 by John Wiley & Sons, Inc.
The mechanical properties of freestanding near-frictionless carbon films relevant to MEMS (2006)

Amorphous, diamond-like carbon films with a mixture of sp2 and sp3 hybridizations have exhibited excellent material properties such as chemical stability, wear resistance and optical transparency resulting in their wide use as protective coatings in numerous applications. The hydrogenated forms of these films, a-C:H, and specifically the near-frictionless carbon (NFC) films developed at Argonne National Laboratory have exhibited the lowest ever recorded friction coefficient, 0.001, and ultra-low wear rates of 10−11−10−10 mm3 N−1 m−1, even under dry sliding conditions and at very high contact pressures (Robertson 2002 Diamond-like amorphous carbon Mater. Sci. Eng. R 37 129). Application of these films to sliding or rotating microelectromechanical systems (MEMS) would open up an entirely new class of commercialized MEMS devices. With this in mind, this paper reports on thin-film mechanical property measurements of the NFC films relevant to MEMS. The membrane deflection experiment was employed to subject microfabricated freestanding films to pure tension and measure mechanical properties such as Young's modulus, residual stress and fracture strength. Young's modulus was consistently measured at 35.13 ± 2.29 GPa. The fracture strength varied from 0.12 GPa to 0.90 GPa and the residual stress state was compressive and ranged from 79 MPa to 310 MPa. Width and thickness effects of the membranes were also observed in this work, where fracture strength increased with decreasing membrane width and thickness. Weibull analysis of the fracture strength is also presented in the paper.
Silicon Nitride Nanosieve Membrane (2004)

An array of very uniform cylindrical nanopores with a pore diameter as small as 25 nm has been fabricated in an ultrathin micromachined silicon nitride membrane using focused ion beam (FIB) etching. The pore size of this nanosieve membrane was further reduced to below 10 nm by coating it with another silicon nitride layer. This nanosieve membrane possesses adequate mechanical strength up to several bars of transmembrane pressure, and it can withstand high temperatures up to 900 °C. In addition, it is inert to many aggressive chemicals such as hot concentrated potassium hydroxide (KOH), piranha (H2SO4 + H2O2), and nitric acid (HNO3).
Automated pipe inspection robot (1997)

Automated inspection of the inner surface of a pipe can be achieved by a mobile robot. Pipe inspection is necessary to locate defects due to corrosion and wear while the pipe is transporting fluids. Pipe inspection devices are available for these tasks; they commonly use ultrasonic or magnetic flux variation to detect defects. Says that the magnitude of the costs involved in the development and implementation of these inspection techniques is such that it inhibits their more frequent and widespread use. Posits that the automated pipe inspection robot presented is a proposed cost‐effective alternative solution. The inspection device is a PC‐based design that uses mechatronic principles to ensure a purposeful interaction between the robot and its environment.
ARE THE TWIN DEFICITS REALLY RELATED? (1989)

The emergence of record current‐account and fiscal deficits in the United States during the 1980s draws increasing attention to what has become known as the “twin deficit” problem. Conventional wisdom is that a shift to larger government deficits entails a decline in government saving and results in larger trade deficits, Persistently large trade deficits are troublesome because they imply a transfer of wealth to foreigners and possibly a reduction in future generations' living standards. This paper examines whether post‐World War II data for the United States reveal a long‐run secular relationship between the trade deficit and the fiscal deficit. The focus is on the secular relationship since that is the one most relevant to long‐run policy concerns. The authors employ three different statistical techniques: (i) a deterministic technique for separating the secular components from the cyclical components to derive secular measures of the twin deficits, (ii) a stochastic procedure to isolate the secular components, (Hi) cointegration analysis to test for a long‐run equilibrium relationship. The authors conclude that, based on the first two approaches, evidence of a positive secular relationship between the twin deficits exists only under flexible exchange rates. This relationship appears quite strong–that is, a $1 change in the fiscal deficit eventually leads to roughly a $1 change in the trade deficit. On the other hand, findings based on cointegration analysis indicate no long‐run equilibrium relationship between the twin deficits. This latter finding, however, may reflect a low power of the relevant statistical tests stemming from the shortness of the sample period.
Evaluation of the dimethylsilyl-bis(2-methyl-4-phenyl-1-indenyl) ligand with group 4 triad metals in propene polymerizations with methylaluminoxane (1998)

Dimethylsilyl-bis(2-methyl-4-phenyl-1-indenyl)MCl2 (M = Ti, Zr, Hf) complexes in combination with methylaluminoxanes produce isotactic polypropene. The Ti catalysts produce isotactic polypropene which is more stereoregular than that obtained with traditional, heterogeneous catalysts. Zr produces low molecular weight, weakly isotactic waxes at phenomenal rates greater than 32 · 106 gPP/[(mol catalyst) · h · (mol/l monomer)]. Hf produces long, softer isotactic chains with good activities.
Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri. (1993)

Viruses are known to acquire and modify the genes of their hosts to attain a survival advantage in the host environment. Herpesvirus saimiri (HVS) is a T-lymphotropic virus that causes fatal lymphoproliferative diseases in several non-human primates. The gene ECRF3 of HVS was most likely acquired from a primate host. ECRF3 encodes a putative seven-transmembrane-domain receptor that is remotely related (approximately 30% amino acid identity) to the known mammalian alpha and beta chemokine receptors, namely interleukin-8 receptor (IL8R) types A and B and the MIP-1 alpha/RANTES receptor, respectively. Chemokines regulate the trafficking, activation, and, in some cases, proliferation of myeloid and lymphoid cell types. We now show that ECRF3 encodes a functional receptor for the alpha chemokines IL-8, GRO/melanoma growth stimulatory activity (MGSA), and NAP-2 but not for beta chemokines, a specificity identical to that of IL8RB. Paradoxically, IL8RA shares 77% amino acid identity with IL8RB but is not a receptor for GRO/MGSA or NAP-2. This is the first functional characterization of a viral seven-transmembrane-domain receptor. It suggests a novel role for alpha chemokines in the pathogenesis of HVS infection by transmembrane signaling via the product of ECRF3.
ABC of heart failure: Aetiology (2000)

### Causes of heart failure

#### Coronary artery disease

#### Hypertension Cardiomyopathy

##### Valvar and congenital heart disease

##### Arrhythmias

##### Alcohol and drugs

##### “High output” failure

##### Pericardial disease

##### Primary right heart failure

The relative importance of aetiological factors in heart failure is dependent on the nature of the population being studied, as coronary artery disease and hypertension are common causes of heart failure in Western countries, whereas valvar heart disease and nutritional cardiac disease are more common in the developing world. Epidemiological studies are also dependent on the clinical criteria and relevant investigations used for diagnosis, as it remains difficult, for example, to distinguish whether hypertension is the primary cause of heart failure or whether there is also underlying coronary artery disease.

Coronary heart disease is the commonest cause of heart failure in Western countries. In the studies of left ventricular dysfunction (SOLVD) coronary artery disease accounted for almost 75% of the cases of chronic heart failure in male white patients, although in the Framingham heart study, coronary heart disease accounted for only 46% of cases of heart failure in men and 27% of chronic heart failure cases in women. Coronary artery disease and hypertension (either alone or in combination) were implicated as the cause in over 90% of cases of heart failure in the Framingham study.

Recent studies that have allocated aetiology on the basis of non.invasive investigations-such as the Hillingdon heart failure study-have identified coronary artery disease as the primary etiology in 36% of cases of heart failure. In the Hillingdon study, however, researchers were not able to identify the primary aetiology in …
Studies of lymphocyte transendothelial migration: analysis of migrated cell phenotypes with regard to CD31 (PECAM-1), CD45RA and CD45RO. (1993)

CD31 is a 130,000 MW cell-surface glycoprotein expressed on endothelial cells, polymorphonuclear leucocytes, monocytes and about 50% of peripheral blood lymphocytes, and it has been proposed that it plays a role in transendothelial migration. If it is involved in endothelial transmigration of lymphocytes then the proportion of CD31+ cells should be increased in the lymphocyte population which has crossed an endothelial monolayer. This was tested using two endothelial types, namely human umbilical vein endothelial cells (HUVEC) and rat high endothelial venule (RHEV) cells. As a control, lymphocyte CD45RA and CD45RO expression was also determined since there is a correlation between lymphocytes bearing these isoforms and different migratory patterns. Double labelling techniques showed a close correlation between CD31 and CD45RA expression. With HUVEC monolayers, the transmigrated lymphocyte population was depleted of CD31+ cells. This depletion was even more marked if the HUVEC monolayers had been stimulated with interleukin-1 beta (IL-1 beta). The migrated lymphocytes were enriched for CD31-CD45RO+ cells but depleted of CD31+CD45RA+ cells. In addition, lymphocyte populations depleted of CD31+ cells by immunopanning were also able to migrate across HUVEC monolayers. Taken together these data suggest that lymphocyte CD31 expression is not necessary for transmigration across HUVEC monolayers and, if anything, is negatively correlated with transmigration. With the second endothelial cell type, RHEV cells, there was no consistent change in the proportion of CD31+ lymphocyte in the transmigrated population, suggesting neither a positive nor a negative correlation between CD31+ expression and lymphocyte transmigration across RHEV cells. However, with both endothelial cell types, the migrated lymphocyte populations were enriched for the marker CD45RO. In conclusion, lymphocyte surface expression of CD31 is not necessary for transmigration across the endothelial cell types used in this study, but with both cell types an enrichment of CD45RO+ lymphocytes is seen in the migrated population.