gebhart/patrepeval huggingface dataset:
A transdisciplinary perspective of chronic stress in relation to psychopathology throughout life span development (2011)

The allostatic load (AL) model represents an interdisciplinary approach to comprehensively conceptualize and quantify chronic stress in relation to pathologies throughout the life cycle. This article first reviews the AL model, followed by interactions among early adversity, genetics, environmental toxins, as well as distinctions among sex, gender, and sex hormones as integral antecedents of AL. We next explore perspectives on severe mental illness, dementia, and caregiving as unique human models of AL that merit future investigations in the field of developmental psychopathology. A complimenting transdisciplinary perspective is applied throughout, whereby we argue that the AL model goes beyond traditional stress-disease theories toward the advancement of person-centered research and practice that promote not only physical health but also mental health.
Annexin A1 released from apoptotic cells acts through formyl peptide receptors to dampen inflammatory monocyte activation via JAK/STAT/SOCS signalling (2010)

The immunosuppressive effects of apoptotic cells involve inhibition of pro-inflammatory cytokine release and establishment of an anti-inflammatory cytokine profile, thus limiting the degree of inflammation and promoting resolution. We report here that this is in part mediated by the release of the anti-inflammatory mediator annexin A1 from apoptotic cells and the functional activation of annexin A1 receptors of the formyl peptide receptor (FPR) family on target cells. Supernatants from apoptotic neutrophils or the annexin A1 peptidomimetic Ac2-26 significantly reduced IL-6 signalling and the release of TNF-α from endotoxin-challenged monocytes. Ac2-26 activated STAT3 in a JAK-dependent manner, resulting in upregulated SOCS3 levels, and depletion of SOCS3 reversed the Ac2-26-mediated inhibition of IL-6 signalling. This identifies annexin A1 as part of the anti-inflammatory pattern of apoptotic cells and links the activation of FPRs to established signalling pathways triggering anti-inflammatory responses.
An operator interaction framework for visualization systems (2002)

Information visualization encounters a wide variety of different data domains. The visualization community has developed representation methods and interactive techniques. As a community, we have realized that the requirements in each domain are often dramatically different. In order to easily apply existing methods, researchers have developed a semiology of graphic representations. We have extended this research into a framework that includes operators and interactions in visualization systems, such as a visualization spreadsheet. We discuss properties of this framework and use it to characterize operations spanning a variety of different visualization techniques. The framework developed in the paper enables a new way of exploring and evaluating the design space of visualization operators, and helps end users in their analysis tasks.
Retrieval models for audience selection in display advertising (2011)

Web applications often rely on user profiles of observed user actions, such as queries issued, page views, etc. In audience selection for display advertising, the audience that is likely to be responsive to a given ad campaign is identified via such profiles. We formalize the audience selection problem as a ranked retrieval task over an index of known users. We focus on the common case of audience selection where a small seed set of users who have previously responded positively to the campaign is used to identify a broader target audience. The actions of the users in the seed set are aggregated to construct a query, the query is then executed against an index of other user profiles to retrieve the highest scoring profiles. We validate our approach on a real-world dataset, demonstrating the trade-offs of different user and query models and that our approach is particularly robust for small campaigns. The proposed user modeling framework is applicable to many other applications requiring user profiles such as content suggestion and personalization.
Hydration of sickle cells using the sodium ionophore Monensin. A model for therapy. (1982)

Mean cell hemoglobin concentration (MCHC) is thought to have an important influence in sickle cell disease, both through the strong dependence of sickling rates on hemoglobin S concentration, and through the profoundly limiting effect of high MCHC on the rheologic competence of oxygenated, irreversibly sickled cells (ISC). Recent studies have tested the ability of antidiuretic hormone to reduce sickle cell MCHC by reducing plasma sodium (Na) and osmolality. An alternative means of reducing MCHC is to elevate intracellular cation content, rather than to depress extracellular cation concentration. In an effort to do this, we have treated sickle cells with Monensin, an antibiotic that selectively enhances membrane Na permeability. At submicromolar concentrations, Monensin substantially reduced the MCHC of whole sickle blood and isolated ISC, causing an improvement in cell deformability. Monensin's effectiveness in producing a controlled increase in erythrocyte water content suggests that agents that selectively increase membrane Na permeability could be therapeutically useful.
The Use of Probiotics in Gastrointestinal Disease (2001)

Probiotics are living microorganisms that can affect the host in a beneficial manner. Prebiotics are nondigestible food ingredients that stimulate the growth and activity of probiotic bacteria already established in the colon. Efficacy of probiotic compounds has been shown in a wide range of gastrointestinal diseases. Lactobacillus GG alone, or the combination of Bifidobacterium bifidum and Streptococcus thermophilus, is effective in the treatment of Clostridium difficile, as well as in preventing the frequency and severity of infectious acute diarrhea in children. Prevention of antibiotic-induced diarrhea with the concomitant administration of either Lactobacillus GG or Saccharomyces boulardii has been demonstrated. The most successful studies involve the use of Lactobacillus GG at a dose of 1 x 1010 viable organisms per day and the yeast boulardii at a dose of 1 g/day. A probiotic preparation (VSL#3 - 6 g/day) that uses a combination of three species of Bifidobacterium, four strains of Lactobacillus and one strain of Streptocccus has shown promise in maintaining remission in ulcerative colitis and pouchitis, as well as in preventing the postoperative recurrence of Crohn's disease. The mechanism of action of probiotics may include receptor competition, effects on mucin secretion or probiotic immunomodulation of gut-associated lymphoid tissue. Oral administration of probiotic compounds has been demonstrated to be well tolerated and safe. However, while probiotics have the potential to improve human health and to prevent and treat some diseases, major improvements are needed in labelling and quality assurance procedures for probiotic compounds. In addition, well planned and controlled clinical studies are necessary to delineate fully the potential for probiotic compounds.
Association between Virus-Specific Cytotoxic T-Lymphocyte and Helper Responses in Human Immunodeficiency Virus Type 1 Infection (1999)

Cellular immune responses are thought to be an important antiviral host defense, but the relationship between virus-specific T-helper and cytotoxic-T-lymphocyte (CTL) responses has not been defined. To investigate a potential link between these responses, we examined functional human immunodeficiency virus type 1 (HIV-1)-specific memory CTL precursor frequencies and p24-specific proliferative responses in a cohort of infected untreated persons with a wide range of viral loads and CD4 cell counts. Levels of p24-specific proliferative responses positively correlated with levels of Gag-specific CTL precursors and negatively correlated with levels of plasma HIV-1 RNA. These data linking the levels of HIV-specific CTL with virus-specific helper cell function during chronic viral infection provide cellular immunologic parameters to guide therapeutic and prophylactic vaccine development.
Design and Development of Signal Transduction Inhibitors for Cancer Treatment: Experience and Challenges with Kinase Targets (2006)

The last several years have seen major progress towards the goal of translating our growing understanding of the molecular basis of cancer into drugs with improved therapeutic activity and selectivity. Tremendous advances have been made but significant obstacles remain. In this review we assess our experience in the design and development of signal transduction drugs for cancer treatment, with a specific focus on small molecule kinase inhibitors. The druggability of cancer kinome targets is exemplified by imatinib, gefitinib, erlotinib and many other emerging agents. We assess the current status of the design of potent and selective kinase inhibitors, which has benefited greatly from high throughput screening and structure-based approaches. A diverse range of kinase inhibitory scaffolds is now available based on these methods. Multi-parameter optimisation now focuses as much on pharmacokinetic and metabolic properties as it does on target potency and selectivity. Development of a molecular audit trail requiring assays to demonstrate mechanism of action in vitro and in vivo is essential. Current issues include our relatively poor ability to predict the level of kinase selectivity in the intact cell, uncertainties around the most desirable selectivity profile, and the emergence of drug resistance.
Identification of mycobacteria from culture by using the Gen-Probe Rapid Diagnostic System for Mycobacterium avium complex and Mycobacterium tuberculosis complex (1988)

Commercially available kits (Mycobacterium avium Complex Rapid Diagnostic System and Mycobacterium tuberculosis Complex Rapid Diagnostic System; Gen-Probe, Inc., San Diego, Calif.) utilizing nucleic acid hybridization for the rapid identification of members of the M. avium-M. intracellulare complex and M. tuberculosis complex were evaluated by using 339 clinical and American Type Culture Collection (Rockville, Md.) isolates. The tests, which can be performed in approximately 2 h, use specific [125I]DNA probes complementary to the rRNAs of M. avium, M. intracellulare, and M. tuberculosis complex, the latter of which includes M. tuberculosis, M. bovis, M. bovis BCG, M. africanum, and M. microti. The M. avium-M. intracellulare probes correctly identified 99 of 114 M. avium-M. intracellulare isolates, with 7 false-negatives and 8 false-positives, for a sensitivity of 93.4% and a specificity of 96.6%. After repeat testing, 110 of 114 were correctly identified, with 4 false-negatives and no false-positives, for a sensitivity of 96.5% and a specificity of 100%. The M. tuberculosis complex probe correctly identified 99 of 102 M. tuberculosis isolates, with 1 false-negative and 2 false-positives, for a sensitivity of 99% and a specificity of 99.2%. After repeat testing, 100 of 102 isolates were correctly identified, with no false-negatives and 2 false-positives, for a sensitivity of 100% and a specificity of 99.2%. Overall, there were 15 discrepant M. avium-M. intracellulare results, with 4 such results after repeat testing, and 3 discrepant M. tuberculosis complex results, with 2 such results after repeat testing. The Gen-Probe kits are highly sensitive and specific for use in identifying M. avium-M. intracellulare complex and M. tuberculosis complex isolates and will be useful in the clinical laboratory which can use the present radionuclide-containing kits cost effectively.
Isolation and characterization of IS 31831, a transposable element from Corynebacterium glutamicum (1994)

A transposable element from a coryneform bacterium, Corynebacterium glutamicum ATCC 31831 was isolated and characterized. The element IS31831 is a 1453 bp insertion sequence with 24 bp imperfect terminal inverted repeats. It contains one open reading frame highly homologous at the amino acid level to the transposase of IS1096 from Mycobacterium smegmatis. Both IS31831 and IS1096 exhibit several common characteristics suggesting that they constitute a new family of insertion sequences. IS31831 was isolated by taking advantage of the sucrose sensitivity of coryneform bacteria conferred by expression of the Bacillus subtilis sacB gene. An Escherichia coli/Corynebacterium shuttle vector useful for the isolation of transposable elements from the coryneform group of bacteria was constructed.
Multiwall Carbon Nanotubes Made of Monochirality Graphite Shells (2006)

A multiwall carbon nanotube (MWCNT) consists of several or many concentric carbon shells, each of which could be metallic or semiconducting. Both theoretical predictions and experimental results suggest that MWCNTs have exotic electronic structures and intriguing transport properties, which are highly dependent on chirality of each shell. However, the structural defects and the random distribution of chirality of each concentric graphitic shell make the MWCNTs difficult for basic research and technological applications. Thus far, it is still a challenge to get the high crystalline MWCNTs with limited atomic conformation. Here, we report the synthesis of high crystalline MWCNTs made of monochirality graphite shells by a low-temperature chemical vapor deposition (CVD) process in plasma environment. Structural analysis, carried out by transmission electron microscopy (TEM) image and electron diffraction methods, reveal that the MWCNTs are well-crystallized and that most of them have nearly identical chiralities.
Thalamocortical dysrhythmia: A neurological and neuropsychiatric syndrome characterized by magnetoencephalography (1999)

Spontaneous magnetoencephalographic activity was recorded in awake, healthy human controls and in patients suffering from neurogenic pain, tinnitus, Parkinson's disease, or depression. Compared with controls, patients showed increased low-frequency theta rhythmicity, in conjunction with a widespread and marked increase of coherence among high- and low-frequency oscillations. These data indicate the presence of a thalamocortical dysrhythmia, which we propose is responsible for all the above mentioned conditions. This coherent theta activity, the result of a resonant interaction between thalamus and cortex, is due to the generation of low-threshold calcium spike bursts by thalamic cells. The presence of these bursts is directly related to thalamic cell hyperpolarization, brought about by either excess inhibition or disfacilitation. The emergence of positive clinical symptoms is viewed as resulting from ectopic gamma-band activation, which we refer to as the "edge effect." This effect is observable as increased coherence between low- and high-frequency oscillations, probably resulting from inhibitory asymmetry between high- and low-frequency thalamocortical modules at the cortical level.
THE MIXED LYMPHOCYTE REACTION: AN IN VITRO TEST FOR TOLERANCE (1968)

Tolerance, as defined by an inability to produce runt disease and the failure to elicit a normal lymphocyte transfer reaction, was induced in Lewis and Brown Norway rats by the neonatal injection of bone marrow from the opposite strain. When thymus, thoracic duct lymph, or lymph node cells from such tolerant Lewis and Brown Norway rats were cultured together, or were individually cultured with similar cells from an F(1) hybrid of these strains, transformation was suppressed to the levels observed in nonmixed control cultures. In contrast, mixtures of cells involving nontolerant donors demonstrated significant transformation as measured by per cent enlarged cells and thymidine-(3)H uptake. The specificity of the tolerance was confirmed by the presence of transformed cells in mixtures involving cells from a tolerant donor and an unrelated or a partially related third strain of rats. From these results, it is suggested that the mixed lymphocyte reaction may be used as a simple test for tolerance and that it most likely represents an in vitro immune response.
Structure and Base Pairing Properties of a Replicable Nonpolar Isostere for Deoxyadenosine (1998)

We report the synthesis, structure, and pairing properties in DNA of an isostere for deoxyadenosine which lacks all hydrogen-bonding functionality on the Watson-Crick pairing edge. A deoxyribo-nucleoside derivative of 4-methylbenzimidazole (1), which was recently shown to be inserted into DNA by Klenow DNA polymerase (Morales, J. C.; Kool, E. T. Nature Struct. Biol.1998, 5, 950), is prepared from 1-chloro-2-deoxy-3,5-bis-O-p-toluoyl-α-D-erythro-pentofuranose. The X-ray crystal structure of the nucleoside confirms that the compound is a close steric match for deoxyadenosine (2), although the methylbenzimidazole base is in the syn glycosidic orientation in the crystal. In D(2)O solution, 1H NMR studies show that 1 and 2 have similar (60% vs 70% S) sugar conformations and anti glycosidic orientations. Compound 1 is incorporated into a 12mer oligodeoxynucleotide and its base pairing properties in duplexes assessed by thermal denaturation. The results show that 1 has low affinity for the four natural bases but displays a stronger preference for being situated opposite a nonpolar difluorotoluene nucleoside analogue of thymine (3). The structural similarities of 1 and 2, combined with recent polymerase studies, add support to the hypothesis that steric complementarity plays an important role in base pair replication by polymerase enzymes and that Watson-Crick hydrogen bonds are not absolute requirements. Compound 1 should have significant utility as a probe of the importance of electrostatic effects in protein-DNA and protein-nucleotide binding as well as in DNA replication.
Linear discriminant analysis for speechreading (2002)

This paper investigates the use of Fisher-Rao (1965) linear discriminant analysis (LDA) as a means of visual feature extraction for hidden Markov model based automatic speechreading. For every video frame, a three-dimensional region of interest containing the speaker's mouth over a sequence of adjacent frames is lexicographically arranged into a data vector. Such vectors are then projected onto the space of the most discriminant "eigensequences", estimated by means of LDA on a training set of image sequence vectors, labeled from a set of a-priori chosen classes. The resulting projections, as well as their first and second derivatives over time, are used as features for automatic speechreading. The proposed method is applied to single-speaker, multi-speaker, and speaker-independent visual-only recognition tasks, consistently outperforming principal component analysis and discrete wavelet transform based visual features. Specific issues relevant to LDA are also discussed, namely, class selection, automatic data class labelling, and dimensionality reduction prior to LDA.
Structural studies of phospholipid cubic phases (2007)

In our previous work, we have shown that a general feature of saturated phosphatidylethanolamines is that they exhibit lamellar — inverse hexagonal (HII) phase transitions with increasing temperature, at all water contents. We have found that the effect of decreasing the lipid chainlength to C12(didodecyl) is to cause the appearance of three intermediate bicontinuous cubic phases in different regions of the binary phase diagram. We have identified these phases as being of cubic aspects 4, 8 and 12, corresponding to probable spacegroups Pn3m (Q224), Im3m (Q229) and Ia3d (Q230). Furthermore, we find that for the C16(dihexadecyl) lipid, cubic phases are also induced in qualitatively the same regions of the phase diagram by methylation of the polar headgroup, which increases its hydrophilicity. We have investigated whether the chirality of the lipid influences the chirality of the cubic phase formed, and have found that, at least for these phospholipids, it does not. We have also found that cubic phases are formed by hydrated phosphatidylcholine/fatty acid 1/2 (mol/mol) stoichiometric mixtures, when the chainlength is reduced, and we report preliminary results obtained by X-ray and neutron diffraction on these systems.
CRISPR-Cas9 off-targeting assessment with nucleic acid duplex energy parameters (2018)

The impact of the binding energies provides a direction for further studies of off-targeting mechanisms. The performance of CRISPRoff and CRISPRspec enables more accurate off-target evaluation for gRNA selections, prior to any CRISPR-Cas9 genome-editing application. For given gRNA sequences or all potential gRNAs in a given target region, CRISPRoff-based off-target predictions and CRISPRspec-based specificity evaluations can be carried out through our webserver at https://rth.dk/resources/crispr/ .
Optimal linear inverse solution with multiple priors in diffuse optical tomography (2005)

A general framework for incorporating single and multiple priors in diffuse optical tomography is described. We explore the use of this framework for simultaneously utilizing spatial and spectral priors in the context of imaging breast cancer. The utilization of magnetic resonance images of water and lipid content as a statistical spatial prior for the diffuse optical image reconstructions is also discussed. Simulations are performed to demonstrate the significant improvement in image quality afforded by combining spatial and spectral priors.
Discriminative structure and parameter learning for Markov logic networks (2008)

Markov logic networks (MLNs) are an expressive representation for statistical relational learning that generalizes both first-order logic and graphical models. Existing methods for learning the logical structure of an MLN are not discriminative; however, many relational learning problems involve specific target predicates that must be inferred from given background information. We found that existing MLN methods perform very poorly on several such ILP benchmark problems, and we present improved discriminative methods for learning MLN clauses and weights that outperform existing MLN and traditional ILP methods.
Susceptibility of human immunodeficiency virus type 1 group O isolates to antiretroviral agents: in vitro phenotypic and genotypic analyses (1997)

We investigated the phenotypic and genotypic susceptibility of 11 human immunodeficiency virus type 1 (HIV-1) group O strains to nucleoside and nonnucleoside reverse transcriptase (RT) inhibitors and protease inhibitors in vitro. Phenotypic susceptibility was determined by using a standardized in vitro assay of RT inhibition, taking into account the replication kinetics of each strain. HIV-1 group M and HIV-2 isolates were used as references. DNA from cocultured peripheral blood mononuclear cells was amplified by using pol-specific group O primers and cloned for sequencing. Group O isolates were highly sensitive to nucleoside inhibitors, but six isolates were naturally highly resistant to all of the nonnucleoside RT inhibitors tested. Phylogenetic analysis of the pol gene showed that these isolates formed a separate cluster within group O, and genotypic analysis revealed a tyrosine-to-cysteine substitution at residue 181. Differences in susceptibility to saquinavir and ritonavir (RTV) were not significant between group O and group M isolates, although the 50% inhibitory concentration of RTV for group O isolates was higher than that for the HIV-1 subtype B strains. The study of HIV-1 group O susceptibility to antiretroviral drugs revealed that the viruses tested had specific phenotypic characteristics contrasting with the group M phenotypic expression.