gebhart/patrepeval huggingface dataset:
Structure−activity Relationships among Random Nylon-3 Copolymers That Mimic Antibacterial Host-Defense Peptides (2009)

Host-defense peptides are natural antibiotics produced by multicellular organisms to ward off bacterial infection. Since the discovery of these molecules in the 1980s, a great deal of effort has been devoted to elucidating their mechanisms of action and to developing analogues with improved properties for possible therapeutic use. The vast majority of this effort has focused on materials composed of a single type of molecule, most commonly a peptide with a specific sequence of alpha-amino acid residues. We have recently shown that sequence-random nylon-3 copolymers can mimic favorable properties of host-defense peptides, and here we document structure-activity relationships in this polymer family. Although the polymers are heterogeneous in terms of subunit order and stereochemistry, these materials display structure-activity relationships comparable to those that have been documented among host-defense peptides and analogous synthetic peptides. Previously such relationships have been interpreted in terms of a specific and regular folding pattern (usually an alpha-helix), but our findings show that these correlations between covalent structure and biological activity do not require the adoption of a specific or regular conformation. In some cases our observations suggest alternative interpretations of results obtained with discrete peptides.
Inflammation and its impact on anaemia in chronic kidney disease: from haemoglobin variability to hyporesponsiveness (2008)

The availability of erythropoiesis-stimulating agents (ESAs) has revolutionized the treatment of anaemia in patients with chronic kidney disease. However, maintaining patients at haemoglobin (Hb) levels that are both safe and provide maximal benefit is a continuing challenge in the field. Based on emerging data on the potential risks of Hb treatment targets >13 g/dL, treatment targets have recently been lowered. In the latest revision (March 2008) of the European product labelling for the ESA class of drugs, the target treatment range was lowered to 10-12 g/dL. Fluctuation of Hb levels or 'Hb variability' during treatment with ESAs is a well-documented phenomenon. Hb levels that are either too high or too low may have an adverse effect on patient outcomes; thus, it is important to understand the causes of Hb variability in order to achieve optimal treatment. Several factors are believed to contribute to variation in the Hb level, including patient comorbidities and intercurrent events. Inflammation is also an important factor associated with Hb variability, and the consequences of persistent inflammatory activity are far-reaching in affected patients. This review addresses the complex role of inflammation in chronic kidney disease, as evidenced by the apparent state of deranged inflammatory markers. The mechanisms by which inflammatory cytokines may affect the response to ESAs, the development of anaemia and poor treatment outcomes are also examined. In addition, various options for intervention to enhance the response to ESAs in haemodialysis patients with inflammation are considered.
CD40-CD40 Ligand Costimulation Is Required for Generating Antiviral CD4 T Cell Responses But Is Dispensable for CD8 T Cell Responses (1999)

This study documents a striking dichotomy between CD4 and CD8 T cells in terms of their requirements for CD40-CD40 ligand (CD40L) costimulation. CD40L-deficient (-/-) mice made potent virus-specific CD8 T cell responses to dominant as well as subdominant epitopes following infection with lymphocytic choriomeningitis virus. In contrast, in the very same mice, virus-specific CD4 T cell responses were severely compromised. There were 10-fold fewer virus-specific CD4 T cells in CD40L-/- mice compared with those in CD40L+/+ mice, and this inhibition was seen for both Th1 (IFN-gamma, IL-2) and Th2 (IL-4) responses. An in vivo functional consequence of this Th cell defect was the inability of CD40L-/- mice to control a chronic lymphocytic choriomeningitis virus infection. This study highlights the importance of CD40-CD40L interactions in generating virus-specific CD4 T cell responses and in resolving chronic viral infection.
A rapid fluorescent assay to distinguish attached from phagocytized yeast particles (1987)

In studies of phagocytosis and its consequences for cell activation, it is important to distinguish those particulate stimuli which are completely ingested and internalized from those which are only attached to phagocytic surfaces. Ingestion can be profoundly influenced by both the type of opsonins on the surface of the stimulus and the expression and activation of receptors on the phagocytes for these opsonins. We report a new fluorescent assay which facilitates rapid and reproducible quantitation of attached versus fully internalized live or dead yeast particles by phagocytes. The assay employs the fluorescent dye diaethanol (Uvitex 2B) which stains chitin on the cell wall of fungi and is excluded from live phagocytes. The diaethanol assay and a standard, previously published methylene blue dye exclusion assay yielded comparable results using human neutrophils or monocytes incubated with heat-killed, serum-opsonized Candida albicans. The diaethanol assay proved useful in distinguishing differences in effects of various opsonins, as human neutrophils selectively opsonized with either pooled human serum (PHS), IgG (heat-inactivated PHS) or complement (IgG-depleted PHS) completely internalized 69.5%, 91.3% and 52.5% of cell-associated zymosan particles respectively. Finally, the new assay permitted comparisons of differing macrophage populations, as resident murine peritoneal macrophages internalized only 10.6% of complement-opsonized, cell-associated zymosan particles compared with 41.7% when the macrophages were elicited with thioglycolate. The assay should prove useful to investigators studying both fungal phagocytosis and killing, as well as to those performing general studies of receptor expression, regulation and function.
3D point-of-gaze estimation on a volumetric display (2008)

Eye-gaze tracking devices are typically used to estimate the point-of-gaze (POG) of a subject on a 2D surface such as a computer screen. Using model based methods for POG estimation we have developed a system based on the vergence of the eyes which can be used to estimate the POG on a real-world volumetric display.
Induction of a chloracne phenotype in an epidermal equivalent model by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is dependent on aryl hydrocarbon receptor activation and is not reproduced by aryl hydrocarbon receptor knock down (2013)

Ligand-induced CYP1A1 and AhR degradation did not correlate with their chloracnegenic potential, indicating that neither CYP1A1 nor AhR are suitable biomarkers. Mechanistic studies showed that the TCDD-induced chloracne-like phenotype depends on AhR activation whereas AhR knock down did not appear sufficient to induce the phenotype.
Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy (2014)

High allopregnanolone serum concentrations may protect against depressed mood during pregnancy.
Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects (2014)

The β-site APP cleaving enzymes 1 and 2 (BACE1 and BACE2) were initially identified as transmembrane aspartyl proteases cleaving the amyloid precursor protein (APP). BACE1 is a major drug target for Alzheimer's disease because BACE1-mediated cleavage of APP is the first step in the generation of the pathogenic amyloid-β peptides. BACE1, which is highly expressed in the nervous system, is also required for myelination by cleaving neuregulin 1. Several recent proteomic and in vivo studies using BACE1- and BACE2-deficient mice demonstrate a much wider range of physiological substrates and functions for both proteases within and outside of the nervous system. For BACE1 this includes axon guidance, neurogenesis, muscle spindle formation, and neuronal network functions, whereas BACE2 was shown to be involved in pigmentation and pancreatic β-cell function. This review highlights the recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism-based liabilities, in particular for BACE inhibitors in Alzheimer's disease. The protease BACE1 is a major drug target in Alzheimer disease. Together with its homolog BACE2, both proteases have an increasing number of functions within and outside of the nervous system. This review highlights recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism-based liabilities, in particular for BACE inhibitors in Alzheimer disease.
SAR by MS:  A Ligand Based Technique for Drug Lead Discovery Against Structured RNA Targets (2002)

A technique for lead discovery vs RNA targets utilizing mass spectrometry (MS) screening methods is described. The structure-activity relationships (SAR) derived from assaying weak binding motifs allows the pharmacophores discovered to be elaborated via "SAR by MS" to higher affinity ligands. Application of this strategy to a subdomain of the 23S rRNA afforded a new class of compounds with functional activity.
Peptides 1994 : proceedings of the twenty-third European Peptide Symposium, September 4-10, 1994, Braga, Portugal (1995)

This book collects a major part of the contributions to the 23rd European Peptide Symposium, held at the University of Minho at Braga, Portugal. It contains 414 papers, 53 summarizing oral presentations held during the Symposium, and 361 selected from 450 poster presentations. The contributions are grouped into 18 sections: Synthesis and Analysis of Amino Acids and Peptides Isolation, Purification, Conformation and Physical Chemistry of Peptides Peptide Mimetics, de novo Design and Peptide Libararies Structure-Activity Relationships, Peptide Vaccines and Immunology of Peptides Receptors, other Binding Proteins and Biological Aspects of Peptides Amino Acid and Peptide Synthesis Synthesis of Biologically Active Peptides Analytical Methods for Peptides Isolation and Purification of Peptides de novo Design and Peptide Libraries Conformation and Phsyical Chemistry of Peptides Structure-Activity Relationships Glyco, Lipo, Phospho and Nucleopeptides Biology and Mechanisms of Action of Peptides Receptors and other Binding Immunology Peptide Pharmacology Miscellaneous. This 1000-page compendium includes many enlightening contributions in fields of recent interest, such as peptide libraries and peptide mimetics.
Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. (1984)

We have examined the amino-terminal sequence of the kappa light chains of a set of monoclonal antibodies specific for one of the major antigenic determinants (Sb) on the influenza virus PR8[A/PR/8/34(H1N1)] hemagglutinin molecule. This set was believed to be structurally related from earlier serological analysis that typed these kappa chains as members of the variable (V) region V kappa 21 group [ Staudt , L. M. & Gerhard , W. (1983) J. Exp. Med. 157, 678-704]. Our sequence analysis confirms and extends this conclusion; all examples of this set belong to a subgroup of the V kappa 21 group, V kappa 21C . A special feature of this set of kappa light chains is that all examples were derived from the same mouse (designated H36 ). This sequence analysis along with the characterization of gene rearrangements at the kappa light chain loci of these hybridomas is consistent with the idea that certain members of this set are the progeny of one or two lymphocytes. Because of this potential clonal relationship, we can reach several conclusions about the diversity observed among these kappa light chains: (i) the diversity is due to somatic mutation, (ii) somatic mutations occur sequentially and accumulate in the first complementarity-determining region, and (iii) the extent of somatic variation in this sample is high, suggesting a somatic mutation rate of about 10(-3) per base pair per generation.
Fatal Disseminated Adenovirus Infections in Immunocompromised Patients (2003)

Adenovirus has emerged as an important pathogen in immunocompromised patients, in whom disseminated disease occurs frequently and is associated with a high mortality rate. In a retrospective review of 1,847 consecutive autopsies, we identified 84 cases where adenovirus infection was suspected clinically. Adenovirus infection was confirmed at autopsy in 8 (10%) of 84 cases; all were immunocompromised patients. Six (75%) of these cases had disseminated adenovirus infection that contributed to death. Pathologic findings attributed to adenovirus infection included pneumonia with or without intra-alveolar hemorrhage, hepatic necrosis, enterocolitis with or without mucosal hemorrhage, epicardial hemorrhage, and ulcerations of the larynx, trachea, and ileum. This work shows that severe and fatal adenovirus infections are not infrequent, particularly in the immunocompromised population. Both clinicians and pathologists must become aware of the pathogenicity of adenovirus in this patient population, including its potential for causing life-threatening hemorrhage.
Exact Pattern Matching with Feed-Forward Bloom Filters (2011)

This paper presents a new, memory efficient and cache-optimized algorithm for simultaneously searching for a large number of patterns in a very large corpus. This algorithm builds upon the Rabin-Karp string search algorithm and incorporates a new type of Bloom filter that we call a feed-forward Bloom filter. While it retains the asymptotic time complexity of previous multiple pattern matching algorithms, we show that this technique, along with a CPU architecture aware design of the Bloom filter, can provide speedups between 2x and 30x, and memory consumption reductions as large as 50x when compared with grep.
Role of surface defect sites: from Pt model surfaces to shape-controlled nanoparticles (2011)

In the present paper, preferentially oriented (111) Pt nanoparticles (mostly octahedral and tetrahedral, namely {111}Pt nanoparticles) have been characterized and compared with a Pt(554) single-crystal electrode as their voltammetric features are quite similar in 0.5 M H2SO4. The anion and Bi adsorption behaviours suggest that the {111}Pt nanoparticles contain relatively wide hexagonal domains and also isolated sites which could adsorb solely hydrogen. Bi step decoration has been successfully extended to modify the defects of {111}Pt nanoparticles without blocking terrace sites. CO charge displacement has been applied to determine the potential of zero total charge (pztc) of non-decorated and Bi decorated surfaces. It has found that the positive shift of pztc on defect-decorated {111}Pt nanoparticles is not so significant in comparison with that of Pt(554) due to the relative short mean length of (111) domains on the {111}Pt nanoparticles. CO stripping demonstrates that {111}Pt nanoparticles exhibit higher reactivity toward CO oxidation. This reflects the role of the defect sites in nanoparticles, evidenced by the disappearance of the “pre-wave” in the stripping voltammogram once the defects were blocked by Bi. The stripping peaks shift to higher potential on Bi decorated surfaces, indicating the active role of both steps and defects for CO oxidation. By comparing the CO stripping charge and the change in hydrogen adsorption charge of surfaces with and without Bi decoration, including reasonable deconvolution, the local CO coverage on defect and terrace sites were obtained for the first time for the {111}Pt nanoparticles, and the results are in good agreement with those obtained on Pt(554). Chronoamperometry studies show tailing in all current–time transients of CO oxidation on all surfaces studied. The kinetics of CO oxidation can be satisfactorily simulated by a modified Langmuir–Hinshelwood model, demonstrating that CO oxidation on all studied surfaces follows the same mechanism.
Application of intelligent agent technology for managerial data analysis and mining (1999)

Data analysis and mining technologies help bring business intelligence into organizational decision support systems (DSS). While a myriad of data analysis and mining technologies are commercially available today, organizations are seeing a growing gap between powerful storage (data warehouse) systems and the business users' ability to analyze and act effectively on the information they contain. We contend that to narrow this gap effectively, a data analysis and mining environment is needed that can bring together and make available for use many of these technologies, that can support business users with different backgrounds, and with which the users can work comfortably.This paper illustrates the design and construction of such an environment, called the Intelligent Data Miner. IDM is Web-based and it is intended to provide an organization-wide decision support capability for business users. Intelligent agent technology is used as the basis for IDM design. IDM provides several types of data access capabilities to access and analyze the data contained in a data warehouse to obtain the critical information needed by business decision-makers. It supports both predefined and ad hoc data access, data analysis, data presentation, and data mining requests from non-technical users.An operational prototype of IDM, implemented using Java and JATLite (Java Agent Template, Lite from Stanford University), allowed us to examine the feasibility of having the "agents" automatically control and coordinate activities and tasks on the business users' behalf. These agents proved to hide the complexity of data analysis and mining activities, techniques, and methods from the business users, for effective use of the warehouse data.
Flavonoid Composition of Fruit Tissues of Citrus Species (2006)

An HPLC analysis was performed on the concentrations of flavonoids in 42 species and cultivars of the Citrus genus and those of two Fortunella and one Poncirus species according to the classification system established by Tanaka. The composition of 8 flavanones and 9 flavone/ols for these species was determined in the albedo, flavedo, segment epidermis and juice vesicle tissues, and those in the fruit and peel tissues were calculated from the composition data of the tissues. A principal component analysis showed that such neohesperidosyl flavonoids as neoeriocitrin, naringin, neohesperidin, and rhoifolin had large factor loading values in the first principal component for each tissue. The flavonoid composition of citrus fruits was approximately the same within each section of Tanaka's system, except for the species in the Aurantium section and those with a peculiar flavonoid composition such as Bergamot (C. bergamia), Marsh grapefruit (C. paradisi), Sour orange (C. aurantium), and Shunkokan (C. shunkokan). The Aurantium section included both naringin-rich and hesperidin-rich species.
Mediation ofin vivo glucose sensor inflammatory response via nitric oxide release (2005)

In vivo glucose sensor nitric oxide (NO) release is a means of mediating the inflammatory response that may cause sensor/tissue interactions and degraded sensor performance. The NO release (NOr) sensors were prepared by doping the outer polymeric membrane coating of previously reported needle-type electrochemical sensors with suitable lipophilic diazeniumdiolate species. The Clarke error grid correlation of sensor glycemia estimates versus blood glucose measured in Sprague-Dawley rats yielded 99.7% of the points for NOr sensors and 96.3% of points for the control within zones A and B (clinically acceptable) on Day 1, with a similar correlation for Day 3. Histological examination of the implant site demonstrated that the inflammatory response was significantly decreased for 100% of the NOr sensors at 24 h. The NOr sensors also showed a reduced run-in time of minutes versus hours for control sensors. NO evolution does increase protein nitration in tissue surrounding the sensor, which may be linked to the suppression of inflammation. This study further emphasizes the importance of NO as an electroactive species that can potentially interfere with glucose (peroxide) detection. The NOr sensor offers a viable option for in vivo glucose sensor development.
<title>Discovery of uniform multicarrier frameworks for multiple-access technologies</title> (2001)

Multi-carrier technologies are emerging as a considerable force in the wireless world. OFDM charges ahead, with MC-CDMA close behind. However, as this tutorial demonstrates, multi- carrier technologies are not limited to OFDM and MC-CDMA. By application of Carrier Interferometry (CI) principles, we create CI/TDMA and CI/DS-CDMA, multi-carrier implementations of existing TDMA and DS-CDMA technologies. These implementations enable significant improvements in both performance and network capacity. Specifically, we double the network capacity of existing TDMA and DS-CDMA system and simultaneously outperform their traditional implementations. Of course, the benefits of Carrier Interferometry are not limited to TDMA and DS-CDMA: It also significantly improves the existing MC-CDMA and OFDM multi-carrier systems. What emerges is a very powerful technology that creates a common multi-carrier architecture for DS-CDMA, TDMA, OFDM, and MC- CDMA, bridging the hardware gap between the world's most promising technology, all the while enhancing network capacity and probability of error performance.
Antisense-induced exon skipping restores dystrophin expression in DMD patient derived muscle cells (2001)

Due to frame-shifting mutations in the DMD gene that cause dystrophin deficiency, Duchenne muscular dystrophy (DMD) patients suffer from lethal muscle degeneration. In contrast, mutations in the allelic Becker muscular dystrophy (BMD) do not disrupt the translational reading frame, resulting in a less severe phenotype. In this study, we explored a genetic therapy aimed at restoring the reading frame in muscle cells from DMD patients through targeted modulation of dystrophin pre-mRNA splicing. Considering that exon 45 is the single most frequently deleted exon in DMD, whereas exon (45+46) deletions cause only a mild form of BMD, we set up an antisense-based system to induce exon 46 skipping from the transcript in cultured myotubes of both mouse and human origin. In myotube cultures from two unrelated DMD patients carrying an exon 45 deletion, the induced skipping of exon 46 in only approximately 15% of the mRNA led to normal amounts of properly localized dystrophin in at least 75% of myotubes. Our results provide first evidence of highly effective restoration of dystrophin expression from the endogenous gene in DMD patient-derived muscle cells. This strategy may be applicable to not only >65% of DMD mutations, but also many other genetic diseases.
Cytosolic calcium concentrations and cell death in vitro. (1996)

Although the concept of Ca2+ ions as mediators of cytotoxicity has been accepted, there have been past difficulties in correlating intra-cellular Ca2+ levels and neurotoxicity. It is now apparent that neurons that succumb to Ca2+ loading sustain a failure of Ca2+ homeostatic mechanisms due to processes set into motion very early following the initial insult. Recent work suggests that there exists a linear correlation between total neuronal Ca2+ loading and neurodegeneration. However, the slope of this linear relationship may be modulated by numerous factors such as the transmembrane Ca2+ gradient, the route of Ca2+ influx, and the presence of various Ca2+ buffering and extrusion systems within the cell. In the future, processes responsible for neurodegeneration may be better understood through the study of the subcellular interplay between membrane receptors, second messenger systems, and Ca2+ buffering mechanisms. Refinements on past techniques will be necessary to place further quantitative boundaries on global and subcellular neurotoxic Ca2+ increases.