gebhart/patrepeval huggingface dataset:
Five PDGF B amino acid substitutions convert PDGF A to a PDGF B-like transforming molecule. (1992)

We used site-directed mutagenesis to determine the minimum number of PDGF B residues needed to convert PDGF A to a potently transforming PDGF B-like molecule. Substitution of two PDGF B subdomains, 106-115 and 135-144, were found to be critical. These substitutions were sufficient to broaden the ability of PDGF A to activate beta as well as alpha platelet-derived growth factor (PDGF) receptors and increase its transforming efficiency to that of PDGF B. Within subdomain I, either PDGF B residues Arg-109 and Asn-115 or Arg-109, Leu-110, and Arg-113, in combination with subdomain II PDGF B residues Asn-136, Arg-137, and Arg-142 were identified as being essential. Those mutants with transforming ability comparable with PDGF B showed significantly lower efficiencies of beta receptor triggering. Thus, our studies identify a small number of PDGF B amino acids indispensable for beta PDGF receptor interaction and suggest that a low level of beta PDGF receptor activation is sufficient to dramatically increase PDGF transforming efficiency in NIH 3T3 cells.
Immunotherapy in Rheumatoid Arthritis: A Review (1993)

The starting mode of the pathological process in rheumatoid arthritis (RA) is the presentation of an unknown 'rheumatoid' antigen by an antigen presenting cell to the receptor on the CD4+ T cell. The activation of the CD4+ T cell, and consequently of the cytokine network, is the second step in the inflammatory process. Immunosuppression in RA, obtained using either immunosuppressive drugs (azathioprine, cyclophosphamide, methotrexate), or physical procedures (lymphoapheresis, total lymphoid irradiation) acts specifically on all lymphocyte populations, and can induce a number of side effects, such as myelotoxicity and opportunistic infections. Two promising new therapeutic approaches are being developed, one aimed at specifically reducing the proliferation of activated T cell clones, and the second designed to modulate the activity of the cytokines involved in the inflammatory process. Encouraging results have been so far obtained with: a) cyclosporine A, a somewhat more specific immunosuppressive agent; b) monoclonal antibodies against surface antigens (CD4, CD5, CD7, CD25, CD54) expressed on activated T cells; c) T cell vaccination; and finally (i.v.) recombinant cytokines, their agonists or antagonists. Besides their utility in the treatment of the disease, these new therapeutical procedures should also lead to a better understanding of pathological processes in RA.
Distribution of multicopy single-stranded DNA among myxobacteria and related species (1985)

Multicopy single-stranded DNA (msDNA) is a short single-stranded linear DNA originally discovered in Myxococcus xanthus and subsequently found in Stigmatella aurantiaca. It exists at an estimated 500 to 700 copies per chromosome (T. Yee, T. Furuichi, S. Inouye, and M. Inouye, Cell 38:203-209, 1984). We found msDNA in other myxobacteria, including Myxococcus coralloides, Cystobacter violaceus, Cystobacter ferrugineus (Cbfe17), Nannocystis exedens, and nine independently isolated strains of M. xanthus. The presence of msDNA in N. exedens would extend its phylogenetic distribution into another family of myxobacteria. Flexibacter elegans, a Cytophaga-like gliding bacteria which may be even more distantly related, also contained an msDNA but at a much lower copy number. msDNA was not detected in closely related strains of the myxobacteria Cystobacter fuscus and C. ferrugineus (Cbfe16 and Cbfe18) and the more distantly related eubacteria Herpetosiphon giganteus, Taxeobacter ocellatus, Lysobacter antibioticus, Lysobacter enzymogenes, Cytophaga johnsonae, Rhodopseudomonas sphaeroides, and Rhodospirillum rubrum. Thus far, msDNA has been found in certain gliding bacteria but not in others.
Once-Daily Atomoxetine Treatment for Children and Adolescents With Attention Deficit Hyperactivity Disorder: A Randomized, Placebo-Controlled Study (2002)

Once-daily administration of atomoxetine is an effective treatment for children and adolescents with ADHD.
Monosomy of a specific chromosome determines l -sorbose utilization: A novel regulatory mechanism in Candida albicans (1998)

We report the identification of the gene, SOU1, required for L-sorbose assimilation in Candida albicans. The level of the expression of SOU1 is determined by the copy number of chromosome III (also denoted chromosome 5), such that monosomic strains assimilate L-sorbose, whereas disomic strains do not, in spite of the fact that SOU1 is not on this chromosome. We suggest that C. albicans contains a resource of potentially beneficial genes that are activated by changes in chromosome number, and that this elaborate mechanism regulates the utilization of food supplies and possibly other important functions, thus representing a novel general means for regulating gene expression in microbes.
Intermittent versus continuous brain retraction (1983)

Brain damage due to retraction was studied morphologically and physiologically in the dog brain. Two methods of retraction were compared using a retractor with a strain gauge: 1) continuous retraction; and 2) intermittent retraction. Total retraction time was 60 minutes for each method. Brain damage started to appear at a retraction force of 30 gm with continuous retraction, and increased in proportion to the force used. The power spectrum of the electrocorticogram showed full recovery after the release of retraction when the retraction force was less than 40 gm. With intermittent retraction, the damage was morphologically minimal with a retraction force of less than 50 gm, and recovery of the power spectrum of the electrocorticogram was prompt in comparison with continuous retraction. The results indicate the superiority of intermittent over continuous retraction.
A Review of Routing and Wavelength Assignment Approaches for Wavelength- Routed Optical WDM Networks (2000)

This study focuses on the routing and Wavelength-Assignment (RWA) problem in wavelength-routed optical WDM networks. Most of the attention is devoted to such networks operating under the wavelength-continuity constraint, in which lightpaths are set up for connection requests between node pairs, and a single lightpath must occupy the same wavelength on all of the links that it spans. In setting up a lightpath, a route must be selected and a wavelength must be assigned to the lightpath. If no wavelength is available for this lightpath on the selected route, then the connection request is blocked. We examine the RWA problem and review various routing approaches and wavelengthassignment approaches proposed in the literature. We also briefly consider the characteristics of wavelength-converted networks (which do not have the wavelength-continuity constraint), and we examine the associated research problems and challenges. Finally, we propose a new wavelengthassignment scheme, called Distributed Relative Capacity Loss (DRCL), which works well in distributed-controlled networks, and we demonstrate the performance of DRCL through simulation. 1
Automatic color scheme picker for document templates based on image analysis and dual problem (2006)

This paper presents two complementary methods to help in the area of document creation where the document includes color templates (banners, clipart, logos, etc.) as well as photographs. The problems that are being addressed are: given a photograph that a document needs to be built around, extract a good palette of colors that harmonize with the selected photograph, which may be used to generate the color template; The images are segmented with a color based morphological approach, which identifies regions with a dominant color. Based on the morphology of such "color" regions, and the other color objects in the template the scheme will pick a set of possible color harmonies (affine, complementary, split complementary, triadic) for such color elements within the document based on the combined morphology image-document. If the image is changed in the future the color scheme could be changed automatically. Given a document color template, identify from a collection of images the best set that will harmonize with it. The document color template is analyzed in the same way as above, and the results are used to query an image database in order to pick a set of images that will harmonize the best with such a color scheme.
Chipped Stone Nodules: Theory, Method, and Examples (1997)

With the recent proliferation of refitting studles, grouping artifacts into raw material nodules in preparation for refitting is becoming more common. Even if little is found to fit, the nodules formed in the refitting process still yield Information beyond that which can be gained by Just identifying raw material type, or even raw material source locations for assemblages. We discuss minimumanalytical nodules (MAN) and their analysts (MANA) as a means of further understanding chipped stone technological organization. We use several case studies from the Northwest Plains and Rocky Mountain chipped stone assemblages ranging in age from more than 10.000 to 100 years old in order to address implications for forager technology.
The Primary Structure of Sperm Whale Hemoglobin(Physeter catodon,Cetacea) (1986)

The complete primary structure of the two major hemoglobin components of sperm whale (Physeter catodon) is presented. The major components A and B account for 55% and 40% respectively whereas the minor component constitutes for 5% of the total hemoglobin. The globin chains were separated on CM-Cellulose in 8M urea buffer. The sequence was determined by automatic Edman degradation of tryptic and hydrolytic peptides in a liquid phase sequencer. Alignment of the sequence with human hemoglobin shows 22 exchanges each for the alpha I and alpha II and 21 exchanges for the beta I and beta II chains. Within the two beta-chains three differences have been located, beta NA2 His/Gln, beta A2 Gly/Ala and beta A8 Leu/Val. The two alpha-chains are characterized by heterogeneities at position alpha A8 Val/Ile or Ala/Ile (ratio of the phenylthiohydantoin derivatives of the amino acids 1:1) and alpha AB1 Asn/Ser (ratio of the phenylthiohydantoin derivatives of the amino acids 6:4). The role of these exchanges in modulating oxygen affinity is discussed.
A Neutrophil-Derived Anti-Infective Molecule: Bactericidal/Permeability-Increasing Protein (2000)

Effective host defense against microbial invasion requires an innate immune system whose response is both rapid and independent of prior exposure (25). The neutrophil is a central cellular effector of the innate immune system whose importance to host defense is manifest in the increased frequency and severity of infections in patients who have defects in neutrophil quantity or quality.

The mechanisms by which neutrophils exert their antimicrobial activity have been under investigation since the seminal work of Eli Metchnikoff, who demonstrated the phagocytic activity of these cells at the beginning of the 20th century. Activated neutrophils increase oxygen consumption during inflammatory responses in what has been termed the “respiratory burst,” reflecting assembly of a multicomponent neutrophil oxidase which transfers electrons to molecular oxygen, forming toxic radicals (6). Defects in the phagocyte oxidase proteins underlie chronic granulomatous disease (CGD), which is characterized by increased frequency of infections with certain bacterial and fungal pathogens (38). Nitric oxide is another small, readily diffusible antimicrobial mediator generated by activated neutrophils (54).

Over the past two decades, there has been increasing recognition of oxygen-independent killing mechanisms relating to the following observations: (i) neutrophils from CGD patients are capable of killing a variety of microorganisms (52), (ii) normal neutrophils deprived of oxygen in vitro are also able to efficiently kill certain bacterial pathogens (52), (iii) crude acid extracts of neutrophils possess direct microbicidal activity which is oxygen independent (24), and (iv) cationic proteins and peptides isolated from such extracts are able to directly kill microorganisms in vitro (29). Encouraged by these observations, investigators have made use of protein chromatography and molecular cloning in order to isolate, sequence, and define a growing number of neutrophil granule-derived antimicrobial proteins and peptides (15, 22, 23).

Neutrophil protein and peptide antibiotics are deployed by degranulation either extracellularly into inflammatory fluids or intracellularly into the phagolysosome, thereby exposing microorganisms to high concentrations of these agents. The antimicrobial proteins and peptides share in common a net positive charge which contributes to electrostatic interactions with negatively charged microbial surface components. However, despite similar charges, these agents vary markedly in size and structure as well as the mechanisms and selectivities of their cytotoxic actions. Here the focus is on a remarkably selective anti-infective component of human neutrophils known as the bactericidal/permeability-increasing protein (BPI).
Neuronal Nicotinic Acetylcholine Receptors - Targets for the Development of Drugs to Treat Cognitive Impairment Associated with Schizophrenia and Alzheimers Disease (2010)

Nicotinic acetylcholine receptors (nAChR) have been strongly implicated as therapeutic targets for treating cognitive deficits in disorders such as schizophrenia and Alzheimer's disease (AD). In particular alpha7 and alpha4beta2 subtype-selective nAChR agonists and partial agonists have been developed as potential candidates for the treatment of schizophrenia, cognitive disorders (including Alzheimer's disease), and inflammation. Further development of positive allosteric modulators and antagonists were also recently reported in the literature. In this review we will cover recent developments focused on the above mentioned nAChR subtypes, starting from the most advanced clinical candidate followed by an overview of literature compounds where potency, selectivity, central nervous system access, pharmacological activity and pharmacokinetic properties are disclosed.
Microwave Synthesis of a Porous Metal-Organic Framework, Nickel(II) Dihydroxyterephthalate and its Catalytic Properties in Oxidation of Cyclohexene (2010)

A porous coordination solid of nickel(II) dihydroxyterephthalate has been synthesized by the microwave-assisted (MW) method. The synthesized nickel(II) dihyroxylterephthalate was designated by the general formula of [<TEX>$Ni_2$</TEX>(dhtp) <TEX>$(H_2O)_2]{\cdot}8H_2O$</TEX> (where, dhtp = 2,5-dihydroxyterephthalate, denoted by Ni-DHTP). The effect of microwave-irradiation temperature and time of irradiation on the porosity and morphological changes in the solids have also been investigated. The catalytic performance of Ni-DHTP synthesized by MW method has been studied in the oxidation of cyclohexene with aqueous <TEX>$H_2O_2$</TEX>, which gave cyclohexene oxide as the primary product and 2-cyclohexene-1-ol as a major product.
Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound (2017)

Results from this blinded nonclinical study demonstrated significant differences between the originator FCM and this FCMS.
Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA (1996)

We have recently shown that oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides (CpG motif) can induce B cells to proliferate, differentiate, and secrete cytokines. In this study we demonstrate that CpG motifs contained in ODN as short as 15 bases in length were quite effective at inducing NK cell lytic activity in vitro in both human and murine lymphocytes. Such ODN were also effective at inducing NK lytic activity, in vivo, in mice. Experiments designed to determine the cellular and cytokine requirements for NK cell induction revealed that B and T cells are not necessary, that the ODN do not augment the activity of highly purified NK cells, and that the ODN augment NK cell activity indirectly by inducing the secretion of IL-12, IFN-alpha beta, and TNF-alpha. Various ODN sequences were prepared to determine the optimal ODN length, motif, palindrome, backbone modification, and dose requirements. We found no requirement for a palindromic sequence but a definite requirement for an unmethylated CpG motif. While necessary, however, a CpG motif was not sufficient for NK cell induction. Instead, there appeared to be stringent requirements for the immediate flanking bases at the 5' and 3' ends as well as for flanking sequences outside the immediate 5' and 3' bases. In particular poly(G) ends seemed to exert a complex qualitative and quantitative effect which could be up- or down-modulating depending on whether the ODN backbone was phosphorothioate modified or not.
Amino-acid sequence of activation cleavage site in plasminogen: homology with "pro" part of prothrombin. (1975)

A 38-residue fragment is isolated from carboxymethylated plasminogen. Residues 29-38 have the same sequence as the amino-terminal end of the light chain of plasmin. The sequence 1-28 is therefore the sequence of the carboxyl-terminal end of the heavy chain and contains the specific sequence at which urokinase (EC 3.4.99.26) and other plasminogen-activating serine proteases split. Two of the five carboxymethyl-cysteine residues in the isolated fragment are situated close to the cleavage site and the fragment is not itself a substrate for plasminogen-activators. Residues 1-11 show extensive sequence homology with residues 137-147 and 242-252 in prothrombin, which are located in corresponding regions of the two internally homologous 83-residue structures in the non-thrombin part of the molecule, indicating that such structures may be a common feature of the non-protease part of the larger serine protease zymogens.
Keratoconjunctivitis sicca (dry eye) : eye care (2012)

Dry eye is an extremely common condition, which affects most people at some stage in their lives. It is also the most common ocular condition that is seen by eye care practitioners.
Electrospun Chitosan-Gelatin Biopolymer Composite Nanofibers for Horseradish Peroxidase Immobilization in a Hydrogen Peroxide Biosensor (2017)

A biosensor based on chitosan-gelatin composite biopolymers nanofibers is found to be effective for the immobilization of horseradish peroxidase to detect hydrogen peroxide. The biopolymer nanofibers were fabricated by an electrospining technique. Upon optimization of synthesis parameters, biopolymers nanofibers, an average of 80 nm in diameter, were obtained and were then modified on the working electrode surface. The effects of the concentration of enzyme, pH, and concentration of the buffer and the working potential on the current response of the nanofibers-modified electrode toward hydrogen peroxide were optimized to obtain the maximal current response. The results found that horseradish peroxidase immobilization on chitosan-gelatin composite biopolymer nanofibers had advantages of fast response, excellent reproducibility, high stability, and showed a linear response to hydrogen peroxide in the concentration range from 0.1 to 1.7 mM with a detection limit of 0.05 mM and exhibited high sensitivity of 44 µA∙mM<sup>-1∙</sup>cm<sup>-2</sup>. The developed system was evaluated for analysis of disinfectant samples and showed good agreement between the results obtained by the titration method without significant differences at the 0.05 significance level. The proposed strategy based on chitosan-gelatin composite biopolymer nanofibers for the immobilization of enzymes can be extended for the development of other enzyme-based biosensors.
Evaluation of immunotherapy‐induced changes in specific IgE, IgG and IgG subclasses in birch pollen allergic patients by means of immunoblotting (1990)

Sera from 27 birch pollen-allergic patients who had undergone hyposensitization treatment for 22-41 months were studied by immunoblotting before and after therapy, whereby the levels of IgE, IgG and IgG1-4 antibodies directed against the major allergen Bet v I and minor allergens of birch pollen were monitored. The clinical benefit of immunotherapy (IT) was evaluated using a symptom specific questionnaire. In patients with good clinical response (responders, n = 18), as defined by improvement of symptoms, anti-Bet v I IgE antibodies were found to decrease in 10/18 patients (55.5%), whereas in 6/18 (33.3%) no change and in two cases (11.2%) an increase of specific IgE was observed. In the group of patients with unsatisfactory clinical outcome (non-responders, n = 9), 3/9 patients (33.3%) showed a decrease, 3/9 (33.3%) no change and 3/9 (33.3%) an increase in levels of IgE antibodies directed against Bet v I. In the case of minor allergens, 5/18 responders (27.7%) and 8/9 non-responders (88.8%) showed specific IgE before IT. In the responder group, no increase of specific IgE could be observed after IT. In non-responders, however, an increase of IgE directed against minor allergens was seen in 3/9 patients (33.3%). In all patients, regardless of therapeutical success, IT-induced elevated levels of specific IgG, IgG1 and in particular IgG4 directed against Bet v I were found. Regarding minor allergens, a heterogeneous pattern of IgG responses without significant correlation to clinical benefit was observed. Our results indicate that changes in IgG reactivity patterns against Bet v I and minor allergens, as shown by the immunoblot technique, did not correlate with good or bad clinical outcome.
Role of IL-6, IL-2, and IL-4 in the in vitro induction of cytotoxic T cells (1992)

The mode of IL-6-induced differentiation of Con A-stimulated CD4-CD8+ CTL-P was examined. Through application of neutralizing anti-IL-6, anti-IL-2, and anti-IL-4 mAb it was shown that IL-6 is an "early acting" factor for development of accessory cell-depleted thymocytes. IL-2 and IL-4 are obligatory "late acting" factors for this process. In accordance IL-4, but not IL-6, induced active CTL from CD4-CD8+ CTL-P. The increase of CD4-CD8+ CTL originates at least partially from CD4+CD8+ cells differentiating to active CTL in vitro. CTL development was paralleled by an increase in CD4-CD8+ cells and by a distinct increase in [3H]TdR uptake on day 2 of cultivation. Our data suggest that IL-6 induces Th cells to produce IL-2 and IL-4, the mediators for final differentiation of CD4-CD8+ cells.
Novel Molecular and Nanosensors for In Vivo Sensing (2013)

In vivo sensors are an emerging field with the potential to revolutionize our understanding of basic biology and our treatment of disease. In this review, we highlight recent advances in the fields of in vivo electrochemical, optical, and magnetic resonance biosensors with a focus on recent developments that have been validated in rodent models or human subjects. In addition, we discuss major challenges in the development and translation of in vivo biosensors and present potential solutions to these problems. The field of nanotechnology, in particular, has recently been instrumental in driving the field of in vivo sensors forward. We conclude with a discussion of emerging paradigms and techniques for the development of future biosensors.
Efficacy of ADAM Zolmitriptan for the Acute Treatment of Difficult‐to‐Treat Migraine Headaches (2019)

Severe pain, delayed treatment, awakening with a headache, and the presence of nausea are factors that predict a poorer response to acute migraine treatment. In these post hoc analyses of subgroups of patients with each of these characteristics in the ZOTRIP trial, participants receiving ADAM zolmitriptan 3.8 mg displayed nearly uniformly better headache responses (2-hour headache freedom and 2-hour MBS freedom) compared with those who received placebo.