gebhart/patrepeval huggingface dataset:
Discordant expression of CD28 ligands, BB-1, and B7 on keratinocytes in vitro and psoriatic cells in vivo. (1993)

The process for optimal T-cell activation requires not only engagement of the T-cell receptor/CD3 complex, but also the delivery of additional co-stimulatory signals that synergize with the primary response mediated through the T-cell receptor. Thus, the regulated expression of ligands for such co-stimulatory molecules can be critical in determining whether a cell can effectively activate T cells following the presentation of a foreign antigen. The CD28 antigen has recently been shown to mediate such co-stimulatory signals by interacting with the B7/BB-1 molecule expressed on activated B cells and monocytes. We show in this study that activated keratinocytes, both in vitro and in vivo display a discordance in expression between B7 and BB-1 based on differential monoclonal antibody (MAb) reactivity. Activated keratinocytes in vitro, as well as psoriatic keratinocytes and epithelial cells in the thymus, are reactive with the BB-1 MAb but not anti-B7 MAbs. These BB-1 positive cells fail to express detectable B7 messenger RNA by Northern blot analysis. Furthermore, keratinocytes bind specifically to CD28-transfected COS7 cells, and this binding is inhibited by anti-CD28 and anti-BB-1 but not B7 MAbs. These studies suggest: 1) that the MAb against BB-1 binds a functional epitope on a molecule distinct from B7 as detected on activated keratinocytes in vitro and in vivo and 2) that keratinocytes in skin and epithelial cells in thymus can express cell-surface molecules that might mediate T-cell co-stimulation via CD28.
Die Ringschluß-Olefin-Metathese als hocheffiziente Methode zur Synthese kovalent querverbrückter Peptide (1998)

Die Olefin-Metathese wurde erfolgreich zur Synthese makrocyclischer, helicaler Peptide angewendet [Gl. (a)]. C-C-Brücken zwischen den Aminosäure-Seitenketten wurden durch Ringschluß-Metathese gebildet. Diese Makrocyclisierung ist eine neuartige und milde Methode zur Einführung nichtnatürlicher kovalenter Brücken in Peptidhelices.
Empirical Entropy Manipulation for Real-World Problems (1995)

No finite sample is sufficient to determine the density, and therefore the entropy, of a signal directly. Some assumption about either the functional form of the density or about its smoothness is necessary. Both amount to a prior over the space of possible density functions. By far the most common approach is to assume that the density has a parametric form. By contrast we derive a differential learning rule called EMMA that optimizes entropy by way of kernel density estimation. Entropy and its derivative can then be calculated by sampling from this density estimate. The resulting parameter update rule is surprisingly simple and efficient. We will show how EMMA can be used to detect and correct corruption in magnetic resonance images (MRI). This application is beyond the scope of existing parametric entropy models. 1 Introduction Information theory is playing an increasing role in unsupervised learning and visual processing. For example, Linsker has used the concept of information ma...
Mycobacterium smegmatis d -Alanine Racemase Mutants Are Not Dependent on d -Alanine for Growth (2002)

Mycobacterium smegmatis is a fast-growing nonpathogenic species particularly useful in studying basic cellular processes of relevance to pathogenic mycobacteria. This study focused on the D-alanine racemase gene (alrA), which is involved in the synthesis of D-alanine, a basic component of peptidoglycan that forms the backbone of the cell wall. M. smegmatis alrA null mutants were generated by homologous recombination using a kanamycin resistance marker for insertional inactivation. Mutants were selected on Middlebrook medium supplemented with 50 mM D-alanine and 20 microg of kanamycin per ml. These mutants were also able to grow in standard and minimal media without D-alanine, giving rise to colonies with a drier appearance and more-raised borders than the wild-type strain. The viability of the mutants and independence of D-alanine for growth indicate that inactivation of alrA does not impose an auxotrophic requirement for D-alanine, suggesting the existence of a new pathway of D-alanine biosynthesis in M. smegmatis. Biochemical analysis demonstrated the absence of any detectable D-alanine racemase activity in the mutant strains. In addition, the alrA mutants displayed hypersusceptibility to the antimycobacterial agent D-cycloserine. The MIC of D-cycloserine for the mutant strain was 2.56 microg/ml, 30-fold less than that for the wild-type strain. Furthermore, this hypersusceptibility was confirmed by the bactericidal action of D-cycloserine on broth cultures. The kinetic of killing for the mutant strain followed the same pattern as that for the wild-type strain, but at a 30-fold-lower drug concentration. This effect does not involve a change in the permeability of the cell wall by this drug and is consistent with the identification of D-alanine racemase as a target of D-cycloserine. This outcome is of importance for the design of novel antituberculosis drugs targeting peptidoglycan biosynthesis in mycobacteria.
Improved Yield and Stability of L49-sFv−β-Lactamase, a Single-Chain Antibody Fusion Protein for Anticancer Prodrug Activation, by Protein Engineering (2003)

The L49 single-chain Fv fused to beta-lactamase (L49-sFv-bL) combined with the prodrug C-Mel is an effective anticancer agent against tumor cells expressing the p97 antigen. However, large-scale production of L49-sFv-bL from refolded E. coli inclusion bodies has been problematic due to inefficient refolding and instability of the fusion protein. Sequence analysis of the L49-sFv framework regions revealed three residues in the framework regions at positions L2, H82B, and H91, which are not conserved for their position, occurring in <1% of sequences in Fv sequence databases. One further unusual residue, found in <3% of variable sequences, was observed at position H39. Each unusual residue was mutated to a conserved residue for its position and tested for refolding yield from inclusion bodies following expression in E. coli. The three V(H) single mutants showed improvement in the yield of active protein and were combined to form double and triple mutants resulting in a 7-8-fold increased yield compared to the parental protein. In an attempt to further improve yield, the orientation of the triple mutant was reversed to create a bL-L49-sFv fusion protein resulting in a 3-fold increase in expressed inclusion body protein and producing a 20-fold increase in the yield of purified protein compared to the parental protein. The triple mutants in both orientations displayed increased stability in murine plasma and binding affinity was not affected by the introduced mutations. Both triple mutants also displayed potent in vitro cytotoxicity and in vivo antitumor activity against p97 expressing melanoma cells and tumor xenografts, respectively. These results show that a rational protein-engineering approach improved the yield, stability, and refolding characteristics of L49-sFv-bL while maintaining binding affinity and therapeutic efficacy.
Childhood and adolescent sports-related overuse injuries. (2006)

Youth sports participation carries an inherent risk of injury, including overuse injuries. Little leaguer's shoulder, a stress fracture of the proximal humerus that presents as lateral shoulder pain, usually is self-limited. Little leaguer's elbow is a medial stress injury; treatment consists of complete rest from throwing for four to six weeks followed by rehabilitation and a gradual throwing program. Spondylolysis is a stress fracture of the pars interarticularis. Diagnostic modalities include plain film radiography, bone scan, computed tomography, single photon emission computed tomography, and magnetic resonance imaging. Treatment usually is conservative. Spondylolisthesis is the forward or anterior displacement of one vertebral body over another and may be related to a history of spondylolysis. Diagnosis is made with plain film radiography and graded according to the amount of displacement. Osgood-Schlatter disease presents as anterior knee pain localized to the tibial tubercle. Diagnosis is made clinically, and most patients respond to conservative measures. Calcaneal apophysitis (or Sever's disease) is a common cause of heel pain in young athletes, presenting as pain in the posterior aspect of the calcaneus.
Direct Comparison of the Safety and Efficacy of Ferric Carboxymaltose versus Iron Dextran in Patients with Iron Deficiency Anemia (2013)

Several intravenous iron complexes are available for the treatment of iron deficiency anemia (IDA). Iron dextran (DEX) is associated with an elevated risk of potentially serious anaphylactic reactions, whereas others must be administered in several small infusions to avoid labile iron reactions. Ferric carboxymaltose (FCM) is a nondextran intravenous iron which can be administered in high single doses. A randomized, open label, and multicenter comparison of FCM to DEX in adults with IDA and baseline hemoglobin of ≤11.0 g/dL was conducted. A total of 160 patients were in the safety population (FCM n = 82; DEX n = 78). Adverse events, including immune system disorders (0% in FCM versus 10.3% in DEX, P = 0.003) and skin disorders (7.3% in FCM versus 24.4% in DEX, P = 0.004), were less frequently observed in the FCM group. A greater portion of patients in the FCM group experienced a transient, asymptomatic decrease in phosphate compared to patients in the DEX group (8.5% in FCM versus 0% in DEX, P = 0.014). In the FCM arm, the change in hemoglobin from baseline to the highest observed level was 2.8 g/dL, whereas the DEX arm displayed a change of 2.4 g/dL (P = 0.20). Treatment of IDA with FCM resulted in fewer hypersensitivity-related reactions than DEX.
The Role of Subcutaneous Infiltration in Suction-Assisted Lipoplasty: A Review (1997)

Dallas, Texas, and Los Angeles, Calif. From the Department of Plastic Surgery at the University of Texas Southwestern Medical Center and the Division of Plastic and Reconstructive Surgery at the UCLA Medical Center. Received for publication March 28, 1996; revised May 24, 1996. Rod J. Rohrich, M.D. Department of Plastic Surgery University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, Texas 75235-9031
Photon burst detection of single near-infrared fluorescent molecules (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhoton burst detection of single near-infrared fluorescent moleculesSteven A. Soper, Quincy L. Mattingly, and Pradeep. VeguntaCite this: Anal. Chem. 1993, 65, 6, 740–747Publication Date (Print):March 1, 1993Publication History Published online1 May 2002Published inissue 1 March 1993https://pubs.acs.org/doi/10.1021/ac00054a015https://doi.org/10.1021/ac00054a015research-articleACS PublicationsRequest reuse permissionsArticle Views455Altmetric-Citations121LEARN 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
Vaccination with Melanoma Helper Peptides Induces Antibody Responses Associated with Improved Overall Survival (2015)

Vaccination with helper peptides induced both Ab responses and T-cell responses, associated with favorable clinical outcome. Such immune responses may predict favorable clinical outcome to guide combination immunotherapy. Further studies are warranted to understand mechanisms of interaction of these Abs, T-cell responses, and tumor control.
The human aquaporin-CHIP gene. Structure, organization, and chromosomal localization (1993)

Aquaporin-CHIP is the first known molecular water channel. Originally identified in red cells and renal tubules, transcripts and proteins related to AQP-CHIP are also expressed in diverse epithelia with distinct developmental patterns. Northern analyses of RNA from several tissues revealed transcripts of 3.1 kilobases and other sizes. The nucleotide sequences of human kidney AQP-CHIP cDNAs are identical to the human bone marrow AQP-CHIP cDNA. The 17-kilobase human AQP-CHIP structural gene was isolated, and restriction maps were constructed and partially sequenced. The TATA consensus sequence is located 87 bp 5' to the translation initiation site, and sequences surrounding the polyadenylation consensus were determined. Four exons were identified corresponding to amino acids 1-128, 129-183, 184-210, and 211-269, separated by introns of 9.6, 0.43, and 0.80 kilobases. Genomic Southern analyses indicated the existence of a single AQP-CHIP gene which was located at human chromosome 7p14 by in situ hybridization. Sequence comparisons of AQP-CHIP and cDNAs of similar proteins from diverse species suggested a common evolutionary origin. At least three of these proteins are now known to function as membrane water pores and are referred to as the "Aquaporins." These genomic AQP-CHIP DNA sequences should permit molecular characterization of the complex patterns of AQP-CHIP expression.
Structure and expression of human germline VH transcripts. (1991)

The human VH5 family consists of two functional genes and one pseudogene. We have found a novel 1.2-kb VH5 gene transcript in normal fetal liver and cord blood and in transformed B lineage cells. VH5-positive cDNA clones were isolated from precursor B acute lymphoblastic leukemia, B chronic lymphoblastic leukemia, Epstein-Barr Virus-transformed B cell lines, and cord blood, and were identified as transcripts of unrearranged VH5 genes (germline transcripts). The cDNA clones were derived from both functional and pseudo-VH5 genes. Most germline transcripts appear to initiate at the normal VH promoter and are cleaved and polyadenylated at sites several hundred bases downstream of the VH5 coding region. Correct splicing of the leader intron was observed in all clones. In functional and pseudo-VH5 cDNAs, an open translational reading frame extends from the leader to a termination codon in the nonamer. Only limited polymorphisms were observed in the coding as well as flanking regions of the VH5 transcripts. Functional and pseudo-VH5 transcripts and previously identified murine germline VHJ558 transcripts are discussed.
Soluble Factors of Amnion-Derived Cells in Treatment of Inflammatory and Fibrotic Pathologies (2013)

Inflammation is a complex defense mechanism characterized by leukocyte migration from the vasculature into damaged tissues and subsequent deposition of extracellular matrix resulting in tissue repair. The inflammatory process is generally categorized into an acute, rapid response, and a persistent but slowly evolving chronic condition, which may progress into inflammatory diseases. An excessive deposition of extracellular matrix leads to overgrowth, hardening, and/or scarring of tissues, defined as fibrosis. The amnion has been used as biomaterial in medicine for over 100 years and has been proven valuable for the treatment of different pathological conditions including wound healing. In light of recent reports, this article will review the effects of the amnion and its cellular components within the inflammatory-fibrotic scenario and the factors described so far that could be involved in these immunomodulatory actions. As proof of principles, we will also discuss pre-clinical and clinical applications of the amnion where advantage has been taken of its anti-inflammatory and anti-fibrotic properties. It is conceivable that the local host environment in which the amnion is placed may have a profound role in influencing the production and function of soluble factors and the shift towards different steps in triggering healing. The healing effect depends on time, dosage, and location of cytokine/growth factor production by the amnion, together with the influence of the host microenvironment. Indeed, determining the specific cascade of events that may define the role of the amnion in a given clinical situation remains a challenge.
The Epidermal Growth Factor Receptor Pathway: A Model for Targeted Therapy (2006)

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase receptor that is frequently expressed in epithelial tumors. The EGFR was the first receptor to be proposed as a target for cancer therapy, and after 2 decades of intensive research, there are several anti-EGFR agents available in the clinic. Recent advances in our understanding in the mechanisms of receptor activation and function, discovery of primary and secondary EGFR somatic mutations, as well as a new generation of anti-EGFR agents provide new leads on the clinical targeting of this receptor and may serve as a model for strategies aimed at targeting other receptors.
Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor. (1994)

The desmoplastic small round cell tumor (DSRCT) is a recently recognized type of primitive sarcoma defined by a predilection for young males, aggressive clinical behavior, widespread abdominal serosal involvement, and a primitive histological appearance with prominent desmoplasia and striking divergent, multilineage differentiation. Previous cytogenetic case reports have identified a recurrent translocation, t(11;22) (p13;q12). We have characterized this translocation at the molecular level in a panel of five DSRCTs using a candidate gene approach. Southern blot analysis revealed recurrent rearrangement of both EWS, located at 22q12, and rearranged in other tumor-specific translocations in Ewing's sarcoma and clear cell sarcoma, and of WT1, the gene at 11p13 involved in a subset of Wilms' tumor. Consistent comigration of the rearranged EWS and WT1 bands in multiple enzyme digests indicated fusion of the genomic sequences, presumably due to the translocation t(11;22) (p13;q12). Northern blotting showed aberrant EWS and WT1 transcripts of the same size, suggesting the presence of a chimeric messenger RNA. This was confirmed by reverse transcriptase polymerase chain reaction using an EWS exon 7 primer and WT1 exon 8 or 9 primers, which revealed single polymerase chain reaction products consistent with a junction of EWS exon 7 to WT1 exon 8. DSRCT thus represents the third primitive sarcoma in which the EWS gene is involved and the first instance of recurrent rearrangement of a tumor suppressor gene, WT1, in a specific tumor type. The different translocation partners of the EWS gene, all of which are putative or definite transcription factor genes, may be responsible for the biological differences between DSRCT, Ewing's sarcoma, and clear cell sarcoma.
The Effects of Phosphorus and Organic Matter on the Concentration of Certain Decomposition Products of Cyanamid in Tobacco Plantbeds (1957)

Abstract Field experiments were conducted to determine the effects of superphosphate and organic matter in preventing the accumulation of toxic residues where Cyanamid was used for weed control in tobacco plantbeds on heavy silt loam soils of central Kentucky. Toxic materials or conditions in some cases following treatment with Cyanamid resulted in stunted tobacco seedlings or even death. Soil conditions where seedling injury was noted include soil pH above 8 and ammonium‐N concentration exceeding 350 ppm. of soil at seeding time (about April 1). Three‐fourths pound per square yard of 20% superphosphate applied with the Cyanamid decreased soil pH and ammonium‐N concentration, resulting in improved plant growth. Organic matter decreased soil pH and ammonium‐N content, but not until May which is too late for seeding. In laboratory studies ammonium ions from the decomposition of Cyanamid were more readily leached from the soil when superphosphate or other materials supplying cations had been added. Leaching ammonium‐N from the soil resulted in improved plant growth particularly when superphosphate had been used. In greenhouse studies ammonium‐N in soil was found to be toxic to tobacco seedings, particularly at high soil pH as occurs when Cyanamid (equivalent to 70% calcium hydroxide) is applied to soil in sufficient quantity to act as a weed control agent.
Missorting of Tau in Neurons Causes Degeneration of Synapses That Can Be Rescued by the Kinase MARK2/Par-1 (2007)

Early hallmarks of Alzheimer's disease include the loss of synapses, which precedes the loss of neurons and the pathological phosphorylation and aggregation of tau protein. Mitochondrial dysfunction has been suggested as a reason, but evidence on the role of tau was lacking. Here, we show that transfection of tau in mature hippocampal neurons leads to an improper distribution of tau into the somatodendritic compartment with concomitant degeneration of synapses, as seen by the disappearance of spines and of presynaptic and postsynaptic markers. This is accompanied by transport inhibition of vesicles and organelles, concomitant with an increase and bundling of microtubules. Mitochondria degenerate, thus causing ATP levels to decrease. The tau-induced synaptic decay can be relieved by the activation of the kinase MARK2 (microtubule-associated protein/microtubule affinity regulating kinase 2)/Par-1 (protease-activated receptor 1), which can remove tau from the microtubule tracks and reverses the transport block. This leads to the rescue of dendritic spines, synapses, mitochondrial transport and ATP levels.
Trivalent α-D-mannoside clusters as inhibitors of type-1 fimbriae-mediated adhesion of Escherichia coli: structural variation and biotinylation (2001)

Structural modifications of trivalent cluster mannosides are presented to further elucidate the ligand preferences of the type-1 fimbrial lectin of Escherichia coli. Two types of variations are performed, either regarding the aglycone part of cluster mannosides of type 2, leading to 27, or altering the spacer lengths of mannosyl clusters of type 1, leading to clusters 20–22. Biotinylation of the cluster mannoside with the highest affinity to the type-1 fimbrial lectin is also shown (33). Testing of the inhibitory potencies of the synthesised cluster glycosides as inhibitors of mannose-specific (type-1 fimbriae-mediated) binding of E. coli to mannan in an enzyme-linked immunosorbent assay (ELISA) suggests that a structural preorganisation as given in cluster 2a can be favourably combined with greater spacer flexibility as in cluster 22.