gebhart/patrepeval huggingface dataset:
Skin grafting of a chronic leg ulcer with combined Versajet™‐V.A.C. therapy (2006)

A new method for surgical wound debridement is the Versajet hydrosurgery technique. This technique uses a high velocity jet of sterile saline with a speed up to 1,078 km/h (670 miles/h). By using the Venturi effect (fluid speeds up in a restriction, reducing its pressure and producing a partial vacuum), a simultaneous vacuum is created across the operating window of the handpiece. The application of this high velocity fluid jet to a chronic wound enables precise debridement without collateral tissue damage. The vacuum-assisted closure (V.A.C.) therapy is used for chronic wounds to induce faster wound healing. This system creates a vacuum-induced negative pressure to a specific wound area resulting in an accelerated formation of granulation tissue in the wound bed. We present a patient who experienced rapid wound healing when both of these techniques were combined to clean the wound. After split-thickness skin grafting, V.A.C. therapy was continued. The result was excellent graft acceptance with complete wound healing. This case is unique in that a combination of both therapies resulted in complete wound healing.
Subtyping of triple‐negative breast cancer: Implications for therapy (2014)

Triple‐negative breast cancer (TNBC) is a heterogeneous disease; gene expression analyses recently identified 6 distinct TNBC subtypes, each of which displays a unique biology. Exploring novel approaches for the treatment of these subtypes is critical, especially because the median survival for women with metastatic TNBC is less than 12 months, and virtually all women with metastatic TNBC ultimately will die of their disease despite systemic therapy. To date, not a single targeted therapy has been approved for the treatment of TNBC, and cytotoxic chemotherapy remains the standard treatment. In this review, the authors discuss recent developments in subtyping TNBC and the current and upcoming therapeutic strategies being explored in an attempt to target TNBC. Cancer 2015;121:8–16 . © 2014 American Cancer Society .
Effect of obesity on pulmonary inflammation induced by acute ozone exposure: role of interleukin-6 (2008)

To determine the role of interleukin (IL)-6 in the increased ozone (O3)-induced inflammation and injury observed in obese vs. lean mice, lean wild-type and leptin-deficient obese (ob/ob) mice were injected with anti-IL-6 antibody (Ab) or isotype control Ab 24 h before exposure to either O3 (2 ppm for 3 h) or room air. Four or 24 h after O3 exposure, bronchoalveolar lavage (BAL) was performed, and the lungs were harvested for Western blotting. Anti-IL-6 Ab caused substantial reductions in O3-induced increases in BAL IL-6 in mice of both genotypes. Four hours following O3, ob/ob mice had increased BAL neutrophils compared with controls, and anti-IL-6-Ab virtually abolished this difference. At 24 h, O3-induced increases in BAL protein and BAL serum albumin were augmented in ob/ob vs. wild-type mice, and anti-IL-6 Ab ablated these obesity-related differences in epithelial barrier injury. O3 increased tyrosine phosphorylation of STAT-3 and STAT-1. There was no effect of obesity on STAT-3 phosphorylation, whereas obesity decreased STAT-1 expression, resulting in reduced STAT-1 phosphorylation. IL-6 neutralization did not alter STAT-3 or STAT-1 phosphorylation in ob/ob or wild-type mice. O3 increased BAL leukemia inhibitory factor (LIF) to a greater extent in obese than in lean mice, and LIF may account for effects on STAT phosphorylation. Our results suggest that IL-6 plays a complex role in pulmonary responses to O3, a role that differs between wild-type and ob/ob mice. Moreover, obesity-related differences in activation of STAT proteins may contribute to some of the differences in the response of obese vs. lean mice.
Multiplex Particle Focusing via Hydrodynamic Force in Viscoelastic Fluids (2013)

We introduce a multiplex particle focusing phenomenon that arises from the hydrodynamic interaction between the viscoelastic force and the Dean drag force in a microfluidic device. In a confined microchannel, the first normal stress difference of viscoelastic fluids results in a lateral migration of suspended particles. Such a viscoelastic force was harnessed to focus different sized particles in the middle of a microchannel, and spiral channel geometry was also considered in order to take advantage of the counteracting force, Dean drag force that induces particle migration in the outward direction. For theoretical understanding, we performed a numerical analysis of viscoelastic fluids in the spiral microfluidic channel. From these results, a concept of the 'Dean-coupled Elasto-inertial Focusing band (DEF)' was proposed. This study provides in-depth physical insight into the multiplex focusing of particles that can open a new venue for microfluidic particle dynamics for a concrete high throughput platform at microscale.
Human SP-A 3′-UTR variants mediate differential gene expression in basal levels and in response to dexamethasone (2003)

Human surfactant protein A (SP-A) is encoded by two genes (SP-A1, SP-A2), and each is identified with several alleles. SP-A is involved in normal lung function, innate immunity, inflammatory processes, and is regulated by glucocorticoids. We investigated the role of 3'-untranslated region (UTR) of 10 SP-A variants on gene expression using transient transfection of 3'-UTR constructs in the human lung adenocarcinoma cell line NCI-H441. We found: 1) both basal mRNA and protein levels of the reporter gene of SP-A 3'-UTR constructs are significantly (P < 0.01) reduced compared with controls (vector pGL3 and surfactant protein B pGL3) and that differences exist among alleles; and 2) after dexamethasone (Dex) treatment (100 nM for 16 h), mRNA was reduced (31-51%). Seven alleles showed a significant decrease (P < 0.05) in mRNA, and three did not. Reporter activity was also decreased, from 17% (1A(1)) to 38% (1A), with six alleles showing a significant decrease. The data indicate that the 3'-UTR of SP-As play a differential role in SP-A basal expression and in response to Dex. Therefore, a careful consideration of individual use of steroid treatment may be considered.
Nonspecific Adherence byActinobacillus actinomycetemcomitansRequires Genes Widespread inBacteriaandArchaea (2000)

The gram-negative coccobacillus, Actinobacillus actinomycetemcomitans, is the putative agent for localized juvenile periodontitis, a particularly destructive form of periodontal disease in adolescents. This bacterium has also been isolated from a variety of other infections, notably endocarditis. Fresh clinical isolates of A. actinomycetemcomitans form tenacious biofilms, a property likely to be critical for colonization of teeth and other surfaces. Here we report the identification of a locus of seven genes required for nonspecific adherence of A. actinomycetemcomitans to surfaces. The recently developed transposon IS903phikan was used to isolate mutants of the rough clinical isolate CU1000 that are defective in tight adherence to surfaces (Tad(-)). Unlike wild-type cells, Tad(-) mutant cells adhere poorly to surfaces, fail to form large autoaggregates, and lack long, bundled fibrils. Nucleotide sequencing and genetic complementation analysis revealed a 6.7-kb region of the genome with seven adjacent genes (tadABCDEFG) required for tight adherence. The predicted TadA polypeptide is similar to VirB11, an ATPase involved in macromolecular transport. The predicted amino acid sequences of the other Tad polypeptides indicate membrane localization but no obvious functions. We suggest that the tad genes are involved in secretion of factors required for tight adherence of A. actinomycetemcomitans. Remarkably, complete and highly conserved tad gene clusters are present in the genomes of the bubonic plague bacillus Yersinia pestis and the human and animal pathogen Pasteurella multocida. Partial tad loci also occur in strikingly diverse Bacteria and Archaea. Our results show that the tad genes are required for tight adherence of A. actinomycetemcomitans to surfaces and are therefore likely to be essential for colonization and pathogenesis. The occurrence of similar genes in a wide array of microorganisms indicates that they have important functions. We propose that tad-like genes have a significant role in microbial colonization.
Oriented Immobilization of Fab' Fragments on Silica Surfaces (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOriented Immobilization of Fab' Fragments on Silica SurfacesBin. Lu, Jiamin. Xie, Chunlin. Lu, Changru. Wu, and Yu. WeiCite this: Anal. Chem. 1995, 67, 1, 83–87Publication Date (Print):January 1, 1995Publication History Published online1 May 2002Published inissue 1 January 1995https://pubs.acs.org/doi/10.1021/ac00097a014https://doi.org/10.1021/ac00097a014research-articleACS PublicationsRequest reuse permissionsArticle Views509Altmetric-Citations74LEARN 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
Stem Cell Therapy and Breast Cancer Treatment: Review of Stem Cell Research and Potential Therapeutic Impact Against Cardiotoxicities Due to Breast Cancer Treatment (2014)

A new problem has emerged with the ever-increasing number of breast cancer survivors. While early screening and advances in treatment have allowed these patients to overcome their cancer, these treatments often have adverse cardiovascular side effects that can produce abnormal cardiovascular function. Chemotherapeutic and radiation therapy have both been linked to cardiotoxicity; these therapeutics can cause a loss of cardiac muscle and deterioration of vascular structure that can eventually lead to heart failure (HF). This cardiomyocyte toxicity can leave the breast cancer survivor with a probable diagnosis of dilated or restrictive cardiomyopathy (DCM or RCM). While current HF standard of care can alleviate symptoms, other than heart transplantation, there is no therapy that replaces cardiac myocytes that are killed during cancer therapies. There is a need to develop novel therapeutics that can either prevent or reverse the cardiac injury caused by cancer therapeutics. These new therapeutics should promote the regeneration of lost or deteriorating myocardium. Over the last several decades, the therapeutic potential of cell-based therapy has been investigated for HF patients. In this review, we discuss the progress of pre-clinical and clinical stem cell research for the diseased heart and discuss the possibility of utilizing these novel therapies to combat cardiotoxicity observed in breast cancer survivors.
Identification of a High Affinity FcγRIIA-binding Peptide That Distinguishes FcγRIIA from FcγRIIB and Exploits FcγRIIA-mediated Phagocytosis and Degradation (2008)

FcgammaRIIA is a key activating receptor linking immune complex formation with cellular effector functions. FcgammaRIIA has 93% identity with an inhibitory receptor, FcgammaRIIB, which negatively regulates FcgammaRIIA. FcgammaRIIA is important in the therapeutic action of several monoclonal antibodies. Binding molecules that discriminate FcgammaRIIA from FcgammaRIIB may optimize receptor activity and serve as a lead for development of therapeutics with FcgammaRIIA as a key target. Here we report the use of phage display libraries to select short peptides with distinct FcgammaRIIA binding properties. An 11-mer peptide (WAWVWLTETAV) was characterized that bound FcgammaRIIA with a K(d) of 500 nm. It mediated cell internalization and degradation of a model antigen. The peptide-binding site on FcgammaRIIA was shown to involve Phe(163) and the IgG binding amino acids Trp(90) and Trp(113). It is thus overlapping but not identical to that of IgG. Neither activating receptors FcgammaRI and FcgammaRIII, nor FcgammaRIIB, all of which lack Phe(163), bound the peptide.
Extinction of IL-12 Signaling Promotes Fas-Mediated Apoptosis of Antigen-Specific T Cells (1999)

In previous studies we have shown that peripheral tolerance achieved by high dose feeding of OVA to intact OVA-TCR transgenic mice was enhanced when endogenous IL-12 was neutralized simultaneously. To generalize this phenomenon, in the present study we investigated the tolerogenic mechanisms underlying the blockade of IL-12 signaling following oral and systemic Ag delivery. We found that the numbers of Ag-specific T cells in several lymphoid organs were significantly reduced due to T cell apoptosis following oral OVA or systemic OVA administration when combined with anti-IL-12 injection, but there was no decrease in T cell numbers for OVA-fed, OVA-injected, or anti-IL-12 alone-treated mice compared with those in untreated control mice. In addition, mostly Fas+ T cells were subject to apoptotic deletion in the OVA- plus anti-IL-12-treated groups, and an enhanced cell death of T cells upon OVA restimulation in vitro could be partially reversed by blockade of the Fas/Fas ligand interaction. Finally, in a murine model of superantigen-driven T cell expansion and deletion, we observed no deletional effects of anti-IL-12 treatment on CD4+ cells in Fas-deficient (MRL/lpr) mice, but did find these effects in MRL wild-type mice. In summary, our data suggest that in the course of Ag-induced cell proliferation of Th1 cells, signaling through IL-12 is required to prevent an induction of Fas-mediated apoptosis. Thus, the use of anti-IL-12 may be potentially useful in modulating peripheral immune responses by promotion of Fas-mediated cell death.
The mechanism of cell adhesion by classical cadherins: the role of domain 1 (2005)

The mechanism by which classical cadherins mediate cell adhesion and, in particular, the roles played by calcium and Trp2, the second amino acid in the N-terminal domain, have long been controversial. We have used antibodies to investigate the respective contributions of Trp2 and calcium to the stability of the N-terminal domain of N-cadherin. Using a peptide antibody to the betaB strand in domain 1, which detects a disordered structure, we show that both Trp2 and calcium play crucial parts in regulating stability of the domain. The epitope for another antibody, mAb GC4, has been mapped to the base of domain 1. Binding of GC4 to this epitope was shown to depend on intramolecular 'docking' of Trp2 into the domain 1 structure. Using this property, we provide evidence that calcium regulates a dynamic equilibrium between docked and undocked Trp2. Finally, a novel technique has been developed to test whether Trp2 cross-intercalation between cadherin molecules from adjacent cells (strand exchange) is central to cadherin-mediated cell adhesion. Guided by crystal structures showing strand exchange, we have introduced single cysteine point mutations into N-cadherin domain 1 in such a way that a disulphide bond will form between opposing N-cadherin molecules during cell adhesion if strand exchange occurs. The bond requires complementary cysteines to be precisely juxtaposed according to the strand exchange model. Our results demonstrate that the disulphide bond forms as predicted. This provides compelling evidence that strand exchange is indeed a primary event in cell adhesion by classical cadherins.
Volatile Sulfur Compounds in Yeast Extracts (1994)

Yeast extracts represent an important source of volatile sulfur compounds, many of which possess low odor threshold values. They are used as sources of flavor for a range of savory foods, especially when a meaty note is required. In spite of the usefulness of yeast extracts, there are very few reports of their volatile flavor components. The production of yeast extracts is briefly reviewed, and the volatile sulfur compounds which have been identified are discussed. A recent study is presented in which the aroma components of some yeast extracts were analyzed. A total of 268 compounds were identified, including 67 sulfur compounds. The 34 sulfur compounds reported for the first time comprised 3 aliphatic sulfur compounds, one sulfur—substituted benzene derivative, 10 thiophenes, 18 thiazoles and 2 alicyclic sulfur compounds. Their importance as components of flavors and routes to their formation are considered.
Bioengineered corneas for transplantation and in vitro toxicology (2009)

Bioengineered corneas have been designed to replace partial or the full-thickness of defective corneas, as an alternative to using donor tissues. They range from prosthetic devices that solely address replacement of the cornea's function, to tissue engineered hydrogels that permit regeneration of host tissues. In cases where corneal stem cells have been depleted by injury or disease, most frequently involving the superficial epithelium, tissue engineered lamellar implants reconstructed with stem cells have been transplanted. In situ methods using ultraviolet A (UVA) crosslinking have also been developed to strengthen weakened corneas. In addition to the clinical need, bioengineered corneas are also rapidly gaining importance in the area of in vitro toxicology, as alternatives to animal testing. More complex, fully innervated, physiologically active, three-dimensional organotypic models are also being tested.
Architecture of virtual machines (1973)

Virtual machine (VM) systems are a major development in computer systems design. By providing an efficient facsimile of one or more complete computer systems, virtual machines have extended the multi-access, multi-programming, multi-processing systems of the past decade to be multi-environment systems as well. Thus, many of the advantages in ease of system use previously enjoyed only by application programmers have been made available to systems programmers.
Characterization of multivalent pneumococcal conjugate vaccines. (2000)

A new heptavalent pneumococcal conjugate vaccine, designed to protect against disease due to serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, was formulated with aluminium phosphate adjuvant and analysed before testing in infants. Analyses were complicated by the presence of the adjuvant, and by the low level of each antigen; for example, all serotypes were formulated at 2 microg of saccharide /dose (except 6B which was formulated at 4 microg). Type specific analyses were performed on the formulated vaccine, and included determination of immunogenicity and antigenicity; the former was measured by ELISA following immunization of rabbits, the latter was measured by rate nephelometry. Non serotype specific information was also collected, and included total and adsorbed saccharide (by Anthrone assay), and total and adsorbed protein (by Lowry assay). These preclinical data supported the use of the vaccine in infants in a large randomized double-blinded clinical trial in a multiethnic population. The results of this trial show that the vaccine is safe and efficacious. Collectively, the data will be used to support licensure of the heptavalent vaccine, and documents successful scale-up of the formulation process to manufacturing level.
A Novel Ex Vivo Isolation and Expansion Procedure for Chimeric Antigen Receptor Engrafted Human T Cells (2014)

Genetically engineered T lymphocytes are a promising option for cancer therapy. Prior to adoptive transfer they have to be expanded in vitro to reach therapeutically sufficient numbers. So far, no universal method exists for selective in vitro expansion of engineered T lymphocytes. In order to overcome this problem and for proof of concept we incorporated a novel unique peptide sequence of ten amino acids as epitope (E-Tag) into the binding domains of two novel chimeric antigen receptors (ECARs) directed against either prostate stem cell antigen (PSCA) for the treatment of prostate cancer (PCa) or CD33 for the treatment of acute myeloide leukemia (AML). The epitope tag then was utilized for expanding ECAR engrafted T cells by triggering the modified T cells via a monoclonal antibody directed against the E-Tag (Emab). Moreover, the E-Tag served as an efficient selection epitope for immunomagnetic isolation of modified T cells to high purity. ECAR engrafted T cells were fully functional and mediated profound anti-tumor effects in the respective models of PCa or AML both in vitro and in vivo. The method can be integrated straightforward into clinical protocols to improve therapeutic efficiency of tumor treatment with CAR modified T lymphocytes.
Identification of a Central Phosphorylation Site in p21-activated Kinase Regulating Autoinhibition and Kinase Activity (1999)

p21-activated kinases (Pak)/Ste20 kinases are regulated in vitro and in vivo by the small GTP-binding proteins Rac and Cdc42 and lipids, such as sphingosine, which stimulate autophosphorylation and phosphorylation of exogenous substrates. The mechanism of Pak activation by these agents remains unclear. We investigated Pak kinase activation in more detail to gain insight into the interplay between the GTPase/sphingosine binding, an intramolecular inhibitory interaction, and autophosphorylation. We present biochemical evidence that an autoinhibitory domain (ID) contained within amino acid residues 67-150 of Pak1 interacts with the carboxyl-terminal kinase domain and that this interaction is regulated in a GTPase-dependent fashion. Cdc42- and sphingosine-stimulated Pak1 activity can be inhibited in trans by recombinant ID peptide, indicating similarities in their mode of activation. However, Pak1, which was autophosphorylated in response to either GTPase or sphingosine, is highly active and is insensitive to inhibition by the ID peptide. We identified phospho-acceptor site threonine 423 in the kinase activation loop as a critical determinant for the sensitivity to autoinhibition and enzymatic activity. Phosphorylation studies suggested that the stimulatory effect of both GTPase and sphingosine results in exposure of the activation loop, making it accessible for intermolecular phosphorylation.
Activation of endothelial nitric oxide synthase by red wine polyphenols: impact of grape cultivars, growing area and the vinification process (2007)

The biological activity of red wines on eNOS transcription depends neither on grape cultivars nor on growing area in general. Resveratrol may be the most promising ingredient in red wine polyphenol extracts, but does not account for the complete effect. A large part of the active components are genuine grape compounds, since extracts of grape juice that did not undergo a fermentation process also showed activity.