gebhart/patrepeval huggingface dataset:
Derivatives of a Novel Cyclopeptolide. 2. Synthesis, Activity against Multidrug Resistance in CHO and KB Cells in vitro, and Structure-Activity Relationships (1994)

A series of derivatives of the novel cyclopeptolide 1 was prepared, and their ability to chemosensitize multi drug resistant CHO and KB cells in vitro was evaluated. In contrast to the parent compound, several of the derivatives were found to be highly active. In particular, conversion of the R-lactic acid residue of 1 into its S-isomer via lactone ring cleavage and recyclization with inversion resulted in a marked enhancement of activity. Some of these derivatives (e.g., 15a, SDZ 280.446) belong to the most potent resistance modulating compounds known so far.
Association of gut microbiota with post-operative clinical course in Crohn’s disease (2013)

These observations permitted an association of gut microbial profiles with probability of recurrence in this limited single-center study. These results suggest that profiling the gut microbiota may be useful in guiding treatment of Crohn's patients undergoing surgery.
Modulating IgG effector function by Fc glycan engineering (2017)

IgG antibodies contain a conserved <i>N</i>-glycosylation site on the Fc domain to which a complex, biantennary glycan is attached. The fine structures of this glycan modulate antibody effector functions by affecting the binding affinity of the Fc to diverse Fc receptor family members. For example, core fucosylation significantly decreases antibody-dependent cellular cytotoxicity (ADCC), whereas terminal α2,6-sialylation plays a critical role in the anti-inflammatory activity of human i.v. immunoglobulin therapy. The effect of specific combinations of sugars in the glycan on ADCC remains to be further addressed, however. Therefore, we synthesized structurally well-defined homogeneous glycoforms of antibodies with different combinations of fucosylation and sialylation and performed side-by-side in vitro FcγR-binding analyses, cell-based ADCC assays, and in vivo IgG-mediated cellular depletion studies. We found that core fucosylation exerted a significant adverse effect on FcγRIIIA binding, in vitro ADCC, and in vivo IgG-mediated cellular depletion, regardless of sialylation status. In contrast, the effect of sialylation on ADCC was dependent on the status of core fucosylation. Sialylation in the context of core fucosylation significantly decreased ADCC in a cell-based assay and suppressed antibody-mediated cell killing in vivo. In contrast, in the absence of fucosylation, sialylation did not adversely impact ADCC.
The caspase family of cysteine proteases (1997)

The discovery that CED-3, the product of a gene necessary for programmed cell death in the nematode Caenorhabditis elegans, is related to the mammalian cysteine protease interleukin-1 beta converting enzyme (ICE/caspase-1) has led to intense interest in the role of proteases in apoptosis. It is now clear that at least some members of the caspase (ICE/CED-3) family, which at present includes ten homologues of human origin, are essential components of an evolutionarily conserved pathway of apoptosis. These enzymes appear to be involved in both the initial signaling events and the downstream proteolytic cleavages that result in the apoptotic phenotype. Selective macromolecular and peptide-based inhibitors attenuate apoptosis in whole cells, suggesting that one or more of these enzymes will be suitable targets for therapeutic intervention in diseases resulting from inappropriate cell death.
Selective Laser Sintering of Zirconia with Micro-Scale Features (1999)

Recent work in Selective Laser Sintering of ceramics at the University of Texas at Austin demonstrates the capability to produce zirconia parts with fine features. Zirconia powder was pre-processed into spherical particles, laser sintered with a sacrificial polymer binder, infiltrated and post-sintered to higher density. Optical micrographs show that hole sizes of 180 /-tm are possible in fully ceramic components.
Percutaneous Transcatheter Implantation of an Aortic Valve Prosthesis for Calcific Aortic Stenosis (2002)

Nonsurgical implantation of a prosthetic heart valve can be successfully achieved with immediate and midterm hemodynamic and clinical improvement. After further device modifications, additional durability tests, and confirmatory clinical implantations, PHV might become an important therapeutic alternative for the treatment of selected patients with nonsurgical aortic stenosis.
After the diagnosis (1997)

When the words "Alzheimer's disease" are first used regarding a patient with increasing memory and judgment problems, the person involved and his or her family members usually leave the office with sinking hearts. However, Dr. Ham believes that using the term is important, because it gives structure to management and can be the impetus to seek information about the disease and learn about local support organizations. Clarifying the diagnosis is but the first of many ways that primary care physicians can assist families in deciding about home care, intensity of treatment, and long-term placement.
Cranial Pole Nephrectomy in the Pig Model: Anatomic Analysis of Arterial Injuries in Tridimensional Endocasts (2011)

As previously demonstrated in humans, sections at 1.0 cm or more cranially to the hilus in pigs also showed a significant decrease in damage to the major intrarenal arteries. Therefore, as regards arterial damage, the pig kidney is a useful model for partial nephrectomy in the cranial (upper) pole.
Strong Luminescence of Solubilized Carbon Nanotubes (2000)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTStrong Luminescence of Solubilized Carbon NanotubesJason E. Riggs, Zhixin Guo, David L. Carroll, and Ya-Ping SunView Author Information Department of Chemistry and Center for Advanced Engineering Fibers and Films Howard L. Hunter Chemistry Laboratory Department of Physics and Astronomy, Kinard Laboratory Clemson University, Clemson, South Carolina 29634 Cite this: J. Am. Chem. Soc. 2000, 122, 24, 5879–5880Publication Date (Web):June 2, 2000Publication History Received3 December 1999Published online2 June 2000Published inissue 1 June 2000https://pubs.acs.org/doi/10.1021/ja9942282https://doi.org/10.1021/ja9942282rapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views5350Altmetric-Citations675LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Carbon nanotubes,Luminescence,Polymer solutions,Solubilization,Solution chemistry Get e-Alerts
The metabolic syndrome: an introduction (2007)

It is my pleasure to introduce this special thematic issue of Applied Physiology, Nutrition, and Metabolism (APNM) on metabolic syndrome (MetS). This publication comes at an exciting time, in the midst of debates encompassing the most appropriate clinical definition of MetS, its potential etiological pathways, and questions about the very existence of MetS as an entity unto itself. This compilation of invited reviews and original research articles provides an overview and sampling of the latest research on MetS. It has been designed to meet the interests of the diverse readership of APNM and to stimulate further research in this important area of investigation.
Clinical advances in therapies targeting the interleukin-2 receptor (2003)

A dominant theme in modern immunological research is the elucidation of how the different branches of the immune system communicate. Identification of receptors for antigens, co‐receptors such as CD4 and CD8, major histocompatibility complex (MHC) molecules and cytokine receptors, has gone a long way to giving a clearer view of the complexities of this interaction. More recently, this new information has opened up avenues for therapeutic intervention by directing novel treatments towards these various receptors. This new strategy of immune‐receptor‐directed therapy has been applied to an array of human disorders both in the laboratory and clinical settings.

Perhaps one of the most important, and certainly most studied, cytokines is interleukin‐2 (IL‐2). This molecule was first identified in 1976 by Morgan as a substance present in the supernatant of activated peripheral blood lymphocytes that was capable of driving the growth and proliferation of lymphocytes in vivo .1 Recent molecular biological advances have allowed development of recombinant IL‐2 and inhibitors of its cellular receptor. This review focuses on the basic biology of IL‐2 and its receptor, and examines the clinical applications of IL‐2 receptor‐targeted therapies. Recombinant IL‐2 has also been extensively used in treatment of various malignancies, but for reasons of space, I will not further examine this issue.

I searched through the databases Medline, Embase and Pre‐Medline using the key words interleukin‐2 and interleukin‐2 receptor. I used recent reviews from these searches along with original articles on the subject.

IL‐2 is a single polypeptide of molecular weight 15.5 kDa, 133 amino acid residues long. There is only a single IL‐2 gene locus in humans, on chromosome 4. IL‐2 is a globular protein containing two sets of α‐helical domains, lying at right angles to each other.2 These α‐helical regions are involved in the binding to the receptor, and indeed this helical …
Extracellular ATP-induced Proliferation of Adventitial Fibroblasts Requires Phosphoinositide 3-Kinase, Akt, Mammalian Target of Rapamycin, and p70 S6 Kinase Signaling Pathways (2004)

Extracellular nucleotides are increasingly recognized as important regulators of growth in a variety of cell types. Recent studies have demonstrated that extracellular ATP is a potent inducer of fibroblast growth acting, at least in part, through an ERK1/2-dependent signaling pathway. However, the contributions of additional signaling pathways to extracellular ATP-mediated cell proliferation have not been defined. By using both pharmacologic and genetic approaches, we found that in addition to ERK1/2, phosphatidylinositol 3-kinase (PI3K), Akt, mammalian target of rapamycin (mTOR), and p70 S6K-dependent signaling pathways are required for ATP-induced proliferation of adventitial fibroblasts. We found that extracellular ATP acting in part through G(i) proteins increased PI3K activity in a time-dependent manner and transient phosphorylation of Akt. This PI3K pathway is not involved in ATP-induced activation of ERK1/2, implying activation of independent parallel signaling pathways by ATP. Extracellular ATP induced dramatic increases in mTOR and p70 S6K phosphorylation. This activation of the mTOR/p70 S6 kinase (p70 S6K) pathway in response to ATP is because of independent contributions of PI3K/Akt and ERK1/2 pathways, which converge on the level of p70 S6K. ATP-dependent activation of mTOR and p70 S6K also requires additional signaling inputs perhaps from pathways operating through Galpha or Gbetagamma subunits. Collectively, our data demonstrate that ATP-induced adventitial fibroblast proliferation requires activation and interaction of multiple signaling pathways such as PI3K, Akt, mTOR, p70 S6K, and ERK1/2 and provide evidence for purinergic regulation of the protein translational pathways related to cell proliferation.
New Backstrap Vagus Electrode for Continuous Intraoperative Neuromonitoring in Thyroid Surgery (2011)

The new backstrap vagal stimulation electrode meets the requirements for reliable CIONM.
Vaccination of Dendritic Cells Loaded with Interleukin-12-Secreting Cancer Cells Augments In vivo Antitumor Immunity: Characteristics of Syngeneic and Allogeneic Antigen-Presenting Cell Cancer Hybrid Cells (2005)

Cancer immunotherapy by fusion of antigen-presenting cells and tumor cells has been shown to induce potent antitumor immunity. In this study, we characterized syngeneic and allogeneic, murine macrophage/dendritic cell (DC)-cancer fusion cells for the antitumor effects. The results showed the superiority of allogeneic cells as fusion partners in both types of antigen-presenting cells in an in vivo immunotherapy model. A potent induction of tumor-specific CTLs was observed in these immunized conditions. In addition, the immunization with DC-cancer fusion cells was better than that with macrophage-cancer fusion cells. Both syngeneic and allogeneic DC-cancer fusion cells induced higher levels of IFN-gamma production than macrophage-cancer fusion cells. Interestingly, allogeneic DC-cancer fusion cells were superior in that they efficiently induced Th1-type cytokines but not the Th2-type cytokines interleukin (IL)-10 and IL-4, whereas syngeneic DC-cancer fusion cells were powerful inducers of both Th1 and Th2 cytokines. These results suggest that allogeneic DCs are suitable as fusion cells in cancer immunotherapy. To further enhance the antitumor immunity in the clinical setting, we prepared DCs fused with IL-12 gene-transferred cancer cells and thus generated IL-12-secreting DC-cancer fusion cells. Immunization with these gene-modified DC-cancer fusion cells was able to elicit a markedly enhanced antitumor effect in the in vivo therapeutic model. This novel IL-12-producing fusion cell vaccine might be one promising intervention for future cancer immunotherapy.
Direct imaging of single UvrD helicase dynamics on long single-stranded DNA (2013)

Fluorescence imaging of single-protein dynamics on DNA has been largely limited to double-stranded DNA or short single-stranded DNA. We have developed a hybrid approach for observing single proteins moving on laterally stretched kilobase-sized ssDNA. Here we probed the single-stranded DNA translocase activity of Escherichia coli UvrD by single fluorophore tracking, while monitoring DNA unwinding activity with optical tweezers to capture the entire sequence of protein binding, single-stranded DNA translocation and multiple pathways of unwinding initiation. The results directly demonstrate that the UvrD monomer is a highly processive single-stranded DNA translocase that is stopped by a double-stranded DNA, whereas two monomers are required to unwind DNA to a detectable degree. The single-stranded DNA translocation rate does not depend on the force applied and displays a remarkable homogeneity, whereas the unwinding rate shows significant heterogeneity. These findings demonstrate that UvrD assembly state regulates its DNA helicase activity with functional implications for its stepping mechanism, and also reveal a previously unappreciated complexity in the active species during unwinding.
The glomerular basal lamina in hereditary nephritis (1981)

Characteristic ultrastructural alterations of the glomerular basal lamina have been reported in hereditary nephritis. The basal lamina is irregularly thickened and the lamina densa shows replication with a "basket weave" pattern, enclosing electron-lucent lacunae which frequently contain small dense particles. However there is controversy regarding the specificity of this lesion in hereditary nephritis. To determine the specificity, 366 renal biopsies from 310 children were studied retrospectively. Twenty-four out of 27 patients with hereditary nephritis showed the characteristic changes of the basal lamina and they were widespread in 17. Two patients with recurrent haematuria but no family history of deafness or haematuria showed similar extensive changes and are regarded as new mutant cases of hereditary nephritis. Similar changes were seen in 17 of the 281 patients with other conditions but were always localized to a few capillary loops. We conclude that a widespread "basket weave" pattern appears to be confined to hereditary nephritis and is seen in the great majority of such cases.
Nucleotide sequence of the LuxA and LuxB genes of the bioluminescent marine bacteriumVibrio fischeri (1988)

Luminescence in marine bacteria is catalyzed by the heterodimeric enzyme luciferase, whose alpha and beta suibunits are encoded by the lujxA and lljxB genes respectively (1). In Vibrio harveyi, these genes have been sequenced (2,3). We have determined the nucleotide (nt) sequence of both strands of a cloned DNA fragment that contains these genes from a second species, V. fischeri strain MJ-1 (4). Start and stop codons are uinderlined. LujxA (startE89) and lujxB (start=1392) are 1065 and 981 nt in length (355 and 327 aa), respectively, and are separated by 38 nt. The 3' end of an open reading
In VivoBinding of Mouse IgG Via Polyreactive Surface IgM Abrogates Progressive Lymphocytosis in Prolymphocytic Leukemia (1998)

Surface IgM expressed by malignant CD5+ B-cells from patients with B-chronic lymphocytic leukemia (B-CLL) has previously been shown to bind mouse Ig in what appears to be an example of polyreactive antigen-binding activity. This report demonstrates the in vitro and in vivo binding of mouse Ig to the surface of malignant B-cells from a patient with B-cell prolymphocytic leukemia (B-PLL). In vitro studies showed that K121, a mouse monoclonal antibody, bound to the B-PLL cells via the same low-affinity binding interaction demonstrated to occur between mouse Ig and surface IgM expressed by B-CLL cells rather than in the conventional sense against a specific antigen via its antigen-binding site. With the view to using this phenomenon to target malignant B-cells, it was important to determine whether the low-affinity interaction also occurred in vivo. Infusions of K121 totalling 286 mg were administered to a B-PLL patient over 7 days. Binding of K121 to circulating B-PLL cells was demonstrable after the administration of 36 mg of antibody and was preceded by the appearance of free antibody in the serum. Throughout the period of the infusion, the rapid rise in the peripheral blood white cell count normally observed after leukopheresis was abrogated. However, the count rose markedly after cessation of the antibody infusion in parallel with a decrease in both free and cell-bound K121. There were no observable side effects and no host immune response to either species specific or idiotypic determinants on the mouse Ig was detected. The in vivo binding of mouse Ig together with the previous in vitro data suggest the potential for a novel targeting mechanism using a region of the mouse Ig molecule to target polyreactive Ig expressed by malignant cells in B-CLL and B-PLL.
Space-time block codes from orthogonal designs (1999)

We introduce space-time block coding, a new paradigm for communication over Rayleigh fading channels using multiple transmit antennas. Data is encoded using a space-time block code and the encoded data is split into n streams which are simultaneously transmitted using n transmit antennas. The received signal at each receive antenna is a linear superposition of the n transmitted signals perturbed by noise. Maximum-likelihood decoding is achieved in a simple way through decoupling of the signals transmitted from different antennas rather than joint detection. This uses the orthogonal structure of the space-time block code and gives a maximum-likelihood decoding algorithm which is based only on linear processing at the receiver. Space-time block codes are designed to achieve the maximum diversity order for a given number of transmit and receive antennas subject to the constraint of having a simple decoding algorithm. The classical mathematical framework of orthogonal designs is applied to construct space-time block codes. It is shown that space-time block codes constructed in this way only exist for few sporadic values of n. Subsequently, a generalization of orthogonal designs is shown to provide space-time block codes for both real and complex constellations for any number of transmit antennas. These codes achieve the maximum possible transmission rate for any number of transmit antennas using any arbitrary real constellation such as PAM. For an arbitrary complex constellation such as PSK and QAM, space-time block codes are designed that achieve 1/2 of the maximum possible transmission rate for any number of transmit antennas. For the specific cases of two, three, and four transmit antennas, space-time block codes are designed that achieve, respectively, all, 3/4, and 3/4 of maximum possible transmission rate using arbitrary complex constellations. The best tradeoff between the decoding delay and the number of transmit antennas is also computed and it is shown that many of the codes presented here are optimal in this sense as well.
CKβ8, a novel CC chemokine that predominantly acts on monocytes (1997)

We have studied the biological properties of a new human CC chemokine, CKbeta8, consisting of 99 amino acids including six cysteines. CKbeta8 mRNA transcripts were induced in monocytes by IL-1beta and, to a lesser extent, by IFNgamma, and were detected in RNA extracted from normal human liver and gastrointestinal tract. CKbeta8 is chemotactic for monocytes, but is inactive on IL-2 conditioned T lymphocytes, eosinophils and neutrophils. Desensitization experiments indicate that CKbeta8 and MIP-1beta completely share receptors on monocytes and that the CKbeta8 receptor, which appears to differ from the known ones, is also recognized by MCP-1, MCP-2, MCP-3, MCP-4, MIP-1alpha and RANTES.
Activation of critical, host-induced, metabolic and stress pathways marks neutrophil entry into cystic fibrosis lungs (2009)

Cystic fibrosis (CF) patients undergo progressive airway destruction caused in part by chronic neutrophilic inflammation. While opportunistic pathogens infecting CF airways can cause inflammation, we hypothesized that host-derived metabolic and stress signals would also play a role in this process. We show that neutrophils that have entered CF airways have increased phosphorylation of the eukaryotic initiation factor 4E and its partner the 4E-binding protein 1; 2 key effectors in the growth factor- and amino acid-regulated mammalian target of rapamycin (mTOR) pathway. Furthermore CF airway neutrophils display increased phosphorylation of the cAMP response element binding protein (CREB), a major transcriptional coactivator in stress signaling cascades. These active intracellular pathways are associated with increased surface expression of critical adaptor molecules, including the growth factor receptor CD114 and the receptor for advanced glycation end-products (RAGE), a CREB inducer and sensor for host-derived damage-associated molecular patterns (DAMPs). Most CF airway fluids lack any detectable soluble RAGE, an inhibitory decoy receptor for DAMPs. Concomitantly, CF airway fluids displayed high and consequently unopposed levels of S100A12; a potent mucosa- and neutrophil-derived DAMP. CF airway neutrophils also show increased surface levels of 2 critical CREB targets, the purine-recycling enzyme CD39 and the multifunctional, mTOR-inducing CXCR4 receptor. This coordinated set of events occurs in all patients, even in the context of minimal airway inflammation and well-preserved lung function. Taken together, our data demonstrate an early and sustained activation of host-responsive metabolic and stress pathways upon neutrophil entry into CF airways, suggesting potential targets for therapeutic modulation.