gebhart/patrepeval huggingface dataset:
Cytokine Gene Expression During the Development of Graft Coronary Artery Disease in Mice (1999)

Immunologic injury to heart allografts is an initial and essential event in the pathogenesis of graft coronary artery disease (GAD). A variety of cytokines expressed in heart allografts modify both acute rejection and chronic inflammation, and could contribute to the development of GAD. The present study investigated the gene expression of interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and Fas ligand in chronically rejecting DBA/2-to-B 10.D2 mouse heart allografts at defined intervals of 7, 14, 28, or 70 days after transplantation by semiquantitative reverse transcriptase-polymerase chain reaction. GAD developed gradually, showing the highest value for mean intima/media ratio at day 70. Fas ligand, and the Th1 cytokines IL-2 and IFN-gamma, were vigorously induced in allografts at day 7, when histology showed pronounced parenchymal rejection, and rapidly decreased by day 28. However, the level of mRNA expression of Th2 cytokines, IL-6 and IL-10, and other inflammatory cytokines, TNF-alpha and IL-1beta, were still elevated on day 28. The persistent expression of specific cytokines suggests an important role in chronic inflammation. Thus, a persistently high level expression of inflammatory cytokines could be associated with chronic inflammation in the allografts, which promotes the development of GAD.
Correlations of DNA, RNA and protein levels in duodenal mucosa with antiinflammatory potency and disposition to gut damage of non-steroidal agents. Comparative behaviour of glucametacine, indometacin, phenylbutazone and ibuprofen. (1978)

As far as molar ratio is concerned, glucametacine was half as potent as indometacin, twice as active as phenylbutazone and four times more effective than ibuprofen in preventing cotton granuloma. Both indometacin and phenylbutazone induced dose related gastrointestinal ulcerations and increase of 51Cr tagged erythrocytes in feces. The former drug displayed gut toxicity at anti-inflammatory doses, the latter at doses approximately four times larger. Glucametacine was still devoid of damaging effects at a dose ten times larger than the minimal one capable of inhibiting granuloma growth. Ibuprofen, too, failed to induce ulcers at all doses examined; however, it displayed a trend toward gut bleeding when doses that increased blood corticosterone were attained. Studies on duodenal mucosa showed that in rats on cotton granuloma, DNA, proteins and DNA:RNA ratio increase as compared to unimplanted rats. Glucametacine and phenylbutazone reversed the increase of DNA and proteins, respectively. Indometacin decreased all forementioned constituents of duodenal mucosa while inducing haemorrhages and ulcers on gut. Furthermore, in naive rats, unlike glucametacine and phenylbutazone, indometacin induced a decrease in protein content of duodenal mucosa. Differences in disposition of gut toxicity among glucametacine and other anti-inflammatory drugs are discussed.
Time series compressibility and privacy (2007)

In this paper we study the trade-offs between time series compressibility and partial information hiding and their fundamental implications on how we should introduce uncertainty about individual values by perturbing them. More specifically, if the perturbation does not have the same compressibility properties as the original data, then it can be detected and filtered out, reducing uncertainty. Thus, by making the perturbation “similar ” to the original data, we can both preserve the structure of the data better, while simultaneously making breaches harder. However, as data become more compressible, a fraction of the uncertainty can be removed if true values are leaked, revealing how they were perturbed. We formalize these notions, study the above trade-offs on real data and develop practical schemes which strike a good balance and can also be extended for on-the-fly data hiding in a streaming environment. 1.
Zoledronic acid in the management of metastatic bone disease (2008)

Many patients with advanced cancer experience decreased bone strength due to metastatic foci, underlying osteoporosis and/or cancer treatment induced bone loss. The clinical consequences of metastatic disease involving the skeleton are widespread. This review focuses on the efficacy, pharmacology, and safety when using intravenous biphosphonate such a zoledronic acid for cancer bone metastases. Zoledronic acid is the gold standard for the medical management of metastatic bone disease. The indications for treatment include prevention of skeletal relevant events (SRE), osteoporotic complications, and palliation of bone pain, among others. Zoledronic acid is the only bisphosphonate effective in decreasing SREs associated with bone metastases from advanced renal cell carcinoma and prostate cancer. Regarding prostate cancer, zoledronic acid effectively prevents both bone loss in patients with locally advanced disease receiving androgen deprivation therapy and SREs in men with hormone-refractory or hormone-sensitive metastatic disease. Zoledronic acid has an acceptable safety profile and tolerability, and has been effective at significantly decreasing the incidence, delaying the onset, and reducing the overall risk of experiencing an SRE compared to placebo. It is the only bisphosphonate currently approved for the prevention and treatment of skeletal complications in patients with bone metastases due to all solid tumors.
Optimization Procedure For A Holographic Lens Solar Concentrator (1989)

The subject matter of this report is the presentation of an optimization technique developed for the design and manufacturing of a holographic lens solar concentrator. The emphasis is placed on the realization of a homogeneous diffraction efficiency distribution across the aperture of the holographic lens. The nature of the holographic process requires precise control of the mechanical properties of the gelatin layer such as moisture content, shrinking, swelling, hardness and elasticity, which specify the slant angle, the mean index of refraction, the spatial frequency and the amplitude of the refractive index variatrion. These parameters determine then uniquely the Bragg condition and the diffraction efficiency. The range of parameter variation is obtained from a large number of experimentally analyzed transmission gratings with spatial frequencies that are comparable to those expected across the aperture of the holographic lens
An antidote forStaphylococcus aureuspneumonia? (2008)

Methicillin-resistant Staphylococcus aureus (MRSA) is the leading cause of bacterial infections in the United States. Severe invasive MRSA infections, which include pneumonia, are difficult to treat because the bacteria are resistant to antibiotics. A new report now shows that immunization against alpha-hemolysin (Hla), a cytolytic toxin secreted by most S. aureus strains, protects mice against lethal pneumonia. This finding represents the first successful vaccine strategy for the treatment of staphylococcal pneumonia.
Plasmonic nanotweezers: strong influence of adhesion layer and nanostructure orientation on trapping performance (2012)

Using Au bowtie nanoantennas arrays (BNAs), we demonstrate that the performance and capability of plasmonic nanotweezers is strongly influenced by both the material comprising the thin adhesion layer used to fix Au to a glass substrate and the nanostructure orientation with respect to incident illumination. We find that a Ti adhesion layer provides up to 30% larger trap stiffness and efficiency compared to a Cr layer of equal thickness. Orientation causes the BNAs to operate as either (1) a 2D optical trap capable of efficient trapping and manipulation of particles as small as 300 nm in diameter, or (2) a quasi-3D trap, with the additional capacity for size-dependent particle sorting utilizing axial Rayleigh-Bénard convection currents caused by heat generation. We show that heat generation is not necessarily deleterious to plasmonic nanotweezers and achieve dexterous manipulation of nanoparticles with non-resonant illumination of BNAs.
Model and Algorithms for Point Cloud Construction Using Digital Projection Patterns (2007)

This paper describes a computational framework for constructing point clouds using digital projection patterns. The basic principle behind the approach is to project known patterns on the object using a digital projector. A digital camera is then used to take images of the object with the known projection patterns imposed on it. Due to the presence of 3D faces of the object, the projection patterns appear distorted in the images. The images are analyzed to construct the 3D point cloud that is capable of introducing the observed distortions in the images. The approach described in this paper presents three advances over the previously developed approaches. First, it is capable of working with the projection patterns that have variable fringe widths and curved fringes and hence can provide improved accuracy. Second, our algorithm minimizes the number of images needed for creating the 3D point cloud. Finally, we use a hybrid approach that uses a combination of reference plane images and estimated system parameters to construct the point cloud. This approach provides good run-time computational performance and simplifies the system calibration.
Characterization of the TCL-1 transgenic mouse as a preclinical drug development tool for human chronic lymphocytic leukemia (2006)

Drug development in human chronic lymphocytic leukemia (CLL) has been limited by lack of a suitable animal model to adequately assess pharmacologic properties relevant to clinical application. A recently described TCL-1 transgenic mouse develops a chronic B-cell CD5(+) leukemia that might be useful for such studies. Following confirmation of the natural history of this leukemia in the transgenic mice, we demonstrated that the transformed murine lymphocytes express relevant therapeutic targets (Bcl-2, Mcl-1, AKT, PDK1, and DNMT1), wild-type p53 status, and in vitro sensitivity to therapeutic agents relevant to the treatment of human CLL. We then demonstrated the in vivo clinical activity of low-dose fludarabine in transgenic TCL-1 mice with active leukemia. These studies demonstrated both early reduction in blood-lymphocyte count and spleen size and prolongation of survival (P = .046) compared with control mice. Similar to human CLL, an emergence of resistance was noted with fludarabine treatment in vivo. Overall, these studies suggest that the TCL-1 transgenic leukemia mouse model has similar clinical and therapeutic response properties to human CLL and may therefore serve as a useful in vivo tool to screen new drugs for subsequent development in CLL.
Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design (2011)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTSynopsis of Some Recent Tactical Application of Bioisosteres in Drug DesignNicholas A. Meanwell*View Author Information Department of Medicinal Chemistry, Bristol-Myers Squibb Pharmaceutical Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, United StatesContact information. Phone: 203-677-6679. Fax: 203-677-7884. E-mail: [email protected]Cite this: J. Med. Chem. 2011, 54, 8, 2529–2591Publication Date (Web):March 17, 2011Publication History Received20 October 2010Published online17 March 2011Published inissue 28 April 2011https://pubs.acs.org/doi/10.1021/jm1013693https://doi.org/10.1021/jm1013693review-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views91020Altmetric-Citations2203LEARN 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 SUBJECTS:Antagonists,Heterocyclic compounds,Inhibitors,Molecules,Peptides and proteins Get e-Alerts
Decreased focal adhesion kinase suppresses papilloma formation during experimental mouse skin carcinogenesis. (2001)

Although focal adhesion kinase (FAK) is elevated in epithelial cancers, it is not known whether FAK expression influences tumor development in vivo. We found that fak +/- heterozygous mice display reduced 7,12-dimethylbenz[a]anthracene-induced papilloma formation that correlates with reduced FAK protein expression in the skin. However, the frequency of malignant conversion of papillomas into carcinomas is indistinguishable in fak +/- mice and their wild-type fak +/+ littermates, most likely because papilloma FAK protein expression is elevated to wild-type levels. We also found that keratinocyte FAK protein expression is important for cellular responses downstream of ras in vitro (monitored by extracellular signal-regulated kinase activation after integrin engagement). Because 7,12-dimethylbenz[a]anthracene induces an activating mutation of H-ras, this provides one possible explanation for suppression of papilloma formation when FAK protein is limiting.
Matrix Metalloproteases in Aberrant Fibrotic Tissue Remodeling (2006)

Pulmonary fibrosis, the final result of a large variety of interstitial lung diseases, is characterized by an aberrant remodeling of extracellular matrix (ECM) with a profound disturbance of the normal lung architecture. This remodeling includes the exaggerated accumulation of ECM components in the interstitial and alveolar spaces and the disruption of the basement membranes. It has long been accepted that matrix metalloproteases (MMPs) play an important role in the pathogenesis of pulmonary fibrosis, but the exact mechanisms are not well characterized. Several MMPs are strongly up-regulated in human and experimental lung fibrosis, highlighting the dynamic nature of scarring within the lung. MMPs are collectively capable of cleaving all components of the ECM and basement membranes, but importantly, they also process bioactive mediators such as growth factors, cytokines, chemokines, and cell-surface receptors. Moreover, they participate in the initiation of proteinase cascades that impact much broader substrates. Consequently, MMPs may play a central role in several interrelated processes observed in fibrosis such as ECM remodeling, basement-membrane breakdown, epithelial-cell apoptosis, cell migration, and angiogenesis.
Generalized indicator plate for genetic, metabolic, and taxonomic studies with microorganisms (1977)

We have developed an indicator plate that works well for diverse types of substrates and microorganisms. The plates are inexpensive and easy to prepare. The essential components are agar, buffer, growth-supporting nutrients, a test substrate, and 2,3,5-triphenyl tetrazolium chloride (TTC). Using various strains of Salmonella typhimurium and Escherichia coli, we have studied and defined the contribution of each component to the satisfactory function of the plate. Colonies capable of catabolizing the test substrate reduce TTC and produce a deep red formazan, whereas colonies failing to catabolize the substrate remain uncoloured. Those with intermediate rates of catabolism differ in rate and/or extent of color formation. In all cases the color is stable because TTC reduction is essentially irreversible. Since the mode of action of these plates is fairly well understood, alternative formulations can be devised to meet specific needs. The general applicability of this TTC indicator system makes it an extremely useful tool in microbial genetics, metabolism, and taxonomy.
Graft-versus-leukemia reactions in allogeneic chimeras (2003)

There is a strong graft-versus-leukemia (GVL) effect of allogeneic stem cell transplantation (SCT) due to elimination of tumor cells by alloimmune effector lymphocytes. When leukemia relapses after allogeneic SCT, donor lymphocyte transfusions (DLTs) can induce sustained remissions in some patients. This review summarizes the current status on clinical use of DLT, the basis of GVL reactions, problems associated with this therapy, and new strategies to improve DLT. Several multicenter surveys demonstrated that the GVL effect of DLT is most effective in chronic myelogenous leukemia (CML), whereas it is less pronounced in acute leukemia and myeloma. Cytokine stimulation to induce differentiation of myeloid progenitor cells or to up-regulate costimulatory molecules on tumor cells may improve the efficacy of DLT. Infections and graft-versus-host disease (GVHD) are major complications of DLT. Control of GVHD may be improved using suicide gene-modified T cells for DLT, allowing T-cell elimination if severe GVHD develops. Hopefully, in the future, GVL effect can be separated from GVHD through adoptive transfer of selected T cells that recognize leukemia-specific antigens or minor histocompatibility antigens, which are expressed predominantly on hematopoietic cells, thereby precluding attack of normal tissues. In patients with leukemia and lymphomas with fast progression, tumor growth may outpace development of effector T cells. Here it may be preferable to select stem cell transplant donors with HLA-mismatches that allow alloreactive natural killer cells, which appear early after transplantation, to retain their cytolytic function. New approaches for adoptive immune therapy of leukemia, which promise a better prognosis for these patients, are being developed.
Investigating the Interactions of Hyaluronan Derivatives with Biomolecules. The Use of Diffusional NMR Techniques (2006)

[Chemical structure: see text] The interactions between a biomaterial and biomolecules present in body fluids often determine the fate of the biomaterial. This paper presents a study on hyaluronan (HA)-containing materials (in soluble or colloidal form) that focuses on their interactions with lipids and proteins and for the first time uses PFG NMR as an analytical technique for probing these events. The interactions of HA-based polymers with phospholipids (DPPC and DPPG liposomes) are shown to depend both on charge and hydrophobicity factors. Despite the difference in behavior between albumin (substantially non-adhesive) and fibrinogen (adhesive), the interactions of the polymers with proteins do not seem to be based on hydrophobic effects but on surface polar interactions.
Humanization of an Anti-CCR4 Antibody That Kills Cutaneous T-Cell Lymphoma Cells and Abrogates Suppression by T-Regulatory Cells (2012)

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of neoplastic disorders characterized by clonally derived and skin-homing malignant T cells that express high level of chemokine receptor CCR4, which is associated with their skin-homing capacity. CCR4 is also highly expressed on T-regulatory cells (Tregs) that can migrate to several different types of chemotactic ligand CCL17- and CCL22-secreting tumors to facilitate tumor cell evasion from immune surveillance. Thus, its high-level expression on CTCL cells and Tregs makes CCR4 a potential ideal target for antibody-based immunotherapy for CTCL and other types of solid tumors. Here, we conducted humanization and affinity optimization of a murine anti-CCR4 monoclonal antibody (mAb), mAb1567, that recognizes both the N-terminal and extracellular domains of CCR4 with high affinity and inhibits chemotaxis of CCR4(+) CTCL cells. In a mouse CTCL tumor model, mAb1567 exhibited a potent antitumor effect and in vitro mechanistic studies showed that both complement-dependent cytotoxicity (CDC) and neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) likely mediated this effect. mAb1567 also exerts human NK cell-mediated ADCC activity in vitro. Moreover, mAb1567 also effectively inhibits chemotaxis of CD4(+)CD25(high) Tregs via CCL22 and abrogates Treg suppression activity in vitro. An affinity-optimized variant of humanized mAb1567, mAb2-3, was selected for further preclinical development based on its higher binding affinity and more potent ADCC and CDC activities. Taken together, this high-affinity humanized mAb2-3 with potent antitumor effect and a broad range of mechanisms of action may provide a novel immunotherapy for CTCL and other solid tumors.
Expanded microporous polytetrafluoroethylene as a vascular substitute: a two year follow-up. (1979)

Since 1974, 131 femoropopliteal, distal popliteal, and tibial bypasses have been performed using expanded microporous polytetrafluoroethylene (PTFE). Forty patients were operated on for limb salvage, and 21 had had previous bypass procedures. The overall patency rate was 82%. Early occlusions possibly were related to technical error, but most probably were due to severity of disease and poor runoff. Late occlusions were related to progressive atherosclerosis in the proximal or distal arterial tree. A 75.7% cumulative patency rate was noted at 28 months. In man the PTFE prosthesis demonstrates a smooth intimal lining with fibroblastic ingrowth into the interstices of the graft. These results are considered to be excellent in this high-risk patient population. The patency rates achieved with PTFE are better than those accomplished with alternative conduits and approach the patency rates reported with autogenous saphenous vein. Expanded microporous polytetrafluoroethylene with its high patency, pliability, and tissue incorporation is an excellent arterial substitute. Only with continued use of this material and a more uniform patient selection can more equitable comparisons be made between expanded PTFE and the autogenous vein.
The Role of Cell Cycle in Determining Levels of Gene Expression in Cho Cells (2006)

Understanding relationships between cell cycle and protein expression is critical as a means to optimising media and environmental conditions for successful commercial operation. Using flow cytometry and centrifugal elutriation together with synchronisation techniques, the possible role of CHO cell cycle dependent features in product expression was evaluated. The production of interferon-.ν was found to be time dependent. Maximum specific productivity was achieved at the mid-exponential phase of batch culture and was always associated with maximum cellular concentration of protein and a high proportion of S phase cells. However, in experiments using sorted G1, S and G2 phase cells the apparent correlation between S phase and productivity was shown not to be causal since there was no significant difference in specific productivity between the different cell cycle phases.