gebhart/patrepeval huggingface dataset:
Mechanism‐Based Fluorogenic <i>trans</i>‐Cyclooctene–Tetrazine Cycloaddition (2016)

The development of fluorogenic reactions which lead to the formation of fluorescent products from two nonfluorescent starting materials is highly desirable, but challenging. Reported herein is a new concept of fluorescent product formation upon the inverse electron-demand Diels-Alder reaction of 1,2,4,5-tetrazines with particular trans-cyclooctene (TCO) isomers. In sharp contrast to known fluorogenic reagents the presented chemistry leads to the rapid formation of unprecedented fluorescent 1,4-dihydropyridazines so that the fluorophore is built directly upon the chemical reaction. Attachment of an extra fluorophore moiety is therefore not needed. The photochemical properties of the resulting dyes can be easily tuned by changing the substitution pattern of the starting 1,2,4,5-tetrazine. We support the claim with NMR measurements and rationalize the data by computational study. Cell-labeling experiments were performed to demonstrate the potential of the fluorogenic reaction for bioimaging.
Morphine treatment of human monocyte‐derived macrophages induces differential miRNA and protein expression: Impact on inflammation and oxidative stress in the central nervous system (2010)

HIV-1-infected opiate abusers often exhibit an accelerated form of HIV-1-associated dementia and enhanced neurological dysfunction. Productive HIV-1 infection of microglia and perivascular macrophages and the resultant secretion of neurotoxic molecules by these cells contribute to this phenomenon. In order to understand the role of morphine in this process, we performed a genome-wide association study at the micro RNA (miRNA) and protein levels in human monocyte-derived macrophages (h-mdms). A total of 26 differentially expressed miRNA were identified (P < 0.01), of which hsa-miR-15b and hsa-miR-181b had the greatest increase and decrease in expression levels, respectively. Computational analysis predicted fibroblast growth factor-2 (FGF-2) as the strongest target gene for hsa-miR15b. Of note, we observed a decrease in FGF-2 protein expression in response to morphine. Both hsa-miR-15b and hsa-miR-181b have several predicted gene targets involved in inflammation and T-cell activation pathways. In this context, we observed induction of MCP-2 and IL-6 by morphine. Moreover, proteomic analysis revealed the induction of mitochondrial superoxide dismutase in response to morphine treatment. HIV-1 infection did not induce mitochondrial superoxide dismutase. Collectively, these observations demonstrate that morphine induces inflammation and oxidative stress in h-mdms thereby contributing to expansion of HIV-1 CNS reservoir expansion and disease progression. Of note, differentially expressed miRNAs (hsa-miR-15b and 181-b) may have a potential role in regulating these processes.
Third-Generation Human Epidermal Growth Factor Receptor 2 Chimeric Antigen Receptor Expression on Human T Cells Improves with Two-Signal Activation (2018)

Patient derived T cells activated ex vivo with CD3/CD28 beads show superior expansion. Therefore, CD3/CD28 beads have huge potential to be used in the clinic for immunotherapy applications. Two protocols were devised to evaluate if the expression of third-generation human epidermal growth factor receptor 2 chimeric antigen receptor (CAR) can be improved on human T cells activated with CD3/CD28 beads. In protocol 1, unconcentrated human epidermal growth factor receptor 2 CAR retroviral supernatants were used, and in protocol 2, concentrated virus was used. The results demonstrate that compared to unconcentrated viral supernatants, transduction with the concentrated virus improved the infection rate of bead activated CD4 T cells from ∼40% to ∼70%, and the fluorescent intensity values improved from ∼12,000 to ∼28,000 mean fluorescence intensity units. These results demonstrate the utility of these protocols for CAR immunotherapies.
Comparsion of an immunochromatographic strip with ELISA for simultaneous detection of thiamphenicol, florfenicol and chloramphenicol in food samples (2015)

Rapid and sensitive indirect competitive enzyme-linked immunosorbent assays (ic-ELISA) and gold nanoparticle immunochromatographic strip tests were developed to detect thiamphenicol (TAP), florfenicol (FF) and chloramphenicol (CAP) in milk and honey samples. The generic monoclonal antibody for TAP, FF and CAP was prepared based on a hapten [D-threo-1-(4-aminophenyl)-2- dichloroacetylamino-1,3-propanediol], and the haptenwas linked to a carrier protein using the diazotization method. After the optimization of several parameters (coating, pH, sodium chloride content and methanol content), the ic-ELISA was established. The quantitative working range for TAP was 0.11-1.36 ng/mL, with an IC50 of 0.39 ng/mL. The optimized ELISA showed cross-reactivity to CAP (300%) and FF (15.6%), with IC50 values of 0.13 and 2.5 ng/mL, respectively. The analytical recovery of TAP, FF and CAP in milk and honey samples in the ic-ELISA ranged from 81.2 to 112.9%. Based on this monoclonal antibody, a rapid and sensitive immunochromatographic test strip was also developed. This strip had a detection limit of 1 ng/mL for TAP, FF and CAP in milk and honey samples. Moreover, the test was completed within 10 min. Our results showed that the proposed ic-ELISA and immunochromatographic test strip method are highly useful screening tools for TAP, FF and CAP detection in milk and honey samples.
Demand v need v physician prerogatives in the use of the WBC differential (1983)

The clinical use of the WBC differential was investigated before and after it was made available on demand. The results indicate that no consistent policy existed in our hospital for the ordering of a differential. When differentials were made available on demand, the number of differentials did not increase compared with earlier periods. The demand for differentials may have been caused more by the denial of a physician's prerogative to order a differential rather than by its requirement for patient care. (<i>JAMA</i>1983;249:613-616)
Front Matter and Introduction (2016)

The writers in this issue of Occasional Papers advocate for models of inclusion that support children’s capabilities and challenge systemic inequities based on ableism and cultural biases. They examine the complex and changing nature of collaboration between general and special educators in inclusion settings. Underlying these essays, though not always explicitly stated, is recognition that the fields of special education and disability studies can deepen and inform each other.
Peripheral T‐Cell Lymphoma (2023)

This chapter includes answers to practice-based questions with case studies covering the new principles of diagnosis, staging, treatment, and outcomes in peripheral T-cell lymphoma (PTCL). PTCL are a group of non-Hodgkin lymphomas, with varying geographic patterns of incidence and clinical outcomes. With improved understanding of the disease biology and incorporation of novel agents in the front-line setting, the role of hematopoietic stem cell transplantation in T-cell lymphomas is being redefined. The role of allogeneic stem cell transplantation is controversial in relapsed/refractory PTCL. Angioimmunoblastic T-cell lymphoma is an aggressive subtype of PTCL primarily occurring in older adults. It typically presents as an advanced-stage disease and is often associated with autoimmune findings such as positive rheumatoid factor, skin rash, and autoimmune hemolytic anemias, which can often mask the diagnosis. Cellular therapy may have the potential to improve outcomes in chemotherapy-refractory PTCL and could potentially lead to improved outcomes.
Cyclosporin A combined with vincristine, doxorubicin and dexamethasone (VAD) compared with VAD alone in patients with advanced refractory multiple myeloma: an EORTC–HOVON randomized phase III study (06914) (2001)

Patients with multiple myeloma (MM) refractory to alkylating agents frequently express P-glycoprotein (Pgp), which is associated with the multidrug resistance (MDR) phenotype. We have conducted a randomized phase II/III study of the MDR reversal agent cyclosporin A combined with VAD (vincristine, doxorubicin, dexamethasone) compared with standard VAD in patients with MM stage IIA/IIIA who were refractory to or progressive after treatment with alkylating agents. Out of 81 patients who were randomized, 75 were eligible and evaluable: 34 in the VAD + cyclosporin A arm versus 41 in the VAD arm. Toxicities of grade 2-3 were observed more often with VAD + cyclosporin A than with VAD only: nausea (30% versus 8%, P = 0.015), mucositis (18% versus 5%, P = 0.13), infection (45% versus 35%, P = 0.50). The treatment results were similar in the two arms: 53% versus 49% responded [95% CI (-18.5%, 26.9%)]. The median progression-free survival (PFS) was 8.6 months (VAD + cyclosporin A) versus 5.8 months (VAD): [log rank P = 0.16, hazard ratio = 0.71, 95% CI (0.44, 1.15)], and median overall survival was 13 months versus 14.6 months [log rank P = 0.89, hazard ratio = 0.96, 95% CI (0.62, 1.72)]. The cause of death was progressive disease (85%), toxicity (10%) or other (5%). Bone marrow analysis performed in 23 patients showed that the response rate was 67% in Pgp-positive versus 55% in Pgp-negative patients. Cyclosporin A combined with VAD is relatively well tolerated. There is no effect of cyclosporin A on the overall response rate, PFS and overall survival with VAD.
Sources of funding as an influence on alcohol studies (2016)

Room, R. (2016). Sources of funding as an influence on alcohol studies. The International Journal Of Alcohol And Drug Research, 5(1), 15-16. doi:http://dx.doi.org/10.7895/ijadr.v5i1.231When I first read Thomas Kuhn’s (1962) seminal work, shortly after its first publication, I was awakened to the historical evidence that even the “hardest” science is a human construction deeply influenced by the social order and the conceptual traditions in which the scientist works. On the other hand, as constructivism took hold in sociology, I realized I was a “soft” constructivist, willing to acknowledge that our conceptual and other constructions face some limits from the physical world and its operating rules (Room, 1984). But in fields like ours, the constraints are quite broad, so that what constitutes alcohol social science—what its research questions are, and how it approaches them—has varied a great deal over the last century or so, and varies considerably among the societies which have been willing to fund such research. I remember discovering that temperance-oriented survey studies, when they turned attention at all beyond the boundary between drinker and abstainer, focused only on frequency of drinking, ignoring amount per occasion (Lindgren, 1973)— a pattern found also in drug war–era drug surveys. What we collect as material for study and what we focus on in analyzing it are deeply influenced by our intellectual and cultural-political heritage and environment.
Magnetic properties of ultrathin discontinuous Co/Pt multilayers: Comparison with short-range ordered and isotropic<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>CoPt</mml:mi><mml:mn>3</mml:mn></mml:msub></mml:math>films (2016)

Magnetic properties of thin Co/Pt multilayers have been investigated in order to study the dependence of magnetization $M$, uniaxial anisotropy ${K}_{u}$, and Curie temperature ${T}_{\mathrm{C}}$ on the multilayer thickness, composition, and structure. A comparison between epitaxial submonolayer multilayers and epitaxial fcc ${\mathrm{CoPt}}_{3}$ alloy films with large perpendicular magnetic anisotropy (PMA) attributed to growth-induced Co clustering reveals significant differences in the temperature dependence of magnetization $M(T)$, despite the presence of thin planar Co platelets in both cases. Even the thinnest discontinuous multilayered structure shows a Langevin-like $M(T)$, while the alloy films with PMA show a broadened and enhanced $M(T)$ indicating a distribution of environments, including monolayer Co platelets separated by only 1--2 layers of Pt. These differences have been reproduced in Monte Carlo simulations, and are shown to be due to different distributions of Co-Co and Co-Pt nearest neighbors. The relatively uniform Co-Co coordination of even a discontinuous rough multilayer produces a Langevin-like $M(T)$, whereas the broader distribution associated with platelets in the PMA films results in a nearly linear $T$ dependence of $M$.
Regularized k-means clustering of high-dimensional data and its asymptotic consistency (2012)

K-means clustering is a widely used tool for cluster analysis due to its conceptual simplicity and computational efficiency. However, its performance can be distorted when clustering high-dimensional data where the number of variables becomes relatively large and many of them may contain no information about the clustering structure. This article proposes a high-dimensional cluster analysis method via regularized k-means clustering, which can simultaneously cluster similar observations and eliminate redundant variables. The key idea is to formulate the k-means clustering in a form of regularization, with an adaptive group lasso penalty term on cluster centers. In order to optimally balance the trade-off between the clustering model fitting and sparsity, a selection criterion based on clustering stability is developed. The asymptotic estimation and selection consistency of the regularized k-means clustering with diverging dimension is established. The effectiveness of the regularized k-means clustering is also demonstrated through a variety of numerical experiments as well as applications to two gene microarray examples. The regularized clustering framework can also be extended to the general model-based clustering.
Experimental and Numerical Study of the Evaporation of Water at Low Pressures (2017)

Although evaporation is considered to be a surface phenomenon, the rate of molecular transport across a liquid-vapor boundary is strongly dependent on the coupled fluid dynamics and heat transfer in the bulk fluids. Recent experimental thermocouple measurements of the temperature field near the interface of evaporating water into its vapor have begun to show the role of heat transfer in evaporation. However, the role of fluid dynamics has not been explored sufficiently. Here, we have developed a mathematical model to describe the coupling of the heat, mass, and momentum transfer in the fluids with the transport phenomena at the interface. The model was used to understand the experimentally obtained velocity field in the liquid and temperature profiles in the liquid and vapor, in evaporation from a concave meniscus for various vacuum pressures. By using the model, we have shown that an opposing buoyancy flow suppressed the thermocapillary flow in the liquid during evaporation at low pressures in our experiments. As such, in the absence of thermocapillary convection, the evaporation is controlled by heat transfer to the interface, and the predicted behavior of the system is independent of choosing between the existing theoretical expressions for evaporation flux. Furthermore, we investigated the temperature discontinuity at the interface and confirmed that the discontinuity strongly depends on the heat flux from the vapor side, which depends on the geometrical shape of the interface.
Migraine: an ophthalmologist's perspective (2003)

Our understanding of migraine is rapidly evolving with functional neuroimaging. There are several unanswered questions. In this article, we will review the epidemiology, genetics, and clinical features of various forms of migraine with emphasis on ocular migraine, pathogenesis, and briefly the management of migraine.
Multiples attenuation using trace randomization and empirical mode decomposition (2016)

We propose a new approach for removing multiples based on trace randomization and empirical mode decomposition (EMD). We first flatten the primary reflections in common CMP gather using the picked NMO velocities that correspond to the primaries and then randomly permutate all the traces. Next, we removed the spatially distributed random spikes that correspond to the multiples using the EMD based smoothing approach that is implemented in the f − x domain. The trace randomization approach can make the spatially coherent multiples random along the space direction and can decrease the coherency of near-offset multiples. The EMD based smoothing method is superior to median filter and prediction error filter in that it can help preserve the flattened signals better, without the need of exact flattening, and can preserve the amplitude variation much better. In addition, EMD is a fully adaptive algorithm and the parameterization for EMD based smoothing can be very convenient. Presentation Date: Monday, October 17, 2016 Start Time: 2:15:00 PM Location: 142 Presentation Type: ORAL
Differential growth characteristics and immunogenicity of tight and coasting temperature-sensitive mutants of Pseudomonas aeruginosa (1987)

Genetically attenuated vaccines capable of limited replication in the vaccinate may elicit stronger, longer-lasting immunity than that induced by component, killed whole-cell, or nonreplicating live vaccines. We have isolated and partially characterized temperature-sensitive Pseudomonas aeruginosa mutants of two different phenotypes: a tight mutant, which ceases all growth immediately after its transfer to 36 degrees C, and a coaster, which continues to replicate for five generations at 36 degrees C. The growth profiles of the two temperature-sensitive phenotypes were compared both in vitro and in vivo; maintenance of the coasting phenotype in vivo was confirmed. The immunogenicity of the two phenotypes was compared in two models. In model 1, ICR mice were immunized intraperitoneally (i.p.) with graded doses of either mutant and challenged 3 weeks later i.p. with lethal doses of the wild-type strain. In model 2, DBA/2J mice were immunized intranasally with either mutant and subsequently challenged with an aerosolized inoculum of the wild-type strain, and lung clearance was measured over 4 h. In both models, the coaster demonstrated slightly higher immunogenic potential and, in addition, induced significantly higher levels of immunotype-specific serum immunoglobulin G after i.p. immunization.
Fast Message Authentication Code for Multiple Messages with Provable Security (2010)

In this paper we consider authentication of multiple messages m <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> , m <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> , …., m <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">L</sub> where each message mi consists of s bits. We propose a scheme for the computation of a message authentication code (MAC) tag t, of m <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> , m <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> , …., m <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">L</sub> that takes constant time (time that is independent of L) and has a tag length that is constant or independent of L. The verification time of the proposed scheme is also constant. Current schemes result in tag computation and verification times proportional to L and are hence less efficient than the proposed scheme. The proposed scheme uses a modification of division by an irreducible polynomial over GF(2) in order to compress the L messages. The compressed result is then input to a pseudorandom function F <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k</sub> (.) to obtain a secure tag t. We prove the security of the proposed MAC scheme. The proposed scheme has applications in sensor networks where many messages having one tag can reduce the number of bits being transmitted by a sensor node, thereby reducing the power consumption at a sensor node. Another application is in multimedia authentication, where a large multimedia data file can be split up into smaller segments whose MAC tag can be computed at high speed using the proposed scheme.
Investigation on doping dependency of solution-processed Ga-doped ZnO thin film transistor (2008)

Ga-doped ZnO (GZO) thin film transistors (TFTs) were fabricated based on the solution-processed method and GZO TFTs were investigated according to the variation of the Ga doping concentration [Ga∕Zn (%)]. A field-effect mobility of 1.63cm2∕Vs and a drain current on/off ratio of 4.17×106 were observed in the 5.4 % Ga-doped TFT. This result shows good agreement with its structural properties and electrical properties of the GZO channel layer. It is believed that the optimal and desirable electrical properties of the TFTs can be obtained by adjusting the Ga doping concentration.
Practical sonochemistry (2002)

This updated version of Practical Sonochemistry for advanced students and teachers in chemistry and chemical engineering conveys the increasing growth in applications and equipment to power ultrasound. Equipment now on the market offers a wider range of frequencies with more reproducible experimentation and a variety of scale-up systems. The book provides detailed descriptions of newer ultrasonic equipment and its applications, and practical laboratory uses of ultrasound technology for industrial scale performance. Modern exercises familiarise readers with recent sonochemical operations. The book also includes methods for estimating ultrasonic energy entering the system (dosimetry), which will standardise sonochemical methodology and enable practitioners to reproduce results from other laboratories.
Lipid rafts are essential for release of phosphatidylserine-exposing extracellular vesicles from platelets (2018)

Platelets protect the vascular system during damage or inflammation, but platelet activation can result in pathological thrombosis. Activated platelets release a variety of extracellular vesicles (EVs). EVs shed from the plasma membrane often expose phosphatidylserine (PS). These EVs are pro-thrombotic and increased in number in many cardiovascular and metabolic diseases. The mechanisms by which PS-exposing EVs are shed from activated platelets are not well characterised. Cholesterol-rich lipid rafts provide a platform for coordinating signalling through receptors and Ca<sup>2+</sup> channels in platelets. We show that cholesterol depletion with methyl-β-cyclodextrin or sequestration with filipin prevented the Ca<sup>2+</sup>-triggered release of PS-exposing EVs. Although calpain activity was required for release of PS-exposing, calpain-dependent cleavage of talin was not affected by cholesterol depletion. P2Y<sub>12</sub> and TPα, receptors for ADP and thromboxane A<sub>2</sub>, respectively, have been reported to be in platelet lipid rafts. However, the P2Y<sub>12</sub> antagonist, AR-C69931MX, or the cyclooxygenase inhibitor, aspirin, had no effect on A23187-induced release of PS-exposing EVs. Together, these data show that lipid rafts are required for release of PS-exposing EVs from platelets.
Novel Linkers and Connections for antibody–drug Conjugates to Treat Cancer and Infectious Disease (2017)

Antibody-drug conjugates (ADCs) are an exciting therapeutic, combining the extreme potency of a small molecule cytotoxic drug with the exquisite selectivity of a monoclonal antibody. Despite the promising concept and many decades of research and clinical experiments, only two ADCs are approved for human use. Among the lessons learned, have been the need for highly stable and potentially releasable linkers and the empirical nature of therapeutic index supporting the testing of many diverse cytotoxics, many requiring new linker connections for the drug's available functional groups. This article will focus on our efforts at Genentech to develop a new disulfide linker as well as our discovery of a novel quaternary ammonium salt linker connection and the application to ADCs for cancer and infectious disease.