gebhart/patrepeval huggingface dataset:
Diagnostic Applications of Nucleic Acid Circuits (2014)

CONSPECTUS: While the field of DNA computing and molecular programming was engendered in large measure as a curiosity-driven exercise, it has taken on increasing importance for analytical applications. This is in large measure because of the modularity of DNA circuitry, which can serve as a programmable intermediate between inputs and outputs. These qualities may make nucleic acid circuits useful for making decisions relevant to diagnostic applications. This is especially true given that nucleic acid circuits can potentially directly interact with and be triggered by diagnostic nucleic acids and other analytes. Chemists are, by and large, unaware of many of these advances, and this Account provides a means of touching on what might seem to be an arcane field. We begin by explaining nucleic acid amplification reactions that can lead to signal amplification, such as catalytic hairpin assembly (CHA) and the hybridization chain reaction (HCR). In these circuits, a single-stranded input acts on kinetically trapped substrates via exposed toeholds and strand exchange reactions, refolding the substrates and allowing them to interact with one another. As multiple duplexes (CHA) or concatemers of increasing length (HCR) are generated, there are opportunities to couple these outputs to different analytical modalities, including transduction to fluorescent, electrochemical, and colorimetric signals. Because both amplification and transduction are at their root dependent on the programmability of Waston-Crick base pairing, nucleic acid circuits can be much more readily tuned and adapted to new applications than can many other biomolecular amplifiers. As an example, robust methods for real-time monitoring of isothermal amplification reactions have been developed recently. Beyond amplification, nucleic acid circuits can include logic gates and thresholding components that allow them to be used for analysis and decision making. Scalable and complex DNA circuits (seesaw gates) capable of carrying out operations such as taking square roots or implementing neural networks capable of learning have now been constructed. Into the future, we can expect that molecular circuitry will be designed to make decisions on the fly that reconfigure diagnostic devices or lead to new treatment options.
urg1: A Uracil-Regulatable Promoter System for Fission Yeast with Short Induction and Repression Times (2008)

We exploited the urg1 promoter system to rapidly induce pom1 expression at defined cell-cycle stages, showing that ectopic pom1 expression leads to cell branching in G2-phase but much less so in G1-phase. The high temporal resolution provided by the urg1 promoter should facilitate experimental design and improve the genetic toolbox for the fission yeast community.
Targeting Human C‐Type Lectin‐like Molecule‐1 (CLL1) with a Bispecific Antibody for Immunotherapy of Acute Myeloid Leukemia (2014)

Acute myeloid leukemia (AML), which is the most common acute adult leukemia and the second most common pediatric leukemia, still has a poor prognosis. Human C-type lectin-like molecule-1 (CLL1) is a recently identified myeloid lineage restricted cell surface marker, which is overexpressed in over 90% of AML patient myeloid blasts and in leukemic stem cells. Here, we describe the synthesis of a novel bispecific antibody, αCLL1-αCD3, using the genetically encoded unnatural amino acid, p-acetylphenylalanine. The resulting αCLL1-αCD3 recruits cytotoxic T cells to CLL1 positive cells, and demonstrates potent and selective cytotoxicity against several human AML cell lines and primary AML patient derived cells in vitro. Moreover, αCLL1-αCD3 treatment completely eliminates established tumors in an U937 AML cell line xenograft model. These results validate the clinical potential of CLL1 as an AML-specific antigen for the generation of a novel immunotherapeutic for AML.
Human Motor Neuron Differentiation from Human Embryonic Stem Cells (2005)

The therapeutic potential of embryonic stem (ES) cells is promising, but in many cases limited by our inability to promote their differentiation to specific cell types, such as motor neurons. Here we provide the first report of the successful differentiation of human ES cells to cells of a motor neuron phenotype. A renewable source of neuroepithelial cells was generated from human ES cells. Extracellular signals were then employed to induce motor neuron differentiation and related gene expression by these cells. OLIG2 and HLXB9 gene expression increased upon the addition of basic fibroblast growth factor, retinoic acid, and sonic hedgehog, as a motor neuron phenotype expressing Islet1 and choline acetyltransferase (ChAT) developed. This study demonstrates that neuroepithelial cells derived from human ES cells are renewable progenitors capable of generating motor neurons at levels that may be therapeutically useful. Sonic hedgehog, basic fibroblast growth factor, and retinoic acid differentially influence human motor neuron differentiation by mechanisms that remain to be defined.
The Pleiotropic Effects of Erythropoietin in the Central Nervous System (2003)

Erythropoietin (Epo) is a hydrophobic sialoglycoproteic hormone produced by the kidney and responsible for the proliferation, maturation, and differentiation of the precursors of the erythroid cell line. Human recombinant erythropoietin (rHuEpo) is used to treat different types of anemia, not only in uremic patients but also in newborns with anemia of prematurity, in patients with cancer-related anemia or myeloproliferative disease, thalassemias, bone marrow transplants, or those with chronic infectious diseases. The pleiotropic functions of Epo are well known. It has been shown that this hormone can modulate the inflammatory and immune response, has direct hemodynamic and vasoactive effects, could be considered a proangiogenic factor because of its interaction with vascular endothelial growth factor, and its ability to stimulate mitosis and motility of endothelial cells. The multifunctional role of Epo has further been confirmed by the discovery in the central nervous system of a specific Epo/Epo receptor (EpoR) system. Both Epo and EpoR are expressed by astrocytes and neurons and Epo is present in the cerebrospinal fluid (CSF). Therefore, novel functions of Epo, tissue-specific regulation, and the mechanisms of action have been investigated. In this review we have tried to summarize the current data on the role of Epo on brain function. We discuss the different sites of cerebral expression and mechanisms of regulation of Epo and its receptor and its role in the development and maturation of the brain. Second, we discuss the neurotrophic and neuroprotective function of Epo in different conditions of neuronal damage, such as hypoxia, cerebral ischemia, and subarachnoid hemorrhage, and the consequent possibility that rHuEpo therapy could soon be used in clinical practice to limit neuronal damage induced by these diseases.
Condensed Monte Carlo simulations for the description of light transport (1993)

A novel method, condensed Monte Carlo simulation, is presented that applies the results of a single Monte Carlo simulation for a given albedo micro(s)/(micro(alpha) & micro(s)) to obtaining results for other albedos; micro(s) and micro(alpha), are the scattering and absorption coefficients, respectively. The method requires only the storage of the number of interactions of each photon with the medium. The reflectance and transmittance of turbid slabs can thus be found from a limited number of condensed Monte Carlo simulations. We can use an inversion procedure to obtain the absorption and scattering coefficients from the total reflectance and total transmittance of slabs. Remitted photon densities from a semi-infinite medium as a function of the distance between the light source and the detector for all albedos can be found even from the results of a single condensed Monte Carlo simulation. The application of similarity rules may reduce further the number of Monte Carlo simulations that are needed to describe the influence of the distribution of scattering angles on the results.
Analysis of T-cell repertoire in hepatitis-associated aplastic anemia (2004)

Hepatitis-associated aplastic anemia (HAA) is a syndrome of bone marrow failure following an acute attack of seronegative hepatitis. Clinical features and liver histology suggest a central role for an immune-mediated mechanism. To characterize the immune response, we investigated the T-cell repertoire (T-cell receptor [TCR] V(beta) chain subfamily) of intrahepatic lymphocytes in HAA patients by TCR spectratyping. In 6 of 7 HAA liver samples, a broad skewing pattern in the 21 V(beta) subfamilies tested was observed. In total, 62% +/- 18% of HAA spectratypes showed a skewed pattern, similar to 68% +/- 18% skewed spectratype patterns in 3 of 4 patients with confirmed viral hepatitis. Additionally, the T-cell repertoire had similarly low levels of complexity. In the peripheral blood lymphocytes (PBLs) of a separate group of HAA patients prior to treatment, 60% +/- 15% skewed spectratypes were detected, compared with only 18% +/- 8% skewed spectratypes in healthy controls. After successful immunosuppressive treatment, an apparent reversion to a normal T-cell repertoire with a corresponding significant increase in T-cell repertoire complexity was observed in the HAA samples. In conclusion, our data suggest an antigen-driven T-cell expansion in HAA and achievement of a normal T-cell repertoire during recovery from HAA.
Sequence Pattern Query Processing over Out-of-Order Event Streams (2009)

Complex event processing has become increasingly important in modern applications, ranging from RFID tracking for supply chain management to real-time intrusion detection. A key aspect of complex event processing is to extract patterns from event streams to make informed decisions in real-time. However, network latencies and machine failures may cause events to arrive out-of-order at the event processing engine. State-of-the-art event stream processing technology experiences significant challenges when faced with out-of-order data arrival including output blocking, huge system latencies, memory resource overflow, and incorrect result generation. To address these problems, we propose two alternate solutions: aggressive and conservative strategies respectively to process sequence pattern queries on out-of-order event streams. The aggressive strategy produces maximal output under the optimistic assumption that out-of-order event arrival is rare. In contrast, to tackle the unexpected occurrence of an out-of-order event and with it any premature erroneous result generation, appropriate error compensation methods are designed for the aggressive strategy. The conservative method works under the assumption that out-of-order data may be common, and thus produces output only when its correctness can be guaranteed. A partial order guarantee (POG) model is proposed under which such correctness can be guaranteed. For robustness under spiky workloads, both strategies are supplemented with persistent storage support and customized access policies. Our experimental study evaluates the robustness of each method, and compares their respective scope of applicability with state-of-art methods.
Characterization of the Nonstructural Proteins of the Bocavirus Minute Virus of Canines (2012)

We present a detailed characterization of a single-cycle infection of the bocavirus minute virus of canines (MVC) in canine WRD cells. This has allowed identification of an additional smaller NS protein that derives from an mRNA spliced within the NS gene that had not been previously reported. In addition, we have identified a role for the viral NP1 protein during infection. NP1 is required for read-through of the MVC internal polyadenylation site and, thus, access of the capsid gene by MVC mRNAs. Although the mechanism of NP1's action has not yet been fully elucidated, it represents the first parvovirus protein to be implicated directly in viral RNA processing.
Immunosensitization of Tumor Cells to Dendritic Cell-Activated Immune Responses with the Proteasome Inhibitor Bortezomib (PS-341, Velcade) (2006)

Proteasome inhibition results in proapoptotic changes in cancer cells, which may make them more sensitive to immune effector cells. We established a murine model to test whether the proteasome inhibitor bortezomib could sensitize established B16 melanoma tumors to dendritic cell (DC)-activated immune effector cells. Day 3-established s.c. B16 tumors had significantly decreased tumor outgrowth when treated with a combination of bortezomib and DC, regardless of whether the DC were loaded or not with a tumor Ag. In vivo Ab-depletion studies demonstrated that the effector cells were NK and CD8+ cells, but not CD4+ cells. NF-kappaB nuclear transcription factor assay and gene-expression profiling of B16 treated with bortezomib was consistent with inhibition of NF-kappaB target genes leading to a proapoptotic phenotype. In vitro lytic assays demonstrated that TNF-alpha, but not perforin, Fas-ligand, or TRAIL, was responsible for bortezomib-sensitized B16 cytotoxicity. In conclusion, the proteasome inhibitor bortezomib can pharmacologically sensitize tumor cells to the lytic effects of DC-activated immune effector cells.
The interleukin-1 receptor binds the human interleukin-1 alpha precursor but not the interleukin-1 beta precursor. (1987)

Both IL-1 alpha and IL-1 beta are initially translated as approximately Mr 30,000 polypeptides and processed to approximately Mr 17,500 prior to, or during, release from macrophages. The current study utilizes an in vitro transcription-translation system to produce these four forms of IL-1 directly from cloned cDNAs, in order to investigate the relative receptor binding and biological activities of the proteins. The data show that the initial translation product from IL-1 beta mRNA must be processed in order to bind to the IL-1 receptor and hence express biological activity. By contrast, the initial translation product of IL-1 alpha mRNA can bind to the IL-1 receptor without further proteolytic processing. These data suggest that the IL-1 biological activity previously associated with proteins having Mr values in the range 30,000-40,000 is due to IL-1 alpha gene products.
Adolf von Baeyer and the naming of barbituric acid (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdolf von Baeyer and the naming of barbituric acidGeorge B. Kauffman Cite this: J. Chem. Educ. 1980, 57, 3, 222Publication Date (Print):March 1, 1980Publication History Received3 August 2009Published online1 March 1980Published inissue 1 March 1980https://doi.org/10.1021/ed057p222RIGHTS & PERMISSIONSArticle Views255Altmetric-Citations5LEARN 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 InReddit PDF (1 MB) Get e-Alerts Get e-Alerts
Glucose Biosensors: An Overview of Use in Clinical Practice (2010)

Blood glucose monitoring has been established as a valuable tool in the management of diabetes. Since maintaining normal blood glucose levels is recommended, a series of suitable glucose biosensors have been developed. During the last 50 years, glucose biosensor technology including point-of-care devices, continuous glucose monitoring systems and noninvasive glucose monitoring systems has been significantly improved. However, there continues to be several challenges related to the achievement of accurate and reliable glucose monitoring. Further technical improvements in glucose biosensors, standardization of the analytical goals for their performance, and continuously assessing and training lay users are required. This article reviews the brief history, basic principles, analytical performance, and the present status of glucose biosensors in the clinical practice.
Latent class models for collaborative filtering (1999)

This paper presents a statistical approachto collaborative filtering and investigates the use of latent class models for predicting individual choices and preferences based on observed preference behavior. Two models are discussed and compared: the aspect model, a probabilistic latent space model which models individual preferences as a convex combination of preference factors, and the two-sided clustering model, which simultaneously partitions persons and objects into clusters. We present EM algorithms for different variants of the aspect model and derive an approximate EM algorithm based on a variational principle for the two-sided clustering model. The benefits of the different models are experimentally investigated on a large movie data set.
Development of a sen sor-embedded flexible texti le structure for apparel or large area applications (2005)

during demodulation due to the interlacement of the fiber in the fabric structure. These optical sensors, such as Extrinsic Fabry-Perot Interf erometer (EFPI), Fiber Bragg Grating (FBG) and Long Period Grating (LPG), are capable of measuring strain and temperature of the devices to which they are attached. LPG sensor can be conf igured as a chemical sensor. Reflected spectrum from the sensor has been produced by injecting light into the fiber to check the functionality of the sensor. Both EFPI and FBG sensors, successfully embedded into the fabric without any damage, have been found to be functional when demodulated. A brief description of the optical frequency domain reflectometry (OFDR) demodulation method has also been provided.
Effect of a Nuclease-Resistant Derivative of PolyriboinosinicPolyribocytidylic Acid Complex on Yellow Fever in Rhesus Monkeys (Macaca mulatta) (1977)

Rhesus monkeys (Macaca mulatta) treated with a newly developed nuclease-resistant complex of polyriboinosinic-polyribocytidylic acid, poly-L-lysine, and carboxymethylcellulose [poly (ICLC)] did not die after challenge with virulent Asibi strain yellow fever (YF) virus. The strain of virus is sensitive to the effects of interferon in vitro and is lethal for rhesus monkeys four to six days after subcutaneous administration of 1,000 plaque-forming units of the virus. The mortality rate was reduced in monkeys initially treated 8 hr before or after inoculation of virus but was unchanged in monkeys initially treated 24 hr after challenge. Treated monkeys developed neutralizing antibody to YF virus. The successful treatment of yellow fever in a primate model with use of poly (ICLC) suggests a meaningful role for the interferon system in the host defense against this viral infection.
The visual hull concept for silhouette-based image understanding (1994)

Many algorithms for both identifying and reconstructing a 3-D object are based on the 2-D silhouettes of the object. In general, identifying a nonconvex object using a silhouette-based approach implies neglecting some features of its surface as identification clues. The same features cannot be reconstructed by volume intersection techniques using multiple silhouettes of the object. This paper addresses the problem of finding which parts of a nonconvex object are relevant for silhouette-based image understanding. For this purpose, the geometric concept of visual hull of a 3-D object is introduced. This is the closest approximation of object S that can be obtained with the volume intersection approach; it is the maximal object silhouette-equivalent to S, i.e., which can be substituted for S without affecting any silhouette. Only the parts of the surface of S that also lie on the surface of the visual hull can be reconstructed or identified using silhouette-based algorithms. The visual hull depends not only on the object but also on the region allowed to the viewpoint. Two main viewing regions result in the external and internal visual hull. In the former case the viewing region is related to the convex hull of S, in the latter it is bounded by S. The internal visual hull also admits an interpretation not related to silhouettes. Algorithms for computing visual hulls are presented and their complexity analyzed. In general, the visual hull of a 3-D planar face object turns out to be bounded by planar and curved patches.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Catalytic Deoxygenation of Fatty Acids and Their Derivatives (2006)

Catalytic deoxygenation including decarboxylation/decarbonylation of fatty acids and their esters has been investigated over Pd supported on active carbons in a semibatch reactor. The main studied parameters were catalyst acidity, type of feed, effect of solvent, and gas atmosphere. High yields of the desired product, n-heptadecane, were achieved in the decarboxylation of stearic acid at 300 °C under helium. The results demonstrate that the catalytic transformation of fatty acids proceeded mainly via decarboxylation, whereas decarbonylation was the main route for esters, according to gas-phase analysis. The gas atmosphere and the acidity of the catalyst were important factors for determining product selectivity. Over alkaline catalysts as well as under a hydrogen atmosphere, higher yields of n-heptadecane were obtained. The decarboxylation of unsaturated fatty acids leads to hydrogenated products, which reacted further to hydrocarbons.
A natural single-guide RNA repurposes Cas9 to autoregulate CRISPR-Cas expression (2020)

SUMMARY CRISPR-Cas systems provide their prokaryotic hosts with acquired immunity against viruses and other foreign genetic elements, but how these systems are regulated to prevent auto-immunity is poorly understood. In type II CRISPR-Cas systems, a transactivating CRISPR RNA (tracrRNA) scaffold functions together with a CRISPR RNA (crRNA) guide to program Cas9 for the recognition and cleavage of foreign DNA targets. Here, we show that a long-form tracrRNA performs an unexpected second function by folding into a natural single guide that directs Cas9 to transcriptionally repress its own promoter. Further, we demonstrate that P cas9 serves as a critical regulatory node; de-repression causes a dramatic induction of Cas genes, crRNAs and tracrRNAs resulting in a 3,000-fold increase in immunization rates against unrecognized viruses. Heightened immunity comes at the cost of increased auto-immune toxicity, demonstrating the critical importance of the controller. Using a bioinformatic analysis, we provide evidence that tracrRNA-mediated autoregulation is widespread in type II CRISPR-Cas systems. Collectively, we unveil a new paradigm for the intrinsic regulation of CRISPR-Cas systems by natural single guides, which may facilitate the frequent horizontal transfer of these systems into new hosts that have not yet evolved their own regulatory strategies.
Bridging Antiplatelet Therapy With Cangrelor in Patients Undergoing Cardiac Surgery (2012)

clinicaltrials.gov Identifier: NCT00767507.
Biphasic amplification of very dilute DNA samples via ‘booster‘ PCR (1989)

PCR amplification of fewer than 1000 copies of template is hampered by synthesis of so-called primer dimers and other spurious products. These artifacts consume the stock of primers and occupy enzyme, with consequent reduction in yield of target. To overcome this problem, we have devised Booster PCR, a biphasic amplification strategy. During Stage I, primers are diluted to obtain an initial 107-fold molar excess of primer to template. At the beginning