gebhart/patrepeval huggingface dataset:
Comprehensive Studies on Dual Excitation Behavior of Double Proton versus Charge Transfer in 4-(N-Substituted amino)-1H-pyrrolo[2,3-b]pyridines (2003)

Comprehensive spectroscopic and dynamical studies on the dual excitation behavior of proton vs charge transfer for 4-(dimethylamino)-1H-pyrrolo[2,3-b]pyridine (DPP) and its related derivatives are reported. In cyclohexane, DPP dimer and/or dual hydrogen-bonded complex are formed with association constants Ka as high as ∼4.2 × 103 and 5.2 × 104 M-1 (e.g., the DPP/acetic acid complex) at 298 K, respectively, which upon electronic excitation undergo ultrafast rate (≫6.7 × 1010 s-1) of double-proton transfer, resulting in a unique tautomer emission. Dual fluorescence was observed in polar, aprotic solvents, in which the large Stokes shifted emission band originates from the charge-transfer species incorporating a dimethylamine and pyridine ring as electron donor and acceptor, respectively. Detailed solvent−polarity and temperature-dependent studies in combination with theoretical approaches have been performed to determine the excited-state charge-transfer properties such as dipole moment, orbital configuration, etc. Supplementary support for the dual charge/proton-transfer behavior was provided by the comparative spectroscopy and dynamics of various DPP-related derivatives. Further time-resolved measurements conclude that dual emissions share a common Franck−Condon excited state but undergo two independent relaxation channels. In protic solvents, such as ethanol, following fast solvent relaxation dynamics, the excited charge-transfer state further undergoes a solvent (i.e. alcohol) assisted proton-transfer reaction. The charge versus proton-transfer emission can be distinguished via the temporal spectral evolution. The results demonstrate DPP to be a unique model among 7-azaindole analogues in which the interplay between charge and proton-transfer reactions is operative in the excited state.
CLINICAL USE OF PRODUCTS OF HUMAN PLASMA FRACTIONATION (1944)

In the course of large scale fractionation of human blood plasma in the Department of Physical Chemistry at the Harvard Medical School<sup>1</sup>purified fractions of human fibrinogen and thrombin have become available in large amounts. From these proteins, several materials have been prepared for use in surgery; these materials have a wide variety of physical properties and differ greatly in the surgical uses for which they are adapted. Two products have thus far proved satisfactory in clinical and experimental trials and are now ready for distribution. One is fibrin foam, which is used with a solution of thrombin as an absorbable hemostatic agent. Another is fibrin film, which has been employed as a dural substitute and in the prevention of meningocerebral adhesions. To a less extent the solutions of fibrinogen and thrombin have been used directly in certain special locations, where they provide a physiologic adhesive material by virtue
Alternative splice form of type II procollagen mRNA (IIA) is predominant in skeletal precursors and non‐cartilaginous tissues during early mouse development (1994)

Type II collagen, generally considered to be characteristic of cartilage, has been localized in specific non-cartilaginous structures during embryogenesis and development of the skeleton. Type II procollagen is synthesized in two different forms generated by alternative splicing of exon 2 in the precursor mRNA transcript. One form (type IIA procollagen) contains a large cysteine-rich domain in the NH2-terminal propeptide, while the second form (type IIB procollagen) does not. These two forms are spatially expressed during development and chondrogenesis with the type IIB procollagen mRNA primarily expressed by chondrocytes while the IIA form is expressed in chondroprogenitor cells (Sandell et al. [1991] J. Cell Biol. 114:1307-1319). The present study demonstrates that the early non-cartilage expression, by somites, mesenchymal and epithelial cells, is predominantly the alternate splice form, type IIA procollagen mRNA. Later in development, the type IIB mRNA splice form is expressed by chondrocytes. During the development of intramembranous bones, such as the mandible, type IIA procollagen mRNA is also expressed. In this tissue, the splice form does not switch to type IIB mRNA and no cartilage is formed. These results show that expression of type IIA mRNA, whether by epithelial or mesenchymal cells, precedes formation of overt skeletal structures.
THE ACTION OF THE GRIGNARD REAGENT ON HIGHLY BRANCHED CARBONYL COMPOUNDS1 (1929)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTHE ACTION OF THE GRIGNARD REAGENT ON HIGHLY BRANCHED CARBONYL COMPOUNDS1J. B. Conant and A. H. BlattCite this: J. Am. Chem. Soc. 1929, 51, 4, 1227–1236Publication Date (Print):April 1, 1929Publication History Published online1 May 2002Published inissue 1 April 1929https://pubs.acs.org/doi/10.1021/ja01379a035https://doi.org/10.1021/ja01379a035research-articleACS PublicationsRequest reuse permissionsArticle Views280Altmetric-Citations25LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Target cell lysis by cytotoxic T lymphocytes redirected by antibody-coated polystyrene beads. (1989)

Cytotoxic T lymphocytes were found to mediate rapid lysis of target cells not normally recognized in the presence of small polystyrene beads coated with a combination of anti-T3 and antitarget cell antibodies. Lysis was not seen with beads bearing one of these antibodies alone, nor with a mixture of two types of beads each coated with a single antibody. The effector cells mediating this lysis include long term allospecific human CTL, and both human and mouse CTL clones recognizing mouse class I MHC Kb Ag. TNP-modified mouse tumor cells, a human lymphoblastoid line, and human red cells were found to be good targets for this cytotoxicity. Polystyrene beads with diameters of 3 to 15 mu caused target lysis, with a dose-response curve which typically went through a maximum and declined at high bead numbers. Maximal bead-redirected lysis by CTL was less efficient than that mediated by soluble antibody heteroconjugates of the same two antibodies. Bead-redirected target lysis was calcium dependent. These results are interpreted as a form of bystander lysis induced by the beads, since the target cell membrane is not directly crosslinked to the region of CTL activation. These observations thus favor a mechanism of lysis involving the polarized secretion of a locally acting lytic agent by CTL.
Multidrug-resistance phenotype and clinical responses to gemtuzumab ozogamicin (2001)

Expression of multidrug resistance (MDR) features by acute myeloid leukemia (AML) cells predicts a poor response to many treatments. The MDR phenotype often correlates with expression of P-glycoprotein (Pgp), and Pgp antagonists such as cyclosporine (CSA) have been used as chemosensitizing agents in AML. Gemtuzumab ozogamicin, an immunoconjugate of an anti-CD33 antibody linked to calicheamicin, is effective monotherapy for CD33(+) relapsed AML. However, the contribution of Pgp to gemtuzumab ozogamicin resistance is poorly defined. In this study, blast cell samples from relapsed AML patients eligible for gemtuzumab ozogamicin clinical trials were assayed for Pgp surface expression and Pgp function using a dye efflux assay. In most cases, surface expression of Pgp correlated with Pgp function, as indicated by elevated dye efflux that was inhibited by CSA. Among samples from patients who either failed to clear marrow blasts or failed to achieve remission, 72% or 52%, respectively, exhibited CSA-sensitive dye efflux compared with 29% (P =.003) or 24% (P <.001) among samples from responders. In vitro gemtuzumab ozogamicin--induced apoptosis was also evaluated using an annexin V--based assay. Low levels of drug-induced apoptosis were associated with CSA-sensitive dye efflux, whereas higher levels correlated strongly with achievement of remission and marrow blast clearance. In vitro drug-induced apoptosis could be increased by CSA in 14 (29%) of 49 samples exhibiting low apoptosis in the absence of CSA. Together, these findings indicate that Pgp plays a role in clinical resistance to gemtuzumab ozogamicin and suggest that treatment trials combining gemtuzumab ozogamicin with MDR reversal agents are warranted. (Blood. 2001;98:988-994)
Modified XYZ System of Producing Hybrid Wheat1 (1985)

A modification to the XYZ system of producing hybrid seed of wheat ( Triticum aestivum L.) is proposed in which a selfed Vline replaces a Y‐line to maintain and increase the male‐sterile Z‐Iine. This modification removes the need of the X‐line, which in the original system, was needed to generate a large quantity of Y‐line. In turn, the requirements of the alien chromosome are eased, and an isochromosome can be used to carry the compensating male‐fertility gene, which has distinct advantages. The modified XYZ system has fewer stages than the XYZ system, and these are comparable to those of the cytoplasmic‐male‐sterility system; however, both of the special genetic components are in the female parent of the hybrid. The Cornerstone male‐sterile mutant provides a satisfactory Z‐line, and a 4α isochromosome of Triticum urartu Jakubz. and a 4HmL isochromosome of barley ( Hordeum vulgare L.) are being tested as the second genetic component.
Sirtuins, Aging, and Metabolism (2011)

Sirtuins are nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylases that link protein acetylation, metabolism, aging, and diseases of aging. Sirtuins were initially found to slow aging in lower organisms and more recently shown to mediate many effects of calorie restriction on metabolism and longevity in mammals. This chapter focuses on two key mammalian sirtuins, SIRT1 (which resides mainly in the nucleus) and SIRT3 (which is mitochondrial). I discuss the many protein substrates of these sirtuins and how they determine the metabolic strategy most efficacious under scarce or abundant food supplies. I also discuss the logic by which sirtuins link protein acetylation and metabolism. Finally, I discuss emerging data showing protection by sirtuins against most of the common diseases of aging. It is possible that sirtuins will be novel targets to combat these diseases pharmacologically.
Pyruvate Dehydrogenase, Substrate Specificity and Product Inhibition (1969)

Studies with intact mitochondria and with soluble pyruvate dehydrogenase indicate that pyruvate and α‐ketobutyrate are oxidized by the same enzyme (pyruvate dehydrogenase), while α‐ketovalerate is oxidized by a different enzyme. Pyruvate and α‐ketobutyrate have about the same affinity for the enzyme, but pyruvate is oxidized at a much higher rate. Acetyl‐CoA and propionyl‐CoA both behave as competitive inhibitors to CoA. The K i for both is slightly higher than the K m for CoA. Accordingly the enzyme is only moderately inhibited by a high acetyl‐CoA/CoA ratio. NADH behaves mainly as a competitive inhibitor to NAD. The K i is significantly lower than the K m for NAD. Accordingly the enzyme is strongly inhibited by a high NADH/NAD ratio. The significance of these properties of the enzyme for the regulation of the activity of pyruvate dehydrogenase in vivo is discussed.
Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. (1989)

The relationship between the two estimates of genetic variation at the DNA level, namely the number of segregating sites and the average number of nucleotide differences estimated from pairwise comparison, is investigated. It is found that the correlation between these two estimates is large when the sample size is small, and decreases slowly as the sample size increases. Using the relationship obtained, a statistical method for testing the neutral mutation hypothesis is developed. This method needs only the data of DNA polymorphism, namely the genetic variation within population at the DNA level. A simple method of computer simulation, that was used in order to obtain the distribution of a new statistic developed, is also presented. Applying this statistical method to the five regions of DNA sequences in Drosophila melanogaster, it is found that large insertion/deletion (greater than 100 bp) is deleterious. It is suggested that the natural selection against large insertion/deletion is so weak that a large amount of variation is maintained in a population.
People-centric urban sensing (2006)

The vast majority of advances in sensor network research over the last five years have focused on the development of a series of small-scale (100s of nodes) testbeds and specialized applications (e.g., environmental monitoring, etc.) that are built on low-powered sensor devices that self-organize to form application-specific multihop wireless networks. We believe that sensor networks have reached an important crossroads in their development. The question we address in this paper is how to propel sensor networks from their small-scale application-specific network origins, into the commercial mainstream of people's every day lives; the challenge being: how do we develop large-scale general-purpose sensor networks for the general public (e.g., consumers) capable of supporting a wide variety of applications in urban settings (e.g., enterprises, hospitals, recreational areas, towns, cities, and the metropolis). We propose MetroSense, a new people-centric paradigm for urban sensing at the edge of the Internet, at very large scale. We discuss a number of challenges, interactions and characteristics in urban sensing applications, and then present the MetroSense architecture which is based fundamentally on three design principles: network symbiosis, asymmetric design, and localized interaction. The ability of MetroSense to scale to very large areas is based on the use of an opportunistic sensor networking approach. Opportunistic sensor networking leverages mobility-enabled interactions and provides coordination between people-centric mobile sensors, static sensors and edge wireless access nodes in support of opportunistic sensing, opportunistic tasking, and opportunistic data collection. We discuss architectural challenges including providing sensing coverage with sparse mobile sensors, how to hand off roles and responsibilities between sensors, improving network performance and connectivity using adaptive multihop, and importantly, providing security and privacy for people-centric sensors and data.
CloudNet (2011)

Virtual machine technology and the ease with which VMs can be migrated within the LAN, has changed the scope of resource management from allocating resources on a single server to manipulating pools of resources within a data center. We expect WAN migration of virtual machines to likewise transform the scope of provisioning compute resources from a single data center to multiple data centers spread across the country or around the world. In this paper we present the CloudNet architecure as a cloud framework consisting of cloud computing platforms linked with a VPN based network infrastructure to provide seamless and secure connectivity between enterprise and cloud data center sites. To realize our vision of efficiently pooling geographically distributed data center resources, CloudNet provides optimized support for live WAN migration of virtual machines. Specifically, we present a set of optimizations that minimize the cost of transferring storage and virtual machine memory during migrations over low bandwidth and high latency Internet links. We evaluate our system on an operational cloud platform distributed across the continental US. During simultaneous migrations of four VMs between data centers in Texas and Illinois, CloudNet's optimizations reduce memory migration time by 65% and lower bandwidth consumption for the storage and memory transfer by 19GB, a 50% reduction.
New Paths to Housing and Transportation Affordability (2013)

Reducing parking and focusing on transit-oriented development allows affordable housing developers to direct housing funds efficiently into more housing units instead of excess parking space.
Expression of the multidrug resistance-associated P-glycoprotein (P- 170) in 59 cases of de novo acute lymphoblastic leukemia: prognostic implications [see comments] (1993)

Abstract Immunocytochemical detection of the multidrug resistance (MDR)- associated membrane protein (P-170) was performed at time of diagnosis in a series of 36 children and 23 adults with acute lymphoblastic leukemia (ALL) using two monoclonal antibodies JSB1 and C219. Immunophenotypes were obtained in all cases and karyotypes were analyzed in 37 cases. Detection with JSB1 or with C219 led to similar results in terms of positive cells and cases, but the intensity of staining was higher with JSB1. In the populations studied, the rate of first complete remission differed between MDR-positive and MDR-negative in adult patients only (56% v 93%, respectively, P = .05). Of the 16 MDR-positive patients who had presented a first complete remission, 13 (81%) relapsed, compared with 13 of 35 (37%) MDR-negative (P = .008) patients. A higher rate of relapse among MDR-positive compared with MDR- negative patients was observed in adults and in children taken separately (adults 100% v 46%; children 73% v 32%, respectively). The survival rates (Kaplan-Meier method) were significantly higher in MDR- negative compared with MDR-positive populations as a whole (P = .002) and among children (P = .05) and adults (P = .03) taken separately. Event-free survival curves followed this trend. The percentage of second complete remission was very low in the MDR-positive group (15%) compared with 38% for the MDR-negative group. These results were shown by multivariate analysis to be independent of age, immunophenotypes, and karyotypes and clearly show the importance of MDR phenotype detection in ALL.
Identification of the Single Specific IQ Motif of Myosin V from Which Calmodulin Dissociates in the Presence of Ca2+ (2006)

Each heavy chain of dimeric chick brain myosin V (BMV) has a neck domain consisting of six IQ motifs with different amino acid sequences. The six IQ motifs form binding sites for five calmodulin (CaM) molecules and one essential light chain (either 17 or 23 kDa). When the calcium concentration is high, a small fraction of the 10 total CaM molecules dissociates from one molecule of BMV, resulting in loss of actin-based motor activity. At low Ca2+ concentrations, two molecules of exogenous CaM associate with one molecule of CaM-released BMV. This suggests that there is a single specific IQ motif responsible for the calcium-induced dissociation of CaM. In this study, we identify the specific IQ motif to be IQ2, the second IQ motif when counted from the N-terminal end of the neck domain. In addition, we showed that the essential light chains do not reside on IQ1 and IQ2. These findings were derived from proteolysis of BMV at high Ca2+ concentrations specifically at the neck region and SDS-PAGE analyses of the digests.
X-means: Extending K-means with Efficient Estimation of the Number of Clusters (2000)

Despite its popularity for general clustering, K-means suffers three major shortcomings; it scales poorly computationally, the number of clusters K has to be supplied by the user, and the search is prone to local minima. We propose solutions for the first two problems, and a partial remedy for the third. Building on prior work for algorithmic acceleration that is not based on approximation, we introduce a new algorithm that efficiently, searches the space of cluster locations and number of clusters to optimize the Bayesian Information Criterion (BIC) or the Akaike Information Criterion (AIC) measure. The innovations include two new ways of exploiting cached sufficient statistics and a new very efficient test that in one K-means sweep selects the most promising subset of classes for refinement. This gives rise to a fast, statistically founded algorithm that outputs both the number of classes and their parameters. Experiments show this technique reveals the true number of classes in the underlying distribution, and that it is much faster than repeatedly using accelerated K-means for different values of K.
Pharmacokinetic modelling of morphine, morphine-3-glucuronide and morphine-6-glucuronide in plasma and cerebrospinal fluid of neurosurgical patients after short-term infusion of morphine (2002)

From the population pharmacokinetic model presented, CSF concentration profiles can be derived for M, M3G and M6G on the basis of dosing information and creatinine clearance without collecting CSF samples. Such profiles may then serve as the link between dose regimen and effect measurements in future clinical effect studies.
Personalized treatment strategies in glioblastoma: MGMT promoter methylation status (2013)

The identification of molecular genetic biomarkers considerably increased our current understanding of glioma genesis, prognostic evaluation, and treatment planning. In glioblastoma, the most malignant intrinsic brain tumor entity in adults, the promoter methylation status of the gene encoding for the repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) indicates increased efficacy of current standard of care, which is concomitant and adjuvant chemoradiotherapy with the alkylating agent temozolomide. In the elderly, MGMT promoter methylation status has recently been introduced to be a predictive biomarker that can be used for stratification of treatment regimes. This review gives a short summery of epidemiological, clinical, diagnostic, and treatment aspects of patients who are currently diagnosed with glioblastoma. The most important molecular genetic markers and epigenetic alterations in glioblastoma are summarized. Special focus is given to the physiological function of DNA methylation-in particular, of the MGMT gene promoter, its clinical relevance, technical aspects of status assessment, its correlation with MGMT mRNA and protein expressions, and its place within the management cascade of glioblastoma patients.
Recent developments in analytical and functional protein microarrays. (2003)

In recent years, the genomes of many different organisms have been fully sequenced and annotated. As a consequence of this information, a number of methods have emerged to study the function of many genes and proteins in parallel. One recent approach for the large-scale analysis of proteins is the use of protein microarrays in which hundreds to thousands of proteins are arrayed and assayed simultaneously. Protein arrays can be used for assessing protein levels and following disease markers, identifying biochemical activities, analyzing post-translational modifications, building interaction networks, and for drug discovery and development. In this review, we discuss the construction of different types of protein arrays, and their numerous and diverse applications.