gebhart/patrepeval huggingface dataset:
Targeting chemokine receptors in allergic disease (2011)

The directed migration of cells in response to chemical cues is known as chemoattraction, and plays a key role in the temporal and spatial positioning of cells in lower- and higher-order life forms. Key molecules in this process are the chemotactic cytokines, or chemokines, which, in humans, constitute a family of approx. 40 molecules. Chemokines exert their effects by binding to specific GPCRs (G-protein-coupled receptors) which are present on a wide variety of mature cells and their progenitors, notably leucocytes. The inappropriate or excessive generation of chemokines is a key component of the inflammatory response observed in several clinically important diseases, notably allergic diseases such as asthma. Consequently, much time and effort has been directed towards understanding which chemokine receptors and ligands are important in the allergic response with a view to therapeutic intervention. Such strategies can take several forms, although, as the superfamily of GPCRs has historically proved amenable to blockade by small molecules, the development of specific antagonists has been has been a major focus of several groups. In the present review, I detail the roles of chemokines and their receptors in allergic disease and also highlight current progress in the development of relevant chemokine receptor antagonists.
Immune-Mediated Adverse Events Associated with Ipilimumab CTLA-4 Blockade Therapy: The Underlying Mechanisms and Clinical Management (2013)

Immunomodulation with the anti-CTLA-4 monoclonal antibody ipilimumab has been shown to extend overall survival (OS) in previously treated and treatment-naive patients with unresectable stage III or IV melanoma. Blockade of CTLA-4 signaling with ipilimumab prolongs T-cell activation and restores T-cell proliferation, thus amplifying T-cell-mediated immunity and the patient's capacity to mount an effective antitumor immune response. While this immunostimulation has unprecedented OS benefits in the melanoma setting, it can also result in immune-mediated effects on various organ systems, leading to immune-related adverse events (irAEs). Ipilimumab-associated irAEs are common and typically low grade and manageable, but can also be serious and life threatening. The skin and gastrointestinal tract are most frequently affected, while hepatic, endocrine, and neurologic events are less common. With proper management, most irAEs resolve within a relatively short time, with a predictable resolution pattern. Prompt and appropriate management of these irAEs is essential and treatment guidelines have been developed to assist oncologists and their teams. Implementation of these irAE management algorithms will help ensure that patients are able to benefit from ipilimumab therapy with adequate control of toxicities.
A new paradigm for operative dentistry (2007)

It is over 100 years since GV Black gathered together most of the knowledge then current on the caries process and set clear parameters for the discipline of operative dentistry. His four-volume treatise set standards that were relevant for the times and, in fact, were so well described that they remained dominant in this discipline until quite recently. However, over the last 50 years there has been great progress in scientific method and in knowledge of the common diseases of the oral environment, including the caries process, so maybe it is time for change. The term "paradigm" describes a philosophy of science, a generally accepted model of how ideas relate to one another, forming a conceptual framework within which scientific research is carried out. Black defined the paradigm within which further research was to be conducted during the following years and the profession accepted his lead. However, it is not expected that the parameters of a profession should remain unchanged over a substantial period so it is suggested that the dental profession should, at this time, recognize a new paradigm. Improvements in scientific method have led to a better understanding of the oral environment, resulting in extensive changes for this profession. It is suggested that the standards set by Black should be now consigned to history and an entirely new paradigm adopted. First, the profession must recognize that dental caries is a bacterial disease and its primary efforts should be directed towards identification and elimination of the disease prior to initiating repair of the damage that it has caused. Preservation of natural tooth structure is then the next responsibility. There should be maximum use made of preventive strategies, including remineralization, followed by minimal intervention cavity designs and the use of bioactive restorative materials to restore the lesions. The profession should be prepared to move on.
Closed-form methods for on-off control of multi-mode flexible structures (2002)

A method is presented for generating on-off command profiles for multi-mode flexible systems. The shape of the command profiles are described by closed-form functions of the system frequencies, actuator force-to-mass ratio, and the desired move distance. The profiles are generated by first cancelling the flexible-body vibration and then accounting for rigid-body requirements. Performance measures of the commands, such as slew duration, fuel usage, peak transient deflection, and robustness to modeling errors are presented and compared to time-optimal commands. The proposed method is demonstrated using a simulation of the Space Shuttle with the Hubble space telescope attached to the remote manipulator.
Estimating the Principal of an Application's Technical Debt (2012)

This article characterizes technical debt across 700 business applications, comprising 357 MLOC. These applications were analyzed against more than 1,200 rules of good architectural and coding practice. The authors present a formula with adjustable parameters for estimating the principal of technical debt from structural quality data.
Synthesis of metal complexes of 2,9-bis(2-hydroxyphenyl)-1,10-phenanthroline and their DNA binding and cleaving activities (1998)

A series of metal complexes that combine the structure of phenanthroline and salen have been synthesized and characterized by electron paramagnetic resonance spectroscopy. The effects of the 2,9-bis(2-hydroxyphenyl)-1,10-phenanthroline compounds complexed with CuII, NiII, CoII or MnIII on the temperature-dependent helix-to-coil transition of DNA have been measured. The interaction with DNA is metal-dependent and the highest stabilization is observed with the Co complex. The DNA cleaving activities have been studied with plasmid DNA and/or with a 32P-labelled duplex oligonucleotide depending on the redox properties of the complexes. The Cu complex is inactive whereas the Co chelate efficiently cleaves DNA in the presence of a reducing agent. Cleavage of DNA by the Mn complex can occur either in the presence of a reducing agent via the production of oxygen radicals (which are detected by EPR spectroscopy) or in the presence of an oxidant such as KHSO5. In both cases, the cleavage of nucleic acids is very efficient whereas no cleavage is observed with the Ni complex. The complexes of bis(hydroxyphenyl)phenanthroline with Mn and Co complement the tool-box of reagents available for cleavage of DNA.
Developments in world aquaculture, feed formulations and role of carotenoids (1994)

Abstract
Investigation of Potentially Deleterious Alleles for Response to Cancer Treatment with 5-Fluorouracil. (2015)

Potentially deleterious alleles are present under diverse frequencies in different populations. Therefore, genotyping prior to 5-fluorouracil administration should be recommended.
Membrane Oligomerization and Cleavage Activates the Caspase-8 (FLICE/MACHα1) Death Signal (1998)

Many forms of apoptosis, including that caused by the death receptor CD95/Fas/APO-1, depend on the activation of caspases, which are proteases that cleave specific intracellular proteins to cause orderly cellular disintegration. The requirements for activating these crucial enzymatic mediators of death are not well understood. Using molecular chimeras with either CD8 or Tac, we find that oligomerization at the cell membrane powerfully induces caspase-8 autoactivation and apoptosis. Death induction was abrogated by the z-VAD-fmk, z-IETD-fmk, or p35 enzyme inhibitors or by a mutation in the active site cysteine but was surprisingly unaffected by death inhibitor Bcl-2. Amino acid substitutions that prevent the proteolytic separation of the caspase from its membrane-associated domain completely blocked apoptosis. Thus, oligomerization at the membrane is sufficient for caspase-8 autoactivation, but apoptosis could involve a death signal conveyed by the proteolytic release of the enzyme into the cytoplasm.
Demonstration of the Existence of the Alternatively Spliced Form of Thyroid Peroxidase in Normal Thyroid* (1991)

We have investigated whether the alternatively spliced form of thyroid peroxidase (TPO), which has been shown clearly to occur in Graves' thyroid, is present in normal thyroid. We have performed a polymerase chain reaction on cDNAs prepared from normal thyroid mRNAs using primers 100 bases up-stream and down-stream from the 171 nucleotides that have been shown to be spliced out. Size analysis of the polymerase chain reaction products by agarose gel electrophoresis revealed bands at 0.2 and 0.37 kilobases (kb), sizes predicted to be obtained when the two forms of TPO cDNA are present. This was confirmed by hybridization with a 32P-labeled probe corresponding to the 20 nucleotides of the junction site. After stringent washing, the 0.2-kb band gave a clear positive signal, which was stronger than that of the 0.37-kb band despite the latter cDNA being more abundant. This demonstrates clearly that the alternatively spliced form of TPO exists in normal thyroid. Its significance is discussed.
Synthesis, in Vitro Anti-Breast Cancer Activity, and Intracellular Decomposition of Amino Acid Methyl Ester and Alkyl Amide Phosphoramidate Monoesters of 3‘-Azido-3‘-deoxythymidine (AZT) (2000)

We report the synthesis and anticancer activity of a series of AZT phosphoramidate monoesters containing amino acid methyl ester (3a-11a) and N-alkyl amide (3b-11b, 9c-9f) moieties. The aromatic amino acid methyl esters were found to be more cytotoxic than the aliphatic analogues toward MCF-7 cells (human pleural effusion breast adenocarcinoma cell line). A marked stereochemical preference for the L-amino acid stereochemistry was also observed in MCF-7 cells. There was no consistent enhancement of cytotoxicity of the methyl amides over the corresponding methyl esters. AZT and the two AZT aromatic amino acid methyl ester phosphoramidates 8a and 9a were found to be more cytotoxic toward MCF-7 cells than to CEM cells (human T-cell lymphoblastic leukemia). The selective cytotoxicity toward MCF-7 cells may be associated with greater intracellular levels of phosphoramidate monoester and/or phosphorylated AZT.
The she-wolf mirror: an interpretation (1993)

LO SPECCHIO DELLA LUPA: UNA INTERPRETAZIONE Lo specchio prenestino del IV secolo a.C. che raffigura la lupa con i gemelli, la cui autenticità è stata sostenuta da Adam e Briquel nel 1982, è stato generalmente interpretato come una rappresentazione della storia di Romolo e Remo. Di fatto considerazioni sulla presenza di altre figure nel disegno portano ad un'ipotesi diversa: vale a dire che i gemelli siano i Lares Praestites, ed i testimoni della scena siano Mercurio (Hermes) e Lara (Dea Tacita), genitori dei bambini; Pan Lykaios e Quirinus, che rappresentano i Lupercalia e i Quirinalia; ed una bestia selvatica ( fera ) che rappresenta i Feralia.
X-ray Mapping in the Spectrum Image Mode at Output Count Rates above 100 kHz with the Silicon Drift Detector (SDD) (2006)

Extended abstract of a paper presented at Microscopy and Microanalysis 2006 in Chicago, Illinois, USA, July 30 – August 3, 2006
Down-regulation of Survivin by Antisense Oligonucleotides Increases Apoptosis, Inhibits Cytokinesis and Anchorage-Independent Growth (2000)

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is detected in most common human cancers but not in adjacent normal cells. Previous studies suggest that survivin associates with the mitotic spindle and directly inhibits caspase activity. To further investigate the function of survivin, we used a survivin antisense (AS) oligonucleotide to downregulate survivin expression in normal and cancer cells. We found that inhibition of survivin expression increased apoptosis and polyploidy while decreasing colony formation in soft agar. Immunohistochemistry showed that cells without survivin can initiate the cleavage furrow and contractile ring, but cannot complete cytokinesis, thus resulting in multinucleated cells. These findings indicate that survivin plays important roles in a late stage of cytokinesis, as well as in apoptosis.
Deletion of the DQ52 Element Within the Ig Heavy Chain Locus Leads to a Selective Reduction in VDJ Recombination and Altered D Gene Usage (2001)

The process of V(D)J recombination that leads to the assembly of Ig gene segments is tightly controlled during B cell differentiation. Two germline transcripts, one of which (mu(0)) originates from the promoter region of DQ52, may control the accessibility of the heavy chain locus. Here, we present the analysis of a mouse line in which the DQ52 gene together with its regulatory sequences is deleted by a Cre/loxP-based strategy. In F(1) (DQ52(+/-)) mice, the use of the JH3 and JH4 elements in DJ or VDJ junctions of the DQ52(-) allele was strongly reduced in both the bone marrow pre-B and spleen cells, while the JH1 and JH2 elements were used with normal frequencies. In addition, IgM(+) B cells of bone marrow and spleen used the DQ52(-) allele less frequently. On DJ joints of the DQ52(-) allele, there was 2 times less processing of JH3 ends, which resulted in clearly increased addition of P nucleotides. Although the use of D elements in DJ joints was quite similar, an altered D repertoire was found in VDJ joints of the DQ52(-) allele. In splenic B cells of the DQ52(-/-) mouse the amino acid distribution of the CDR3 was skewed, probably to compensate for the altered processing of JH3 ends. Thus, we have shown an interesting selective effect of the DQ52 region on controlling accessibility to 3' JH elements on the Ig locus, which also seems to influence the processing of DJ joints. We propose a model in which the DQ52 promoter region enhances the induction of secondary DJ rearrangements.
Chronic inflammation and asthma (2009)

Allergic asthma is a complex and chronic inflammatory disorder which is associated with airway hyper-responsiveness and tissue remodelling of the airway structure. Although originally thought to be a Th2-driven inflammatory response to inhaled innocuous allergen, the immune response in asthma is now considered highly heterogeneous. There are now various in vivo systems which have been designed to examine the pathways leading to the development of this chronic immune response and reflect, in part this heterogeneity. Furthermore, the emergence of endogenous immunoregulatory pathways and active pro-resolving mediators hold great potential for future therapeutic intervention. In this review, the key cellular and molecular mediators relating to chronic allergic airway disease are discussed, as well as emerging players in the regulation of chronic allergic inflammation.
A Method for Isolating Condensed Tannins from Crude Plant Extracts with Trivalent Ytterbium (1997)

A method to precipitate condensed tannin from crude plant extracts using trivalent ytterbium has been developed. The new method requires less time and resources than the condensed isolation procedure using Sephadex LH-20 recommended by Hagerman (1991, Tannin Analysis, Miami University, Oxford, OH, USA). The absorbance of the preparations obtained by precipitation with trivalent ytterbium was similar to the preparations obtained with the original isolation procedure, when the acid butanol method (Porter et al 1986, Phytochemistry 1 223–230) was used to measure condensed tannins. Condensed tannins were isolated from crude plant extracts of three plant species, Desmodium ovalifolium, Gliricidia sepium and Manihot esculenta, and the condensed tannin content of the lyophilised leaf tissue was determined. For each plant species, the amounts of the soluble, insoluble and fibre-bound condensed tannins were estimated using five different standards. These standards included two tannin preparations obtained either by (1) isolation with Sephadex LH-20, or (2) by the precipitation with trivalent ytterbium and three external standards: (3) cyanidin, (4) delphinidin and (5) purified quebracho (Schinopsis balansae). When external standards were used (cyanidin, delphinidin, purified quebracho), it was likely that the condensed tannin content of the plant tissue would be under- or overestimated. When an internal standard based on the isolated tannin from the respective plant species was used, accurate estimates were obtained. © 1997 SCI
Selected values of electric dipole moments for molecules in the gas phase (1967)

This table revises, brings up to date, and extends the coverage on numerical values for dipole moments which was included in NBS Circular 537, Tables of Dielectric Constants and Electric Dipole Moments of Substances in the Gaseous State, prepared by Maryott and Buckley in 1953. A recommended value with an estimate of accuracy is presented for more than five hundred organic and inorganic compounds. Extensive comments are given on the definition of dipole moment and principal methods of dipole moment measurement, as well as an exposition of the criteria employed in selecting the tabulated data.
The Isolation and Identification of the B Protein of Lactose Synthetase as α-Lactalbumin (1967)

The B protein, a subunit of lactose synthetase (EC 2.4.1.c), was crystallized from bovine skim milk and bovine mammary tissue.The B protein was identified as cu-lactalbumin, based on the following criteria: substitution in the enxymic rate assays, spectra, immunological titrations, amino acid composition, mobility on starch gel electrophoresis, molecular weight, and cochromatography on diethylaminoethyl cellulose and Sephadex G-100.Thus the biological function of cr-ladalbumin is as a natural occurring subunit of lactose synthetase.
Resource control for java database extensions (1999)

While object-relational database servers can be extended with user-defined functions (UDFs), the security of the server may be compromised by these extensions. The use of Java to implement the UDFs is promising because it addresses some security concerns. However, it still permits interference between different users through the uncontrolled consumption of resources. In this paper, we explore the use of a Java resource management mechanism (JRes) to monitor resource consumption and enforce usage constraints. JRes enhances the security of the database server in the presence of extensions allowing for (i) detection and neutralization of denial-of-service attacks aimed at resource monopolization, (ii) monitoring resource consumption which enables precise billing of users relying on UDFs, and (iii) obtaining feedback that can be used for adaptive query optimization.

The feedback can be utilized either by the UDFs themselves or by the database system to dynamically modify the query execution plan. Both models have been prototyped in the Cornell Predator database system. We describe the implementation techniques, and present experiments that demonstrate the effects of the adaptive behavior facilitated by JRes. We conclude that, minimally, a database system supporting extensions should have a built-in resource monitoring and controlling mechanism. Moreover, in order to fully exploit information provided by the resource control mechanisms, both the query optimizer and the UDFs themselves should have access to this information.
The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines (2021)

The current COVID-19 pandemic is a massive source of global disruption, having led so far to two hundred and fifty million COVID-19 cases and almost five million deaths worldwide. It was recognized in the beginning that only an effective vaccine could lead to a way out of the pandemic, and therefore the race for the COVID-19 vaccine started immediately, boosted by the availability of the viral sequence data. Two novel vaccine platforms, based on mRNA technology, were developed in 2020 by Pfizer-BioNTech and Moderna Therapeutics (comirnaty® and spikevax®, respectively), and were the first ones presenting efficacies higher than 90%. Both consisted of N1-methyl-pseudouridine-modified mRNA encoding the SARS-COVID-19 Spike protein and were delivered with a lipid nanoparticle (LNP) formulation. Because the delivery problem of ribonucleic acids had been known for decades, the success of LNPs was quickly hailed by many as the unsung hero of COVID-19 mRNA vaccines. However, the clinical trial efficacy results of the Curevac mRNA vaccine (CVnCoV) suggested that the delivery system was not the only key to the success. CVnCoV consisted of an unmodified mRNA (encoding the same spike protein as Moderna and Pfizer-BioNTech's mRNA vaccines) and was formulated with the same LNP as Pfizer-BioNTech's vaccine (Acuitas ALC-0315). However, its efficacy was only 48%. This striking difference in efficacy could be attributed to the presence of a critical RNA modification (N1-methyl-pseudouridine) in the Pfizer-BioNTech and Moderna's mRNA vaccines (but not in CVnCoV). Here we highlight the features of N1-methyl-pseudouridine and its contributions to mRNA vaccines.
p53 is required for both radiation-induced differentiation and rescue of V(D)J rearrangement in scid mouse thymocytes. (1996)

The murine scid mutation affects both V(D)J recombination and DNA repair. This mutation has been mapped to the gene encoding the catalytic subunit of the DNA-dependent protein kinase (DNA-PK), which is activated by DNA damage in normal cells. In scid mice, antigen receptor gene rearrangements are initiated normally, but impaired joining of coding ends prevents assembly of functional receptor genes, resulting in arrest of B- and T-cell development. Others have shown that exposure of scid mice to genotoxic agents such as gamma-irradiation rescues rearrangement at the T-cell receptor (TCR) beta locus and promotes thymocyte development. Here we demonstrate that irradiation rescues rearrangements at multiple TCR loci, suggesting a general effect on the recombination mechanism. Furthermore, our data show that p53 is required for irradiation-mediated rescue of both thymocyte development and V(D)J recombination. We also find that thymocyte proliferation and differentiation in the absence of DNA damage do not require p53 and are not sufficient to rescue V(D)J recombination. These results suggest that exposure to ionizing radiation facilitates a partial bypass of the scid defect, perhaps by inducing p53-dependent DNA damage response pathways.
Exterior Gateway Protocol formal specification (1984)

RFC-904 is the specification of the Exterior Gateway Protocol (EGP).
This memo updates portions of RFC-888 and RFC-827. This RFC specifies
an official protocol of the DARPA community for use between gateways
of different autonomous systems in the ARPA-Internet.