gebhart/patrepeval huggingface dataset:
Novel Human Interleukin-15 Agonists (2009)

IL-15 is an immunostimulatory cytokine trans-presented with the IL-15 receptor alpha-chain to the shared IL-2/IL-15Rbeta and common gamma-chains displayed on the surface of T cells and NK cells. To further define the functionally important regions of this cytokine, activity and binding studies were conducted on human IL-15 muteins generated by site-directed mutagenesis. Amino acid substitutions of the asparagine residue at position 72, which is located at the end of helix C, were found to provide both partial agonist and superagonist activity, with various nonconservative substitutions providing enhanced activity. Particularly, the N72D substitution provided a 4-5-fold increase in biological activity of the IL-15 mutein compared with the native molecule based on proliferation assays with cells bearing human IL-15Rbeta and common gamma-chains. The IL-15N72D mutein exhibited superagonist activity through improved binding ability to the human IL-15Rbeta-chain. However, the enhanced potency of IL-15N72D was not observed with cells expressing the mouse IL-15Ralpha-IL-15Rbeta-gamma(c) complex, suggesting that this effect is specific to the human IL-15 receptor. The enhanced biological activity of IL-15N72D was associated with more intense phosphorylation of Jak1 and Stat5 and better anti-apoptotic activity compared with the wild-type IL-15. IL-15N72D superagonist activity was also preserved when linked to a single-chain TCR domain to generate a tumor-specific fusion protein. Thus, the human IL-15 superagonist muteins and fusions may create opportunities to construct more efficacious immunotherapeutic agents with clinical utility.
RGD-Tachyplesin inhibits tumor growth. (2001)

Tachyplesin is an antimicrobial peptide present in leukocytes of the horseshoe crab (Tachypleus tridentatus). In this study, a synthetic tachyplesin conjugated to the integrin homing domain RGD was tested for antitumor activity. The in vitro results showed that RGD-tachyplesin inhibited the proliferation of both cultured tumor and endothelial cells and reduced the colony formation of TSU prostate cancer cells. Staining with fluorescent probes of FITC-annexin V, JC-1, YO-PRO-1, and FITC-dextran indicated that RGD-tachyplesin could induce apoptosis in both tumor and endothelial cells. Western blotting showed that treatment of cells with RGD-tachyplesin could activate caspase 9, caspase 8, and caspase 3 and increase the expression of the Fas ligand, Fas-associated death domain, caspase 7, and caspase 6, suggesting that apoptotic molecules related to both mitochondrial and Fas-dependent pathways are involved in the induction of apoptosis. The in vivo studies indicated that the RGD-tachyplesin could inhibit the growth of tumors on the chorioallantoic membranes of chicken embryos and in syngenic mice.
Saphenous nerve block is an effective regional technique for post‐menisectomy pain (2008)

In this study we have evaluated the post menisectomy pain relief offered by Saphenous nerve block. This study was planned on 40 patients with a pre-operative and post operative diagnosis of medial meniscus lesion undergoing partial menisectomy arthroscopically. Patients were randomized into 2 groups where Group I received a preoperative Saphenous block while group 2 did not receive a peripheral block, but received 1 ml of saline as placebo injection. After blocks both groups received general anesthesia and IV patient controlled analgesia (PCA) with tramadol for post operative pain relief. Patients rest and activity pain scores were evaluated on post operative 0, 2, 4, 6, 12 and 24 h using visual analog scale (VAS). Total tramadol consumption as well as pain at rest, when weight bearing and the need for external support while walking were recorded. Group I VAS scores were statistically lower then group II during the time of observation periods at rest as well as active movement periods. Tramadol consumption through IV PCA was statistically significantly lower in group I than in group II (P < 0.05). Pain during walking measured at 24 h was significantly different with better results in group I (P < 0.001). Saphenous nerve block is used for different indications; it can also be a good analgesic method for arthroscopic interventions. We have shown it to be effective after medial partial menisectomies. According to our knowledge this report is the first one utilizing saphenous nerve block for pain after arthroscopic medial menisectomy.
Lanthanide(III) Complexes of Phosphorus Acid Analogues of H4DOTA as Model Compounds for the Evaluation of the Second‐Sphere Hydration (2008)

Abstract Five DOTA‐like ligands lacking a water molecule in the first coordination sphere of their Gd III complexes, namely the phosphinates H 4 DOTP H , H 4 DOTP hm and H 4 DOTP Et , and the phosphonate monoesters H 4 DOTP OEt and H 4 DOTP OBu , were synthesized with the aim of exploring the influence of the second hydration sphere on the relaxivity of Gd III complexes. The H 4 DOTP H , H 4 DOTP hm and H 4 DOTP OEt ligands and their Ln III complexes were characterized by potentiometry and time‐resolved luminescence; the Gd III complexes are thermodynamically much less stable than that of H 4 DOTA, and no water is coordinated in the inner sphere. The crystal structures of the free ligand H 4 DOTP OEt and of the Gd III complexes of H 4 DOTP H and H 4 DOTP OEt were determined by X‐ray diffraction. The complexes have the expected octadentate coordination mode with an N 4 O 4 arrangement; no water molecule is bound to the Gd III ion. Information on the structures of the Ln III complexes of all five ligands in aqueous solution were obtained from 1 H and 31 P NMR spectra. The NMR spectra of the [Ln(DOTP hm )] – and [Ln(DOTP Et )] – complexes show that these compounds have a clear preference for a specific arrangement of phosphorus atoms which gives rise to the symmetrical RRRR (or SSSS ) isomer. However, many diastereoisomers were observed for all other complexes. Ln III ‐induced 17 O NMR shift data reveal that the spatial location of the second‐sphere water molecules for the two groups of complexes differs. The parameters governing the effect of the second hydration sphere on the relaxivity of the Gd III complexes of all ligands were evaluated by EPR, variable‐temperature 17 O NMR spectroscopy and 1 H NMRD relaxometry. The presence of second‐sphere water molecules is clearly confirmed, depending on the character of the pendant arms. As the relaxivity does not depend significantly on the nature of the phosphorus substituents and/or on the isomerism present in solution, the second‐sphere water molecules should be located close to the phosphorus–oxygen atoms.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)
HMGB1 Is a Therapeutic Target for Sterile Inflammation and Infection (2011)

A key question in immunology concerns how sterile injury activates innate immunity to mediate damaging inflammation in the absence of foreign invaders. The discovery that HMGB1, a ubiquitous nuclear protein, mediates the activation of innate immune responses led directly to the understanding that HMGB1 plays a critical role at the intersection of the host inflammatory response to sterile and infectious threat. HMGB1 is actively released by stimulation of the innate immune system with exogenous pathogen-derived molecules and is passively released by ischemia or cell injury in the absence of invasion. Established molecular mechanisms of HMGB1 binding and signaling through TLR4 reveal signaling pathways that mediate cytokine release and tissue damage. Experimental strategies that selectively target HMGB1 and TLR4 effectively reverse and prevent activation of innate immunity and significantly attenuate damage in diverse models of sterile and infection-induced threat.
CT Screening for Lung Cancer: Update 2007 (2008)

Screening is the pursuit of the early diagnosis of cancer before symptoms occur. The purpose of early diagnosis is to provide early treatment, which potentially prevents death from the cancer. The usefulness of screening depends on how early the cancer can be diagnosed and how many deaths can be prevented by early treatment as compared with later symptom-prompted diagnosis and treatment. The goal of the Early Lung Cancer Action Project investigators was to develop an efficient methodology that would provide an ever-accumulating, continually updated body of evidence for evaluation of emerging new technologies for screening for cancer. This methodology recognizes that screening is a sequential process that starts with the pursuit of the early diagnosis of cancer followed by early treatment. It also recognizes that diagnostic research is fundamentally different from treatment research. To fully understand the current discussions on the evidence for lung cancer screening, key definitions are provided, including the differentiation between the first, baseline round of screening and all subsequent rounds of repeat screening and baseline and repeat cancers and their distribution by cell type. These definitions are critical in analyzing the results of various screening reports as they are not used by all. To provide optimal screening, a regimen for the diagnostic workup must be specified starting with the definition of the initial test, its positive result, and the workup for a positive result leading to a diagnosis of cancer. Assessment of diagnostic performance does not require a control group, but does require confirmation of the diagnosis. For assessment of the effectiveness of early treatment, a comparison group is needed. The comparison group may be formed by randomly assigning people with screen-diagnosed lung cancer to immediate or delayed treatment, as has been done for prostate cancer. This provides a direct assessment of any potential overdiagnosis of the cancer resulting from screening. Alternatively, a quasiexperimental control group can be used consisting of participants diagnosed with the cancer who have refused or delayed their treatment even though they are candidates for it.
Redirecting Pseudomonas exotoxin. (1991)

Pseudomonas exotoxin (PE) is a three-domain bacterial toxin that kills mammalian cells by gaining entry to the cytosol and inactivating protein synthesis. The pathway of toxin entry includes binding to a surface receptor, internalization via coated pits and endosomes, proteolytic processing, reduction of disulfide bonds and finally the translocation of an enzymatically active C-terminal fragment to the cytosol. Once in the cytosol this fragment inhibits protein synthesis by ADP ribosylating elongation factor 2. Because of its potency PE and its derivatives have been directed to kill various target cells. It is hoped this strategy will lead to the development of a novel kind of therapeutic agent for the treatment of various human diseases including cancer, AIDS and various immunological disorders.
Primary structure and gene localization of human prolidase (1989)

Complementary DNA clones of prolidase (imidodipeptidase, EC 3.4.13.9) were isolated from human liver and placental cDNA libraries. Two clones named lambda PL21 and lambda PP6 from the liver and placental cDNA libraries, respectively, were analyzed in detail. The first clone, lambda PL21, carried a cDNA insert of 1.7 kilobase pairs and covered all the coding region of human prolidase mRNA. The second clone, lambda PP6, contained a 1.8-kilobase insert with a full-length 3'-untranslated region. Comparison of the amino acid sequence predicted from the nucleotide sequence of the cDNA insert of the two clones with the partial amino acid sequence determined by Edman degradation of peptides derived from human erythrocyte prolidase established that both clones code for human prolidase. The amino terminus of the human mature enzyme is blocked and seems to begin with the sequence X-Ala-Ala-Ala. Presumably no processing occurs at the carboxyl terminus. The mature enzyme is composed of 492 residues, corresponding to Mr 54,305. The sequence of prolidase is unique and not similar to any known protein, except for a significant similarity to regions of F1-ATPase alpha and beta subunits from various sources. The gene has been mapped to the short arm of chromosome 19 (19p13.2). Elucidation of the complete amino acid sequence and the gene location of prolidase should provide the basis for understanding structure-function relationships and also inherited disorders caused by deficiency of this metabolically important enzyme.
Dentin Evaluation after Nd:YAG Laser Irradiation Using Short and Long Pulses (2004)

Our results suggest that longer interaction times resulted in more evident effects with more melted substrate than shorter pulses, and in both cases the resultant melted layer contains a greater concentration of inorganic substances than non-irradiated dentin.
Efficient nuclear export of p65-IκBα complexes requires 14-3-3 proteins (2006)

IkappaB are responsible for maintaining p65 in the cytoplasm under non-stimulating conditions and promoting the active export of p65 from the nucleus following NFkappaB activation to terminate the signal. We now show that 14-3-3 proteins regulate the NFkappaB signaling pathway by physically interacting with p65 and IkappaBalpha proteins. We identify two functional 14-3-3 binding domains in the p65 protein involving residues 38-44 and 278-283, and map the interaction region of IkappaBalpha in residues 60-65. Mutation of these 14-3-3 binding domains in p65 or IkappaBalpha results in a predominantly nuclear distribution of both proteins. TNFalpha treatment promotes recruitment of 14-3-3 and IkappaBalpha to NFkappaB-dependent promoters and enhances the binding of 14-3-3 to p65. Disrupting 14-3-3 activity by transfection with a dominant-negative 14-3-3 leads to the accumulation of nuclear p65-IkappaBalpha complexes and the constitutive association of p65 with the chromatin. In this situation, NFkappaB-dependent genes become unresponsive to TNFalpha stimulation. Together our results indicate that 14-3-3 proteins facilitate the nuclear export of IkappaBalpha-p65 complexes and are required for the appropriate regulation of NFkappaB signaling.
Retinal metabolic state of the proline-23-histidine rat model of retinitis pigmentosa (2009)

We determined the metabolic changes that precede cell death in the dystrophic proline-23-histidine (P23H) line 3 (P23H-3) rat retina compared with the normal Sprague-Dawley (SD) rat retina. Metabolite levels and metabolic enzymes were analyzed early in development and during the early stages of degeneration in the P23H-3 retina. Control and degenerating retinas showed an age-dependent change in metabolite levels and enzymatic activity, particularly around the time when phototransduction was activated. However, lactate dehydrogenase (LDH) activity was significantly higher in P23H-3 than SD retina before the onset of photoreceptor death. The creatine/phosphocreatine system did not contribute to the increase in ATP, because phosphocreatine levels, creatine kinase, and expression of the creatine transporter remained constant. However, Na(+)-K(+)-ATPase and Mg(2+)-Ca(2+)-ATPase activities were increased in the developing P23H-3 retina. Therefore, photoreceptor apoptosis in the P23H-3 retina occurs in an environment of increased LDH, ATPase activity, and higher-than-normal ATP levels. We tested the effect of metabolic challenge to the retina by inhibiting monocarboxylate transport with alpha-cyano-4-hydroxycinnamic acid or systemically administering the phosphodiesterase inhibitor sildenafil. Secondary to monocarboxylate transport inhibition, the P23H-3 retina did not demonstrate alterations in metabolic activity. However, administration of sildenafil significantly reduced LDH activity in the P23H-3 retina and increased the number of terminal deoxynucleotidyl transferase biotin-dUPT nick end-labeled photoreceptor cells. Photoreceptor cells with a rhodopsin mutation display an increase in apoptotic markers secondary to inhibition of a phototransduction enzyme (phosphodiesterase), suggesting increased susceptibility to altered cation entry.
Total synthesis of (±)-allosamizoline from a symmetric trisubstituted cyclopentene (1994)

A convergent synthesis of the aminocyclitol allosamizoline 1, which is found in a class of pseudotrisaccharide chitinase inhibitors known as the allosamidins, is reported.
Imaging single DNA molecules for high precision NIPT (2018)

Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing. The primary objective of this study was to assess the Vanadis NIPT assay with respect to analytical precision and clinical feasibility. Analysis of reference DNA samples indicate that samples which are challenging to analyze with low fetal-fraction can be readily detected with a limit of detection determined at <2% fetal-fraction. In total of 286 clinical samples were analysed and 30 out of 30 pregnancies affected by trisomy 21 were classified correctly. This method has the potential to make cost effective NIPT more widely available with more women benefiting from superior detection and false positive rates.
Intranasal immunization against herpes simplex virus infection by using a recombinant glycoprotein D fused with immunomodulating proteins, the B subunit of Escherichia coli heat-labile enterotoxin and interleukin-2. (1993)

To establish a novel strategy of mucosal immunization against herpes simplex virus type 1 (HSV-1) infection, we studied the immune responses elicited by intranasal immunization with several forms of a recombinant glycoprotein D (gD) of HSV-1. A truncated gD (t-gD) co-administered with heat-labile enterotoxin B subunit (LTB) from Escherichia coli induced both a mucosal immune response involving secretion of anti-gD IgA and serum IgG production. The levels of these responses are comparable to those in mice which have recovered from intranasal HSV-1 infections. The fusion protein (t-gD-LTB), consisting of t-gD and LTB, induced the responses more efficiently than did co-administration of t-gD and LTB, although GM1 ganglioside binding activity was significantly reduced in t-gD-LTB. We found that another fusion protein, consisting of t-gD and human interleukin-2 (t-gD-IL-2), also elicited antibody responses comparable to those induced by t-gD-LTB. Immunity acquired by intranasal immunization with t-gD-IL-2 protected mice from intraperitoneal HSV-1 infections, whereas t-gD-LTB or t-gD alone failed to provide protection against infection. Even in a mouse strain that responded highly to subcutaneously administered gD, intranasally administered t-gD did not elicit antibody responses. The lack of response to gD was clearly abrogated by co-administration with IL-2, and administration of t-gD-IL-2 induced an excellent level of antibody responses in this strain. These results suggest that the IL-2 fusion strategy yields a new type of mucosal immunization, the mechanism of which differs from that speculated for the mucosal adjuvant activity of LTB.
Similarity Detection for Free-Form Parametric Models (2014)

In this article, we propose a framework for detecting local similarities in free-form parametric models, in particular\non B-Splines or NURBS based B-reps: patches similar up to an approximated isometry are identified. Many recent\narticles have tackled similarity detection on 3D objects, in particular on 3D meshes. The parametric B-splines, or\nNURBS models are standard in the CAD (Computer Aided Design) industry, and similarity detection opens the\ndoor to interesting applications in this domain, such as model editing, objects comparison or efficient coding. Our\ncontributions are twofold: we adapt the current technique called votes transformation space for parametric surfaces\nand we improve the identification of isometries. First, an orientation technique independent of the parameterization\npermits to identify direct versus indirect transformations. Second, the validation step is generalized to extend to\nthe whole B-rep. Then, by classifying the isometries according to their fixed points, we simplify the clustering\nstep. We also apply an unsupervised spectral clustering method which improves the results but also automatically\nestimates the number of clusters.
Highly available systems for database applications (1984)

As users entrust more and more of their applications to computer systems, the need for systems that are continuously operational (24 hours per day) has become even greater. This paper presents a survey and analysis of representative architectures and techniques that have been developed for constructing highly available systems for database applications. It then proposes a design of a distributed software subsystem that can serve as a unified framework for constructing database application systems that meet various requirements for high availability.
Use of Light-Off Catalysts to Meet the California LEV/ULEV Standards (1993)

&lt;div class="htmlview paragraph"&gt;Hydrocarbon conversion across emission control catalysts is a strong function of inlet temperature. The bulk of unconverted hydrocarbon emissions arises in Bag 1 of the FTP-75 cycle before the emission control system goes closed-loop. A general strategy for improving converter hydrocarbon efficiency is to heat up the catalyst early in Bag 1. One strategy for doing this is to place a small catalytic converter near the engine manifold. This approach to hydrocarbon control is well established and represents a production feasible method. This paper explores the use of close-coupled catalysts in conjunction with conventional underfloor converters for achieving the California low emission vehicle standards. The paper identifies catalytic formulations for both converters that optimize emission system performance. The benefits of double wall exhaust pipe connecting the two converters and thin walled substrate for the light-off catalyst were also studied.&lt;/div&gt;
STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES (1944)

1. From Type III pneumococci a biologically active fraction has been isolated in highly purified form which in exceedingly minute amounts is capable under appropriate cultural conditions of inducing the transformation of unencapsulated R variants of Pneumococcus Type II into fully encapsulated cells of the same specific type as that of the heat-killed microorganisms from which the inducing material was recovered. 2. Methods for the isolation and purification of the active transforming material are described. 3. The data obtained by chemical, enzymatic, and serological analyses together with the results of preliminary studies by electrophoresis, ultracentrifugation, and ultraviolet spectroscopy indicate that, within the limits of the methods, the active fraction contains no demonstrable protein, unbound lipid, or serologically reactive polysaccharide and consists principally, if not solely, of a highly polymerized, viscous form of desoxyribonucleic acid. 4. Evidence is presented that the chemically induced alterations in cellular structure and function are predictable, type-specific, and transmissible in series. The various hypotheses that have been advanced concerning the nature of these changes are reviewed.