gebhart/patrepeval huggingface dataset:
Development of DS‐5573a: A novel afucosylated mAb directed at B7‐H3 with potent antitumor activity (2016)

B7-H3 is highly overexpressed in a variety of human clinical tumors, and its expression is significantly associated with poor outcomes. In our study, we aimed to develop new antitumor mAbs by employing cancer cell immunization, and succeeded in generating a mouse anti-human B7-H3 antibody (M30) that shows antitumor activity. M30 was humanized (Hu-M30), and an afucosylated Hu-M30 (DS-5573a) was also generated. To assess the potency of DS-5573a as a therapeutic mAb, we characterized this mAb and evaluated its antitumor activity in vitro and in vivo. Flow cytometry analysis showed that B7-H3 proteins were expressed on various types of cancer cell lines broadly, and DS-5573a binds to IgC1 and IgC2 domains of human B7-H3. Antibody-dependent cellular cytotoxicity activity of DS-5573a was drastically enhanced against medium to high B7-H3-expressing cancer cell lines MDA-MB-231 and NCI-H322. DS-5573a also induced high antibody-dependent cellular cytotoxicity activity against low B7-H3-expressing cancer cell line COLO205, whereas Hu-M30 induced little activity against it. In addition, DS-5573a was found to be a novel anti-B7-H3 antibody which showed antibody-dependent cellular phagocytosis activity. Furthermore, DS-5573a showed dose-dependent and significant antitumor efficacy (0.03-3 mg/kg) in MDA-MB-231-bearing SCID mice (which have functional natural killer cells and macrophages), but little antitumor efficacy in NOG mice (which lack natural killer cells and have reduced macrophage function). These results suggest that antitumor activity of DS-5573a is mediated by effector cells, and this mAb could be a promising antitumor therapy for patients with a wide range of B7-H3-expressing tumors.
The Melanocortin 1 Receptor and the UV Response of Human Melanocytes—A Shift in Paradigm† (2008)

Cutaneous pigmentation is the major photoprotective mechanism against the carcinogenic and aging effects of UV. Epidermal melanocytes synthesize the pigment melanin, in the form of eumelanin or pheomelanin. Synthesis of the photoprotective eumelanin by human melanocytes is regulated mainly by the melanocortins alpha-melanocortin (alpha-MSH) and adrenocorticotropic hormone (ACTH), which bind the melanocortin 1 receptor (MC1R) and activate the cAMP pathway that is required for UV-induced tanning. Melanocortins stimulate proliferation and melanogenesis and inhibit UV-induced apoptosis of human melanocytes. Importantly, melanocortins reduce the generation of hydrogen peroxide and enhance repair of DNA photoproducts, independently of pigmentation. MC1R is a major contributor to the diversity of human pigmentation and a melanoma susceptibility gene. Certain allelic variants of this gene, namely R151C, R160W and D294H, are strongly associated with red hair phenotype and increased melanoma susceptibility. Natural expression of two of these variants sensitizes melanocytes to the cytotoxic effect of UV, and increases the burden of DNA damage and oxidative stress. We are designing potent melanocortin analogs that mimic the effects of alpha-MSH as a strategy to prevent skin cancer, particularly in individuals who express MC1R genotypes that reduce but do not abolish MC1R function, or mutations in other melanoma susceptibility genes, such as p16.
Structure–function relationships in spruce budworm antifreeze protein revealed by isoform diversity (2000)

The spruce budworm, Choristoneura fumiferana, produces antifreeze protein (AFP) to assist in the protection of the overwintering larval stage. AFPs are thought to lower the freezing point of the hemolymph, noncolligatively, by interaction with the surface of ice crystals. Previously, we had identified a cDNA encoding a 9-kDa AFP with 10-30 times the thermal hysteresis activity, on a molar basis, than that shown by fish AFPs. To identify important residues for ice interaction and to investigate the basis for the hyperactivity of the insect AFPs, six new spruce budworm AFP cDNA isoforms were isolated and sequenced. They differ in amino-acid identity as much as 36% from the originally characterized AFP and can be divided into three classes according to the length of their 3' untranslated regions (UTRs). The new isoforms have at least five putative 'Thr-X-Thr' ice-binding motifs and three of the new isoforms encode larger, 12-kDa proteins. These appear to be a result of a 30 amino-acid insertion bearing two additional ice-binding motifs spaced 15 residues apart. Molecular modeling, based on the NMR structure of a short isoform, suggests that the insertion folds into two additional beta-helix loops with their Thr-X-Thr motifs in perfect alignment with the others. The first Thr of the motifs are often substituted by Val, Ile or Arg and a recombinantly expressed isoform with both Val and Arg substitutions, showed wild-type thermal hysteresis activity. The analysis of these AFP isoforms suggests therefore that specific substitutions at the first Thr in the ice binding motif can be tolerated, and have no discernible effect on activity, but the second Thr appears to be conserved. The second Thr is thus likely important for the dynamics of initial ice contact and interaction by these hyperactive antifreezes.
Mapping of quantitative trait loci by using genetic markers: an overview of biometrical models used (1994)

In crop plants quantitative variation is a feature of many important traits, such as yield, quality or disease resistance. Means of analyzing quantitative variation and especially of uncovering its potential genetic basis are therefore of prime importance for breeding purposes. It has been demonstrated in the early 20th century that such quantitative variation results from the combined action of multiple segregating genes and environmental factors. An intrinsic feature of such traits is, however, that the individual genes contributing to quantitative variation can hardly be distinguished. The genetics of such complex traits is therefore studied in general terms (population means and variances, covariances between progenies, heritabilities and so on) of classical quantitative genetics, rather than in terms of individual gene effects. Only by the use of genetically marked chromosomes, is it possible to detect and locate the affecting quantitative traits (quantitative trait loci or QTLs). Linkage between QTLs and morphological markers has been reported, but accurate and systematic genetic mapping has been hampered by the lack of a sufficient number of genetic markers covering an entire genome. Recently, new tooh have become available by the advent of molecular markers, such as restriction fragment length polymorphisms (RFLPs). Now, dense genetic linkage maps exist for many plant and animal species, which heralds a new era for quantitative genetics. Powerful and accurate biometrical methods are needed, so as to make possible the dissection of quantitative variation of complex characters into individual QTL effects. Mapped QTLs can be traced in breeding programmes, for instance, indirectly by selection for linked markers, or they can be cloned and introgressed via molecular or cell-biological techniques. The traditional methods for mapping of QTLs are, however, neither powerful nor accurate and the development of better methods is an area open to research. Not surprisingly, the detection and mapping of QTLs is gaining rapidly growing attention from biometrical geneticists.
Room-temperature slot microplasma in atmospheric pressure air between cylindrical electrodes with a nanoporous alumina dielectric (2007)

Slot microplasma in low temperature, atmospheric pressure air is developed for applications in surface, gas, or biomedical treatments. Dielectric barrier discharge between two parallel aluminum (Al) rods covered with nanoporous alumina films, ∼60μm thick and mean pore diameters of ∼40nm, is driven by 20kHz ac power. The glow microplasma is stable and spatially uniform, using 2–10W, in the gap of 100–500μm between the rods of 3mm diameter and 5cm long. This type of slot discharge operational in ambient temperature atmospheric pressure air can provide large-scale nonthermal plasma for any applications requiring continuous low temperature treatments.
Self-consistent order-Ndensity-functional calculations for very large systems (1996)

We present a method to perform fully self-consistent density-functional calculations that scales linearly with the system size and which is well suited for very large systems. It uses strictly localized pseudoatomic orbitals as basis functions. The sparse Hamiltonian and overlap matrices are calculated with an $O(N)$ effort. The long-range self-consistent potential and its matrix elements are computed in a real-space grid. The other matrix elements are directly calculated and tabulated as a function of the interatomic distances. The computation of the total energy and atomic forces is also done in $O(N)$ operations using truncated, Wannier-like localized functions to describe the occupied states, and a band-energy functional which is iteratively minimized with no orthogonality constraints. We illustrate the method with several examples, including carbon and silicon supercells with up to 1000 Si atoms and supercells of $\ensuremath{\beta}$-${\mathrm{C}}_{3}$${\mathrm{N}}_{4}$. We apply the method to solve the existing controversy about the faceting of large icosahedral fullerenes by performing dynamical simulations on ${\mathrm{C}}_{60}$, ${\mathrm{C}}_{240}$, and ${\mathrm{C}}_{540}$.
Low Temperature Silicon Epitaxy by Hot Wall Ultrahigh Vacuum/Low Pressure Chemical Vapor Deposition Techniques: Surface Optimization (1986)

Fundamental equilibrium considerations derived from the system have been successfully employed in the design and operation of a novel low temperature epitaxial silicon process. Films have been deposited in the range, with all resulting material epitaxial. TEM studies showed the transition to high quality, low defect density material to occur between 750° and 800°C, and such films were found to be of high chemical purity as well. In addition, UHV/CVD is shown to be a high throughput multiwafer system, achieving good film uniformities in a high wafer packing density environment, attributable to operation in the low pressure limit of chemical kinetics.
Inter-database instance identification in composite information systems (1988)

HD28 .M414 no.2029-, 88,
Pyrrolidine Derivatives as New Inhibitors of ?-Mannosidases and Growth Inhibitors of Human Cancer Cells (2006)

New pyrrolidine-3,4-diol derivatives were prepared from D-(?)- and L-(+)-phenylglycinol and tested for their ability to inhibit 25 commercial glycosidases. The influence of the substitution of the lateral side chain and of the pyrrolidine ring on the enzyme inhibition was evaluated. (2R,3R,4S)-2-({[(1R)-2-Hydroxy-1-phenylethyl]amino} methyl)pyrrolidine-3,4-diol was a potent and selective inhibitor of ?-mannosidase from jack bean. This compound was derivatized into lipophilic esters in order to allow its internalization by human cancer cells. In particular, the 4-bromobenzoate derivative demonstrated promising inhibition of glioblastoma and melanoma cells whereas it was less effective on healthy human fibroblasts.
PbS quantum dot electroabsorption modulation across the extended communications band 1200–1700nm (2005)

We report electric field-induced modulation of absorption in PbS nanocrystal quantum dots across the spectral region 600–2000nm, encompassing the entire telecommunications band. The maxima in the electroabsorption spectra correspond with the positions of the first excitonic peak, confirming the predominance of excitonic broadening as the basis for the observed effect. We estimate the change in dipole moment to be on the order of 20 D in 7nm diameter PbS nanocrystals compared to previously-reported ∼100D in CdSe.
Inhibition of influenza virus transcription by 2'-deoxy-2'-fluoroguanosine (1995)

The nucleoside analog 2'-deoxy-2'-fluoroguanosine (2'-fluorodGuo) is phosphorylated by cellular enzymes and reversibly inhibits influenza virus replication in chick embryo cells within the first 4 h of infection. RNA hybridization studies revealed that primary and secondary transcription of influenza virus RNA were blocked at a compound concentration of 10 microM, but no inhibition of cell protein synthesis was seen even at high compound concentrations (200 microM). In vitro, the triphosphate of 2'-fluorodGuo is a competitive inhibitor of influenza virus transcriptase activity from disrupted virus, with a Ki of 1.0 microM. The cellular polymerases DNA polymerase alpha and RNA polymerase II were only weakly inhibited or were insusceptible to 2'-fluorodGTP. In kinetic studies with the influenza virus transcriptase, 2'-fluorodGTP, in the absence of GTP, blocked elongation of the virus RNA chain. Similarly, by using purified ribonucleoprotein complexes it was found that the addition of a single nucleotide of 2'-fluorodGTP to the virus RNA caused chain termination, which resulted in the blockage of further virus transcription. Furthermore, the specificity for influenza virus transcriptase was confirmed when the transcriptase from partially resistant virus was found to be 10-fold less susceptible to 2'-fluorodGTP (Ki = 13.1 microM).
Reduced peripheral arterial blood flow with preserved cardiac output during submaximal bicycle exercise in elderly heart failure (2009)

During CMR submaximal bike exercise in the elderly with heart failure, mechanisms other than low cardiac output are responsible for reduced lower extremity blood flow.
Listeriolysin is processed efficiently into an MHC class I-associated epitope in Listeria monocytogenes-infected cells (1995)

Listeria monocytogenes is an intracellular pathogen that enters the cytoplasm of infected cells by secreting listeriolysin (LLO), a protein that destroys the phagosomal membrane. In infected mice, LLO is a major Ag detected by protective, MHC class I-restricted CTLs. Although the role of LLO in pathogenesis and host immunity is well established, its rate of intracellular synthesis has yet to be determined. Herein we show that cytosolic L. monocytogenes secrete LLO at a relatively low rate of approximately one molecule per bacterium per minute. Under extracellular labeling conditions, the rate of LLO secretion is approximately 50-fold higher. Intracellular LLO synthesis suffices, however, for the accumulation of 600 to 1000 H-2Kd-associated LLO 91-99 epitopes per cell. We calculate that between four and 11 LLO molecules are degraded for each LLO 91-99 epitope bound by H-2Kd. Our findings indicate that the antigenicity of LLO, with respect to MHC class I-restricted CTLs, cannot be attributed to high levels of intracellular secretion. Rather, LLO is a dominant Ag because it is rapidly degraded and very efficiently processed into an MHC class I-associated epitope.
A practical guide to anaphylaxis. (2003)

Anaphylaxis is a life-threatening reaction with respiratory, cardiovascular, cutaneous, or gastrointestinal manifestations resulting from exposure to an offending agent, usually a food, insect sting, medication, or physical factor. It causes approximately 1,500 deaths in the United States annually. Occasionally, anaphylaxis can be confused with septic or other forms of shock, asthma, airway foreign body, panic attack, or other entities. Urinary and serum histamine levels and plasma tryptase levels drawn after onset of symptoms may assist in diagnosis. Prompt treatment of anaphylaxis is critical, with subcutaneous or intramuscular epinephrine and intravenous fluids remaining the mainstay of management. Adjunctive measures include airway protection, antihistamines, steroids, and beta agonists. Patients taking beta blockers may require additional measures. Patients should be observed for delayed or protracted anaphylaxis and instructed on how to initiate urgent treatment for future episodes.
Determination of each neutral oligosaccharide in the milk of Japanese women during the course of lactation (2003)

Using reverse-phase HPLC after pyridylamination, we quantified the concentrations of major neutral oligosaccharides in the milk of sixteen Japanese women collected at 4, 10, 30 and 100 d postpartum. In colostrum and mature milk (30 d lactation), lacto-N-fucopentaose (LNFP) I was the most abundant oligosaccharide, followed by 2'-fucosyllactose (2'-FL) + lacto-N-difucotetraose (LNDFT), LNFP II + lacto-N-difucohexaose II (LNDFH II), and 3-fucosyllactose (3-FL). Together these accounted for 73 % of the total weight of neutral oligosaccharides in colostrum and mature milk. Changes in concentration occurred during the course of lactation. LNFP I and 2'-FL + LNDFT increased from 4 to 10 d postpartum, and then declined by 100 d. LNFP II + LNDFH II steadily increased during the first 30 d and then declined. In contrast, 3-FL increased steadily throughout the entire 100 d of study. Large differences were observed between our data and previously published data in Italian women, in terms of both the concentration and temporal changes of each oligosaccharide. These differences may be caused by different assay methodology, although racial differences cannot be ruled out.
Manipulation of Hyaluronan Synthase Expression in Prostate Adenocarcinoma Cells Alters Pericellular Matrix Retention and Adhesion to Bone Marrow Endothelial Cells (2002)

Prostate cancer metastasis to bone marrow involves initial adhesion of tumor cells to the bone marrow endothelium, followed by transmigration and proliferation within the marrow. Rapid, specific adhesion of highly metastatic prostate adenocarcinoma cells (PC3M-LN4) to bone marrow endothelial cell (BMEC) lines requires a pericellular hyaluronan (HA) matrix and correlates with dramatically up-regulated HA synthase (HAS) expression. Non-metastatic prostate tumor cells (LNCaP) do not assemble a HA matrix, adhere poorly to BMECs, and express normal levels of HAS. Preferential bone metastasis of prostate carcinoma cells may therefore be facilitated by tumor cell HA biosynthesis. In this report, HAS gene expression was manipulated to investigate the direct impact of prostate tumor cell HA production on adhesion to BMECs. PC3M-LN4 cells stably transfected with antisense HAS2 and HAS3 failed to form pericellular matrices. Adhesion of these transfectants to BMECs was significantly diminished, comparable to the low level exhibited by LNCaP cells. Upon transfection with full-length HAS2 or HAS3, the non-adherent LNCaP cells retained pericellular HA and adhered to BMECs. The results of this study are consistent with a model in which HA matrix formation, BMEC adhesion, and metastatic potential are mediated by HAS expression.
Ascending dose‐controlled trial of beloranib, a novel obesity treatment for safety, tolerability, and weight loss in obese women (2013)

Beloranib treatment was well tolerated and associated with rapid weight loss and improvements in lipids, C-reactive protein, and adiponectin.
A novel clustering-based approach of indoor location fingerprinting (2013)

This study proposes a clustering-based Wi-Fi fingerprinting localization algorithm. The proposed algorithm first presents a novel support vector machine based clustering approach, namely SVM-C, which uses the margin between two canonical hyperplanes for classification instead of using the Euclidean distance between two centroids of reference locations. After creating the clusters of fingerprints by SVM-C, our positioning system embeds the classification mechanism into a positioning task and compensates for the large database searching problem. The proposed algorithm assigns the matched cluster surrounding the test sample and locates the user based on the corresponding cluster's fingerprints to reduce the computational complexity and remove estimation outliers. Experimental results from realistic Wi-Fi test-beds demonstrated that our approach apparently improves the positioning accuracy. As compared to three existing clustering-based methods, K-means, affinity propagation, and support vector clustering, the proposed algorithm reduces the mean localization errors by 25.34%, 25.21%, and 26.91%, respectively.
Myb proteins: angels and demons in normal and transformed cells (2010)

A key regulator of proliferation, differentiation and cell fate, the c-Myb transcription factor regulates the expression of hundreds of genes and is in turn regulated by numerous pathways and protein interactions. However, the most unique feature of c-Myb is that it can be converted into an oncogenic transforming protein through a few mutations that completely change its activity and specificity. The c-Myb protein is a myriad of interactions and activities rolled up in a protein that controls proliferation and differentiation in many different cell types. Here we discuss the background and recent progress that have led to a better understanding of this complex protein, and outline the questions that have yet to be answered.
Simulation of steam unit start up by combustion units (2008)

The very first control action in a restoration procedure concerns the production restart. Traditionally, the black start up manoeuvre is accomplished by hydro power plants with black start capability and combustion turbine units. This requires that the plant be capable of responding quickly to incremental load changes during load pickup while ensuring that frequency deviation remain within limits. Aim of this paper is to investigate how the black start capability of combustion power plants can be used for black start simulation studies and hence for evaluating the stability and frequency response of combustion power plant during black start in the early stages of power system restoration. This paper presents black start simulation and cranking power for steam unit utilizing combustion units. Start up scheme has been developed based on using a pair of interconnected units.