gebhart/patrepeval huggingface dataset:
Cytoplasmic domains of the reduced folate carrier are essential for trafficking, but not function (2002)

The reduced folate carrier (RFC) protein has a secondary structure consistent with the predicted 12 transmembrane (TM) domains, intracellular N- and C-termini and a large cytoplasmic loop between TM6 and TM7. In the present study, the role of the cytoplasmic domains in substrate transport and protein biogenesis were examined using an array of hamster RFC deletion mutants fused to enhanced green fluorescent protein and expressed in Chinese hamster ovary cells. The N- and C-terminal tails were removed both individually and together, or the large cytoplasmic loop was modified such that the domain size and role of conserved sequences could be examined. The loss of the N- or C-terminal tails did not appear to significantly disrupt protein function, although both termini appeared to have a role in the efficiency with which molecules exited the endoplasmic reticulum to localize at the plasma membrane. There appeared to be both size and sequence requirements for the intracellular loop, which are able to drastically affect protein stability and function unless met. Furthermore, there might be an indirect role for the loop in substrate translocation, since even moderate changes significantly reduced the V(max) for methotrexate transport. Although these cytoplasmic domains do not appear to be absolutely essential for substrate transport, each one is important for biogenesis and localization.
MK-801 has neuroprotective and antiproliferative effects in retinal laser injury. (1997)

A potent noncompetitive NMDA-receptor blocker, MK-801 exhibits neuroprotective and antiproliferative properties in the retina. Glutamate-receptor blockers should be investigated further as potential adjuvant therapy in retinal photocoagulation treatments.
A New Application of Modified Peptides and Peptidomimetics: Potential Anticancer Agents (1994)

Potent competitive inhibitors of oncogenic Ras proteins include modified peptides and peptidomimetics such as 1 and 2, respectively. They prevent the attachment of these mutated proteins to the cell membrane and the resulting unregulated cell proliferation and malignant transformation. This opens new perspectives for the development of anticancer agents, since oncogenic forms of the ras genes, which encode these proteins, frequently occur in human cancer cells.
The present safety assessment of deet. (1995)

Deet is considered to be the best "all around" insect repellent ever developed and is the most widely used insect repellent in the world. Since its first use in a consumer product in 1956, billions of applications have been made to human skin. Information about the safety of deet comes from the human clinical literature, animal toxicology studies, and poison control centers' experiences with deet. The clinical literature reports the association of deet with neurotoxicity in 14 individuals. Three of the cases resulted in death, whereas all of the other patients completely recovered. The exact role of deet in the toxicity reported is difficult to determine from the reports. Recently reported animal safety studies have examined potential neurotoxicity following multigenerational dosing. Effects on the nervous system were only seen when generalized toxicity was also observed. Thus deet is not a selective neurotoxin. Important information about deet also comes from an investigation into the reports of adverse affects reported to 71 poison control centers in the USA. An important conclusion from this study is that there is no evidence that increasing deet concentration has any effect on the severity of the symptoms reported. The vast majority of reported cases had either no symptoms or ones that resolved rapidly. In conclusion, a thorough examination of all information available indicates that the risk of serious adverse effects following the use of deet is extremely low.
Homophilic interaction of NTBA, a member of the CD2 molecular family: induction of cytotoxicity and cytokine release in human NK cells (2004)

NK-T-B antigen (NTBA) is a CD2 family member that functions as a coreceptor in human NK cell activation. Several receptor/ligand interactions occur between different members of this molecular family. In this study, in order to identify the natural ligand of NTBA, we produced a chimeric protein formed by the NTBA extracellular region fused with the Fc portion of human IgG1 (termed NTBA-Fc*). NTBA-Fc* specifically binds to NTBA cell transfectants but not to cells transfected with other CD2 family members including CD2, CD48, CD84, CD150, CD229, and CD244. Moreover, NTBA-Fc* also binds to NTBA(+) but not to NTBA(-) T cell lines. Enzyme-linked immunosorbent assays, plasmon resonance analysis, as well as NTBA-Fc*-mediated down-regulation of NTBA surface expression further confirmed the occurrence of NTBA/NTBA homophilic interaction. Functionally, in NK cells, NTBA-Fc* promoted a strong production of IFN-gamma and TNF-alpha. Moreover, NTBA-transfected targets displayed increased susceptibility to NK-mediated killing as compared to untransfected cells and this effect was specifically inhibited by anti-NTBA mAb. Altogether our data indicate that NTBA is characterized by self recognition.
Constructive feedforward ART clustering networks. II (2002)

For pt.I see ibid., p.645-61 (2002). Part I of this paper defines the class of constructive unsupervised on-line learning simplified adaptive resonance theory (SART) clustering networks. Proposed instances of class SART are the symmetric fuzzy ART (S-Fuzzy ART) and the Gaussian ART (GART) network. In Part II of our work, a third network belonging to class SART, termed fully self-organizing SART (FOSART), is presented and discussed. FOSART is a constructive, soft-to-hard competitive, topology-preserving, minimum-distance-to-means clustering algorithm capable of: 1) generating processing units and lateral connections on an example-driven basis and 2) removing processing units and lateral connections on a minibatch basis. FOSART is compared with Fuzzy ART, S-Fuzzy ART, GART and other well-known clustering techniques (e.g., neural gas and self-organizing map) in several unsupervised learning tasks, such as vector quantization, perceptual grouping and 3-D surface reconstruction. These experiments prove that when compared with other unsupervised learning networks, FOSART provides an interesting balance between easy user interaction, performance accuracy, efficiency, robustness, and flexibility.
The Organic Chemistry of Isotopic Labelling (2011)

The chemical synthesis of isotopically labelled compounds is a pre-requisite for many chemical, biochemical and medicinal investigations. The constraints imposed by the requirements for regiospecific labelling and, in some instances, the time-scale of the synthesis often lead to quite different synthetic strategies to those that are used for the unlabelled material. Whilst there are many specialist papers, reviews and long books devoted to particular isotopes, there is no currently available short introductory book devoted to the organic chemistry of isotopic labelling. The aim of this book is to introduce research workers to a variety of methods that have been used to achieve these synthetic labelling objectives before exploring a particular method in detail. It covers a number of different isotopes and the methods that have been used to introduce them into organic compounds. Labelling methods also provide useful undergraduate teaching examples of modern synthetic reactions and their stereochemical consequences using relatively simple substrates. The book will therefore have a wider appeal than just those involved in using isotopes in research such as environmental and pharmaceutical chemists as well as organic chemists.
Detailed Structure of Molecularly Thin Polyelectrolyte Multilayer Films on Solid Substrates as Revealed by Neutron Reflectometry (1998)

Using neutron reflectometry we have resolvedto high resolutionthe internal structure of self-assembled polyelectrolyte multilayer films and have developed a detailed molecular picture of such systems by analyzing the data with a composition-space refinement technique. We show that such surface films consist of stratified structures in which polyanions and polycations of individual layers interdigitate one another intimately. Nevertheless, the deposition technique leads to results that are predictable, if well-defined and constant environmental conditions are maintained during the preparation. For alternating layers of poly(styrenesulfonate) (PSS) and poly(allylamine hydrochloride) (PAH), adsorbed onto atomically flat surfaces, a roughening of successively deposited layers leads to a progressively larger number of adsorption sites for consecutive generations of adsorbed polymer, and thus to an increase in layer thicknesses with an increasing number of deposited layers. Because of the interpenetration of adjacent polyelectrolyte species, however, this increase settles quickly into an equilibrium thickness. In fully hydrated films (100% relative humidity), water occupies ≥40% of the volume within the films. About twice as much water (by volume) is associated with PSS as with PAH. Incorporated inorganic salt plays a minor role only, if any. The equilibrium thickness of the deposited layer structure may be fine-tuned via the ionic strength, I, of the solutions used for the preparation. We show that the dependence of the thickness dlp per layer pair on I is linear, with a sensitivity, Δdlp/ΔI = 16 Å × L/mol. Concurrently with the layer thickness the interface roughness σ between adjacent layers increases: σ ∼ 0.4 × dlp. In contrast to the ionic strength of the deposition solutions, the degree of polymerization of the polyanions used in the preparation plays a minor role only in determining the overall structure of the deposited films. The results reported here are quantitatively consistent with those of a recent study (Tarabia et al. J. Appl. Phys. 1998, 83, 725−732), if one assumes that the hydration of the polyelectrolyte molecules in the sample films investigated in the two studies is similar.
An amino acid residue in the middle of the fingers subdomain is involved in Neq DNA polymerase processivity: enhanced processivity of engineered Neq DNA polymerase and its PCR application (2010)

Neq DNA polymerase is the first archaeal family B DNA polymerase reported to lack uracil recognition function and successfully utilize deaminated bases. We have focused on two amino acid residues (Y515, A523) in the fingers subdomain of Neq DNA polymerase, which were predicted to be located in the middle of the fingers subdomain, based on amino acid sequence alignment of the Neq DNA polymerase with structurally determined archaeal DNA polymerases. Those two residues were replaced by site-directed mutagenesis, and the enzymatic properties of the mutants were analyzed. Here, we show that the A523 residue located in the middle of the fingers subdomain affects the processivity of Neq DNA polymerase. Mutational analysis has allowed us to enhance the protein function as well as understand the function of the residues. One mutant protein, Neq A523R DNA polymerase, exhibited a roughly 3-fold enhanced processivity and extension rate compared to wild type, enabling more efficient PCR. In the presence of uracil, Neq A523R DNA polymerase outperformed Taq DNA polymerase with enhanced specificity and sensitivity. These results suggest that Neq A523R DNA polymerase could be most effectively utilized in real-time PCR using uracil-DNA glycosylase without the risk of carry-over contamination.
Molecular Modeling and Functional Mapping of B7-H1 and B7-DC Uncouple Costimulatory Function from PD-1 Interaction (2003)

B7-H1 and B7-DC are ligands for PD-1, a receptor implicated in negative regulation of T and B cell functions. These ligands, however, also costimulate T cell responses. It remains elusive whether or not costimulation is mediated through PD-1. By comparative molecular modeling and site-directed mutagenesis, we found that nonconserved residues between these ligands on the A'GFCC'C" face mediate interaction with PD-1. This indicates significant structural heterogeneity of the interactions between PD-1 and its ligands. Importantly, ligand mutants with abolished PD-1 binding capacity could still costimulate proliferation and cytokine production of T cells from normal and PD-1-deficient mice. Our results reveal unique binding characteristics of B7-H1 and B7-DC and provide direct evidence for an independent costimulatory receptor other than PD-1.
In vivo assessment of optimal viewing angles from X-ray coronary angiography (2011)

The proposed approach is able to accurately and quickly determine the optimal viewing angles for the online support of coronary interventions.
Inhibitory effects of P2Y12receptor antagonists on TRAP-induced platelet aggregation, procoagulant activity, microparticle formation and intracellular calcium responses in patients with acute coronary syndromes (2005)

Thrombin induces platelet aggregation and membrane rearrangements leading to enhanced procoagulant activity and microparticle production, all of which are thought to contribute to thrombus formation in patients with acute coronary syndromes (ACS). Clopidogrel, an adenosine diphosphate (ADP) receptor antagonist acting at the P2Y(12) receptor, has been shown to provide clinical benefit in ACS. We aimed to investigate the effects of clopidogrel ex vivo and another ADP-antagonist, AR-C69931MX in vitro on thrombin receptor activating peptide (TRAP)-induced platelet aggregation, procoagulant activity, microparticle formation and [Ca(2+)]i responses in patients with ACS. Measurements were performed in platelet-rich plasma using aggregometry and flow cytometry (n = 12). Clopidogrel (300 mg loading dose plus 75 mg daily) significantly inhibited TRAP-induced aggregation, procoagulant activity (annexin V binding) and microparticle production (all P < 0.05) but not as extensively as AR-C69931MX (400 nmol/l). [Ca(2+)]i responses induced by a combination of TRAP and ADP designed to mimic the physiological effects of released ADP showed that clopidogrel partially and AR-C69931MX completely removed the ADP component of the [Ca(2+)]i responses (n = 6). The results provide new information on the mechanisms involved in the beneficial effects of P2Y(12) antagonists in patients with ACS.
Selective matrix metalloproteinase (MMP) inhibitors in cancer therapy: Ready for prime time? (2009)

Commentary to:A novel and selective membrane type-1 matrix metalloproteinase (MT1-MMP) inhibitor reduces cancer cell motility and tumor growthJuho Suojanen, Tuula Salo, Erkki Koivunen, Timo Sorsa and Emma Pirilä
Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production. (1995)

During human immunodeficiency virus infection and allergic diseases, characterized by a dominant T helper (Th) 2 response, overproduction of prostaglandin E2 (PGE2) is observed. In this paper we studied the effect of PGE2 on interleukin (IL)-12 synthesis, because this cytokine has been described to be essential in induction of Th1 responses. IL-12 synthesis was induced in monocytes that were stimulated with Neisseria meningitidis-derived lipopolysaccharide in whole blood cultures. PGE2 almost completely inhibited lipopolysaccharide induced IL-12 production, whereas IL-6 production was only partially inhibited by PGE2. In contrast, the production of IL-10 was approximately twofold enhanced at these conditions. The effects of PGE2 were due to its cAMP-inducing capacity, since they could be mimicked by other cAMP inducers. Recombinant human IL-10 also inhibited IL-12 and IL-6 production. However, the inhibitory effect of PGE2 on IL-12 production was independent of IL-10 since neutralizing anti-IL-10 antibodies were unable to reverse this inhibition. These results suggest that the capacity of an antigen to induce PGE2 synthesis may play a crucial role in the development of either a Th1 or Th2 response.
Anticancer drug resistance and inhibition of apoptosis. (1995)

Apoptosis is a new concept which could be of great importance in the understanding and treatment of cancer. An important feature is the discovery of inhibitors of apoptosis, because they induce resistance to chemotherapeutic drugs and irradiation. Bcl-2 is the most well known of these apoptosis inhibitors. When it is overexpressed cells are less sensitive to cytotoxic drugs; on the contrary, when it is underexpressed they are more sensitive. Clinically, bcl-2 expression is associated with a poor prognosis in several cancers. Bcl-2 protein, p26-bcl-2, is located in the outer mitochondrial membrane, the nuclear envelope and the smooth endoplasmic reticulum. P26-bcl-2 is an antioxidant; this property could explain the anti-apoptotic activity since peroxides seem to be important mediators of apoptosis. Bcl-2 antisense oligonucleotides are able to reverse the apoptosis inhibition. New cancer treatments should take into account the expression of bcl-2.
Efficient Priming of CD4+ and CD8+ T Cells by DNA Vaccination Depends on Appropriate Targeting of Sufficient Levels of Immunologically Relevant Antigen to Appropriate Processing Pathways (2002)

The initial cellular events and interactions that occur following DNA immunization are likely to be key to determining the character and magnitude of the resulting immune response, and as such, a better understanding of these events could ultimately lead to the design of more effective pathogen-appropriate DNA vaccines. Therefore, we have used a variety of sensitive cell-based techniques to study the induction of adaptive immunity in vivo. We examined the efficacy of induction of Ag-specific CD4(+) and CD8(+) T cell responses in vivo by the adoptive transfer of fluorescently labeled Ag-specific TCR transgenic T cells and have demonstrated how such approaches can be used to study the effect of simple DNA construct manipulations on immunological priming. OVA-specific CD8(+) and CD4(+) T cells were activated and divided in vivo following immunization with DNA constructs that targeted OVA expression to different subcellular locations; however, the kinetics and degree of cell proliferation were dependent on the cellular location of the expressed protein. DNA vectors encoding cell-associated OVA resulted in greater CD8(+) T cell division compared with other forms of OVA. In contrast, soluble secreted OVA targeted to the classical secretory pathway enhanced division of CD4(+) T cells. Furthermore, the inclusion of mammalian introns to enhance protein expression increased the ability of poorly immunogenic forms of Ag to activate naive T cells, indicating that not only the location, but also the amount of Ag expression, is important for efficient T cell priming following DNA injection.
Grass Field Detection for TV Picture Quality Enhancement (2008)

Current TV image enhancement can be improved if the image is analyzed, objects of interest are segmented, and each segment is processed with content-specific enhancement algorithms. In this paper we present an algorithm for segmenting grass areas in video sequences. The system employs multi-scale texture analysis and adaptive color and position models for computing a pixel-based soft segmentation map. Compared to previously reported algorithms, our system shows a clear improvement in the detection result: at 10% false positive rate, the true positive rate of our algorithm yields 91%, vs. 66% and 58% of two existing methods.
Additive Protection against Congenital Cytomegalovirus Conferred by Combined Glycoprotein B/pp65 Vaccination Using a Lymphocytic Choriomeningitis Virus Vector (2016)

Subunit vaccines for prevention of congenital cytomegalovirus (CMV) infection based on glycoprotein B (gB) and pp65 are in clinical trials, but it is unclear whether simultaneous vaccination with both antigens enhances protection. We undertook evaluation of a novel bivalent vaccine based on nonreplicating lymphocytic choriomeningitis virus (rLCMV) vectors expressing a cytoplasmic tail-deleted gB [gB(dCt)] and full-length pp65 from human CMV in mice. Immunization with the gB(dCt) vector alone elicited a comparable gB-binding antibody response and a superior neutralizing response to that elicited by adjuvanted subunit gB. Immunization with the pp65 vector alone elicited robust T cell responses. Comparable immunogenicity of the combined gB(dCt) and pp65 vectors with the individual monovalent formulations was demonstrated. To demonstrate proof of principle for a bivalent rLCMV-based HCMV vaccine, the congenital guinea pig cytomegalovirus (GPCMV) infection model was used to compare rLCMV vectors encoding homologs of pp65 (GP83) and gB(dCt), alone and in combination versus Freund's adjuvanted recombinant gB. Both vectors elicited significant immune responses, and no loss of gB immunogenicity was noted with the bivalent formulation. Combined vaccination with rLCMV-vectored GPCMV gB(dCt) and pp65 (GP83) conferred better protection against maternal viremia than subunit or either monovalent rLCMV vaccine. The bivalent vaccine also was significantly more effective in reducing pup mortality than the monovalent vaccines. In summary, bivalent vaccines with rLCMV vectors expressing gB and pp65 elicited potent humoral and cellular responses and conferred protection in the GPCMV model. Further clinical trials of LCMV-vectored HCMV vaccines are warranted.
The IgE‐binding epitopes of rPar j 2, a major allergen of Parietaria judaica pollen, are heterogeneously recognized among allergic subjects (2000)

Pollen allergens are multivalent proteins that cross-link IgE antibodies on mast or basophil cells, inducing secretion of biologic mediators, and resulting in various allergic symptoms. The IgE-binding regions of the Parietaria judaica (Pj) pollen major allergen rPar j 2 were investigated. Twenty-nine single sera from Pj-allergic subjects were tested by Western blot against five recombinant peptides. At least four putative IgE-binding epitopes were identified. The analysis of their diffusion suggested a heterogeneous IgE-binding response. In fact, 75% of the sera reacted with peptide 1-54, 48% with peptide 48-101, 24% with peptide 1-30, 7% with peptide 29-54, and none with peptide 48-76. These five peptides were analyzed with the histamine-release assay. Only peptide 48-101 was capable of inducing degranulation and release of histamine. These results suggest that the recombinant rPar j 2 allergen contains IgE epitopes that are heterogeneously recognized by sensitive patients, and that therefore the therapeutic approach based on the use of haptenic peptides needs a careful evaluation.
Data analysis in multiple-frequency bioelectrical impedance analysis (1998)

The performance of three analytical methods for multiple-frequency bioelectrical impedance analysis (MFBIA) data was assessed. The methods were the established method of Cole and Cole, the newly proposed method of Siconolfi and co-workers and a modification of this procedure. Method performance was assessed from the adequacy of the curve fitting techniques, as judged by the correlation coefficient and standard error of the estimate, and the accuracy of the different methods in determining the theoretical values of impedance parameters describing a set of model electrical circuits. The experimental data were well fitted by all curve-fitting procedures (r = 0.9 with SEE 0.3 to 3.5% or better for most circuit-procedure combinations). Cole-Cole modelling provided the most accurate estimates of circuit impedance values, generally within 1-2% of the theoretical values, followed by the Siconolfi procedure using a sixth-order polynomial regression (1-6% variation). None of the methods, however, accurately estimated circuit parameters when the measured impedances were low (< 20 omega) reflecting the electronic limits of the impedance meter used. These data suggest that Cole-Cole modelling remains the preferred method for the analysis of MFBIA data.