gebhart/patrepeval huggingface dataset:
Molecular basis of the diversity of calcium channels in cardiovascular tissues (1997)

Voltage-dependent calcium (Ca2+) channels control a variety of physiological functions, such as excitation-contraction coupling in cardiac and smooth muscle. secretion of hormones and release of neurotransmitters. Studies on dissociated or cultured cells enabled us to compare their electrophysiological and pharmacological properties and their regulation in various tissues. Molecular genetics has provided a structural basis with which to observe the functional diversity of Ca2+ channels, which are composed of several subunits (alpha 1, alpha 2-delta, beta, gamma). Structure-function experiments, using expression in Xenopus oocytes, were designed to explain the molecular basis underlying this functional diversity. Six genes have been identified encoding the pore subunit (alpha 1) which determines the basic profile, i.e. the pharmacology of any Ca2+ channel. However, using a reconstitution model, the auxiliary subunits, but mainly beta subunits, for which four genes and several variants have been isolated, are able to modify the level of expression and the properties of a Ca2+ current directed by an alpha 1 subunit. Our structure-function studies are mainly designed to investigate the functional consequences of alpha 1-beta interaction on electrophysiological and pharmacological properties, especially in the case of cardiovascular Ca2+ channels. These studies should lead to a better understanding of the molecular basis underlying the differences between cardiac and vascular Ca2+ channels and also their implication in pathophysiology. Functional expression of the various combinations of subunit isoforms and identification of the precise oligomeric structure of voltage-dependent Ca2+ channels in specific cell types should help in the development of new therapeutic drugs.
Aβ immunization: Moving Aβ peptide from brain to blood (2001)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Safety, Pharmacokinetics, Pharmacodynamics, and Plasma Lipoprotein Distribution of Eritoran (E5564) during Continuous Intravenous Infusion into Healthy Volunteers (2004)

Eritoran, a structural analogue of the lipid A portion of lipopolysaccharide (LPS), is an antagonist of LPS in animal and human endotoxemia models. Previous studies have shown that low doses (350 to 3,500 microg) of eritoran have demonstrated a long pharmacokinetic half-life but a short pharmacodynamic half-life. The present study describes the safety, pharmacokinetics and pharmacodynamics, and lipid distribution profile of eritoran during and after a 72-h intravenous infusion of 500, 2,000, or 3,500 microg/h into healthy volunteers. Except for the occurrence of phlebitis, eritoran administration over 72 h was safe and well tolerated. Eritoran demonstrated a slow plasma clearance (0.679 to 0.930 ml/h/kg of body weight), a small volume of distribution (45.6 to 49.8 ml/kg), and a relatively long half-life (50.4 to 62.7 h). In plasma, the majority (approximately 55%) of eritoran was bound to high-density lipoproteins. During infusion and for up to 72 h thereafter, ex vivo response of blood to 1- or 10-ng/ml LPS was inhibited by > or =85%, even when the lowest dose of eritoran (500 microg/h) was infused. Inhibition of response was dependent on eritoran dose and the concentration of LPS used as an agonist. Finally, in vitro analysis with purified lipoprotein and protein fractions from plasma obtained from healthy volunteers indicated that eritoran is inactivated by high-density but not low-density lipoproteins, very-low-density lipoproteins, or albumin. From these results, we conclude that up to 252 mg of eritoran can be safely infused into normal volunteers over 72 h and even though it associates extensively with high-density lipoproteins, antagonistic activity is maintained, even after infusion ceases.
A MOBILE ROLE BASED ACCESS CONTROL SYSTEM USING IDENTITY BASED ENCRYPTION WITH NON-INTERACTIVE ZERO KNOWLEDGE PROOF OF AUTHENTICATION (2012)

Controlled access to confidential information and resources is a critical element in security systems. Role based access control (RBAC) has gained widespread usage in modern enterprise systems. Extensions have been proposed to RBAC for incorporating spatial constraints into such systems. Several solutions have been proposed for such models and much research has now been directed towards enforcing system policies. \nThe thesis proposes a security framework for RBAC systems with spatial constraints based on identity based encryption. Integration of identity based encryption and with zero knowledge proof is proposed to provide authentication and information security. We also show how Near Field Communication can be used to establish the integrity of a userâs proof of location. We discuss the design choices made in the protocol and explain the protocol implementation. Simulation results in Java validate our model. Furthermore, security analysis has been done to show how our framework protects against well-known attacks.
Black Market Botnets (2007)

Botnets have yet to be exploited to their full potential, because they have yet to take advantage of all the information available to them. The zombie computers that comprise a botnet have access to the private documents of the people that use the computers. A botmaster who controls the botnet can harvest the documents and sell them to third parties, creating a viable if illegal online business. We outline motivations for such a business model, as well as the mechanics of a possible implementation. We then present a variety of defenses against this scenario.
Single-molecule surface- and tip-enhanced raman spectroscopy (2010)

A review is given on single-molecule surface- and tip-enhanced Raman spectroscopy (SERS and TERS). It sketches the historical development along different routes toward huge near-field enhancements, the basis of single-molecule enhanced Raman spectroscopy; from SNOM to apertureless SNOM to tip-enhanced Raman spectroscopy (TERS) and microscopy; from SERS to single-molecule SERS to single-molecule TERS. The claim of extremely high enhancement factors of 1014 in single-molecule SERS is critically discussed, in particular in the view of recent experimental and theoretical results that limits the electromagnetic enhancement to ⩽ 1011. In the field of TERS only very few reports on single-molecule TERS exist: single-molecule TERS on dyes and on a protein (cytochrome c). In the latter case, TERS ‘sees’ even subunits of this protein, either amino-acids or the heme, depending on the orientation of the protein relative to the tip. The former case concerns the dye brilliant cresyl blue adsorbed either on a Au surface under ambient conditions or on a Au(111) surface in ultra high vacuum. These results indicate that significant progress is to be expected for TERS in general and for single-molecule TERS in particular.
Cyclopsychotride A, a Biologically Active, 31-Residue Cyclic Peptide Isolated from Psychotria longipes (1994)

A preliminary characterization is provided of a naturally occurring cyclic peptide with interesting and potent biological activity. A 31-residue cyclic peptide, designated cyclopsychotride A [1], was obtained from the organic extract of the tropical plant, Psychotria longipes. Compound 1 inhibited [125I] neurotensin (NT) binding to HT-29 cell membranes (IC50 3 microM) and also stimulated increased levels of cytosolic Ca2+ in two unrelated cell lines that do not express NT receptors. The peptide was found to dose-dependently increase intracellular Ca2+ at concentrations ranging from 3 to 30 microM, and this response was not blocked by a known NT antagonist. Cyclopsychotride A [1] possesses three disulfide linkages and is thought to be the largest cyclic peptide isolated from a natural source. Both 1H-nmr and cd spectroscopy showed 1 to be highly structured.
Designing Heterodimeric Two-stranded α-Helical Coiled-coils (2002)

The E/K coil, a heterodimeric coiled-coil, has been designed as a universal peptide capture and delivery system for use in applications such as biosensors and as an expression and affinity purification tag. In this design, heterodimer formation is specified through the placement of charged residues at the e and g positions of the heptad repeat such that the E coil contains all glutamic acid residues at these positions, and the K coil contains all lysine residues at these positions. The affinity and stability of the E/K coil have been modified to allow a greater range of conditions for association and dissociation. Increasing the hydrophobicity of the coiled-coil core, by substituting isoleucine for valine, gave increases in stability of 2.81 and 3.73 kcal/mol (0.47 kcal/mol/substitution). Increasing the alpha-helical propensity of residues outside the core, by substituting alanine for serine, yielded increases in stability of 2.68 and 3.28 kcal/mol (0.41 and 0.45 kcal/mol/substitution). These sequence changes yielded a series of heterodimeric coiled-coils whose stabilities varied from 6.8 to 11.2 kcal/mol, greatly expanding their scope for use in protein engineering and biomedical applications.
A Neural Attention Model for Abstractive Sentence Summarization (2015)

Summarization based on text extraction is inherently limited, but generation-style abstractive methods have proven challenging to build. In this work, we propose a fully data-driven approach to abstractive sentence summarization. Our method utilizes a local attention-based model that generates each word of the summary conditioned on the input sentence. While the model is structurally simple, it can easily be trained end-to-end and scales to a large amount of training data. The model shows significant performance gains on the DUC-2004 shared task compared with several strong baselines.
Aberrant methylation of TMS1 in small cell, non small cell lung cancer and breast cancer (2003)

TMS1 (target of methylation-induced silencing) is a CpG island-associated gene that functions in the regulation of apoptosis and encodes a caspase recruitment domain, a recently described motif found in apoptotic signaling molecules. Recent evidence suggests that silencing of genes in the apoptotic pathway contribute to human carcinogenesis. We examined the DNA methylation status of the TMS1 promoter in lung and breast tumor tissues, tumor cell lines and nonmalignant tissues by methylation-specific polymerase chain reaction (MSP) and its mRNA expression by reverse transcription PCR. Aberrant methylation of TMS1 was present in 70% (40 of 57) of small cell lung cancer (SCLC) cell lines and 41% (13 of 32) of SCLC tumor tissues, 48% (29 of 61) of non small cell lung cancer (NSCLC) cell lines and 40% (28 of 70) of NSCLC tumor tissues and 46% (12 of 26) of breast cancer cell lines and 32% (20 of 63) of breast tumor tissues. Methylation was absent in the peripheral blood lymphocytes and buccal epithelium from healthy volunteers, as well as in nonmalignant lung tissues and was rare in nonmalignant breast tissues 7% (2 of 30). DNA methylation was confirmed by sequence analysis and the methylation status correlated inversely with TMS1 RNA expression in 18 cell lines tested. RNA expression was restored by treatment with the demethylating agent 5-aza-2'-deoxycytidine, in 4 of 4 methylated cell lines that lacked the TMS1 transcript. Our results suggest that methylation of TMS1 may play a role in the pathogenesis of small cell and non small lung and breast cancers.
Nuclear envelope defects associated withLMNAmutations cause dilated cardiomyopathy and Emery-Dreifuss muscular dystrophy (2001)

Nuclear lamin A and C alleles that are linked to three distinct human diseases have been expressed both in HeLa cells and in fibroblasts derived from Lmna null mice. Point mutations that cause dilated cardiomyopathy (L85R and N195K) and autosomal dominant Emery-Dreifuss muscular dystrophy (L530P) modify the assembly properties of lamins A and C and cause partial mislocalization of emerin, an inner nuclear membrane protein, in HeLa cells. At the same time, these mutant lamins interfere with the targeting and assembly of endogenous lamins and in this way may cause significant changes in the molecular organization of the nuclear periphery. By contrast, lamin A and C molecules harboring a point mutation (R482W), which gives rise to a dominant form of familial partial lipodystrophy, behave in a manner that is indistinguishable from wild-type lamins A and C, at least with respect to targeting and assembly within the nuclear lamina. Taken together, these results suggest that nuclear structural defects could contribute to the etiology of both dilated cardiomyopathy and autosomal dominant Emery-Dreifuss muscular dystrophy.
Aromatase inhibitors in men: effects and therapeutic options (2011)

Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men Therefore, aromatase inhibitors may be used to increase adult height in boys with gonadotropin-independent precocious puberty, idiopathic short stature and constitutional delay of puberty. Long-term efficacy and safety of the use of aromatase inhibitors has not yet been established in males, however, and their routine use is therefore not yet recommended.
Tactile mapping of palpable abnormalities for breast cancer diagnosis (2003)

This paper presents the development of a prototype tactile mapping device (TMD) system comprised mainly of a tactile sensor array probe, a 3D camera and a force/torque sensor, which can provide the means to produce tactile maps of the breast lumps during a breast palpation. Focusing on the key tactile topology features from breast palpation such as spatial location, size and shape of the detected lesion, and the force levels used to demonstrate the palpable abnormalities, these maps can record the results of clinical breast examination with a set of pressure distribution profiles and force sensor measurements due to detected lesion. These maps will serve as an objective documentation of palpable lesions for future comparative examinations. Preliminary results of simulated experiments and limited pre-clinical evaluations of the TMD prototype have pilot-tested our hypothesis and provided solid promising data showing the feasibility of the TMD in real clinical applications.
Unoccupied molecular orbital states of tris (8-hydroxy quinoline) aluminum: Observation and dynamics (1997)

Electrons photoexcited into the normally unoccupied states of vacuum deposited thin films of tris (8-hydroxy quinoline) aluminum (Alq) have been studied with excite-probe harmonic laser photoemission. Both valence and transiently excited empty states are observed. A surface recombination velocity of 75±30 cm/s has been determined.
Comparative modelling and analysis of amino acid substitutions suggests that the family of pregnancy-associated glycoproteins includes both active and inactive aspartic proteinases (1996)

The pregnancy-associated glycoproteins (PAGs) are secretory products synthesized by the outer epithelial cell layer (chorion) of the placentas of various ungulate species. The amino acid sequences of eight PAGs have been inferred from cloned cDNA of cattle and sheep, as well as of the non-ruminant pig and horse. We compare the PAG sequences and present results of the three-dimensional models of boPAG-1 and ovPAG-1 that were constructed on the basis of the crystal structures of homologous porcine pepsin and bovine chymosin using a rule-based comparative modelling approach. Further, we compare peptide binding subsites defined by interactions with pepstatin and a decapeptide inhibitor (CH-66) modelled on the basis of crystal structures of other aspartic proteinases. We have extended our analysis of the peptide binding subsites to the other PAG molecules of known sequence by aligning the PAG sequences to the structural template derived from the pepsin family and by making use of the three-dimensional models of the boPAG-1 and ovPAG-1. The residues that are likely to affect peptide binding in the boPAG-1, ovPAG-1 and other PAG molecules have been identified. Sequence comparisons reveal that all PAG molecules may have evolved from a pepsin-like progenitor molecule with the equine PAG most closely related to the pepsins. The presence of substitutions at the S1 and other subsites relative to pepsin make it unlikely that either bovine, ovine or the porcine PAG-1 have catalytic activity. Only two of the eight PAGs examined (porcine PAG-2 and equine PAG-1) retain features of active aspartic proteinases with pepsin-like activity. Our results indicate that in the PAGs so far characterized the peptide binding specificities differ significantly from each other and from pepsin, despite their high sequence identities. Analysis of the various peptide binding subsites demonstrates why both bovine and ovine PAG-1 are capable of binding pepstatin. The strong negative charge in the binding cleft of boPAG-1 and ovPAG-1 indicates a preference for lysine- or arginine-rich peptides. PAGs represent a family where the possible peptide binding function may be retained through their binding specificities, but where the catalytic activity may be lost in some cases, such as the boPAG-1, ovPAG-1 and the poPAG-1.
Density of Demodex folliculorum in rosacea: a case-control study using standardized skin-surface biopsy (1993)

A standardized skin-surface biopsy (1 cm2) of the check was performed in 49 patients with rosacea [13 with erythemato-telangiectatic rosacea (ETR), three with squamous rosacea (SR), 33 with papulopustular rosacea (PPR)], and 45 controls. A mean density of 0.7 Demodex folliculorum/cm2 was found in controls, 98% of whom had less than five Demodex/cm2. When all clinical types of rosacea were considered collectively, the density of Demodex was significantly higher in patients with rosacea than in controls (mean = 10.8/cm2; P < 0.001). When the various clinical types of rosacea were considered separately, Demodex density was statistically significantly higher than in controls only in the PPR patients (mean = 12.8/cm2; P < 0.001). The same type of comparison was also made for three other groups of subjects--patients with isolated inflammatory papules (n = 4), rhinophyma (n = 3), and HIV infection (n = 21), respectively: in these groups, the Demodex density did not differ significantly from controls. The present study demonstrates a high density of D. folliculorum in PPR, and supports its pathogenic role in the papulopustular phase of rosacea. The study suggests that standardized surface biopsy could be a useful diagnostic tool for PPR, with a 98% specificity when Demodex density is higher than 5/cm2.
Accurate and Robust Quantification of Circulating Fetal and Total DNA in Maternal Plasma from 5 to 41 Weeks of Gestation (2004)

The high sensitivity of PCR-based detection, together with quantification provided by real-time DNA analysis, has clear potential for clinical application in noninvasive prenatal diagnosis. However, accurate quantification using best-fit data analysis, standardization of methods, and performance control indicators are necessary for robust routine noninvasive diagnostics.
Gain in erbium-doped fiber amplifiers: a simple analytical solution for the rate equations (1990)

The solution of the rate equations that describe an erbium-doped fiber amplifier is investigated, and the possibility of obtaining an analytical solution for several field and erbium transverse distributions in the active fiber is determined. With the obtained equations it is possible to find directly the signal gain and the main parameters that influence it. The validity of this research is extended to the case of high signal power.
Dose–Response Efficacy of a Proprietary Probiotic Formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for Antibiotic-Associated Diarrhea and Clostridium difficile -Associated Diarrhea Prophylaxis in Adult Patients (2010)

The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov number NCT00958308).
Block copolymer conjugated Au-coated Fe3O4 nanoparticles as vectors for enhancing colloidal stability and cellular uptake (2017)

Precisely engineered architectures based on neutral-cationic block copolymer-conjugated heterogeneous NPs provide a valuable strategy for improving the applicability and efficacy of synthesized vectors.
OmpR Regulates the Two-Component System SsrA-SsrB in Salmonella Pathogenicity Island 2 (2000)

Salmonella pathogenicity island 2 (SPI-2) encodes a putative, two-component regulatory system, SsrA-SsrB, which regulates a type III secretion system needed for replication inside macrophages and systemic infection in mice. The sensor and regulator homologs, ssrAB (spiR), and genes within the secretion system, including the structural gene ssaH, are transcribed after Salmonella enters host cells. We have studied the transcriptional regulation of ssrAB and the secretion system by using gfp fusions to the ssrA and ssaH promoters. We found that early transcription of ssrA, after entry into macrophages, is most efficient in the presence of OmpR. An ompR mutant strain does not exhibit replication within cultured macrophages. Furthermore, footprint analysis shows that purified OmpR protein binds directly to the ssrA promoter region. We also show that minimal medium, pH 4.5, induces SPI-2 gene expression in wild-type but not ompR mutant strains. We conclude that the type III secretion system of SPI-2 is regulated by OmpR, which activates expression of ssrA soon after Salmonella enters the macrophage.
Macrophage inhibitory factor 1 acts as a potential biomarker in patients with esophageal squamous cell carcinoma and is a target for antibody‐based therapy (2013)

Macrophage inhibitory factor 1 (MIC1) is frequently altered in various cancers. The aim of this study was to investigate the clinical significance of MIC1 for esophageal squamous cell carcinoma (ESCC). Serum MIC1 of 286 ESCC and 250 healthy subjects was detected, the diagnostic performance was assessed and compared with SCC, CEA, CA199 and CA724, and the value as a prognostic indicator was also evaluated. The expression of MIC1 in ESCC cell lines, tissues were detected, and the inhibition of MIC1 antibody on ESCC was carried out in vitro and in vivo. The results showed that the serum MIC1 of ESCC was significantly higher than normal groups (P < 0.001), and was positively associated with tumor invasion (P = 0.030) as well as lymph node metastasis (P = 0.007). The sensitivity of MIC1 was significantly better than SCC, CEA, CA199 and CA724, especially for stage I ESCC. Patients with higher serum MIC1 also had a poorer prognosis in relapse-free (P = 0.050) and tumor-specific survival (P = 0.005). In vitro studies showed that the expression of MIC1 was upregulated in 37.5% (3/8) ESCC cell lines and 45% (18/40) tissues, and the transcription of MIC1 in tumor tissues was significantly higher than paired adjacent normal tissues (P = 0.001). The antibody of MIC1 inhibited the tumor growth (P < 0.001), and showing preference for tumor tissues in xenograft model. The decreased formation of neovascularization lumen may be involved in the mechanism. We conclude that MIC1 plays an important role in the progression of ESCC and can serve as a potential biomarker and therapeutic target for ESCC.