gebhart/patrepeval huggingface dataset:
The ion channel of the nicotinic acetylcholine receptor is formed by the homologous helices M II of the receptor subunits (1986)

A binding site for the channel-blocking noncompetitive antagonist [3H]triphenylmethylphosphonium ([3H]TPMP+) was localized in the alpha-, beta- and delta-chains of the nicotinic acetylcholine receptor (AChR) from Torpedo marmorata electric tissue. The photolabel was found in homologous positions of the highly conserved sequence helix II, alpha 248, beta 254, and delta 262. The site of the photoreaction appears to not be affected by the functional state of the receptor. [3H]TPMP+ was found in position delta 262 independent of whether photolabeling was performed with the receptor in its resting, desensitized or antagonist state. A model of the AChR ion channel is proposed, according to which the channel is formed by the five helices II contributed by the five receptor subunits.
Apodization functions in Fourier transform ion mobility spectrometry (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTApodization functions in Fourier transform ion mobility spectrometryRobert H. St. Louis, William F. Siems, and Herbert H. HillCite this: Anal. Chem. 1992, 64, 2, 171–177Publication Date (Print):January 15, 1992Publication History Published online1 May 2002Published inissue 15 January 1992https://pubs.acs.org/doi/10.1021/ac00026a015https://doi.org/10.1021/ac00026a015research-articleACS PublicationsRequest reuse permissionsArticle Views256Altmetric-Citations31LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Qualitative differences in estrogenic/antiestrogenic effects of clomiphene and zuclomiphene. (1992)

Depending upon the rat assay end point, the estrogenic or antiestrogenic activity of clomiphene (CC) or its isomer, zuclomiphene (Zu), varies considerably. For uterine/body weight ratio, Zu = estradiol greater than CC; for the estrogenic effect on uterine epithelium, Zu greater than estradiol = CC; higher CC doses were antiestrogenic. For endometrial stroma, Zu = estradiol much greater than CC. In the effect of estrogen receptor, low-dose CC = estradiol; high-dose CC was antiestrogenic. For Zu, both doses were about equal and highly antiestrogenic. Essentially the same was seen with progesterone receptor. For plasma LH suppression, Zu much greater than CC much greater than estradiol; but for plasma FSH, estradiol much greater than CC = Zu. The intrinsic estrogenicity of these compounds was made more apparent by the castrate status of the rats. This spectrum of activities may make it possible to select estrogenic or antiestrogenic activities for clinical purposes, depending upon the end-organ effect desired.
IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach. (1998)

Overexpression of proinflammatory, type 1 cytokines has been demonstrated in psoriasis and is believed to be of pathophysiological importance. IL-10 is a type 2 cytokine with major impact on immunoregulation, since it inhibits type 1/proinflammatory cytokine formation. Therefore, we investigated its role in psoriasis. We found a relative deficiency in cutaneous IL-10 mRNA expression compared with other inflammatory dermatoses. Interestingly, patients during established antipsoriatic therapy showed higher IL-10 mRNA expression of peripheral blood mononuclear cells than patients before therapy. This suggested that IL-10 may have antipsoriatic capacity. Therefore, we performed a phase 2 pilot trial with subcutaneous IL-10 administration (8 microg/kg/d) over 24 d in three patients. Clinical efficiency measured by objective and subjective parameters was found. Immunosuppressive effects (depressed monocytic HLA-DR expression, TNF-alpha and IL-12 secretion capacity, IL-12 plasma levels, and responsiveness to recall antigens) as well as a shift toward a type 2 cytokine pattern (increasing proportion of IL-4, IL-5, and IL-10 producing T cells, selective increase in IgE serum levels) were observed. Remarkably, IL-10 administration also enhanced the intracutaneous IL-10 mRNA expression. Our investigations demonstrate the major importance of IL-10 in psoriasis and show that IL-10 administration represents a new therapeutic approach. This is the first report on IL-10 therapy for cutaneous disorders.
Cross-linking of CD4 and CD8 with the T-cell receptor complex: (1988)

The T-cell differentiation antigens CD4 and CD8 have been attributed functions as accessory molecules. Based on antibody cross-linking studies, F. Emmrich discusses a putative role for these ant~ens in contributing a positive signal during T-cell activation and the possibility of a quaternary complex involved i,~ T-cell activation. These differentiation antigens may also influence T-cell repertoire selection in the thymus.
A new faster sphere decoder for MIMO systems (2004)

The sphere decoding technique is an efficient fast algorithm for maximum likelihood (ML) detection. In this paper, we propose a new and faster sphere decoding algorithm for multiple-input multiple-output (MIMO) systems, where it's complexity is much less than the conventional algorithm. In our method, the initial selection of the sphere radius is not important. It is shown that both the performance and the complexity of the proposed algorithm are simultaneously controlled by two parameters. Therefore, there is a trade-off between the performance and the complexity in the proposed algorithm. By computer simulations, we have shown that the performance of our method is very close to ML decoding algorithm. Furthermore, if we tolerate some degradation in the performance, we can speed up the proposed algorithm to ten times. Our results have shown that even in the fastest case, the novel decoder outperforms the V-BLAST decoding algorithm.
Sustaining the silicon revolution: From 3-D transistors to 3-D integration (2015)

Technological pathways for sustaining continual improvement in silicon integrated-circuit “chip” functionality at ever lower cost and energy per function, toward the vision of the Internet of Everything, are discussed.
Nonsteroidal Anti-inflammatory Drugs as Anticancer Agents: Mechanistic, Pharmacologic, and Clinical Issues (2002)

Numerous experimental, epidemiologic, and clinical studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the highly selective cyclooxygenase (COX)-2 inhibitors, have promise as anticancer agents. NSAIDs restore normal apoptosis in human adenomatous colorectal polyps and in various cancer cell lines that have lost adenomatous polyposis coli gene function. NSAIDs also inhibit angiogenesis in cell culture and rodent models of angiogenesis. Many epidemiologic studies have found that long-term use of NSAIDs is associated with a lower risk of colorectal cancer, adenomatous polyps, and, to some extent, other cancers. Two NSAIDs, sulindac and celecoxib, have been found to inhibit the growth of adenomatous polyps and cause regression of existing polyps in randomized trials of patients with familial adenomatous polyposis (FAP). However, unresolved questions about the safety, efficacy, optimal treatment regimen, and mechanism of action of NSAIDs currently limit their clinical application to the prevention of polyposis in FAP patients. Moreover, the development of safe and effective drugs for chemoprevention is complicated by the potential of even rare, serious toxicity to offset the benefit of treatment, particularly when the drug is administered to healthy people who have low annual risk of developing the disease for which treatment is intended. This review considers generic approaches to improve the balance between benefits and risks associated with the use of NSAIDs in chemoprevention. We critically examine the published experimental, clinical, and epidemiologic literature on NSAIDs and cancer, especially that regarding colorectal cancer, and identify strategies to overcome the various logistic and scientific barriers that impede clinical trials of NSAIDs for cancer prevention. Finally, we suggest research opportunities that may help to accelerate the future clinical application of NSAIDs for cancer prevention or treatment.
Tilted alignment of MBBA induced by short-chain surfactants (1976)

Alignments induced by short chained surfactants in MBBA are observed : tilted orientations with different tilt angles. The anchoring energies associated with this type of alignment are approximately measured. In the last section, interpretations of the rather complex mechanisms involved are proposed.
The reactivity of α‐chymotrypsin immobilized on radiation‐grafted hydrogel surfaces (1977)

Abstract The enzymatic activity of α‐chymotrypsin (CT), immobilized on hydrogelcoated polymer film supports, has been investigated. The support was prepared by radiation‐graft copolymerization of 2‐hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAAc) on silicone rubber films. The enzyme was covalently coupled to the carboxylic group of MAAc via the N ‐hydroxysuccinimide (NHS) ester active intermediate. Increasing MAAc contents of the hydrogel resulted in increased attachment of CT. The integrity of the CT active site after attachment was assessed by an active site titration with diisopropyl fluorophosphate (DFP). As the MAAc content of the hydrogel was increased, an increasing fraction of the attached CT retained its activity to DFP. A greater fraction of CT was active towards DFP when adsorbed than when coupled. The rates of hydrolysis of some synthetic model substrates by the immobilized CT were also measured. The negative charge on the hydrogel had a large effect on the rates of these hydrolyses. The pH optimum for the hydrolysis of N ‐acetyl‐ L ‐tyrosine ethyl ester (ATEE) by immobilized CT was higher than that of free CT. Increasing MAAc content of the hydrogel resulted in larger shifts in the pH optimum. The maximum rates of ATEE hydroylsis per mg CT declined sharply with increasing MAAc content of the hydrogel. This is probably related to the increasing repulsive force between the ATEE (negatively charged above ⋍ pH 9.5) and the hydrogel with increasing MAAc content. The activity of immobilized CT to ATEE is small compared to that of free CT, partly due to this charge effect. Conversely, the rate of hydrolysis of BAEE, a positively charged substrate, by immobilized CT at pH 11, is almost fourfold greater than that by free CT at its pH optimum.
Tsp: a tail-specific protease that selectively degrades proteins with nonpolar C termini. (1992)

An Escherichia coli protease designated Tsp (tail-specific protease) has been purified, and its gene has been cloned and sequenced. Tsp specifically degrades a variant of the N-terminal domain of lambda repressor in which the five C-terminal residues, which are polar in wild type, have been replaced by nonpolar residues. This substrate specificity in vitro parallels the previously reported selective degradation in vivo of N-terminal-domain variants with nonpolar C-terminal residues. The gene sequence and N-terminal protein sequence of Tsp predict a protein of 660 amino acids. The deduced protein sequence of Tsp shows no significant homology to known protease sequences but does show sequence similarity to the human and bovine interphotoreceptor retinoid-binding proteins, which bind hydrophobic ligands.
Design and Development of Multiparticulate System for Targeted Drug Delivery to Colon (2004)

A multiparticulate system combining pH-sensitive property and specific biodegradability for colon-targeted delivery of metronidazole has been investigated. Cross-linked chitosan microspheres were prepared from an emulsion system using liquid paraffin as the external phase and solution of chitosan in acetic acid as the disperse phase. The multiparticulate system was prepared by coating cross-linked chitosan microspheres exploiting Eudragit L-100 and S-100 as pH-sensitive polymers. Morphology and surface characteristics of the formulations were determined by scanning electron microscopy. Particle size of the chitosan microspheres was determined by optical microscopy while that of coated microspheres was determined by particle size analyzer. In vitro drug-release studies were performed in conditions simulating stomach-to-colon transit in presence and absence of rat caecal contents. The size of the microspheres was small and they were efficiently microencapsulated within Eudragit microspheres, forming a multireservoir system. By coating the microspheres with Eudragit pH-dependant release profiles were obtained. No release was observed at acidic pH; however, when it reached the pH where Eudragit starts solublizing there was continuous release of drug from the formulation. Further, the release of drug was found to be higher in the presence of rat caecal contents, indicating the susceptibility of chitosan matrix to colonic enzymes released from rat caecal contents.
Involvement of human interleukin 6 in experimental cachexia induced by a human uterine cervical carcinoma xenograft. (1995)

A human tumor xenograft model for cancer cachexia was established by growing a uterine cervical carcinoma, Yumoto, in nude mice. The tumor transplanted into the mice induced severe body weight loss (30% of body weight) when the tumor weight was only 1 g. In addition, other indicators for cachexia, such as adipose tissue and muscle wasting and hypoglycemia, were also observed in the tumor-bearing mice, suggesting that this is a proper model for experimental cachexia induced by a human tumor. We then examined the association of this model with various cytokines, such as tumor necrosis factor alpha, interleukin (IL)-1alpha, IL-1beta, IFN-gamma, IL-6, and leukemia inhibitory factor, and identified human IL-6, which was produced by the tumor cells, as a mediator of cachexia. A neutralizing antibody against hIL-6 administered to the mice after the development of cachexia symptoms significantly improved body weight loss, adipose tissue wasting, hypoglycemia, acute phase reaction, and leukocytosis, although it did not suppress the tumor growth. These results demonstrate that the hIL-6 produced by the tumor cells is an essential mediator of the cachexia induction in this model.
Surface Modification of Functional Nanoparticles for Controlled Drug Delivery (2003)

Abstract Surface‐modified nanoparticles have received much attention as drug carriers. Natural and synthetic polymers are used as the materials to prepare nanoparticles and the properties of these nanoparticles originate with these polymeric materials. In particular, these nanoparticles are modified for specific objectives. The surface characteristics of (shell) nanoparticles are more important than those of the core, because the shell layer directly contacts body fluids and organs. Generally, the nanoparticles are coated with hydrophilic polymer to give long circulation and/or are conjugated with functional ligands or proteins for site‐specific delivery. In this review, the preparative methods and the applications of surface modification of polymeric functionalized nanoparticles for long‐circulation, site‐specific delivery, and oral delivery are discussed.
Nanoengineered multimodal contrast agent for medical image guidance (2005)

Multimodality imaging has gained momentum in radiation therapy planning and image-guided treatment delivery. Specifically, computed tomography (CT) and magnetic resonance (MR) imaging are two complementary imaging modalities often utilized in radiation therapy for visualization of anatomical structures for tumour delineation and accurate registration of image data sets for volumetric dose calculation. The development of a multimodal contrast agent for CT and MR with prolonged <i>in vivo</i> residence time would provide long-lasting spatial and temporal correspondence of the anatomical features of interest, and therefore facilitate multimodal image registration, treatment planning and delivery. The multimodal contrast agent investigated consists of nano-sized stealth liposomes encapsulating conventional iodine and gadolinium-based contrast agents. The average loading achieved was 33.5 ± 7.1 mg/mL of iodine for iohexol and 9.8 ± 2.0 mg/mL of gadolinium for gadoteridol. The average liposome diameter was 46.2 ± 13.5 nm. The system was found to be stable in physiological buffer over a 15-day period, releasing 11.9 ± 1.1% and 11.2 ± 0.9% of the total amounts of iohexol and gadoteridol loaded, respectively. 200 minutes following <i>in vivo</i> administration, the contrast agent maintained a relative contrast enhancement of 81.4 ± 13.05 differential Hounsfield units (&#916;HU) in CT (40% decrease from the peak signal value achieved 3 minutes post-injection) and 731.9 ± 144.2 differential signal intensity (&#916;SI) in MR (46% decrease from the peak signal value achieved 3 minutes post-injection) in the blood (aorta), a relative contrast enhancement of 38.0 ± 5.1 &#916;HU (42% decrease from the peak signal value achieved 3 minutes post-injection) and 178.6 ± 41.4 &#916;SI (62% decrease from the peak signal value achieved 3 minutes post-injection) in the liver (parenchyma), a relative contrast enhancement of 9.1 ± 1.7 &#916;HU (94% decrease from the peak signal value achieved 3 minutes post-injection) and 461.7 ± 78.1 &#916;SI (60% decrease from the peak signal value achieved 5 minutes post-injection) in the kidney (cortex) of a New Zealand white rabbit. This multimodal contrast agent, with prolonged <i>in vivo</i> residence time and imaging efficacy, has the potential to bring about improvements in the fields of medical imaging and radiation therapy, particularly for image registration and guidance.
1,25(OH)2 vitamin D3 stimulates membrane phosphoinositide turnover, activates protein kinase C, and increases cytosolic calcium in rat colonic epithelium. (1990)

The hormonal form of vitamin D, 1,25(OH)2 vitamin D3 [1,25(OH)2D3], regulates colonic calcium absorption and colonocyte proliferation and differentiation. In this study, we have examined the effect of 1,25(OH)2D3 on membrane phosphoinositide turnover, protein kinase C activation, and regulation of intracellular calcium concentration [( Ca+2]i) in isolated rat colonic epithelium. In a concentration-dependent manner, 1,25(OH)2D3 stimulated breakdown of membrane phosphoinositides within 15 s, generating diacylglycerol and inositol 1,4,5-triphosphate (IP3). 1,25(OH)2D3 rapidly activated colonic protein kinase C, with maximal translocation of activity from the cytosol to the membrane occurring within 1 min of exposure to the secosteroid. Studies performed in isolated colonocytes with the fluorescent dye fura-2 demonstrated that 10(-8) M 1,25(OH)2D3 caused a rapid rise in [Ca+2]i which then transiently decreased before rising to a new plateau value. When these experiments were performed in a calcium-free buffer, an increase in [Ca+2]i was observed, but both the transient and secondary rise were diminished in magnitude, suggesting that 1,25(OH)2D3 may stimulate both release of intracellular calcium stores and calcium influx. 1,25(OH)2D3 stimulated [3H]thymidine uptake in rat colonocytes, 4 h after an in vivo injection. These studies indicate that 1,25(OH)2D3 exerts a rapid influence on membrane phosphoinositide metabolism which may mediate certain of the secosteroid's effects on colonocyte calcium transport and proliferation.
Magnetic resonance diffraction using the magnetic field from a ferromagnetic sphere (2002)

The theory of magnetic resonance diffraction is developed for the case of a crystal in close proximity of a ferromagnetic sphere. Distinct spectral peaks in the magnetic resonance signal are discovered for the specific ferromagnetic sphere and magnetic field configurations, and the appearance of the peaks is a direct signature of the presence of discrete atomic sites in the crystal lattice. The positions of the spectral peaks are sensitive to the crystal unit-cell size, thereby providing a method for determination of the basic parameters of the crystal at the atomic scale. The appearance of the spectral peaks is explained, and the dependence of the magnetic resonance spectra on the sphere size and the angle of the sphere magnetization with respect to the sample surface is analyzed. Applications to the studies of crystals, thin films, and crystallites are reviewed, and potential measurement methods for the confirmation of the diffraction theory are proposed. The analysis suggests that the long-desired goal of detecting atomic resolution magnetic resonance diffraction is well within reach of current experimental techniques.
Direct Association of the Gap Junction Protein Connexin-43 with ZO-1 in Cardiac Myocytes (1998)

The gap junction protein connexin-43 is normally located at the intercalated discs of cardiac myocytes, and it plays a critical role in the synchronization of their contraction. The mechanism by which connexin-43 is localized within cardiac myocytes is unknown. However, localization of connexin-43 likely involves an interaction with the cytoskeleton; immunofluorescence microscopy showed that in cardiac myocytes, connexin-43 specifically colocalizes with the cytoskeletal proteins ZO-1 and alpha-spectrin. In transfected HEK293 cells, immunoprecipitation experiments using coexpressed epitope-tagged connexin-43 and ZO-1 indicated that ZO-1 links connexin-43 with alpha-spectrin. The domains responsible for the protein-protein interaction between connexin-43 and ZO-1 were identified using affinity binding assays with deleted ZO-1 and connexin-43 fusion proteins. Immunoblot analysis of associated proteins showed that the C-terminal domain of connexin-43 binds to the N-terminal domain of ZO-1. The role of this linkage in gap junction formation was examined by a dominant-negative assay using the N-terminal domain of ZO-1. Overexpression of the N-terminal domain of ZO-1 in connexin-43-expressing cells resulted in redistribution of connexin-43 from cell-cell interfaces to cytoplasmic structures; this intracellular redistribution of connexin-43 coincided with a loss of electrical coupling. We therefore conclude that the linkage between connexin-43 and alpha-spectrin, via ZO-1, may serve to localize connexin-43 at the intercalated discs, thereby generating functional gap junctions in cardiac myocytes.
Ultraviolet upconversion fluorescence in rare-earth-ion-doped Y_2O_3 induced by infrared diode laser excitation (2006)

Room-temperature ultraviolet emission of Tm(3+) ions at 298 ((1)I(6)-->(3)H(6)), 364 ((1)D(2)-->(3)H(6)), and 391 nm ((1)I(6)-->(3)H(5)) was obtained in Y(2)O(3):Yb(3+)-Tm(3+) by continuous-wave diode laser excitation of 980 nm. Power dependence analysis demonstrates that five- and six-photon upconversion processes populate the (1)D(2) and (1)I(6) states, respectively. We believe that the (1)D(2) population originates from the cross relaxation (1)G(4)+(3)F(4)-->(3)H(4)+(1)D(2) of the Tm(3+) ions, while subsequent energy transfer from Yb(3+) to Tm(3+) excites the (1)D(2) state to the upper (1)I(6) state. High multiphoton-induced ultraviolet emission is also expected for other trivalent rare-earth ions similar to Tm(3+).