gebhart/patrepeval huggingface dataset:
Quantitative Computed Tomography Scanning for Measurement of Bone and Bone Marrow Fat Content (1987)

Quantitative CT (QCT) has become a popular method for estimating bone mineral content. In addition, QCT can be used to estimate the fat content of trabecular bone. Although the latter has received little attention, it may prove to be clinically significant. Using a set of custom-built, tissue-mimicking plastic inserts in an anthropomorphic phantom, we tested a variety of methods for estimating mineral and fat content. We also investigated the influence of patient size, reconstruction circle size, and reference phantom choice on the accuracy of the results. Best estimates were obtained when there was a match between patient and reconstruction circle size. Single-energy methods yielded the best estimates of mineral content for inserts that did not contain fat, and dual-energy methods yielded the best estimates for inserts that contained fat. A dual-energy method that we developed was best in estimating the mineral and fat content of the latter inserts. We found that an external calibration reference phantom containing aqueous solutions of K2HPO4 could be used satisfactorily to estimate the mineral content of trabecular bone mimicking inserts; however, more representative materials must be used for accurate estimates of fat content.
MAGEA4 induces growth in normal oral keratinocytes by inhibiting growth arrest and apoptosis (2012)

Cancer testis antigens (CTAs) are proteins that are normally expressed only in male germ cells and are aberrantly upregulated in a variety of cancers such as melanomas and lung cancer. MAGEA proteins belong to Class I CTAs and are being utilized as targets for cancer immunotherapy. Despite the discovery of the first CTA (MAGEA1) 20 years ago, the functions of these proteins remain poorly understood and evidence suggests both oncogenic as well as tumor suppressive roles for these proteins. Herein, we investigated the role of MAGEA4 in promoting cell growth. When overexpressed, MAGEA4 promotes growth of spontaneously transformed normal oral keratinocytes (NOK-SI). To understand the mechanism of growth stimulation by MAGEA4, we explored the effect of overexpressing MAGEA4 on cell cycle and apoptosis. MAGEA4 inhibits growth arrest of cells in the G1 phase of the cell cycle. We also found that overexpression of MAGEA4 inhibits G418-induced apoptosis of NOK-SI cells. Interestingly, this inhibition was accompanied by repression of two p53 downstream genes, BAX and CDKN1A. Our results indicate that MAGEA4 promotes growth by preventing cell cycle arrest and by inhibiting apoptosis mediated by the p53 transcriptional targets.
Psychophysical elements of wearability (2007)

Wearable technology presents a wealth of new HCI issues. In particular, this paper addresses the impact of the physical interaction between the user's body and the device's physical form on the user's mental representation of self and cognitive abilities, a blend of HCI and ergonomics that is unique to wearable computing. We explore the human sensory mechanisms that facilitate perception of worn objects and the elements of sensation that influence the comfort of worn objects, and discuss the psychological elements that may cause worn objects to be forgotten or detected, wearable or not. We discuss the implications of un-wearability on attention and cognitive capability.
Secondary structure of component 8c-1 of α-keratin. An analysis of the amino acid sequence (1986)

The amino acid sequence of component 8c-1 from alpha-keratin was analysed by using secondary-structure prediction techniques, homology search methods, fast Fourier-transform techniques to detect regularities in the linear disposition of amino acids, interaction counts to assess possible modes of chain aggregation and assessment of hydrophilicity distribution. The analyses show the following. The molecule has two lengths of coiled-coil structure, each about 20 nm long, one from residues 56-202 with a discontinuity from about residue 91 to residue 101, and the other from residues 219-366 with discontinuities from about residue 238 to residue 245 and at about residue 306. The acidic and basic residues in the coiled-coil segment between residues 102 and 202 show a 9,4-residue structural period in their linear disposition, whereas between residues 246 and 366 a period of 9.9 residues is observed in the positioning of ionic residues. Acidic and basic residues are out of phase by 180 degrees. Similar repeats occur in corresponding regions of other intermediate-filament proteins. The overall mean values for the repeats are 9.55 residues in the N-terminal region and 9.85 residues in the C-terminal region. The regions at each end of the protein chain (residues 1-55 and 367-412) are not alpha-helical and contain many potential beta-bends. The regions specified in have a significant degree of homology mainly due to a semi-regular disposition of proline and half-cystine residues on a three-residue grid; this is especially apparent in the C-terminal segment, in which short (Pro-Cys-Xaa)n regions occur. The coiled-coil segments of component 8c-1 bear a striking similarity to corresponding segments of other intermediate-filament proteins as regards sequence homology, structural periodicity of ionic residues and secondary/tertiary-structure predictions. The assessments of the probabilities that these homologies occurred by chance indicate that there are two populations of keratin filament proteins. The non-coiled-coil regions at each end of the chain are less hydrophilic than the coiled-coil regions. Ionic interactions between the heptad regions of components 8c-1 and 7c from the microfibrils of alpha-keratin are optimized when a coiled-coil structure is formed with the heptad regions of the constituent chains both parallel and in register.
Glucocorticoid Receptor Antagonists (2008)

This review covers recent progress in the discovery of selective glucocorticoid receptor (GR) antagonists. Potential therapeutic applications of selective GR antagonists are described including the pharmacological rationale and, in some cases, clinical evidence that underlies these proposed uses. Disease areas that are discussed are Cushing's syndrome, psychotic depression, diabetes, obesity, Alzheimer's disease, neuropathic pain, drug abuse, and glaucoma. Methods for evaluating GR antagonist properties (binding, functional, and in vivo assays) are briefly covered. Early research on steroidal ligands which led to the identification of the non-selective GR antagonist RU-486 (mifepristone) and the GR-selective steroid RU-43044 is reviewed as is subsequent work on related steroidal compounds. Structure activity relationships (SAR) of nonsteroidal GR antagonists from the following structural classes are presented: octahydrophenanthrenes, spirocyclic dihydropyridines, triphenylmethanes and diaryl ethers, chromenes, dibenzyl anilines, dihydroisoquinolines, pyrimidinediones, azadecalins, and aryl pyrazolo azadecalins.
92‐kDa type IV collagenase and TIMP‐3, but not 72‐kDa type IV collagenase or TIMP‐1 or TIMP‐2, are highly expressed during mouse embryo implantation (1995)

Expression of 72 kDa and 92 kDa type IV collagenases and the metalloproteinase inhibitors TIMPs 1, 2, and 3 was studied by in situ hybridization in implanting mouse embryos of days 5.5 to 7.5. The 92 kDa type IV collagenase was strongly expressed in invading trophoblasts, signals above background not being observed in the embryonic proper or placental tissue. In contrast, signals above background were not seen for the 72 kDa enzyme in any cells of the implantation region, including trophoblasts and stromal cells of the decidual tissue. Only cells in the mucosal stroma outside the decidual region displayed some expression. TIMP-3 was intensily expressed in maternal cells in the area surrounding the invading embryonic tissue. No expression was observed for TIMP-1 or TIMP-2 in the embryo proper, trophoblasts, or the area of the uterine decidual reaction. Weak signals appeared for TIMP-1 only in the circular layer of myometrial smooth muscle and in some uterine stroma cells distant from the site of embryo implantation. The results suggest a central role for 92 kDa type IV collagenase and TIMP-3 in the extracellular proteolysis associated with implantation of the early embryo.
Photoalignment of liquid crystals: basics and current trends (2011)

The review describes the status of the studies and the recent achievements in the field of photoalignment of liquid crystals. An update classification of photoaligning materials and exposure schemes, and analyzes of the relationship between the molecular structure of the materials and characteristics of LC alignment are provided. In addition, bulk mediated photoalignment and combination of photoalignment with other alignment methods are discussed. Along with traditional, recently proposed applications of the photoalignment technique are considered.
Methyl‐isobutyl amiloride reduces brain Lac/NAA, cell death and microglial activation in a perinatal asphyxia model (2012)

Na⁺/H⁺ exchanger (NHE) blockade attenuates the detrimental consequences of ischaemia and reperfusion in myocardium and brain in adult and neonatal animal studies. Our aim was to use magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry to investigate the cerebral effects of the NHE inhibitor, methyl isobutyl amiloride (MIA) given after severe perinatal asphyxia in the piglet. Eighteen male piglets (aged < 24 h) underwent transient global cerebral hypoxia-ischaemia and were randomized to (i) saline placebo; or (ii) 3 mg/kg intravenous MIA administered 10 min post-insult and 8 hourly thereafter. Serial phosphorus-31 (³¹P) and proton (¹H) MRS data were acquired before, during and up to 48 h after hypoxia-ischaemia and metabolite-ratio time-series Area under the Curve (AUC) calculated. At 48 h, histological and immunohistochemical assessments quantified regional tissue injury. MIA decreased thalamic lactate/N-acetylaspartate and lactate/creatine AUCs (both p < 0.05) compared with placebo. Correlating with improved cerebral energy metabolism, transferase mediated biotinylated d-UTP nick end-labelling (TUNEL) positive cell density was reduced in the MIA group in cerebral cortex, thalamus and white matter (all p < 0.05) and caspase 3 immunoreactive cells were reduced in pyriform cortex and caudate nucleus (both p < 0.05). Microglial activation was reduced in pyriform and midtemporal cortex (both p < 0.05). Treatment with MIA starting 10 min after hypoxia-ischaemia was neuroprotective in this perinatal asphyxia model.
Antisense RNA Inactivation of Myosin Heavy Chain Gene Expression in Dictyostelium discoideum (1987)

The role of myosin in the contraction of striated muscle cells is well known, but its importance in nonmuscle cells is not yet clear. The function of myosin in Dictyostelium discoideum has been investigated by isolating cells which specifically lack myosin heavy chain (MHC A) protein. Cells were transformed with a vector encoding RNA complementary to mhcA messenger RNA (antisense RNA). Stable transformants have a dramatic reduction in the amount of MHC A protein, grow slowly, and generate giant multinucleated progeny, indicating an impairment in cytokinesis. Surprisingly, the cells adhere to surfaces, extend pseudopods and are capable of ameboid locomotion. The developmental sequence that is initiated by starving cells is severely impaired by the lack of myosin. The cells are unable to form multicellular aggregates normally and do not undergo subsequent morphogenesis. By changing the food source from liquid medium to bacteria, expression of the endogenous mhcA messenger RNA can be increased relative to expression of antisense RNA. When grown in this way, the transformed cells accumulate MHC A protein, remain mononucleate, and proceed through development normally.
Collagen structure: The molecular source of the tendon magic angle effect (2007)

This review of tendon/collagen structure shows that the orientational variation in MRI signals from tendon, which is referred to as the "magic angle" (MA) effect, is caused by irreducible separation of charges on the main chain of the collagen molecule. These charges are held apart in a vacuum by stereotactic restriction of protein folding due in large part to a high concentration of hydroxyproline ring residues in the amino acids of mammalian collagen. The elevated protein electrostatic energy is reduced in water by the large dielectric constant of the highly polar solvent (kappa approximately 80). The water molecules serve as dielectric molecules that are bound by an energy that is nearly equivalent to the electrostatic energy between the neighboring positive and negative charge pairs in a vacuum. These highly immobilized water molecules and secondary molecules in the hydrogen-bonded water network are confined to the transverse plane of the tendon. Orientational restriction causes residual dipole coupling, which is directly responsible for the frequency and phase shifts observed in orientational MRI (OMRI) described by the MA effect. Reference to a wide range of biophysical measurements shows that native hydration is a monolayer on collagen h(m) = 1.6 g/g, which divides into two components consisting of primary hydration on polar surfaces h(pp) = 0.8 g/g and secondary hydration h(s) = 0.8 g/g bridging over hydrophobic surface regions. Primary hydration further divides into side-chain hydration h(psc) = 0.54 g/g and main-chain hydration h(pmc) = 0.263 g/g. The main-chain fraction consists of water that bridges between charges on the main chain and is responsible for almost all of the enthalpy of melting DeltaH = 70 J/g-dry mass. Main-chain water bridges consist of one extremely immobilized Ramachandran water bridge per tripeptide h(Ra) = 0.0658 g/g and one double water bridge per tripeptide h(dwb) = 0.1974 g/g, with three water molecules that are sufficiently slowed to act as the spin-lattice relaxation sink for the entire tendon.
Inhibition of Proteasome Activities and Subunit-Specific Amino-Terminal Threonine Modification by Lactacystin (1995)

Lactacystin is a Streptomyces metabolite that inhibits cell cycle progression and induces neurite outgrowth in a murine neuroblastoma cell line. Tritium-labeled lactacystin was used to identify the 20S proteasome as its specific cellular target. Three distinct peptidase activities of this enzyme complex (trypsin-like, chymotrypsin-like, and peptidylglutamyl-peptide hydrolyzing activities) were inhibited by lactacystin, the first two irreversibly and all at different rates. None of five other proteases were inhibited, and the ability of lactacystin analogs to inhibit cell cycle progression and induce neurite outgrowth correlated with their ability to inhibit the proteasome. Lactacystin appears to modify covalently the highly conserved amino-terminal threonine of the mammalian proteasome subunit X (also called MB1), a close homolog of the LMP7 proteasome subunit encoded by the major histocompatibility complex. This threonine residue may therefore have a catalytic role, and subunit X/MB1 may be a core component of an amino-terminal-threonine protease activity of the proteasome.
CpG island methylation status of miRNAs in esophageal squamous cell carcinoma (2011)

Abstract Previous studies on esophageal squamous cell carcinoma (ESCC) indicated that it contains much dysregulation of microRNAs (miRNAs). DNA hypermethylation in the miRNA 5′ regulatory region is a mechanism that can account for the downregulation of miRNA in tumors (Esteller, N Engl J Med 2008;358:1148–59). Among those dysregulated miRNAs, miR‐203, miR‐34b/c, miR‐424 and miR‐129‐2 are embedded in CpG islands, as is the promoter of miR‐34a. We investigated their methylation status in ESCC by bisulfite sequencing PCR (BSP) and methylation specific PCR (MSP). The methylation frequency of miR‐203 and miR‐424 is the same in carcinoma and in the corresponding non‐tumor tissues. The methylation ratio of miR‐34a, miR‐34b/c and miR‐129‐2 is 66.7% (36/54), 40.7% (22/54) and 96.3% (52/54), respectively in ESCC, which are significantly higher than that in the corresponding non‐tumor tissues( p &lt; 0.01). Quantitative RT‐PCR analysis in clinical samples suggested that CpG island methylation is significantly correlated with their low expression in ESCC, 5‐aza‐2′‐deoxycytidine (DAC) treatment partly recovered their expression in EC9706 cell line. We conclude that CpG island methylation of miR‐34a, miR‐34b/c and miR‐129‐2 are frequent events and important mechanism for their low expression in ESCC. DNA methylation changes have been reported to occur early in carcinogenesis and are potentially good early indicators of carcinoma (Laird, Nat Rev Cancer 2003;3:253–66). The high methylation ratio of miR‐129‐2 indicated its potential as a methylation biomarker in early diagnosis of ESCC.
Mutational analysis of mouse Wnt-1 identifies two temperature-sensitive alleles and attributes of Wnt-1 protein essential for transformation of a mammary cell line. (1992)

The proto-oncogene Wnt-1 encodes a cysteine-rich, secretory glycoprotein implicated in virus-induced mouse mammary cancer and intercellular signaling during vertebrate neural development. To attempt to correlate structural motifs of Wnt-1 protein with its function, 12 mutations were introduced singly and in several combinations into the coding sequence of Wnt-1 cDNA by site-directed mutagenesis. Mutant alleles in a retroviral vector were tested for their ability to transform the mouse mammary epithelial cell line C57MG in two ways: by direct infection of C57MG cells and by infection of NIH3T3 cells that serve as donors of Wnt-1 protein to adjacent C57MG cells in a secretion-dependent (paracrine) assay. In addition, the synthesis and secretion of mutant proteins were monitored in multiple cell types by immunological assays. Deletion of the signal peptide demonstrated that transformation in both direct and paracrine assays depends upon entry of Wnt-1 protein into the endoplasmic reticulum. Changes in potential proteolytic processing sites (two basic dipeptides and a probable signal peptidase cleavage site) did not adversely impair biological activity or protein processing and uncovered a second site for cleavage by signal peptidase. Replacement of each of the four asparagine-linked glycosylation sites did not affect transforming activity at normal temperatures, but one glycosylation site mutant was found to be temperature-sensitive for transformation. An allele encoding a protein that lacks all four glycosylation sites was also transformation competent. In two of four cases, substitution of serine for a cysteine residue impaired transforming activity at the usual temperature, and transformation was temperature sensitive in a third case, implying that at least some of the highly conserved cysteine residues are important for Wnt-1 function.
Hyperosmotic activation of CNS sympathetic drive: implications for cardiovascular disease (2010)

Evidence now indicates that exaggerated sympathetic nerve activity (SNA) significantly contributes to salt-sensitive cardiovascular diseases. Although CNS mechanisms that support the elevation of SNA in various cardiovascular disease models have been intensively studied, many mechanistic details remain unknown. In recent years, studies have shown that SNA can rise as a result of both acute and chronic increases of body fluid osmolality. These findings have raised the possibility that salt-sensitive cardiovascular diseases could result, at least in part, from direct osmosensory activation of CNS sympathetic drive. In this brief review we emphasize recent findings from several laboratories, including our own, which demonstrate that neurons of the forebrain organum vasculosum laminae terminalis (OVLT) play a pivotal role in triggering hyperosmotic activation of SNA by recruiting neurons in specific regions of the hypothalamus, brainstem and spinal cord. Although OVLT neurons are intrinsically osmosensitive and shrink when exposed to extracellular hypertonicity, it is not yet clear if these processes are functionally linked. Whereas acute hypertonic activation of OVLT neurons critically depends on TRPV1 channels, studies in TRPV1(-/-) mice suggest that acute and long-term osmoregulatory responses remain largely intact. Therefore, acute and chronic osmosensory transduction by OVLT neurons may be mediated by distinct mechanisms. We speculate that organic osmolytes such as taurine and possibly novel processes such as extracellular acidification could contribute to long-term osmosensory transduction by OVLT neurons and might therefore participate in the elevation of SNA in salt-sensitive cardiovascular diseases.
Helichrysum gymnocephalum Essential Oil: Chemical Composition and Cytotoxic, Antimalarial and Antioxidant Activities, Attribution of the Activity Origin by Correlations (2011)

Helichrysum gymnocephalum essential oil (EO) was prepared by hydrodistillation of its leaves and characterized by GC-MS and quantified by GC-FID. Twenty three compounds were identified. 1,8-Cineole (47.4%), bicyclosesquiphellandrene (5.6%), γ-curcumene (5.6%), α-amorphene (5.1%) and bicyclogermacrene (5%) were the main components. Our results confirmed the important chemical variability of H. gymnocephalum. The essential oil was tested in vitro for cytotoxic (on human breast cancer cells MCF-7), antimalarial (Plasmodium falciparum: FcB1-Columbia strain, chloroquine-resistant) and antioxidant (ABTS and DPPH assays) activities. H. gymnocephalum EO was found to be active against MCF-7 cells, with an IC(50) of 16 ± 2 mg/L. The essential oil was active against P. falciparum (IC(50) = 25 ± 1 mg/L). However, the essential oil exhibited a poor antioxidant activity in the DPPH (IC(50) value > 1,000 mg/L) and ABTS (IC(50) value = 1,487.67 ± 47.70 mg/L) assays. We have reviewed the existing results on the anticancer activity of essential oils on MCF-7 cell line and on their antiplasmodial activity against the P. falciparum. The aim was to establish correlations between the identified compounds and their biological activities (antiplasmodial and anticancer). β-Selinene (R² = 0.76), α-terpinolene (R² = 0.88) and aromadendrene (R² = 0.90) presented a higher relationship with the anti-cancer activity. However, only calamenene (R² = 0.70) showed a significant correlation for the antiplasmodial activity.
Clay-Reinforced Epoxy Nanocomposites: Synthesis, Properties, and Mechanism of Formation (1996)

Epoxy-clay nanocomposites have been synthesized by exfoliation of organoclays during the epoxy thermosetting process. The extent of silicate layer separation is governed by the chain length of gallery cations, the clay layer charge density and the acidity of the gallery cations. By using different curing agents, we obtained both glassy and rubbery epoxy matrices. Reinforcement was substantially greater for the rubbery matrix. Both the tensile strength and the modulus of the rubbery epoxy-clay nanocomposite increased with increasing clay content. The reinforcement provided by the silicate layers at 15 wt% loading was manifested by a more than ten-fold improvement in tensile strength. The rubbery state of the matrix may allow alignment of the exfoliated silicate layers upon applying strain, thereby enhancing reinforcement.