cssi/SciSciGPT-SciSciNet huggingface dataset:
Exome sequencing for gene discovery: time does not stand still

The rapid evolution and continued refinement of whole-exome sequencing renders attempts to establish standards almost futile. Moreover, whole-genome sequencing may entirely replace whole-exome sequencing in the very near future. For all high-throughput DNA sequencing technologies, it should be emphasized that read accuracy is much more important than read depth. Even with deep reads, read errors are not uncommon. Theoretically, only shallow coverage would be needed if all reads were long, unbiased and 100% accurate. At this time, coverage depends on a variety factors including method of exome capture, sequencing platform, average read length, definition of coverage, definition of the exome (CCDS +/− RefSeq, +/− GENCODE) and the number of distinct DNA samples analyzed per run. Ultra-deep coverage is prohibitively expensive in many situations and does not eliminate false positives and false negatives. Given the known limitations of next-generation sequencing technologies, Sanger sequencing (forward and reverse directions) of gDNA and cDNA was used to confidently exclude coding and non-coding (untranslated regions, introns and promoter) TOR1A mutations in our kindred with cervical dystonia. 1 Copy number variants were excluded with qPCR of gDNA. A significant proportion of the variants reported in dbSNP, Exome Variant Server, and 1000 Genomes have not been validated with Sanger sequencing and are probably read errors. For example, Exome Variant Server reports 11missense variants in TOR1A (a 5 exon gene associated with early-onset generalized dystonia) that are predicted to be possibly or probably damaging by PolyPhen and average sample read depth was > 80X for all of these variants. On the other hand, it would not be surprising to find potentially causal variants in large databases of putatively normal controls given the reduced penetrance and population prevalence of autosomal-dominant dystonia (SGCE, GCH1, TOR1A, CIZ1 and THAP1). The quality of data found in dbSNP is also questionable with some studies reporting false positive rates of 15 to 17%.2 The dbSNP database is contaminated by single nucleotide differences which are artifacts due to the presence of paralogous sequences in the genome.3 False positive rates are probably much higher in databases derived from massively parallel sequencing (Exome Variant Server and 1000 Genomes). In brief, sequence variants identified with massively parallel sequencing should be validated with Sanger sequencing in the forward and reverse directions, correctly defined with Human Genome Variation Society (HGVS) nomenclature, characterized with molecular and cellular analyses, corroborated with carefully-designed case-control studies,4 and cautiously associated with neurological phenotypes.5,6
Identification by mutagenesis of conserved arginine and glutamate residues in the C-terminal domain of rat liver carnitine palmitoyltransferase I that are important for catalytic activity and malonyl-CoA sensitivity.

Abstract Carnitine palmitoyltransferase I (CPTI) catalyzes the conversion of long chain fatty acyl-CoAs to acylcarnitines in the presence of l-carnitine. To determine the role of the conserved glutamate residue, Glu-603, on catalysis and malonyl-CoA sensitivity, we separately changed the residue to alanine, histidine, glutamine, and aspartate. Substitution of Glu-603 with alanine or histidine resulted in complete loss of L-CPTI activity. A change of Glu-603 to glutamine caused a significant decrease in catalytic activity and malonyl-CoA sensitivity. Substitution of Glu-603 with aspartate, a negatively charged amino acid with only one methyl group less than the glutamate residue in the wild type enzyme, resulted in partial loss in CPTI activity and a 15-fold decrease in malonyl-CoA sensitivity. The mutant L-CPTI with a replacement of the conserved Arg-601 or Arg-606 with alanine also showed over 40-fold decrease in malonyl-CoA sensitivity, suggesting that these two conserved residues may be important for substrate and inhibitor binding. Since a conservative substitution of Glu-603 to aspartate or glutamine resulted in partial loss of activity and malonyl-CoA sensitivity, it further suggests that the negative charge and the longer side chain of glutamate are essential for catalysis and malonyl-CoA sensitivity. We predict that this region of L-CPTI spanning these conserved C-terminal residues may be the region of the protein involved in binding the CoA moiety of palmitoyl-CoA and malonyl-CoA and/or the putative low affinity acyl-CoA/malonyl-CoA binding site.
Coherent disintegration and stability of vortices in trapped Bose condensates

We consider the intrinsic stability of the vortex states of a pure Bose-Einstein condensate confined in a harmonic potential under the effects of a coherent atom-atom interaction. We find that stable vortices can be supported and vortex stability can be controlled by changing the interparticle interaction strength. At unstable regimes, a vortex will spontaneously disintegrate into states with different angular momenta even without external perturbations, with the lifetime determined by its imaginary excitation frequencies.
Determination of plasma-ion velocity distribution via charge-exchange recombination spectroscopy

Spectroscopy of line radiation from plasma impurity ions excited by charge-exchange recombination reactions with energetic neutral beam atoms is rapidly becoming recognized as a powerful technique for measuring ion temperature, bulk plasma motion, impurity transport, and more exotic phenomena such as fast alpha particle distributions. In particular, this diagnostic offers the capability of obtaining space- and time-resolved ion temperature and toroidal plasma rotation profiles with relatively simple optical systems. Cascade-corrected excitation rate coefficients for use in both fully stripped impurity density studies and ion temperature measurements have been calculated to the principal ..delta..n = 1 transitions of He+, C/sup 5 +/, and O/sup 7 +/ with neutral beam energies of 5 to 100 keV/amu. A fiber optically coupled spectrometer system has been used on PDX to measure visible He/sup +/ radiation excited by charge exchange. Central ion temperatures up to 2.4 keV and toroidal rotation speeds up to 1.5 x 10/sup 7/ cm/s were observed in diverted discharges with P/sub INJ/ less than or equal to 3.0 MW.
New Data on Intracultural Variability: The Hot-Cold Concept of Medicine and Illness

Anthropologists have frequently described the hot-cold concept as important and universal in popular Latin American medical theory. In the hot-cold concept of humoral medicine, health is believed to be a balance between hot and cold elements in the body. When the body's equilibrium is upset by being too "hot" or too "cold," illness can occur. Balance can be restored by treatment with foods, remedies, or medicines of the opposite valence. This relationship between disease and treatment has sometimes complicated the delivery of Western health care to Latin patients. Recent articles cite a need for the collection of more systematic, empirical data regarding the hot-cold classification system (Logan 1977), as well as a need to measure and account for intracultural variation (Foster 1979) to achieve a better understanding of the hot-cold system.
Localization of endogenous ATPases at the nerve terminal

We have investigated the localization of a set of intrinsic ATPase activities associated with purified synaptic plasma membranes and consisting of (a) a Mg2+-ATPase; (b) an ATPase active at high concentrations of Ca2+ in the absence of Mg2+ (CaH-ATPase); (c) a Ca2+ requiring Mg2+-dependent ATPase (Ca + Mg)-ATPase, stimulated by calmodulin (Ca-CaM-ATPase); (d) a Ca2+-dependent ATPase stimulated by dopamine (DA-ATPase); and (e) the ouabain-sensitive (Na + K)-ATPase. The following results were obtained: (1) All ATPases are largely confined to the presynaptic membrane; (2) the DA-, (Ca + Mg)-, (Ca-CaM)-, and (Na + K)-ATPases are oriented with their ATP hydrolysis sites facing the synaptoplasm; (3) the Mg- and CaH-ATPases are oriented with their ATP hydrolysis sites on the junctional side of the presynaptic membrane and are therefore classified as ecto-ATPases of as yet unknown function.
A survey of college radio carrier-current broadcasting facilities

An aggregate audience of 800,000 resident students is reached by 137 college radio stations via a closed-circuit medium known as AM carrier-current broadcasting. Fundamental FCC rules governing the carrier-current systems, some basic system problems, and several examples of operational systems are presented
MNDO study of ozone and its decomposition into (O2 + 0)

Abstract Calculations are reported for ozone and for its dissociation into (O 2 + 0), using an unrestricted version (UMNDO) of the recently developed MNDO semi-empirical SCF MO method. Ozone is predicted to have a singlet, but biradical-like, ground state, in agreemnt with GVB—CI calculations by Goddard et al. it is also correctly predicted to dissociate into triplet products ( 3 Σ − g (O 2 + 3 P O). The dissociation is predicted to involve crossing an energy barrier, implying (again correctly) that the absorption spectrum of ozone should exhibit predissociation. The calculated barrier is much higher than has been suspected, a conclusion which, if correct, should have important consequences.
Surfactant Therapy Modulates Levels of Interleukin-6 (IL-6) and Interleukin-1B (IL-1B) in Tracheal Aspirates of Premature Infants with Respiratory Distress Syndrome (RDS)

Surfactant Therapy Modulates Levels of Interleukin-6 (IL-6) and Interleukin-1B (IL-1B) in Tracheal Aspirates of Premature Infants with Respiratory Distress Syndrome (RDS)
A radiation model for the vela pulsar

We model the Vela emission in radio, optical and gamma wavelengths. We assume that radio emission occurs near the polar axis deep in the magnetosphere. Optical and gamma radiation arises through ordinary synchrotron mechanisms in a wide hollow cone, near the light cylinder. Fitting of observed frequencies and luminosities in the gamma and optical give reasonable plasma parameters, and indicate that field-plasma pressure balance breaks down before the light cylinder, as required by the picture. Some optical coherence is necessary if we attribute both radio and optical emission to the same species of particles, with γ∼100, but it is not required otherwise. Gamma-ray pulses arise from γ∼105 electrons. We suggest a single-pole orthogonal rotor picture which might account for the Vela pulse phases.
Advances in 2-5 micrometer (Hg, Cd)Te photodiodes

Detection of 2-5 micrometer infrared radiation is important both for earth resources and for thermal imaging applications. In this paper we present new results on 2-5µm (Hg, Cd)Te photodiode arrays. 2.1µm photodiodes achieve D* = 6.0 × 1010cm Hz1/2/W at 300K and D* = 5.0 × 1012cm Hz1/2/W at 193K. The photodiodes have surface leakage resistance greater than 1.0 × 1012Ω. The devices display no 1/f noise to less than 0.1 Hz and have response linear in signal power to better than 0.5 percent. Arrays display uniformity of responsivity within ± 3 percent. The diode saturation current is limited by generation-recombination in the depletion layer with an effective lifetime of 6.0 × 10-8sec. 2.7µm photodiodes achieve D* λ = 1.0 × 1010cm Hz1/2/W at 300K and D* λ = 5.0 × 1011cm Hz1/2/W at 193K. 4.8µm photodiodes achieve D* λ = 8.0 × 1010cm Hz1/2/W at 170K and 2.0 × 1012cm Hz1/2/W at 77K and zero background. This paper will present these recent data and compare them with theory.
Spin Coating of Photoresists Using Liquid Carbon Dioxide

A novel high-pressure carbon dioxide (CO2) spin-coating apparatus was designed and constructed to produce high-quality thin films of CO2-soluble photoresists based on 1H,1H-perfluorooctyl methacryl...
Human serum albumin interactions with C 60 fullerene studied by spectroscopy, small-angle neutron scattering, and molecular dynamics simulations

Concern about the toxicity of engineered nanoparticles, such as the prototypical nanomaterial C60 fullerene, continues to grow. While, evidence continues to mount that C60 and its derivatives may pose health hazards, the specific molecular interactions of these particles with biological macromolecules require further investigation. In this article, we report combined experimental and theoretical studies on the interaction of one of the most prevalent proteins in the human body, human serum albumin (HSA), with C60 in an aqueous environment. The C60–HSA interaction was probed by circular dichroism (CD) spectroscopy, small-angle neutron scattering (SANS), and atomistic molecular dynamics (MD) simulations to understand C60-driven changes in the structure of HSA in solution. The CD spectroscopy demonstrates that the secondary structure of the protein decreases in α-helical content in response to the presence of C60 (0.68 nm in diameter). Similarly, C60 produces subtle changes in the solution conformation of HSA (an 8.0 nm × 3.8 nm protein), as evidenced by the SANS data and MD simulations, but the data do not indicate that C60 changes the oligomerization state of the protein, such as by inducing aggregation. The results demonstrate that the interaction is not highly disruptive to the protein in a manner that would prevent it from performing its physiological function.
Dual Plating of Humeral Shaft Fractures: Orthogonal Plates Biomechanically Outperform Side-by-Side Plates

Background Single large-fragment plate constructs currently are the norm for internal fixation of middiaphyseal humerus fractures. In cases where humeral size is limited, however, dual small-fragment locking plate constructs may serve as an alternative. The mechanical effects of different possible plate configurations around the humeral diaphysis may be important, but to our knowledge, have yet to be investigated.
Prolactin can stimulate general protein synthesis in human breast cancer cells (MCF-7) in long-term culture

Abstract Prolactin significantly stimulated protein synthesis rates in a human breast cancer cell line, MCF-7. Total protein per culture also increased to 148% of controls. Proteins precipitated from cell homogenates at pH 4.65 in the presence of calcium ions were resolved by sodium dodecyl sulfate- polyacrylamide gel electrophoresis. The specific radioactivity for almost every polypeptide band increased as a result of protlactin treatment. Cell-type specificity for this prolactin action was indicated by the failure of two other human cell lines (HBL-100 and HEL) to respond similarly. This report is the first demonstration that prolactin has the capability to stimulate general protein synthesis in human breast cancer cells in long-term culture.
Strategies to reduce transmission of Toxoplasma gondii to animals and humans

Toxoplasma gondii is found in the tissues of food animals and is an important cause of abortion and mortality in sheep and goats throughout the world. It causes mental retardation and loss of vision in congenitally infected children and death in immunosuppressed patients. A live vaccine, using a nonpersistent strain of T. gondii, is available in New Zealand, the UK and Europe which prevents T. gondii abortion in sheep. A live vaccine using a mutant strain of T. gondii (T-263) is being developed in the USA to reduce oocyst shedding by cats. As yet, there are no drugs to kill T. gondii tissue cysts in human or animal tissues. Freezing to -12 degrees C, cooking to an internal temperature of 67 degrees C, or gamma irradiation (0.5 kGy) can kill tissue cysts in meat.
Development of a telemetry unit for bone strain monitoring

A telemetry unit designed to monitor strain in bones is presented. This unit allows studying the relationship between bone load and bone mass in small animals such as mice and rats. The unit measures 2.5 cm × 1.5 cm and consumes less than 20 mA of power while measurements are been transmitted. The telemetry unit was tested on an ex-vivo setting. The strain gage was attached to the ulna of a mouse and the readings were wirelessly transmitted to a remote computer at the rates of 76.7 kBaud. The low power consumption allows the unit to be powered by a small battery weighing less than 3 grams. Currently, strain gage data is collected by a bench top load instrument and a data acquisition unit. The current setup is accurate but is bulky and the subjects have to be sedated and immobilized to take accurate measurements. We present the readings from both setups and show that our telemetry unit is comparable in accuracy to the current setup and can easily replace it.
Search for radio emission from the young supernova remnants in NGC6946

Although recent supernovae in our own Galaxy are among the brightest radio sources in the sky—particularly Cas A and the Crab Nebula (500-1,000 yr post-outburst)—the evolution of their radio emission from outburst to the present is, of course, unknown. Unless and until we have the opportunity to study a new galactic supernova, our information on the immediate post-outburst radio properties of supernova remnants must come from studies of identified supernovae in external galaxies. NGC6946 is one galaxy in which such a study is particularly favourable both because supernovae occur frequently in this galaxy—four supernovae have been identified since 1917—and because of its relative proximity. Two previous searches have failed to detect radio emission from these remnants1,2. However, the greater sensitivity presently available at radio wavelengths allows us not only to conduct a more sensitive search for these remnants but also to determine whether the radio emission has brightened since the last surveys ∼ 5 yr ago.
Hepatic lipid partitioning and liver damage in nonalcoholic fatty liver disease: role of stearoyl-CoA desaturase.

Hepatic lipid overloading mainly in the form of triglycerides is considered a prerequisite for the development of nonalcoholic fatty liver disease (NAFLD). However, triglyceride accumulation in the liver in response to lipid overflow may represent a protective mechanism against lipotoxicity. Our aims were to assess the fundamental cellular mechanisms that link lipid compartmentation in hepatocytes to liver damage and disease progression in NAFLD by using both in vivo dietary models of NAFLD and in vitro cell models of lipid overloading. Exposure of murine or human hepatocytes to monounsaturated fatty acids (MUFAs) resulted in lipid accumulation without changes in cell viability. In contrast, cell incubation with saturated fatty acids (SFAs) significantly decreased cell viability and increased caspase activation and apoptosis, with only minor lipid droplet accumulation. Genetic or pharmacological inhibition of stearoyl-CoA desaturase-1 (SCD1), the enzyme that converts SFA to MUFA, sensitized cells to SFA-induced apoptosis. Hepatic SCD1 expression increased in experimental steatosis resulting from high fat diet and decreased in a methionine-choline-deficient (MCD) dietary model of steatohepatitis resulting in the latter situation in significantly increased hepatic SFA levels. SCD1–/– mice on the MCD diet had decreased steatosis and markedly increased hepatocellular apoptosis, liver injury, and fibrosis compared with the SCD1+/+, whereas MUFA feeding prevents the MCD-induced injury. In conclusion, this study suggests hepatic SCD1 plays a key role in prevention of steatohepatitis by partitioning excess lipid into MUFA that can be safely stored. This concept has important implications for the development of novel treatment strategies for patients with this condition.
Bargaining Among Nations Culture, History, and Perceptions in Regime Formation

The goal of this article is to see how the underlying cultural, historical, or perceptual elements that form the basis for the establishment of international agreements and organizations affect bar...
Pleural Fluid Characteristics in Hantavirus Pulmonary Syndrome

Hantavirus pulmonary syndrome (HPS), is a rodentborne, acute, often fulminant cardiorespiratory illness. Noncardiogenic pulmonary edema is prominent in HPS as is cardiac dysfunction. Pleural effusions are commonly noted in patients with HPS and have been thought to be exudative. This report describes the prevalence and characteristics of pleural effusions by an assessment of chest radiographs for the presence of pleural fluid and reviews all pleural fluid specimens obtained from patients with HPS. Of 23 patients treated at the University of New Mexico Hospital for HPS, 22 had evidence of pleural fluid while 4 had sampling of their pleural fluid. Two samples met criteria for an exudate by pleural fluid protein to serum protein ratio of more than 0.5; one was clearly a transudate and the other had inconsistent characteristics. The two exudative samples were obtained 7 days after admission, while the other 2 were obtained within 1 day of admission. Pleural fluid cultures were sterile, and the total of nucleated cells was less than 170/mm 3 , and predominately mononuclear. A hypothesis may be formulated that the pleural fluid in HPS is initially transudative, consistent with the observed cardiopulmonary dysfunction. However, following aggressive resuscitative efforts and as the acute illness resolves, fluid shifts occur as cardiac function normalizes; the pleural fluid may take on characteristics of an exudate.
Is the Purpose of Educational Research to Make the Job of Teachers Easier

(1984). Is the Purpose of Educational Research to Make the Job of Teachers Easier? Action in Teacher Education: Vol. 6, No. 3, pp. 53-64.
Deposit insurance and risk-taking behavior in the credit union industry

Abstract This paper examines the relationship between deposit insurance and risk-taking behavior within the credit union industry. Time series tests employing industry average financial ratios for federal and state credit unions did not support the increased risk-taking hypothesis. Although federal credit union capital declined immediately following the adoption of deposit insurance, this was most likely the result of reduced capital requirements, not deposit insurance. Liquidity and loan delinquency ratios had a negative time trend coefficient, implying a decline in risk-taking behavior during the post-insurance period. Cross-sectional test results employing Iowa state-chartered credit union data indicated that insured credit unions were better capitalized and more liquid than their uninsured counterparts. Overall there was no evidence that the adoption of deposit insurance increased the risk-taking behavior of credit unions.
Gene expression profile studies of human keratoconus cornea for NEIBank: a novel cornea-expressed gene and the absence of transcripts for aquaporin 5.

Purpose To increase the database of genes expressed in human cornea and to gain insights into the molecular basis of keratoconus (KC). Methods A cDNA library was constructed from KC corneas harvested at keratoplasty and used for expressed sequence tag (EST) analysis. Data were analyzed using grouping and identification of sequence tags (GRIST). Expression of selected clones was examined by RT-PCR. Results A total of 7680 clones was sequenced from the 5' end. After bioinformatics analysis, 4090 clusters of clones, each potentially representing individual genes, were identified. Of these, 887 genes were represented by more than one clone. The five most abundant transcripts, represented by >60 clones each, were for keratin-12, TGFBI (BIGH3), decorin, ALDH3, and enolase 1, all known markers for cornea. Many other markers for epithelial, stromal, and endothelial genes were also present. One cluster of six clones came from an apparently novel gene (designated KC6) located on chromosome 18 at p12.3. RT-PCR of RNA from several human tissues detected KC6 transcripts only in cornea. In addition, no clones were observed for the usually prominent corneal epithelial cell marker aquaporin 5 (AQP5), a water channel protein. Semiquantitative RT-PCR confirmed that expression of AQP5 is much lower in KC cornea than in non-KC cornea. Conclusions This analysis increases the database of genes expressed in the human cornea and provides insights into KC. KC6 is a novel gene of unknown function that shows cornea-preferred expression, whereas the suppression of transcripts for AQP5 provides the first clear evidence of a molecular defect identified in KC.
On the Role of Inorganic Phosphate in Divalent‐Cation Sequestration by Mitochondria

Rat liver mitochondria which have actively accumulated Mn2+ ions exhibit an electron para-magnetic resonance (EPR) spectrum dominated by a component E in which the usual hyperfine sextet has been collapsed to a single line through the process of spin exchange narrowing. When uptake occurs in the absence of added Pi, the line width of E shows considerable variation. By comparing experimentally observed spectra with computer-generated simulations it is demonstrated however that, under these conditions, E can be as narrow as approximately equal to 190 Oe, considerably narrower than the spectrum from a manganese phosphate precipitate. Furthermore parallel quantification on a single mitochondrial sample shows the level of Pi to be several times lower than the amount of Mn2+ observable in E. It is concluded therefore that the spectral component E, obtained under these conditions, cannot be accounted for in terms of manganese phosphate precipitate. These findings further indicate that a substantial number of sites (approximately equal to 100 nmol/mg protein), other than Pi, must exist inside the mitochondria which are capable of complexing divalent cations in regions of high local concentration.
Effects of extracellular pH reductions on [3H]d-aspartate and [3H]noradrenaline release by presynaptic nerve terminals isolated from rat cerebral cortex

We analyzed the effects of extracellular pH reductions on the release of [(3)H]D: -aspartate ([(3)H]D: -ASP) and [(3)H]noradrenaline ([(3)H]NA) from cerebrocortical synaptosomes isolated from rats. Synaptosomes were superfused with standard medium at a physiologic pH of 7.4 and with acidified medium with a pH of 6.00, 5.50, or 5.0. Medium acidification produced pH-dependent stimulation of [(3)H]D: -ASP release. The increase amounted to 202 +/- 12.6% when the pH was reduced to 5.5. The [(3)H]D: -ASP release evoked by low pH (5.50) was still observed in the absence of Ca(2+) ions, but it was abolished by DL: -threo-beta-benzyloxyaspartate (DL: -TBOA) (100 microM), which inhibits neuronal glutamate/aspartate transport. Exposure to 5-(N,N-hexamethylene)-amiloride (EIPA) (30-100 microM), a selective inhibitor of Na(+)/H(+) exchange, caused concentration-dependent stimulation of [(3)H]D: -ASP release; the increase observed with EIPA 30 microM was 160 +/- 12%. The EIPA-induced release was not dependent on the presence of Ca(2+) ions in the medium, but it was abolished when synaptosomes were pretreated with 100 microM DL: -TBOA. Reduction of the extracellular pH (5.50-5.0) also stimulated the release of [(3)H]NA from rat cortical synaptosomes. Exposure to medium with a pH of 5.50 increased basal release by 136 +/- 9.5%. The release-stimulating effect of this medium was calcium-independent and abolished by 3 muM desipramine (DMI). [(3)H]NA release was also stimulated by EIPA. The increase induced by a concentration of 30 muM amounted to 136 +/- 9.50%, and this effect was calcium-independent and abolished by pretreatment with DMI (3 muM). These findings suggest that reduction of the extracellular pH stimulates release of [(3)H]D-ASP and [(3)H]NA by reversing neurotransmitter transport in the nerve terminal. This reversal might be activated by increased cytosolic concentrations of the transmitters caused by reduction of the pH gradient between the cytoplasm and the synaptic vesicles that take up the transmitters. This hypothesis is confirmed by the results of experiments conducted with EIPA. Selective blockade of Na(+)/H(+) exchange with this compound induces accumulation of H(+) in the nerve terminals and intracellular acidification, which leads to calcium-independent, transporter-mediated release of [(3)H]D: -ASP and [(3)H]NA.
Morphologic and pathologic aspect of intercalated disc of the heart

Abstract Myocardial tissue is divided into discreet cellular units by the intercalated disc at the intercellular boundary. The intercalated disc is structurally differentiated into four regions. The tight junction or nexal region of the intercalated disc has been considered the region of low electrical resistance, thus acting as a pathway for the electrotonic coupling between myocytes. Under various pathologic and physiologic conditions, there is a variable degree of separation of the intercalated disc. The role of the intercalated disc in the propagation of the excitation impulse in normal and diseased states is discussed.
Differentiating skin-limited and multisystem Langerhans cell histiocytosis

Objective To identify features associated with multisystem involvement and therapeutic failure in patients with skin Langerhans cell histiocytosis (LCH). Study design We reviewed medical records of 71 consecutive patients with LCH with skin involvement evaluated at Texas Children's Hospital and analyzed clinical features, laboratory results, and the presence of circulating cells with the BRAF-V600E mutation with respect to initial staging and clinical outcomes. Results Skin disease in patients older than 18 months of age at diagnosis was associated with the presence of multisystem disease (OR, 9.65; 95% CI, 1.17-79.4). Forty percent of patients referred for presumed skin-limited LCH had underlying multisystem involvement, one-half of these with risk-organ involvement. Patients with skin-limited LCH had a 3-year progression-free survival of 89% after initial therapy, and none developed multisystem disease. Patients with skin/multisystem involvement had a 3-year progression-free survival of 44% with vinblastine/prednisone therapy, and risk-organ involvement did not correlate with failure to achieve nonactive disease. Circulating cells with BRAF-V600E were detected at higher frequency in patients with multisystem involvement (8 of 11 skin/multisystem vs 1 of 13 skin-limited; P = .002). Conclusion Skin-limited LCH necessitates infrequent therapeutic intervention and has a lower risk of progression relative to skin plus multisystem LCH. The less-aggressive clinical course and lack of circulating cells with the BRAF-V600E mutation in skin-limited LCH suggest a different mechanism of disease origin compared with multisystem or risk-organ disease.
Identification of a functional transposon insertion in the maize domestication gene tb1

Genetic diversity created by transposable elements is an important source of functional variation upon which selection acts during evolution. Transposable elements are associated with adaptation to temperate climates in Drosophila, a SINE element is associated with the domestication of small dog breeds from the gray wolf and there is evidence that transposable elements were targets of selection during human evolution. Although the list of examples of transposable elements associated with host gene function continues to grow, proof that transposable elements are causative and not just correlated with functional variation is limited. Here we show that a transposable element (Hopscotch) inserted in a regulatory region of the maize domestication gene, teosinte branched1 (tb1), acts as an enhancer of gene expression and partially explains the increased apical dominance in maize compared to its progenitor, teosinte. Molecular dating indicates that the Hopscotch insertion predates maize domestication by at least 10,000 years, indicating that selection acted on standing variation rather than new mutation.
A comparison of suture versus laser-assisted microvascular anastomosis (LAMA) in the pig buttock flap model.

Introduction of microvascular free-tissue transfer to head and neck surgery has completely altered the current approach to extirpation and reconstruction. The increased flexibility now available offers multiple options for reconstruction and has essentially removed the limitations of size and geometry which existed with other types of repair. Despite these advantages, increased surgical time and potential flap failure loom as limiting factors. Since the initial use of sutures to perform microvascular anastomoses, numerous experiments have been conducted in order to identify other options for vessel approximation. Laser-assisted microvascular anastomosis (LAMA) was first attempted with the neodymium-yttrium aluminum garnet (Nd:YAG) laser and, subsequently, other wavelengths were used in experimental models. Success with this technique has been repeatedly documented. Although a comparable animal model to study skin flaps was initially described in 1979, little is currently available in the literature that describes the actual use of a microvascular free flap model. Certainly, nothing exists regarding the role of LAMA and microvascular free-tissue transfer. This study was designed to establish a reliable and reproducible animal model to study free-tissue transfer. Through the use of laser Doppler flowmetry, values of blood perfusion of flaps can be determined. Anastomoses with standard suture and various laser-assisted techniques could then be done and compared, analyzing the parameters of time and blood flow. Histologic evaluation could be correlated with clinical observations. In so doing, LAMA could be objectively evaluated as a potentially viable method of vascular reconstruction in microsurgical free-tissue transfer.
Using Bibliometrics and Text Mining to Explore the Trends of E-Marketing Literature from 2001 to 2010

This paper describes a hybrid approach, using bibliometrics and text-mining, used to analyze longitudinal trends in the literature of e-marketing research from 2001 to 2010. The abstracts of 888 articles from six leading marketing journals were analyzed. The analysis identifies several core topics and themes of e-marketing research and reveals trends occurring in this growing area. The study reveals that combing bibliometrics with text-mining is a useful way to identify themes and trends for a topic in the literature and can produce meaningful results to help researchers achieve a deeper understanding of an area of interest.
High pressure liquid chromatography analysis of heroin

Abstract A liquid-solid chromatographic system is described that will separate heroin from 26 substances encountered in heroin seizures. The effects of ammonia and water concentration on the retention of the drug substances were investigated. Three ‘brown’ heroin samples were analyzed by high pressure liquid chromatography (HPLC) and by gas-liquid chromatography (GLC) and the results evaluated and compared.
EARLY LIFE SOCIAL INCONGRUITIES, HEALTH RISK FACTORS AND CHRONIC DISEASE*

Abstract This study tested specific hypotheses concerned with the relationships between three early life stress variables occurring between 0 and 16 yr of age and a variety of adult health status measures ascertained some 20–60 yr later in a 40% sample of the Tecumseh Community Health Study population 35–69 yr of age. The hypotheses stated that each of the following characteristics, relatively greater residential geographic mobility during childhood, being deprived of one or both natural parents for one or more years during this early formative period, and experiencing parental status incongruence, would be associated with higher levels of nine risk factors, greater prevalence of five chronic diseases, and a greater rate of mortality. The risk factors were systolic and diastolic blood pressure, blood glucose level, serum cholesterol, serum uric acid, the F.E.V. 1.0 measure of lung function; adiposity, number of cigarettes smoked currently, and amount of alcohol consumed currently. The chronic conditions were CHD, hypertension, diabetes, chronic bronchitis and asthma. Also measured were the aggregation of these chronic conditions and whether or not the respondents ever smoked cigarettes or drank alcohol. Five mobility measures and an index were developed. As predicted, in general, significant relationships were found among women between the five separate mobility variables and the health measures. Specifically, all five separate measures of mobility were related to CHD among older women, and most were related to cigarette smoking and alcohol consumption among all women. Various of the five mobility measures were related to various other specific health measures. In general, mobility was not related to the health measures studied among men. The hypotheses concerning parental deprivation and parental status incongruency were not substantiated by the data.
Anomalous acousto optic effects in acrylic plastics

An anomalous acoustic effect is observed when a laser beam is guided into an acrylic plastic plate and is modulated by acoustic waves. The laser beam spreads into various beams with the modulation frequency, the double frequency and the triple frequency, simultaneously.
Design, synthesis, and docking studies of telmisartan analogs for the treatment of metabolic syndrome

In our early studies, telmisartan was found to be a moderate peroxisome proliferator-activated receptor (PPAR) gamma activator in the human PPARγ-GAL-4 cell-based transactivation assay. Thus, novel analogs of telmisartan were designed, synthesized, and evaluated in the AT1 receptor binding assay and PPAR gamma transactivation assay. A total of 11 compounds were designed based on docking in both AT1 receptor model and PPAR gamma active pocket and synthesized. Introduction of an additional acidic group at the para position of the distal phenyl ring of telmisartan decreased affinity towards AT1 receptor and PPARγ activity. In the present study, the molecule with best results was MT003 with weak PPARγ activity (8% of maximum PPARγ activation achieved by full agonist rosiglitazone at 10 μM) and good binding affinity (K i = 650 ± 139 nM) towards the AT1 receptor. Docking of MT003 into AT1 receptor model and PPAR gamma showed very similar interactions with the receptors as AT1 antagonist telmisartan and PPAR gamma agonist rosiglitazone.
HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration

Human immunodeficiency virus-1 (HIV-1) has infected more than 60 million people and caused nearly 30 million deaths worldwide, ultimately the consequence of cytolytic infection of CD4(+) T cells. In humans and in macaque models, most of these cells contain viral DNA and are rapidly eliminated at the peak of viraemia, yet the mechanism by which HIV-1 induces helper T-cell death has not been defined. Here we show that virus-induced cell killing is triggered by viral integration. Infection by wild-type HIV-1, but not an integrase-deficient mutant, induced the death of activated primary CD4 lymphocytes. Similarly, raltegravir, a pharmacologic integrase inhibitor, abolished HIV-1-induced cell killing both in cell culture and in CD4(+) T cells from acutely infected subjects. The mechanism of killing during viral integration involved the activation of DNA-dependent protein kinase (DNA-PK), a central integrator of the DNA damage response, which caused phosphorylation of p53 and histone H2AX. Pharmacological inhibition of DNA-PK abolished cell death during HIV-1 infection in vitro, suggesting that processes which reduce DNA-PK activation in CD4 cells could facilitate the formation of latently infected cells that give rise to reservoirs in vivo. We propose that activation of DNA-PK during viral integration has a central role in CD4(+) T-cell depletion, raising the possibility that integrase inhibitors and interventions directed towards DNA-PK may improve T-cell survival and immune function in infected individuals.
Synthesis of BN Using BPO4 as the Boron Source

The reaction of BPO4 with different amounts of NaCN to yield BN and sodium phosphates was studied, mainly as a function of temperature and of the ratio NaCN/BPO4. Gravimetric data, together with analytical results, allowed us to postulate and confirm that the yield of reaction products is dependent on the initial ratio NaCN/BPO4. An additional reaction between NaCN, BPO4, and Na3PO4 yielding BN was also studied.
Structural and electronic properties of C70

Abstract Using the Car—Parrinello method based on the local density approximation of density functional theory, we have investigated the structural and electronic properties of the C 70 fullerene cluster in the prolate spheroidal structure of symmetry D 5h . The C 70 structure has been fully relaxed and an interesting pattern of deformations obtained. The electronic structure is in satisfactory agreement with photoemission data. Comparison is made with other theoretical results.
Should average shear-wave velocity in the top 30 m of soil be used to describe seismic amplification?

Abstract The average velocity of shear waves in the top 30 m of soil, νL, has become the parameter used by many engineering design codes and most recently by published empirical-scaling equations to estimate the amplitudes of strong ground motion. Yet there are few studies to determine whether this is a meaningful parameter to use—and whether estimates that do use it are reliable. In 1995, the authors studied this problem and concluded that νL should not be used. We reported then that an older site characterization in terms of the soil site parameter proposed by Seed et al. [1] , sL, worked better because it included a measure of the thickness of the soil layers to considerably greater depths. Our report, however, made no difference; numerous papers continued to be published based only on scaling in terms of νL, and worse, they also ignored the geological site conditions. The purpose of this paper is to emphasize that the average shear-wave velocity in the top 30 m of soil should not be the only site parameter used to scale strong-motion amplitudes. While the search continues for the more meaningful site parameters to use in empirical scaling of strong earthquake ground motion, it is better to use sL to describe the amplification of seismic waves by soil deposits near the surface.
The reproductive organs of the male spotted skunk (Spilogale putorius).

A relatively well developed prostrate is the only accessory sex gland present in the spotted skunk (Spilogale putorius). The distal end of the vas deferens is quite glandular, but there is no distinct ampullary swelling. The gross morphology of this species is compared with that of several other members of the family Mustelidae.
Centroid-moment tensor solutions for April–June, 1998

Abstract Centroid-moment tensor solutions are presented for 219 earthquakes that occurred during the second quarter of 1998. The solutions are obtained using corrections for aspherical earth structure represented by a whole mantle shear velocity model SH8/U4L8 of Dziewonski and Woodward [Dziewonski, A.M., Woodward, R.L., 1992. Acoustic imaging at the planetary scale. In: Emert, H., Harjes, H.-P. (Eds.), Acoustical Imaging. Plenum, Vol. 19, pp. 785–797.]. A new model of anelastic attenuation of Durek and Ekstrom [Durek, J.J., Ekstrom, G., 1996. A radial model of anelasticity consistent with long-period surface wave attenuation. Bull. Seismol. Soc. Am. 86, 144–158.] is used to predict the decay of the waveforms.
Mathematical guidance for axons

Abstract Axon guidance by gradients plays an important role in wiring up the developing nervous system. Growth cones seem to sense a concentration difference across their spatial extent, and convert this into a signal to move up or down a gradient. In this article, a simple mathematical framework is developed to understand when and where gradient detection can occur as a function of gradient shape. This framework is applied to two examples: the guidance of axons by target-derived diffusible factors in vivo and in collagen gels, and guidance by substrate-bound gradients of optimal shape, as might be relevant in the retinotectal system. Two distinct spatial limits on guidance emerge: 1mm for a target-derived diffusible gradient, and 1cm for a substrate-bound gradient.
Structural optimization under uncertain loads and nodal locations

This paper presents algorithms for solving structural topology optimization problems with uncertainty in the magnitude and location of the applied loads and with small uncertainty in the location of the structural nodes. The second type of uncertainty would typically arise from fabrication errors where the tolerances for the node locations are small in relation to the length scale of the structural elements. We first review the discrete form of the uncertain loads problem, which has been previously solved using a weighted average of multiple load patterns. With minor modifications, we extend this solution to include loads described by continuous joint probability density functions. We then proceed to the main contribution of this paper: structural optimization under uncertainty in the nodal locations. This optimization problem is computationally difficult because it involves variations of the inverse of the structural stiffness matrix. It is shown, however, that for small uncertainties the problem can be recast into a simpler but equivalent structural optimization problem with equivalent uncertain loads. By expressing these equivalent loads in terms of continuous random variables, we are able to make use of the extended form of the uncertain loads problem presented in the first part of this paper. The optimization algorithms are developed in the context of minimum compliance (maximum stiffness) design. Simple examples are presented. The results demonstrate that load and nodal uncertainties can have dramatic impact on optimal design. For structures containing thin substructures under axial loads, it is shown that these uncertainties (a) are of first-order significance, influencing the linear elastic response quantities, and (b) can affect designs by avoiding unrealistically optimistic and potentially unstable structures. The additional computational cost associated with the uncertainties scales linearly with the number of uncertainties and is insignificant compared to the cost associated with solving the deterministic structural optimization problem.
Effects of ethanol and other constituents of alcoholic beverages on coronary heart disease: a review

Moderate consumption of alcoholic beverages has been shown to reduce the incidence of coronary artery disease (CAD) compared to abstinence and heavy drinking. Epidemiologic studies suggest that any form of alcoholic beverage offers this protection. However, several studies have shown that the polyphenolic compounds found in many alcoholic beverages are more effective than pure alcohol for improving specific biologic factors known to contribute to atherosclerotic development. The alcoholic beverage polyphenols improve endothelial function, protect LDL from oxidation, inhibit platelet activity, inhibit vascular smooth muscle cell (VSMC) proliferation and migration, and reduce the activation of monocytes in the post-prandial period. Not only does pure alcohol not provide these benefits, but it has also been shown to act as a pro-oxidant, impair endothelial function, and possibly be proinflammatory. In studies comparing red wine, white wine, beer, and liquor, the red wine and dark-colored beer seem to provide more protection than liquor, even though the alcohol contents (per serving) are similar. The results suggest that the type of alcoholic beverage consumed does make a difference because pure alcohol cannot fully account for the beneficial effects.
Insertion of a new gene of viral origin into bone marrow cells of mice

DNA containing the herpes simplex virus thymidine kinase (HSVtk) gene was used to transform wild-type tk+ mouse L cells to a tk++ status in vitro using methotrexate as a selective agent. HSVtk DNA was also used to transform mouse bone marrow cells in vitro. Transformed marrow cells injected into irradiated and methotrexate-treated recipient mice gave rise to proliferating cells which in some cases dominated the marrow population and which contained HSVtk gene sequences.