cssi/SciSciGPT-SciSciNet huggingface dataset:
An in vivo reporter system for measuring increased inclusion of exon 7 in SMN2 mRNA: potential therapy of SMA

Spinal muscular atrophy (SMA) is a degenerative motor neuron disorder resulting from homozygous loss of the SMN1 gene. SMN2, a nearly identical copy gene, is preserved in SMA patients. A single nucleotide difference between SMN1 and SMN2 causes exon 7 skipping in the majority of SMN2 mRNA. Gene therapy through modulation of SMN2 gene transcription in SMA patients may be possible. We constructed a series of SMN mini-genes comprised of SMN exon 6 to exon 8 sequences fused to green fluorescence protein (GFP) or luciferase reporters, to monitor SMN exon 7 splicing. These reporters recapitulated the splicing patterns of the endogenous SMN gene in stable cell lines. The SMN1-luciferase reporter was approximately 3.5-fold more active than SMN2-luciferase and SMN1-GFP intensities were visually distinguishable from SMN2-GFP. We have screened chemical inducers and inhibitors of kinase pathways using stable SMN-reporter lines and found that the phosphatase inhibitor sodium vanadate specifically stimulated exon 7 inclusion within SMN2 mRNAs. This is the first compound identified that can stimulate exon 7 inclusion into transcripts derived from the endogenous SMN2 gene. These results demonstrate that this system can be utilized to identify small molecules that regulate the splicing of SMN exon 7.
A Discussion On Possible Mechanisms of Nonlinear Hysteretic Behavior In Sedimentary Granular Rocks: Grain Contact Adhesion Versus Stick-slip Sliding

The stress-strain behavior of dry and saturated Berea sandstones has been studied in detail in order to investigate the relative contributions of grain contact adhesion hysteresis and stick-slip sliding on energy loss in granular sedimentary rocks. The information gathered from the uniaxial stress cycling experiments show evidence of frictional stick-slip sliding when the samples were saturated with hexadecane and CTAB solutions. Dry and brine saturated cases did not show any stick-slip effects. The pore fluids at the grain contacts were found to play an important role in the observed hysteresis in the stress-strain diagrams and in determining the stick-slip effects.
The ‘intestinal–renal’ arginine biosynthetic axis in the aging rat

It has been suggested that l-arginine availability declines with advanced age, which could contribute to the endothelial dysfunction and decreased nitric oxide (NO) production that are features of aging. l-Arginine is made in the kidney and since the aging kidney develops progressive injury there may be decreased synthesis limiting availability. In this study we investigated the impact of aging on the regulation, at the gene level, of the various enzymes that synthesize l-arginine in the kidney (argininosuccinate synthetase and argininosuccinate lyase) and citrulline, the precursor of l-arginine made in the small intestine (phosphate-dependent glutaminase, carbamyl phosphate synthetase-1 and ornithine transcarbamylase). Studies were in young (3–5 months), middle-aged (11–13 months) and old (18–22 months) male and female Sprague–Dawley rats aged under barrier conditions. The plasma, renal cortical and brain cerebellar levels of l-arginine are unchanged in the old male rat, and expression of the genes involved in renal arginine synthesis and small intestinal citrulline synthesis is unchanged or upregulated with age in both males and females. This study shows that the synthesis of l-arginine is maintained with aging despite developing kidney damage. Therefore, the reduced NO generating capacity that occurs in aging must be due to downstream changes in the NO biosynthesis pathway, such as reduced abundance of NO biosynthetic enzymes.
LDL receptor-related protein LRP6 regulates proliferation and survival through the Wnt cascade in vascular smooth muscle cells.

Initial studies have established expression of low-density lipoprotein (LDL) receptor-related protein 6 (LRP6) in vascular smooth muscle cells (VSMCs). We hypothesized that LRP6 is a critical media...
A Comprehensive Approach to the Treatment of Uterine Leiomyomata

Leiomyomas (fibroids) are the most common tumors in women, with a prevalence between 30% and 50%. They affect women primarily during their reproductive years, spontaneously regressing after menopause in most women. They may cause significant symptoms of pain, dysmenorrhea, abnormal uterine bleeding, and infertility. Because leiomyomas are so common, treatment should be reserved for those patients with symptoms. Treatment options have recently expanded beyond hysterectomy. Medical therapies, including gonadotropin-releasing hormone agonists and progesterone modulators, have become more widely used. Less invasive options such as uterine fibroid embolization, magnetic resonance imaging-guided focused ultrasound, and radiofrequency ablation are being used to avoid more invasive surgery. Because of limited and negative information regarding these alternatives to surgery, they are not recommended for women desiring future fertility. If surgery is desired or required, often less invasive approaches via hysteroscopy for intracavitary lesions or robot-assisted laparoscopy for patients with a small number of myomas have become preferred options. Treatment should be tailored to the patient.
Near-surface current shear measured by marine X-band radar

This paper presents a new method to measure the near-surface currents' vertical shear by marine X-band radar (MR). The data used here were acquired from R/V Roger Revelle during the Impact of Typhoons on the Ocean in the Pacific (ITOP) field campaign in 2010. Existing techniques use MR surface wave signatures to retrieve a single near-surface current vector per analysis period. In essence, this is done by measuring the phase velocity of a wave on a current, which is then compared with the known still-water linear dispersion relationship. The resulting current corresponds to a depth-weighted average over the near-surface ocean layer. We introduce a new method that yields multiple estimates as a function of ocean wavenumber. The “effective” depth of the radar current measurement increases with the length of the ocean wave it was derived from. Our wavenumber-dependent near-surface currents thus provide information on vertical current shear. This method is analogous to an approach that has already proven successful for multi-frequency high-frequency (HF) radars. Here, we present first results which are put into the context of shipboard wind, surface wave, and background current measurements.
Randomized trial comparing 3 methods of postoperative analgesia in gynecology patients: patient-controlled intravenous, scheduled intravenous, and scheduled subcutaneous.

Objective The objective of the study was to determine whether any of 3 routes of opioid administration (patient-controlled analgesia [PCA], scheduled intermittent intravenous [IV], or scheduled intermittent subcutaneous [SQ]) provides superior pain relief and satisfaction among patients undergoing abdominal gynecologic surgery. Study Design Patients were randomized to intravenous hydromorphone by PCA, IV hydromorphone via scheduled nurse-administered doses, or SQ hydromorphone via scheduled nurse-administered doses. Self-reported pain and satisfaction were recorded over 48 hours following arrival at the nursing unit. Linear mixed effects modeling was used to compare outcomes among the groups. Results Neither pain scores nor satisfaction differed by group. PCA patients had higher total opioid use ( P P = .04). Conclusion Given these findings as well as those in previous literature, no specific method of postoperative analgesia appears to be superior.
Likelihood Ratio Test-Based Method for Signal Detection in Drug Classes Using FDA's AERS Database

In 1968 the Food and Drug Administration (FDA) established the Adverse Event Reporting System (AERS) database containing data on adverse events (AEs) reported by patients, health care providers, and other sources through a spontaneous reporting system. FDA uses AERS for monitoring the safety of the drugs on the market after approval. Most statistical methods that are available in the literature to analyze large postmarket drug safety data for identifying drug-event combinations with disproportionately high frequencies are designed to explore signals of a single drug-AE combination, but not signals including a drug class or a group of AEs simultaneously. Those methods are also not designed to control type I error and are subject to high false discovery rates. In this paper, we first briefly review a recently developed method, known as the likelihood ratio test (LRT)-based method, which has been demonstrated to control the family-wise type I error and false discovery rates. By introducing a concept of weight matrix for the drugs (or for AEs), we then extend the LRT method for detecting signals including a class of drugs (or AEs) in addition to detecting signals of single drug (or AE). A simplified Bayesian method is also proposed and compared with LRT method. The proposed methods are applied to study the signal patterns of drug classes, namely, the gadolinium drug class for magnetic resonance imaging (MRI) and statins for hypercholesterolemia, over different time periods, using the datasets with only suspect drugs and with both suspect and concomitant drugs from the AERS database. The signals detected by the statistical methods can be confirmed by signals detected across different databases, existing medical evidence from research or regulatory resources, prospective biological studies, and also through simulation as illustrated in the application.
The myth of bacterial species and speciation

The Tree of Life hypothesis frames the evolutionary process as a series of events whereby lineages diverge from one another, thus creating the diversity of life as descendent lineages modify properties from their ancestors. This hypothesis is under scrutiny due to the strong evidence for lateral gene transfer between distantly related bacterial taxa, thereby providing extant taxa with more than one parent. As a result, one argues, the Tree of Life becomes confounded as the original branching structure is gradually superseded by reticulation, ultimately losing its ability to serve as a model for bacterial evolution. Here we address a more fundamental issue: is there a Tree of Life that results from bacterial evolution without considering such lateral gene transfers? Unlike eukaryotic speciation events, lineage separation in bacteria is a gradual process that occurs over tens of millions of years, whereby genetic isolation is established on a gene-by-gene basis. As a result, groups of closely related bacteria, while showing robust genetic isolation as extant lineages, were not created by an unambiguous series of lineage-splitting events. Rather, a temporal fragmentation of the speciation process results in cognate genes showing different genetic relationships. We argue that lineage divergence in bacteria does not produce a tree-like framework, and inferences drawn from such a framework have the potential to be incorrect and misleading. Therefore, the Tree of Life is an inappropriate paradigm for bacterial evolution regardless of the extent of gene transfer between distantly related taxa.
Perchlorate, Thiocyanate, and Nitrate in Edible Cole Crops (Brassica sp.) Produced in the Lower Colorado River Region

The Colorado River is contaminated with low levels of perchlorate. Perchlorate has the potential to disrupt thyroid function by inhibiting the uptake of iodide. Brassica are rich sources of thiocyanate and nitrate, also inhibitors of iodide uptake. This study was conducted to estimate potential human exposure to perchlorate, thiocyanate, and nitrate from Brassica sp. irrigated with Colorado River water. Results indicate that Brassica sp. irrigated with Colorado River water do accumulate trace levels of perchlorate. However, the levels of perchlorate observed are low relative to the nitrate and thiocyanate naturally present in these species and low relative to the reference dose recommended by the NAS and the USEPA.
Growth of polycrystalline Cd3As2 films on room temperature substrates by a pulsed-laser evaporation technique

Abstract Cd 3 As 2 films were prepared by a pulsed-laser evaporation technique. The deposition onto fused quartz substrates was carried out in a vacuum chamber under a background pressure of about 0.6 × 10 −4 Pa. Energy-dispersive X-ray analysis, scanning electron microscopy, transmission electron microscopy and Hall measurements were used to characterize the films. The properties of the film as a function of their thickness and of the deposition parameters are discussed. It is shown that polycrystalline layers of Cd 3 As 2 grow on substrates held at temperatures as low as 295 K. The room temperature electron concentrations and mobilities for such layers were (3.5–5.3) × 10 18 cm −3 and (0.6–1.06) × 10 3 cm 2 V −1 s −1 respectively.
Inter- and intrarater reliability of a back range of motion instrument.

Abstract Kachingwe AF, Phillips BJ. Inter- and intrarater reliability of a back range of motion instrument. Objective To examine the interrater and intrarater reliability of a back range of motion (BROM) instrument when measuring lumbar spine active planar motions and pelvic inclination. Design Single-group repeated measures for inter- and intrarater reliability. Setting Academic institution. Participants Ninety-one participants (61 women, 30 men; mean age, 28y) without a current complaint of low back pain volunteered. Intervention Two examiners measured pelvic inclination and all lumbar motions by using the BROM device. Subjects alternated between examiners for 4 complete trials; examiners remained blinded to the measurements. Main Outcome Measures Intraclass correlation coefficients (ICCs) were used to determine intrarater and interrater reliability. Regression analysis was performed to determine the role palpation played in sagittal plane measurement error. Results Intrarater reliability for side bending was good (ICC range, .85–.83), lumbar forward flexion and pelvic inclination was good to fair (ICC range, .84–.79), and extension and rotation was fair to poor (ICC range, .76–.58). Interrater reliability was fair to poor for all lumbar motions and for pelvic inclination (ICC range, .79–.55). Less than 2% of the variation in sagittal plane measurements was explained by consistency of palpation for device placement. Conclusions The BROM provides a reliable means of measuring lumbar forward flexion, side bending, and pelvic inclination when performed by the same examiner in asymptomatic subjects.
On-Plate Desalting and SALDI-MS Analysis of Peptides with Hydrophobic Silicate Nanofilms on a Gold Substrate

We report the use of silicate nanofilms for on-plate desalting and subsequently direct laser desorption/ionization-mass spectrometric (LDI-MS) analysis of peptides. A hydrophobic octadecyltrichlorosilane (OTS) monolayer is formed on a calcinated nanofilm on a gold substrate to facilitate sample deposition and interaction with the surface that allows effective removal of MS-incompatible contaminants such as salts and surfactants by simple on-plate washing while the peptides are retained on the spot. By elimination of interferences from matrix-related ions and contaminants, sensitivity of MS analysis has been enhanced over ca. 20 times, leading to improved detection of peptides at the low-femtomolar level. A high recovery rate of the peptides is obtained by using relatively rough nanofilms, which are prepared through a modified layer-by-layer deposition/calcination process. The performance of the films has been investigated with peptide samples in the presence of high salts (NaCl and sodium acetate) and ure...
Localized opacification of hydrophilic acrylic intraocular lenses after procedures using intracameral injection of air or gas.

Purpose To describe clinical and laboratory findings in a series of cases of intraocular lens (IOL) opacification after procedures involving intracameral injections of air or gas. Setting John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Design Experimental study. Methods Seven hydrophilic acrylic IOLs explanted after Descemet-stripping endothelial keratoplasty (DSEK) or Descemet-stripping automated endothelial keratoplasty (DSAEK) because of a localized central optic opacification associated with decrease in visual acuity and complaints of foggy vision were analyzed. The explanted IOLs were sent to our laboratory in the dry state or in fixative by the explanting surgeons. They underwent pathological and histochemical evaluation (alizarin red and von Kossa method). Light scattering measurements were also performed on the surface of 1 explant using Scheimpflug photography. A questionnaire was sent to the surgeons to obtain information pertinent to each case. Results The 7 explanted IOLs were represented by 6 hydrophilic acrylic designs from 5 manufacturers. Gross and light microscopy showed that granular deposits were densely distributed in an overall round pattern within the margins of the capsulorhexis or the pupil on the anterior surface/subsurface of the IOLs. The granules stained positive for calcium (alizarin red and von Kossa method). Light scattering on the anterior optic surface was very high (228 versus 13 computer-compatible tapes on a control IOL). Conclusions A localized pattern of calcification was seen on the anterior surface/subsurface of various hydrophilic acrylic IOLs. Surgeons should be aware of this phenomenon following DSEK/DSAEK procedures in pseudophakic patients with hydrophilic acrylic IOLs. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.
A Point Mutation in HLA-A*0201 Results in Failure to Bind the TAP Complex and to Present Virus-Derived Peptides to CTL

Mutating the HLA-A*0201 heavy chain from threonine to lysine at position 134 (T134K) results in a molecule that presents exogenous peptide, but cannot present endogenously derived antigen. This is reflected in diminished cell surface expression and altered intracellular trafficking of T134K. The failure of T134K to present endogenous antigen can be overcome by using an ER targeting sequence, suggesting that the antigen presentation defect is restricted to TAP-dependent peptide loading. The ability of T134K to load peptide in a TAP-dependent manner is dramatically reduced compared with HLA-A*0201. By coimmunoprecipitation there is no detectable association of the T134K molecule with the TAP complex. Thus, T134K selectively affects TAP association and peptide loading, suggesting a requirement for the direct interaction of MHC class I heavy chain and the TAP complex for efficient presentation of endogenous antigen.
Effects of weak disorders on quantum Hall critical points

We study the consequences of the random mass, random scalar potential, and random vector potential on the line of fixed points between integer and/or fractional quantum Hall states and an insulator. This line of fixed points was first identified in a clean Dirac fermion system with both Chern-Simon coupling and Coulomb interaction [Phys. Rev. Lett. 80, 5409 (1998)]. By performing a renormalization-group analysis in $1/N$ $(N$ is the number of species of Dirac fermions) and the variances of three disorders ${\ensuremath{\Delta}}_{M},{\ensuremath{\Delta}}_{V},{\ensuremath{\Delta}}_{A},$ we find that ${\ensuremath{\Delta}}_{M}$ is irrelevant along this line, and both ${\ensuremath{\Delta}}_{A}$ and ${\ensuremath{\Delta}}_{V}$ are marginal. With the presence of all three disorders, the pure fixed line is unstable. Setting Chern-Simon interaction to zero, we find one nontrivial line of fixed points in the $({\ensuremath{\Delta}}_{A},w)$ plane with dynamic exponent $z=1$ and continuously changing \ensuremath{\nu}; it is stable against small $({\ensuremath{\Delta}}_{M},{\ensuremath{\Delta}}_{V})$ in a small range of the line $1lwl1.31,$ therefore it may be relevant to integer quantum Hall transition. Setting ${\ensuremath{\Delta}}_{M}=0,$ we find a fixed plane with $z=1,$ the part of this plane with $\ensuremath{\nu}g1$ is stable against small ${\ensuremath{\Delta}}_{M},$ therefore it may be relevant to fractional quantum Hall transition. Although we do not find a generic fixed point with all the couplings nonvanishing, we prove that the theory is renormalizable to the order ${(1/N)}^{2},(1/N)\ensuremath{\Delta},{\ensuremath{\Delta}}^{2},$ and we explore the interesting processes which describe the interferences between the Chern-Simon interaction, the Coulomb interaction, and the three kinds of disorders.
An Investigation of the Factors that Contribute to Pilots' Decisions to Continue Visual Flight Rules Flight into Adverse Weather

Pilots' decisions to continue or divert from a visual flight rules flight (VFR) into instrument meteorological conditions (IMC) were investigated using a dynamic simulation of a hypothetical cross-country flight. Issues related to decision-making were investigated. Specifically, differences in situation assessment, risk perception and motivation, between pilots who chose to continue or divert from a VFR flight into IMC situation were examined. Results indicate that the simulation was successful in identifying pilots who would choose to either continue or divert and that differences existed between these two groups of pilots. Accuracy of visibility estimates, appraisal of one's own skill and judgment and frequency of risk-taking behavior were most important in predicting whether a pilot would continue or divert from a VFR flight into IMC situation. Findings suggest that overconfidence in personal ability and inaccurate diagnoses of visibility conditions precipitate VFR flight into IMC.
Kinetics of the lamellar and hexagonal phase transitions in phosphatidylethanolamine. Time-resolved x-ray diffraction study using a microwave-induced temperature jump.

The kinetics of the thermotropic lamellar gel (L beta')/lamellar liquid crystal (L alpha) and L alpha/inverted hexagonal (HII) phase transitions in fully hydrated dihexadecylphosphatidylethanolamine (DHPE) have been studied. Measurements were made by using time-resolved x-ray diffraction (TRXRD) to monitor progress of the transitions. In these studies microwave energy at 2.5 GHz was used to increase the sample temperature rapidly and uniformly through the phase transition regions. The L beta'/L alpha and L alpha/HII transitions of DHPE were examined under active microwave heating and passive cooling. The transitions were found to be repeatable and reversible, and to have an upper bound on the time required to complete the transition of less than 3 s. Regardless of the direction of the transition, both phase transitions appeared to be two-state with no accumulation of intermediates to within the sensitivity limits of the TRXRD method. The rate and amplitude of the temperature jump can be controlled by regulating microwave radiation input power. A temperature jump rate of 29 degrees C/s was obtained at a final microwave power setting of 120 W. Comparisons between previously reported fluid flow (Caffrey, M. 1985. Biochemistry. 24:4826–4844) and microwave heating studies suggest that the determination of limiting transit times will require faster heating.
Rapid Increases in Glial Fibrillary Acidic Protein mRNA and Protein Levels in the Copper-Deficient, Brindled Mouse

: The brindled mouse (Mobr/y) carries an X-linked mutation that produces severe copper deficiency. Affected males suffer profound deficits in oxidative metabolism. We have examined astrocyte pathology in Mobr/y during development and have found marked changes in the metabolism of glial fibrillary acidic protein (GFAP). Immunocytochemistry with anti-GFAP antisera revealed a marked increase in staining at postnatal day 12 (P12), compared to heterozygous female and unaffected male littermates, particularly in neocortex and thalamus. Septum, hypothalamus, and striatum showed little change. Western blot analysis revealed increased levels of GFAP in Mobr/y forebrain and cerebellum. Levels of GFAP mRNA were determined by Northern blotting with a mouse GFAP cDNA probe. At P10, mRNA levels were normal, but increased to 8–10 times normal by P12. Levels at P15 remained similarly elevated. Thus, immunostaining and protein determinations correlate with mRNA elevations. Astrocytes can alter GFAP mRNA and protein levels over a relatively short time. Counts of neocortical cells did not reveal differences in cell numbers between Mobr/y and controls, indicating that the observed changes reflect increased cellular levels and not a large increase in the numbers of astrocytes.
Validity of the FACT Hepatobiliary (FACT-Hep) questionnaire for assessing disease-related symptoms and health-related quality of life in patients with metastatic pancreatic cancer

Purpose Evaluate reliability and validity of the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire and its derivative FACT Hepatobiliary Symptom Indexes (FHSI-18 and FHSI-8) in people with metastatic pancreatic cancer.
Ursodeoxycholic acid in the treatment of cholesterol cholelithiasis part II

Effectiveness Dissolution of Gallstones. In almost every report of treatment of patients with cholesterol gallstones with UDCA, the calculation of the success rate is based on the sum of the complete and partial dissolutions, in this review~ only complete disappearance of the gallstones is accepted as a successful result, since reduction of size during treatment does not guarantee that continued treatment will result in complete dissolution. Data from publications which do not distinguish between partial and complete dissolution in presenting the rate of successful treatment are therefore not included in the tabulations. Furthermore, some of the authors display their data in a way which makes it impossible to understand their results. This is attributable in no small measure to changes of dosage during the trial instead of continuing with a given dose in a given patient. Where the dose is stated in mg/kg/day, it was certainly not prescribed that way. The investigators prescribed the number of tablets or capsules to be taken daily, then calculated the dose on a weight basis. The smallest number of patients in any series was 12 (140), the largest 106 (145), the latter a multicenter study. The total number of patients entered in all series (Table 18) was 852, of whom 128 (15%) dropped out. Drop-outs are defined in this review as
Twin Tornado Cyclones within a Severe Thunderstorm: Single Doppler Radar Observations

(1973). Twin Tornado Cyclones within a Severe Thunderstorm: Single Doppler Radar Observations. Weatherwise: Vol. 26, No. 2, pp. 63-71.
Ultrastructural localization of urate oxidase in nodules of Sesbania exaltata, Glycine max, and Medicago sativa.

The localization of urate oxidase (=uricase, E.C. 1.7.3.3) was determined cytochemically in nodules of Sesbania exaltata (Raf.) Cory, soybean (Glycine max [L.] Merr.) and alfalfa (Medicago sativa [L.]), using the precipitation of peroxide (produced during the oxidation of urate) by cerium chloride. Cerium perhydroxide reaction product was noted only in the microbodies, a localization consistent with biochemical fractionation studies on urate oxidase. Urate oxidase was present not only in the uninfected cells of the cortical tissue, but also in both infected and interstitial cells in the central tissue, suggesting that at least this enzyme of ureide metabolism is not confined to interstitial cells. Urate oxidase cytochemistry of nodules from alfalfa (Medicago sativa L.), an amide producer, also resulted in microbody staining but the microbodies were infrequently noted in cell profiles.
Thermal conductivity: A review of some important developments

Abstract Some recent developments are presented which relate to the thermal conductivity of metals and its measurement. These include the influence of sample size on the electronic thermal conductivity of very pure metals, the thermal conductivity minimum of aluminium and a few other metals at sub-normal temperatures, the high-temperature thermal conductivity and increasing Lorenz function of platinum, with particular reference to the experiments of Flynn and O'Hagan (1967), the thermal conductivity of molten metals and the recently reported Lorenz functions decreasing with increase in temperature to well below the theoretical value, and the encouraging results of an investigation in progress at the Thermophysical Properties Research Center (TPRC) on direct electrical heating methods for the measurement of metallic thermal conductivities to high temperatures. Modern computer techniques avoid the restrictions and approximations introduced in the many existing methods and allow thermal conductivity to be ac...
Combining ridge and principal component regression:a money demand illustration

In this paper we examine a class of estimators which includes ordinary least squares, ordinary ridge regression, and principal components regression. It is demonstrated that gains exist from jointly utilizing the PCR and ORR techniques.A money demand example is utilized to illustrate alternative estimators.
A chemical approach for site-specific identification of NMR signals from protein side-chain NH 3 + groups forming intermolecular ion pairs in protein–nucleic acid complexes

Protein–nucleic acid interactions involve intermolecular ion pairs of protein side-chain and DNA or RNA phosphate groups. Using three protein–DNA complexes, we demonstrate that site-specific oxygen-to-sulfur substitution in phosphate groups allows for identification of NMR signals from the protein side-chain NH3+ groups forming the intermolecular ion pairs. A characteristic change in their 1H and 15N resonances upon this modification (i.e., substitution of phosphate to phosphorodithioate) can represent a signature of an intermolecular ion pair. Hydrogen-bond scalar coupling between protein side-chain 15N and DNA phosphorodithiaote 31P nuclei provides direct confirmation of the intermolecular ion pair. The same approach is likely applicable to protein–RNA complexes as well.
Posttranscriptional regulation of ATA2 transport during liver regeneration.

Abstract The recent cloning of ATA2, a cDNA displaying characteristics identical to the System A transporter, has provided the first molecular tool for study of System A-mediated amino acid transport in liver. Despite the 233 ± 9 and 472 ± 11% increase in System A transport activity following partial hepatectomy at 6 and 12 h, respectively, the steady-state level of ATA2 mRNA did not show a corresponding marked increase. Examination of the kinetic properties of System A following partial hepatectomy revealed a Km of 0.26 ± 0.04 mM which is consistent with the reported Km for ATA2. These results indicate that a System A transporter present in regenerating liver and ATA2 are identical, but that the increase in System A activity following partial hepatectomy does not result from an increase in steady-state levels of ATA2 mRNA. These observations suggest that ATA2-mediated transport of amino acids is regulated at the posttranscriptional level.
Ultrafiltration for Congestive Heart Failure

Relief of congestive symptoms is a primary goal in treating heart failure. Ultrafiltration is a tool that can be used to safely remove sodium and water from whole blood at a controlled rate. Ultrafiltration decreases symptoms, relieves congestion, and improves hemodynamics, neurohormonal balance, and exercise capacity. This article describes the importance of congestion as a therapeutic target in heart failure and outlines the development of ultrafiltration as a treatment to address this important physiologic state.
Travel Mode Choice of the Elderly: Effects of Personal, Household, Neighborhood, and Trip Characteristics:

The travel patterns and travel mode choice of the elderly are analyzed. The elderly are here defined as those who are both 65 or older and retired. A rapid increase in the older population and their proportion in society has tremendous implications for transportation planning and the policy arena. Previous studies on mode choice have been largely focused on working-age people, and existing studies on the travel mode choice of the elderly are limited to descriptive analyses. A systematic analysis is presented of the mode choice of the elderly and how it relates to activity purpose. It is found that neighborhood and trip characteristics, as well as personal and household characteristics, are associated with the mode choice of this group. For example, the elderly are more likely to use transit if they live within five blocks of a bus stop, and they are more likely to share a ride with others when chaining trips, doing errands, or going to a medical appointment and are less likely to use transit when going sh...
Malignant Mixed Mullerian Tumor of the Female Peritoneum: Treatment and Outcome of Three Cases

Three cases of malignant mixed mullerian tumor of the peritoneum are presented. One patient had a complete clinical and pathologic response and remains disease-free 42 months following diagnosis. As with peritoneal carcinoma and ovarian sarcoma, aggressive surgical cytoreduction and postoperative chemotherapy appear indicated.
Purification and Characterization of an NADH-Dependent Alcohol Dehydrogenase from Candida maris for the Synthesis of Optically Active 1-(Pyridyl)ethanol Derivatives

A novel (R)-specific alcohol dehydrogenase (AFPDH) produced by Candida maris IFO10003 was purified to homogeneity by ammonium sulfate fractionation, DEAE-Toyopearl, and Phenyl-Toyopearl, and characterized. The relative molecular mass of the native enzyme was found to be 59,900 by gel filtration, and that of the subunit was estimated to be 28,900 on SDS-polyacrylamide gel electrophoresis. These results suggest that the enzyme is a homodimer. It required NADH as a cofactor and reduced various kinds of carbonyl compounds, including ketones and aldehydes. AFPDH reduced acetylpyridine derivatives, β-keto esters, and some ketone compounds with high enantioselectivity. This is the first report of an NADH-dependent, highly enantioselective (R)-specific alcohol dehydrogenase isolated from a yeast. AFPDH is a very useful enzyme for the preparation of various kinds of chiral alcohols.
The role of cytokines and adhesion molecules in the development of inflammatory injury

Clinicians are constantly challenged by patients who demonstrate the ill effects of an uncontrolled host inflammatory response. Patients with sepsis and adult respiratory distress syndrome (ARDS) are frequently encountered examples of this syndrome. Despite advances in intensive care, mortality from these syndromes remains unchanged over the past two decades. In order to gain a better understanding of this pathophysiological response and to identify more specific therapeutic targets, the techniques of molecular biology have been applied to in vivo inflammatory models. Recent data indicate that the inflammatory response is dependent on the presence of both cytokines and adhesion molecules that mediate neutrophil-endothelial cell adhesive interactions. In this article, we review our experience using a lung model of inflammation that has provided insight into the events leading to injury. Cytokines [particularly, interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha)], and endothelial, as well as leukocyte, adhesion molecules appear to coordinate a cascade of interactions between leukocytes and endothelial cells, which results in tissue injury.
Local area network applications of plastic optical fiber

The information explosion that occurred in the 1980s led to the widespread introduction of personal computers to the office, laboratory, and factory environments. The need to share information and resources amongst workstations demanded a networking solution, specifically a local area network (LAN). Since that time many media have been developed for use in LANs, each meeting a specific user demand. Glass fiber was developed for use in long distance, high bandwidth applications, but the high cost of hardware and installation has daunted users. Twisted pair was developed as a low cost alternative medium for use in shorter distance applications. However, as computer applications have become more graphics intensive, LANs have been required to transmit a much greater volume of information, necessitating a media with much higher bandwidth. Since twisted pair cannot support the higher signalling rates, there has been significant interest in a low cost fiber solution. This paper discusses the suitability of plastic optical fiber (POF) for use in local area networks. It outlines the cost and performance advantages offered by POF, discusses the inherent limitations of the medium, and defines an application space where POF is the optimal solution.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Family Engagement within Schoolwide Positive Behavioral Interventions and Supports.

Parent educational involvement is an important avenue for enhancing student outcomes. Schools seek myriad ways to include families; however, the parent involvement practices used by schools lack coordination and are disconnected from existing school approaches. Schoolwide Positive Behavioral Interventions and Supports (PBIS) is a systematic and coordinated framework used in more than 19,000 schools to support student behavior. Despite its success, PBIS implementation underemphasizes comprehensive systems for engaging families. The purpose of this article is to present a framework of family engagement within PBIS. The purpose of coordinating and sequencing family engagement within PBIS is to increase the efficiency, effectiveness, relevance, and durability of PBIS by supporting students across settings. Furthermore, this model extends current parent involvement frameworks by coordinating systematic family engagement in education.
Catalysis by cationic polyelectrolytes and micelles in bisulfite oxidation

The oxidation of sodium bisulfite in the presence of cationic polyelectrolytes or micelles has been studied. The formation of cationic-bisulfite complexes is indicated, and a kinetic analysis suggests the validity of the enzyme kinetics applied to determine the kinetic parameters. Distinct differences in the activity of cationics depend on the configuration of the cationics in solution; micelle-forming cationics are more effective than nonmicellar polycationics, except in the case of poly(diallyldimethylammonium chloride), (PDADM). The oxidation rate is strongly affected by the presence of monomer in the system, especially where nonmicellar polycationics are involved.
Thermostating extended Lagrangian Born-Oppenheimer molecular dynamics.

Extended Lagrangian Born-Oppenheimer molecular dynamics is developed and analyzed for applications in canonical (NVT) simulations. Three different approaches are considered: the Nose and Andersen thermostats and Langevin dynamics. We have tested the temperature distribution under different conditions of self-consistent field (SCF) convergence and time step and compared the results to analytical predictions. We find that the simulations based on the extended Lagrangian Born-Oppenheimer framework provide accurate canonical distributions even under approximate SCF convergence, often requiring only a single diagonalization per time step, whereas regular Born-Oppenheimer formulations exhibit unphysical fluctuations unless a sufficiently high degree of convergence is reached at each time step. The thermostated extended Lagrangian framework thus offers an accurate approach to sample processes in the canonical ensemble at a fraction of the computational cost of regular Born-Oppenheimer molecular dynamics simulations.
Incoherent Combining and Atmospheric Propagation of High-Power Fiber Lasers for Directed-Energy Applications

High-power fiber lasers can be incoherently combined to form the basis of a directed high-energy laser system which is highly efficient, compact, robust, low-maintenance and has a long operating lifetime. This approach has a number of advantages over other beam combining methods. We present results of the first field demonstration of incoherent beam combining using kilowatt-class, single-mode fiber lasers. The experiment combined four fiber lasers using a beam director consisting of individually controlled steering mirrors. Propagation efficiencies of ~90%, at a range of 1.2 km, with transmitted continious-wave power levels of 3 kW were demonstrated in moderate atmospheric turbulence. We analyze the propagation of combined single-mode and multimode beams in atmospheric turbulence and find good agreement between theory, simulations and experiments.
Formalization and abstract implementation of rewriting with nested rules

This paper formalizes term rewriting systems (TRSs), called scoped, in which a rewrite rule can be nested within another rewrite rule. The right-hand side and/or the condition of a nested rule can refer to any variable in the left-hand side of a nesting rule. Nesting of rewrite rules is intended to define a lexical scope with static binding. Our work is applicable to programming languages in which programs are modeled by TRSs and computations are executed by rewriting or narrowing. In particular, we consider a class of non-confluent and non-terminating TRSs well suited for modeling modern functional logic programs. We describe an abstract implementation of rewriting and narrowing for scoped TRSs to show that scopes can be easily handled irrespective of the evaluation strategy. The efficiency of rewriting within a scoped TRS, measured using a narrowing virtual machine, is comparable to the efficiency of rewriting for non-scoped TRSs.
Hedgehog pathway-regulated gene networks in cerebellum development and tumorigenesis

Many genes initially identified for their roles in cell fate determination or signaling during development can have a significant impact on tumorigenesis. In the developing cerebellum, Sonic hedgehog (Shh) stimulates the proliferation of granule neuron precursor cells (GNPs) by activating the Gli transcription factors. Inappropriate activation of Shh target genes results in unrestrained cell division and eventually medulloblastoma, the most common pediatric brain malignancy. We find dramatic differences in the gene networks that are directly driven by the Gli1 transcription factor in GNPs and medulloblastoma. Gli1 binding location analysis revealed hundreds of genomic loci bound by Gli1 in normal and cancer cells. Only one third of the genes bound by Gli1 in GNPs were also bound in tumor cells. Correlation with gene expression levels indicated that 116 genes were preferentially transcribed in tumors, whereas 132 genes were target genes in both GNPs and medulloblastoma. Quantitative PCR and in situ hybridization for some putative target genes support their direct regulation by Gli. The results indicate that transformation of normal GNPs into deadly tumor cells is accompanied by a distinct set of Gli-regulated genes and may provide candidates for targeted therapies.
Ovine Prion Polymorphisms Investigated by Threading to a Model Left Handed Beta Helical Structure using Molecular Dynamics Simlation

We use AMBER all atom molecular dynamics (MD) to assess the stability of a model of the prion protein in its disease-causing conformation, PrPsc. The model is based upon threading the ovine prion sequence onto a template left-handed beta-helical (LHBH) structure with 18 residues per turn. Five polymorphisms in the sheep prion protein, VRQ, ARQ, ARH, AHQ, and ARR, have been identified at residues 136, 154, and 171 respectively, which are roughly 18 amino acids apart which thus align approximately on the LHBH. Threading of the sequence was thus done with an emphasis on the locations of these special sites as a means to investigate their possible role in disease susceptibility as well as investigating the overall viability of the LHBH as a structural candidate for PrPsc. In comparison to known left handed beta-helical proteins, the resulting model for VRQ is shown in all atom MD to 10 ns to exhibit similar stability as indicated by a low root mean square deviation, the presence of substantial side-chain to side-chain hydrogen bonding, and volume packing fraction. Interestingly, and in corroboration with experimental data that it is a disease resistant variant, the same model for ARR exhibits much less stability. Each polymorphic site was also investigated individually by comparing results from models with only one site different and showed a good correlation to experimental data regarding the relation of the variants to disease susceptibility.
Elevated urinary norepinephrine in interstitial cystitis.

Objectives. To measure urinary catecholamines and determine the extent to which they may be elevated in urine from patients with interstitial cystitis (IC). Methods. Random urine samples from patients with IC (n = 111) and urine from normal volunteers (n = 92) were acidified on collection (voided and catheterized specimens) and assayed for catecholamine (norepinephrine or normetanephrine) by enzyme-linked immunosorbent assay. Creatinine levels in these urine samples were also measured. Results. Analysis of the data indicated that patients with IC had a higher urinary level of the neurotransmitter norepinephrine compared with the measured levels in the urine of normal volunteers (89.1 ± 58.3 versus 54.9 ± 37.1 μg/g creatinine, P <0.05). The metabolite normetanephrine was similar in the urine samples from these two groups. Urine from patients with bladder outlet obstruction (n = 11) did not have elevated amounts of urinary norepinephrine. The norepinephrine levels were not statistically different in the urine samples from patients with symptomatic and asymptomatic IC. The elevated urinary levels in patients with IC did not decrease after treatment with sodium pentosanpolysulfate (Elmiron), heparinoids, dimethyl sulfoxide, or combinations of these during 1 to 15 months of treatment. Conclusions. Norepinephrine was found to be elevated in the urine from patients with IC compared with urine from normal controls. This would be consistent with increased sympathetic (adrenergic) activity from the bladders of patients with IC or possibly from increased adrenal activity, since stress is associated with symptom increase in some patients with IC. Norepinephrine levels did not decrease with treatment nor did they differ between symptomatic and asymptomatic patients at the time of urine collection.
The distribution of cell generation times.

Two different distributions of generation times, log-normal and reciprocal normal, were compared by fitting them to experimental generation time distributions for bacteria, yeast, protozoa, and mammalian cells. In every case, the reciprocal normal distribution gave better agreement, whether the original frequency distributions or their cumulatives were compared. the log-normal distribution failed to give significant agreement for three of the original distributions. It is concluded that the reciprocal normal distribution of generation times, or more precisely, the truncated normal distribution of generation rates, is consistent with the published data for steady state populations of all kinds of cells that divide by regular binary fission. A model is suggested for this distribution of generation times, associating it with control of transport of materials into the cell, and with linear cell growth.