cssi/SciSciGPT-SciSciNet huggingface dataset:
Nicotinic control of adult-born neuron fate.

The hippocampus is one of only two regions in the adult brain where neurons are generated in significant numbers throughout the lifetime of the animal. Numerous studies have demonstrated that these adult-born neurons are essential for optimal cognitive function with unimpaired memory formation and retrieval. The extent to which adult-born neurons survive through an early “critical period” and become integrated into functional networks has been shown to depend on the richness of stimulation they receive during these formative stages. The dentate gyrus in the hippocampus – home of the adult-born neurons – receives extensive cholinergic innervation, and newly generated neurons in the adult hippocampus express substantial numbers of both major types of neuronal nicotinic acetylcholine receptors. Early studies indicated that nicotinic signaling may be important for the development of adult-born neurons: repeated exposure to nicotine impaired their long-term survival. Recent studies with mutant mice lacking either one of the two major nicotinic receptor subtypes demonstrate that receptor loss results in fewer adult-born neurons surviving the critical period and becoming integrated into neural networks. The key nicotinic receptor mediating the largest effects is one that has a high relative permeability to calcium. In view of this feature, it may not be surprising that excessive exposure to nicotine can have detrimental effects on survival and maturation of adult-born neurons in the dentate; these same receptors appear to be key. The results pose serious challenges for therapeutic strategies targeting an individual class of nicotinic receptors for global treatment in the recipient.
LC/ESI/MS method development for the analysis of hepatotoxic cyclic peptide microcystins in animal tissues.

Abstract Microcystins (MCYSTs) are a family of related cyclic heptapeptides produced by several genera and species of blue-green algae (cyanobacteria). MCYSTs are potent and specific inhibitors of the serine threonine family of protein phosphatases, especially PP1 and PP2A. MCYSTs inhibit a liver's protein phosphatase by forming a covalent linkage between MCYSTs' Mdha residue and the phosphatase's cysteine residue. Due to the covalent linkage, analysis of MCYSTs in animal tissues has been limited to determination of unbound MCYST concentration. The MMPB (2-methyl-3-methoxy-4-phenylbutyric acid) oxidation procedure allows for the detection of total MCYST burden by releasing the carboxylic acid MMPB from MCYST's Adda amino acid. An internal standard 4-phenylbutyric acid (4PB) accounts for losses during the method. LC/MS conditions were developed using a ThermoFinnigan LCQDuo ion trap in negative electrospray ionization (ESI). Since both compounds produce the [M–H]− ion, analysis occurs in selected ion monitoring (SIM) mode for both MMPB (m/z 207.1) and 4PB (m/z 163.1). Complete oxidation of MCYST-LR in liver tissues occurs in 3 h. A solid phase extraction (SPE) cartridge removes MMPB and 4PB from the oxidant solution. The process efficiency for the SPE procedure is only 51.3%; however, suppression experiments indicate a 41.8% loss in signal strength due to matrix interferences. Therefore, the extraction efficiency for the SDB-XC cartridge procedure is 93.1%. This research has been successful in developing an LC/MS method for the analysis of total MCYST burden in animal tissues.
S9-6 Elemental sulfur reduction by eukaryotic cytoplasm consistent with an ancient sulfur symbiosis

An accepted theory for the origin of eukaryotic cells postulates a methanogenic ancestor, although no evidence of methanogenesis exists in modern eukaryotic cells. Instead, sulfur reactions are ubiquitous. The seminal event in eukaryotic evolution might have been a sulfur-based symbiosis between a S°-reducing host and a sulfide-oxidizing bacterium. A vestige of those activities might remain in modern cells. To test this, Tetrahymena thermophila was examined as a representative eukaryotic cell. Aerobic cells consumed H 2 S at a rate of 140 nmol (g protein) −1 s −1 . Anoxic cells produced H 2 S at 1.1 nmol g −1 s −1 , but H 2 S production was suppressed by AOAA, an inhibitor of cysteine catabolism. When aerobic cells were fed H 2 S slowly so that all the H 2 S was oxidized, and then made anoxic, H 2 S was produced at up to 3.6 nmol g −1 s −1 , and not inhibited by AOAA. Evidently, H 2 S is oxidized to a compound that is available for H 2 S production. When aerobic incubation was continued after H 2 S addition had stopped, subsequent H 2 S production decreased with t 1/2 = 11 min. When S° was added to 7 mg cells at 85 pmol s −1 , H 2 S production was 4.4 nmol g −1 s −1 and not inhibited by AOAA. When cells were lysed and fractionated, there was NADH-stimulated S° reductase activity in the membrane fraction, distinguishing it from NADPH disulfide oxidoreductases and linking S° reduction to glycolysis. Thus, there is evidence of a sulfur cycle in which S° is reduced in the cytoplasm and H 2 S is oxidized in mitochondria.
SEQUENCES OF THE RRN18 GENES OF CHLAMYDOMONAS HUMICOLA AND C. DYSOSMOS ARE IDENTICAL, IN AGREEMENT WITH THEIR COMBINATION IN THE SPECIES C. APPLANATA (CHLOROPHYTA)1

The nuclear Rrn18 gene coding for small-subunit ribosomal RNA was amplified from Chlamydomonas humicola and C. dysosmos. The sequences were identical, in agreement with the combination of these two species under the name C. applanata on morphological and physiological grounds by Ettl and Schlosser (1992).
Effects of various implicit operators on a flux vector splitting method

Three different implicit operators in a numerical method for solving the two-dimensional steady Euler equations using flux vector splitting are investigated. These include the implementation of the true Jacobian matrices in the implicit part, the use of their splitting approximate form, and a modification of the implicit part of the scheme that uses the scalar form of the implicit part based on the spectral radii of the split Jacobian matrices. The three versions of the basic algorithm are compared with the results given by two common numerical methods using several two-dimensional test cases. Special attention is paid to the quality of results as well as computational efficiency and convergence properties.
Interference to linear superposability of collisionally activated decomposition spectra at high resolution

A new factor causing the superposability of collisionally activated decomposition spectra of ions to fail has been established for isobaric ions. If the two isobaric ion beams are not transmitted in their entirety simultaneously to the collision cell, the resulting spectrum is not a linear combination of the two spectra of the individually transmitted complete ion beams. Apparently the energy content of collimated ions varies across the ion beam, so that transmission of different portions of the ion beam produces samples of ions with different energy contents.
Music in Diaspora: The View from Euro-America

Diaspora has been kind enough to host a small set of articles focused on diaspora and music in Europe and North America, to which these essays can serve as introduction. Music is central to the dia...
Estimating curvature from volume fractions

An interface represented by discrete, abruptly-varying volume fractions poses particular challenges for the accurate estimation of interfacial curvature. Most approaches within a volume-of-fluid (VOF) framework do not estimate curvature directly from the VOF function, but instead from a smoothly-varying function derived from some mapping (e.g., convolution, discrete quadrature) of the VOF function. In this study we assess and compare the accuracy and robustness of curvature estimates derived from three smooth, VOF-based functions: a convolved VOF (CV) function, a height function (HF), and a reconstructed distance function (RDF). The methodology used in reconstructing a distance function from volume fractions is new and therefore presented in detail along with an analysis of the resulting sensitivities. We find that curvature estimates derived from the height function provide superior results, as measured in smaller error and higher (second-order) convergence rate. While curvature estimates from the RDF provides smaller errors relative to those derived from the CV, both techniques exhibit similar convergence behaviour. Numerical results, including a new cosine wave verification test, are presented to substantiate the findings.
Distance constraints in graph color extensions

Let G be an r-chromatic graph with an s-colorable subgraph, each of whose components is s-colored with (possibly different) s colors taken from a set of r+s colors. Then if the components of the precolored subgraph are sufficiently far apart, the precoloring extends to an (r+s)-coloring of G. We determine in all cases the best possible distance bounds between precolored components that allow for this extension result. Next suppose that G is K"r"+"1-minor-free for r=2,3,4, or 5 (and so is r-colorable by proven cases of Hadwiger's Conjecture). Then similarly to the first result there is an extension of a precoloring of a subgraph, each component of which receives s colors from a set of r+s-1, to an (r+s-1)-coloring of the whole graph; we determine bounds on the distance between precolored components that ensures this extension. We include some open problems in this area, building on our joint work with M.O. Albertson.
Correlation between structure and thermodynamic properties of aqueous sulfur species

Abstract The thermodynamic properties of aqueous sulfur species can be estimated using a structurebased, group contribution additivity method that is based upon first-order approximations. Free energy and enthalpy data used to calibrate the additivity model were critically selected from a variety of sources. Structural groups were chosen so as to minimize subjectivity and maximize the ease of recognition. We have chosen five fundamental groups to represent the major structural components: 1. (1)Sn∗, polymeric sulfur (as 1/n, where n is the length of the longest continuous sulfur chain in the species), 2. (2) O3SIV; 3. (3) O3SVI; 4. (4) O2SIII and 5. (5) bridging oxygen. In addition, a modified “charge-to-size” ratio (C) is used to model the coulombic interaction between ions and the solvent. Thermodynamic data were broken into two sets, one for monovalent species and another for divalent species. Multiple linear regressions of these thermodynamic data were performed in terms of structural groups to yield the following relationships: ΔG f divalent 0 = −176.7O 3 S IV − 1270.4O 3 S VI − 691.8O 2 S III + 1954.5S n ∗ + 757.3O − 1182.2C + 55.0 ΔH f divalent 0 = −231.3O 3 S IV − 1316.9O 3 S VI − 734.1O 2 S III + 2006.5S n ∗ + 734.7O − 1212.5C − 33.2 ΔG f momovalent 0 = −536.9O 3 S IV − 635.1O 3 S VI − 351.7O 2 S III − 128.0S n ∗ − 140.3O − 828.0C + 64.1 ΔH f monovalent 0 = −105.4O 3 S IV − 366.5O 3 S VI − 0.0O 2 S III + 505.8S n ∗ + 0.0O + 0.0C − 520.8. R2 values for regressions exceeded 0.9999 and all residuals were normally distributed. Large values for the regression coefficients indicate that the choice of structural parameters is significant. These coefficients were used to estimate thermodynamic properties of a number of aqueous species for which no experimental data currently exist. Model-derived thermodynamic data were used to find the thermodynamic stability of intermediate sulfur species that occur during the aqueous oxidation of sulfide minerals. This exercise identified at least one thermodynamically feasible pathway for the overall reaction. The data were also used to construct an Eh-pH diagram for aqueous sulfur species with average sulfur oxidation states less than sulfate (VI). The structure-thermodynamic correlation was used to determine the likely structure of the aqueous S2O52− ion, which has been debated over the past 50 years.
Small Molecule Inhibition of the Steroid Receptor Coactivators, SRC-3 and SRC-1

Overexpression of steroid receptor coactivator (SRC)-1 and SRC-3 is associated with cancer initiation, metastasis, advanced disease, and resistance to chemotherapy. In most of these cases, SRC-1 and SRC-3 have been shown to promote tumor cell growth by activating nuclear receptor and multiple growth factor signaling cascades that lead to uncontrolled tumor cell growth. Up until now, most targeted chemotherapeutic drugs have been designed largely to block a single pathway at a time, but cancers frequently acquire resistance by switching to alternative growth factor pathways. We reason that the development of chemotherapeutic agents against SRC coactivators that sit at the nexus of multiple cell growth signaling networks and transcriptional factors should be particularly effective therapeutics. To substantiate this hypothesis, we report the discovery of 2,2'-bis-(Formyl-1,6,7-trihydroxy-5-isopropyl-3-methylnaphthalene (gossypol) as a small molecule inhibitor of coactivator SRC-1 and SRC-3. Our data indicate that gossypol binds directly to SRC-3 in its receptor interacting domain. In MCF-7 breast cancer cells, gossypol selectively reduces the cellular protein concentrations of SRC-1 and SRC-3 without generally altering overall protein expression patterns, SRC-2, or other coactivators, such as p300 and coactivator-associated arginine methyltransferase 1. Gossypol reduces the concentration of SRC-3 in prostate, lung, and liver cancer cell lines. Gossypol inhibits cell viability in the same cancer cell lines where it promotes SRC-3 down-regulation. Additionally, gossypol sensitizes lung and breast cancer cell lines to the inhibitory effects of other chemotherapeutic agents. Importantly, gossypol is selectively cytotoxic to cancer cells, whereas normal cell viability is not affected. This data establish the proof-of-principle that, as a class, SRC-1 and SRC-3 coactivators are accessible chemotherapeutic targets. Given their function as integrators of multiple cell growth signaling systems, SRC-1/SRC-3 small molecule inhibitors comprise a new class of drugs that have potential as novel chemotherapeutics able to defeat aspects of acquired cancer cell resistance mechanisms.
Getting Even More Specific About Physicians’ Obligations: Justice, Responsibility, and Professionalism

Jon Tilburt (2014) explores a logical problem for the concept of professionalism in contemporary medicine, especially as this concept is articulated in the ABIM Physician Charter on professionalism...
Weight-loss maintenance for 10 years in the National Weight Control Registry.

Background The challenge of weight-loss maintenance is well known, but few studies have followed successful weight losers over an extended period or evaluated the effect of behavior change on weight trajectories. Purpose To study the weight-loss trajectories of successful weight losers in the National Weight Control Registry (NWCR) over a 10-year period, and to evaluate the effect of behavior change on weight-loss trajectories. Methods A 10-year observational study of self-reported weight loss and behavior change in 2886 participants (78% female; mean age 48 years) in the NWCR who at entry had lost at least 30 lbs (13.6 kg) and kept it off for at least one year. Data were collected in 1993-2010; analysis was conducted in 2012. Main outcome measures Weight loss (kilograms; percent weight loss from maximum weight). Results Mean weight loss was 31.3 kg (95% CI=30.8, 31.9) at baseline, 23.8 kg (95% CI=23.2, 24.4) at 5 years and 23.1±0.4 kg (95% CI=22.3, 23.9) at 10 years. More than 87% of participants were estimated to be still maintaining at least a 10% weight loss at Years 5 and 10. Larger initial weight losses and longer duration of maintenance were associated with better long-term outcomes. Decreases in leisure-time physical activity, dietary restraint, and frequency of self-weighing and increases in percentage of energy intake from fat and disinhibition were associated with greater weight regain. Conclusions The majority of weight lost by NWCR members is maintained over 10 years. Long-term weight-loss maintenance is possible and requires sustained behavior change.
Totally extraperitoneal (TEP) approach for inguinal hernia: The favorable learning curve for trainees

Abstract Purpose Endoscopic inguinal herniorrhaphy has become an established approach to groin hernia. The use of a totally extraperitoneal (TEP) approach allows a tension-free, preperitoneal approach with potentially less discomfort and morbidity than do classic repairs. Concerns have been raised regarding excessive cost, need for general anesthesia, and an extensive learning curve for surgeon and resident trainee alike. Methods A retrospective analysis of 264 consecutive patients undergoing TEP for inguinal hernia repair from September 1995 to April 2000 was performed. All repairs were performed by surgical trainees under the supervision of a single staff surgeon. Results Mean age of 256 men and 8 women undergoing 386 inguinal hernia repairs was 54 years (range, 15-86). Inguinal hernias were unilateral (n = 142) or bilateral (n = 122); indirect (52%), direct (33%), or pantaloon (15%); 37 defects (10%) were recurrent. Surgical residents (n = 74) participated in all 264 operations and were considered the “junior surgeon” in 211 cases: 19 chief residents did 35 operations, 9 PG-4s performed 27, 8 PG-3s did 17, 10 PG-2s completed 41, and 28 interns did 91 procedures. Mean operative time was 96 minutes (range, 30-261) with no statistical difference among PG-1s, 2s, 3s, 4s, or chief residents learning the procedure. Early postoperative complications included urinary retention (n = 25), seroma (n = 3), ileus (n = 3), and subcutaneous wound infection (n = 1). Fully 24% of patients desired or required overnight admission. All patients (100%) operated on for recurrence (n = 37) or a previous contralateral repair (n = 19) favored the current TEP approach over their prior repair. Hernia recurrence has developed in 8 patients, with 6 (75%) occurring within the first 40 study patients. Mean follow-up was 3.5 years (range, 1.2-5.9 years). Conclusions The totally extraperitoneal approach is a safe and effective method of inguinal hernia repair. Following a learning curve of 40 patients for the staff surgeon, the recurrence rate has been less than 1%, with surgical trainees safely performing TEP repairs under supervision.
Body mass scaling of projected frontal area in competitive cyclists.

The primary purpose of this study was to evaluate the scaling relationship between body mass (m b) and projected frontal area (A P) of competitive male cyclists whilst allowing statistically for the influence of bicycle geometry. A group of 21 cyclists [mean m b 74.4 (SD 7.2) kg, mean height 1.82 (SD 0.06) m, mean age 23.6 (SD 5.1) years] volunteered to have A p determined from photographs at three trunk angles (TA: 5°, 15°, 25°) for each of three seat-tube angles (STA: 70°, 75°, 80°) using a modified cycle ergometer. Using multiple log-linear regression analysis procedures, the following equation was developed: Body A p (meters squared)=0.00433×(STA0.172)×(TA0.0965)×(m b 0.762) (r2=0.73, SEE=0.017 m2) (n=183 images total). This equation indicates that after allowing for the independent influence of STA and TA on A p, A p was proportional to m b raised to the +0.762 power (i.e. A p∝m b 0.762). The 95% confidence interval for this exponent (0.670–0.854) barely included the theoretical two-thirds value but not the +0.55 value for A p or the +0.32 value for submaximal metabolic power ( $$ \dot W_{\rm s} $$ ) of outdoor cycling reported in the literature. Further analysis of wind tunnel data reported in the literature suggests that the coefficient of drag (C D) is proportional to m b raised to the –0.45 power. When combined with the present study findings, it is suggested that the drag area (C D×A P), which should be proportional to $$ \dot W_{\rm s} $$ at submaximal cycling velocities, is proportional to m b to the +0.312 power (i.e. C D×A p∝(m b –0.45)×(m b +0.762)=m b +0.312), which is consistent with the +0.32 exponent for $$ \dot W_{\rm s} $$ in the literature.
Remodeling of organelle-bound actin is required for yeast vacuole fusion

Actin participates in several intracellular trafficking pathways. We now find that actin, bound to the surface of purified yeast vacuoles in the absence of cytosol or cytoskeleton, regulates the last compartment mixing stage of homotypic vacuole fusion. The Cdc42p GTPase is known to be required for vacuole fusion. We now show that proteins of the Cdc42p-regulated actin remodeling cascade (Cdc42p → Cla4p → Las17p/Vrp1p → Arp2/3 complex → actin) are enriched on isolated vacuoles. Vacuole fusion is dramatically altered by perturbation of the vacuole-bound actin, either by mutation of the ACT1 gene, addition of specific actin ligands such as latrunculin B or jasplakinolide, antibody to the actin regulatory proteins Las17p (yeast Wiskott-Aldrich syndrome protein) or Arp2/3, or deletion of actin regulatory genes. On docked vacuoles, actin is enriched at the “vertex ring” membrane microdomain where fusion occurs and is required for the terminal steps leading to membrane fusion. This role for actin may extend to other trafficking systems.
Safety Behaviour Enhances the Acceptability of Exposure

Compulsive washing and contamination fears are among the most common symptoms of obsessive-compulsive disorder (OCD). Research suggests that exposure and response prevention (ERP) is effective for OCD. However, ERP is prone to dropouts and refusals, and a substantial proportion of clients therefore do not receive the care they need. A proposed solution involves the judicious use of safety behaviour to enhance the acceptability of exposure-based interventions. The current study aimed to test this proposed solution. Participants were 70 undergraduate students who completed two exposure exercises for contamination fear, one with safety behaviour and one without. Participants then rated the acceptability of the two exercises. Exposure with safety behaviour (ESB) was rated as significantly more acceptable than ERP. Furthermore, subjective fear ratings were lower and behavioural approach to a series of contaminants was greater in the ESB condition. Results demonstrated the acceptability-enhancing potential of s...
A comparison of six cover crop types in terms of nitrogen uptake and effect on response to nitrogen by a subsequent spring barley crop

A field experiment was conducted at nine sites in England (1991-94) to compare six sown species of cover crop and natural regeneration in terms of nitrogen uptake and effect on response to applied N by a subsequent spring barley crop. The success and extent of cover crop establishment varied among sites and was insignificant in two. This may be associated with the relatively late sowing of the cover crops, the earliest site being sown on 27 August and the latest on 19 October. Dry matter (DM) yield of the sown cover crop at time of incorporation was related to sowing date, earlier sowing giving the higher yields. Maximum total DM yield and N uptake by the above-ground portion of cover crops were 1280 kg DM/ha and 38 kg N/ha respectively. The extent of N uptake by the cover crops appeared to be related to the success of establishment rather than to the level of soil nitrate-N at the time of their sowing. Effects of cover crop incorporation on the subsequent spring barley were small. There was no evidence for any positive effect of the cover crop on N supply to the barley. In one trial, incorporation of forage rye significantly reduced grain yield of the barley by 0.7-1.2 t/ha compared to other cover crop species.
A Computational Methodology for Large-Eddy Simulation of Tip-Clearance Flows

A large-eddy simulation (LES) solver which combines an immersed-boundary technique with a curvilinear structured grid has been developed to study the temporal and spatial dynamics of an incompressible rotor tip-clearance flow. The overall objective of these simulations is to determine the underlying mechanisms for low-pressure fluctuations downstream of the rotor near the endwall. Salient features of the numerical methodology, including the mesh topology, the immersed boundary method, the treatment of numerical instability for non-dissipative schemes on highly skewed meshes, and the parallelization of the code for shared memory platforms are discussed. The computational approach is shown to be capable of capturing the evolution of the highly complicated flowfield characterized by the interaction of distinct blade-associated vortical structures with the turbulent endwall boundary layer. Simulation results are compared with experiments and qualitative as well as quantitative agreement is observed.Copyright © 2003 by ASME
Physical analysis of antibiotic-resistance genes from Streptomyces and their use in vector construction

Restriction endonuclease cleavage maps of five DNA fragments carrying genes for neomycin phosphotransferase and neomycin acetyltransferase (from Streptomyces fradiae), viomycin phosphotransferase (from S. vinaceus), and ribosomal methylases determining resistance to thiostrepton (from S. azureus) and MLS antibiotics (from S. erythreus) are described, together with a map for the SLP1.2 Streptomyces plasmid used to isolate the fragments. Construction of a versatile Streptomyces cloning vector (pIJ61) is reported. pIJ61 carries neomycin phosphotransferase and thiostrepton resistance genes and has unique BamHI and PstI sites which will allow clone recognition by insertional inactivation of neomycin resistance; cloning sites for several other endonucleases are also present. pIJ28, a shuttle vector for Streptomyces and E. coli, carries neomycin resistance and the SLP1.2 and pBR322 replicons.
Reducing the pain of local anesthetic infiltration: Warming and buffering have a synergistic effect

Study objective: To compare room-temperature unbuffered lidocaine, warm lidocaine, buffered lidocanine, and warm buffered lidocaine to determine which of the four solutions is least painful during infiltration. Design: Randomized, controlled, double-blinded, volunteer study. Type of participant: Thirty-two young healthy adults. Main results: Each subject recieved four subcutaneous injections of 1 % lidocaine: room-temperature unbuffered, warm, buffered, and warm buffered. After each injection, participants recorded their perception of pain associated with infiltration of the solution on a visual analog scale. Mean pain scores for the four solutions were determined and analyzed. The mean perceived pain score for the warm buffered solution was significantly lower than for any of the other solutions (versus warm: P =.0005; versus buffered: P =.0028; versus room temperature: P =.0001). There was no statistically significant difference between either the warm solution or buffered solution and the room-temperature unbuffered lidocaine. The difference in mean pain score for the warm buffered solution, compared with those for the warm, buffered, and room-temperature solutions, suggests that warming and buffering have a synergistic effect. Conclusion: Skin infiltration with warm buffered lidocaine is significantly less painful than infiltration with room-temperature unbuffered lidocaine, warm lidocaine, or buffered lidocaine.
Characteristics of a discrimination among two doses of morphine and saline in pigeons

As reported by Gauvin and Young [1987], a robust discrimination can be established among saline, 10 mg/kg morphine, and 1.8 mg/kg morphine. The present experiment further examined the pharmacological characteristics of this discrimination. Pigeons were trained to discriminate among i.m. injections of saline, 1.8 mg/kg morphine (the low-dose, or LD, stimulus), and 10 mg/kg morphine (the high-dose, or HD, stimulus). Performance was maintained under FR 30 schedules of food delivery in 30-min experimental sessions. After establishment of stimulus control, various doses of morphine, the agonist-antagonist nalbuphine, and the nonopioid pentobarbital were tested for generalization to the LD and HD stimuli. For morphine itself, generalization of the LD and HD stimuli varied as a function of dose. A dose of 0.10 mg/kg morphien occasioned responses to only the saline key. As the dose of morphine was increased to 1.8 mg/kg, the proportion of responses to the LD key increased from 0 to 100%. As the dose was increased further, the proportion of responses to the LD key decreased, with a commensurate increase in responses to the HD key. Complete HD generalization occurred at 5.6 or 10 mg/kg morphine. In contrast, the opioid agonist-antagonist nalbuphine (1.0 to 56 mg/kg) evoked generalization to only the LD stimulus. The highest dose of nalbuphine markedly suppressed response rates. The nonopioid pentobarbital (0.1 to 18 mg/kg) evoked neither LD nor HD generalization. This pattern of generalization suggests that the discrimination among saline and two doses of morphine may provide a fruitful assay for the agonist efficacy of novel opioids.
Processing of sinusoidally amplitude modulated signals in the nuclei of the lateral lemniscus of the big brown bat, Eptesicus fuscus

Changes in amplitude are a characteristic feature of most natural sounds, including the biosonar signals used by bats for echolocation. Previous evidence suggests that the nuclei of the lateral lemniscus play an important role in processing timing information that is essential for target range determination in echolocation. Neurons that respond to unmodulated tones with a sustained discharge are found in the dorsal nucleus (DNLL), intermediate nucleus (INLL) and multipolar cell division of the ventral nucleus (VNLLm). These neurons provide a graded response over a broad dynamic range of intensities, and would be expected to provide information about the amplitude envelope of a modulated signal. Neurons that respond only at the onset of a tone make up a small proportion of cells in DNLL, INLL and VNLLm, but are the only type found in the columnar division of the ventral nucleus (VNLLc). Onset neurons in VNLLc maintain a constant latency across a wide range of stimulus frequencies and intensities, thus providing a precise marker for when a sound begins. To determine how these different functional classes of cells respond to amplitude changes, we presented sinusoidally amplitude modulated (SAM) signals monaurally to awake, restrained bats and recorded the responses of single neurons extracellularly. There were clear differences in the ability of neurons in the different cell groups to respond to SAM. In the VNLLm, INLL and DNLL, 90% of neurons responded to SAM with a synchronous discharge. Neurons in the VNLLc responded poorly or not at all to SAM signals. This finding was unexpected given the precise onset responses of VNLLc neurons to unmodulated tones and their ability to respond synchronously to sinusoidally frequency modulated (SFM) signals. Among neurons that responded synchronously to SAM, synchronization as a function of modulation rate described either a bandpass or a lowpass function, with the majority of bandpass functions in neurons that responded to unmodulated tones with a sustained discharge. The maximal modulation rates that elicited synchronous responses were similar for the different cell groups, ranging from 320 Hz in VNLLm to 230 Hz in DNLL. The range of best modulation rates was greater for SAM than for SFM; this was also true of the range of maximal modulation rates at which synchronous discharge occurred. There was little correlation between a neuron's best modulation rate or maximal modulation rate for SAM signals and those for SFM signals, suggesting that responsiveness to amplitude and frequency modulations depends on different neural processing mechanisms.
Transforming Individual Civic Engagement into Community Collective Efficacy: The Role of Bonding Social Capital

Collective efficacy is defined as residents' perceived collective capacity to take coordinated and interdependent action on issues that affect their lives. This study explored factors associated with neighborhood collective efficacy among residents. Utilizing a national sample of 4,120 urban households provided by Annie E. Casey Foundation's Making Connection Initiative, we investigated the mediating role of residents' perceptions of bonding social capital (i.e. reciprocity, trust, and shared norms) in the association between civic engagement and collective efficacy. Multiple regression analyses revealed that civic engagement and bonding social capital were both directly related to collective efficacy. Additionally, bonding social capital partially mediated the relationship between civic engagement and collective efficacy. Specifically, residents who reported greater levels of civic engagement also reported higher levels of bonding social capital. In turn, residents who reported higher levels of bonding social capital also reported higher levels of neighborhood collective efficacy. We discuss implications of these findings for researchers and practitioners interested in associations of neighborhood collective efficacy.
Algorithms for determining network robustness

In this paper, we study algorithms for determining the robustness of a network. Network robustness is a novel graph theoretic property that provides a measure of redundancy of directed edges between all pairs of nonempty, disjoint subsets of nodes in a graph. The robustness of a graph has been shown recently to be useful for characterizing the class of network topologies in which resilient distributed algorithms that use purely local strategies are able to succeed in the presence of adversary nodes. Therefore, network robustness is a critical property of resilient networked systems. While methods have been given to construct robust networks, algorithms for determining the robustness of a given network have not been explored. This paper introduces several algorithms for determining the robustness of a network, and includes centralized, decentralized, and distributed algorithms.
Effect of orally administered phenethyl isothiocyanate on hepatic gene expression in rats.

Phenethyl isothiocyanate (PEITC) is a constituent of cruciferous vegetables that has demonstrated cancer preventive activity in a number of cancer models including lung, prostate, and breast cancer. Our objective was to examine the effects of the oral administration of PEITC for 7 days on the hepatic expression of genes important in drug metabolism and toxicity in Sprague Dawley rats. The liver is the major site for the metabolism of various xenobiotics and carcinogens, and determining the effects of PEITC on the gene expression of hepatic enzymes may provide insight into mechanisms underlying the cancer preventive activity of PEITC. Using a microarray containing 282 genes, we observed that PEITC significantly up-regulated UDPglucuronosyltransferase UGT1A6 and strongly down-regulated nicotinamide N-methyltransferase (NNMT). We also confirmed the down-regulation of NNMT by real-time quantitative RT-PCR. NNMT was recently shown to be elevated in the serum of tumor bearing patients with pancreatic, lung, and colorectal cancer, and may be involved in cell migration. Other genes that were significantly up-regulated were the drug metabolizing enzyme cyp2b15, the anti-apoptotic gene bcl2l2, and the stress regulators Gadd45b, Dnajb9, Dnajb5 and Hspb1. Our results indicate new targets that may be important in the mechanisms of the anticancer effects of PEITC. Of particular significance was the down-regulation of NNMT which may represent a new target for the treatment of a variety of cancers.
Induction of Polyploidy by Kinetin in Triturus viridescens

IN 1962 Buckley, Witkus and Berger1 reported that kinetin induced mitotic divisions throughout the digestive tract of the salamander, Triturus viridescens. It was also reported that these were diploid divisions. The effect followed exposure for 9 days to kinetin and was most evident in the duodenum. Since this was one of the first clear cases of mitotic stimulation in animal tissues by kinetin, a more detailed examination was made of the duodenum. As in the previous work1, the animals were immersed in a 10 mg per cent solution of kinetin for 9 days. During the period of treatment the animals were not fed and the solutions were changed every third day. After 9 days exposure the animals were returned to spring water and allowed a 9-day period of recovery. Immediately after treatment and after daily periods of recovery the tissue was fixed, sectioned and stained using the standard iron alum haematoxylin technique. Acetoorcein smears were also made of the same regions.
Centroid-moment-tensor analysis of the 2011 off the Pacific coast of Tohoku Earthquake and its larger foreshocks and aftershocks

Centroid moment tensors (CMTs) for the March 11, 2011, off the Pacific coast of Tohoku Earthquake and its larger foreshocks and aftershocks are presented. The CMTs are calculated using long-period data from the Global Seismographic Network retrieved in near-real time, and the inversion algorithm employed in the Global CMT Project. Owing to its large size and long duration, the mainshock CMT analysis is performed at periods longer than 300 s. The resulting moment tensor has a scalar moment of 5.3 · 1029 dyne-cm, and a geometry that indicates thrust motion of the Pacific Plate beneath the island of Honshu on a plane dipping 10°. The large scalar moment, translating to moment magnitude M W = 9.1, makes this the fourth largest earthquake in the last 100 years. The mainshock was preceded by several large foreshocks with similar underthrusting mechanisms, the largest of which having M W = 7.4. The aftershock sequence extends over a portion of the plate boundary more than 500 km long, and exhibits an unusual diversity of faulting geometries. Reverse, normal, and strike-slip faulting events with widely varying directions of maximum tension and compression occur throughout the upper plate. A M W = 7.9 aftershock occurred near the southern end of the aftershock zone approximately 30 minutes after the mainshock, and is, at the time of writing, the largest aftershock in the sequence. The second-largest aftershock is a M W = 7.6 normal-faulting outer-rise earthquake that occurred 40 minutes after the mainshock.
DIELS-ALDER REACTIONS OF N-ALKENYL-IMINIUM SALTS : A NOVEL ROUTE TO INDOLIZIDINE DERIVATIVES

Abstract The Diels-Alder reaction of N-alkenyl-2-ethoxyiminium salts and simple alkenes gave Diels-Alder cycloadducts upon heating in nitromethane. Reduction of the intractable cycloadducts with hydride resulted in poor to moderate yields of indolizidine alkaloids.
Treatment of co-occurring PTSD-AUD: effects of exposure-based and non-trauma focused psychotherapy on alcohol and trauma cue-reactivity.

Laboratory studies have shown that exposure to trauma memories increases both craving and salivation responses to alcohol cues among individual with co-occurring posttraumatic stress disorder (PTSD) and alcohol dependence (AD). The purpose of the present study was to examine 1) whether this cue reactivity is dampened following exposure-based treatment for PTSD and 2) how changes in reactivity to trauma cues correspond to changes in alcohol cue-reactivity. Adults with current PTSD and AD (N = 120) were randomly assigned to 9-12 sessions of either Trauma-focused Exposure Therapy (EXP) for PTSD or Health & Lifestyles (HLS, a non-trauma focused comparison treatment), concurrent with 6-week residential AD treatment-as-usual. Participants completed trauma and alcohol cue-reactivity laboratory sessions before and after treatment. Compared to HLS, individuals receiving EXP showed significantly greater reductions in negative affect elicited by trauma cues following treatment. Both treatments demonstrated similar, moderate to large reductions in craving and salivary reactivity over time. Interestingly, latent change in trauma cue-elicited distress over the course of treatment predicted latent change in both trauma cue-elicited alcohol craving and salivation. Overall, findings highlight the utility of integrating trauma-focused therapies like EXP into substance use treatment in the interests of reducing PTSD symptoms and distress associated with trauma cues.
Super-wetting, wafer-sized silicon nanowire surfaces with hierarchical roughness and low defects

This paper reports the fabrication of wafer-sized silicon nanowire (SiNW) surfaces using a modified metal-assisted chemical etching method. The complete fabrication and coating process can be performed in less than three hours, is easily size-scalable, and produces surfaces with very low surface defects, complex, hierarchical surface roughness, and large nanowire height. These surfaces exhibit extreme wettabilities depending on surface coating: oxidized SiNW surfaces are superhydrophilic, while surfaces coated with a fluorinated hydrocarbon are superhydrophobic. The wetting and morphological properties of SiNW surfaces made with one and two etches of different duration are characterized vis-a-vis their effect on water drop mobility. Compared to a single etch process, a double etch followed by coating with a fluorinated hydrocarbon more efficiently produces SiNW surfaces with high contact angles on which microliter-sized water drops roll-off at approximately 0° tilt angle. Due to their very low friction, extreme wetting properties, ease of fabrication, low-cost, and large-sizes, these SiNW surfaces may be advantageous in microfluidic devices, bioanalysis systems sensitive to cross-contamination that require disposable substrates, and other applications.
Modeling and analysis of flow-induced vibrations in circular saws

Modelisation et analyse de deux types de vibrations induites par l'ecoulement dans les scies circulaires fonctionnant a vide, la vibration aleatoire et la vibration resonnante. Modelisation de la source d'excitation, representee par les fluctuations de pression de l'ecoulement, sous forme de forces discretes agissant sur les dents de la scie. Resultats expliquant de nombreux phenomenes de vibration observes experimentalement
Nature of Charge Carriers in Disordered Molecular Solids: Are Polarons Compatible with Observations?

Polaronic theories for charge transport in disordered organic solids, particularly molecularly doped polymers, have been plagued by issues of internal consistency related to the magnitude of physical parameters. We present a natural resolution of the problem by showing that, in the presence of correlated disorder, polaronic carriers with binding energies $\ensuremath{\Delta}\ensuremath{\sim}50--500\mathrm{meV}$ and transfer integrals $J\ensuremath{\sim}1--20\mathrm{meV}$ are completely consistent with the magnitudes of field and temperature dependent mobilities observed.
Nitric oxide nanoparticles for wound healing: Future directions to overcome challenges

Chronic, nonhealing wounds inflict significant patient morbidity and mortality and impose considerable economic burdens to health care systems. This has prompted investigations of the potential wound healing therapies, and exogenous delivery of nitric oxide (NO) is one avenue that has been explored. NO is crucial for normal wound repair: it mediates many vital processes that take place after cutaneous injury and helps to ward off invading pathogens due to its inherent antimicrobial and cytostatic properties. Because of its dual wound repair and antimicrobial features, exogenous NO delivery for the acceleration of wound healing is an attractive therapeutic strategy. Several exogenous NO delivery methods have been studied, but limitations preclude their widespread clinical use. Nanotechnology can be exploited for therapeutic delivery of a variety of active ingredients including NO. A hybrid hydrogel/glass composite NO-releasing nanoparticles platform has demonstrated wound healing efficacy both in vitro and...
Agreement Between Large And Small Cuffs In Sphygmomanometry: A Quantitative Assessment

Objective. The objective of this study is to quantify agreement and differences between blood pressure (BP) measurements by large cuffs (15 X 33 cm) and small cuffs (12 X 23 cm) in a representative sample of the U.S. population with varying arm circumferences. Methods. The arm circumference and blood pressure (12 readings of each) of 85 subjects were measured, the latter with a mercury column sphygmo-manometer. Data were classified according to arm circumference (small arm circumference, ≤ 29 cm; large arm circumference, > 29 cm). Results were submitted to ANOVA, linear regression, difference between means (aggregate agreement), upper and lower limits of agreement at 95% confidence intervals, and intraclass correlation (individual-subject agreement/ quantification of agreement). Results. Small cuffs overestimated BP obtained from the large cuffs for the sample population as a whole, regardless of arm circumference. Limits of agreement at the lower end of 95% confidence interval were not clinically acceptable (SBP -1.56 to 11.05 mm Hg; DBP-2.06 to 8.63 mm Hg). However, measurements by both cuffs agreed among subjects with small arm circumferences (≤ 29 cm). Conclusion. Arm circumference plays an important role in determining proper cuff size for BP measurement. The small cuff overestimates BP in patients with large arm circumferences (> 29 cm), which represents more than 75% of the U.S. adult population. However, measurements of BP with the large cuff are not significantly different from those of small cuff measurements in subjects with small arm circumferences (≤ 29 cm). Therefore, we propose that the large cuff be used for routine BP measurement of the adults in the United States.
Vasodilator and inotropic therapy for severe chronic heart failure: Passion and skepticism

Although substantial progress has been made in the last 5 years in the development of vasodilator and inotropic drugs for the management of patients with severe chronic heart failure, much of the enthusiasm that surrounded the introduction of many of these agents has subsequently been tempered by reports of drug failure or adverse reactions. In this review and analysis, currently available vasodilator and inotropic agents are critically and comparatively evaluated to assess their respective advantages and limitations. It is apparent that the ability of most of these drugs to produce substantial clinical benefits in patients with severe heart failure has probably been overstated. Therapy fails to achieve the desired clinical results all too frequently, possibly as the result of: the choice of an ineffective drug; the administration of an effective drug in subtherapeutic doses; the administration of an effective drug to improperly selected patients; the failure of initial hemodynamic benefits to be sustained; the occurrence of severe or serious adverse reactions; and the failure to alter concomitant therapy appropropriately. The present analysis indicates that there is no uni* formly effective or safe vasodilator or inotropic drug for patients with severe heart failure; all agents have important limitations. Of the available therapeutic choices, however, long-term converting enzyme inhibition appears to produce more consistent hemodynamic and clinical benefits with an acceptable degree of adverse reactions than other pharmacologic approaches for the management of these severely ill patients.
Temperature Measurements Using a High-Temperature Blackbody Optical Fiber Thermometer

A blackbody optical fiber thermometer consists of an optical fiber whose sensing tip is given a metallic coating. The sensing tip of the fiber forms an isothermal cavity and the emission from this cavity is approximately equal to the emission from a blackbody. When a short length of the fiber is exposed to a high temperature environment, the temperature at the sensing tip can be inferred using the standard two-color approach. If however, more than a short length of the fiber is exposed to elevated temperatures, emission by the fiber will result in erroneous temperature measurements. We present experimental results that show it is possible to use additional spectral measurements to eliminate errors due to emission by the fiber and measure the tip temperature. In addition, the technique described in this paper can be used to obtain an estimate of the temperature profile along the fiber