cssi/SciSciGPT-SciSciNet huggingface dataset:
Virtual state of the three nucleon system

The existence of a virtual state of the three nucleon system is established on the basis of three different analyses. Values for its pole position and residue in the doublet, $s$-wave, $n\ensuremath{-}d$ elastic scattering amplitude, are obtained from a fit to the experimental data, from partial wave dispersion relations, and from an exact three-particle, separable potential calculation. The calculations indicate that these parameters are determined mainly by the one-nucleon exchange mechanism and the doublet scattering length ${a}_{2}$. For ${a}_{2}=0.65$ fm our best calculation gives an energy of 0.482 MeV below the elastic threshold, on the second Riemann sheet, and a residue parameter ${{C}_{\ensuremath{\nu}}}^{2}=0.0504$, where ${{C}_{\ensuremath{\nu}}}^{2}$ is defined in analogy to the triton asymptotic normalization parameter.NUCLEAR REACTIONS Three-nucleon virtual state; fits to data; dispersion relations; separable potential calculations.
Profiling patterns of glutathione reductase inhibition by the natural product illudin S and its acylfulvene analogues.

Acylfulvenes (AFs) are a class of antitumor agents with favorable cytotoxic selectivity profiles compared to their natural product precursor, illudin S. Like many alkylating agents, illudin S and AFs readily react with thiol-containing small molecules such as cysteine, glutathione and cysteine-containing peptides; reduced cellular glutathione levels can affect illudin S toxicity. Glutathione reductase (GR) is a critical cellular antioxidant enzyme that regulates the intracellular ratio of reduced–oxidized glutathione. In this study, we found that acylfulvene analogues are GRinhibitors, and evaluated aspects of the drug–enzyme interactions as compared with the structurally related natural productilludin S and the known irreversible GRinhibitor, carmustine. Acylfulvene analogues exhibited concentration-dependent GR inhibitory activity with micromolar IC50s; however, up to 2 mM illudin S did not inhibit GR activity. The absence of NADPH attenuates GR inhibition by AFs and the presence of glutathione disulfide (GSSG), the natural GR substrate, which binds to the enzyme active site, has a minimal effect in protecting GR from AFs. Furthermore, each compound can induce GR conformation changes independent of the presence of NADPH or GSSG. These results, together with gel-filtration analysis results and mass spectrometry data, indicate AF is a reversible inhibitor and HMAF an irreversible inhibitor that can form a bis-adduct with GR by reacting with active site cysteines. Finally in a cell-based assay, illudin S and HMAF were found to inhibit GR activity, but this inhibition was not associated with the reduction of GR levels in the cell. A model accounting for differences in mechanisms of GR inhibition by the series of compounds is discussed.
The presence of high-grade prostatic intraepithelial neoplasia or atypia on prostate biopsy does not adversely affect prostatectomy outcomes for patients otherwise eligible for active surveillance.

Objective To investigate if the presence of concomitant high-grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP) on biopsy increases the risk of occult adverse pathology in patients otherwise suitable for active surveillance (AS). Methods Patients with D'Amico low-risk prostate cancer on ≥10-core biopsy who underwent radical prostatectomy at our academic center were evaluated for eligibility for AS by either Epstein criteria or Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Prostatectomy specimens of patients eligible for AS were compared to determine if the presence of clinical HGPIN or ASAP affected the primary outcomes of pathologic upstaging and Gleason score upgrading. Results Of 553 patients with low-risk prostate cancer, 400 patients (72.3%) met the MSKCC criteria, whereas only 170 patients (30.7%) met the Epstein criteria. HGPIN was present in approximately 32%, and ASAP in approximately 12%, of each AS cohort. On univariate and multivariate analyses, HGPIN and ASAP had no impact on the rate of upgrading and upstaging in either Epstein or MSKCC AS-eligible patients. Furthermore, the presence of HGPIN and ASAP had no impact on the 5-year biochemical recurrence-free survival. Conclusion The presence of HGPIN or ASAP does not increase the risk of upgrading, upstaging, or adverse pathology at the time of prostatectomy for patients who meet the AS criteria. If otherwise suitable, HGPIN and ASAP should not impact the decision to choose AS. However, analysis of prospective AS trials is required to determine if HGPIN or ASAP impacts tumor progression once on AS.
Modulation of 17α-hydroxylase/C17,20-lyase activity in porcine theca cells

The major source of ovarian androgen is the theca cells. Androgens are produced by the conversion of progestins by the 17 alpha-hydroxylase/C17,20 lyase enzymatic system (lyase). The 3 beta-hydroxysteroid dehydrogenase and aromatase enzymes in the theca cells are modulated by gonadotropins as well as by steroids produced locally. Therefore, the combined effects of hCG plus progesterone, estradiol, or dihydrotestosterone (DHT) on microsomal lyase activity in theca cells from large and medium-sized follicles were determined. Theca cells (3 x 10(6) cells/6 ml/well) were cultured in Medium 199 (M199) containing only insulin (10 micrograms/ml) and transferrin (5 micrograms/ml). At 24 h, theca cells were treated with M199, hCG (15 ng/ml), progesterone, estradiol, or DHT (100 ng/ml) or a combination of hCG + one of the three steroids. Media were removed at various times of culture (27-72 h) and levels of androgen determined by RIA. Microsomes were incubated with 1 microCi [3H]progesterone +0.5 mM NADPH and radioactive conversion products were measured after purification by thin layer chromatography. Administration of progesterone, estradiol, or DHT alone had little effect on lyase activity in theca cells from medium-sized follicles whereas the addition of hCG alone significantly increased lyase activity in these cells. However, concomitant addition of any steroid with hCG inhibited the increase in lyase activity after the addition of hCG alone. Theca cells from large porcine follicles had a higher basal level of lyase activity compared to theca cells from the smaller follicles. Lyase activity in theca cells from large follicles was enhanced by progesterone; estradiol was inhibitory. DHT initially stimulated lyase activity in theca cells from large follicles, but was inhibitory later in culture. In contrast to its marked effect on theca cells from medium follicles, hCG had only a small effect on lyase activity in theca cells from large follicles. Thus, thecal lyase activity increased as the follicle matured, providing more androgen substrate for the production of estrogen. Lyase activity in theca cells of medium follicles appears to be regulated predominantly by gonadotropin from the pituitary while intraovarian regulation of lyase activity by steroids may be more important in larger follicles.
Effects of Ti(C,N) Nanoparticles on Mechanical Properties of the Si 3 N 4 Ceramics

Si3N4-Ti(C,N) nanocomposites fabricated by vacuum hot pressing with Al2O3 and Y2O3 as additives were investigated. The results showed that the α-Si3N4 phase converted completely into whisker-shaped β-Si3N4 grains after vacuum sintering at 1700°C. Suitable addition and well dispersion of the Ti(C,N) particles can restrained the lateral growth of the β-Si3N4 grains, increasing aspect ratio of the β-Si3N4 grains and improving bending strength of the composites. Fracture toughness of the composites is higher than that of the β-Si3N4 ceramics, and the main toughening mechanism is crack bridging due to the higher aspect ratio of the β-Si3N4 grains.With the addition of 1vol% of Ti(C,N), the composite has a relative density of 99.31%, Vicker’s hardness of 15.9 GPa, bending strength of 993 MPa, and fracture toughness of 9.9 MPa·m1/2.
Singularity Characterization by Monoscale Analysis: Application to Seismic Imaging

Abstract Seismological images represent maps of the Earth's structure. Apparent bandwidth limitation of seismic data prevents successful estimation by the multiscale wavelet transform of Lipschitz/Holder regularity of nonoscillating singularities. To overcome this fundamental problem, a new method is proposed which provides local estimates from information, essentially residing at only one single scale. Within this method, the exponents are no longer calculated from the decay or growth rate of the wavelet coefficients. Instead, the estimates are obtained by transforming the data with respect to a family of generalized “wavelets” of fractional order. This generalized family is defined in terms of causal and anticausal, fractional integro-differentiations of a fixed-scale, Gaussian smoothing function. Supplementing this transform with criteria that predict the onset or disappearance of modulus maxima as a function of the wavelet order, we provide exponent estimates at the scale of the smoothing function. The estimated exponents are equivalent to Holder exponents when the scale of the smoothing function approaches zero.
Parametric models for line transect surveys

SUMMARY With data from line transect surveys, the pattern of distances at which animals are detected provides the information for estimating the area which the observer effectively surveys. This paper suggests a parametric structure for the problem wherein this area is characterized by an effective half-width parameter which appears as a scale parameter in the distributions of detection distances. Several suggestions for classes of models are given, different members of a class giving different shapes to the distributions. And some examples are discussed.
Classifying pro-fibrations and shape fibrations

We use techniques of J.P. May to construct classifying spaces for fibrations in the category of inverse sequences of spaces (towers) and level-preserving maps. These spaces are used to classify fibrations in Top N , fibrations in pro-Top, and shape fibrations; the latter modulo certain compactness questions.
Dynamic simulation of chemical processes described by distributed and lumped parameter models

Abstract Currently available dynamic simulation routines are limited to processes in which the units can be described by lumped parameter models. In this paper, a general procedure is presented which permits the units to be described by both distributed and lumped parameter models. The partial differential equations resulting from a distributed parameter model are transformed into a set of ordinary differential equations by discretizing the spatial variable. The coupling of this set of discretized equations to the sets from other units is accomplished through the boundary conditions which represent the inlet and outlet of the unit. The resulting large set of time-dependent ordinary differential equations is solved simultaneously using a Gear-type integrator. The method is demonstrated by considering the start-up of a process composed of a tubular reactor, a gas absorption column and a completely mixed tank.
Evaluating the compliance of Keck’s LGSAO automated aircraft protection system with FAA adopted criteria

The W. M. Keck Observatory (WMKO) applied for and received a determination of no-objection from the Federal Aviation Administration (FAA) for laser guide star adaptive optics (LGS-AO) operations using an automated aircraft protection system (APS) in late 2013. WMKO’s APS, named AIRSAFE, uses transponder based aircraft detection (TBAD) to replace human aircraft spotters. The FAA required WMKO to self-certify AIRSAFE compliance with SAE Aerospace Standard 6029A: “Performance Criteria for Laser Control Measures Used for Aviation Safety”[1] (AS- 6029A). AS-6029A prescribes performance and administrative criteria for an APS; essentially, requiring AIRSAFE to adequately protect all types of aircraft, traveling at any speed, altitude, distance and direction reasonably expected in the operating environment. A description of the analysis that comprises this compliance evaluation is the main focus of this paper. Also discussed is the AIRSAFE compliance with AS-6029A administrative criteria that includes characterization of site specific air traffic, failure modes, limitations, operating procedures, preventative maintenance procedures, and periodic system test procedures.
MODULAR MAGIC SUDOKU

A modular magic sudoku solution is a sudoku solution with symbols in f0;1;:::;8g such that rows, columns, and diagonals of each subsquare add to zero modulo nine. We count these sudoku solutions by using the action of a suitable symmetry group and we also describe maximal mutually orthogonal families.
Normal patterns of 18F-FDG appendiceal uptake in children

Prior to interpreting PET/CT, it is crucial to understand the normal biodistribution of fluorodeoxyglucose (FDG). It is also important to realize that the normal biodistribution can vary between adults and children. Although many studies have defined normal patterns of pediatric FDG uptake in structures like the thymus, brown fat and bone marrow, patterns of normal pediatric bowel activity, specifically uptake within the appendix, have not been well described. Active lymphoid tissue has increased FDG uptake when compared with inactive tissue. Since children have more active lymphoid tissue than adults, and because the appendix contains aggregated lymphoid tissue, we postulated that appendiceal uptake may be increased in pediatric patients. To define the normal level of appendiceal FDG activity in children by evaluating a series of consecutive FDG PET/CT scans performed for other indications. After obtaining IRB approval, we retrospectively reviewed 128 consecutive whole-body pediatric FDG PET/CT examinations obtained for a variety of clinical indications. CT scans on which the appendix could not be visualized were excluded from analysis. CT scans on which the appendix could be visualized were evaluated for underlying appendiceal pathology. Studies with appendiceal or periappendiceal pathology by CT criteria were excluded. A region of interest (ROI) was placed over a portion of each appendix and appendiceal maximum standardized uptake value (SUVmax) was calculated. If an adjacent loop of bowel activity interfered with accurate measurements of the appendix SUVmax, the scan was excluded from the analysis. A chart review was performed on patients with elevated appendiceal SUVmax values to ensure that the patients did not have clinical symptomatology suggestive of acute appendicitis. When the appendix or a portion of the appendix could be visualized and accurately measured, the SUVmax was determined. SUVmax of the appendix was compared to the SUVmax of normal liver and ratios were recorded. A total of 128 scans were reviewed, patient ages 1 month to 21 years (mean age: 11.6 years). Thirty-one scans were excluded because of inability to visualize the appendix on CT. No scans were excluded for appendiceal/periappendiceal pathology on CT or chart review. No scans had to be excluded for inability to obtain an accurate SUVmax measurement because measurements were calculated on portions of the appendix separate from adjacent bowel using small ROIs. Maximum appendiceal SUVs ranged from 0.5 to 9.4 (mean: 2.2) with an appendix-to-liver background ratio ranging from 0.3 to 3.1 (mean: 1.1). FDG uptake in the appendix is typically similar to that of background activity. However, slight variations in appendiceal FDG uptake do occur, which should not be misinterpreted as pathological.
Safety of biologic therapy in rheumatoid arthritis and other autoimmune diseases: focus on rituximab.

Objectives To review the safety of biologic agents used to treat rheumatoid arthritis (RA) and other autoimmune diseases, with a focus on rituximab. Methods Information was gathered from a search of the PubMed database and from major congress abstract listings through June 2007. Results Rituximab is approved for treating RA in patients with an inadequate response to TNF inhibitors and is under study in other indications for RA and other autoimmune disorders. The current safety profile of rituximab in RA is known from Phase II and III studies conducted preapproval, treating approximately 750 patients, as well as from long-term extension studies with repeated therapy. Clinical trials have established that the most common adverse events are infusion-associated reactions, seen in 29 to 40% of patients, most of which are mild to moderate and occur following the first rituximab infusion, with incidence and severity decreasing with subsequent infusions. Rates of infections and serious infections to date are within the range expected for RA patients treated with other biologic agents, but the longer term effects of B-cell depletion and the effects of repeated treatment on the risk of infections are uncertain. Information is limited for rituximab safety in other autoimmune disorders but current data do not suggest that there is a significant difference in adverse events from that previously reported. Conclusions Rituximab is an important addition to the rheumatologist's armamentarium for the treatment of difficult RA and ongoing trials will determine its utility in other indications for RA and other autoimmune conditions. The true safety profile of rituximab will emerge as larger numbers of patients are treated in routine clinical practice.
On modeling boundary layer and gravity‐driven fluid mud transport

[1] A model for fine sediment transport processes in the fluvial and coastal environment is proposed based on a simplified two-phase formulation. This simplified approach for fine-sediment transport is essentially single-phased; however, it retains several critical mechanisms originated from the complete two-phase formulation. By incorporating closures of carrier fluid turbulence and turbulent suspension and rheology of the sediment, the model is first tested with laboratory measurements of flow velocity and concentration for fine-sand transport driven by steady currents. Next, particle diameter and density are prescribed in the model according to fractal dimensions of typical flocs for fluid mud observed on the continental shelf. The model is able to predict the dynamics of tidal-driven lutocline behavior observed on the Amazon shelf and wave-supported gravity-driven fluid mud transport measured at the Po prodelta. Model results also indicate strong interplay between flow turbulence and fluid-mud concentration, suggesting that the mechanism of sediment-induced stratification on damping the carrier fluid turbulence is crucial in determining the fluid mud behavior. Results are encouraging for incorporation in the future of more comprehensive descriptions on floc dynamics, mud-bed consolidation and various mud rheology closures.
Preoperative Patient Education Reduces In-hospital Falls After Total Knee Arthroplasty

Background Inpatient hospital falls after orthopaedic surgery represent a major problem, with rates of about one to three falls per 1000 patient days. These falls result in substantial morbidity for the patient and liability for the institution.
Understanding the GIOVE-B broadcast codes of the Galileo system

Europe's second Galileo In-Orbit Validation Element (GIOVE-B) satellite was launched on April 27, 2008, at 22:16 UTC and successfully began transmission on May 7. On the same day, we observed signals in the L1, E5a, and E5b bands, with the L1 spectrum showing multiplexed binary offset carrier (MBOC) modulation. We then identified the generators for the Pseudo Random Noise (PRN) codes in each band. We revealed these codes to be 13- or 14-stage Gold codes, different from the memory codes in the Galileo Interface Control Document (ICD). The GIOVE-B PRN codes have the same code structure as those of the first Galileo test satellite, GIOVE-A. The code generators are the same except for the initial states. However, the signal modulation type in one of the frequency bands is different. The new modulation applied by GIOVE-B ensures more robustness to multipath.
VASCULAR ACCESS IN TRAUMA: Options, Risks, Benefits, and Complications

After airway patency and ventilation concerns are evaluated and managed in trauma patients, the circulatory adequacy is the next concern. In trauma patients presenting with multiple severe injuries and hemorrhagic shock, vascular access is necessary. Timely restoration of intravascular volume improves systemic perfusion, alleviates tissue hypoxia and the acidosis resulting from anaerobic metabolism, and can arrest cell death and progression to irreversible shock. Therapy is directed toward restoring volume deficits and preventing further blood loss. The urgency of the placement and the size and number of intravenous (IV) catheters are dictated by the degree of shock, the duration and rate of bleeding, and type of injury. This article discusses the factors that should be considered in establishing vascular access in trauma patients, as well as the options available and the advantages and disadvantages of each.
Revenue enhancement and wealth effects of mergers and acquisitions in Asian emerging markets

Revenue enhancement and value creation are core issues of mergers and acquisitions (M&A). Revenue enhancing synergy associated with cross-industry M&A is supported by Asian emerging markets. Both within-industry M&A and cross-industry M&A deals realise significant positive abnormal returns. The difference between the two categories of M&A is statistically significant in a three-day window, but not statistically significant in a two-day window. Information leakages may be driving the larger valuation effects because a three-day window includes one day before the announcement date. Since large firms tend to diversify their business, the result that cross-industry M&A deals realise lower abnormal returns than within-industry may be driven by the firm size effect.
Effects of ligation of the pulmonary vasculature in the rabbit fetus.

Abstract Ligation of the pulmonary vessels in the rabbit fetus is compatible with a good yield of surviving animals (more than 60%). Ligation of the pulmonary artery, or pulmonary artery and vein, results in infarction, with some preservation of islands of pulmonary tissue in the periphery. Ligation of all the pulmonary veins to the left lung results in death within a few hours.
The optimal sequencing of carrots

Abstract When aid organizations contract with local agents aid funds have the potential to be diverted to purposes other than the intended project. A multi-stage game is presented where the benefit from the project is cumulative, with the application of funds in each stage increasing both the agent's and the organization's benefit from the project. As the agent's utility of diversion increases, the allocation in each stage decreases and the project takes more stages to complete. When contracting with agents with high utilities of diversion the optimal contract involves bloated projects and a side payment to the agent upon completion. If the organization's commitment to the contract is not credible both the agent's and the organization's benefit is reduced.
Steroids I. Alkylation of β-ketoesters via their Cu(II) enolates in aqueous media. Application of the synthesis of C-18 functionalized steroids via the torgov approach.

Abstract Three steroidal pentaenes ( 8 ˜ a− c ˜ ) have been synthesized, the key step being the alkylation of the Cu(II) chelates to the ring D precursors ( 3 ˜ − 5 ˜ ) by the isothiouronium acetate 1 ˜ in aqueous solution.
The Gaver-Stehfest algorithm for approximate inversion of Laplace transforms

An approximate technique for the inversion of Laplace transforms is represented and some simple applications are given. The limitations of the method were explored and it is clear that functions which have oscillatory inverses present difficulty for the method. Better approximations result from the use of computers with longer word lengths and there is considerable improvement when an averaging algorithm is employed. Eight-bit microcomputers are generally sufficiently accurate for nonoscillatory time functions but transforms for lightly damped sinusoids and Bessel functions require large main-frame computers with relatively long word length.
Suspended lipid bilayer for optical and electrical measurements of single ion channel proteins.

Making and holding an artificial lipid bilayer horizontally in an aqueous solution within the microscopic working distance of ∼100 μm are essential for simultaneous single molecule imaging and single ion-channel electrical current recording. However, preparation of such a lipid bilayer without a solid support is technically challenging. In a typical supported lipid bilayer, the asymmetric local environments and the strong perturbation of the underneath solid or dense surface can diverge the normal behavior of membrane proteins and lipids. On the other hand, the suspended lipid bilayers can provide a native local environment for the membrane proteins and lipids by having fluids on both sides. In this technical report, we present a simple and novel methodology for making a suspended lipid bilayer that can be used for recording the single-molecule diffusion and single ion-channel electrical measurements of ion-channel proteins. Our approach has a higher validity for studying the molecular diffusions and conf...
The minimum wage can harm workers by reducing unemployment

Economists may disagree over how much raising the minimum wage increases unemployment, though few argue that the unemployment effect is zero. According to the standard model, the less the unemployment caused by a minimum wage increase, the less the harm (or greater the good) that results. But by recognizing that minimum wage workers receive fringe benefits, I show that increasing the minimum wage may not cause any unemployment and harms workers because it doesn 't. Furthermore, when there is lumpiness in providing fringe benefits, a minimum wage increase may harm workers by
Comparison of soft-sphere models to measurements of collision properties during normal impacts

Abstract Simultaneous measurements of the restitution coefficient and collision duration are used as a basis of comparison for soft-sphere models. The experiments were characterized by spherical, cohesionless, steel particles undergoing a normal (head-on) impact. A range of impact velocities was tested. For soft-sphere models requiring two (adjustable) inputs, the inputs were chosen such that model predictions match the experimental values of restitution coefficient and collision duration obtained at an intermediate impact velocity. For the soft-sphere model requiring a single input, only the restitution coefficient is matched. A comparison between model predictions and experimental data indicates that three of the six models considered [G. Kuwabara, K. Kono, Restitution coefficient in a collision between two spheres, Jpn. J. Appl. Phys. 26 (1987) 1230–1233.; O.R. Walton, R.L. Braun, Viscosity, granular–temperature, and stress calculations for shearing assemblies of inelastic, frictional disks, J. Rheol. 30, (1986) 949–980.; C. Thornton, Coefficient of restitution for collinear collisions of elastic–perfectly plastic spheres, J. Appl. Mech. 64 (1997) 383–386. [1] , [2] , [3] ] agree with the experimental trends, namely that both coefficient of restitution and the collision duration decrease with an increase in impact velocity. Furthermore, an examination of the force vs. overlap behavior reveals that some of the soft-sphere models predict an unrealistic attractive force toward the end of the rebound phase. From a quantitative perspective, the measured collision durations are within 10% of those predicted by Hertzian theory for perfectly elastic spheres. Hence, the matching of a Hertzian collision time, along with the desired restitution coefficient, appears to provide a reasonable basis for choosing input values for soft-sphere models characterized by two input parameters. Finally, a soft-sphere model with no adjustable parameters was also investigated, though estimating values for the required physical inputs was non-trivial.
An Evolutionary Approach to Harnessing Complex Systems Thinking in the Science and Technology Classroom

Educational efforts to incorporate ethical decision‐making in science classrooms about current science and technology issues have met with great challenges. Some research suggests that the inherent complexity in both the subject matter content and the structure and dynamics of classrooms contribute to this challenge. This study seeks to investigate the viability of an educational heuristic based on a complex s ystems evolutionary approach to both harness complexity inherent in the learning system of the classroom and to improve student knowledge of a complex scientific issue. The evolutionary mechanisms of variation, interaction, and selection were used to construct a 10‐day curriculum and instruction unit on the topic of genetic engineering. Eleven Grade 9 students participated in the study. The data analysis was completed using three data sources: daily database discussions and ratings and rationales provided over four time‐points, probing student opinions and understanding of genetic engineering resear...
Recording inhibition and excitation in the cat's retinal ganglion cells with intracellular electrodes.

IN the light-adapted state, the receptive fields of retinal ganglion cells in the cat consist of excitatory and inhibitory areas. Thus predominantly excitatory and inhibitory pathways converging on a ganglion cell can be stimulated selectively1 and thereby the mechanism of excitation and inhibition can be studied. It has recently become possible to record from retinal ganglion cells with intracellular leads for short periods2. In the present study, penetrations into cells were fairly frequent; but most cells gave injury discharges and their membrane potentials declined within several minutes. However, intracellular records from some ganglion cells were recorded with stable membrane potentials of 50–70 mV. for as long as 20 min. Discharge patterns were similar to those obtained during extracellular recordings.
A Drosophila Model of Myosin-Based Inclusion Body Myopathy Type 3: Effects on Muscle Structure, Muscle Function and Aggregated Protein Profiles

Inclusion body myopathy type 3 (IBM-3) is a progressive dominant disease affecting fast skeletal muscle. It results from a point mutation in the SH1 helix of the myosin motor. Previously, we showed that homozygous expression of the analogous mutation in Drosophila indirect flight muscle (IFM) results in a flightless phenotype, severe abnormalities in myofibril structure, dramatically reduced ATPase and in vitro motility, increased myosin aggregation and production of autophagic and membranous inclusions (Wang et al., 2012, Mol Biol Cell 23:2057-65). We have now examined the dominant effects of the IBM-3 mutation in our model. Mutant and wild-type proteins accumulate in equimolar amounts in heterozygotes, since ATPase and in vitro motility levels display intermediate values. Heterozygotes show progressive defects in IFM function that are less severe than in homozygotes, correlating with deficits in fiber mechanics (Corcione et al., 2010, Biophys. J. 98: 544a). Surprisingly, we detect no defects in muscle morphology in heterozygotes. While increasing the mutant:wild-type gene dosage to 2:1 further compromises muscle function and produces minor myofibrillar defects in aged flies, no inclusion bodies are observed. We examined the accumulation of Ref(2)P, a polyubiquitin-binding protein that is commonly associated with protein aggregates, and found a dramatic upregulation only in the IBM-3 homozygotes. We defined the makeup of these aggregates by proteomic analysis and found alterations in proteins associated with mitochondrial function and the unfolded protein response. We plan to manipulate expression levels of such proteins in an attempt to improve mutant phenotypes.Supported by MDA grant 217900. We appreciate the assistance of Robert N. Cole and Robert O’Meally, JHU Mass Spectrometry and Proteomics Facility.
An analysis of mandibular movement trajectories and masticatory muscle EMG activity during drinking in the guinea pig.

Abstract Electromyographic (EMG) activity of the anterior digastric, lateral pterygoid, and deep masseter muscles as well as the associated jaw movements during drinking were studied in the awake guinea pig. Drinking was characterized by rhythmic, vertically directed jaw movements with little or no associated lateral movements. The jaw opening phase of each cycle was associated with bilaterally synchronized EMG activity in the digastric and lateral pterygoid muscles, and the jaw closing phase with bilaterally synchronized activity in the masseter muscles. The mean EMG burst durations (± 1 S.E.) in the digastric and masseter muscles were 164.2 ± 14.93 ms and 94.3 ± 26.44 ms, respectively. The digastric muscle EMG burst duration was significantly correlated with drinking cycle time and with masseter muscle EMG onset; on the other hand, masseter muscle EMG burst duration was not correlated with cycle time. These patterns of EMG activity and jaw movement trajectories are similar to those induced by apomorphine in the ketamine-anesthetized guinea pig.
Phase evolution in laser-deposited titanium-chromium alloys

Ti-Cr alloys have been laser deposited from powder feedstock consisting of a blend of elemental powders using the laser-engineered net-shaping (LENS) process. The microstructure of the as-deposited Ti-Cr alloys primarily consists of a metastable bcc matrix of β-Ti(Cr) with precipitates along the grain boundaries. The grain-boundary precipitates have been identified to be of three types, essentially pure hcp Ti, an alloyed hcp phase designated α-Ti(Cr), and the C14 TiCr2 Laves phase. Initial stages of decomposition, visible within the β matrix, suggest a spinodal clustering process resulting in a fine dispersion of second phases. Diffraction studies have revealed the presence of fine precipitates of α within the β matrix. The evidence for the precipitation of the metastable ω phase within the β matrix is not strong. The phase evolution in the LENS-deposited Ti-Cr alloy has been discussed in the context of rapid solidification and the enthalpy of mixing of the elemental powders.
IMPACTS OF UNDERGRADUATE EXPERIENCES ON ASPIRATIONS AND PLANS FOR GRADUATE AND PROFESSIONAL EDUCATION

This paper describes a longitudinal path-analytic study of influences upon educational aspirations and plans for graduate and professional schooling among 418 undergraduates at two U.S. universities. The analysis suggests that academic performance, parental supportiveness, faculty-student interaction, and major department context played significant roles in outcomes, beyond the role played by freshman-year background characteristics. There were some differences in the results for men and women, suggesting further attention to gender differences in postcollege educational attainment processes. Overall, the analysis suggests that greater attention to subenvironments, such as major departments, may be warranted in studies of this kind.
Mast Cell Activation Syndrome as a Significant Comorbidity in Sickle Cell Disease

Some sickle cell anemia (SCA) patients suffer significantly worse phenotypes than others. Causes of such disparities are incompletely understood. Comorbid chronic inflammation likely is a factor. Recently, mast cell (MC) activation (creating an inflammatory state) was found to be a significant factor in sickle pathobiology and pain in a murine SCA model. Also, a new realm of relatively noncytoproliferative MC disease termed MC activation syndrome (MCAS) has been identified recently. MCAS has not previously been described in SCA. Some SCA patients experience pain patterns and other morbidities more congruent with MCAS than traditional SCA pathobiology (eg, vasoocclusion). Presented here are 32 poor-phenotype SCA patients who met MCAS diagnostic criteria; all improved with MCAS-targeted therapy. As hydroxyurea benefits some MCAS patients (particularly SCA-like pain), its benefit in SCA may be partly attributable to treatment of unrecognized MCAS. Further study will better characterize MCAS in SCA and identify optimal therapy.
A simple, biologically motivated neural network solves the transitive inference problem

Configural learning problems can be resolved by both rats and humans if they are not too difficult. The configural learning problem which we explore here is transitive inference. Transitive inference (learn the four pairs A>B, B>C, C>D, D>E, then test with the novel pair B?D) was once viewed as a logical problem. However; it is now acknowledged that when the stimuli are appropriate even three year old humans can solve this problem and, as well, so can pigeons and rats. Thus, even though the problem is a simple exercise in logic, there is reason to suspect that mammals, or for that matter neural networks, will solve such a problem without recourse to any explicit syllogistic reasoning. In fact, by casting the input stimuli in a form appropriate for a sequence learning neural network a hippocampal-like network can solve the transitive inference problem. Furthermore, performance is appropriately disrupted by turning the linear sequence of relationships into a nonlinear (circular) relationship.
Complex Partnerships: Self-authorship and Provocative Academic- Advising Practices

Self-authorship is an additional orientation to traditional college student, epistemological, development theories. Facilitation of self-authorship, via academic advising, may help students meet the desired outcomes outlined by the Council for the Advancement of Standards in Higher Education and integrate these abilities into their knowing and decision-making processes. Through investigation of 132 student narratives about advising and selection of academic majors, I examined advising practices that are consistent with Baxter Magolda's (2001) learning partnerships model for self-authorship development. Findings suggest that student decision-making and self-authoring abilities were enhanced by advising sessions that focused explicitly on goal reflection and associated volitional planning. Students benefited from advising in which nonacademic factors were addressed. Implications for practice are discussed. Relative emphasis: * theory, research, practice
Infection and xenotransplantation: Assessing the risks

The success of human-to-human organ transplantation in the treatment of a variety of types of organ failure has resulted in a growing shortage in the availability of human organs for such procedures. Xenotransplantation, or transplantation of organs or tissues from non-human species into human recipients, has been proposed as a potential solution to the shortage of human organ and tissue donors. As is the case for allotransplantation, the need for long-term immune suppression for the prevention of graft rejection has as a major side effect the development of opportunistic infections and malignancy in the xenotransplant recipient. The use of non-human species as organ donors carries a risk in that organisms derived from another species and possibly not normally associated with human disease may gain entry and cause infection in the new human host. The unique aspect of this risk is that organisms from other
What if the Construct of Dysrationalia Were an Example of Itself

The concept of dysrationalia is intriguing at a dysrational level—but the construct needs much better conceptualization and elaboration, a theory, operationalization, convergent and discriminant-validation, and safeguards against misuse.
An efficient gradient computation approach to discriminative fusion optimization in semantic concept detection

In this paper, we propose an efficient gradient computation approach for discriminative fusion optimization in TRECVID high-level feature extraction. Numerical approximation was exploited in gradient calculation and model parameter update. The gradient of the performance measure was approximated by a sum of instance point-wise gradient instead of instance pair-wise gradient used in maximum figure-of-merit learning such that performance metrics like average precision can be optimized directly and efficiently on large training set. Experiments on the TRECVID 2005 high-level feature extraction test set showed that the proposed algorithm can improve the mean average precision from 0.254 of a state-of-the-art baseline system to 0.285.
Magnetic properties of oceanic pillow basalts: evidence from Macquarie Island

Summary A combined pdaeomagnetic, hysteresis, thermomagnetic, and electron microprobe study has been carried out on pillow basalts from Late Tertiary oceanic crust exposed on Macquarie Island. Oriented cores were collected from four sites in the North Head region where the basalts are unmetamorphosed but have suffered pervasive seafloor weathering and at four sites near Langdon Point where the pillow lavas have experienced metamorphism to the greenschist facies. Field geologic and petrologic evidence suggests that the North Head samples are representative of the weathered zone of Late Tertiary oceanic crust while the specimens from Langdon Point are representative of pillow basalts from > 500m into the oceanic lithosphere. Geometric mean intensities of natural remanence (NRM) were 0.7 × 10−3 G for North Head samples and 0.6 × 10−3 G for specimens from Langdon Point. The geometric mean values of low field susceptibility (x) and Koenigsberger ratio (Q) for North Head samples (0.1 × 10−3 G Oe−1 and 9.8) are similar to those of DSDP basalts. The mean value of X and Q for Langdon Point samples (2.8 × 10−3 G Oe−1 and 0.3) is similar to those observed in metabasalt dredged from oceanic escarpments. Hysteresis, thermomagnetic and electron microprobe data indicate that the titanomaghemites in the North Head samples have suffered a high degree of low temperature oxidation. Langdon Point samples show reversible thermomagnetic curves with a magnetic Curie temperature (580° C), indicating that metamorphism has altered the magnetic mineralogy. This metamorphism is thought to occur at or near the ridge during the seafloor spreading process. Thus, the NRM of the metamorphosed pillow basalts would still record geomagnetic reversals and contribute to magnetic lineations. The low NRM intensities are ascribed to prolonged seafloor weathering of North Head samples and to metamorphism of the basalts from Langdom Point. Since the 10−3 G NRM intensities of pillow basalts are too low to account for the observed amplitude of marine magnetic anomalies, the underlying basaltic and doleritic sheeted dyke complex must also contribute to the anomalies.
Species and strain sensitivity to the induction of peroxisome proliferation by chloroacetic acids

B6C3F1 mice and Sprague-Dawley rats were provided drinking water containing 6-31 mM (1-5 g/liter) trichloroacetic acid (TCA), 8-39 mM (1-5 g/liter) dichloroacetic acid (DCA), or 11-32 mM (1-3 g/liter) monochloroacetic acid (MCA) for 14 days. TCA and DCA, but not MCA, increased the mouse relative liver weight in a dose-dependent manner. Rat liver weights were not altered by TCA or DCA treatment, but were depressed by MCA. Hepatic peroxisome proliferation was demonstrated by (1) increased palmitoyl-CoA oxidase and carnitine acetyl transferase activities, (2) appearance of a peroxisome proliferation-associated protein, and (3) morphometric analysis of electron micrographs. Mouse peroxisome proliferation was enhanced in a dose-dependent manner by both TCA and DCA, but only the high DCA concentration (39 mM) increased rat liver peroxisome proliferation. MCA was ineffective in both species. Three other mouse strains (Swiss-Webster, C3H, and C57BL/6) and two strains of rat (F344 and Osborne-Mendel) were examined for sensitivity to TCA. TCA (12 and 31 mM) effectively enhanced peroxisome proliferation in all mouse strains, especially the C57BL/6. A more modest enhancement in the Osborne-Mendel (288%) and F344 rat (167%) was seen. Dosing F344 rats with 200 mg/kg TCA in water or corn oil for 10 days increased peroxisome proliferation 179 and 278%, respectively, above the vehicle controls. These studies demonstrate that the mouse is more sensitive than the rat with respect to the enhancement of liver peroxisome proliferation by TCA and DCA and suggest that if peroxisome proliferation is critical for the induction of hepatic cancer by TCA and DCA, then the rat should be less sensitive or refractory to tumor induction.
Who needs theory of therapeutic action

(2007). Who Needs Theory of Therapeutic Action? The Psychoanalytic Quarterly: Vol. 76, No. sup1, pp. 1635-1662.
Optofluidically reconfigurable channel based microfluidics

Here we demonstrate the use of optofluidics to create rapidly reconfigurable channel based microfluidic systems, implemented through reversible rheological changes in a polymer solution flowing within the microfluidic device and dynamic photomasking.
The neural basis for establishing a focal point in pure coordination games

When making a decision, humans often have to ‘coordinate’—reach the same conclusion—as another individual without explicitly communicating. Relatively, little is known about the neural basis for coordination. Moreover, previous fMRI investigations have supported conflicting hypotheses. One account proposes that individuals coordinate using a ‘gut feeling’ and that this is supported by insula recruitment. Another account proposes that individuals recruit strategic decision-making mechanisms in prefrontal cortex in order to coordinate. We investigate the neural basis for coordination in individuals with behavioral-variant frontotemporal dementia (bvFTD) who have limitations in social decision-making associated with disease in prefrontal cortex. We demonstrate that bvFTD are impaired at establishing a focal point in a semantic task (e.g. ‘Tell me any boy's name’) that requires coordination relative to a similar, control semantic task that does not. Additionally, coordination limitations in bvFTD are related to cortical thinning in prefrontal cortex. These findings are consistent with behavioral economic models proposing that, beyond a ‘gut feeling’, strategic decision-making contributes to the coordination process, including a probabilistic mechanism that evaluates the salience of a response (e.g. is ‘John’ a frequent boy's name), a hierarchical mechanism that iteratively models an opponent's likely response and a mechanism involved in social perspective taking.
Business Intelligence at the crossroads: Convergence or confusion ahead?

Business Intelligence (BI) innovation may have stagnated given the combined forces of a down economy and the mergers and acquisitions that have reshaped the BI vendor space. To catalyze needed innovation, a new challenge is issued that focuses on advancing global services growth. That challenge is contextualized as one requiring piecemeal advancements within specific service industries before generalization to aggregate service categories like B2B, B2C and self-services. While advocating this stepwise approach, the concomitant emergence of what is referred to as the ‘servitizing’ of BI is addressed. This refers to notions of ‘analytics as a service,’ ‘data warehousing in the cloud,’ ‘elastic data marts,’ etc. While applying the service metaphor to BI (as in servitizing BI), and while addressing growth in the global services economy, there will be significant confusion surrounding BI innovation in the years ahead. Three case studies are used to demonstrate the advocated investigative approach.