cssi/SciSciGPT-SciSciNet huggingface dataset:
Estimation of the number of extreme pathways for metabolic networks.

The set of extreme pathways (ExPa), {p i }, defines the convex basis vectors used for the mathematical characterization of the null space of the stoichiometric matrix for biochemical reaction networks. ExPa analysis has been used for a number of studies to determine properties of metabolic networks as well as to obtain insight into their physiological and functional states in silico. However, the number of ExPas, p = |{p i }|, grows with the size and complexity of the network being studied, and this poses a computational challenge. For this study, we investigated the relationship between the number of extreme pathways and simple network properties. We established an estimating function for the number of ExPas using these easily obtainable network measurements. In particular, it was found that log [p] had an exponential relationship with , where R = |R eff | is the number of active reactions in a network, and the incoming and outgoing degrees of the reactions r i ∈ R eff , and c i the clustering coefficient for each active reaction. This relationship typically gave an estimate of the number of extreme pathways to within a factor of 10 of the true number. Such a function providing an estimate for the total number of ExPas for a given system will enable researchers to decide whether ExPas analysis is an appropriate investigative tool.
Ten filmless years and ten lessons: A 10th-anniversary retrospective from the Baltimore VA Medical Center

The authors review a decade's experience in the nation's first filmless radiology department and outline the challenges and rewards of the transition. They summarize their experience with 10 cautionary and informative lessons on making the process more successful, more efficient, and less stressful. A number of possible avenues of new research and assessment on the effects of filmless operation on radiologists, imaging staff, referring clinicians, and patients are highlighted.
Epidemic Oral Ulceration in Largemouth Bass (Micropterus salmoides) Associated with the Leech Myzobdella lugubris

An epidemic of severe ulcerations of the tongue and buccal cavity was documented in subadult and adult largemouth bass (Micropterus salmoides) from Currituck Sound, North Carolina (USA). Other external clinical signs were not present. Between November 1986 and May 1987, reports from fishermen indicated that as many as 90% of large (>300 mm total length) bass were affected. Older fish were the most commonly involved. The leech, Myzobdella lugubris (=Illinobdella moorei), was consistently present on or near the lesions. Lesions were heavily infected with several different bacteria that were apparently secondary invaders. Stressful (high) salinity or an interruption in the normal migratory cycle of the parasite are suggested as possible causes for this condition in these bass.
Peptidyl-transferase ribozymes: trans reactions, structural characterization and ribosomal RNA-like features

Abstract Background: One of the most significant questions in understanding the origin of life concerns the order of appearance of DNA, RNA and protein during early biological evolution. If an ‘RNA world' was a precursor to extant life, RNA must be able not only to catalyze RNA replication but also to direct peptide synthesis. Iterative Iterative RNA selection previously identified catalytic RNAs (ribozymes) that form amide bonds between RNA and an amino acid or between two amino acids. Results: We characterized peptidyl-transferase reactions catalyzed by two different families of ribozymes that use substrates that mimic A site and P site tRNAs. The family II ribozyme secondary structure was modeled using chemical modification, enzymatic digestion and mutational analysis. Two regions resemble the peptidyl-transferase region of 23S ribosomal RNA in sequence and structural context; these regions are important for peptide-bond formation. A shortened form of this ribozyme was engineered to catalyze intermolecular (‘ trans ') peptide-bond formation, with the two amino-acid substrates binding through an attached AMP or oligonucleotide moiety. Conclusions: An in vitro -selected ribozyme can catalyze the same type of peptide-bond formation as a ribosome; the ribozyme resembles the ribosome because a very specific RNA structure is required for substrate binding and catalysis, and both amino acids are attached to nucleotides. It is intriguing that, although there are many different possible peptidyl-transferase ribozymes, the sequence and secondary structure of one is strikingly similar to the ‘helical wheel' portion of 23S rRNA implicated in ribosomal peptidyl-transferase activity.
Asymptotic normality of multivariate trimmed means

Abstract We prove the asymptotic normality of the trimmed mean, obtained by deleting the data which is further away from a parameter of location θ n . To get this trimmed mean, equivariant by rotations, dilations and translations, we choose θ n in a class of multivariate parameters of location, which are equivariant by these transformations. Given the data X 1 , … , X n , we take as θ n , the value such that n −1 ∑ j=1 n h(|X j −θ n |)= inf n −1 ∑ j=1 n h(|X j −θ|), where h is a nondecreasing function and | x | is the Euclidean distance in B d . This estimator θ n is equivariant by rotations and translations. If h ( x ) = x p , θ n is also equivariant by dilations.
LQ-Based Trajectory Tracking of Robotic Manipulators With “Near” Dynamically Feasible Time-Optimal Trajectory

In this paper we study the trajectory tracking of robotic manipulators using LQ methods. We also present the development of an algorithm that generates “near” dynamically feasible time-optimal trajectories with complete dynamics model, which incorporates both Coulomb and viscous friction. It is shown how to incorporate the viscous-friction term through a convex relaxation of the original non-convex formulation. Viscous friction is traditionally ignored in all existing related formulations due to the intractability in solving the non-convex problem. As a case study, the methodology is applied to a 6-DOF industrial manipulator.Copyright © 2012 by ASME
Technologies for machine translation

Abstract Advances in hardware have made available micro-coded LISP and PROLOG workstations, supported by text editing and formatting software. Some of these have been augmented with linguistic technology including large bilingual dictionaries, parsers, generators, and translators to make them powerful tools for research and development of automated translation. Some techniques of linguistic engineering for accomplishing translation are described, and it is suggested that the present barely satisfactory approach involving sentence-by-sentence translation will eventually be improved by incorporating the results of research on analyzing discourse.
Comparison Orthogonal Tube Turning Data Versus Finite Element Simulation Using LS Dyna

The current study focuses on building a 2-Dimensional finite element model to simulate the orthogonal machining process under a dry machining environment in a commercially available FEA solver LS DYNA. One of the key objectives of this thesis is to carefully document the use of LS Dyna to model metal cutting, allowing other researchers to more quickly build on this work. Actual force data is obtained using an Orthogonal Tube Turning apparatus that has been statistically validated to an accuracy of 99+%. The work material used in this study is Aluminum 6061-T6 alloy. The tool material is tool steel, which is modeled as a rigid body. A Plastic Kinematic Material Hardening model is used to define the work material. Chip formation is based on the effective failure plastic strain. A constant coefficient of friction between the tool and work piece is used, obtained from the actual experimental results. The simulation is carried out with the same constant velocity, different rake angles and depth cuts as in the real world experiment. The cutting force and thrust force values obtained for each combination of rake angle and cut depth are validated against the experimental data obtained at Auburn University. The resulting model is considered valid enough to use for sensitivity analysis of the metal cutting process in aluminum alloy 6061-T6 in the university environment. The model is available publicly to any university from a website provided.Copyright © 2013 by ASME
Pore network model of transport and separation of binary gas mixtures in nanoporous membranes

Abstract We develop a pore network model of transport and separation of a binary gaseous mixture through a nanoporous membrane. A three-dimensional network is used to represent the membrane’s pore space, in which the effective pores’ radius is distributed according to a pore size distribution (PSD). The connectivity of the pores, as well as the broadness of the PSD, are varied in order to study their effect on the transport and separation processes. The Maxwell–Stefan equations are used for describing the pore-level transport processes, which include Knudsen and hindered diffusion, as well as viscous flow. The simulations indicate that Knudsen diffusion is the dominant mechanism of transport in pores as small as 7 A. In smaller pores it is hindered diffusion that controls the rate of the molecular transport. Excellent agreement is found between the simulation results and our experimental data for the single-gas permeances and the ideal selectivity of a silicon–carbide membrane for a helium–argon system, if the thickness of the network and its average pore size are adjusted. The results also indicate the fundamental significance to the permselectivity of a membrane of the tail of the PSD, as well as the percolation effect which is manifested through the interconnectivity of the pores that are accessible to the gases.
On The Politics of Indigeneity: North American and Pacific Histories

The field of comparative indigenous studies has grown tremendously in recent years. Tiya Miles, Paige Raibmon, and J. Kehaulani Kauanui offer some of the most thought-provoking reflections on the politics of indigeneity. Highlighting debates over indigenous identity in the United States and Canada during the nineteenth and early-twentieth centuries, these authors uncover how Native peoples in modern industrial nation-states have reshaped their identities while resisting colonialism and maintaining degrees of their autonomy. Miles, Raibmon, and Kauanui provide glimpses into the dynamics of social change within indigenous communities. Miles explores how Cherokees incorporated slavery into their economic life, and how interrelationships between African Americans and Cherokees changed notions of race within the Cherokee Nation. Raibmon narrates three episodes of cultural encounter in which Indians on the Northwest Coast engaged in wage labor and the tourist economy, as well as grappled with non-Indian notions of "authenticity" and "civilization." Kauanui's work assesses the enduring cultural and political divide that the blood quantum system created within the Native Hawaiian community. Taken together, these stories provide a sense of indigenous struggles to ensure the survival of their families and communities, and how Native peoples have made the best of unfavorable situations in rather unexpected ways.
Effects of nifedipine on the hemodynamic response to clamping and declamping of the abdominal aorta in dogs

Abstract Clamping and declamping of the infrarenal abdominal aorta may adversely affect cardiovascular function, particularly in the presence of heart disease. This effect may be further altered by drugs used in the treatment of symptomatic coronary artery disease. The effect of nifedipine on the hemodynamic response to aortic clamping and declamping was determined in 12 dogs anesthetized with 50% nitrous oxide and 0.6% end-tidal isoflurane and monitored with aortic, left ventricular (LV), and thermodilution pulmonary artery catheters. Six dogs received a nifedipine bolus of 100 μg/kg followed by an infusion of 4 /gmg/kg/min. Six dogs did not receive any nifedipine and served as controls. Before clamping, nifedipine produced immediate decreases in arterial pressure, systemic vascular resistance (SVR), and LV dP/dt, and a modest increase in cardiac output (CO). During aortic clamping, nifedipine-treated dogs demonstrated marked increases in heart rate (HR), dP/dt, and CO while maintaining a low SVR. There were no significant changes upon declamping. The nifedipine-treated animals maintained a high CO and low SVR. Thus, nifedipine greatly altered the hemodynamic responses to aortic clamping and declamping. Awareness of these alterations is important when caring for patients being treated with nifedipine who are undergoing aortic surgery.
Aberrant Cx26 hemichannels and keratitis-ichthyosis-deafness syndrome: Insights into syndromic hearing loss

Mutation of the GJB2 gene, which encodes the connexin Cx26 gap junction (GJ) protein, is the most common cause of hereditary, sensorineural hearing loss. Cx26 is not expressed in hair cells, but is widely expressed throughout the non-sensory epithelial cells of the cochlea. Most GJB2 mutations produce non-syndromic deafness, but a subset produces syndromic deafness in which profound hearing loss is accompanied by a diverse array of infectious and neoplastic cutaneous disorders that can be fatal. Although GJ channels, which are assembled by the docking of two, so-called hemichannels (HCs), have been the main focus of deafness-associated disease models, it is now evident that the HCs themselves can function in the absence of docking and contribute to signaling across the cell membrane as a novel class of ion channel. A notable feature of syndromic deafness mutants is that the HCs exhibit aberrant behaviors providing a plausible basis for disease that is associated with excessive or altered contributions of Cx26 HCs that, in turn, lead to compromised cell integrity. Here we discuss some of the aberrant Cx26 HC properties that have been described for mutants associated with keratitis-ichthyosis-deafness (KID) syndrome, a particularly severe Cx26-associated syndrome, which shed light on genotype-phenotype relationships and causes underlying cochlear dysfunction.
Microscopic description of 2p-2h states in 208Pb

Abstract 0+ and 2+2p-2h states in 208Pb have been studied using a realistic nucleon-nucleon interaction. The model space included both proton and neutron pairing vibrations as well as appropriate coupling of the lowest 3− and 5− 1p-1h states of 208Pb. The calculation indicates that the resulting eigenstates do not have a simple structure. For the 0+ states in particular the inclusion of 2np-2nh states (>1) was necessary. The latter were included in the framework of the quasi-boson approximation.
Phonons and the green exciton series in cuprous oxide, Cu2O

Abstract Examination of the optical absorption edge spectra of samples of melt-grown cuprous oxide enables identification of features of the green exciton series overlying the yellow series. Identification of the green series n = 1 line allows new interpretations of various features seen earlier by other workers.
Suppression of the effects of cross-correlation between dipolar and anisotropic chemical shift relaxation mechanisms in the measurement of spin-spin relaxation rates

Cross correlation between dipolar and anisotropic chemical shift relaxation mechanisms complicates measurements of heteronuclear spin-spin relaxation rate constants by the Carr-Purcell-Meiboom-Gill (CPMG) technique if the magnitudes of the chemical shift anisotropy and the dipolar interaction are comparable. Experimental schemes are described that attenuate the effects of cross correlation and permit accurate measurements of spin-spin relaxation rate constants for heteronuclei with significant chemical shift anisotropies. The theoretical analysis is confirmed by measurements of 15N and 13C spin-spin relaxation in a peptide. Application of 180° pulses to the protons directly attached to the heteronuclei in synchrony with the even echoes of the heteronuclear spins yields more accurate results than continuous irradiation of the protons with a composite pulse decoupling sequence or application of a single 180° pulse to the protons in the middle of the CPMG pulse train.
A Rothalpy Analysis for the Isothermal Boundary Condition at Casing Applied to the Rotor 37 Transonic Axial Flow Compressor

CFD simulations have been set-up with an isothermal boundary condition at the casing for running the NASA Rotor 37 axial compressor. The casing temperature was set to the inlet total temperature. The comparison to data was much improved for the efficiency for the 100% speed line relative to the adiabatic simulations. The efficiency difference between the isothermal and adiabatic solutions is about 1%, with the isothermal calculation matching the low flow test condition. The profiles of total temperature with the isothermal boundary condition matched the data near the casing without any overshoot, typical of most compressor calculations. Also the efficiency profile had a similar improvement in matching the data because of its relationship to temperature.A similar comparison between isothermal and adiabatic cases has been carried out for the same geometry with double the design clearance. The working range based on the steady CFD calculations is about half that of the design clearance case which is felt to be realistic.Moreover a detailed analysis based on conservation of Rothalpy has been made and applied to the rotor. Mass averaged Rothalpy is not conserved due to a frictional power term associated with the stationary case as well as heat transfer. The effects of these terms show the extent of the heat transfer is between 10–20% of span away from the casing.The heat transfer effect calculated with the isothermal boundary condition simulation is thought to be real, and accounting for it matches data better than using an adiabatic assumption. However, the real rig would probably not be isothermal at the casing and may require more complex simulations such as a conjugate heat transfer approach.Copyright © 2013 by ASME
Discontinuous Galerkin least-squares finite element methods for singularly perturbed reaction-diffusion problems with discontinuous coefficients and boundary singularities

In this paper, a discontinuous Galerkin least-squares finite element method is developed for singularly perturbed reaction-diffusion problems with discontinuous coefficients and boundary singularities by recasting the second-order elliptic equations as a system of first-order equations. In a companion paper (Lin in SIAM J Numer Anal 47:89–108, 2008) a similar method has been developed for problems with continuous data and shown to be well-posed, uniformly convergent, and optimal in convergence rate. In this paper the method is modified to take care of conditions that arise at interfaces and boundary singularities. Coercivity and uniform error estimates for the finite element approximation are established in an appropriately scaled norm. Numerical examples confirm the theoretical results.
Action of biogenic amines on crustacean chromatophores--IV. Analysis of the synergistic erythrophoric pigment dispersion evoked by 5-hydroxytryptamine and lysergic acid diethylamide in the dwarf crayfish, Cambarellus shufeldti.

Abstract 1. 1. The effects of injection of 5-hydroxytryptamine (5-HT, serotonin) and D -lysergic acid diethylamide (LSD) on the erythrophores of the dwarf crayfish, Cambarellus shufeldti, were determined. 2. 2. 5-HT and LSD evoked synergistic pigment-dispersing responses in the erythrophores of intact crayfish. 3. 3. 5-HT and LSD failed to evoke red pigment dispersion when tested in vitro on isolated pieces of carapace. In contrast, an extract of the eyestalks evoked red pigment dispersion in vitro. 4. 4. Injection of the acetone-soluble fraction of the eyestalks evoked red pigment concentration in eyestalkless crayfish. 5-HT and LSD were both capable of antagonizing the action of the red pigment-concentrating hormone. 5. 5. The red pigment-concentrating hormone from Cambarellus eyestalks and a synthetic red pigment-concentrating octapeptide (Pandalus hormone) were able to antagonize the action of LSD in intact crayfish. 6. 6. It is concluded that 5-HT and LSD act primarily on the neuroendocrine system to stimulate the release of a red pigment-dispersing hormone. The latter stimulates the erythrophores directly and antagonizes the action of the red pigment-concentrating hormones tested.
On lunar asymmetries. 2. Origin and distribution of mare basalts and mascons

[1] A novel mechanism is proposed for the emplacement of mare basalts and the formation of mascons that does not involve melting or remelting of the source region. The source magmas are the remnants of the primordial lunar magma ocean and are rich in incompatible elements, including radioactive isotopes; potassium, rare earth elements, and phosphorus (KREEP); and volatiles. Exsolution of volatiles as the magmas cooled and crystallized (a process called second boiling) produced overpressures which drove the dense basalts upward to the surface, creating the mascons. This process occurred preferentially beneath nearside mare basins, where the crust is thinnest and lithostatic pressure is lowest. The delay between impact and magmatic extrusion reflects the time needed for the volatile-rich magma to cool to its second boiling point. Radioactive heating buffered the magmas against cooling and solidification, allowing for an extended period of magmatism.
Highly efficient incoherent slab-pumped fiber amplifier/laser designs

The problem of delivering a multimode pump to a single mode core is considered. Original designs of double-clad fiber amplifiers are analyzed. A slab pump geometry of a fiber amplifier is suggested. The partially coherent pump should be coupled to the narrow slab which supports propagation of the pump and absorbs highest modes of the core, then the core itself has no need to be single-mode. The slab plays the role of cladding in conventional double-clad fibers. Such a cladding has no need to surround the core and its refractive index can be higher than that of the core. Then the highest modes of the slab are absorbed at the very beginning of the amplifier. This allows for tapering of the slab, providing almost constant pump power in the core. The end result is a the high efficiency of a compact device with scaling to high pump power. We provide the key design formulars for such a device.
Roles of the three major phosphorylation sites of hepatitis B virus core protein in viral replication.

Hepatitis B virus (HBV) core protein is a phosphoprotein. Its three major phosphorylation sites have been identified at the serine residues located at amino acids 157, 164, and 172. In order to investigate the role of core protein phosphorylation in HBV replication, these three serine residues were mutated to alanine to mimic nonphosphorylated serine or to glutamic acid to mimic phosphoserine. The nonphosphorylated core protein analog did not package the HBV pregenomic RNA, and the phosphorylated analog packaged the pregenomic RNA but failed to support viral DNA replication. These results indicate that the core protein phosphorylation may be important for pregenomic RNA packaging and that its dephosphorylation may be important for viral DNA replication. The individual roles of these three major phosphorylation sites in HBV replication were further investigated by being mutated to alanine in different combinations. The results showed that the serine residue at amino acid 157 was not essential for pregenomic RNA packaging, whereas the serine residues at amino acids 164 and 172 were more important. Furthermore, the serine residue at amino acid 157 was not essential for viral DNA replication or viral maturation.
Abstract C140: RIT1 mutations define a new genetic subset of lung adenocarcinoma.

Lung adenocarcinoma is comprised of distinct mutational subtypes characterized by mutually exclusive oncogenic mutations in RTK/RAS pathway members KRAS, EGFR, BRAF, and ERBB2, and translocations involving ALK, RET, and ROS1. Identification of these oncogenic events has transformed therapy of lung adenocarcinoma via application of therapies targeted towards specific genetic lesions in stratified patient populations. However, such mutations have been identified in only ∼55% of lung adenocarcinoma cases in the United States, suggesting other mechanisms of malignancy may be involved in the remaining cases. We analyzed exome sequencing data from 413 lung adenocarcinomas and identified somatic mutations in the small GTPase gene RIT1 in ∼2% of samples. Mutations in RIT1 cluster in a hotspot near the switch II domain of the protein that is homologous to the Q61 region in RAS genes. RIT1 switch II domain mutations are mutually exclusive with all other known lung adenocarcinoma driver mutations. Ectopic expression of mutated RIT1 induces activation of AKT and ERK signaling pathways and transforms NIH3T3 cells in vitro and in vivo. These data identify RIT1 as a driver oncogene in a specific subset of lung adenocarcinomas. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C140. Citation Format: Alice Berger, Marcin Imielinski, Fujiko Duke, Jeremiah Wala, Nathan Kaplan, Geng-Xian Shi, Douglas Andres, Matthew Meyerson. RIT1 mutations define a new genetic subset of lung adenocarcinoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C140.
The ROI fieldbook: Strategies for implementing ROI in HR and training by Patti Pulliam Phillips, CPT, Jack J. Phillips, Ron Drew Stone, and Holly Burkett, CPT

Patti Pulliam Phillips, CPT, PhD, CEO of the ROI Institute, Inc., consults with U.S. and international organizations on implementing the ROI Methodology. Jack J. Phillips, PhD, a world-renowned expert on measurement and evaluation, developed the ROI Methodology; his expertise in measurement and evaluation comes from nearly 30 years of experience. Ron Drew Stone is an author, international consultant, and authority on improving and measuring performance improvement interventions. Holly Burkett, CPT, MA, SPHR, principal of Evaluation Works, has more than 20 years' experience assisting in the design and measurement of performance improvement initiatives. The ROI Fieldbook: Strategies for Implementing ROI in HR and Training (ISBN: 978-0-7506-7622-9) is published by Elsevier Butterworth-Heinemann (price: $44.95; paperback with a CD). This publisher may be reached online at http://www.elsevier.com.
Further evidence on the association between corporate social responsibility and financial performance

Purpose – The purpose of this paper is to examine the association between corporate social responsibility (CSR) and financial performance.Design/methodology/approach – This paper performs an empirical test on the association between CSR and financial performance of a firm.Findings – The regression analysis reveals a significant and positive association between CSR and financial performance. In addition, it finds that the age of long‐term assets is highly correlated with CSR.Originality/value – This paper extends Cochran and Wood by using a larger and more recent sample to examine the association between CSR and financial performance of a firm. It contributes to the CSR literature.
Sequences Found on Staphylococcal β-Lactamase Plasmids Integrated into the Chromosome ofEnterococcus faecalisCH116

Abstract We have previously reported the presence of the staphylococcal β-lactamase gene in chromosomes ofEnterococcus faecalisstrains CH19 and CH116. CH116 also harbors a 26-kb mobile element, designated Tn5384,which confers resistance to erythromycin and gentamicin. Sequence analysis of the rightmost 9 kb of Tn5384indicates that this element lies immediately upstream of the β-lactamase determinant inE. faecalisCH116. This 9-kb region consists of sequences highly homologous to those previously described in staphylococcal β-lactamase plasmids, including a β-lactamase transposon indistinguishable from Tn552,an open reading frame encoding a deduced amino acid sequence 94% identical to a previously described potential staphylococcal invertase, an intact copy of staphylococcal insertion-like element IS257,and the major portion of the staphylococcal organomercurial lyase (merB) gene. These data are consistent with the hypothesis that several of the resistance genes encoded within the large transferable region of the CH116 chromosome were originally components of a staphylococcal β-lactamase plasmid.
Radiosensitizing effect of anti-HER2/neu agents: Report of 2 cases and review of the literature.

The human epidermal growth factor receptors (HERs), including HER1, HER2, HER3, and HER4, are transmembrane tyrosine kinase receptors involved in the regulation of cell growth and survival. Overexpression of HER type 2 (HER2) is seen in approximately 20% to 30% of invasive breast carcinomas. Trastuzumab and pertuzumab (Herceptin and Perjeta, Genentech-Roche, South San Francisco, CA) are humanized recombinant monoclonal antibodies that bind to the extracellular domain of the HER2 receptor and prevent activation of the downstream signaling cascade.1 Pertuzumab and trastuzumab bind to different HER2 epitopes, resulting in a greater antitumor effect through complementary mechanisms of action.2 Multiple randomized clinical trials have demonstrated the efficacy of trastuzumab, pertuzumab, and other antiHER2 agents in early-stage and metastatic HER2-positive breast cancer3-6; therefore, their use has become standard of care in the management of this breast cancer subtype. Trastuzumab remains the first and the best-studied agent in the class of anti-HER2 drugs. Adverse effects of trastuzumab and pertuzumab have been observed primarily when these antibodies were coadministered with chemotherapy. These adverse effects include infusion-
Mouse and human CRKL is dosage sensitive for cardiac outflow tract formation

The human chromosome 22q11.2 region is susceptible to rearrangements during meiosis leading to velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome (22q11DS) characterized by conotruncal heart defects (CTDs) and other congenital anomalies. The majority of individuals have a 3 Mb deletion whose proximal region contains the presumed disease-associated gene TBX1 (T-box 1). Although a small subset have proximal nested deletions including TBX1, individuals with distal deletions that exclude TBX1 have also been identified. The deletions are flanked by low-copy repeats (LCR22A, B, C, D). We describe cardiac phenotypes in 25 individuals with atypical distal nested deletions within the 3 Mb region that do not include TBX1 including 20 with LCR22B to LCR22D deletions and 5 with nested LCR22C to LCR22D deletions. Together with previous reports, 12 of 37 (32%) with LCR22B–D deletions and 5 of 34 (15%) individuals with LCR22C–D deletions had CTDs including tetralogy of Fallot. In the absence of TBX1, we hypothesized that CRKL (Crk-like), mapping to the LCR22C–D region, might contribute to the cardiac phenotype in these individuals. We created an allelic series in mice of Crkl, including a hypomorphic allele, to test for gene expression effects on phenotype. We found that the spectrum of heart defects depends on Crkl expression, occurring with analogous malformations to that in human individuals, suggesting that haploinsufficiency of CRKL could be responsible for the etiology of CTDs in individuals with nested distal deletions and might act as a genetic modifier of individuals with the typical 3 Mb deletion.
Numerical simulations of coronal mass ejection on 2011 March 7: One-temperature and two-temperature model comparison

During Carrington rotation (CR) 2107, a fast coronal mass ejection (CME; >2000 km s −1 ) occurred in active region NOAA 11164. This event is also associated with a solar energetic particle event. In this study, we present simulations of this CME with one-temperature (1T) and two-temperature (2T: coupled thermodynamics of the electron and proton populations) models. Both the 1T and 2T models start from the chromosphere with heat conduction and radiative cooling. The background solar wind is driven by Alfv´ en-wave pressure and heated by Alfv´ en-wave dissipation in which we have incorporated the balanced turbulence at the top of the closed field lines. The magnetic field of the inner boundary is set up using a synoptic map from Solar Dynamics Observatory/ Helioseismic and Magnetic Imager. The Titov–D´ emoulin flux-rope model is used to initiate the CME event. We compare the propagation of fast CMEs and the thermodynamics of CME-driven shocks in both the 1T and 2T CME simulations. Also, the synthesized white light images are compared with the Solar and Heliospheric Observatory/ Large Angle and Spectrometric Coronagraph observations. Because there is no distinction between electron and proton temperatures, heat conduction in the 1T model creates an unphysical temperature precursor in front of the CME-driven shock and makes the shock parameters (e.g., shock Mach number, compression ratio) incorrect. Our results demonstrate the importance of the electron heat conduction in conjunction with proton shock heating in order to produce the physically correct CME structures and CME-driven shocks.
Intergenerational volunteering and quality of life for persons with mild to moderate dementia: results from a 5-month intervention study in the United States.

Objectives To evaluate whether a structured intergenerational volunteering intervention would enhance quality of life (QOL) for persons with mild to moderate dementia. Methods Fifteen participants were randomized into intervention and control groups. The intervention group participated in hour-long structured volunteer sessions with a kindergarten class and an older elementary class in alternating weeks during a 5-month interval. Data on cognitive functioning, stress, depression, sense of purpose, and sense of usefulness were collected at baseline and at the close ofthe intervention. Change scores were computed and analyzed for all variables. Results There was a significant decrease in stress for the intervention group. Conclusions This study adds preliminary findings that intergenerational volunteering interventions might contribute to QOL for persons with dementia, in part through a reduction in stress.
Evaluation of presence of aspirin-related warnings with willow bark.

BACKGROUNDThe dietary supplement willow bark, also known simply as willow, contains salicylates that may present a safety risk to people. Current regulations do not require willow bark to include any cautions on its label.OBJECTIVETo evaluate the absence or presence of label warnings related to salicylates contained in willow bark to ascertain whether a potentially dangerous lack of information exists.METHODSThe label of each willow supplement and willow-containing product was assessed for the presence or absence of 3 warnings: (1) aspirin allergy/sensitivity, (2) use of anticoagulants or “blood thinners,” and (3) children with flu-like symptoms or Reye's syndrome. Products from pharmacies and health food stores were targeted and their labels analyzed. A compilation of the identified products was used to conduct a similar evaluation of warnings from their Web sites.RESULTSA total of 58 willow bark–containing and 12 single-ingredient willow bark products were assessed. Of the 70 products evaluated, only 8....
Family interactions of schizophrenic and schizoaffective patients: determinants of relatives' negativity

Videotaped family problem-solving interactions of 57 schizophrenic or schizoaffective patients and their relatives were examined for predictors of negativity of their communication behavior. Ratings of patients' behaviors and independent assessments of patients' symptomatology were used to predict the negativity of relatives in the videotaped interaction. The results indicated that severity of symptomatology was not related to relatives' negativity. Patients' social skill, as independently assessed by a role-play test, also was not associated with relatives' negativity. The regression results suggest that with both members of a patient-relative dyad, the quality of communication in a discussion is related to the other participant's level of negativity.
Native protein sequences are close to optimal for their structures

How large is the volume of sequence space that is compatible with a given protein structure? Starting from random sequences, low free energy sequences were generated for 108 protein backbone structures by using a Monte Carlo optimization procedure and a free energy function based primarily on Lennard–Jones packing interactions and the Lazaridis–Karplus implicit solvation model. Remarkably, in the designed sequences 51% of the core residues and 27% of all residues were identical to the amino acids in the corresponding positions in the native sequences. The lowest free energy sequences obtained for ensembles of native-like backbone structures were also similar to the native sequence. Furthermore, both the individual residue frequencies and the covariances between pairs of positions observed in the very large SH3 domain family were recapitulated in core sequences designed for SH3 domain structures. Taken together, these results suggest that the volume of sequence space optimal for a protein structure is surprisingly restricted to a region around the native sequence.
A Framework for the Concurrent Consideration of Occupational Hazards and Obesity

Occupational hazards and obesity can lead to extensive morbidity and mortality and put great financial burden on society. Historically, occupational hazards and obesity have been addressed as separate unrelated issues, but both are public health problems and there may be public health benefits from considering them together. This paper provides a framework for the concurrent consideration of occupational hazards and obesity. The framework consists of the following elements: (i) investigate the relationship between occupational hazards and obesity, (ii) explore the impact of occupational morbidity and mortality and obesity on workplace absence, disability, productivity and healthcare costs, (iii) assess the utility of the workplace as a venue for obesity prevention programs, (iv) promote a comprehensive approach to worker health and (v) identify and address the ethical, legal and social issues. Utilizing this framework may advance the efforts to address the major societal health problems of occupational hazards and obesity.
Molecular Clock: Testing

The molecular clock hypothesis originally rested on the assumption of rate constancy across lineages of a phylogeny, which would produce an approximately steady rate of accumulation of deoxyribonucleic acid or amino acid changes through time. This assumption has been questioned on the basis of increasingly large data sets, which have shown significant variability of rates in evolutionary lineages. To address this issue, tests have been developed to examine whether rates of molecular evolution vary significantly among taxonomic groups or phylogenetic lineages. Two major types of tests exist: those based on comparisons of genetic distances and those based on likelihood ratios. The first ones compare genetic distances between two species (or groups of species) relative to an outgroup; the latter ones compare maximum likelihood values for the same phylogeny calculated with and without the constant rate assumption. In those cases where the rate constancy assumption is violated, modern molecular clocks (relaxed clocks) are now being applied to implement the rate heterogeneity in the time estimation process. Key Concepts: The original formulation of the molecular clock hypothesis refers to the approximately steady rate of accumulation of DNA or amino acid changes through time. The assumption underlying the strict molecular clock is that evolutionary rates across lineages are constant. Molecular clock tests have been developed to assess the validity of the rate constancy assumption for DNA and amino acid sequences. Rate testing relies on a measure of genetic distance (branch length) for two or more lineages relative to an outgroup or on likelihood ratio tests. Distance-based rate tests compare rates between two lineages or groups of lineages using the number of nucleotide or amino acid differences between them. Likelihood ratio tests use the chi-square statistic to compare the likelihoods of a tree calculated with and without the rate constancy assumption. Unequal rates can be modelled by relaxed molecular clocks assuming two alternative models: ancestor and descendant lineages are autocorrelated or uncorrelated. Local rate testing using Bayes Factors is used to distinguish between autocorrelated and uncorrelated rate variation in Bayesian-based relaxed clock methods. If evolutionary rates are heterogeneous among lineages, the violating lineages can be pruned from the data set or divergence times can be estimated with relaxed clock methods. Molecular clocks can be used to time divergences for which rare or incomplete palaeontological records exist. Keywords: molecular clock; relative rate test; molecular evolution; sequence analysis; maximum likelihood; phylogenetic tests; evolutionary distance; relaxed clock
Immature granulocyte measurement using the Sysmex XE-2100. Relationship to infection and sepsis

We determined the usefulness of immature granulocyte measurement as a predictor of infection or positive blood culture and compared the results with total WBC count and absolute neutrophil count (ANC). Blood samples from 102 infected and 69 noninfected patients were analyzed using the Sysmex XE-2100 automated blood cell counter (Sysmex, Kobe, Japan). The percentage of immature granulocytes was significantly higher in infected than in noninfected patients and in patients with positive than patients with negative blood cultures. Receiver operating characteristic curves showed that the percentage of immature granulocytes was a better predictor of infection than the WBC count and comparable to the ANC. Automated immature granulocyte measurements reflect a biologically and clinically relevant phenomenon but are not sensitive enough to be used as screening assays for prediction of infection or bacteremia. However, although infrequently encountered, a percentage of immature granulocytes of more than 3 was a very specific predictor of sepsis and might help expedite microbiologic laboratory evaluation of a subset of patients.
Bugs versus drugs: addressing the pharmacist's challenge.

Purpose. To address how the high endemic levels of antimicrobial resistance and multidrug resistance in hospitals have challenged clinicians to select appropriate therapy for effectively treating bacterial infections among seriously ill patients. Summary. Among gram-positive bacterial infections, differentiating between healthcare-associated and community-associated methicillin-resistant Staphylococcus aureus infections is becoming more difficult and can seriously impact therapeutic strategies and hence outcomes. Furthermore, the rising prevalence of multidrug-resistant gram-negative bacterial infections is increasing the pressure on proper antimicrobial selection given the dearth of new antimicrobial agents under development. Optimized dosing strategies will be instrumental in minimizing emergence of resistance and preserving the utility of currently available agents. Antimicrobial stewardship programs in conjunction with stringent infection control policies will be critical in improving the appropriate use of antimicrobials while reducing the spread of nosocomial pathogens. Conclusion. Addressing the challenges of antimicrobial resistance in hospitals will require a multidisciplinary approach, with clinical pharmacists taking a proactive role in ensuring the appropriate use of antimicrobials.
Areas of concern in psychiatric music therapy: A descriptive analysis

Abstract Psychiatric settings remain a large area of clinical practice for the music therapy profession. However, the percentage of psychiatric music therapists has remained relatively constant and music therapy students seem to be increasingly interested in other clinical areas. The purpose of this descriptive study was to survey psychiatric music therapists and identify their potential areas of concern for the future of psychiatric music therapy. The researcher emailed a brief survey to all members of the American Music Therapy Association listed in the “mental health” section of the 2009 Member Sourcebook . Fifty-three respondents participated for a response rate of 18.40%. There were significant main effects in areas of concern and theoretical orientations and there was a significant interaction between these two variables. Results indicated that outpatient care was the highest concern, followed by healthcare reform, brief treatment, and evidence-based practice. Participants rated job security as the lowest area of concern. Participants who identified themselves as having cognitive behavioral, eclectic, and humanistic orientations rated the importance of qualitative research and quantitative research equally. To corroborate data, themes from participants’ free response comments were coded. Participants most frequently indicated that research, training, employment, and licensure/credentials/reimbursement were areas of concern. Overall, results seem to be congruent with contemporary trends in the literature base and clinical practice. Limitations of the study, implications for clinical practice, and suggestions for future research are provided.
Outcomes after whole brain reirradiation in patients with brain metastases.

Purpose Patients with brain metastases are often treated with whole brain radiation therapy (WBRT) for purposes of palliation. The treatment of those who experience subsequent intracranial disease progression can include a second course of WBRT, although there is controversy surrounding its safety and efficacy. This study examines the outcomes in patients at Massachusetts General Hospital who underwent reirradiation. Patients and Methods We examined the medical records of 17 patients at Massachusetts General Hospital with brain metastases who were initially treated with WBRT between 2002 and 2008 and were subsequently retreated with a second course of WBRT. The median dose for the first course of WBRT was 35 Gy (range, 28–40 Gy), with a fraction size of 2 to 3 Gy (median, 2.5 Gy). The median dose at reirradiation was 21.6 Gy (range, 14–30 Gy), with a fraction size of 1.5 to 2 Gy (median, 1.8 Gy). Results The second course of WBRT was administered upon radiographic disease progression in all patients. Of 10 patients with complete follow-up data, 8 patients experienced complete or partial symptom resolution, and 2 did not show clinical improvement. The time to radiographic progression was 5.2 months. The median overall survival for all patients after diagnosis of metastases was 24.7 months. The median survival time after initiation of reirradiation was 5.2 months (95% CI, 1.3–8.7). In 6 patients with stable extracranial disease, the median survival time after retreatment was 19.8 months (95% CI, 2.7–∞), compared with 2.5 months (95% CI, 0.8–5.5) for those with extracranial disease progression ( p = 0.05). Acute adverse reactions occurred in 70.5% of patients but were mild to moderate in severity. Conclusion In select patients and especially those with stable extracranial disease, reirradiation may be an appropriate and effective intervention to provide symptomatic relief and slow intracranial disease progression. Side effects were minimal and did not cause substantial changes in quality of life.