cssi/SciSciGPT-SciSciNet huggingface dataset:
Discovery Tactics To Mitigate Toxicity Risks Due to Reactive Metabolite Formation with 2-(2-Hydroxyaryl)-5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one Derivatives, Potent Calcium-Sensing Receptor Antagonists and Clinical Candidate(s) for the Treatment of Osteoporosis

The synthesis and structure-activity relationship studies on 5-trifluoromethylpyrido[4,3-d]pyrimidin-4(3H)-ones as antagonists of the human calcium receptor (CaSR) have been recently disclosed [ Didiuk et al. ( 2009 ) Bioorg. Med. Chem. Lett. 19 , 4555 - 4559 ). On the basis of its pharmacology and disposition attributes, (R)-2-(2-hydroxyphenyl)-3-(1-phenylpropan-2-yl)-5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one (1) was considered for rapid advancement to first-in-human (FIH) trials to mitigate uncertainty surrounding the pharmacokinetic/pharmacodynamic (PK/PD) predictions for a short-acting bone anabolic agent. During the course of metabolic profiling, however, glutathione (GSH) conjugates of 1 were detected in human liver microsomes in an NADPH-dependent fashion. Characterization of the GSH conjugate structures allowed insight(s) into the bioactivation pathway, which involved CYP3A4-mediated phenol ring oxidation to the catechol, followed by further oxidation to the electrophilic ortho-quinone species. While the reactive metabolite (RM) liability raised concerns around the likelihood of a potential toxicological outcome, a more immediate program goal was establishing confidence in human PK predictions in the FIH study. Furthermore, the availability of a clinical biomarker (serum parathyroid hormone) meant that PD could be assessed side by side with PK, an ideal scenario for a relatively unprecedented pharmacologic target. Consequently, progressing 1 into the clinic was given a high priority, provided the compound demonstrated an adequate safety profile to support FIH studies. Despite forming identical RMs in rat liver microsomes, no clinical or histopathological signs prototypical of target organ toxicity were observed with 1 in in vivo safety assessments in rats. Compound 1 was also devoid of metabolism-based mutagenicity in in vitro (e.g., Salmonella Ames) and in vivo assessments (micronuclei induction in bone marrow) in rats. Likewise, metabolism-based studies (e.g., evaluation of detoxicating routes of clearance and exhaustive PK/PD studies in animals to prospectively predict the likelihood of a low human efficacious dose) were also conducted, which mitigated the risks of idiosyncratic toxicity to a large degree. In parallel, medicinal chemistry efforts were initiated to identify additional compounds with a complementary range of human PK predictions, which would maximize the likelihood of achieving the desired PD effect in the clinic. The back-up strategy also incorporated an overarching goal of reducing/eliminating reactive metabolite formation observed with 1. Herein, the collective findings from our discovery efforts in the CaSR program, which include the incorporation of appropriate derisking steps when dealing with RM issues are summarized.
Mitigation of Residential Formaldehyde Contamination by Indoor Climate Control

The effectiveness of indoor climate as a mitigation measure for indoor formaldehyde contamination was studied in a mobile home. The effects of nine indoor climate regimes on formaldehyde levels were evaluated for the temperature and humidity ranges of 20°C to 30°C and 30% RH to 70% RH. Formaldehyde levels at the lowest combination of temperature and relative humidity (20°C, 30% RH) were only 20% of those measured at the highest combination of temperature and relative humidity (30°C, 70% RH) evaluated. Reducing temperature alone (from 30°C to 20°C) was shown to result in an approximate 70% reduction in formaldehyde levels. Reducing relative humidity alone (from 70% to 30%) resulted in an approximate 40% reduction in formaldehyde levels. A high linear correlation was observed between formaldehyde levels and temperature and between formaldehyde levels and relative humidity. Analysis of energy consumption and associated costs indicated that temperature reduction from 25°C to 20°C during the cooling season wou...
Crystal Quality and Physical Reactivity in the Case of Flufenamic Acid (FFA)

ABSTRACT In reality, no crystal is perfect. Crystals bear defects both in the bulk and on the surface. The purpose of this project is to study the correlation between crystal defect density and reactivity of physical transformation. The hypothesis is that larger crystals have the opportunity to pick up more defects during crystal growth than smaller crystals, therefore, have higher reactivity. Flufenamic acid (FFA) was used as a model compound. Phase transformation of crystal Form I (white) to Form III (yellow) of FFA was studied, and observed that larger crystals of FFA Form I transform faster. Furthermore, the etching pits identified on the major crystal faces (1 0 0) using atomic form microscopy (AFM) also showed that larger crystals had higher surface defect density than smaller ones, which correlates with the finding that larger crystals transforms faster than smaller ones. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3839–3848, 2010
Long-term effects of behavioral treatment of chronic headache*

Ten reports of prospective follow-ups of at least 12 months duration for behavioral treatment of chronic headache are summarized and reviewed. The available data support two tentative conclusions for tension headache: headache relief from cognitive therapy or relaxation training (possibly followed by frontal EMG biofeedback) is maintained for 2 and 4 years, respectively, while the initial headache reduction obtained with frontal EMG biofeedback alone deteriorates progressively (but not back to pretreatment level_ at 2 and 3 years. For migraine headache, there is good maintenance of headache reduction at 12 months. However, for vascular headache (migraine and combined migraine and tension) treated with relaxation and thermal biofeedback, there is tentative support for a persistent, progressive deterioration, year-by-year, to a four-year follow-up point.
Knockout of plasminogen activator inhibitor 1 gene reduces amyloid beta peptide burden in a mouse model of Alzheimer’s disease

Accumulation of amyloid beta peptide (Aβ) in the brain is a pathological hallmark of Alzheimer's disease (AD); the underlying mechanism, however, is not well understood. In this study, we show that expression of plasminogen activator inhibitor 1 (PAI-1), a physiological inhibitor of tissue type and urokinase type plasminogen activators (tPA and uPA), increases with age in the brain of wild type and Aβ precursor protein-presenilin 1 (APP/PS1) transgenic mice as well as in AD patients. Most importantly, we show that knocking out the PAI-1 gene dramatically reduces Aβ burden in the brain of APP/PS1 mice but has no effect on the levels of full-length APP, alpha or beta C-terminal fragments. Furthermore, we show that knocking out the PAI-1 gene leads to increases in the activities of tPA and plasmin, and the plasmin activity inversely correlates with the amounts of SDS insoluble Aβ40 and Aβ42. Together, these data suggest that increased PAI-1 expression/activity contributes importantly to Aβ accumulation during aging and in AD probably by inhibiting plasminogen activation and thus Aβ degradation.
Developmental expression of fibroblast growth factor receptor-1 (cek-1; flg) during heart development

Previous work in this laboratory has indicated that fibroblast growth factor-2 (FGF-2; bFGF) regulates the initial stages of avian heart development in paracrine and autocrine fashion (Parlow et al. [1991] Dev. Biol. 146:139-147; Sugi et al. [1993] Dev. Biol. 157:28-37). Because these findings inferred the presence of a functional receptor for fibroblast growth factor (FGFR), we have immunochemically assessed the appearance of FGFR-1 (cek-1; flg) during development. Using a peptide-generated antibody, Western blots of total embryonic proteins revealed that FGFR-1 was barely detectable at pre-heart stages, followed by sequential increases in relative abundance that peaked at stage 24, followed by a decline at days 7-14. Western blots of proteins from isolated embryonic hearts demonstrated a similar developmental pattern, except that FGFR-1 expression was not decreased at later stages. The presence of FGFR-1 mRNA was verified by reverse transcription/polymerase chain reaction (RT/PCR) amplification. Immunohistochemical examination revealed punctate deposits of FGFR-1 in the precardiac endoderm at stage 6, followed by detection in the endoderm, foregut, and pre-cardiac splanchnic mesoderm at stage 8 and in the newly formed myocardium at the heart tube stage (9/10). By stage 13, FGFR-1 staining was observed only in the myocardium, a pattern which persisted at least until stage 30 (day 7), after which only isolated hearts were examined. After stage 30, staining was diminished in the ventricle, but not in the atrium. Staining of cardiac endothelial cells was not observed at any stage. A functional role for FGFR-1 was indicated by experiments in which anti-FGFR-1, but not pre-absorbed antiserum, retarded proliferation and multilayering of cardiogenic cells in an in vitro model of cardiac morphogenesis.
Radiation Resistance of a Baffled Beam

The radiation resistance of a beam is theoretically determined from the total acoustic power radiated into the farfield. The beam is supported in an infinite baffle, with both hinged and clamped supports considered. Asymptotic solutions are derived for frequencies well below the critical frequency. Curves, covering the entire frequency range between the low‐ and high‐frequency asymptotic solutions, are obtained through numerical integration for the first ten modes of beams with various width‐to‐length ratios. For frequencies well below the critical frequency, the ratio of the radiation resistance of a beam clamped at each end to that of a beam hinged at each end is 0.851 for the first mode, 0.711 for the second mode, and asymptotically approaches 2 as the mode number tends to infinity. For both hinged and clamped supports, the radiation resistance of all modes increases with the beam width‐to‐length ratio.
Strengths and lorentz broadening coefficients for spectral lines in the ν3 and ν2 + ν4 bands of 12CH4 and 13CH4

Abstract Line strengths and self- and nitrogen-broadened half-widths were measured for spectral lines in the ν3 and ν2 + ν4 bands of 12CH4 and 13CH4 from 2870–2883 cm−1 using a tunable diode laser spectrometer. From measurements made over a temperature range from 215 to 297 K, on samples of 12CH4 broadened with N2, we deduced that the average temperature coefficients n, defined as b L 0 (T) = b L 0 (T 0 )( T T 0 ) −n , of the Lorentz broadening coefficients for the ν3 and ν2 + ν4 bands of 12CH4 were 0.97 ± 0.03 and 0.89 ± 0.04, respectively. A smaller increase is observed in line half-width with increasing pressure for E-species lines, for both self- and nitrogen-broadening, than for other symmetry species lines over the range of pressures measured, 70 to 100 Torr.
3D Shape Matching and Inspection Using Geometric Features and Relational Learning

In this paper we consider the problem of matching 3D sensed data with models and inspection for defects where the correspondence between models and data needs to be solved in robust and efficient ways. We explore the use of machine learning (in particular, relational learning) as an efficient method for solving correspondence (and so, pose estimation) as well as automatically generating rules for acceptable shape variations from training data. As an additional but necessary issue, we also consider the use of view-independent covariance methods for the extraction of surface features used to determine shape signatures which correspond to curvature-like surface attributes. Such features are utilized in the relational learning model.
Small Molecules CK-666 and CK-869 Inhibit Actin-Related Protein 2/3 Complex by Blocking an Activating Conformational Change

Actin-related protein 2/3 (Arp2/3) complex is a seven-subunit assembly that nucleates branched actin filaments. Small molecule inhibitors CK-666 and CK-869 bind to Arp2/3 complex and inhibit nucleation, but their modes of action are unknown. Here, we use biochemical and structural methods to determine the mechanism of each inhibitor. Our data indicate that CK-666 stabilizes the inactive state of the complex, blocking movement of the Arp2 and Arp3 subunits into the activated filament-like (short pitch) conformation, while CK-869 binds to a serendipitous pocket on Arp3 and allosterically destabilizes the short pitch Arp3-Arp2 interface. These results provide key insights into the relationship between conformation and activity in Arp2/3 complex and will be critical for interpreting the influence of the inhibitors on actin filament networks in vivo.
Increasing Resilience: Strategies for Reducing Dropout Rates for College Students with Psychiatric Disabilities

Individuals with psychiatric disabilities are less likely to enter college and, after enrolling in college, are more likely to drop out. In response, psychiatric rehabilitation practitioners have used a program called supported education (SEd) to improve retention rates for college students with psychiatric disabilities. As an emerging research paradigm, resilience offers a new direction for understanding and implementing SEd. Congruent with the objectives of SEd, this article presents ways that resilience research can be used to improve the retention of students with psychiatric disabilities in 2- and 4-year colleges.
Molecular cloning and characterization of a murine hemicholinium-3-sensitive choline transporter.

In cholinergic neurons, a specific requirement for precursor choline in the biosynthesis of acetylcholine (ACh) is thought to be sustained by a presynaptic, hemicholinium-3 (HC-3)-sensitive choline transporter (CHT). This transporter exhibits micromolar affinity for choline and transport activity is Na + - and Cl − -dependent. Based on the sequence information available with the recent cloning of rat and human CHTs [Okuda, Haga, Kanai, Endou, Ishihara and Katsura (2000) Nat. Neurosci. 3 , 120–125; Apparsundaram, Ferguson, George Jr and Blakely (2000) Biochem. Biophys. Res. Commun. 276 , 862–867; Okuda and Haga (2000) FEBS Lett. 484 , 92–97], we have identified a murine CHT orthologue (mCHT) by reverse transcriptase-PCR of spinal cord mRNA and confirmed this sequence using assembled mouse genomic DNA. Inferred splice junctions for mCHT exons are conserved with those of hCHT. The mCHT cDNA encodes a protein of 580 amino acids with 93 % and 98 % amino acid identity to human CHT and rat CHT1, respectively. Hydropathy analysis of the predicted amino acid sequence of mCHT indicates a protein containing 13 transmembrane domains (TMDs), with the N-terminus oriented extracellularly and the C-terminus oriented intracellularly. Northern blot analysis of mouse tissues reveals the expression of mCHT as a single transcript of ~ 5 kb with highest expression in regions that are rich in cholinergic cell bodies, e.g. the spinal cord, brainstem, mid-brain and striatum, whereas hybridization signals are absent in regions lacking cholinergic soma, e.g. the cerebellum and kidney. Expression of mCHT in COS-7 cells results in high-affinity [ 3 H]HC-3-binding sites ( K d = 5 nM), and Na + - and Cl − -dependent HC-3-sensitive choline uptake ( K m = 2 μM), assessed in resealed membrane vesicles. The availability of cloned, functional mCHT and its cognate genomic DNA should prove useful for studies of mCHT regulation and should open possibilities for evaluation of CHT dysfunction in murine models.
Experimental evidence for strong plasmon coupling in the soft X-ray appearance potential spectrum of graphite☆

Abstract Plasmon satellite structure is known to be weak in X-ray absorption experiments because of the effective cancellation between the couplings to the conduction electrons of the excited electron and core hole. Data on the soft X-ray appearance potential spectrum for the K-shell excitation of graphite however are shown to exhibit strong plasmon effects illustrating the enhanced coupling that results from the creation of an additional conduction electron.
Relation of biofuel to bioelectricity and agriculture: Food security, fuel security, and reducing greenhouse emissions

Biofuels are being developed in the context of three broad economic and policy drivers: reducing greenhouse gas emissions, increasing energy security, and supporting agriculture. Projections of the land and feedstock potentially available for bioenergy indicate that bioenergy development could be resource limited, and food crops may be partially displaced by biofuel feedstocks. One motivation for biofuel development is to reduce greenhouse gas emissions, yet bioelectricity typically provides greater greenhouse gas reductions than biofuel. Moreover, carbon prices affect electricity prices more than petroleum prices. Biofuel development can reduce petroleum supply risks, and the relative balance of policy emphasis on climate change and petroleum security will shape the policies for biofuel development.
Properties of CP: Coefficient of Thermal Expansion, Decomposition Kinetics, Reaction to Spark, Friction and Impact

The properties of pentaamine (5-cyano-2H-tetrazolato-N2) cobalt (III) perchlorate (CP), which was first synthesized in 1968, continues to be of interest for predicting behavior in handling, shipping, aging, and thermal cook-off situations. We report coefficient of thermal expansion (CTE) values over four specific temperature ranges, decomposition kinetics using linear and isothermal heating, and the reaction to three different types of stimuli: impact, spark, and friction. The CTE was measured using a Thermal Mechanical Analyzer (TMA) for samples that were uniaxially compressed at 10,000 psi and analyzed over a dynamic temperature range of -20 C to 70 C. Differential scanning calorimetry, DSC, was used to monitor CP decomposition at linear heating rates of 1-7 C min{sup -1} in perforated pans and of 0.1-1.0 C min{sup -1} in sealed pans. The kinetic triplet was calculated using the LLNL code Kinetics05, and predictions for 210 and 240 C are compared to isothermal thermogravimetric analysis (TGA) experiments. Values are also reported for spark, friction, and impact sensitivity.
Ignition & Growth and JWL++ Detonation Models in Coarse Zones

“Ignition & Growth” (I&G) and JWL++ models are compared for a variety of problems. The detonation velocity becomes nearly constant with zoning at the edge of convergence, which for TATB, is 8 zones/mm for I&G and 4 for JWL++. The use of pressure in the rate for I&G makes the detonation velocity rapidly decrease as the zones are coarsened. Using pressure plus artificial viscosity to some power in the rate for JWL++ allows the correction for coarsening zones. In coarse zones, the pressure and the burn fraction turn on independently and this feature dominates model behavior. If pressure lags burn fraction, then the maximum pressure will be lower than expected. An unexpected phenomenon is saturation, i.e. the slowing down of the detonation velocity as a function of the fast rate constant. This slowing can be weak and produce a plateau, or it can be strong and cause the detonation velocity to approach an asymptote. The saturation effect comes from a combination of the 1−F term and declining pressures. Failure (critical diameter effect) occurs in reactive flow but optimizing for this undoes the settings for other results. In JWL++ , the fast reaction pressure exponent is near −1 for the best fit for the size (diameter) effect, 2 for the Pop plot and near −3 to fit failure. The Pop plot deflagration rate is derived, although it needs not to be the same as the detonation rate. The use of additive pressures is compared with the pressure equilibrator and no difference is found. Increased zoning by a factor of 5 and improved code structure will be needed for future improvement.
In vivo optical spectroscopy detects radiation damage in brain tissue.

OBJECTIVE: Magnetic resonance imaging abnormalities in malignant brain tumors after irradiation may represent either recurrent tumor or radiation injury. Optical spectroscopy may represent a novel technique to identify radiation damage in brain tissues and to differentiate contrast-enhancing lesions from recurrent tumor. METHODS: Fluorescence and diffuse reflectance spectra were acquired from 90 patients: 15 undergoing surgical resection for presumed recurrent tumor after radiation therapy, 15 with epilepsy and hippocampal sclerosis, and 60 with tumors who had not received irradiation. Optical spectra were acquired from 6 to 10 sites and were compared with a biopsy obtained from beneath the optical spectroscopy probe; the data then were classified by a neuropathologist blinded to the spectroscopy data. A probe for the intraoperative collection of diffuse reflectance and fluorescence spectra was used. RESULTS: Thirteen of 15 patients (29 of 129 spectra) with previous irradiation showed a unique spectral feature characterized by a fluorescence peak centered at 500 nm (F 500 ). All biopsy specimens showing histopathological signs of radiation injury had the F 500 on their corresponding spectra (18 of 18). The F 500 was identified in another 10% (11 of 111 spectra) of samples with previous irradiation but no histologically identifiable signs of radiation damage. The F 500 was never seen in the normal temporal lobe of epilepsy patients with hippocampal sclerosis (0 of 105) and was seen in only 1.5% of tumor patients who did not undergo previous irradiation (6 of 433). CONCLUSION: Optical spectroscopy detects radiation damage in brain tissues. The F 500 spectral peak may allow accurate selection of tissues for biopsy in evaluating patients with new, contrast-enhancing lesions in the setting of previous irradiation.
Decreasing effective nanofluidic filter size by modulating electrical double layers: Separation enhancement in microfabricated nanofluidic filters

Conventional methods for separating biomolecules are based on steric interactions between the biomolecules and randomly oriented gel fibers. The recently developed artificial molecular sieves also rely on steric interactions for separation. In this work, we present an experimental investigation of a method that can be used in these sieves to increase separation selectivity and resolution. This method exploits the electrostatic repulsion between the charged molecules and the charged nanofluidic structure. Although this method has been mentioned in the previous work, it has not been examined in detail. We characterize this method by comparing the selectivity with that achieved in devices with different dimensions. The results of this study are relevant to the optimization of chip-based gel-free biomolecule separation and analysis.
Rates and predictors of renewed quitting after relapse during a one-year follow-up among primary care patients.

Background Most people who quit smoking relapse within a year of quitting. Little is known about what prompts renewed quitting after relapse or how often this results in abstinence.
Microcomputer-based tutorials for teaching statistics

A set of computational and exploratory exercises is described for teaching and remediation in undergraduate statistics. The materials consist of an ensemble of BASIC programs written for the use of a variety of popular microcomputers and a system-independent workbook.
Locally compact, countably paracompact spaces in the constructible universe

Abstract It is proven that under V = L, every locally compact, countably paracompact space is collectionwise normal with respect to compact sets. From this it can be shown that under V = L, submetacompact implies paracompact in the class of locally compact, countably paracompact spaces.
Managing workforce diversity as an essential resource for improving organizational performance

Today, human resource management is being renewed in organizations and is gradually affirming its strategic role. The need for highly qualified managers will increase as more organizations globalize their operations. The research presented in this paper highlights the need for management who are sensitive to the concerns of multicultural employees. The effects of cultural diversity on organizational behavior are complex and powerful. Within this perspective, the definition of diversity in the USA and the goals in achieving a more diverse workplace will be discussed. This paper will also examine the different facets involved in managing and developing a diverse human resource base. Organizations take into account their human resource base before hiring employees. One factor they look at is the possible advantages and disadvantages of a multicultural and diverse organization. This paper will examine ways by which managers and employees can learn about diversity, understand it, and respect it on a day‐to‐day basis when dealing with people from other diverse backgrounds.
Effect of Surface Passivation on the Electrogenerated Chemiluminescence of CdSe/ZnSe Nanocrystals

The electrogenerated chemiluminescence (ECL) spectrum of CdSe/ZnSe nanocrystals (NCs) dispersed in a CH2Cl2 solution containing 0.1 M TBAP was obtained by stepping the potential between +2.3 and −2...
MLSE and MAP detectors for high-data-rate DS-CDMA reception in dispersive channels

A maximum likelihood sequence estimation (MLSE) and a maximum a posteriori (MAP) detector for DS-CDMA are proposed. The proposed receivers are attractive when the desired signal is in multi-code reception scenarios and when propagation channels are dispersive. Multipath results in loss of orthogonality among own-cell signals in the downlink and among same-user signals in the uplink. In these cases, receiver performance is limited by self-interference from the desired signal itself and interference from all other signals. The generalized RAKE (C-RAKE) receiver can be used to suppress both forms of interference, treating them as colored noise. To improve receiver performance further, we use an MLSE or a MAP detector to alleviate self-interference. The MAP detector can be used with the outer code decoder to form a turbo equalizer to further improve the receiver performance. Our numerical results show that gains larger than 2 dB over G-RAKE can be achieved by the proposed receivers for a WCDMA radio-access bearer of 4.6 Mbps using a 64-state sequence detector.
Cost of Ventricular Assist Devices: Can We Afford The Progress?

The societal cost of heart failure (HF) is matched by few other medical conditions. More than 670 000 new cases will be diagnosed this year.1 It commonly affects the aged and is associated with other chronic illnesses. Despite significant improvements in outcomes associated with contemporary medical and electric therapies, HF tends to be a progressive condition with a median survival of only 2 to 3 years after diagnosis.2 In addition, HF is the second most costly condition for Medicare.3 The total expenditure on this disease in the United States is estimated between $20 to $39 billion,1,4,5 which corresponds to 1.5% to 4% of total health care costs.6 Further, the majority of medical financial resources are consumed in the final 2 years of life, a cost estimated at nearly $155 000.7 Patients with advanced HF failing optimal treatments have limited therapeutic options. A small subset may qualify for cardiac transplantation, but stringent candidacy criteria and a limited supply of donor hearts limits its value to the larger HF population. In the past 5 years, improvements in left ventricular assist devices (LVAD) have made this a viable option to bridge a patient to transplant (BTT) or as permanent therapy (Destination Therapy, DT). The inability to define the size of the population that may ultimately be candidates for VAD therapy, particularly as DT, has led to widespread angst about the health care cost implications of this technology. The primary focus of this article is to critically review the available literature on the cost of VADs as well as alternative treatments for advanced HF. Patients with advanced HF have a 1-year survival of only 10% to 25%.8 Initial clinical trials of older pulsatile flow LVADs used as destination therapy demonstrated 1-year survival of …
Variables associated with return to sport following anterior cruciate ligament reconstruction: a systematic review

Background As one of the purposes of anterior cruciate ligament reconstruction (ACLR) is to return athletes to their preinjury activity level, it is critical to understand variables influencing return to sport. Associations between return to sport and variables representing knee impairment, function and psychological status have not been well studied in athletes following ACLR. Purpose The purpose of this review was to summarise the literature reporting on variables proposed to be associated with return to sport following ACLR. Study design Systematic review. Methods Medline, EMBASE, CINAHL and Cochrane databases were searched for articles published before November 2012. Articles included in this review met these criteria: (1) included patients with primary ACLR, (2) reported at least one knee impairment, function or psychological measure, (3) reported a return to sport measure and (4) analysed the relationship between the measure and return to sport. Results Weak evidence existed in 16 articles suggesting variables associated with return to sport included higher quadriceps strength, less effusion, less pain, greater tibial rotation, higher Marx Activity score, higher athletic confidence, higher preoperative knee self-efficacy, lower kinesiophobia and higher preoperative self-motivation. Conclusions Weak evidence supports an association between knee impairment, functional and psychological variables and return to sport. Current return to sport guidelines should be updated to reflect all variables associated with return to sport. Utilising evidence-based return to sport guidelines following ACLR may ensure that athletes are physically and psychologically capable of sports participation, which may reduce reinjury rates and the need for subsequent surgery.
Malls and consumption motivation: an exploratory examination of older Generation Y consumers

Although malls have been a topic of interest to marketing researchers for at least 35 years, the attraction between malls and Generation Y consumers has received little interest from marketing academics. This study focuses on the attitudes that the older segment of Generation Y consumers (19‐25) have toward a mall, and on their consumption motivation. Key findings include that Generation Y consumers are more likely to be objectively rather than socially motivated to consume. The findings also suggest that objective motivations to consume predict an individual consumer's perception of a shopping mall's ambience, layout, and his or her involvement in the shopping process. Social motivations to consume predict perceptions of a mall's ambience, design, variety, and excitement, as well as the consumer's desire to stay and intent to return to the mall. Managerial implications include using objective information, such as price‐oriented promotions, when trying to attract older Generation Y consumers.
Combination Therapy with Interferon and Ribavirin in the Treatment of Chronic Hepatitis C Infection

OBJECTIVE:To review and critique the medical literature regarding the combination of interferon and ribavirin in the initial treatment of chronic hepatitis C virus (HCV) infection.DATA SOURCES:A MEDLINE search (January 1966–June 1999) was conducted to identify human clinical trials regarding the combination of interferon and ribavirin therapy for the initial treatment of chronic HCV. Bibliographies were reviewed for relevant literature.STUDY SELECTION:Clinical trials of combination interferon and ribavirin for the treatment of chronic HCV in interferon-naive adults were reviewed.DATA SYNTHESIS:The combination of ribavirin and interferon in the treatment of chronic HCV has been beneficial in patients who are interferon-naive. Patients with predictors of poor response, such as baseline cirrhosis, male gender, age >40 years, high baseline viral loads (>2 times 106 copies/mL), and genotype 1 respond better to combination treatment when compared with those who receive interferon monotherapy. Patients with geno...
RELATION BETWEEN BIRTH WEIGHT AND LITTER SIZE IN MULTIPAROUS MAMMALS.

In multiparous mammals there is a definite relation between the litter size N and the total weight of the litter W. Reasons are given showing that this relationship is independent of the mechanism of parturition. For various forms W = NK + const. Hence the average increment of W due to unit increase of N is directly proportional to W, inversely to N. This signifies proportionality between N and nutritive drain upon the mother, as well as equipartition among the members of the litter. K is non-specific, and is therefore regarded as a partition index.
Primary chylopericardium: a review of the literature and an illustrated case☆

A report of a case of chylous pericardium and a review of previously reported cases are given. The specific diagnosis can be made with pericardiocentesis and analysis of the fluid which is milky in appearance and contains fat droplets microscopically. Thoracic duct obstruction with failure of adequate collateral drainage and resultant reflux of chylous lymph through lymphatics draining the heart and pericardium is proposed as a mechanism of development of this entity. Thoracic duct ligation and partial pericardectomy remain the preferred treatment for chylopericardium.
Photoluminescence decay dynamics of silicon-rich silicon nitride film in photonic crystal nanocavity

We described design and fabrication of the light source, and demonstrated sevenfold photoluminescence (PL) enhancement from a single cavity. In this approach, photonic crystal cavities are used to enhance PL by increasing spontaneous emission rate from Si nanoparticles due to the Purcell effect, and by increasing collection efficiency. Here we report our results on the measured photoluminescence decay time, cavity design optimization, and efficiency of the material.
Chaperone-mediated autophagy: machinery, regulation and biological consequences

Degradation of dysfunctional intracellular components in the lysosome system can occur through three different pathways, i.e., macroautophagy, microautophagy and chaperone-mediated autophagy (CMA). In this review, we focus on CMA, a type of autophagy distinct from the other two autophagic pathways owing to its selectivity, saturability and competitivity by which a subset of long-lived cytosolic soluble proteins are directly delivered into the lysosomal lumen via specific receptors. CMA participates in quality control to maintain normal cell functions by clearing “old” proteins and provides energy to cells under nutritional stress. Deregulation of CMA has recently been shown to underlie some diseases, especially neurodegenerative disorders for which the decline with age in the activity of CMA may become a major aggravating factor. Therefore, targeting aberrant alteration in CMA under pathological conditions could serve as a potential therapeutic strategy for treating related diseases.
Provider Perceptions of Focus Group Research Use: A Multicountry Perspective

This study examines hypotheses about variables affecting focus group research use in organizations. A total of 248 moderators (128 from the United States, 67 from Germany, and 53 from Japan) provided data for this analysis of the relationships between research objectives, moderators, other variables, and the instrumental (direct application to solving a specific problem) and noninstrumental (conceptual and symbolic) uses of focus group research. The results of regression analyses showed that moderators and research objectives play important roles in the reporting and uses of focus group research and that these effects do not differ by country.
An Enactive Model of Creativity for Computational Collaboration and Co-creation

The modern landscape of computing has rapidly evolved with breakthroughs in new input modalities and interaction designs, but the fundamental model of humans giving commands to computers is still largely dominant. A small but growing number of projects in the computational creativity field are beginning to study and build creative computers that are able to collaborate with human users as partners by simulating, to various degrees, the collaboration that naturally occurs between humans in creative domains (Biles, Leonardo, 36:43–45, 2003; Lubart, Int J Hum Comput Stud, 63:365–369, 2005; Hoffman and Weinberg, Shimon: an interactive improvisational robotic marimba player. In: CHI’10 extended abstracts on human factors in computing systems, ACM, New York, pp 3097–3102, 2010; Zook et al., Understanding human creativity for computational play. In: 8th ACM conference on creativity and cognition, 2011; Davis et al., Building artistic computer colleagues with an enactive model of creativity, 2014). If this endeavor proves successful, the implications for HCI and the field of computing in general could be significant. Creative computers could understand and work alongside humans in a new hybrid form of human-computer co-creativity that could inspire, motivate, and perhaps even teach creativity to human users through collaboration.
A convolution property of the Cantor-Lebesgue measure, II

For 1 p;q 1, we prove that the convolution operator generated by the Cantor{Lebesgue measure on the circleT is a contraction whenever it is bounded from L p (T) to L q (T). We also give a condition on p which is necessary if this operator maps L p (T) into L 2 (T).
Heuristic, storage space minimization methods for facility layouts served by looped AGV systems

Abstract An analytical method for predicting work-in-process storage requirements resulting from a fixed number of looping, automated guided vehicles (AGVs) serving a line layout is described. The method is based on a model of storage queue dynamics that predicts material flow rates and vehicle response times resulting from vehicle dispatching within a single loop system. The method is applied in the development of two heuristic, random number driven procedures designed to perform sequential search for WIP storage minimizing line layouts over alternative AGV fleet sizes. The first algorithm is a greedy, ‘CRAFT like’ procedure based on local improvement in storage requirements using random, pairwise exchanges of workcentre locations. The second algorithm is a modification to the greedy procedure using simulated annealing methods designed to avoid trapping at local minima. Limited computational studies using the methods are reported.
Dimensions of Disrespect Mapping and Measuring Gender Harassment in Organizations

The current study broadens our understanding of workplace gender harassment (a subdomain of sex-based harassment) by developing an expanded taxonomy and measurement instrument. We move beyond sexua...
Measurement of noise characteristics of MEMS accelerometers

Microelectromechanical systems (MEMS) are devices that have static or movable components with dimensions on the scale of a micrometer. One particular device that is widely used commercially is the MEMS accelerometer. Such accelerometers typically contain some movable micro beams that measure acceleration in one or two orthogonal directions. Major markets for MEMS accelerometers are automobile airbag triggers, earthquake detection circuits and health care. MEMS accelerometers have advantages over conventional accelerometers because they are smaller, lighter and cheaper. Since MEMS accelerometers are used in many systems, the noise characteristics of these devices are very important. The noise characteristics will influence the performance of the accelerometers especially when operating at lower g conditions. In this work, we report on the noise characteristics and special measurement techniques for Analog Devices ADXL202, ADXL 105 and ADXL 190 accelerometers.
Electromigration study of magnetic thin films for the electrical reliability of spin-valve read heads

Electromigration-induced failure (EIF) lifetimes of magnetic thin films used in giant magnetoresistive (GMR) spin-valve materials have been studied to predict the fundamental electrical reliability of GMR spin-valve read head. Magnetic thin films exhibited large failure lifetimes (time to failure, TTF) compared to highly conductive materials such as Cu and Al thin films. In addition, TTF of magnetic thin films was found to have a lognormal distribution and to depend on materials, thermally induced stress, applied dc current density (J), and film geometry. The activation energy and the current density factor n were extracted from the "Black equation." The calculated activation energies for NiFe, CoFe, Co, NiFe-CoFe, and Cu thin films were determined to be 0.8 /spl plusmn/ 0.15, 0.9 /spl plusmn/ 0.1, 1.4 /spl plusmn/ 0.2, 1.17 /spl plusmn/ 0.7, and 0.5 /spl plusmn/ 0.2 eV, respectively, depending on applied dc current density. The current density factor "n" value" determined from the slope of a plot /spl bsol/ln (J) versus /spl bsol/ln (TTF) at constant temperature was 3.1 /spl sim/ 3.3 for NiFe, 6.1 for CoFe, 4.6 /spl sim/ 5.5 for NiFe-CoFe (or CoFe-NiFe), 3.4 /spl sim/ 4.2 for NiFe-Cu-NiFe and 1.7 for Cu, respectively. Typical electromigration failures such as voids and hillocks were clearly observed at the cathode and center regions of electromigration tested samples.
Ethnic group differences in the relationship between depressive symptoms and smoking

Objectives. A relationship between depression and smoking has been documented; however, little attention has focused on ethnic variability in how this relationship is manifested. Thus, we examined the interaction between ethnicity and significant depressive symptoms on smoking status. Design. A random digit dial survey (Minnesota Needs Assessment Survey) that oversampled ethnic minorities assessed demographics, smoking status, and depressive symptoms (Patient Health Questionnaire-2 [PHQ-2]). We examined the prevalence of current smoking between individuals with and without depressive symptoms within ethnic group and the interaction of depressive symptoms by ethnic group on smoking status. Results. Of 16,981 participants, 20.8% were current smokers, and 7.7% reported significant depressive symptoms on the PHQ-2 (score ≥3). Ethnic differences were observed in smoking rates (Asians 17.2%, Latinos 19.0%, Whites 20.4%, African-Americans 23.4%, American Indians 51.2%) and depressive symptoms (Asians 4.9%, Latin...
Effect of a selection and postoperative care protocol on survival of infants with hypoplastic left heart syndrome

Abstract Background We report the development and implementation of a program designed to assign patients preoperatively to either transplant or Norwood procedure based on a score derived from known risk factors and to enhance postoperative care of infants undergoing the Norwood procedure. Methods A weighted score for each of six variables comprised the scoring system: ventricular function, tricuspid regurgitation, ascending aortic diameter, atrial septal defect blood flow characteristics, blood type, and age. The scoring system was used to prospectively assign mortality risk and lead to recommendation of either Norwood procedure or transplantation. Results Survival following the Norwood procedure significantly improved after the management program was implemented (88% versus 40% at 48 hours, 57% versus 10% at 30 days, and 50% versus 10% at 1 year, p Conclusions We report improved survival following the Norwood procedure after the implementation of an institutional management approach aimed at improving the outcome of infants with hypoplastic left heart syndrome and may help neutralize historical biases toward Norwood procedure or transplantation.
Loyal to Whom? The Effect of Relational Embeddedness and Managers’ Mobility on Market Tie Dissolution

In this study we use a social embeddedness perspective to investigate the paradoxical role that individual-level embedded relationships have on the dissolution of interorganizational ties. Prior studies have found that managers who form close interpersonal relationships with clients can stabilize market ties, but these relationships can also be a source of increased market tie dissolution in the event of an exchange manager’s departure from the firm. Using data on all state-level lobbyists and clients in the Texas lobbying industry from 2001 to 2009, we confirm that a client is more likely to remain with a firm than to follow a departing manager to a new firm, but the depth, focus, and shared ownership of a manager’s client relationship moderate the impact of his or her mobility on market tie dissolution. We find that the tenure of the relationship with a manager, the number of clients on a manager’s roster, the level of attention received from a manager, and the presence of an additional manager relation...
Hip disease in adults with Down syndrome

The life expectancy of patients with Down syndrome has increased significantly in recent years. Hip abnormalities occur in children with this syndrome but little is known about their natural history in later life. In 65 adults with Down syndrome we found hip abnormalities in 28%, and this was statistically correlated with walking ability. A subgroup of 18 patients was followed by serial examination; this showed that hip instability occurred in adulthood and became worse with time. In some patients, hip instability started after skeletal maturity.
Encouraging hematopoietic and cytogenetic responses to coenzyme Q10 (coQ10) in patients with low and intermediate-1 risk (Int-1) myelodysplastic syndromes (MDS

Proc Amer Assoc Cancer Res, Volume 46, 2005 2544 Excessive intramedullary apoptosis can explain the variable cytopenias, which are the hallmark of the disease, in a majority of MDS patients. Since mitochondria (mt) play a critical role in both the control of apoptosis and heme synthesis, we sequenced mt-DNA and reported certain recurring substitutional and deletional mutations in several genes (BJH 116:564-575, 2002). CoQ10 is coded by mt-DNA, and has been shown to reduce apoptosis of cells in Parkinson’s disease. A pilot study was therefore undertaken in low-Int-1 MDS patients at a dose of 1200mg/day. Therapy was well tolerated, with most patients experiencing improved energy/decreased fatigue. Of 29 patients, 18 were male; median age was 71 years. Normal cytogenetics were present in 16/29. As per FAB, there were 18 RA, 5 RARS, 2 RAEB, 2 CMMoL, 2 unclassified. As per IPSS, 9 had low risk, 16 Int-1, 4 could not be classified. At the end of 6 months, 4 patients could not be evaluated for response. Sixteen of 25 remaining patients showed stable disease, 3 had disease progression, and 6 experienced a response according to the International Working Group (IWG) criteria. One had a trilineage response with hemoglobin increasing from 8 to 14 Gm/dL, platelets increasing from 250,000/ul and normalization of neutropenia. Two experienced a cytogenetic response; one had trisomy 8 which disappeared after 6 months of treatment the platelet count improved by >20,000/ul. The other cytogenetic responder had two abnormal clones; del(20) and del(6q) prior to therapy. At 6 months, she had a platelet response, but the same karyotype. However, after another 6 months of therapy, she lost the del(6q) clone completely. She is still on medication and feeling well. In total, 3/6 patients showed improvement in platelets of >20,000/ul and two patients showed a change in FAB type from CMMoL to RA and RARS. This is a result of decrease in absolute monocyte count which appears to indicate a specific effect of coQ10 on monocytes. In fact, the treatment appears to have a specific effect on both megakaryocytes and monocytes. With continued therapy, it is expected that some more of the stable disease patients will show hematologic improvement and the responders may continue to respond more completely. A clinical trial using a larger number of patients is currently underway to confirm these findings. In conclusion, coQ10 is an innocuous treatment, which appears to be an agent worth further investigation for low-Int-1 risk MDS patients as it has produced a variety of exciting responses ranging from trilineage improvement in counts, especially improving platelet counts, to cytogenetic responses in this pilot study.