bluuebunny/crossref_metadata_2025 huggingface dataset:
Poor Compliance Makes Treatment of Latent Tuberculosis Infection Unsatisfactory
Authors: Larppanichpoonphol Panupong , Bagdure Satish , Amiri Hoda Mojazi , Nugent Kenneth
Published: February 2012

Objectives: The recommended treatment for latent tuberculosis infection is isoniazid for 9 months, but this regimen has a low completion rate. The authors wanted to compare treatment with isoniazid and treatment with isoniazid and rifampin in the typical public health setting in a large diverse state and recover as much information as possible from a state database. Methods: Patients who received latent tuberculosis infection treatment were identified in the Texas Department of State Health Services database for the years 1995-2002. Treatment completion, adverse reactions, and disease development were recorded. Results were analyzed using logistic regression to predict disease development. Results: In sum, 50 578 patients received isoniazid, and 280 received isoniazid/rifampin. Sixty-one percent of the isoniazid group and 54% of the isoniazid/rifampin group completed treatment. Eighteen percent of the isoniazid/rifampin group possibly had adverse reactions and discontinued treatment; 3% of the isoniazid group discontinued therapy because of side effects. More than 70% of patients with adverse reactions in the isoniazid/rifampin group took the treatment for more than 4 months. Overall, 168 patients in the isoniazid group with a normal chest X-ray and a positive skin test developed tuberculosis during follow-up to 2008; no patients in the isoniazid/rifampin group who had a normal X-ray and completed chemoprophylaxis developed tuberculosis during follow-up. Conclusions: The isoniazid/rifampin regimen appears to be as effective as the isoniazid regimen. However, completion rates on combination therapy were slightly lower. This regimen needs more formal clinical study since it has the potential to decrease administrative costs and improve completion rates. In addition, state departments of health need to develop networks using community-based resources to reach patients and increase completion rates.
Gender and Instrument Associations, Stereotypes, and Stratification
Authors: Wych Gina M. F.
Published: February 2012

This literature review examines and synthesizes 30 years of research into the relationship between gender and musical instruments. Specifically, the review focuses on how this relationship affects instrument selection by grade school students entering a school music program. Topics include the gender typing of musical instruments, instrument preferences of young (preband or preorchestra) students, beliefs about which gender should play which instrument, gender influences during the instrument selection process, the status of gender stratification within instrumental ensembles, and perceptions of musicians in relation to their gender and instrument. Also discussed are theories as to why gender associations and stereotypes occur within instrumental music, including social role theory, and ways in which researchers have attempted to counteract gender as a factor in the instrument selection process. The review concludes with implications drawn from the body of research and direction for future studies.
Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease
Authors: Yoneda Masato , Naka Shuhei , Nakano Kazuhiko , Wada Koichiro , Endo Hiroki , Mawatari Hironori , Imajo Kento , Nomura Ryota , Hokamura Kazuya , Ono Masafumi , Murata Shogo , Tohnai Iwai , Sumida Yoshio , Shima Toshihide , Kuboniwa Masae , Umemura Kazuo , Kamisaki Yoshinori , Amano Atsuo , Okanoue Takeshi , Ooshima Takashi , Nakajima Atsushi
Published: February 2012

Background

Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia and type 2 diabetes mellitus. However, other risk factors for the development of NAFLD are unclear. With the association between periodontal disease and the development of systemic diseases receiving increasing attention recently, we conducted this study to investigate the relationship between NAFLD and infection with Porphyromonas gingivalis (P. gingivalis), a major causative agent of periodontitis.

Methods

The detection frequencies of periodontal bacteria in oral samples collected from 150 biopsy-proven NAFLD patients (102 with non-alcoholic steatohepatitis (NASH) and 48 with non-alcoholic fatty liver (NAFL) patients) and 60 non-NAFLD control subjects were determined. Detection of P. gingivalis and other periodontopathic bacteria were detected by PCR assay. In addition, effect of P. gingivalis-infection on mouse NAFLD model was investigated. To clarify the exact contribution of P. gingivalis-induced periodontitis, non-surgical periodontal treatments were also undertaken for 3 months in 10 NAFLD patients with periodontitis.

Results

The detection frequency of P. gingivalis in NAFLD patients was significantly higher than that in the non-NAFLD control subjects (46.7% vs. 21.7%, odds ratio: 3.16). In addition, the detection frequency of P. gingivalis in NASH patients was markedly higher than that in the non-NAFLD subjects (52.0%, odds ratio: 3.91). Most of the P. gingivalis fimbria detected in the NAFLD patients was of invasive genotypes, especially type II (50.0%). Infection of type II P. gingivalis on NAFLD model of mice accelerated the NAFLD progression. The non-surgical periodontal treatments on NAFLD patients carried out for 3 months ameliorated the liver function parameters, such as the serum levels of AST and ALT.

Conclusions

Infection with high-virulence P. gingivalis might be an additional risk factor for the development/progression of NAFLD/NASH.
A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome
Authors: Morris Peter E , Steingrub Jay S , Huang Bee Y , Tang Shamay , Liu Patrick M , Rhode Peter R , Wong Hing C
Published: February 2012

Background

The tissue factor (TF)-dependent extrinsic pathway has been suggested to be a central mechanism by which the coagulation cascade is locally activated in the lungs of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) and thus represents an attractive target for therapeutic intervention. This study was designed to determine the pharmacokinetic and safety profiles of ALT-836, an anti-TF antibody, in patients with ALI/ARDS.

Methods

This was a prospective, randomized, placebo-controlled, dose-escalation Phase I clinical trial in adult patients who had suspected or proven infection, were receiving mechanical ventilation and had ALI/ARDS (PaO2/FiO2 ≤ 300 mm). Eighteen patients (6 per cohort) were randomized in a 5:1 ratio to receive ALT-836 or placebo, and were treated within 48 hours after meeting screening criteria. Cohorts of patients were administered a single intravenously dose of 0.06, 0.08 or 0.1 mg/kg ALT-836 or placebo. Blood samples were taken for pharmacokinetic and immunogenicity measurements. Safety was assessed by adverse events, vital signs, ECGs, laboratory, coagulation and pulmonary function parameters.

Results

Pharmacokinetic analysis showed a dose dependent exposure to ALT-836 across the infusion range of 0.06 to 0.1 mg/kg. No anti-ALT-836 antibody response was observed in the study population during the trial. No major bleeding episodes were reported in the ALT-836 treated patients. The most frequent adverse events were anemia, observed in both placebo and ALT-836 treated patients, and ALT-836 dose dependent, self-resolved hematuria, which suggested 0.08 mg/kg as an acceptable dose level of ALT-836 in this patient population.

Conclusions

Overall, this study showed that ALT-836 could be safely administered to patients with sepsis-induced ALI/ARDS.

Trial registration

ClinicalTrials.gov: NCT01438853
Unsupervised machine-learning method for improving the performance of ambulatory fall-detection systems
Authors: Yuwono Mitchell , Moulton Bruce D , Su Steven W , Celler Branko G , Nguyen Hung T
Published: February 2012

Background

Falls can cause trauma, disability and death among older people. Ambulatory accelerometer devices are currently capable of detecting falls in a controlled environment. However, research suggests that most current approaches can tend to have insufficient sensitivity and specificity in non-laboratory environments, in part because impacts can be experienced as part of ordinary daily living activities.

Method

We used a waist-worn wireless tri-axial accelerometer combined with digital signal processing, clustering and neural network classifiers. The method includes the application of Discrete Wavelet Transform, Regrouping Particle Swarm Optimization, Gaussian Distribution of Clustered Knowledge and an ensemble of classifiers including a multilayer perceptron and Augmented Radial Basis Function (ARBF) neural networks.

Results

Preliminary testing with 8 healthy individuals in a home environment yields 98.6% sensitivity to falls and 99.6% specificity for routine Activities of Daily Living (ADL) data. Single ARB and MLP classifiers were compared with a combined classifier. The combined classifier offers the greatest sensitivity, with a slight reduction in specificity for routine ADL and an increased specificity for exercise activities. In preliminary tests, the approach achieves 100% sensitivity on in-group falls, 97.65% on out-group falls, 99.33% specificity on routine ADL, and 96.59% specificity on exercise ADL.

Conclusion

The pre-processing and feature-extraction steps appear to simplify the signal while successfully extracting the essential features that are required to characterize a fall. The results suggest this combination of classifiers can perform better than MLP alone. Preliminary testing suggests these methods may be useful for researchers who are attempting to improve the performance of ambulatory fall-detection systems.
Reducing widespread pipe sharing and risky sex among crystal methamphetamine smokers in Toronto: do safer smoking kits have a potential role to play?
Authors: Hunter Charlotte , Strike Carol , Barnaby Lorraine , Busch Adam , Marshall Chantel , Shepherd Susan , Hopkins Shaun
Published: February 2012

Background

Crystal methamphetamine smoking is associated with many negative health consequences, including the potential for transmission of hepatitis. We examined whether or not a kit for crystal methamphetamine smoking might have some potential to reduce the negative health effects of crystal methamphetamine smoking.

Methods

Five focus groups were conducted with crystal methamphetamine smokers recruited by community health agencies and youth shelters in Toronto, Canada. Target groups included homeless/street-involved youth, sex workers, men who have sex with men, and youth in the party scene. Participants (n = 32) were asked questions about motivations for crystal methamphetamine use, the process of smoking, health problems experienced, sharing behaviour, risky sexual practices, and the ideal contents of a harm reduction kit.

Results

Pipe sharing was widespread among participants and was deemed integral to the social experience of smoking crystal methamphetamine. Heated pipes were unlikely to cause direct injuries, but participants mentioned having dry, cracked lips, which may be a vector for disease transmission. Many reported having sex with multiple partners and being less likely to use condoms while on the drug. Demand for harm reduction kits was mixed.

Conclusions

Changing pipe sharing behaviours may be difficult because many participants considered sharing to be integral to the social experience of smoking crystal methamphetamine. Within the context of a broader health promotion and prevention program, pilot testing of safer smoking kits to initiate discussion and education on the risks associated with sharing pipes and unprotected sex for some communities (e.g., homeless/street-involved youth) is worth pursuing.
Cyclin D1 overexpression and poor clinical outcomes in Taiwanese oral cavity squamous cell carcinoma
Authors: Huang Shiang-Fu , Cheng Sou-De , Chuang Wen-Yu , Chen I-How , Liao Chun-Ta , Wang Hung-Ming , Hsieh Ling-Ling
Published: February 2012

Background

Cyclin D1 gene regulates cell cycle and plays an important role in the tumorigenesis of human cancers. The association between cyclin D1, clinicopathologic parameters and prognosis in oral cavity squamous cell carcinoma (OSCC) is inconclusive.

Methods

A total of 264 male OSCCs were examined for cyclin D1 protein expression using immunohistochemistry (IHC). The expression levels of cyclin D1 were defined as overexpression when more than 10% of tumor cells displayed nuclear staining with moderate to strong intensity.

Results

Overexpression of cyclin D1 was found in 97 (36.7%) OSCCs. Cyclin D1 protein overexpression was significantly associated with lymph node metastasis (P = 0.002), tumor cell differentiation (P = 0.031) and tumor stage (P = 0.051), but not associated with age onset, cigarette smoking, alcohol drinking, or areca quid chewing. Overexpression of cyclin D1 was also significantly associated with poor clinical outcomes in terms of disease-free survival (DFS, P = 0.002) and overall survival (OS, P < 0.001). The effects of cyclin D1 protein overexpression on DFS (hazard ratio (HR) = 1.540; 95% confidence interval (CI), 1.068 - 2.222) and OS (HR = 1.702; 95% CI, 1.168 - 2.480) were still existed after adjusting for clinicopathological paremeters (such as age, primary tumor status, tumor cell differentiation, and lymph node metastasis) using logistic multivariate analysis.

Conclusion

Cyclin D1 protein worked as an independent prognostic factor and can be as a biomarker for the aggressiveness of OSCC.
Developing the dielectric mechanisms of polyetherimide/multiwalled carbon nanotube/(Ba0.8Sr0.2)(Ti0.9Zr0.1)O3 composites
Authors: Su Chean-Cheng , Wu Chia-Ching , Yang Cheng-Fu
Published: February 2012

Various amounts of multiwalled carbon nanotubes [MWNTs] were embedded into polyetherimide [PEI] to form PEI/MWNT composites, and their dielectric properties were measured at 1 MHz. The Lichtenecker mixing rule was used to find a reasonable dielectric constant for the MWNTs used in this study. The dielectric constants of the developed composites were significantly increased, and the loss tangents were significantly decreased as 2.0 wt.% (Ba0.8Sr0.2)(Ti0.9Zr0.1)O3 ceramic powder [BSTZ] was added to the PEI/MWNTs to form PEI/MWNT/BSTZ composites. The Lichtenecker and Yamada mixing rules were used to predict the dielectric constants of the PEI/MWNT and PEI/MWNT/BSTZ composites. Equivalent electrical conduction models of both composites were established using the two mixing rules. In addition, the theoretical bases of the two mixing rules were used to explain the measured results for the PEI/MWNT and PEI/BSTZ/MWNT composites.
Naloxone inhibits immune cell function by suppressing superoxide production through a direct interaction with gp91 phox subunit of NADPH oxidase
Authors: Wang Qingshan , Zhou Hui , Gao Huiming , Chen Shih-Heng , Chu Chun-Hsien , Wilson Belinda , Hong Jau-Shyong
Published: February 2012

Background

Both (-) and (+)-naloxone attenuate inflammation-mediated neurodegeneration by inhibition of microglial activation through superoxide reduction in an opioid receptor-independent manner. Multiple lines of evidence have documented a pivotal role of overactivated NADPH oxidase (NOX2) in inflammation-mediated neurodegeneration. We hypothesized that NOX2 might be a novel action site of naloxone to mediate its anti-inflammatory actions.

Methods

Inhibition of NOX-2-derived superoxide by (-) and (+)-naloxone was measured in lipopolysaccharide (LPS)-treated midbrain neuron-glia cultures and phorbol myristate acetate (PMA)-stimulated neutrophil membranes by measuring the superoxide dismutase (SOD)-inhibitable reduction of tetrazolium salt (WST-1) or ferricytochrome c. Further, various ligand (3H-naloxone) binding assays were performed in wild type and gp91phox-/-neutrophils and transfected COS-7 and HEK293 cells. The translocation of cytosolic subunit p47phoxto plasma membrane was assessed by western blot.

Results

Both (-) and (+)-naloxone equally inhibited LPS- and PMA-induced superoxide production with an IC50 of 1.96 and 2.52 μM, respectively. Competitive binding of3H-naloxone with cold (-) and (+)-naloxone in microglia showed equal potency with an IC50 of 2.73 and 1.57 μM, respectively.3H-Naloxone binding was elevated in COS-7 and HEK293 cells transfected with gp91phox; in contrast, reduced3H-naloxone binding was found in neutrophils deficient in gp91phoxor in the presence of a NOX2 inhibitor. The specificity and an increase in binding capacity of3H-naloxone were further demonstrated by 1) an immunoprecipitation study using gp91phoxantibody, and 2) activation of NOX2 by PMA. Finally, western blot studies showed that naloxone suppressed translocation of the cytosolic subunit p47phoxto the membrane, leading to NOX2 inactivation.

Conclusions

Strong evidence is provided indicating that NOX2 is a non-opioid novel binding site for naloxone, which is critical in mediating its inhibitory effect on microglia overactivation and superoxide production.
Receptor chimeras demonstrate that the C-terminal domain of the human cytomegalovirus US27 gene product is necessary and sufficient for intracellular receptor localization
Authors: Stapleton Lance K , Arnolds Kathleen L , Lares Angela P , Devito Tori M , Spencer Juliet V
Published: February 2012

Background

Human cytomegalovirus (HCMV) is ubiquitous in the population but generally causes only mild or asymptomatic infection except in immune suppressed individuals. HCMV employs numerous strategies for manipulating infected cells, including mimicry of G-protein coupled receptors (GPCRs). The HCMV US27 gene product is a putative GPCR, yet no ligand or signaling has been identified for this receptor. In the present study, immunofluorescence microscopy was used to examine the cellular distribution of wild type US27, as well as US27 deletion mutants and chimeric receptors.

Results

In transiently transfected cells, wild type US27 was found primarily in intracellular compartments, in striking contrast to the cell surface distribution seen for the human cellular chemokine receptor CXCR3. When the N-terminal extracellular domains of the two receptors were swapped, no change in protein localization was observed. However, swapping of the C-terminal intracellular domains resulted in a significant change in receptor distribution. A chimera that contained US27 fused to the C-terminal intracellular tail of CXCR3 exhibited surface distribution similar to that of wild-type CXCR3. When the C-terminal domain of US27 was fused to CXCR3, this chimeric receptor (CXCR3/US27-CT) was found in the same intracellular pattern as wild-type US27. In addition, a US27 mutant lacking the C-terminus (US27ΔCT) failed to accumulate inside the cell and exhibited cell surface distribution. Co-localization with organelle-specific markers revealed that wild-type US27 was found predominantly in the Golgi apparatus and in endosomal compartments, whereas the US27/CXCR3-CT chimera, US27ΔCT and US27Δ348 mutants were not localized to endosomal compartments.

Conclusions

The results indicate that the C-terminal domain of the HCMV US27 protein, which contains a di-leucine endocytic sorting motif, is both necessary and sufficient for intracellular localization, which may also help explain why no cellular ligands have yet been identified for this viral receptor.
Biology and interactions of two distinct monopartite begomoviruses and betasatellites associated with radish leaf curl disease in India
Authors: Singh AK , Chattopadhyay B , Chakraborty S
Published: February 2012

Background

Emerging whitefly transmitted begomoviruses are major pathogens of vegetable and fibre crops throughout the world, particularly in tropical and sub-tropical regions. Mutation, pseudorecombination and recombination are driving forces for the emergence and evolution of new crop-infecting begomoviruses. Leaf curl disease of field grown radish plants was noticed in Varanasi and Pataudi region of northern India. We have identified and characterized two distinct monopartite begomoviruses and associated beta satellite DNA causing leaf curl disease of radish (Raphanus sativus) in India.

Results

We demonstrate that RaLCD is caused by a complex of two Old World begomoviruses and their associated betasatellites. Radish leaf curl virus-Varanasi is identified as a new recombinant species, Radish leaf curl virus (RaLCV) sharing maximum nucleotide identity of 87.7% with Tomato leaf curl Bangladesh virus-[Bangladesh:2] (Accession number AF188481) while the virus causing radish leaf curl disease-Pataudi is an isolate of Croton yellow vein mosaic virus-[India] (CYVMV-IN) (Accession number AJ507777) sharing 95.8% nucleotide identity. Further, RDP analysis revealed that the RaLCV has a hybrid genome, a putative recombinant between Euphorbia leaf curl virus and Papaya leaf curl virus. Cloned DNA of either RaLCV or CYVMV induced mild leaf curl symptoms in radish plants. However, when these clones (RaLCV or CYVMV) were individually co-inoculated with their associated cloned DNA betasatellite, symptom severity and viral DNA levels were increased in radish plants and induced typical RaLCD symptoms. To further extend these studies, we carried out an investigation of the interaction of these radish-infecting begomoviruses and their associated satellite, with two tomato infecting begomoviruses (Tomato leaf curl Gujarat virus and Tomato leaf curl New Delhi virus). Both of the tomato-infecting begomoviruses showed a contrasting and differential interaction with DNA satellites, not only in the capacity to interact with these molecules but also in the modulation of symptom phenotypes by the satellites.

Conclusion

This is the first report and experimental demonstration of Koch's postulate for begomoviruses associated with radish leaf curl disease. Further observations also provide direct evidence of lateral movement of weed infecting begomovirus in the cultivated crops and the present study also suggests that the exchange of betasatellites with other begomoviruses would create a new disease complex posing a serious threat to crop production.
Integrating palliative care with intensive care for critically ill patients with lung cancer
Authors: Gay Elizabeth B , Weiss Stefanie P , Nelson Judith E
Published: February 2012

With newer information indicating more favorable outcomes of intensive care therapy for lung cancer patients, intensivists increasingly are willing to initiate an aggressive trial of this therapy. Concerns remain, however, that the experience of the intensive care unit for patients with lung cancer and their families often may be distressing. Regardless of prognosis, all patients with critical illness should receive high-quality palliative care, including symptom control, communication about appropriate care goals, and support for both patient and family throughout the illness trajectory. In this article, we suggest strategies for integrating palliative care with intensive care for critically ill lung cancer patients. We address assessment and management of symptoms, knowledge and skill needed for effective communication, and interdisciplinary collaboration for patient and family support. We review the role of expert consultants in providing palliative care in the intensive care unit, while highlighting the responsibility of all critical care clinicians to address basic palliative care needs of patients and their families.
Premenopausal serum androgens and breast cancer risk: a nested case-control study
Authors: Zeleniuch-Jacquotte Anne , Afanasyeva Yelena , Kaaks Rudolf , Rinaldi Sabina , Scarmo Stephanie , Liu Mengling , Arslan Alan A , Toniolo Paolo , Shore Roy E , Koenig Karen L
Published: February 2012

Introduction

Prospective epidemiologic studies have consistently shown that levels of circulating androgens in postmenopausal women are positively associated with breast cancer risk. However, data in premenopausal women are limited.

Methods

A case-control study nested within the New York University Women's Health Study was conducted. A total of 356 cases (276 invasive and 80 in situ) and 683 individually-matched controls were included. Matching variables included age and date, phase, and day of menstrual cycle at blood donation. Testosterone, androstenedione, dehydroandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) were measured using direct immunoassays. Free testosterone was calculated.

Results

Premenopausal serum testosterone and free testosterone concentrations were positively associated with breast cancer risk. In models adjusted for known risk factors of breast cancer, the odds ratios for increasing quintiles of testosterone were 1.0 (reference), 1.5 (95% confidence interval (CI), 0.9 to 2.3), 1.2 (95% CI, 0.7 to 1.9), 1.4 (95% CI, 0.9 to 2.3) and 1.8 (95% CI, 1.1 to 2.9; Ptrend = 0.04), and for free testosterone were 1.0 (reference), 1.2 (95% CI, 0.7 to 1.8), 1.5 (95% CI, 0.9 to 2.3), 1.5 (95% CI, 0.9 to 2.3), and 1.8 (95% CI, 1.1 to 2.8, Ptrend = 0.01). A marginally significant positive association was observed with androstenedione (P = 0.07), but no association with DHEAS or SHBG. Results were consistent in analyses stratified by tumor type (invasive, in situ), estrogen receptor status, age at blood donation, and menopausal status at diagnosis. Intra-class correlation coefficients for samples collected from 0.8 to 5.3 years apart (median 2 years) in 138 cases and 268 controls were greater than 0.7 for all biomarkers except for androstenedione (0.57 in controls).

Conclusions

Premenopausal concentrations of testosterone and free testosterone are associated with breast cancer risk. Testosterone and free testosterone measurements are also highly reliable (that is, a single measurement is reflective of a woman's average level over time). Results from other prospective studies are consistent with our results. The impact of including testosterone or free testosterone in breast cancer risk prediction models for women between the ages of 40 and 50 years should be assessed. Improving risk prediction models for this age group could help decision making regarding both screening and chemoprevention of breast cancer.
Static and dynamic effective stress coefficient of chalk
Authors: Alam M. Monzurul , Fabricius Ida Lykke , Christensen Helle Foged
Published: February 2012

Deformation of a hydrocarbon reservoir can ideally be used to estimate the effective stress acting on it. The effective stress in the subsurface is the difference between the stress due to the weight of the sediment and a fraction (effective stress coefficient) of the pore pressure. The effective stress coefficient is thus relevant for studying reservoir deformation and for evaluating 4D seismic for the correct pore pressure prediction. The static effective stress coefficient [Formula: see text] is estimated from mechanical tests and is highly relevant for effective stress prediction because it is directly related to mechanical strain in the elastic stress regime. The corresponding dynamic effective stress coefficient [Formula: see text] is easy to estimate from density and velocity of acoustic (elastic) waves. We studied [Formula: see text] and [Formula: see text] of chalk from the reservoir zone of the Valhall field, North Sea, and found that [Formula: see text] and [Formula: see text] vary with differential stress (overburden stress-pore pressure). For Valhall reservoir chalk with 40% porosity, [Formula: see text] ranges between 0.98 and 0.85 and decreases by 10% if the differential stress is increased by 25 MPa. In contrast, for chalk with 15% porosity from the same reservoir, [Formula: see text] ranges between 0.85 and 0.70 and decreases by 5% due to a similar increase in differential stress. Our data indicate that [Formula: see text] measured from sonic velocity data falls in the same range as for [Formula: see text], and that [Formula: see text] is always below unity. Stress-dependent behavior of [Formula: see text] is similar (decrease with increasing differential stress) to that of [Formula: see text] during elastic deformation caused by pore pressure buildup, for example, during waterflooding. By contrast, during the increase in differential stress, as in the case of pore pressure depletion due to production, [Formula: see text] increases with stress while [Formula: see text] decreases.
Targeting developmental regulators of zebrafish exocrine pancreas as a therapeutic approach in human pancreatic cancer
Authors: Yee Nelson S. , Zhou Weiqiang , Chun Stephen G. , Liang I-Chau , Yee Rosemary K.
Published: February 2012

Histone deacetylases (HDACs) and RNA polymerase III (POLR3) play vital roles in fundamental cellular processes, and deregulation of these enzymes has been implicated in malignant transformation. Hdacs and Polr3 are required for exocrine pancreatic epithelial proliferation during morphogenesis in zebrafish. We aim to test the hypothesis that Hdacs and Polr3 cooperatively control exocrine pancreatic growth, and combined inhibition of HDACs and POLR3 produces enhanced growth suppression in pancreatic cancer. In zebrafish larvae, combination of a Hdac inhibitor (Trichostatin A) and an inhibitor of Polr3 (ML-60218) synergistically prohibited the expansion of exocrine pancreas. In human pancreatic adenocarcinoma cells, combination of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and ML-60218 produced augmented suppression of colony formation and proliferation, and induction of cell cycle arrest and apoptotic cell death. The enhanced cytotoxicity was associated with supra-additive upregulation of the pro-apoptotic regulator BAX and the cyclin-dependent kinase inhibitor p21CDKN1A. tRNAs have been shown to have pro-proliferative and anti-apoptotic roles, and SAHA-stimulated expression of tRNAs was reversed by ML-60218. These findings demonstrate that chemically targeting developmental regulators of exocrine pancreas can be translated into an approach with potential impact on therapeutic response in pancreatic cancer, and suggest that counteracting the pro-malignant side effect of HDAC inhibitors can enhance their anti-tumor activity.
Histological and MS spectrometric analyses of the modified tissue of bulgy form tadpoles induced by salamander predation
Authors: Mori Tsukasa , Kitani Yoichiro , Ogihara Jun , Sugiyama Manabu , Yamamoto Goshi , Kishida Osamu , Nishimura Kinya
Published: February 2012

The rapid induction of a defensive morphology by a prey species in face of a predation risk is an intriguing in ecological context; however, the physiological mechanisms that underlie this phenotypic plasticity remain uncertain. Here we investigated the phenotypic changes shown by Rana pirica tadpoles in response to a predation threat by larvae of the salamander Hynobius retardatus. One such response is the bulgy morph phenotype, a relatively rapid swelling in size by the tadpoles that begins within 4 days and reaches a maximum at 8 to 10 days. We found that although the total volume of bodily fluid increased significantly (P<0.01) in bulgy morph tadpoles, osmotic pressure was maintained at the same level as control tadpoles by a significant increase (P<0.01) in Na and Cl ion concentrations. In our previous report, we identified a novel frog gene named pirica that affects the waterproofing of the skin membrane in tadpoles. Our results support the hypothesis that predator-induced expression of pirica on the skin membrane causes retention of absorbed water. Midline sections of bulgy morph tadpoles showed the presence of swollen connective tissue beneath the skin that was sparsely composed of cells containing hyaluronic acid. Mass spectrographic (LC-MS/MS) analysis identified histone H3 and 14-3-3 zeta as the most abundant constituents in the liquid aspirated from the connective tissue of bulgy tadpoles. Immunohistochemistry using antibodies against these proteins showed the presence of non-chromatin associated histone H3 in the swollen connective tissue. Histones and 14-3-3 proteins are also involved in antimicrobial activity and secretion of antibacterial proteins, respectively. Bulgy tadpoles have a larger surface area than controls, and their skin often has bite wounds inflicted by the larval salamanders. Thus, formation of the bulgy morph may also require and be supported by activation of innate immune systems.
American Higher Education in Transition
Authors: Ehrenberg Ronald G
Published: February 2012

American higher education is in transition along many dimensions: tuition levels, faculty composition, expenditure allocation, pedagogy, technology, and more. During the last three decades, at private four-year academic institutions, undergraduate tuition levels increased each year on average by 3.5 percent more than the rate of inflation; the comparable increases for public four-year and public two-year institutions were 5.1 percent and 3.5 percent, respectively. Academic institutions have also changed how they allocate their resources. The percentage of faculty nationwide that is full-time has declined, and the vast majority of part-time faculty members do not have Ph.D.s. The share of institutional expenditures going to faculty salaries and benefits in both public and private institutions has fallen relative to the share going to nonfaculty uses like student services, academic support, and institutional support. There are changing modes of instruction, together with different uses of technology, as institutions reexamine the prevailing “lecture/discussion” format. A number of schools are charging differential tuition across students. This paper discusses these various changes, how they are distributed across higher education sectors, and their implications. I conclude with some speculations about the future of American education.
Compensation for State and Local Government Workers
Authors: Gittleman Maury , Pierce Brooks
Published: February 2012

Are state and local government workers overcompensated? In this paper, we step back from the highly charged rhetoric and address this question with the two primary data sources for looking at compensation of state and local government workers: the Current Population Survey conducted by the Bureau of the Census for the Bureau of Labor Statistics, and the Employer Costs for Employee Compensation microdata collected as part of the National Compensation Survey of the Bureau of Labor Statistics. In both data sets, the workers being hired in the public sector have higher skill levels than those in the private sector, so the challenge is to compare across sectors in a way that adjusts suitably for this difference. After controlling for skill differences and incorporating employer costs for benefits packages, we find that, on average, public sector workers in state government have compensation costs 3–10 percent greater than those for workers in the private sector, while in local government the gap is 10–19 percent. We caution that this finding is somewhat dependent on the chosen sample and specification, that averages can obscure broader differences in distributions, and that a host of worker and job attributes are not available to us in these data. Nonetheless, the data suggest that public sector workers, especially local government ones, on average, receive greater remuneration than observably similar private sector workers. Overturning this result would require, we think, strong arguments for particular model specifications, or different data.
Prospects for Nuclear Power
Authors: Davis Lucas W
Published: February 2012

Nuclear power has long been controversial because of concerns about nuclear accidents, storage of spent fuel, and how the spread of nuclear power might raise risks of the proliferation of nuclear weapons. These concerns are real and important. However, emphasizing these concerns implicitly suggests that unless these issues are taken into account, nuclear power would otherwise be cost effective compared to other forms of electricity generation. This implication is unwarranted. Throughout the history of nuclear power, a key challenge has been the high cost of construction for nuclear plants. Construction costs are high enough that it becomes difficult to make an economic argument for nuclear even before incorporating these external factors. This is particularly true in countries like the United States where recent technological advances have dramatically increased the availability of natural gas. The chairman of one of the largest U.S. nuclear companies recently said that his company would not break ground on a new nuclear plant until the price of natural gas was more than double today's level and carbon emissions cost $25 per ton. This comment summarizes the current economics of nuclear power pretty well. Yes, there is a certain confluence of factors that could make nuclear power a viable economic option. Otherwise, a nuclear power renaissance seems unlikely.
Reducing Petroleum Consumption from Transportation
Authors: Knittel Christopher R
Published: February 2012

The United States consumes more petroleum-based liquid fuel per capita than any other OECD high-income country—30 percent more than the second-highest country (Canada) and 40 percent more than the third-highest (Luxembourg). The transportation sector accounts for 70 percent of U.S. oil consumption and 30 percent of U.S. greenhouse gas emissions. Taking the externalities associated with high U.S. gasoline consumption as largely given, I focus on understanding the policy tools that seek to reduce this consumption. I consider four main channels through which reductions in U.S. oil consumption might take place: 1) increased fuel economy of existing vehicles, 2) increased use of non-petroleum-based, low-carbon fuels, 3) alternatives to the internal combustion engine, and 4) reduced vehicle miles traveled. I then discuss how these policies for reducing petroleum consumption compare with the standard economics prescription for using a Pigouvian tax to deal with externalities. Taking into account that energy taxes are a political hot button in the United States, and also considering some evidence that consumers may not “correctly” value fuel economy, I offer some thoughts about the margins on which policy aimed at reducing petroleum consumption might usefully proceed.
The need for early treatment of clubfeet in peripheral hospitals in sub-Saharan Africa: a survey of clubfoot management in Zambia
Authors: De Rosa Antonella , Norrish Alan
Published: February 2012

In the developing world, neglected clubfoot often results in a permanent and disabling deformity with subsequent social implications. Data from the four organizations that manage clubfoot in Zambia were collected using clinic and operating room registries and analyzed using Fisher exact test. In the central hospitals in the capital city 65% (204/313 feet) of clubfeet were suitable for treatment by the Ponseti method compared with only 23% (38/166 feet) in the peripheral hospitals ( P < 0.001, two-tailed Fisher's exact test). In the central hospitals only 14% (42/313 feet) of clubfeet required extensive surgery for neglected clubfeet compared with 29% (49/116 feet) in peripheral hospitals ( P < 0.015, two-tailed Fisher's exact test). Patients from outside the capital have a higher percentage of neglected clubfeet that are no longer suitable for conservative management and require extensive, complex and costly surgical treatment. By allowing earlier access to less invasive procedures the burden of disability may be reduced.
The open reading frame TTC1157 of Thermus thermophilus HB27 encodes the methyltransferase forming N2-methylguanosine at position 6 in tRNA
Authors: Roovers Martine , Oudjama Yamina , Fislage Marcus , Bujnicki Janusz M. , Versées Wim , Droogmans Louis
Published: February 2012

N2-methylguanosine (m2G) is found at position 6 in the acceptor stem of Thermus thermophilus tRNAPhe. In this article, we describe the cloning, expression, and characterization of the T. thermophilus HB27 methyltransferase (MTase) encoded by the TTC1157 open reading frame that catalyzes the formation of this modified nucleoside. S-adenosyl-L-methionine is used as donor of the methyl group. The enzyme behaves as a monomer in solution. It contains an N-terminal THUMP domain predicted to bind RNA and contains a C-terminal Rossmann-fold methyltransferase (RFM) domain predicted to be responsible for catalysis. We propose to rename the TTC1157 gene trmN and the corresponding protein TrmN, according to the bacterial nomenclature of tRNA methyltransferases. Inactivation of the trmN gene in the T. thermophilus HB27 chromosome led to a total absence of m2G in tRNA but did not affect cell growth or the formation of other modified nucleosides in tRNAPhe. Archaeal homologs of TrmN were identified and characterized. These proteins catalyze the same reaction as TrmN from T. thermophilus. Individual THUMP and RFM domains of PF1002 from Pyrococcus furiosus were produced. These separate domains were inactive and did not bind tRNA, reinforcing the idea that the THUMP domain acts in concert with the catalytic domain to target a particular position of the tRNA molecule.
Love, Hate, Ambivalence, or Indifference? A Conceptual Examination of Workplace Crimes and Organizational Identification
Authors: Vadera Abhijeet K. , Pratt Michael G.
Published: February 2012

Although research has shown that there may be very different types of workplace crimes, scholarly work in this area (a) is currently fragmented with very little communication between very similar streams of research and (b) tends to be incomplete and can lead to conflicting findings. We address both of these shortcomings. First, we propose a typology of different types of workplace crimes (consisting of pro-organizational, nonaligned-organizational, and anti-organizational crimes) based on the intentions of the perpetrators. Second, we link these intentions to various identification “pathologies”—such as over-identification and over-disidentification, under-identification and ambivalent identification—and argue that these pathologies are linked to propensities to commit certain types of workplace crimes. Specifically, we contend that over-identification and over-disidentification have direct effects on workplace crimes, whereas under-identification and ambivalent identification indirectly influence the propensity to engage in workplace crimes. We suggest that this research aids us in clarifying the inconsistent conclusions in previous work in the domain of workplace crimes and that it emphasizes the importance of including organizational identification as a key factor in the extant models of workplace crimes. This research also highlights policy implications regarding workplace crimes in that it suggests that different agencies may be more effective in enforcing the law and disciplining those engaged in the different types of workplace crimes.
‘It is Not as Easy as ABC’: Examining Practitioners' Views on Using Behavioural Contracts to Encourage Young People to Accept Responsibility for Their Anti-Social Behaviour
Authors: Brown Kevin J.
Published: February 2012

This article examines the use of acceptable behavioural contracts as a tool for engendering the voluntary acceptance of responsibility in children and young people perceived to be engaging in anti-social behaviour and low-level criminality. Based on the results of a qualitative empirical analysis with local government and social housing anti-social behaviour teams, the article explores the attitudes of practitioners to the use of this unregulated but commonly utilised intervention. Practitioners' views are contrasted with the ideals of voluntary responsibilisation upon which the contracts are supposedly based. It is argued that there is a spectrum of differing approaches among practitioners, with some using the contracts more to encourage the voluntary acceptance of responsibility, whilst others use them more coercively to hold individuals responsible for their behaviour. The implications of these differing approaches are examined.
Microtube Device for Selectin-Mediated Capture of Viable Circulating Tumor Cells from Blood
Authors: Hughes Andrew D , Mattison Jeff , Western Laura T , Powderly John D , Greene Bryan T , King Michael R
Published: February 2012

BACKGROUND

Circulating tumor cells (CTCs) can be used clinically to treat cancer. As a diagnostic tool, the CTC count can be used to follow disease progression, and as a treatment tool, CTCs can be used to rapidly develop personalized therapeutic strategies. To be effectively used, however, CTCs must be isolated at high purity without inflicting cellular damage.

METHODS

We designed a microscale flow device with a functionalized surface of E-selectin and antibody molecules against epithelial markers. The device was additionally enhanced with a halloysite nanotube coating. We created model samples in which a known number of labeled cancer cells were suspended in healthy whole blood to determine device capture efficiency. We then isolated and cultured primary CTCs from buffy coat samples of patients diagnosed with metastatic cancer.

RESULTS

Approximately 50% of CTCs were captured from model samples. Samples from 12 metastatic cancer patients and 8 healthy participants were processed in nanotube-coated or smooth devices to isolate CTCs. We isolated 20–704 viable CTCs per 3.75-mL sample, achieving purities of 18%–80% CTCs. The nanotube-coated surface significantly improved capture purities (P = 0.0004). Experiments suggested that this increase in purity was due to suppression of leukocyte spreading.

CONCLUSIONS

The device successfully isolates viable CTCs from both blood and buffy coat samples. The approximately 50% capture rate with purities >50% with the nanotube coating demonstrates the functionality of this device in a clinical setting and opens the door for personalized cancer therapies.
Correlation of Global MicroRNA Expression With Basal Cell Carcinoma Subtype
Authors: Heffelfinger Christopher , Ouyang Zhengqing , Engberg Anna , Leffell David J , Hanlon Allison M , Gordon Patricia B , Zheng Wei , Zhao Hongyu , Snyder Michael P , Bale Allen E
Published: February 2012

Basal cell carcinomas (BCCs) are the most common cancers in the United States. The histologic appearance distinguishes several subtypes, each of which can have a different biologic behavior. In this study, global miRNA expression was quantified by high-throughput sequencing in nodular BCCs, a subtype that is slow growing, and infiltrative BCCs, aggressive tumors that extend through the dermis and invade structures such as cutaneous nerves. Principal components analysis correctly classified seven of eight infiltrative tumors on the basis of miRNA expression. The remaining tumor, on pathology review, contained a mixture of nodular and infiltrative elements. Nodular tumors did not cluster tightly, likely reflecting broader histopathologic diversity in this class, but trended toward forming a group separate from infiltrative BCCs. Quantitative polymerase chain reaction assays were developed for six of the miRNAs that showed significant differences between the BCC subtypes, and five of these six were validated in a replication set of four infiltrative and three nodular tumors. The expression level of miR-183, a miRNA that inhibits invasion and metastasis in several types of malignancies, was consistently lower in infiltrative than nodular tumors and could be one element underlying the difference in invasiveness. These results represent the first miRNA profiling study in BCCs and demonstrate that miRNA gene expression may be involved in tumor pathogenesis and particularly in determining the aggressiveness of these malignancies.