bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate change reduces the capacity of northern peatlands to absorb the atmospheric carbon dioxide: The different responses of bogs and fens
Authors: Wu Jianghua , Roulet Nigel T.
Published: September 2014

The carbon (C) storage of northern peatlands is equivalent to ~34–46% of the ~795 T g C currently held in the atmosphere as CO2. Most studies report that northern peatlands are a sink of between 20 and 60 g CO2–C m−2 yr−1. Since peatland hydrology and biogeochemistry are very closely related to climate, there is concern whether northern peatlands will continue to function as C sinks with climate change. We used a coupled land surface scheme and peatland C model, called CLASS3W‐MWM, to examine the sensitivity of peatland C to climate change. Based on the data available to constrain our model, we simulated the C dynamics of the Mer Bleue (MB) bog in eastern Canada and the Degerö Stormyr (DS) poor fen in northern Sweden for four Intergovernmental Panel on Climate Change (IPCC) climate change scenarios, i.e., A1B, A2, B1, and Commit, over four time periods, i.e., present day, 2030, 2060, and 2100. When the simulated future C fluxes were compared to the baseline fluxes under the present climate conditions, we found that fens were much more sensitive to climate change than bogs. Gross primary production (GPP) at MB significantly increased by 4–44% up to 2100 for all scenarios except Commit. GPP at DS significantly decreased by 34–39% for A1B and A2, and slightly increased by 6–10% for B1 and Commit. Total ecosystem respiration (TER) significantly increased by 7–57% for MB and 4–34% for DS up to 2100 for all scenarios except Commit. Net ecosystem production (NEP), therefore, significantly decreased. The bog, however, was still a C sink up to 2100, though much reduced, but the fen switched to a C source for A1B and A2 scenarios. Additional experiments where we climatically transplanted the study peatlands or forced vegetation changes when the fen became too dry showed similar but less dramatic results as the standard runs. Our results indicate that northern peatlands should be included in the C‐coupled climate model to fully understand the response of C cycling in terrestrial ecosystems to climate change and to reduce the uncertainties for projecting the future climate.
Symmetry considerations in the two‐fluid theory of the gradient drift instability in the lower ionosphere
Authors: Makarevich Roman A.
Published: September 2014

A general dispersion relation for the gradient drift instability (GDI) in the lower ionosphere is derived and solved analytically for the oscillation frequency and growth rate of unstable GDI waves. The approach presented is applicable in the broad range of altitudes, both within the E region and the lower F region, and for an arbitrary background density gradient. The ion and electron fluids are treated in the same way, and linearized system of fluid equations is solved exactly, with no geometry‐ or altitude‐specific approximations required. It is demonstrated that, in the short‐wavelength limit, the GDI growth rate is maximized along the bisector between the electric current and the cross product of the gradient vector and magnetic field. This result holds at all considered altitudes, including a transitional region between the E and F regions. Symmetries of the resulting expression for the growth rate are discussed, and numerical calculations for representative gradient and current configurations are presented to illustrate and validate analytical results.
New dates for point technology in the Kimberley
Authors: Maloney Tim , O'Connor Sue , Balme Jane
Published: September 2014

New data from Bunuba country in the southern Kimberley provide more robust dates for point technology in the Kimberley than have been previously available. Direct percussion points have been recovered from three sites in the southern Kimberley associated with radiocarbon dates of ∼5000 calBP, whereas the earliest pressure‐flaked points are consistently associated with dates within the past 1000 years. This suggests that pressure‐flaked point technology postdates the earliest occurrence of direct percussion points by ∼4000 years in this region.
HS‐SPME‐GC‐FID method for detection and quantification of Bacillus cereusATCC 10702 mediated 2‐acetyl‐1‐pyrroline
Authors: Deshmukh Yogita , Khare Puja , Patra D. D. , Nadaf Altafhusain B.
Published: September 2014

A rapid micro‐scale solid‐phase micro‐extraction (SPME) procedure coupled with gas‐chromatography with flame ionized detector (GC‐FID) was used to extract parts per billion levels of a principle basmati aroma compound “2‐acetyl‐1‐pyrroline” (2‐AP) from bacterial samples. In present investigation, optimization parameters of bacterial incubation period, sample weight, pre‐incubation time, adsorption time, and temperature, precursors and their concentrations has been studied. In the optimized conditions, detection of 2‐AP produced by Bacillus cereus ATCC10702 using only 0.5 g of sample volume was 85 μg/kg. Along with 2‐AP, 15 other compounds produced by B. cereus were also reported out of which 14 were reported for the first time consisting mainly of (E)−2‐hexenal, pentadecanal, 4‐hydroxy‐2‐butanone, n‐hexanal, 2–6‐nonadienal, 3‐methoxy‐2(5H) furanone and 2‐acetyl‐1‐pyridine and octanal. High recovery of 2‐AP (87 %) from very less amount of B. cereus samples was observed. The method is reproducible fast and can be used for detection of 2‐AP production by B. cereus. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:1356–1363, 2014
Maximizing recombinant human serum albumin production in a MutsPichia pastoris strain
Authors: Mallem Muralidhar , Warburton Shannon , Li Fang , Shandil Ishaan , Nylen Adam , Kim Sehoon , Jiang Youwei , Meehl Michael , d'Anjou Marc , Stadheim Terrance A. , Choi Byung‐Kwon
Published: September 2014

Human serum albumin (HSA) is a cysteine rich molecule that is most abundant in human blood plasma. To remain viable in the market due to lower marketing costs for HSA, it is important to produce a large quantity in an economical manner by recombinant technology. The objective of this study was to maximize recombinant HSA (rHSA) production using a Muts Pichia pastoris strain by fermentation process optimization. We evaluated the impact of process parameters on the production of rHSA, including induction cell density (wet cell weight, g/L) and the control of specific growth rate at induction. In this study, we demonstrated that induction cell density is a critical factor for high level production of rHSA under controlled specific growth rate. We observed higher specific productivities at higher induction cell densities (285 g/L) and at lower specific growth rates (0.0022–0.0024/h) during methanol induction phase, and achieved the broth titer of rHSA up to 10 g/L. The temperature shift from 24 to 28oC was effective to control the specific growth rate at low level (≤0.0024/h) during methanol induction phase while maintaining high specific productivity [0.0908 mgrHSA/(gwcw h)]. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:1488–1496, 2014
Vector time series models for prediction of air quality inside a public transportation bus using available software
Authors: Kadiyala Akhil , Kumar Ashok
Published: September 2014

Development of practical in‐vehicle air quality vector time series models is useful for examining new (or enhancement of existing) control strategies for managing indoor air quality (IAQ) within the considered transit microenvironment. The models are helpful to the vehicle manufacturers in understanding the scope for preventing in‐vehicle contaminant concentration buildup beyond permissible IAQ guidelines, and to the commuters in understanding the risks of exposure to various air contaminants. This study demonstrates the methodology to develop and validate the vector time series models (VARMA/VARMAX) for the in‐bus contaminant concentrations of carbon dioxide and carbon monoxide using available software. © 2014 American Institute of Chemical Engineers Environ Prog, 33: 1069–1073, 2014
T cell‐based targeted immunotherapies for patients with multiple myeloma
Authors: Wang Lei , Jin Nan , Schmitt Anita , Greiner Jochen , Malcherek Georg , Hundemer Michael , Mani Jiju , Hose Dirk , Raab Marc S , Ho Anthony D. , Chen Bao‐an , Goldschmidt Hartmut , Schmitt Michael
Published: September 2014

Despite high‐dose chemotherapy followed by autologs stem‐cell transplantation as well as novel therapeutic agents, multiple myeloma (MM) remains incurable. Following the general trend towards personalized therapy, targeted immunotherapy as a new approach in the therapy of MM has emerged. Better progression‐free survival and overall survival after tandem autologs/allogeneic stem cell transplantation suggest a graft versus myeloma effect strongly supporting the usefulness of immunological therapies for MM patients. How to induce a powerful antimyeloma effect is the key issue in this field. Pivotal is the definition of appropriate tumor antigen targets and effective methods for expansion of T cells with clinical activity. Besides a comprehensive list of tumor antigens for T cell‐based approaches, eight promising antigens, CS1, Dickkopf‐1, HM1.24, Human telomerase reverse transcriptase, MAGE‐A3, New York Esophageal‐1, Receptor of hyaluronic acid mediated motility and Wilms' tumor gene 1, are described in detail to provide a background for potential clinical use. Results from both closed and on‐going clinical trials are summarized in this review. On the basis of the preclinical and clinical data, we elaborate on three encouraging therapeutic options, vaccine‐enhanced donor lymphocyte infusion, chimeric antigen receptors–transfected T cells as well as vaccines with multiple antigen peptides, to pave the way towards clinically significant immune responses against MM.
Increasing participation in colorectal cancer screening: Results from a cluster randomized trial of directly mailed gFOBT kits to previous nonresponders
Authors: Tinmouth Jill , Patel Jigisha , Austin Peter C. , Baxter Nancy N. , Brouwers Melissa C. , Earle Craig , Levitt Cheryl , Lu Yan , Mackinnon Marnie , Paszat Lawrence , Rabeneck Linda
Published: September 2014

Regular screening using guaiac fecal occult blood test (gFOBT) reduces mortality from colorectal cancer (CRC). The objective of this study was to determine whether the addition of a gFOBT kit to a second mailed invitation compared to a second mailed invitation alone increases CRC screening among eligible persons who did not respond to an initial mailed invitation. We conducted a cluster randomized controlled trial, with the physician as the unit of randomization. Participants were persons who had been invited but who had not responded to an invitation for CRC screening in an earlier pilot project. The intervention group received a mailed gFOBT kit and second mailed CRC screening invitation (n = 2,008) while the control group received a second mailed CRC screening invitation alone (n = 1,586). The primary outcome was the uptake of gFOBT within 6 months of the second mailing. We found that the uptake of gFOBT was more than twice as high in the intervention group (20.1%) compared to the control group (9.6%). The absolute difference between the two groups was 10.5% (95% CI: 7.5–13.4%, p ≤ 0.0001). In a subsequent adjusted analysis, participants in the intervention group were twice as likely to complete the test as those in the control group (OR = 2.1; 95% CI: 1.6–2.6). These findings suggest that directly mailed gFOBT kits increase CRC screening participation among previous nonresponders to a mailed invitation and that approximately 10 gFOBT kits would have to be sent by mail in order to screen 1 additional person. (ClinicalTrials.gov: NCT01629004).
The biguanides metformin and phenformin inhibit angiogenesis, local and metastatic growth of breast cancer by targeting both neoplastic and microenvironment cells
Authors: Orecchioni Stefania , Reggiani Francesca , Talarico Giovanna , Mancuso Patrizia , Calleri Angelica , Gregato Giuliana , Labanca Valentina , Noonan Douglas M. , Dallaglio Katiuscia , Albini Adriana , Bertolini Francesco
Published: September 2014

The human white adipose tissue (WAT) contains progenitors with cooperative roles in breast cancer (BC) angiogenesis, local and metastatic progression. The biguanide Metformin (Met), commonly used for Type 2 diabetes, might have activity against BC and was found to inhibit angiogenesis in vivo. We studied Met and another biguanide, phenformin (Phe), in vitro and in vivo in BC models. In vitro, biguanides activated AMPK, inhibited Complex 1 of the respiratory chain and induced apoptosis of BC and WAT endothelial cells. In coculture, biguanides inhibited the production of several angiogenic proteins. In vivo, biguanides inhibited local and metastatic growth of triple negative and HER2+ BC in immune‐competent and immune‐deficient mice orthotopically injected with BC. Biguanides inhibited local and metastatic BC growth in a genetically engineered murine model model of HER2+ BC. In vivo, biguanides increased pimonidazole binding (but not HIF‐1 expression) of WAT progenitors, reduced tumor microvessel density and altered the vascular pericyte/endothelial cell ratio, so that cancer vessels displayed a dysplastic phenotype. Phe was significantly more active than Met both in vitro and in vivo. Considering their safety profile, biguanides deserve to be further investigated for BC prevention in high‐risk subjects, in combination with chemo and/or targeted therapy and/or as post‐therapy consolidation or maintenance therapy for the prevention of BC recurrence.
Adhesion and integration of tissue engineered cartilage to porous polyethylene for composite ear reconstruction
Authors: O'Sullivan Niamh A. , Kobayashi Shinji , Ranka Mitun P. , Zaleski Katherine L. , Yaremchuk Michael J. , Bonassar Lawrence J. , Randolph Mark A.
Published: September 2014

The objective of this study was to assess the ability of tissue engineered cartilage to adhere to and integrate with porous polyethylene (PPE) in vivo and to evaluate the biomechanical integrity of the bond formed at the interface. Porcine auricular, articular, and costal chondrocytes were suspended in fibrin gel polymer and placed between discs of PPE to form tri‐layer constructs. Controls consisted of fibroblasts suspended in gel or gel alone between the discs. Constructs were implanted into nude mice for 6, 12, and 18 weeks. Upon harvest, specimens were evaluated for neocartilage formation and integration into the PPE, using histological, dimensional (mass, thickness, diameter), and biomechanical (adhesion strength, interfacial stiffness, failure energy and failure strain) analyses. Neotissue was formed in all experimental constructs, consisting mostly of neocartilage integrating with discs of PPE. Control samples contained only fibrous tissue. Biomechanical analyses demonstrated that adhesion strength, interfacial stiffness, and failure energy were all significantly higher in the chondrocyte‐seeded samples than in fibroblast‐seeded controls, with the exception of costal constructs at 12 weeks, which were not significantly greater than controls. In general, failure strains did not vary between groups. In conclusion, porous polyethylene supported the growth of neocartilage that formed mechanically functional bonds with the PPE. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 983–991, 2015.
Higher Glucocorticoid Secretion in the Physiological Range Is Associated With Lower Bone Strength at the Proximal Radius in Healthy Children: Importance of Protein Intake Adjustment
Authors: Shi Lijie , Sánchez-Guijo Alberto , Hartmann Michaela F , Schönau Eckhard , Esche Jonas , Wudy Stefan A , Remer Thomas
Published: September 2014

Whether higher production of glucocorticoids (GCs) within the physiological range may already be affecting bone status in healthy children is unknown. Because dietary protein intake affects both bone and GCs, we examined the association of urinary measures of glucocorticoid status and cortical bone in healthy non-obese children, after particularly controlling for protein intake. Proximal forearm bone parameters were measured by peripheral quantitative computed tomography (pQCT). Subjects studied (n = 175, 87 males, aged 6 to 18 years) had two 24-hour urine samples collected: the first sample at 1 year before bone measurement, and the second sample at the time of bone measurement. Major urinary GC metabolites were measured by mass spectrometry and summed to assess daily adrenal GC secretion (∑C21). Urinary free cortisol (UFF) and cortisone (UFE) were summed to assess potentially bioactive free GCs (UFF + UFE). After controlling for several covariates and especially urinary nitrogen (the biomarker of protein intake) cortisol secretion ∑C21 was inversely associated with all analyzed pQCT measures of bone quality. ∑C21 also predicted a higher endosteal and lower periosteal circumference, explaining both a smaller cortical area and (together with lower BMD) a lower strength-strain-index (SSI). UFF + UFE, UFE itself, and a urinary metabolite-estimate of 11beta-hydroxysteroid dehydrogenase type1 (11beta-HSD1) activity showed corresponding reciprocal associations (p < 0.05) with BMD and bone mineral content, but not with SSI and bone geometry variables. In conclusion, higher GC levels, even within the physiological range, appear to exert negative influences on bone modeling and remodeling already during growth. Our physiological data also suggest a relevant role of cortisone as the direct source for intracrine-generated cortisol by bone cell 11beta-HSD1. © 2014 American Society for Bone and Mineral Research.
Growth and Aging of Proximal Femoral Bone: A Study With Women Spanning Three Generations
Authors: Wang Qin , Chen Decai , Cheng Shu Mei , Nicholson Patrick , Alen Markku , Cheng Sulin
Published: September 2014

Osteoporotic hip fracture is a serious clinical event associated with high morbidity and mortality. Understanding femoral growth patterns is important for promoting bone health in the young and preventing fractures in later life. In this study, growth patterns of areal bone mineral density (aBMD) and geometric properties of the proximal femur were measured by dual-energy X-ray absorptiometry. They were studied in 251 girls from premenarche (11.2 ± 0.7 years) to late adolescence (18.3 ± 1.1 years) and compared with their premenopausal mothers (n = 128, aged 44.9 ± 4.1 years) and postmenopausal grandmothers (n = 128, aged 70.0 ± 6.3 years). Hip axis length (HAL) was the first to reach peak growth velocity (−10.5 months before menarche), followed by neck diameter (ND) and neck cross-sectional area (CSA), (−7.1 and −4.1 months before menarche, respectively). Both neck-shaft angle (NSA) and aBMD of neck and total hip peaked at menarche. At 18 years (7-year follow-up), girls already had higher femoral neck aBMD but similar HAL and NSA compared with their mothers. Grandmothers had the longest HAL, narrowest NSA, widest ND but lowest aBMD and CSA. Hip strength index (HSI), an index of femoral neck strength during a fall, dropped rapidly after menarche in girls but thereafter remained relatively constant. Grandmothers had lower HSI than either mothers or girls. In conclusion, differences in proximal femoral bone mass and structure in adulthood are largely established before menarche, indicating that heritable factors are responsible for most of the individual variance. The development of geometric properties precedes aBMD in puberty, resulting in relatively constant hip strength after menarche. This asynchronous growth leads to adaptation of bone strength to the imposed loads, avoiding fractures in a biologically efficient manner. Both deterioration of aBMD and inadequate compensatory change in bone geometry after menopause contribute to the increased fracture risk later in life. © 2014 American Society for Bone and Mineral Research.
FGF23 Is Endogenously Phosphorylated in Bone Cells
Authors: Lindberg Iris , Pang Hong Weng , Stains Joseph P , Clark David , Yang Austin J , Bonewald Lynda , Li Kevin Z
Published: September 2014

Levels of serum phosphate are controlled by the peptide hormone FGF23, secreted from bone osteocytes. Elevated levels of circulating FGF23 are a key factor in several hypophosphatemic disorders and play a role in chronic kidney disease. Posttranslational processing of FGF23 includes multi-site O-glycosylation, which reduces intracellular cleavage by proprotein convertases. The FGF23 protein also contains four serine phosphorylation consensus sequences (S-X-D/E); in this work, we asked whether FGF23 is a substrate for secretory phosphorylation. Both HEK cells as well as IDG-SW3 cells, an osteocyte model, incorporated radiolabeled orthophosphate into intact FGF23, as well as into the 14-kDa carboxy-terminal—but not the 17-kDa N-terminal—fragment. Sequential serine-to-alanine site-directed mutagenesis of four kinase consensus sites showed that labeling occurred on three serines within the carboxy-terminal fragment, Ser180 (adjacent to the cleavage site), Ser207, and Ser212. Liquid chromatography-coupled mass spectroscopy indicated the presence of phosphate at Ser212 in recombinant R&D mouse FGF23R179Q, confirming labeling results. A phosphopeptide-specific antibody was raised against phospho-Ser212 and exhibited immunoreactivity in osteocytes present in mouse long bone, providing further evidence that FGF23 is naturally phosphorylated in bone. Bone SIBLING proteins are serine-phosphorylated by the ubiquitous Golgi secretory kinase FAM20C. Cotransfection of HEK and MC3T3 cells with FGF23 and active, but not inactive, FAM20C kinase increased the storage and release of FGF23 in radiolabeling experiments, indicating potential effects of phosphorylation on FGF23 stability. Collectively, these data point to an important role for phosphorylation of FGF23 in bone. © 2014 American Society for Bone and Mineral Research.
Preparation of a novel polymer monolith with functional polymer brushes by two‐step atom‐transfer radical polymerization for trypsin immobilization
Authors: Li Nan , Zheng Wei , Shen Ying , Qi Li , Li Yaping , Qiao Juan , Wang Fuyi , Chen Yi
Published: September 2014

Novel porous polymer monoliths grafted with poly{oligo[(ethylene glycol) methacrylate]‐co‐glycidyl methacrylate} brushes were fabricated via two‐step atom‐transfer radical polymerization and used as a trypsin‐based reactor in a continuous flow system. This is the first time that atom‐transfer radical polymerization technique was utilized to design and construct polymer monolith bioreactor. The prepared monoliths possessed excellent permeability, providing fast mass transfer for enzymatic reaction. More importantly, surface properties, which were modulated via surface‐initiated atom‐transfer radical polymerization, were found to have a great effect on bioreactor activities based on Michaelis–Menten studies. Furthermore, three model proteins were digested by the monolith bioreactor to a larger degree within dramatically reduced time (50 s), about 900 times faster than that by free trypsin (12 h). The proposed method provided a platform to prepare porous monoliths with desired surface properties for immobilizing various enzymes.
A novel method for mitigating the effects of dynamic coexistence on the operation of IEEE 802.15.4‐based mobile WSNs
Authors: Deylami Mohammad , Jovanov Emil
Published: September 2014

Wireless networks dynamically coexist when their transmission ranges overlap as a result of mobility. Mobile wireless sensor networks (WSNs) may suffer from significant degradation of performance due to the interference caused by dynamic coexistence, which is particularly critical for health monitoring WSNs. In this paper, we propose a novel method to detect and mitigate the harmful effects of dynamic coexistence on the operation of IEEE 802.15.4‐based mobile health monitoring WSNs. IEEE 802.15.4 uses the guaranteed time slots (GTS) mechanism to eliminate contention; however, successful transmissions cannot be guaranteed for coexisting WSNs. We show that using limited clear channel assessments at the beginning of the GTS enables the mobile WSNs to avoid collisions with minimum overhead. This method can also be used in combination with the previously proposed mechanisms for coexistence management. We analytically investigate the effects of using this method on the performance of the dynamically coexisting WSNs. We use OPNET simulation to investigate the coexistence of health monitoring WSNs and also to validate the proposed method. Our results indicate that using the proposed mechanism, 2–10 coexisting mobile WSNs with relatively high transmission rates (20–30% of maximum throughput) can achieve 20–90% higher rates of successful transmissions, with less than 10% increase in power consumption. Copyright © 2014 John Wiley & Sons, Ltd.
Stimulus–responsive ultrasound contrast agents for clinical imaging: motivations, demonstrations, and future directions
Authors: Goodwin Andrew P. , Nakatsuka Matthew A. , Mattrey Robert F.
Published: September 2014

Microbubble ultrasound contrast agents allow imaging of the vasculature with excellent resolution and signal‐to‐noise ratios. Contrast in microbubbles derives from their interaction with an ultrasound wave to generate signal at harmonic frequencies of the stimulating pulse; subtracting the elastic echo caused by the surrounding tissue can enhance the specificity of these harmonic signals significantly. The nonlinear acoustic emission is caused by pressure‐driven microbubble size fluctuations, which in both theoretical descriptions and empirical measurements was found to depend on the mechanical properties of the shell that encapsulates the microbubble as well as stabilizes it against the surrounding aqueous environment. Thus biochemically induced switching between a rigid ‘off’ state and a flexible ‘on’ state provides a mechanism for sensing chemical markers for disease. In our research, we coupled DNA oligonucleotides to a stabilizing lipid monolayer to modulate stiffness of the shell and thereby induce stimulus–responsive behavior. In initial proof‐of‐principle studies, it was found that signal modulation came primarily from DNA crosslinks preventing the microbubble size oscillations rather than merely damping the signal. Next, these microbubbles were redesigned to include an aptamer sequence in the crosslinking strand, which not only allowed the sensing of the clotting enzyme thrombin but also provided a general strategy for sensing other soluble biomarkers in the bloodstream. Finally, the thrombin‐sensitive microbubbles were validated in a rabbit model, presenting the first example of an ultrasound contrast agent that could differentiate between active and inactive clots for the diagnosis of deep venous thrombosis. WIREs Nanomed Nanobiotechnol 2015, 7:111–123. doi: 10.1002/wnan.1285

This article is categorized under:

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

Biology-Inspired Nanomaterials > Lipid-Based Structures

Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures
Using Formative Research to Develop a Counselor Training Program for Newborn Screening in Ghana
Authors: Treadwell Marsha J. , Anie Kofi A. , Grant Althea M. , Ofori‐Acquah Solomon F. , Ohene‐Frempong Kwaku
Published: September 2014

Sickle cell disease (SCD), sickle cell trait (SCT) and related conditions are highly prevalent in sub‐Saharan Africa. Despite the public health implications, there is limited understanding of the unique needs regarding establishing and implementing extensive screening for newborns and appropriate family counseling. We sought to gain understanding of community attitudes and beliefs about SCD/SCT from counselors and potential counselors in Ghana; obtain their input about goals for counseling following newborn screening; and obtain guidance about developing effective counselor education. Five focus groups with 32 health care providers and health educators from 9 of 10 regions in Ghana were conducted by trained facilitators according to a structured protocol. Qualitative data were coded and categorized to reflect common themes. Saturation was achieved in themes related to genetics/inheritance; common complications of SCD; potential for stigmatization; marital strain; and emotional stress. Misconceptions about SCT as a form of SCD were prevalent as were cultural and spiritual beliefs about the causes of SCD/SCT. Potential positive aspects included affected children′s academic achievement as compensation for physical limitations, and family cohesion. This data informed recommendations for content and structure of a counselor training program that was provided to the Ministry of Health in Ghana.
An alternative allosteric regulation mechanism of an acidophilic l‐lactate dehydrogenase from Enterococcus mundtii 15‐1A
Authors: Matoba Yasuyuki , Miyasako Masashi , Matsuo Koichi , Oda Kosuke , Noda Masafumi , Higashikawa Fumiko , Kumagai Takanori , Sugiyama Masanori
Published: September 2014

A plant‐derived Enterococcus mundtii 15‐1A, that has been previously isolated from Brassica rapa L. subsp. nipposinica (L.H. Bailey) Hanelt var. linearifolia by our group, possesses two kinds of l‐lactate dehydrogenase (l‐LDH): LDH‐1 and LDH‐2. LDH‐1 was activated under low concentration of fluctose‐1,6‐bisphosphate (FBP) at both pH 5.5 and 7.5. Although LDH‐2 was also activated under the low concentration of FBP at pH 5.5, a high concentration of FBP is necessary to activate it at pH 7.5. The present study shows the crystal structures of the acidophilic LDH‐2 in a complex with and without FBP and NADH. Although the tertiary structure of the ligands‐bound LDH‐2 is similar to that of the active form of other bacterial l‐LDHs, the structure without the ligands is different from that of any other previously determined l‐LDHs. Major structural alterations between the two structures of LDH‐2 were observed at two regions in one subunit. At the N‐terminal parts of the two regions, the ligands‐bound form takes an α‐helical structure, while the form without ligands displays more disordered and extended structures. A vacuum‐ultraviolet circular dichroism analysis showed that the α‐helix content of LDH‐2 in solution is approximately 30% at pH 7.5, which is close to that in the crystal structure of the form without ligands. A D241N mutant of LDH‐2, which was created by us to easily form an α‐helix at one of the two parts, exhibited catalytic activity even in the absence of FBP at both pH 5.5 and 7.5.
Human papillomavirus among women with atypical squamous cells of undetermined significance in southern Brazil
Authors: Paesi Suelen , Correa Leonardo , Tregnago Márcia Caldart , Mandelli Jovana , Roesch‐Ely Mariana
Published: September 2014

Objective

To determine the prevalence of atypical squamous cells of undetermined significance (ASCUS) and human papillomavirus (HPV) genotypes in a population in southern Brazil.

Methods

In a retrospective cross‐sectional study, the prevalence of ASCUS was determined among women aged 20–60 years who were referred to a private medical center in Caxias do Sul by a gynecologist for assessment of a cervical condition between January 1, 2010, and September 30, 2011. Histologic and cytologic samples were tested for HPV, and polymerase chain reaction (PCR) was used to genotype any HPV DNA identified.

Results

Among the 250 included women, 25 (10.0%) had ASCUS. HPV DNA was found in 15 (60.0%) women with ASCUS and 115 (51.1%) of the 225 without ASCUS. Viral typing showed that 7 (46.7%) HPV‐positive women with ASCUS had multiple infections with up to five different genotypes. Both low‐ and high‐risk HPV genotypes were found in ASCUS samples; the most prevalent genotypes were HPV6/HPV11 (affecting 10 [66.7%] women), HPV51 (6 [40.0%]), and HPV16 (6 [40.0%]).

Conclusion

ASCUS is not an indication of HPV infection. HPV screening and genotyping would benefit women with ASCUS, because treatment can be planned according to risk of carcinogenesis.
Keeping consumers in the red: Hedonic debt prioritization within multiple debt accounts
Authors: Besharat Ali , Varki Sajeev , Craig Adam W.
Published: September 2014

In our paper we contribute to the burgeoning literature in the psychology of debt repayment. Across three experiments, we explore the effects of the type (hedonic or utilitarian) and the timing of debt on consumers' debt repayment when managing multiple debt accounts. While prior literature has demonstrated that debtors who own multiple credit cards behave irrationally by paying down smaller balances rather than balances with higher interest rates, we found that debts incurred for hedonic purchases and in the distant past (versus proximal past) amplify this effect. The anticipated impact of debt repayment on consumption enjoyment is found to mediate this effect.
Additive impact of HER2‐/PTK6‐RNAi on interactions with HER3 or IGF‐1R leads to reduced breast cancer progression in vivo
Authors: Falkenberg Natalie , Anastasov Nataša , Höfig Ines , Bashkueva Ksenia , Lindner Katrin , Höfler Heinz , Rosemann Michael , Aubele Michaela
Published: September 2014

The human epidermal growth factor receptor 2 (HER2) and the protein tyrosine kinase 6 (PTK6) are often co‐ and over‐expressed in invasive breast cancers. At early diagnosis, only distinct groups, such as HER2‐or hormone receptor‐positive benefit from a targeted therapy. However, a part of these tumours develops resistance within a year of administration of the drug but the majority of the patients depends on general therapies with severe side effects. A PTK6‐directed approach does not yet exist.

In our present study, we successfully demonstrate, in vitro and in vivo, a significantly additive reduction of tumourigenesis of breast cancer cells simultaneously depleted of both HER2 and PTK6. In comparison with single RNAi approaches, the combined RNAi (co‐RNAi) led to a stronger reduced phosphorylation of tumour‐promoting proteins. Moreover, the co‐RNAi additively decreased cell migration as well as two and three dimensional cell proliferation in vitro. The in vivo experiments showed an additive reduction (p < 0.00001) in the growth of xenografts due to the co‐RNAi compared with HER2 or PTK6 RNAi alone. Interestingly, the complexes of HER2 or PTK6 with tumour‐relevant interaction partners, such as HER3 or the insulin‐like growth factor receptor 1 (IGF‐1R), respectively, were also reduced in xenografts although their protein expression levels were not affected following the co‐RNAi of HER2 and PTK6. Our present study reveals the potential of using combined HER2‐ and PTK6‐ knockdown as a powerful strategy for the treatment of breast cancers. Therefore, the combined inhibition of these proteins may represent an attractive tool for efficient therapy of breast cancers.
The co‐chaperone p23 promotes prostate cancer motility and metastasis
Authors: Querol Cano Laia , Lavery Derek N. , Sin Soraya , Spanjaard Emma , Brooke Greg N. , Tilman Jessica D. , Abroaf Ahmed , Gaughan Luke , Robson Craig N. , Heer Rakesh , Mauri Francesco , de Rooij Johan , Driouch Keltouma , Bevan Charlotte L.
Published: September 2014

Prostate cancer is an androgen receptor (AR)‐dependent malignancy at initiation and progression, therefore hormone therapy is the primary line of systemic treatment. Despite initial disease regression, tumours inevitably recur and progress to an advanced castration‐resistant state a major feature of which is metastasis to the bone. Up‐regulation of AR cofactors and chaperones that overcome low hormone conditions to maintain basal AR activity has been postulated as a mechanism of therapy relapse.

p23, an essential component of the apo‐AR complex, acts also after ligand binding to increase AR transcriptional activity and target gene expression, partly by increasing chromatin‐loaded holo‐receptor‐complexes. Immunohistochemical studies have demonstrated increased p23 expression in advanced prostate cancer. Here, we further characterise p23 roles in AR signalling and show that it modulates cytosolic AR levels in the absence of hormone, confirming a chaperoning function in the aporeceptor complex and suggesting p23 upregulates AR signalling at multiple stages. Moreover, p23 protein levels significantly increased upon treatment with not only androgen but also clinically relevant anti‐androgens. This was in contrast to the HSP90 inhibitor 17‐AAG, which did not modulate expression of the cochaperone – important given the HSP90‐independent roles we and others have previously described for p23.

Further, we demonstrate p23 is implicated in prostate cancer cell motility and in acquisition of invasiveness capacity through the expression of specific genes known to participate in cancer progression. This may drive metastatic processes in vivo since analysis of prostate tumour biopsies revealed that high nuclear p23 significantly correlated with shorter survival times and with development of metastases in patients with lower grade tumours. We propose that increased p23 expression may allow cells to acquire a more aggressive phenotype, contributing to disease progression, and that p23 is a plausible secondary target in combination with HSP90 inhibition as a potential therapy for advanced prostate cancer.
Spatial Analysis
Authors: Dale Mark R. T. , Fortin Marie-Josée
Published: September 2014

Nowadays, ecologists worldwide recognize the use of spatial analysis as essential. However, because of the fast-growing range of methods available, even an expert might occasionally find it challenging to choose the most appropriate one. Providing the ecological and statistical foundations needed to make the right decision, this second edition builds and expands upon the previous one by:
• Encompassing the basic methods for spatial analysis, for both complete census and sample data
• Investigating updated treatments of spatial autocorrelation and spatio-temporal analysis
• Introducing detailed explanations of currently developing approaches, including spatial and spatio-temporal graph theory, scan statistics, fibre process analysis, and Hierarchical Bayesian analysis
• Offering practical advice for specific circumstances, such as how to analyze forest Permanent Sample Plot data and how to proceed with transect data when portions of the data series are missing.
Written for graduates, researchers and professionals, this book will be a valuable source of reference for years to come.
A Student's Guide to Entropy
Authors: Lemons Don S.
Published: September 2014

Striving to explore the subject in as simple a manner as possible, this book helps readers understand the elusive concept of entropy. Innovative aspects of the book include the construction of statistical entropy from desired properties, the derivation of the entropy of classical systems from purely classical assumptions, and a statistical thermodynamics approach to the ideal Fermi and ideal Bose gases. Derivations are worked through step-by-step and important applications are highlighted in over 20 worked examples. Around 50 end-of-chapter exercises test readers' understanding. The book also features a glossary giving definitions for all essential terms, a time line showing important developments, and list of books for further study. It is an ideal supplement to undergraduate courses in physics, engineering, chemistry and mathematics.
An Introduction to Japanese Society
Authors: Sugimoto Yoshio
Published: September 2014

Now in its fourth edition, An Introduction to Japanese Society remains essential reading for students of Japanese society. Internationally renowned scholar Yoshio Sugimoto uses both English and Japanese sources to update and expand upon his original narrative in this sophisticated yet highly readable text. This book explores the breadth and diversity of Japanese society, with chapters covering class, geographical and generational variation, work, education, gender, minorities, popular culture and the establishment. Updates include an exploration of the 'Cool Japan' phenomenon and the explosion of Japanese culture overseas. This edition also features the latest research into Japanese society, updated statistical data and coverage of recent events including the 2011 earthquake and tsunami, and the change in government. Written in a clear and engaging style, An Introduction to Japanese Society provides an insight into all aspects of a diverse and ever-evolving contemporary Japan.
Great Lakes Creoles
Authors: Murphy Lucy Eldersveld
Published: September 2014

A case study of one of America's many multi-ethnic border communities, Great Lakes Creoles builds upon recent research on gender, race, ethnicity, and politics as it examines the ways that the old fur trade families experienced and responded to the colonialism of United States expansion. Lucy Murphy examines Indian history with attention to the pluralistic nature of American communities and the ways that power, gender, race, and ethnicity were contested and negotiated in them. She explores the role of women as mediators shaping key social, economic, and political systems, as well as the creation of civil political institutions and the ways that men of many backgrounds participated in and influenced them. Ultimately, Great Lakes Creoles takes a careful look at Native people and their complex families as active members of an American community in the Great Lakes region.
The Dutch Revolt and Catholic Exile in Reformation Europe
Authors: Janssen Geert H.
Published: September 2014

The Dutch Revolt of the sixteenth century sparked one of the largest refugee crises of Reformation Europe. This book explores the flight, exile and eventual return of Catholic men and women during the war. By mapping the Catholic diaspora across Europe, Geert H. Janssen explains how exile worked as a catalyst of religious radicalisation and transformed the world views, networks and identities of the refugees. Like their Protestant counterparts, the displaced Catholic communities became the mobilising forces behind a militant International Catholicism. The Catholic exile experience thus facilitated the permanent separation of the northern and southern Netherlands. Drawing on diaries, letters and evidence from material culture, this book offers a penetrating picture of the lives of early modern refugees and their agency in the Counter-Reformation.
Morality
Authors: Williams Bernard
Published: September 2014

In Morality Bernard Williams confronts the problems of writing moral philosophy and offers a stimulating alternative to more systematic accounts which seem nevertheless to have left all the important issues somewhere off the page. Williams explains, analyses and distinguishes a number of key positions, from the purely amoral to notions of subjective or relative morality, testing their coherence before going on to explore the nature of 'goodness' in relation to responsibilities and choice, roles, standards and human nature. A classic in moral philosophy.
Substantive Protection under Investment Treaties
Authors: Bonnitcha Jonathan
Published: September 2014

Substantive Protection under Investment Treaties provides the first systematic analysis of the consequences of the substantive protections that investment treaties provide to foreign investors. It proposes a new framework for identifying and evaluating the costs and benefits of differing levels of investment treaty protection, and uses this framework to evaluate the levels of protection for foreign investors implied by different interpretations of the fair and equitable treatment and indirect expropriation provisions of investment treaties. The author examines the arguments and assumptions of both supporters and critics of investment treaties, seeks to test whether they are coherent and borne out by evidence, and concludes that the 'economic' justifications for investment treaty protections are much weaker than is generally assumed. As such, the 'economic' objectives of investment treaties are not necessarily in tension with other 'non-economic' objectives. These findings have important implications for the drafting and interpretation of investment treaties.
Conjugal Union
Authors: Lee Patrick , George Robert P.
Published: September 2014

This book defends the conjugal view of marriage. Patrick Lee and Robert P. George argue that marriage is a distinctive type of community: the union of a man and a woman who have committed to sharing their lives on every level of their beings (bodily, emotionally, and spiritually) in the kind of union that would be fulfilled by conceiving and rearing children together. The comprehensive nature of this union, and its intrinsic orientation to procreation as its natural fulfillment, distinguishes marriage from other types of community and provides the basis for the norms of marital exclusivity and permanence. Lee and George detail how the basic moral norms regarding sexual acts follow from the ethical requirement to respect the good of marriage and explain how the law should treat marriage, given its conjugal nature, examining both the same-sex-marriage issue and civil divorce.
Hegel, the End of History, and the Future
Authors: Dale Eric Michael
Published: September 2014

In Phenomenology of Spirit (1806) Hegel is often held to have announced the end of history, where 'history' is to be understood as the long pursuit of ends towards which humanity had always been striving. In this, the first book in English to thoroughly critique this entrenched view, Eric Michael Dale argues that it is a misinterpretation. Dale offers a reading of his own, showing how it sits within the larger schema of Hegel's thought and makes room for an understanding of the 'end of history' as Hegel intended. Through an elegant analysis of Hegel's philosophy of history, Dale guides the reader away from the common misinterpretation of the 'end of history' to other valuable elements of Hegel's arguments which are often overlooked and deserve to endure. His book will be of great interest to scholars and advanced students of Hegel, the philosophy of history, and the history of political thought.
Contention and the Dynamics of Inequality in Mexico, 1910–2010
Authors: Brachet-Márquez Viviane
Published: September 2014

This book details how contentious politics - everyday as well as exceptional, local as well as national - that took place in three communal villages of Mexico alternately reproduced and reshaped inequality. Narrated and analyzed as instances of the general process of contention, these events took place during three key periods of Mexico's history: the 1910–20 revolution, the Cold War period from the 1950s to the 1970s, and from the 1980s to the present. Together, these episodes of contention build and test a theory of the making and unmaking of inequality in theoretically ideal conditions, illustrating the dynamics of this all-pervasive facet of social organization.
Empty Labor
Authors: Paulsen Roland
Published: September 2014

While most people work ever-longer hours, international statistics suggest that the average time spent on non-work activities per employee is around two hours a day. How is this possible, and what are the reasons behind employees withdrawing from work? In this thought-provoking book, Roland Paulsen examines organizational misbehavior, specifically the phenomenon of 'empty labor', defined as the time during which employees engage in private activities during the working day. This study explores a variety of explanations, from under-employment to workplace resistance. Building on a rich selection of interview material and extensive empirical research, it uses both qualitative and quantitative data to present a concrete analysis of the different ways empty labor unfolds in the modern workplace. This book offers new perspectives on subjectivity, rationality and work simulation and will be of particular interest to academic researchers and graduate students in organizational sociology, organization studies, and human resource management.