bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Prior Compression Tests on the Plantar Soft Tissue Compressive and Shear Properties
Authors: Pai Shruti , Vawter Paul T. , Ledoux William R.
Published: May 2013

Changes in the shear plantar soft tissue properties with diabetes are believed to play a role in plantar ulceration, yet little is known about these properties. Our group recently conducted shear tests on specimens previously tested in compression to fully characterize the tissue under both these loading modes. However, previously tested specimens may not necessarily provide representative mechanical properties as prior testing may have altered the tissue to an unknown extent. Thus, the purpose of this study was to test the effect of prior compression testing on both the plantar soft tissue shear and compressive properties using paired specimens. First, one specimen from each pair was subject to compression using our standard protocol with modifications to compare compressive properties before and after the protocol while the other specimen from each pair was left untested. Then, both specimens (i.e., one previously compression tested and one previously untested) were subject to shear testing. The results indicate that prior compression testing may affect the tissue compressive properties by reducing peak stress and modulus; however, additional testing is needed since these results were likely confounded by stress softening effects. In contrast, neither the elastic nor the viscoelastic plantar soft tissue shear properties were affected by prior testing in compression, indicating that previously compression tested specimens should be viable for use in future shear tests. However, these results are limited given the small sample size of the study and the fact that only nondiabetic specimens were examined.
High Speed Fracture Fixation: Assessing Resulting Fixation Stability and Fastener Withdrawal Strength
Authors: Philip Prygoski Matthew , Sanchez Caballero Samuel , Schmid Steven R. , Lozier Antony J. , Selles Miguel Angel
Published: May 2013

A new method of bone fracture fixation has been developed in which fixation darts (small diameter nails/pins) are driven across a fracture site at high velocity with a pneumatically powered gun. When fixation darts are inserted oblique to one another, kinematic constraints prevent fragment motion and allow bone healing to progress. The primary aim of this study is to determine if fixation darts can provide reasonable fixation stability compared to bone screws, which were used as a benchmark since they represent a simple, yet well-established, surgical technique. The first objective was to evaluate macro-level stability using different numbers of darts inserted parallel and oblique to each other; experimental comparisons were undertaken in a bone analog model. Experimental results showed fixation darts could not be substituted for screws on a one-to-one basis, but that a plurality of fixation darts provided comparable fixation to two bone screws while allowing for faster insertion and damaging less bone. A second objective was to evaluate micro-level stability; a finite element model was created in order to provide a detailed look at the stress state surrounding the fixation darts and the evolution of the fracture gap. Even with relatively weak fixation dart configurations, the fracture gap was maintained below physiological thresholds for bone healing. Most failures of the fixed fractures were attributed to fixation dart pullout from the cancellous structure. The final objective of the study was to characterize this mode of failure with separate fixation dart and screw pullout tests conducted in Sawbones® cancellous foam and fresh porcine cancellous bone. The results showed that the cancellous foam was an acceptable substitute for real bone and provided a conservative estimate of the fixation darts' performance relative to bone screws. A final comparison between experimental and numerically predicted pullout strengths provided confirmation that the model and experiments were consistent.
Are Geometrical and Structural Variations Along the Length of the Aorta Governed by a Principle of “Optimal Mechanical Operation”?
Authors: Rachev Alexander , Greenwald Stephen , Shazly Tarek
Published: May 2013

It is well-documented that the geometrical dimensions, the longitudinal stretch ratio in situ, certain structural mechanical descriptors such as compliance and pressure-diameter moduli, as well as the mass fractions of structural constituents, vary along the length of the descending aorta. The origins of and possible interrelations among these observed variations remain open questions. The central premise of this study is that having considered the variation of the deformed inner diameter, axial stretch ratio, and area compliance along the aorta to be governed by the systemic requirements for flow distribution and reduction of cardiac preload, the zero-stress state geometry and mass fractions of the basic structural constituents of aortic tissue meet a principle of optimal mechanical operation. The principle manifests as a uniform distribution of the circumferential stress in the aortic wall that ensures effective bearing of the physiological load and a favorable mechanical environment for mechanosensitive vascular smooth muscle cells. A mathematical model is proposed and inverse boundary value problems are solved for the equations that follow from finite elasticity, structure-based constitutive modeling within constrained mixture theory, and stress-induced control of aortic homeostasis, mediated by the synthetic activity of vascular smooth muscle cells. Published experimental data are used to illustrate the predictive power of the proposed model. The results obtained are in agreement with published experimental data and support the proposed principle of optimal mechanical operation for the descending aorta.
The Mechanics of Spiral Springs and Its Application in Timekeeping
Authors: Xie Longhan , Ko Puihang , Du Ruxu
Published: May 2013

Spiral spring is widely used in mechanisms, such as mechanical watch movements and clocks where the spiral spring is used for timekeeping. According to literature, there are only a few studies on spiral springs. In this paper, the mechanics of spiral springs is analyzed in details, and its dynamic performance in mechanical watch movements is further studied to find out its natural frequency, which is the most critical parameter for mechanical watch movements. Based on Castigliano's theorem, the mathematical model of dynamic deformation and natural frequency of the spiral spring under external axial torque is developed, and computer simulation with Matlab® is also conducted. Experimental validations are carried out, which confirm the simulation results. Experiments show that the analytical method in this paper can be used to guide and facilitate the design of spiral spring.
Biomechanics of Porcine Renal Arteries and Role of Axial Stretch
Authors: Avril Stéphane , Badel Pierre , Gabr Mohamed , Sutton Michael A. , Lessner Susan M.
Published: May 2013

It is known that arteries experience significant axial stretches in vivo. Several authors have shown that the axial force needed to maintain an artery at its in vivo axial stretch does not change with transient cyclical pressurization over normal ranges. However, the axial force phenomenon of arteries has never been explained with microstructural considerations. In this paper we propose a simple biomechanical model to relate the specific axial force phenomenon of arteries to the predicted load-dependent average collagen fiber orientation. It is shown that (a) the model correctly predicts the authors' experimentally measured biaxial behavior of pig renal arteries and (b) the model predictions are in agreement with additional experimental results reported in the literature. Finally, we discuss the implications of the model for collagen fiber orientation and deposition in arteries.
Draft Genome Sequence of the Deep-Sea Bacterium Shewanella benthica Strain KT99
Authors: Lauro F. M. , Chastain R. A. , Ferriera S. , Johnson J. , Yayanos A. A. , Bartlett D. H.
Published: May 2013

We report the draft genome sequence of the obligately piezophilic
Shewanella benthica
strain KT99 isolated from the abyssal South Pacific Ocean. Strain KT99 is the first piezophilic isolate from the Tonga-Kermadec trench, and its genome provides many clues on high-pressure adaptation and the evolution of deep-sea piezophilic bacteria.
Identification of Starling Circovirus in an Estuarine Mollusc (
Amphibola crenata
) in New Zealand Using Metagenomic Approaches
Authors: Dayaram Anisha , Goldstien Sharyn , Zawar-Reza Peyman , Gomez Christopher , Harding Jon S. , Varsani Arvind
Published: May 2013

Two complete genomes of starling circovirus (StCV) were recovered from
Amphibola crenata
, an estuarine New Zealand mollusc. This is the first report of StCV outside Europe. The viral genomes were recovered from rolling circle-amplified enriched circular DNA followed by back-to-back primers and specific primer PCR amplification.
Genome Sequence of the Polycyclic Aromatic Hydrocarbon-Degrading Bacterium Strain
Marinobacter nanhaiticus
D15-8W
T
Authors: Cui Zhisong , Gao Wei , Li Qian , Xu Guangsu , Zheng Li
Published: May 2013

Marinobacter nanhaiticus
strain D15-8W
T
was isolated from a phenanthrene-degrading consortium, enriched from sediment of the South China Sea. Here, we present the draft genome of strain D15-8W
T
, which contains 5,358,309 bp with a G+C content of 58.53% and contains 4,829 protein-coding genes and 47 tRNA genes.
Complete Genome Sequence of the Deep-Sea Bacterium
Psychromonas
Strain CNPT3
Authors: Lauro F. M. , Stratton T. K. , Chastain R. A. , Ferriera S. , Johnson J. , Goldberg S. M. D. , Yayanos A. A. , Bartlett D. H.
Published: May 2013

Members of the genus
Psychromonas
are commonly found in polar and deep-sea environments. Here we present the genome of
Psychromonas
strain CNPT3. Historically, it was the first bacterium shown to piezoregulate the composition of its membrane lipids and to have a higher growth rate at 57 megapascals (MPa) than at 0.1 MPa.
Whole-Genome Draft Sequences of Three Multidrug-Resistant Klebsiella pneumoniae Strains Available from the American Type Culture Collection
Authors: Broberg Christopher A. , Palacios Michelle , Miller Virginia L.
Published: May 2013

Infection with multidrug-resistant
Klebsiella pneumoniae
is a significant problem worldwide, requiring a better understanding of how various strains are able to defeat current antibiotic therapies and cause disease. Here, we report the draft genome sequences of three
K. pneumoniae
strains harboring the SHV-18, KPC-2, or NDM-1 β-lactamases.
Acupuncture for Treatment of Arthralgia Secondary to Aromatase Inhibitor Therapy in Women with Early Breast Cancer: Pilot Study
Authors: Oh B , Kimble B , Costa D S J , Davis E , McLean A , Orme K , Beith J
Published: May 2013

Background

Aromatase inhibitors (AIs) are recommended as adjuvant hormone treatment for postmenopausal women with early breast cancer. A substantial proportion of women taking AIs experience joint pain and stiffness. Studies have suggested that acupuncture may be effective in treating joint pain.

Objective

A pilot study was conducted to evaluate the feasibility, safety and efficacy of using acupuncture to treat AI-induced arthralgia.

Methods

A total of 32 patients were randomised to receive either sham or real electroacupuncture (EA) twice weekly for 6 weeks. Outcomes of joint pain, stiffness and physical function were measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), overall pain severity and interference with the BPI-SF and quality of life (QOL) with the Functional Assessment of Cancer Therapy-General (FACT-G) instrument. Hand strength was assessed by a grip test, and a serum marker of inflammation (C reactive protein (CRP)) was also measured. All assessments were performed at baseline, 6 weeks and 12 weeks, except for blood samples at baseline and 6 weeks only.

Results

No serious adverse events were reported during or after acupuncture treatments. There were no significant differences in outcome measures. However, positive trends were observed in stiffness and physical function at week 12 in favour of real EA.

Conclusions

Findings suggest that acupuncture is feasible and safe in patients with breast cancer with joint pain caused by AI. A larger study with adequately powered to confirm these results and detect clinically relevant effects is needed.
An interesting case of acute, severe postoperative hyponatraemia following carotid endarterectomy
Authors: Parkinson Fran , Hopper Andrew Neil , Eggert Sabine , Ferguson Colin J
Published: May 2013

A 62-year-old man with no major comorbidities became acutely hyponatraemic on the second postoperative day following a routine carotid endarterectomy. He developed a headache, became hypertensive and confused, and then had a seizure and required intubation and admission to the intensive care unit. A CT angiogram of his head and carotid arteries was normal, as was a subsequent MRI head. His serum and urine osmolality were low. He was treated by fluid restriction and his hyponatraemia resolved over 3 days. On discontinuation of sedation the patient woke up appropriately. The cause of his hyponatraemia was initially a mystery but when questioned by the medical team he admitted that he drank about 5 litres of water in the afternoon on the second postoperative day. At this point the diagnosis of dilutional hypervolaemic hyponatraemia secondary to water intoxication could be made.
Injuries among adolescents in the United Arab Emirates
Authors: Barakat-Haddad Caroline , Siddiqua Ayesha
Published: May 2013

This study examines the profile of injuries among adolescents in the United Arab Emirates (UAE) and identifies related factors associated with injury. A cross-sectional study design determined incidence of injury for a sample of 6363 adolescents. Data collected information on injury in the past 12 months, socio-demographic, behavioural and sensory data. Logistic regression modelling was used to examine predictors of physical injury for the past 12 months. Among participants, 18% experienced injury; the three top causes include accidental falls (38%), being struck by an object or person (18%), and motor vehicle injuries (MVI) (13%). The majority of injuries took place at the participant's home and surrounding area. Identified risk factors that are amenable for prevention include smoking behaviour, exposure to smoking, physical activity profile, family income, and speeding behaviour. Our findings highlight the need for public health policies and education programmes that reduce injury among the UAE adolescent population.
Ethylenediaminetetraacetic acid-dependent pseudomacrocytosis
Authors: Vagace Jose Manuel , Rodriguez Miguel Ángel , de la Maya María Dolores , Gervasini Guillermo
Published: May 2013

We investigated the case of a 14-year-old girl with an ethylenediaminetetraacetic acid (EDTA)-dependent haemagglutination detected by macrocytosis, which was only evident by an abnormal red blood cell (RBC) population in the histogram. Investigations included haemograms with different anticoagulants and experimental conditions. Immunohaematological studies were performed using a gel-based technology. At admission, the patient had a low RBC count and an increased mean corpuscular volume with normal haemoglobin. A double population appeared in the RBC histogram. However, the peripheral blood smear was normal and macrocytosis was absent when heparin or citrate was used instead of EDTA. Later studies revealed that the patient's serum was able to induce macrocytosis of control RBC only in the presence of EDTA. An EDTA-dependent panagglutinin was then indentified that produced mixed field agglutination. These findings provide evidence of a haemagglutination induced by EDTA as a source of pseudomacrocytosis.
Sacral nerve stimulation for the treatment of faecal incontinence secondary to a pelvic war injury: a case report
Authors: Richardson Jonathan J R , Bowley D , Karandikar S
Published: May 2013

Faecal incontinence can be physically and socially disabling and the level of unmet need in men appears to be high. We report a case of faecal incontinence in a 29-year-old, heterosexual serviceman who sustained a trans-pelvic gunshot injury (without perineal injury) while on active duty. Despite apparently successful surgical treatment, the patient presented to our colorectal department 7 years after injury with disabling faecal incontinence. Following assessment, sacral nerve stimulation (SNS) was initiated with excellent results. We report the successful use of SNS to treat faecal incontinence resulting from a combat gunshot injury. We recommend that surgeons carefully document the anatomical position of retained ballistic fragments after gunshot or blast fragment injury and that attention should be paid to the functional results in a patient's follow-up after intestinal surgery.
Sepsis management in the deployed field hospital
Authors: Johnston Andrew McD , Easby D , Ewington I
Published: May 2013

Sepsis, a syndrome caused by severe infection, affects a small proportion of military casualties but has a significant effect in increasing morbidity and mortality, including causing some preventable deaths. Casualties with abdominal trauma and those with significant tissue loss appear to be at a greater risk of sepsis. In this article, the diagnosis and management of sepsis in military casualties with reference to the Surviving Sepsis Campaign guidelines are examined. We discuss the management considerations specific to military casualties in the deployed setting and also discuss factors affecting evacuation by the UK Royal Air Force Critical Care Air Support Team.
INNOVATION TOOL ADOPTION AND ADAPTATION IN SMALL TECHNOLOGY-BASED FIRMS
Authors: DE WAAL GERRIT A. , KNOTT PAUL
Published: May 2013

In this paper, we present a qualitative, interview-based study of the processes small technology-based firms go through when they adopt tools and adapt them for use. By extracting 59 instances of tool internalisation across five firms, we derived a coding scheme combining existing and emergent forms of tool bricolage. The four types are reconstruction, reinterpretation, evolution, and customisation. We articulate examples of each type. Our findings reinforce the variability of any given tool once enacted in practice, contrary to implied expectations in some innovation tools literature that tool application is a straightforward mechanical process. In the small firms in our study, we found reinterpretation is the most prevalent form of tool adaptation. This type of tool use is prone to being superficial and failing to gain the benefits available from a more carefully customised or reconstructed tool. We also report on the different ways in which practitioners gain awareness of new tools.
INNOVATION PROCESS, DECISION-MAKING, PERCEIVED RISKS AND METRICS: A DYNAMICS TEST
Authors: BROPHEY GLENN , BAREGHEH ANAHITA , HEMSWORTH DAVID
Published: May 2013

Innovation processes result from a series of decisions and these are influenced by the perceived risks and success metrics faced by the decision-maker. Aiming to understand whether innovation risks and success metrics change during and between innovations, four hypotheses were developed and a questionnaire-based survey was adopted targeting managers of mechanically based manufacturers. Respondents were asked to indicate the importance of perceived risks throughout specific innovations for four domains of risk: marketing, technical, organizational and financial. Respondents were also asked to identify changes in type and magnitude of innovation risk and success metric. Descriptive and statistical tests were conducted to analyse the data. The results suggest that innovation risk changes in type and magnitude during and between innovations and success metrics change in type and magnitude during innovation. This study calls for situation specific research to provide helpful advice to practitioners.
Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation?
Authors: Harvey Brian C. , Parameswaran Harikrishnan , Lutchen Kenneth R.
Published: May 2013

Fluctuating forces imposed on the airway smooth muscle due to breathing are believed to regulate hyperresponsiveness in vivo. However, recent animal and human isolated airway studies have shown that typical breathing-sized transmural pressure (Ptm) oscillations around a fixed mean are ineffective at mitigating airway constriction. To help understand this discrepancy, we hypothesized that Ptm oscillations capable of producing the same degree of bronchodilation as observed in airway smooth muscle strip studies requires imposition of strains larger than those expected to occur in vivo. First, we applied increasingly larger amplitude Ptm oscillations to a statically constricted airway from a Ptm simulating normal functional residual capacity of 5 cmH2O. Tidal-like oscillations (5–10 cmH2O) imposed 4.9 ± 2.0% strain and resulted in 11.6 ± 4.8% recovery, while Ptm oscillations simulating a deep inspiration at every breath (5–30 cmH2O) achieved 62.9 ± 12.1% recovery. These same Ptm oscillations were then applied starting from a Ptm = 1 cmH2O, resulting in approximately double the strain for each oscillation amplitude. When extreme strains were imposed, we observed full recovery. On combining the two data sets, we found a linear relationship between strain and resultant recovery. Finally, we compared the impact of Ptm oscillations before and after constriction to Ptm oscillations applied only after constriction and found that both loading conditions had a similar effect on narrowing. We conclude that, while sufficiently large strains applied to the airway wall are capable of producing substantial bronchodilation, the Ptm oscillations necessary to achieve those strains are not expected to occur in vivo.
Peripheral fatigue limits endurance exercise via a sensory feedback-mediated reduction in spinal motoneuronal output
Authors: Amann Markus , Venturelli Massimo , Ives Stephen J. , McDaniel John , Layec Gwenael , Rossman Matthew J. , Richardson Russell S.
Published: May 2013

This study sought to determine whether afferent feedback associated with peripheral muscle fatigue inhibits central motor drive (CMD) and thereby limits endurance exercise performance. On two separate days, eight men performed constant-load, single-leg knee extensor exercise to exhaustion (85% of peak power) with each leg (Leg1 and Leg2). On another day, the performance test was repeated with one leg (Leg1) and consecutively (within 10 s) with the other/contralateral leg (Leg2-post). Exercise-induced quadriceps fatigue was assessed by reductions in potentiated quadriceps twitch-force from pre- to postexercise (ΔQtw,pot) in response to supramaximal magnetic femoral nerve stimulation. The output from spinal motoneurons, estimated from quadriceps electromyography (iEMG), was used to reflect changes in CMD. Rating of perceived exertion (RPE) was recorded during exercise. Time to exhaustion (∼9.3 min) and exercise-induced ΔQtw,pot (∼51%) were similar in Leg1 and Leg2 ( P > 0.5). In the consecutive leg trial, endurance performance of the first leg was similar to that observed during the initial trial (∼9.3 min; P = 0.8); however, time to exhaustion of the consecutively exercising contralateral leg (Leg2-post) was shorter than the initial Leg2 trial (4.7 ± 0.6 vs. 9.2 ± 0.4 min; P < 0.01). Additionally, ΔQtw,pot following Leg2-post was less than Leg2 (33 ± 3 vs 52 ± 3%; P < 0.01). Although the slope of iEMG was similar during Leg2 and Leg2-post, end-exercise iEMG following Leg2-post was 26% lower compared with Leg2 ( P < 0.05). Despite a similar rate of rise, RPE was consistently ∼28% higher throughout Leg2-post vs. Leg2 ( P < 0.05). In conclusion, this study provides evidence that peripheral fatigue and associated afferent feedback limits the development of peripheral fatigue and compromises endurance exercise performance by inhibiting CMD.
Extracellular DNA in Pancreatic Cancer Promotes Cell Invasion and Metastasis
Authors: Wen Fushi , Shen Alex , Choi Andrew , Gerner Eugene W. , Shi Jiaqi
Published: May 2013

Aggressive metastasis is the chief cause of the high morbidity and mortality associated with pancreatic cancer, yet the basis for its aggressive behavior remains elusive. Extracellular DNA (exDNA) is a recently discovered component of inflammatory tissue states. Here, we report that exDNA is present on the surface of pancreatic cancer cells where it is critical for driving metastatic behavior. exDNA was abundant on the surface and vicinity of cultured pancreatic cancer cells but absent from normal pancreas cells. Strikingly, treatment of cancer cell cultures with DNase I to degrade DNA nonspecifically reduced metastatic characters associated with matrix attachment, migration, and invasion. We further assessed the role of exDNA in pancreatic cancer metastasis in vivo using an orthotopic xenograft model established by implantation of pancreatic cancer cells expressing firefly luciferase. Noninvasive bioluminescent imaging confirmed that DNase I treatment was sufficient to suppress tumor metastasis. Mechanistic investigations suggested the existence of a positive feedback loop in which exDNA promotes expression of the inflammatory chemokine CXCL8, which leads to higher production of exDNA by pancreatic cancer cells, with a significant reduction in CXCL8 levels achieved by DNase I treatment. Taken together, our results strongly suggest that exDNA contributes to the highly invasive and metastatic character of pancreatic cancer. Cancer Res; 73(14); 4256–66. ©2013 AACR.
4-Hydroxytamoxifen Induces Autophagic Death through K-Ras Degradation
Authors: Kohli Latika , Kaza Niroop , Coric Tatjana , Byer Stephanie J. , Brossier Nicole M. , Klocke Barbara J. , Bjornsti Mary-Ann , Carroll Steven L. , Roth Kevin A.
Published: May 2013

Tamoxifen is widely used to treat estrogen receptor–positive breast cancer. Recent findings that tamoxifen and its derivative 4-hydroxytamoxifen (OHT) can exert estrogen receptor–independent cytotoxic effects have prompted the initiation of clinical trials to evaluate its use in estrogen receptor–negative malignancies. For example, tamoxifen and OHT exert cytotoxic effects in malignant peripheral nerve sheath tumors (MPNST) where estrogen is not involved. In this study, we gained insights into the estrogen receptor–independent cytotoxic effects of OHT by studying how it kills MPNST cells. Although caspases were activated following OHT treatment, caspase inhibition provided no protection from OHT-induced death. Rather, OHT-induced death in MPNST cells was associated with autophagic induction and attenuated by genetic inhibition of autophagic vacuole formation. Mechanistic investigations revealed that OHT stimulated autophagic degradation of K-Ras, which is critical for survival of MPNST cells. Similarly, we found that OHT induced K-Ras degradation in breast, colon, glioma, and pancreatic cancer cells. Our findings describe a novel mechanism of autophagic death triggered by OHT in tumor cells that may be more broadly useful clinically in cancer treatment. Cancer Res; 73(14); 4395–405. ©2013 AACR.
Cytomegalovirus Contributes to Glioblastoma in the Context of Tumor Suppressor Mutations
Authors: Price Richard L. , Song Jieun , Bingmer Katherine , Kim Tae Hyong , Yi Ji-Yeun , Nowicki Michal O. , Mo Xiaokui , Hollon Todd , Murnan Eric , Alvarez-Breckenridge Christopher , Fernandez Soledad , Kaur Balveen , Rivera Andreana , Oglesbee Michael , Cook Charles , Chiocca E. Antonio , Kwon Chang-Hyuk
Published: May 2013

To study the controversial role of cytomegalovirus (CMV) in glioblastoma, we assessed the effects of murine CMV (MCMV) perinatal infection in a GFAP-cre; Nf1loxP/+; Trp53−/+ genetic mouse model of glioma (Mut3 mice). Early on after infection, MCMV antigen was predominantly localized in CD45+ lymphocytes in the brain with active viral replication and local areas of inflammation, but, by 7 weeks, there was a generalized loss of MCMV in brain, confirmed by bioluminescent imaging. MCMV-infected Mut3 mice exhibited a shorter survival time from their gliomas than control Mut3 mice perinatally infected with mock or with a different neurotropic virus. Animal survival was also significantly shortened when orthotopic gliomas were implanted in mice perinatally infected with MCMV versus controls. MCMV infection increased phosphorylated STAT3 (p-STAT3) levels in neural stem cells (NSC) harvested from Mut3 mice subventricular zone, and, in vivo, there was increased p-STAT3 in NSCs in MCMV-infected compared with control mice. Of relevance, human CMV (HCMV) also increased p-STAT3 and proliferation of patient-derived glioblastoma neurospheres, whereas a STAT3 inhibitor reversed this effect in vitro and in vivo. These findings thus associate CMV infection to a STAT3-dependent modulatory role in glioma formation/progression in the context of tumor suppressor mutations in mice and possibly in humans. Cancer Res; 73(11); 3441–50. ©2013 AACR.
Vinblastine Rapidly Induces NOXA and Acutely Sensitizes Primary Chronic Lymphocytic Leukemia Cells to ABT-737
Authors: Bates Darcy J.P. , Danilov Alexey V. , Lowrey Christopher H. , Eastman Alan
Published: May 2013

Proteins of the BCL2 family provide a survival mechanism in many human malignancies, including chronic lymphocytic leukemia (CLL). The BCL2 inhibitor ABT-263 (navitoclax) is active in clinical trials for lymphoid malignancies, yet resistance is expected on the basis of preclinical models. We recently showed that vinblastine can dramatically sensitize several leukemia cell lines to ABT-737 (the experimental congener of ABT-263). The goal of these experiments was to determine the impact of vinblastine on ABT-737 sensitivity in CLL cells isolated from peripheral blood and to define the underlying mechanism. Freshly isolated CLL cells from 35 patients, as well as normal lymphocytes and platelets, were incubated with various microtubule-disrupting agents plus ABT-737 to assess sensitivity to the single agents and the combination. ABT-737 and vinblastine displayed a range of sensitivity as single agents, and vinblastine markedly sensitized all CLL samples to ABT-737 within six hours. Vinblastine potently induced the proapoptotic protein PMAIP1 (NOXA) in both time- and dose-dependent manner and this was required for the observed apoptosis. Combretastatin A4, which dissociates microtubules by binding to a different site, had the same effect, confirming that interaction of these agents with microtubules is the initial target. Similarly, vincristine and vinorelbine induced NOXA and enhanced CLL sensitivity to ABT-737. Furthermore, vinblastine plus ABT-737 overcame stroma-mediated resistance to ABT-737 alone. Apoptosis was induced with clinically achievable concentrations with no additional toxicity to normal lymphocytes or platelets. These results suggest that vinca alkaloids may improve the clinical efficacy of ABT-263 in patients with CLL. Mol Cancer Ther; 12(8); 1504–14. ©2013 AACR.
Maintenance of Ancestral Sex Chromosomes in Palearctic Tree Frogs: Direct Evidence from Hyla orientalis
Authors: Stöck M. , Savary R. , Zaborowska A. , Górecki G. , Brelsford A. , Rozenblut-Kościsty B. , Ogielska M. , Perrin N.
Published: May 2013

Contrasting with the situation found in birds and mammals, sex chromosomes are generally homomorphic in poikilothermic vertebrates. This homomorphy was recently shown to result from occasional X-Y recombinations (not from turnovers) in several European species of tree frogs (Hyla arborea, H. intermedia and H. molleri). Because of recombination, however, alleles at sex-linked loci were rarely diagnostic at the population level; support for sex linkage had to rely on multilocus associations, combined with occasional sex differences in allelic frequencies. Here, we use direct evidence, obtained from anatomical and histological analyses of offspring with known pedigrees, to show that the Eastern tree frog (H. orientalis) shares the same pair of sex chromosomes, with identical patterns of male heterogamety and complete absence of X-Y recombination in males. Conservation of an ancestral pair of sex chromosomes, regularly rejuvenated via occasional X-Y recombination, seems thus a widespread pattern among Hyla species. Sibship analyses also identified discrepancies between genotypic and phenotypic sex among offspring, associated with abnormal gonadal development, suggesting a role for sexually antagonistic genes on the sex chromosomes.
Histone and DNA Methylation–Mediated Epigenetic Downregulation of Endothelial Kruppel-Like Factor 2 by Low-Density Lipoprotein Cholesterol
Authors: Kumar Ajay , Kumar Santosh , Vikram Ajit , Hoffman Timothy A. , Naqvi Asma , Lewarchik Christopher M. , Kim Young-Rae , Irani Kaikobad
Published: May 2013

Objective—

Low-density lipoprotein (LDL) cholesterol induces endothelial dysfunction and is a major modifiable risk factor for coronary heart disease. Endothelial Kruppel-like Factor 2 (KLF2) is a transcription factor that is vital to endothelium-dependent vascular homeostasis. The purpose of this study is to determine whether and how LDL affects endothelial KLF2 expression.

Approach and Results—

LDL downregulates KLF2 expression and promoter activity in endothelial cells. LDL-induced decrease in KLF2 parallels changes in endothelial KLF2 target genes thrombomodulin, endothelial NO synthase, and plasminogen activator inhibitor-1. Pharmacological inhibition of DNA methyltransferases or knockdown of DNA methyltransferase 1 prevents downregulation of endothelial KLF2 by LDL. LDL induces endothelial DNA methyltransferase 1 expression and DNA methyltransferase activity. LDL stimulates binding of the DNA methyl-CpG–binding protein-2 and histone methyltransferase enhancer of zeste homolog 2, whereas decreases binding of the KLF2 transcriptional activator myocyte enhancing factor-2, to the KLF2 promoter in endothelial cells. Knockdown of myocyte enhancing factor-2, or mutation of the myocyte enhancing factor-2 site in the KLF2 promoter, abrogates LDL-induced downregulation of endothelial KLF2 and thrombomodulin, and KLF2 promoter activity. Similarly, knockdown of enhancer of zeste homolog 2 negates LDL-induced downregulation of KLF2 and thrombomodulin in endothelial cells. Finally, overexpression of KLF2 rescues LDL-induced clotting of platelet-rich plasma on endothelial cells.

Conclusions—

LDL represses endothelial KLF2 expression via DNA and histone methylation. Downregulation of KLF2 by LDL leads to a dysfunctional, hypercoagulable endothelium.
A Case-Controlled Comparison of Thrombolysis Outcomes Between Wake-Up and Known Time of Onset Ischemic Stroke Patients
Authors: Manawadu Dulka , Bodla Shankaranand , Jarosz Jozef , Keep Jeff , Kalra Lalit
Published: May 2013

Background and Purpose—

Wake-up ischemic stroke (WUIS) patients are not thrombolysed even if they meet other criteria for treatment. We hypothesized that patients with WUIS showing no or early ischemic changes on brain imaging will have thrombolysis outcomes comparable with those with known time of symptom onset.

Methods—

Consecutive sampling of a prospective registry of patients with stroke between January 2009 and December 2010 identified 394 thrombolysed patients meeting predefined inclusion criteria, 326 presenting within 0 to 4.5 hours of symptom onset (Reference Group) and 68 WUIS patients. Inclusion criteria were last seen normal <12 hours or >4.5 hours (WUIS) or presented <4.5 hours (Reference Group), had National Institutes of Health Stroke Scale score ≥5, and no or early ischemic changes on imaging at presentation. The primary outcome measure was the modified Rankin Scale of 0 to 2 at 90 days measured by trained assessors blinded to patient grouping. Other outcome measures were symptomatic intracerebral hemorrhage, modified Rankin Scale 0 to 1, and mortality at 90 days.

Results—

The groups were comparable for mean age (72.8 versus 73.9 years;
P
=0.58) and baseline median National Institutes of Health Stroke Scale score (median 13 versus 12;
P
=0.34). The proportions of patients with modified Rankin Scale 0 to 2 (38% versus 37%;
P
=0.89) and modified Rankin Scale 0 to 1 (24% versus 16%;
P
=0.18) at 90 days, any ICH (20% versus 22%;
P
=0.42) and symptomatic intracerebral hemorrhage (3.4% versus 2.9%;
P
=1.0) were comparable after adjusting for age, stroke severity, and imaging changes. Only 9/394 (2%) patients were lost to follow-up.

Conclusions—

Thrombolysis in selected patients with WUIS is feasible, and its outcomes are comparable with those thrombolysed with 0 to 4.5 hours.
Very Low Cerebral Blood Volume Predicts Parenchymal Hematoma in Acute Ischemic Stroke
Authors: Hermitte Laure , Cho Tae-Hee , Ozenne Brice , Nighoghossian Norbert , Mikkelsen Irene Klærke , Ribe Lars , Baron Jean-Claude , Østergaard Leif , Derex Laurent , Hjort Niels , Fiehler Jens , Pedraza Salvador , Hermier Marc , Maucort-Boulch Delphine , Berthezène Yves
Published: May 2013

Background and Purpose—

Parenchymal hematoma (PH) may worsen the outcome of patients with stroke. The aim of our study was to confirm the relationship between the volume of very low cerebral blood volume (CBV) and PH using a European multicenter database (I-KNOW). A secondary objective was to explore the impact of early reperfusion and recanalization.

Methods—

The volume of cerebral tissue with CBV ≤2.5th percentile of the normal hemisphere was calculated within the acute diffusion-weighted imaging lesion. Hemorrhagic transformation was assessed on day 2 MRI according to the European Cooperative Acute Stroke Study II criteria. Recanalization and reperfusion were assessed on 3-hour follow-up MRI.

Results—

Of the 110 patients, hemorrhagic transformation occurred in 59 patients, including 7 PH. In univariate analysis, the acute National Institutes of Health Stroke Scale score (
P
=0.002), acute diffusion-weighted imaging lesion volume (
P
=0.02), and thrombolysis (
P
=0.03), but not very low CBV (
P
=0.52), were associated with hemorrhagic transformation. The volume of very low CBV was the only predictor of PH (
P
=0.007). Early reperfusion and recanalization had no influence on either hemorrhagic transformation or PH.

Conclusion—

Very low CBV was the only independent predictor of PH in patients with acute stroke.
Comparison of Flow Diversion and Coiling in Large Unruptured Intracranial Saccular Aneurysms
Authors: Chalouhi Nohra , Tjoumakaris Stavropoula , Starke Robert M. , Gonzalez L. Fernando , Randazzo Ciro , Hasan David , McMahon Jeffrey F. , Singhal Saurabh , Moukarzel Lea A. , Dumont Aaron S. , Rosenwasser Robert , Jabbour Pascal
Published: May 2013

Background and Purpose—

Flow diversion has emerged as an important tool for the management of intracranial aneurysms. The purpose of this study was to compare flow diversion and traditional embolization strategies in terms of safety, efficacy, and clinical outcomes in patients with unruptured, large saccular aneurysms (≥10 mm).

Methods—

Forty patients treated with the Pipeline Embolization Device (PED) were matched in a 1:3 fashion with 120 patients treated with coiling based on patient age and aneurysm size. Fusiform and anterior communicating artery aneurysms were eliminated from the analysis. Procedural complications, angiographic results, and clinical outcomes were analyzed and compared.

Results—

There were no differences between the 2 groups in terms of patient age, sex, aneurysm size, and aneurysm location. The rate of procedure-related complications did not differ between the PED (7.5%) and the coil group (7.5%;
P
=1). At the latest follow-up, a significantly higher proportion of aneurysms treated with PED (86%) achieved complete obliteration compared with coiled aneurysms (41%;
P
<0.001). In multivariable analysis, coiling was an independent predictor of nonocclusion. Retreatment was necessary in fewer patients in the PED group (2.8%) than the coil group (37%;
P
<0.001). A similar proportion of patients attained a favorable outcome (modified Rankin Scale, 0–2) in the PED group (92%) and in the coil group (94%;
P
=0.8).

Conclusions—

The PED provides higher aneurysm occlusion rates than coiling, with no additional morbidity and similar clinical outcomes. These findings suggest that the PED might be a preferred treatment option for large unruptured saccular aneurysms.
Introduction to Special Issue
Authors: Krause Franz , Strang Veronica
Published: May 2013

Human life is both literally and metaphorically unthinkable without water, which permeates and enlivens every form of human activity. Water is equally important for all living organisms, flowing through plants, animals and humans, through places, river systems and ocean currents, and through the entire hydrological cycle, where it constitutes a fundamental aspect of the weather and climate. For many people water epitomizes the connections and integration of living processes: as the life-giving element enabling production and reproduction, and as a substance of community and belonging. However, the fluid qualities that enable water to connect mean that it can also be a major medium for pollution and a threat when overly abundant. And, being essential to all productive processes, it can readily become a means of control and domination. This special issue explores the ways the vitality of water is constituted, negotiated and used strategically in various socio-ecological contexts. How does water figure in experiences, narratives and symbols of living, creativity and healing, or in practices and discourses about pollution and destruction? In what ways can water be used to support or undermine particular power relations? How are ideas about “living water” articulated in property regimes, development projects and conservation strategies?
“Living Water” in Nguni Healing Traditions, South Africa
Authors: Bernard Penelope S.
Published: May 2013

This paper explores the ideas of “living water” held by Nguni-speaking diviner-healers in South Africa. It considers their beliefs in snake/mermaid water divinities and their claims of being called by them underwater, either physically or in a dream, to obtain knowledge and gifts of healing. Seen as cosmic generators of life, fertility and water/rain, these divinities are believed to reside in certain sites of “living water,” which, while characterized by certain physical features, are dependent on correct human ritual relations to maintain their vitality.
Going Against the Flow: The Biopolitics of Dams and Diversions
Authors: Strang Veronica
Published: May 2013

Interactions with water are indicative not only of relationships between human groups but also of relationships with other species. In biopolitical economies few things express dominance over other species as clearly as damming and redirecting flows of water to give primacy to human needs. Yet despite growing opposition, dams—especially large ones—are still presented triumphantly, as symbols of successful nationhood and economic development. Building on ethnographic research in Australia, this chapter examines the allure of dams. It suggests that they represent not only a competition for wealth, but also an aspiration for control over life itself and the vitality of “living water.”
Rapids on the “Stream of Life”: The Significance of Water Movement on the Kemi River
Authors: Krause Franz
Published: May 2013

This article explores the significance of rapids for the inhabitants of the banks of the Kemi River in Finnish Lapland. The river is frequently called “stream of life,” and people emphasize the critical role rapids play for this label. Starting from narratives, practices and material culture relating to the water movements along rapids, the article suggests two hypotheses: first, human associations of water with life arise not only from its characteristics as a substance in itself, but also from its particular movements through the environment. Second, the idea that “water means life” resonates with the similarity of shapes created by water movements and forms permeating all living processes. Building on the work of Strang (e.g. 2005a), Ingold (e.g. 2006) and Schwenk (1965) conclude that calling the Kemi a “stream of life” relates to people’s active engagement in its particular movements.
Depicting the Medieval Alchemical Cosmos
Authors: Rampling Jennifer M.
Published: May 2013

Alchemical images take many forms, from descriptive illustrations of apparatus to complex allegorical schemes that link practical operations to larger cosmological structures. I argue that George Ripley’s famous Compound of Alchemy (1471) was intended to be read in light of a circular figure appended to the work: the Wheel. In the concentric circles of his “lower Astronomy,” Ripley provided a terrestrial analogue for the planetary spheres: encoding his alchemical ingredients as planets that orbited the earthly elements at the core of the work. The figure alludes to a variety of late medieval alchemical doctrines. Yet the complexity of Ripley’s scheme sometimes frustrated later readers, whose struggles to decode and transcribe the figure left their mark in print and manuscript.
Anatomy, Bloodletting and Emblems
Authors: Ekholm Karin
Published: May 2013

The title-page of Nathaniel Highmore’s Disquisition on the Anatomy of the Human Body (1651) depicts mythological and historical characters, anatomical and medical symbols and embodiments of anatomy, contemplation and different forms of bloodletting. Seventy-five lines of free verse face the engraving and together with inscriptions help identify characters and themes in each scene. The verses begin with the charge to examine the title-page before proceeding, and this article explores what the picture teaches the reader. The emblem entices not only by what it heralds, but also by the complex enigmas it comprises, and interpreting it requires the reader to circulate between the picture, verses and the main text. This process instructs us in Highmore’s methods of investigation, his views on the relationship between anatomy and medicine, and his anatomical findings. In particular, it calls attention to his argument that the effectiveness of bloodletting can only be explained on the premise that blood circulates.
Teaching through Diagrams
Authors: Raphael Renée
Published: May 2013

This contribution examines the role of diagrams in early modern pedagogy. It begins with an analysis of images from the 1632 Dialogo and 1638 Discorsi. I claim that Galileo often employed images in a pedagogical context, illustrating to readers through his dialogue how he may have used images in his own teaching. Building on the work of previous historians, I argue that a classification of Galileo’s images should include not only heuristic images and images used for virtual witnessing, but also pedagogical images designed to illustrate to the reader (or student) how to reach conclusions about a given question. I then turn to the way Galileo’s readers at the University of Pisa employed Galileo’s images in their own teaching. I argue that Galileo’s readers employed his images in their own works in ways which reflected their training and the genre in which they wrote and taught.
Inventing Muslims as the Other in Nineteenth-century Brazil
Authors: Resende Fernando
Published: May 2013

By delving into the endless game of narration and by taking culture as a meaningful practice, this paper seeks to uncover key elements of mediation in order to consider and interpret the lifestyles, beliefs and power struggles shared in the context of what Homi Bhabha calls ‘cultural differences’. The analysis of an Iraqi leader’s travel report of a trip to Brazil in 1865 questions the hegemonic narratives around cultural-political disputes sparked by African slaves in 1835 in the Brazilian state of Bahia. By pondering distance and proximity in a movement fraught with interwoven cultures and processes of inventing the other, this article highlights a scenario of relationships and power use that stresses the symptoms and markers of difference, and unveils the ways in which nineteenth-century Brazil invented the Muslim as ‘the other’.