bluuebunny/crossref_metadata_2025 huggingface dataset:
HDAC6 controls the kinetics of platelet activation
Authors: Sadoul Karin , Wang Jin , Diagouraga Boubou , Vitte Anne-Laure , Buchou Thierry , Rossini Thérèse , Polack Benoît , Xi Xiaodong , Matthias Patrick , Khochbin Saadi
Published: September 2012

HDAC6, a major cytoplasmic deacetylase, is shown here to fine-tune the kinetics of platelet activation, a process that must be precisely regulated to ensure hemostasis after blood vessel injury while preventing pathologic thrombus formation. The discoid shape of resting platelets in the circulation is maintained by several highly acetylated microtubules organized in a marginal band. During platelet activation, microtubules undergo major reorganizations, which contribute to the shape change of activating platelets. We show that, during these activation-induced shape changes, a dramatic HDAC6-mediated tubulin deacetylation takes place, followed by microtubule reacetylation in spread platelets. In addition, although HDAC6-controlled tubulin deacetylation is not required for platelet activation, the capacity of HDAC6 to prevent tubulin hyperacetylation influences the speed of platelet spreading. These results are particularly important in view of HDAC6 inhibitors being currently used in clinical trials and represent the first example of cell signaling by lysine acetylation in platelet biology.
PTH expands short-term murine hemopoietic stem cells through T cells
Authors: Li Jau-Yi , Adams Jonathan , Calvi Laura M. , Lane Timothy F. , DiPaolo Richard , Weitzmann M. Neale , Pacifici Roberto
Published: September 2012

Intermittent parathyroid hormone (iPTH) treatment expands hemopoietic stem and progenitor cells (HSPCs), but the involved mechanisms and the affected HSPC populations are mostly unknown. Here we show that T cells are required for iPTH to expand short-term HSPCs (ST-HSPCs) and improve blood cell engraftment and host survival after BM transplantation. Silencing of PTH/PTH-related protein receptor (PPR) in T cells abrogates the effects of iPTH, thus demonstrating a requirement for direct PPR signaling in T cells. Mechanistically, iPTH expands ST-HSPCs by activating Wnt signaling in HSPCs and stromal cells (SCs) through T-cell production of the Wnt ligand Wnt10b. Attesting to the relevance of Wnt10b, iPTH fails to expand ST-HSPCs in mice with Wnt10b−/− T cells. Moreover, iPTH fails to promote engraftment and survival after BM transplantation in Wnt10b null mice. In summary, direct PPR signaling in T cells and the resulting production of Wnt10b play a pivotal role in the mechanism by which iPTH expands ST-HSPCs. The data suggest that T cells may provide pharmacologic targets for HSPC expansion.
Transmembrane prolyl 4-hydroxylase is a fourth prolyl 4-hydroxylase regulating EPO production and erythropoiesis
Authors: Laitala Anu , Aro Ellinoora , Walkinshaw Gail , Mäki Joni M. , Rossi Maarit , Heikkilä Minna , Savolainen Eeva-Riitta , Arend Michael , Kivirikko Kari I. , Koivunen Peppi , Myllyharju Johanna
Published: September 2012

An endoplasmic reticulum transmembrane prolyl 4-hydroxylase (P4H-TM) is able to hydroxylate the α subunit of the hypoxia-inducible factor (HIF) in vitro and in cultured cells, but nothing is known about its roles in mammalian erythropoiesis. We studied such roles here by administering a HIF-P4H inhibitor, FG-4497, to P4h-tm−/− mice. This caused larger increases in serum Epo concentration and kidney but not liver Hif-1α and Hif-2α protein and Epo mRNA levels than in wild-type mice, while the liver Hepcidin mRNA level was lower in the P4h-tm−/− mice than in the wild-type. Similar, but not identical, differences were also seen between FG-4497–treated Hif-p4h-2 hypomorphic (Hif-p4h-2gt/gt) and Hif-p4h-3−/− mice versus wild-type mice. FG-4497 administration increased hemoglobin and hematocrit values similarly in the P4h-tm−/− and wild-type mice, but caused higher increases in both values in the Hif-p4h-2gt/gt mice and in hematocrit value in the Hif-p4h-3−/− mice than in the wild-type. Hif-p4h-2gt/gt/P4h-tm−/− double gene-modified mice nevertheless had increased hemoglobin and hematocrit values without any FG-4497 administration, although no such abnormalities were seen in the Hif-p4h-2gt/gt or P4h-tm−/− mice. Our data thus indicate that P4H-TM plays a role in the regulation of EPO production, hepcidin expression, and erythropoiesis.
A novel multiplex-protein array for serum diagnostics of colon cancer: a case–control study
Authors: Bünger Stefanie , Haug Ulrike , Kelly Maria , Posorski Nicole , Klempt-Giessing Katja , Cartwright Andrew , Fitzgerald Stephen P , Toner Vicki , McAleer Damien , Gemoll Timo , Laubert Tilman , Büning Jürgen , Fellermann Klaus , Bruch Hans-Peter , Roblick Uwe J , Brenner Hermann , von Eggeling Ferdinand , Habermann Jens K
Published: September 2012

Background

More than 1.2 million new cases of colorectal cancer are reported each year worldwide. Despite actual screening programs, about 50% of the patients are diagnosed at advanced tumor stages presenting poor prognosis. Innovative screening tools could aid the detection at early stages and allow curative treatment interventions.

Methods

A nine target multiplex serum protein biochip was generated and evaluated using a training- and validation-set of 317 highly standardized, liquid nitrogen preserved serum samples comprising controls, adenomas, and colon cancers.

Results

Serum levels of CEA, IL-8, VEGF, S100A11, MCSF, C3adesArg, CD26, and CRP showed significant differences between cases and controls. The largest areas under the receiver operating characteristics curve were observed for CEA, IL-8, and CRP. At threshold levels yielding 90% specificity, sensitivities for CEA, IL-8 and CRP were 26%, 22%, and 17%, respectively. The most promising marker combinations were CEA + IL-8 reaching 37% sensitivity at 83% specificity and CEA + CRP with 35% sensitivity at 81% specificity. In an independent validation set CEA + IL-8 reached 47% sensitivity at 86% specificity while CEA + CRP obtained 39% sensitivity at 86% specificity. Early carcinomas were detected with 33% sensitivity for CEA + IL-8 and 28% for CEA + CRP.

Conclusions

Apart from CEA, IL-8, and CRP, the screening value of additional blood markers and the potential advantage of combining serum biochip testing with fecal occult blood testing needs to be studied. Multiplex biochip array technology utilizing serum samples offers an innovative approach to colorectal cancer screening.
Investigation of volatile organic biomarkers derived from Plasmodium falciparum in vitro
Authors: Wong Rina PM , Flematti Gavin R , Davis Timothy ME
Published: September 2012

Background

There remains a need for techniques that improve the sensitive detection of viable Plasmodium falciparum as part of diagnosis and therapeutic monitoring in clinical studies and usual-care management of malaria infections. A non-invasive breath test based on P. falciparum- associated specific volatile organic compounds (VOCs) could fill this gap and provide insights into parasite metabolism and pathogenicity. The aim of this study was to determine whether VOCs are present in the headspace above in vitro P. falciparum cultures.

Methods

A novel, custom-designed apparatus was developed to enable efficient headspace sampling of infected and non-infected cultures. Conditions were optimized to support cultures of high parasitaemia (>20%) to improve the potential detection of parasite-specific VOCs. A number of techniques for VOC analysis were investigated including solid phase micro-extraction using two different polarity fibres, and purge and trap/thermal desorption, each coupled to gas chromatography–mass spectrometry. Each experiment and analysis method was performed at least on two occasions. VOCs were identified by comparing their mass spectra against commercial mass spectral libraries.

Results

No unique malarial-specific VOCs could be detected relative to those in the control red blood cell cultures. This could reflect sequestration of VOCs into cell membranes and/or culture media but solvent extractions of supernatants and cell lysates using hexane, dichloromethane and ethyl acetate also showed no obvious difference compared to control non-parasitized cultures.

Conclusions

Future in vivo studies analysing the breath of patients with severe malaria who are harbouring a parasite biomass that is significantly greater than achievable in vitro may yet reveal specific clinically-useful volatile chemical biomarkers.
Some results on fixed points of asymptotically strict quasi-ϕ-pseudocontractions in the intermediate sense
Authors: Qin Xiaolong , Wang Lin , Kang Shin Min
Published: September 2012

In this paper, a new nonlinear mapping, asymptotically strict quasi-ϕ-pseudocontraction in the intermediate sense, is introduced. Projection algorithms are considered for the mapping. Strong convergence theorems for fixed points of the mapping are established based on projection algorithms in a real Banach space.

MSC:47H09, 47J05, 47J25.
Comment on ‘Fixed point theorems for contraction mappings in modular metric spaces, Fixed Point Theory and Applications, doi:10.1186/1687-1812-2011-93, 20 pages’
Authors: Dehghan H , Eshaghi Gordji M , Ebadian A
Published: September 2012

In this paper, we provide an example to show that some results obtained in [Mongkolkeha et al. in Fixed Point Theory Appl. 2011, doi:10.1186/1687-1812-2011-93] are not valid.

MSC:47H09, 47H10.
A pragmatic cluster randomized controlled trial of early intervention for chronic obstructive pulmonary disease by practice nurse-general practitioner teams: Study Protocol
Authors: Bunker Jeremy M , Reddel Helen K , Dennis Sarah M , Middleton Sandy , Van Schayck CP , Crockett Alan J , Hasan Iqbal , Hermiz Oshana , Vagholkar Sanjyot , Marks Guy B , Zwar Nicholas A
Published: September 2012

Background

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of disability, hospitalization, and premature mortality. General practice is well placed to diagnose and manage COPD, but there is a significant gap between evidence and current practice, with a low level of awareness and implementation of clinical practice guidelines. Under-diagnosis of COPD is a world-wide problem, limiting the benefit that could potentially be achieved through early intervention strategies such as smoking cessation, dietary advice, and exercise. General practice is moving towards more structured chronic disease management, and the increasing involvement of practice nurses in delivering chronic care.

Design

A pragmatic cluster randomised trial will test the hypothesis that intervention by a practice nurse-general practitioner (GP) team leads to improved health-related quality of life and greater adherence with clinical practice guidelines for patients with newly-diagnosed COPD, compared with usual care. Forty general practices in greater metropolitan Sydney Australia will be recruited to identify patients at risk of COPD and invite them to attend a case finding appointment. Practices will be randomised to deliver either practice nurse-GP partnership care, or usual care, to patients newly-diagnosed with COPD.

The active intervention will involve the practice nurse and GP working in partnership with the patient in developing and implementing a care plan involving (as appropriate), smoking cessation, immunisation, pulmonary rehabilitation, medication review, assessment and correction of inhaler technique, nutritional advice, management of psycho-social issues, patient education, and management of co-morbidities.

The primary outcome measure is health-related quality of life, assessed with the St George’s Respiratory Questionnaire 12 months after diagnosis. Secondary outcome measures include validated disease-specific and general health related quality of life measures, smoking and immunisation status, medications, inhaler technique, and lung function. Outcomes will be assessed by project officers blinded to patients’ randomization groups.

Discussion

This study will use proven case-finding methods to identify patients with undiagnosed COPD in general practice, where improved care has the potential for substantial benefit in health and healthcare utilization. The study provides the capacity to trial a new model of team-based assessment and management of newly diagnosed COPD in Australian primary care.

Trial registration

ACTRN12610000592044\
The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible
Authors: Monson Laura A , Cavaliere Christi M , Deshpande Sagar S , Ayzengart Alexander L , Buchman Steven R
Published: September 2012

The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague–Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction.
Efficient procedures for the numerical simulation of mid-size RNA kinetics
Authors: Aviram Iddo , Veltman Ilia , Churkin Alexander , Barash Danny
Published: September 2012

Motivation

Methods for simulating the kinetic folding of RNAs by numerically solving the chemical master equation have been developed since the late 90's, notably the programs Kinfold and Treekin with Barriers that are available in the Vienna RNA package. Our goal is to formulate extensions to the algorithms used, starting from the Gillespie algorithm, that will allow numerical simulations of mid-size (~ 60–150 nt) RNA kinetics in some practical cases where numerous distributions of folding times are desired. These extensions can contribute to analyses and predictions of RNA folding in biologically significant problems.

Results

By describing in a particular way the reduction of numerical simulations of RNA folding kinetics into the Gillespie stochastic simulation algorithm for chemical reactions, it is possible to formulate extensions to the basic algorithm that will exploit memoization and parallelism for efficient computations. These can be used to advance forward from the small examples demonstrated to larger examples of biological interest.

Software

The implementation that is described and used for the Gillespie algorithm is freely available by contacting the authors, noting that the efficient procedures suggested may also be applicable along with Vienna's Kinfold.
The pretreatment of corn stover with Gloeophyllum trabeum KU-41 for enzymatic hydrolysis
Authors: Gao Ziqing , Mori Toshio , Kondo Ryuichiro
Published: September 2012

Background

Pretreatment is an essential step in the enzymatic hydrolysis of biomass for bio-ethanol production. The dominant concern in this step is how to decrease the high cost of pretreatment while achieving a high sugar yield. Fungal pretreatment of biomass was previously reported to be effective, with the advantage of having a low energy requirement and requiring no application of additional chemicals. In this work, Gloeophyllum trabeum KU-41 was chosen for corn stover pretreatment through screening with 40 strains of wood-rot fungi. The objective of the current work is to find out which characteristics of corn stover pretreated with G. trabeum KU-41 determine the pretreatment method to be successful and worthwhile to apply. This will be done by determining the lignin content, structural carbohydrate, cellulose crystallinity, initial adsorption capacity of cellulase and specific surface area of pretreated corn stover.

Results

The content of xylan in pretreated corn stover was decreased by 43% in comparison to the untreated corn stover. The initial cellulase adsorption capacity and the specific surface area of corn stover pretreated with G. trabeum were increased by 7.0- and 2.5-fold, respectively. Also there was little increase in the cellulose crystallinity of pretreated corn stover.

Conclusion

G. trabeum has an efficient degradation system, and the results indicated that the conversion of cellulose to glucose increases as the accessibility of cellulose increases due to the partial removal of xylan and the structure breakage of the cell wall. This pretreatment method can be further explored as an alternative to the thermochemical pretreatment method.
Evaluation of the efficacy of topically administered imidacloprid + pyriproxyfen and orally administered spinosad against cat fleas (Ctenocephalides felis): Impact of treated dogs on flea life stages in a simulated home environment
Authors: Ross Douglas H , Arther Robert G , von Simson Cristiano , Doyle Veronica , Dryden Michael W
Published: September 2012

Background

Cat fleas, Ctenocephalides felis, are one of the most common ectoparasites infesting dogs and their environments. This study evaluated the efficacy of imidacloprid + pyriproxyfen (PPF) (Advantage® II for Dogs) and spinosad (Comfortis®) against established C. felis populations in dogs’ simulated home environments.

Methods

Thirty Beagle dogs were randomly assigned to three groups of 10 dogs each and treated twice (Study Days 0 and 28) with imidacloprid + PPF, spinosad tablets, or a negative control (untreated). Dogs were housed individually in controlled simulated home environments capable of supporting the flea life cycle. Flea infestations were established in these environments by infesting each dog with 100 adult cat fleas on Study Days −21, -16 and 1. The impact of the treatments on fleas in the dogs’ environments were assessed by collecting floor mat samples from each simulated home environment, incubating them for 32 days, and counting the number of emerging adult fleas. On Study Days 7, 14, 21, 28, 35, 42, 49 and 56, after collection of the cocoa matting samples, each dog was infested with an additional 5 ± 1 fleas to maintain the environmental infestations. Flea comb counts on dogs were conducted on Study Days 0 (pretreatment) and 63.

Results

From Study Days 7–28, flea infestations in the imidacloprid + PPF environments were significantly lower (p < 0.03) than those in the spinosad environments. Following the second treatment, flea infestations in all the imidacloprid + PPF environments fell to zero for the remainder of the study. In contrast, flea infestations persisted in some of the spinosad environments through the study’s end.

On Study Day 63 all 10 dogs treated with imidacloprid + PPF were flea free, while only one of the 10 spinosad treated dogs was flea free. Flea counts on the other 9 spinosad treated dogs ranged from 3 to 46 fleas/dog (geometric mean = 8.6). A mean of 405 adult fleas/animal were recovered from the control dogs on Study Day 63.

Conclusion

Flea infestations in environments of dogs treated with imidacloprid + PPF declined more rapidly than in those containing dogs treated with spinosad. Flea infestations were completely eliminated by Study Day 56 in environments of dogs treated with imidacloprid + PPF, but persisted through the study’s end in some of environments of dogs treated with spinosad.
Functional analysis of transcription factor binding sites in human promoters
Authors: Whitfield Troy W , Wang Jie , Collins Patrick J , Partridge E Christopher , Aldred Shelley Force , Trinklein Nathan D , Myers Richard M , Weng Zhiping
Published: September 2012

Background

The binding of transcription factors to specific locations in the genome is integral to the orchestration of transcriptional regulation in cells. To characterize transcription factor binding site function on a large scale, we predicted and mutagenized 455 binding sites in human promoters. We carried out functional tests on these sites in four different immortalized human cell lines using transient transfections with a luciferase reporter assay, primarily for the transcription factors CTCF, GABP, GATA2, E2F, STAT, and YY1.

Results

In each cell line, between 36% and 49% of binding sites made a functional contribution to the promoter activity; the overall rate for observing function in any of the cell lines was 70%. Transcription factor binding resulted in transcriptional repression in more than a third of functional sites. When compared with predicted binding sites whose function was not experimentally verified, the functional binding sites had higher conservation and were located closer to transcriptional start sites (TSSs). Among functional sites, repressive sites tended to be located further from TSSs than were activating sites. Our data provide significant insight into the functional characteristics of YY1 binding sites, most notably the detection of distinct activating and repressing classes of YY1 binding sites. Repressing sites were located closer to, and often overlapped with, translational start sites and presented a distinctive variation on the canonical YY1 binding motif.

Conclusions

The genomic properties that we found to associate with functional TF binding sites on promoters -- conservation, TSS proximity, motifs and their variations -- point the way to improved accuracy in future TFBS predictions.
Seismic reflection profiling of the Pyhäsalmi VHMS-deposit: A complementary approach to the deep base metal exploration in Finland
Authors: Heinonen Suvi , Imaña Marcello , Snyder David B. , Kukkonen Ilmo T. , Heikkinen Pekka J.
Published: September 2012

In the Pyhäsalmi case study, the seismic data is used in direct targeting of shallowly dipping mineralized zones in a massive sulfide ore system that was deformed in complex fold interference structures under high-grade metamorphic conditions. The Pyhäsalmi volcanic-hosted massive sulfide (VHMS) deposit ([Formula: see text]) is located in a Proterozoic volcanic belt in central Finland. Acoustic impedance of Pyhäsalmi ore ([Formula: see text]) is distinct from the host rocks ([Formula: see text]), enabling its detection with seismic reflection methods. Drill-hole logging further indicates that the seismic imaging of a contact zone between mafic and felsic volcanic rocks possibly hosting additional mineralizations is plausible. Six seismic profiles showed discontinuous reflectors and complicated reflectivity patterns due to the complex geology. The most prominent reflective package at 1–2 km depth was produced by shallowly dipping contacts between interlayered felsic and mafic volcanic rocks. The topmost of these bright reflections coincides with high-grade zinc mineralization. Large acoustic impedances associated with the sulfide minerals locally enhanced the reflectivity of this topmost contact zone which could be mapped over a wide area using the seismic data. Seismic data enables extrapolation of the geologic model to where no drill-hole data exists; thus, seismic reflection profiling is an important method for defining new areas of interest for deep exploration.
Theoretical estimate of the tube-wave modulus in arbitrarily anisotropic media: Comparisons between semianalytical, FEM, and approximate solutions
Authors: Karpfinger Florian , Jocker Jeroen , Prioul Romain
Published: September 2012

We revisit an exact, quasi-static, semianalytical solution for the effective tube-wave modulus for any borehole orientation relative to an anisotropic medium of arbitrary symmetry and strength. This exact solution agrees very well with the one computed from a finite-element model (FEM). We compare the exact solution with several analytical approximations for well deviations from vertical to horizontal and for different transversely isotropic media. For elliptic media, we show that the Rice and Chi-Tang approximations are in accordance with the exact solution because they depend only on the horizontal and vertical shear-wave velocity. For anelliptic media, we show that the maximum difference between the exact solution and the Norris-Sinha or Chi-Tang perturbation approximation becomes increasingly significant with increasing degree of anellipticity and shear-wave anisotropy with a maximum error of 5%, 10%, and 18% for Thomsen parameters less than 0.25, 0.4, and 0.6, respectively.
Migration velocity analysis using traveltime wavefield tomography
Authors: Al-Saleh Saleh M. , Jiao Jianwu
Published: September 2012

We introduce an integrated wave-equation technique for migration velocity analysis (MVA) that consists of three steps: (1) forming the extended data, (2) approximating the correct transmitted wavefield, and (3) using wavefield tomography to update the velocity model. In the first step, the crosscorrelation imaging condition is relaxed to produce other nonzero-lag common image gathers (CIG) that, combined, form a common image cube (CIC). Slicing the CIC at different crosscorrelation lags forms a series of CIGs. Flattened events will occur in the CIGs at a lag other than the zero-lag when an incorrect velocity model is used in the migration. In the second step, for each event on the CIG, we pick the focusing depth and crosscorrelation lag at which it is flattest. We then model a Green’s function by seeding a source at the focusing depth using one-way wave equation modeling, then shift the modeled wavefield with the focusing crosscorrelation lag. This process is repeated for the other primary events at different lateral and vertical positions. The result is a set of modeled data whose wavefield approximates the wavefield that would have been generated if the correct velocity model had been used to simulate these gathers. We then apply wavefield tomography on these data-driven modeled data to update the velocity model. Our inversion scheme is based on wave-equation traveltime tomography that can update the velocity model in the presence of large velocity errors and a complex environment. Tests on synthetic and real 2D seismic data confirm the method’s effectiveness in building velocity models in complex structural areas that have large lateral velocity variations.
3D reflection seismic imaging for open-pit mine planning and deep exploration in the Kevitsa Ni-Cu-PGE deposit, northern Finland
Authors: Malehmir Alireza , Juhlin Christopher , Wijns Chris , Urosevic Milovan , Valasti Petri , Koivisto Emilia
Published: September 2012

A 3D reflection seismic survey was conducted over an area of about [Formula: see text] at the Kevitsa Ni-Cu-PGE (platinum group elements) orebody, northern Finland, where open-pit mining started in mid-2012. The principal objective of the survey was to image major fault and fracture zones at depth that may have an impact on the mine stability and safety. Mine planning would then take into account the geometry of these zones at Kevitsa. Processing results, using conventional prestack DMO and poststack migration methods, show gently dipping and steeply dipping reflections from depths of approximately 2 km to as shallow as 150–200 m. Many of the reflections are interpreted to originate from either fault systems or internal magmatic layering within the Kevitsa main intrusion. Further correlation between the surface seismic data and VSP data suggests that numerous faults are present in the imaged volume based upon time shifts or phase changes along horizontal to gently dipping reflections. Some of these faults cross the planned open-pit mine at depths of about 300–500 m, and are therefore critical for geotechnical planning. In terms of in-pit and near-mine exploration, the magmatic layering internal to the intrusion controls the distribution of the bulk of economic mineralization. The ability to image this magmatic layering could therefore guide future drilling, particularly by constraining the presumed lateral extents of the resource area. Exploration also will target discrete reflectors that potentially represent higher-grade sulfide mineralization.
Delineating ophiolite-derived host rocks of massive sulfide Cu-Co-Zn deposits with 2D high-resolution seismic reflection data in Outokumpu, Finland
Authors: Kukkonen I. T. , Heinonen S. , Heikkinen P. , Sorjonen-Ward P.
Published: September 2012

Seismic reflection data was applied to a study of the upper crustal structures in the Outokumpu mining and exploration area in eastern Finland. The Cu-Co-Zn sulfide ore deposits of the Outokumpu area are hosted by Palaeoproterozoic ophiolite-derived altered ultrabasic rocks (serpentinite, skarn rock, and quartz rock) and black schist within turbiditic mica schist. Mining in the Outokumpu area has produced a total of 36 Mt of ore from three historical and one active mine. Seismic data comprises 2D vibroseis data surveyed along a network of local roads. The seismic sections provide a comprehensive 3D view of the reflective structures. Acoustic rock properties from downhole logging and synthetic seismograms indicate that the strongly reflective packages shown in the seismic data can be identified as the host-rock environments of the deposits. Reflectors show excellent continuity along the structural grain of the ore belt, which allows correlating reflectors with surface geology, magnetic map, and drilling sections into a broad 3D model of the ore belt. Massive ores have acoustic properties that make them directly detectable with seismic reflection methods assuming the deposit size is sufficient for applied seismic wavelengths. The seismic data revealed numerous interesting high-amplitude reflectors within the interpreted host-rock suites potentially coinciding with sulfides.
The Casteized Consciousness: Literary Realism and the Politics of Particularism
Authors: Gajarawala Toral Jatin
Published: September 2012

A product of the last two decades, Dalit (“untouchable caste”) literature in Hindi has fashioned itself as a modern protest literature, drawing on the cultural and political traditions of other Indian languages and literatures. But Hindi Dalit literature is unique in that its fictional movement against casteism, atrocity, and historical elision has effectively embraced the ideologies of realism while developing a strident critique of modernist aesthetics. This essay deconstructs that realist turn by tracing it through the question of caste. Gajarawala reads the present embrace of an aesthetics and politics of realism via the seminal text on caste, Mulk Raj Anand’s Untouchable (1935), which sets a literary precedent for the representation of untouchability. In it modernist form allows for a particular reading of untouchability; through the abstractions of both Marxism and metaphor, untouchability becomes a universalized condition of subjection, and the goal is the production of political consciousness. Contemporary Hindi Dalit texts, however, deny the very category of the universal and insist on consciousness as a given; they do so by relying on the metonymic modes of the realist. Thus realism offers a putative solution to the problem of casteist assertion in the cultural sphere.
Oscillation of APC/C activity during cell cycle arrest promotes centrosome amplification
Authors: Prosser Suzanna L. , Samant Mugdha D. , Baxter Joanne E. , Morrison Ciaran G. , Fry Andrew M.
Published: September 2012

Centrosome duplication is licensed by the disengagement, or ‘uncoupling’, of centrioles during late mitosis. However, arrest of cells in G2 can trigger premature centriole disengagement. Here, we show that premature disengagement results from untimely activation of the APC/C leading to securin degradation and release of active separase. APC/C activation during G2 arrest is dependent on Plk1-mediated degradation of the APC/C inhibitor, Emi1, but Plk1 also has a second APC/C-independent role in promoting disengagement. Importantly, APC/C and Plk1 activity also stimulate centriole disengagement in response to hydroxyurea or DNA damage-induced cell cycle arrest and this leads to centrosome amplification. However, the re-duplication of disengaged centrioles is dependent on Cdk2 activity and Cdk2 activation coincides with a subsequent inactivation of the APC/C and re-accumulation of cyclin A. Release from these arrests leads to mitotic entry but, due to the presence of disengaged and/or amplified centrosomes, formation of abnormal mitotic spindles that lead to chromosome missegregation. Thus, oscillation of APC/C activity during cell cycle arrest promotes both centrosome amplification and genome instability.
RAC1 in keratinocytes regulates crosstalk to immune cells by Arp2/3 dependent control of STAT1
Authors: Pedersen Esben , Wang Zhipeng , Stanley Alanna , Peyrollier Karine , Rösner Lennart M. , Werfel Thomas , Quondamatteo Fabio , Brakebusch Cord
Published: September 2012

Crosstalk between keratinocytes and immune cells is crucial for the immunological barrier function of the skin and aberrant crosstalk contributes to inflammatory skin diseases. Using mice with a keratinocyte-restricted deletion of the RAC1 gene we found that RAC1 in keratinocytes plays an important role in modulating the interferon (IFN) response in skin. RAC1 mutant mice showed increased sensitivity in an irritant contact dermatitis model, abnormal keratinocyte differentiation, and increased expression of immune response genes including the IFN signal transducer STAT1.

Loss of RAC1 in keratinocytes decreased actin polymerization in vivo and in vitro and caused Arp2/3 dependent expression of STAT1, increased interferon sensitivity and upregulation of aberrant keratinoctye differentiation markers. This is inhibitable by the AP-1 inhibitor tanshinone IIA. Loss of RAC1 makes keratinocytes hypersensitive towards inflammatory stimuli both in vitro and in vivo, suggesting a major role for RAC1 in regulating the crosstalk between the epidermis and the immune system.
Dispensable ATP permeability of Pannexin 1 channels in a heterologous system and in mammalian taste cells
Authors: Romanov R. A. , Bystrova M. F. , Rogachevskaya O. A. , Sadovnikov V. B. , Shestopalov V. I. , Kolesnikov S. S.
Published: September 2012

Afferent output in taste cells of the type II is mediated by ATP liberated through ion channels. It is widely accepted that Panx1 channels are responsible for ATP release in diverse cells. While biophysical evidence implicates slowly deactivating ion channels in ATP secretion in taste cells, recombinant Panx1 activates and deactivates rapidly. This inconsistency might indicate that cellular context specifies Panx1 functioning. We cloned Panx1 from the murine taste tissue and heterologously expressed it in cells of three different lines. In cells of each type, HEK-293, CHO, or neuroblastoma SK-N-SH, Panx1 transfection yielded outwardly rectifying anion channels exhibiting fast gating and negligible permeability to anions exceeding 250 Da. Despite expression, Panx1 did not endow host cells with the ability to liberate ATP upon stimulation, questioning whether Panx1 is involved in taste-related ATP secretion. This issue was addressed using mice with genetic ablation of the Panx1 gene. The ATP-biosensor assay revealed that in taste cells devoid of Panx1, ATP secretion was robust and apparently unchanged compared to control. Our data suggest that Panx1 alone forms a channel with insufficient permeability to ATP. Perhaps, a distinct subunit and/or a regulatory circuit absent in taste cells are required to enable a high ATP-permeability mode of a native Panx1-based channel.
An Interpretation of Enhancement and Suppression Effects of Charged Polymers on the Complexation Equilibria of Co2+/SCN− System in Aqueous Solutions
Authors: Kamachi Masashi , Miyajima Tohru , Takisawa Noboru
Published: September 2012

The change in the magnitude of the formation of [Co(NCS)4]2− in a Co2+/SCN− complexation system with the addition of negatively or positively charged polymers has been monitored spectroscopically. Formation of the tetrahedral complexes was suppressed by the addition of poly(vinylsulfonate) ions, i.e., the magnitude of the formation decreased monotonously with an increase in the anionic polymer concentration. On the other hand, the complexation was enhanced by the presence of poly(diallyldimethylammonium) ions, i.e., the magnitude increased drastically with a small addition of the cationic polymer followed by an abrupt decrease with a further increase in the polymer concentration. These peculiar phenomena depending on the nature and the concentration of charged polymers can be interpreted quantitatively by assuming a volume element (a polyelectrolyte phase) formed around the linear polymer backbone.
Preparation of Monodispersed Spherical Titania–Octadecylamine Particles Containing Silane-Coupling Reagents
Authors: Shiba Kota , Sato Soh , Ogawa Makoto
Published: September 2012

Well-defined spherical titania–octadecylamine (titania–ODA) (titania: titanium dioxide) hybrid particles containing silane-coupling reagents including aminopropyl, sulfanylpropyl, octadecyl, and phenyl groups (molar Ti:silane-coupling reagent ratio of 50:1) were prepared by sol–gel reaction of titanium tetraisopropoxide with the aid of a flow reactor. Average particle sizes were 520, 380, 540, and 510 nm for aminopropyl, sulfanylpropyl, octadecyl, and phenyl group containing particles, respectively. ODA was removed by washing the as-synthesized products with acidic EtOH, resulting in the formation of organosilyl group containing nanoporous titania. The porosity was investigated by the nitrogen adsorption/desorption isotherms (BET surface area of 250 to 400 m2 g−1) and the surface hydrophilicity/hydrophobicity is discussed based on the water and benzene vapor adsorption/desorption isotherms. Crystallization of anatase within the spherical particles is possible by postsynthetic hot water or hydrothermal treatment.
Self-Assembly of Zinc Bacteriochlorophyll d Derivative Possessing a Triethoxysilyl Group at the 17-Propionate Residue
Authors: Takahashi Naoya , Shoji Sunao , Tamiaki Hitoshi , Saga Yoshitaka
Published: September 2012

Transformation of pigment assembly in photosynthetic supramolecules is an important event in the performance of efficient photosynthetic activities, and model systems mimicking such transformation are useful to elucidate dynamic processes in natural photosynthetic systems. In this paper, we report stimuli-induced self-aggregation of a synthetic zinc bacteriochlorophyll d derivative possessing a triethoxysilyl group at the 17-propionate (Zn chlorin 1) as a model system of chlorosomes, which are extramembranous and major light-harvesting complexes in green photosynthetic bacteria. A mixture of monomeric and dimeric species of epimerically pure Zn chlorin 1 was gradually converted into chlorosomal self-aggregates that exhibited a red-shifted Qy absorption band and the CD signal at the corresponding region around 750 nm in an aqueous alkaline solution. The finally obtained visible absorption and CD spectra of 1 under the alkaline conditions were almost identical to the spectra of 1 lacking ethoxy groups by alkaline hydrolysis in advance, indicating that the above spectral changes of 1 observed under the alkaline conditions were ascribable to hydrolysis of the ethoxysilyl group in 1. The alteration of assembling states of synthetic zinc chlorin 1 triggered by its chemical modification will be a clue to the construction of model systems for in vivo formation of chlorosomes in green photosynthetic bacteria.
A Special Focus on the Photodegradation of 6′-Indolino-1-isobutyl-3,3-dimethylspiro[indoline-2,3′-[3H]naphtho[2,1-b][1,4]oxazine]
Authors: Alberti Angelo , Aubert Claude , Campredon Mylène , Demadrille Renaud
Published: September 2012

The photodegradation of 6′-indolino-1-isobutyl-3,3-dimethylspiro[indoline-2,3′-[3H]naphtho[2,1-b][1,4]oxazine] (1) following exposure to polychromatic light, was investigated in fluid solution (toluene, T) and in a solid matrix (polyurethane, PU). The photoproducts formed under irradiation were identified using HPLC and GC/MS. These included, beside the expected degradation derivatives, some new photoproducts derived from a secondary degradation pathway.
Alternative Mechanistic Scheme for Salt Effects on Solvolysis Reactions of Haloalkanes and Related Compounds in Binary DMSO/H2O Solvent Mixture
Authors: Hojo Masashi , Aoki Sho
Published: September 2012

In 75% (v/v) DMSO/H2O solvent mixture, salt effects on the solvolysis reaction rates of haloalkanes and related compounds (RX) have been examined. In spite of the decreased water activity in the solvent mixture, the log(k/s−1) values of typical SN1 substrates, such as 1-bromoadamantane, increase with increasing concentration of added metal perchlorates (the order: Li+ < Na+ < Mg2+ < Ba2+), which is attributed to the direct chemical interaction between the leaving-group anion and the metal cation in the “modified” solution. Contrastingly, the log(k/s−1) value of an SN2 substrate decreases with increasing concentration of the metal perchlorates. When nonmetallic salts containing anions (Y− = Cl− or Br−) different from RX (X− = Cl−, Br−, or TsO−) are present, solvolyses of SN2, such as 1-bromohexane, are subjected to an anion-exchange reaction. By the detailed examination of Δlog(k/s−1)/Δ[Mg(ClO4)2] for typical SN1, SN1–SN2 borderline, and SN2 substrates, we were able to demonstrate a linearity between the Mg(ClO4)2 effects in the solvolysis rates and the carbocation stabilities expressed by the Gibbs free energy values (ΔG) of RX in the gas phase. The salt effects on the solvolyses of SN1 to SN2 substrates are accounted for without relying on Winstein’s reaction scheme or the arbitrary function of ion pairs of two types.
Hydrogenation of Phenol Using Silica-Supported Pd and PdAu Catalysts in the Presence of H2 and O2
Authors: Okada Shusuke , Fujiwara Kensei , Kamegawa Takashi , Mori Kohsuke , Yamashita Hiromi
Published: September 2012

2-Cyclohexen-1-one can be synthesized from phenol using silica-supported Pd catalyst by hydrogenation under coexisting hydrogen and oxygen gases. The effects of hydrogen and oxygen ratio, solvent, and alloying Pd with Au were investigated. Similar transformations toward corresponding cyclic enones were observed in other phenolic compounds.
MicroRNA hsa-let-7g targets lectin-like oxidized low-density lipoprotein receptor-1 expression and inhibits apoptosis in human smooth muscle cells
Authors: Ding Zufeng , Wang Xianwei , Khaidakov Magomed , Liu Shijie , Mehta Jawahar L
Published: September 2012

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has been identified as a major receptor for oxidatively modified low density lipoprotein (ox-LDL) in endothelial cells and smooth muscle cells (SMCs). MicroRNAs are small non-coding RNAs that regulate gene expression. Very few studies have reported regulation of LOX-1 expression by microRNAs in SMCs. The present study demonstrates that the microRNA hsa-let-7g can inhibit LOX-1 expression in a time- and dose-dependent fashion, and subsequently inhibit ox-LDL uptake in and proliferation of human aortic SMCs. We also show that hsa-let-7g can reduce SMC apoptosis by down-regulation of cytochrome c and Smac/Diablo and upregulation of Bcl-xL and Bcl-2 expression. Furthermore, we show that hsa-let-7g reduces ox-LDL-induced increase in the expression of NADPH oxidase (p22phox and p47phox subunits) and subsequent intracellular reactive oxygen species generation, phosphorylation of p44/42 mitogen-activated protein kinase and nuclear factor-kappaB p65 expression. These observations suggest that hsa-let-7g is a critical regulator of SMC apoptosis, and may be suitable for therapeutic intervention in disease states characterized by LOX-1 over-expression.
Online Stochastic Matching: Online Actions Based on Offline Statistics
Authors: Manshadi Vahideh H. , Gharan Shayan Oveis , Saberi Amin
Published: September 2012

We consider the online stochastic matching problem proposed by Feldman et al. [Feldman J, Mehta A, Mirrokni VS, Muthukrishnan S (2009) Online stochastic matching: Beating 1 − 1/e. Annual IEEE Sympos. Foundations Comput. Sci. 117–126] as a model of display ad allocation. We are given a bipartite graph; one side of the graph corresponds to a fixed set of bins, and the other side represents the set of possible ball types. At each time step, a ball is sampled independently from the given distribution and it needs to be matched upon its arrival to an empty bin. The goal is to maximize the number of allocations.

We present an online algorithm for this problem with a competitive ratio of 0.702. Before our result, algorithms with a competitive ratio better than 1 − 1/e were known under the assumption that the expected number of arriving balls of each type is integral. A key idea of the algorithm is to collect statistics about the decisions of the optimum offline solution using Monte Carlo sampling and use those statistics to guide the decisions of the online algorithm. We also show that our algorithm achieves a competitive ratio of 0.705 when the rates are integral.

On the hardness side, we prove that no online algorithm can have a competitive ratio better than 0.823 under the known distribution model (and henceforth under the permutation model). This improves upon the 5/6 hardness result proved by Goel and Mehta [Goel G, Mehta A (2008) Online budgeted matching in random input models with applications to adwords. ACM-SIAM Symposium Discrete Algorithms 982–991] for the permutation model.
Stochastic Preplanned Household Activity Pattern Problem with Uncertain Activity Participation (SHAPP)
Authors: Gan Li Ping , Recker Will
Published: September 2012

The so-called activity-based approach to analysis of human interaction with the social and physical environments dates back to the original time-space geography works of Hägerstrand and his colleagues at the Lund School in 1970. Despite their obvious theoretical attractiveness, activity-based approaches to understanding and predicting travel behavior have suffered from the absence of an analytical framework that unifies the complex interactions among the resource allocation decisions made by households in conducting their daily affairs outside the home while preserving the utility-maximizing principles presumed to guide such decisions. In this paper, we develop a computationally tractable system, based on an extension and modification of some rather well-known network-based formulations in operations research, to model human dynamics in uncertain environments. The research builds on the mathematical programming formulation of the household activity pattern problem by embedding stochastic elements in the planned household activity schedule decision process that capture the uncertainty of the need for rescheduling.