bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of cellular uptake of genotoxic silica nanoparticles
Authors: Mu Qingshan , Hondow Nicole S , Krzemiński Łukasz , Brown Andy P , Jeuken Lars JC , Routledge Michael N 
Published: September 2012

Abstract
Mechanisms for cellular uptake of nanoparticles have important implications for nanoparticulate drug delivery and toxicity. We have explored the mechanism of uptake of amorphous silica nanoparticles of 14 nm diameter, which agglomerate in culture medium to hydrodynamic diameters around 500 nm. In HT29, HaCat and A549 cells, cytotoxicity was observed at nanoparticle concentrations ≥ 1 μg/ml, but DNA damage was evident at 0.1 μg/ml and above. Transmission electron microscopy (TEM) combined with energy-dispersive X-ray spectroscopy confirmed entry of the silica particles into A549 cells exposed to 10 μg/ml of nanoparticles. The particles were observed in the cytoplasm but not within membrane bound vesicles or in the nucleus. TEM of cells exposed to nanoparticles at 4°C for 30 minutes showed particles enter cells when activity is low, suggesting a passive mode of entry. Plasma lipid membrane models identified physical interactions between the membrane and the silica NPs. Quartz crystal microbalance experiments on tethered bilayer lipid membrane systems show that the nanoparticles strongly bind to lipid membranes, forming an adherent monolayer on the membrane. Leakage assays on large unilamellar vesicles (400 nm diameter) indicate that binding of the silica NPs transiently disrupts the vesicles which rapidly self-seal. We suggest that an adhesive interaction between silica nanoparticles and lipid membranes could cause passive cellular uptake of the particles.
A case report of para-esophageal bronchogenic cyst with esophageal communication
Authors: Wang Wuping , Ni Yunfeng , Zhang LiWang , Li Xiaofei , Ke Changkang , Lu Qiang , Cheng Qingshu 
Published: September 2012

Abstract
Paraesophageal bronchogenic cyst was one of common mediastinal congenital cystic lesions of foregut origin. Because of an intimate embryologic relationship with the esophagus, they were usually found intramural (intramural esophageal bronchogenic cysts) with the local esophageal mucosa being intact and the paraesophageal bronchogenic cysts were rarely communicated with esophageal lumen. We report a case of para-esophageal bronchogenic cyst communicating to the esophageal lumen thorough a pedicle of canal, which looked liked a diverticulum on X-ray. During the operation, a communication of paraesophageal bronchogenic cyst with esophageal was found and the pathology diagnosis were made then. The symptoms of chest pain and dysphagia were relieved immediately after operation. The follow-up was well 2 years after the surgery.
Daily administration of low molecular weight heparin increases Hepatocyte Growth Factor serum levels in gynaecological patients: pharmacokinetic parameters and clinical implications
Authors: Surbone Anna , Fuso Luca , Passera Roberto , Ferrero Annamaria , Marchese Cristiana , Martino Cosimo , Luchin Annalisa , Di Renzo Maria Flavia , Zola Paolo 
Published: September 2012

Abstract

Background
Hepatocyte Growth Factor (HGF) enhances cytotoxicity of paclitaxel (PTX) and cisplatin (CDDP) in human ovarian cancer cells. Because of potential pitfalls of HGF exogenous administration, we investigated whether HGF serum concentration might be alternatively raised in vivo by administering low molecular weight heparin (LMWH).

Methods
The main HGF pharmacokinetic parameters were evaluated following acute and chronic LMWH treatment. First, women, operated on for gynaecological tumors, were treated with a single dose of calcium nadroparin and studied for 12 hours. Next, women operated on for benign or malignant gynaecological tumors were treated daily with calcic nadroparin for one month. Subsequently, the biological activity of the measured HGF serum levels was tested in assays of ovarian cancer cell sensitization to drugs.

Results
In the short-term treated group, median HGF AUCss, Cmax and Caverage were about four-fold that of the control group, whereas Cmin was three-fold. In the patients treated chronically median HGF serum levels rose about six-fold in the first week, and decreased but remained significantly higher after one month. The pharmacokinetic of nadroparin-dependent HGF increase were similar in the two groups. The HGF concentrations measured after both acute and chronic treatment were found to be effective in sensitising ovarian cancer cells to chemotherapeutics.

Conclusions
This study raises the possibility of using LMWH to increase HGF serum concentration and to take advantage of its biological activities. In particular, nadroparin might be used as a chemo-potentiating agent in epithelial cell ovarian carcinoma through its action on HGF serum concentration.

Trial registration
ClinicalTrials.gov ID: NCT01523652
Circadian Gating of Epithelial-to-Mesenchymal Transition in Breast Cancer Cells Via Melatonin-Regulation of GSK3β
Authors: Mao Lulu , Dauchy Robert T. , Blask David E. , Slakey Lauren M. , Xiang Shulin , Yuan Lin , Dauchy Erin M. , Shan Bin , Brainard George C. , Hanifin John P. , Frasch Tripp , Duplessis Tamika T. , Hill Steven M. 
Published: September 2012

Abstract
Disturbed sleep-wake cycle and circadian rhythmicity are associated with cancer, but the underlying mechanisms are unknown. Employing a tissue-isolated human breast xenograft tumor nude rat model, we observed that glycogen synthase kinase 3β (GSK3β), an enzyme critical in metabolism and cell proliferation/survival, exhibits a circadian rhythm of phosphorylation in human breast tumors. Exposure to light-at-night suppresses the nocturnal pineal melatonin synthesis, disrupting the circadian rhythm of GSK3β phosphorylation. Melatonin activates GSK3β by inhibiting the serine-threonine kinase Akt phosphorylation, inducing β-catenin degradation and inhibiting epithelial-to-mesenchymal transition, a fundamental process underlying cancer metastasis. Thus, chronic circadian disruption by light-at-night via occupational exposure or age-related sleep disturbances may contribute to cancer incidence and the metastatic spread of breast cancer by inhibiting GSK3β activity and driving epithelial-to-mesenchymal transition in breast cancer patients.
Ctip2 is a dynamic regulator of epidermal proliferation and differentiation by integrating EGFR and Notch signaling
Authors: Zhang Ling-juan , Bhattacharya Shreya , Leid Mark , Ganguli-Indra Gitali , Indra Arup K. 
Published: September 2012

Summary
Epidermal morphogenesis results from a delicate balance between keratinocyte proliferation and differentiation, and this balance is perturbed upon deletion of transcription factor Ctip2. Here we demonstrate that Ctip2, in a cell autonomous manner, controls keratinocyte proliferation and cytoskeletal organization, and regulates the onset and maintenance of differentiation in keratinocytes in culture. Ctip2 integrates keratinocyte proliferation and the switch to differentiation by directly and positively regulating EGFR transcription in proliferating cells and Notch1 transcription in differentiating cells. In proliferative cells, the EGFR promoter is occupied by Ctip2, whereas Ctip2 is only recruited to the Notch1 promoter under differentiating conditions. Activation of EGFR signaling downregulates Ctip2 at the transcript level, whereas high calcium signaling triggers SUMOylation, ubiquitination and proteasomal degradation of Ctip2 at the protein level. Together, our findings demonstrate a novel mechanism(s) of Ctip2-mediated, coordinated control of epidermal proliferation and terminal differentiation, and identify a pathway of negative feedback regulation of Ctip2 during epidermal development.
Electron tomography of the microtubule cytoskeleton in multinucleated hyphae of Ashbya gossypii
Authors: Gibeaux Romain , Lang Claudia , Politi Antonio Z. , Jaspersen Sue L. , Philippsen Peter , Antony Claude 
Published: September 2012

Summary
We report the mechanistic basis guiding the migration pattern of multiple nuclei in hyphae of Ashbya gossypii. Using electron tomography, we reconstructed the cytoplasmic microtubule (cMT) cytoskeleton in three tip regions with a total of 13 nuclei and also the spindle microtubules of four mitotic nuclei. Each spindle pole body (SPB) nucleates three cMTs and most cMTs above a certain length grow according to their plus-end structure. Long cMTs closely align for several microns along the cortex, presumably marking regions where dynein generates pulling forces on nuclei. Close proximity between cMTs emanating from adjacent nuclei was not observed. The majority of nuclei carry duplicated side-by-side SPBs, which together emanate an average of six cMTs, in most cases in opposite orientation with respect to the hyphal growth axis. Such cMT arrays explain why many nuclei undergo short-range back and forth movements. Only occasionally do all six cMTs orient in one direction, a precondition for long-range nuclear bypassing. Following mitosis, daughter nuclei carry a single SPB with three cMTs. The increased probability that all three cMTs orient in one direction explains the high rate of nuclear bypassing observed in these nuclei. The A. gossypii mitotic spindle was found to be structurally similar to that of Saccharomyces cerevisiae in terms of nuclear microtubule (nMT) number, length distribution and three-dimensional organization even though the two organisms differ significantly in chromosome number. Our results suggest that two nMTs attach to each kinetochore in A. gossypii and not only one nMT like in S. cerevisiae.
A flavonol present in cocoa [(−)epicatechin] enhances snail memory
Authors: Fruson Lee , Dalesman Sarah , Lukowiak Ken 
Published: September 2012

SUMMARY
Dietary consumption of flavonoids (plant phytochemicals) may improve memory and neuro-cognitive performance, though the mechanism is poorly understood. Previous work has assessed cognitive effects in vertebrates; here we assess the suitability of Lymnaea stagnalis as an invertebrate model to elucidate the effects of flavonoids on cognition. (−)Epicatechin (epi) is a flavonoid present in cocoa, green tea and red wine. We studied its effects on basic snail behaviours (aerial respiration and locomotion), long-term memory (LTM) formation and memory extinction of operantly conditioned aerial respiratory behaviour. We found no significant effect of epi exposure (15 mg l−1) on either locomotion or aerial respiration. However, when snails were operantly conditioned in epi for a single 0.5 h training session, which typically results in memory lasting ~3 h, they formed LTM lasting at least 24 h. Snails exposed to epi also showed significantly increased resistance to extinction, consistent with the hypothesis that epi induces a more persistent LTM. Thus training in epi facilitates LTM formation and results in a more persistent and stronger memory. Previous work has indicated that memory-enhancing stressors (predator kairomones and KCl) act via sensory input from the osphradium and are dependent on a serotonergic (5-HT) signalling pathway. Here we found that the effects of epi on LTM were independent of osphradial input and 5-HT, demonstrating that an alternative mechanism of memory enhancement exists in L. stagnalis. Our data are consistent with the notion that dietary sources of epi can improve cognitive abilities, and that L. stagnalis is a suitable model with which to elucidate neuronal mechanisms.
Backward flight in hummingbirds employs unique kinematic adjustments and entails low metabolic cost
Authors: Sapir Nir , Dudley Robert 
Published: September 2012

SUMMARYBackward flight is a frequently used transient flight behavior among members of the species-rich hummingbird family (Trochilidae) when retreating from flowers, and is known from a variety of other avian and hexapod taxa, but the biomechanics of this intriguing locomotor mode have not been described. We measured rates of oxygen uptake () and flight kinematics of Anna's hummingbirds, Calypte anna (Lesson), within a wind tunnel using mask respirometry and high-speed videography, respectively, during backward, forward and hovering flight. We unexpectedly found that in sustained backward flight is similar to that in forward flight at equivalent airspeed, and is about 20% lower than hovering . For a bird that was measured throughout a range of backward airspeeds up to a speed of 4.5 m s−1, the power curve resembled that of forward flight at equivalent airspeeds. Backward flight was facilitated by steep body angles coupled with substantial head flexion, and was also characterized by a higher wingbeat frequency, a flat stroke plane angle relative to horizontal, a high stroke plane angle relative to the longitudinal body axis, a high ratio of maximum:minimum wing positional angle, and a high upstroke:downstroke duration ratio. Because of the convergent evolution of hummingbird and some hexapod flight styles, flying insects may employ similar kinematics while engaged in backward flight, for example during station keeping or load lifting. We propose that backward flight behavior in retreat from flowers, together with other anatomical, physiological, morphological and behavioral adaptations, enables hummingbirds to maintain strictly aerial nectarivory.
Measurement of transplanted pancreatic volume using computed tomography: reliability by intra- and inter-observer variability
Authors: Lundqvist Eva , Segelsjö Monica , Andersson Anna , Magnusson Anders , Biglarnia Ali-Reza 
Published: September 2012

Background Unlike other solid organ transplants, pancreas allografts can undergo a substantial decrease in baseline volume after transplantation. This phenomenon has not been well characterized, as there are insufficient data on reliable and reproducible volume assessments. We hypothesized that characterization of pancreatic volume by means of computed tomography (CT) could be a useful method for clinical follow-up in pancreas transplant patients. Purpose To evaluate the feasibility and reliability of pancreatic volume assessment using CT scan in transplanted patients. Material and Methods CT examinations were performed on 21 consecutive patients undergoing pancreas transplantation. Volume measurements were carried out by two observers tracing the pancreatic contours in all slices. The observers performed the measurements twice for each patient. Differences in volume measurement were used to evaluate intra- and inter-observer variability. Results The intra-observer variability for the pancreatic volume measurements of Observers 1 and 2 was found to be in almost perfect agreement, with an intraclass correlation coefficient (ICC) of 0.90 (0.77-0.96) and 0.99 (0.98-1.0), respectively. Regarding inter-observer validity, the ICCs for the first and second measurements were 0.90 (range, 0.77-0.96) and 0.95 (range, 0.85-0.98), respectively. Conclusion CT volumetry is a reliable and reproducible method for measurement of transplanted pancreatic volume.
Electrocardiographic enigma of a classical disease: pellagra
Authors: Kavitha B , Balasubramanian R , Kumar Thirumal 
Published: September 2012

Summary Pellagra is caused by a deficiency of niacin. It is endemic in Africa and Asia where the staple diet of the many refugees or displaced people is corn-based and, therefore, nicotinic acid–deficient. It is also frequently seen in developed countries among chronic alcoholics or, occasionally, those suffering from anorexia nervosa. The usual manifestations are diarrhoea, dementia and dermatitis (the 3Ds), which if left untreated may lead to death. Cardiac manifestations and electrocardiographic changes are rarely seen in those suffering from pellagra. We present a case of pellagra in an alcoholic who presented with the classical rash over the upper limbs along with electrocardiographic changes but without any cardiac symptoms, both of which resolved dramatically after he had been given niacin supplements.
Pricing and Hedging with Discontinuous Functions: Quasi–Monte Carlo Methods and Dimension Reduction
Authors: Wang Xiaoqun , Tan Ken Seng 
Published: September 2012

Quasi–Monte Carlo (QMC) methods are important numerical tools in the pricing and hedging of complex financial instruments. The effectiveness of QMC methods crucially depends on the discontinuity and the dimension of the problem. This paper shows how the two fundamental limitations can be overcome in some cases. We first study how path-generation methods (PGMs) affect the structure of the discontinuities and what the effect of discontinuities is on the accuracy of QMC methods. The insight is that the discontinuities can be QMC friendly (i.e., aligned with the coordinate axes) or not, depending on the PGM. The PGMs that offer the best performance in QMC methods are those that make the discontinuities QMC friendly. The structure of discontinuities can affect the accuracy of QMC methods more significantly than the effective dimension. This insight motivates us to propose a novel way of handling the discontinuities. The basic idea is to align the discontinuities with the coordinate axes by a judicious design of a method for simulating the underlying processes. Numerical experiments demonstrate that the proposed method leads to dramatic variance reduction in QMC methods for pricing options and for estimating Greeks. It also reduces the effective dimension of the problem. This paper was accepted by Assaf Zeevi, stochastic models and simulation.
Diagnostic Accuracy Under Congestion
Authors: Alizamir Saed , de Véricourt Francis , Sun Peng 
Published: September 2012

In diagnostic services, agents typically need to weigh the benefit of running an additional test and improving the accuracy of diagnosis against the cost of delaying the provision of services to others. Our paper analyzes how to dynamically manage this accuracy/congestion trade-off. To that end, we study an elementary congested system facing an arriving stream of customers. The diagnostic process consists of a search problem in which the service provider conducts a sequence of imperfect tests to determine the customer's type. We find that the agent should continue to perform the diagnosis as long as her current belief that the customer is of a given type falls into an interval that depends on the congestion level as well as the number of performed tests thus far. This search interval should shrink as congestion intensifies and as the number of performed tests increases if additional conditions hold. Our study reveals that, contrary to diagnostic services without congestion, the base rate (i.e., the prior probability of the customer type) has an effect on the agent's search strategy. In particular, the optimal search interval shrinks when customer types are more ambiguous a priori, i.e., as the base rate approaches the value at which the agent is indifferent between types. Finally, because of congestion effects, the agent should sometimes diagnose the customer as being of a given type, even if test results indicate otherwise. All these insights disappear in the absence of congestion. This paper was accepted by Martin Lariviere, operations management.
First-Party Content and Coordination in Two-Sided Markets
Authors: Hagiu Andrei , Spulber Daniel 
Published: September 2012

The strategic use of first-party content by two-sided platforms is driven by two key factors: the nature of buyer and seller expectations (favorable versus unfavorable) and the nature of the relationship between first-party content and third-party content (complements or substitutes). Platforms facing unfavorable expectations face an additional constraint: their prices and first-party content investment need to be such that low (zero) participation equilibria are eliminated. This additional constraint typically leads them to invest more (less) in first-party content relative to platforms facing favorable expectations when first- and third-party content are substitutes (complements). These results hold with both simultaneous and sequential entry of the two sides. With two competing platforms—incumbent facing favorable expectations and entrant facing unfavorable expectations—and multi-homing on one side of the market, the incumbent always invests (weakly) more in first-party content relative to the case in which it is a monopolist.This paper was accepted by Bruno Cassiman, business strategy.
Vertical Differentiation with Variety-Seeking Consumers
Authors: Zeithammer Robert , Thomadsen Raphael 
Published: September 2012

We analyze price and quality competition in a vertically differentiated duopoly in which consumers have a preference for variety. The preference for variety is a consequence of diminishing marginal utility for repeated experiences with the same product. We find consumer variety seeking can either soften or intensify price competition, depending on the difference in firm qualities and the strength of consumer preference for variety. When the qualities are similar (or the consumer preference for variety is strong), prices and profits are higher than would be obtained in the absence of variety seeking. On the other hand, if qualities differ enough (or the preference for variety is weak), stronger preferences for variety are associated with more intense price competition and lower profits. When firms set their qualities before competing on price and the range of feasible qualities is restricted such that variety seeking softens competition, competing firms choose to minimally differentiate themselves from each other. The preference for variety can drive the firms to offer multiunit discounts, and the greater price flexibility from these discounts does not necessarily reduce profits relative to simple unit pricing. This paper was accepted by J. Miguel Villas-Boas, marketing.
Competitive Incentives: Working Harder or Working Smarter?
Authors: Bracha Anat , Fershtman Chaim 
Published: September 2012

Almost all jobs require a combination of cognitive effort and labor effort. This paper focuses on the effect that competitive incentive schemes have on the chosen combination of these two types of efforts. We use an experimental approach to show that competitive incentives may induce agents to work harder but not necessarily smarter. This effect was stronger for women. This paper was accepted by John List, behavioral economics.
How Costly Is Diversity? Affirmative Action in Light of Gender Differences in Competitiveness
Authors: Niederle Muriel , Segal Carmit , Vesterlund Lise 
Published: September 2012

Affirmative action is often criticized for causing reverse discrimination and lowering the qualifications of those hired under the policy. However, the magnitude of such adverse effects depends on whether the best suited candidate is hired absent the policy. Indeed affirmative action may compensate for the distortion discrimination imposes on the selection of candidates. This paper asks whether affirmative action can have a similar corrective impact when qualified individuals fail to apply for a job. We evaluate the effect of introducing a gender quota in an environment where high-performing women fail to enter competitions they can win. We show that guaranteeing women equal representation among winners increases their entry. The response exceeds that predicted by the change in probability of winning and is in part driven by women being more willing to compete against other women. The consequences are substantial as the boost in supply essentially eliminates the anticipated costs of the policy. This paper was accepted by Uri Gneezy, behavioral economics.