bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I Study of Quizartinib Administered Daily to Patients With Relapsed or Refractory Acute Myeloid Leukemia Irrespective of FMS-Like Tyrosine Kinase 3–Internal Tandem Duplication Status
Authors: Cortes Jorge E. , Kantarjian Hagop , Foran James M. , Ghirdaladze Darejan , Zodelava Mamia , Borthakur Gautam , Gammon Guy , Trone Denise , Armstrong Robert C. , James Joyce , Levis Mark
Published: September 2013

Purpose

FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) are associated with early relapse and poor survival. Quizartinib potently and selectively inhibits FLT3 kinase activity in preclinical AML models.

Patients and Methods

Quizartinib was administered orally at escalating doses of 12 to 450 mg/day to 76 patients (median age, 60 years; range, 23 to 86 years; with a median of three prior therapies [range, 0 to 12 therapies]), enrolled irrespective of FLT3-ITD mutation status in a phase I, first-in-human study in relapsed or refractory AML.

Results

Responses occurred in 23 (30%) of 76 patients, including 10 (13%) complete remissions (CR) of any type (two CRs, three CRs with incomplete platelet recovery [CRp], five CRs with incomplete hematologic recovery [CRi]) and 13 (17%) with partial remissions (PRs). Of 17 FLT3-ITD–positive patients, nine responded (53%; one CR, one CRp, two CRis, five PRs); of 37 FLT3-ITD–negative patients, five responded (14%; two CRps, three PRs); of 22 with FLT3-ITD–indeterminate/not tested status, nine responded (41%; one CR, three CRis, five PRs). Median duration of response was 13.3 weeks; median survival was 14.0 weeks. The most common drug-related adverse events (> 10% incidence) were nausea (16%), prolonged QT interval (12%), vomiting (11%), and dysgeusia (11%); most were ≤ grade 2. The maximum-tolerated dose was 200 mg/day, and the dose-limiting toxicity was grade 3 QT prolongation. FLT3-ITD phosphorylation was completely inhibited in an in vitro plasma inhibitory assay.

Conclusion

Quizartinib has clinical activity in patients with relapsed/refractory AML, particularly those with FLT3-ITD, and is associated with an acceptable toxicity profile.
Modifiable Risk Factors and Major Cardiac Events Among Adult Survivors of Childhood Cancer
Authors: Armstrong Gregory T. , Oeffinger Kevin C. , Chen Yan , Kawashima Toana , Yasui Yutaka , Leisenring Wendy , Stovall Marilyn , Chow Eric J. , Sklar Charles A. , Mulrooney Daniel A. , Mertens Ann C. , Border William , Durand Jean-Bernard , Robison Leslie L. , Meacham Lillian R.
Published: September 2013

Purpose

To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer.

Patients and Methods

Among 10,724 5-year survivors (median age, 33.7 years) and 3,159 siblings in the Childhood Cancer Survivor Study, the prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity was determined, along with the incidence and severity of major cardiac events such as coronary artery disease, heart failure, valvular disease, and arrhythmia. On longitudinal follow-up, rate ratios (RRs) of subsequent cardiac events associated with cardiovascular risk factors and cardiotoxic therapy were assessed in multivariable Poisson regression models.

Results

Among survivors, the cumulative incidence of coronary artery disease, heart failure, valvular disease, and arrhythmia by 45 years of age was 5.3%, 4.8%, 1.5%, and 1.3%, respectively. Two or more cardiovascular risk factors were reported by 10.3% of survivors and 7.9% of siblings. The risk for each cardiac event increased with increasing number of cardiovascular risk factors (all Ptrend < .001). Hypertension significantly increased risk for coronary artery disease (RR, 6.1), heart failure (RR, 19.4), valvular disease (RR, 13.6), and arrhythmia (RR, 6.0; all P values < .01). The combined effect of chest-directed radiotherapy plus hypertension resulted in potentiation of risk for each of the major cardiac events beyond that anticipated on the basis of an additive expectation. Hypertension was independently associated with risk of cardiac death (RR, 5.6; 95% CI, 3.2 to 9.7).

Conclusion

Modifiable cardiovascular risk factors, particularly hypertension, potentiate therapy-associated risk for major cardiac events in this population and should be the focus of future interventional studies.
Maternal Hypoxia Increases the Susceptibility of Adult Rat Male Offspring to High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease
Authors: Su Yi-Ming , Lv Guo-Rong , Xie Jing-Xian , Wang Zhen-Hua , Lin Hui-Tong
Published: September 2013

Exposure to an adverse intrauterine environment increases the risk for adult metabolic syndrome. However, the influence of prenatal hypoxia on the risk of fatty liver disease in offspring is unclear. The purpose of the present study was to evaluate the role of reduced fetal oxygen on the development and severity of high-fat (HF) diet-induced nonalcoholic fatty liver disease (NAFLD). Based on design implicating 2 factors, ie, maternal hypoxia (MH) and postnatal HF diet, blood lipid and insulin levels, hepatic histology, and potential molecular targets were evaluated in male Sprague Dawley rat offspring. MH associated with postnatal HF diet caused a significant increase in plasma concentration of triglycerides, free fatty acids, low-density lipoprotein cholesterol, and insulin. Histologically, a more severe form of NAFLD with hepatic inflammation, hepatic resident macrophage infiltration, and progression toward nonalcoholic steatohepatitis was observed. The lipid homeostasis changes and insulin resistance caused by MH plus HF were accompanied by a significant down-regulation of insulin receptor substrate 2 (IRS-2), phosphoinositide-3 kinase p110 catalytic subunit, and protein kinase B. In MH rats, insulin-stimulated IRS-2 and protein kinase B (AKT) phosphorylation were significantly blunted as well as insulin suppression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Meanwhile, a significant up-regulation of lipogenic pathways was noticed, including sterol-regulatory element-binding protein-1 and fatty acid synthase in liver. Our results indicate that maternal hypoxia enhances dysmetabolic liver injury in response to an HF diet. Therefore, the offspring born in the context of maternal hypoxia may require special attention and follow-up to prevent the early development of NAFLD.
Developmental Timing of the Effects of Maternal Care on Gene Expression and Epigenetic Regulation of Hormone Receptor Levels in Female Rats
Authors: Peña Catherine Jensen , Neugut Y. Dana , Champagne Frances A.
Published: September 2013

Maternal care experienced during postnatal development has enduring effects on neuroendocrine function and behavior. Previous studies in rats have illustrated the effect of maternal licking/grooming (LG) on hormone receptors and maternal behavior of adult female offspring associated with altered DNA methylation. However, the developmental timing of these effects, which provide insight into the cellular and molecular pathways through which early experience alters later behavior, had not been explored. Here, we demonstrate the developmental emergence of these outcomes and use cross-fostering to identify sensitive periods for these effects. Estrogen receptor (ER)α and ERβ mRNA levels within the medial preoptic area (MPOA) of the hypothalamus were increased by postnatal day (PN)21 in female offspring of high LG dams; LG-associated increases in oxytocin receptor mRNA levels were observed beyond the weaning period. Quantification of ERα-immunoreactivity indicated a high degree of neuroanatomical specificity of LG effects within the MPOA that were observed by PN6. Reduced DNA methylation and histone 3 lysine 9 tri-methylation and increased histone 3 lysine 4 tri-methylation at the ERα gene promoter (Esr1) were detected at PN21 in high LG female offspring. Latency to engage in maternal behavior toward donor pups was significantly shorter among high LG females. Cross-fostering revealed that maternal sensitization and MPOA ERα levels are sensitive to maternal care experienced before but not after PN10. Differential windows of plasticity were identified for ERβ and oxytocin receptor mRNA levels. These studies contribute significantly to our understanding of the molecular, neurobiological, and behavioral pathways through which variation in maternal behavior is transmitted from one generation to the next.
Predicting Tumor Control After Resection Bed Radiosurgery of Brain Metastases
Authors: Luther Neal , Kondziolka Douglas , Kano Hideyuki , Mousavi Seyed H. , Engh Johnathan A. , Niranjan Ajay , Flickinger John C. , Lunsford L. Dade
Published: September 2013

BACKGROUND:

Stereotactic radiosurgery (SRS) to the resection bed of a brain metastasis is an important treatment option.

OBJECTIVE:

To identify factors associated with tumor progression after SRS of the resection bed of a brain metastasis and to evaluate patterns of failure for patients who eventually had tumor progression.

METHODS:

We performed a retrospective analysis of 120 patients who underwent tumor bed radiosurgery after an initial gross total resection. The mean imaging follow-up time was 55 weeks. The median margin dose was 16 Gy. Forty-seven patients (39.2%) underwent whole-brain radiation therapy before or shortly after SRS.

RESULTS:

Local tumor control was achieved in 103 patients (85.8%). Progression-free survival was 96% at 6 months, 87% at 12 months, and 74% at 24 months. Recurrence most commonly occurred deep in the cavity (65%) outside the planned treatment volume (PTV) margin (53%). PTV, cavity diameter, and a margin dose < 16 Gy significantly correlated with local failure. For patients with PTVs ≥ 8.0 cm3, local progression-free survival declined to 93% at 6 months, 83% at 12 months, and 65% at 24 months. Development or progression of distant metastases occurred in 40% of patients. Whole-brain radiation therapy was not associated with improved local control.

CONCLUSION:

Resection bed SRS for brain metastases provided excellent local control. The cavity PTV is predictive of tumor control. Because failure usually occurs outside the PTV, inclusion of a judicious 2- to 3-mm margin beyond the area of postoperative enhancement may be prudent.
Economic design in a long-distance migrating molluscivore: how fast-fuelling red knots in Bohai Bay, China, get away with small gizzards
Authors: Yang Hong-Yan , Chen Bing , Ma Zhi-jun , Hua Ning , van Gils Jan A. , Zhang Zheng-Wang , Piersma Theunis
Published: September 2013

We carried out an observational and experimental study to decipher how resource characteristics, in interaction with the predator's phenotype, constrain a fitness-determining performance measure, i.e. refuelling in a migrant bird. Two subspecies of red knot (Calidris canutus rogersi and C. c. piersmai) use northern Bohai Bay, Yellow Sea, China, for the final prebreeding stopover, during their 10,000–15,000 km long migrations between wintering and breeding areas. Here, they feed on small bivalves, especially 2–7 mm long Potamocorbula laevis. With an average stay of 29 days, and the need to store 80 g of fat for the onward flights to high-Arctic breeding grounds, red knots need to refuel fast. Using existing knowledge, we expected them to achieve this on the basis of (1) prey with high flesh to shell mass ratios, (2) large gizzards to crush the ingested molluscs, or (3) a combination of the two. Rejecting all three predictions, we found that red knots staging in Bohai Bay had the smallest gizzards on record (4.9±0.8 g, mean ± s.e.m., N=27), and also found that prey quality of P. laevis is much lower than predicted for the measured gizzard size (i.e. 1.3 rather than the predicted 4.5 kJ g−1 dry shell mass, DMshell). The estimated handling time of P. laevis (0.2 s) is much shorter than the observed time between two prey ingestions (0.7 s), indicating that prey handling time is no constraint. Based on field observations of dropping rates and on indoor digestion trails, the shell processing rate was estimated at 3.9 mg DMshell s−1, i.e. three times higher the rate previously predicted for red knots eating as fast as they can with the measured gizzard size. This is explained by the small and easily crushed P. laevis enabling high processing rates. As P. laevis also occurred in high densities, the metabolizable energy intake rate of red knots with small gizzards at 5 J s−1 was as high as at northward staging sites elsewhere in the world. Currently, therefore, food characteristics in Bohai Bay are such that red knots can refuel fast whilst economizing on the size of their gizzard. These time-stressed migrants thus provide an elegant example of symmorphosis.
Expression analysis of the speech-related genes FoxP1 and FoxP2 and their relation to singing behavior in two songbird species
Authors: Chen Qianqian , Heston Jonathan B. , Burkett Zachary D. , White Stephanie A.
Published: September 2013

Humans and songbirds are among the rare animal groups that exhibit socially learned vocalizations: speech and song, respectively. These vocal-learning capacities share a reliance on audition and cortico-basal ganglia circuitry, as well as neurogenetic mechanisms. Notably, the transcription factors Forkhead box proteins 1 and 2 (FoxP1, FoxP2) exhibit similar expression patterns in the cortex and basal ganglia of humans and the zebra finch species of songbird, among other brain regions. Mutations in either gene are associated with language disorders in humans. Experimental knock-down of FoxP2 in the basal ganglia song control region Area X during song development leads to imprecise copying of tutor songs. Moreover, FoxP2 levels decrease naturally within Area X when zebra finches sing. Here, we examined neural expression patterns of FoxP1 and FoxP2 mRNA in adult Bengalese finches, a songbird species whose songs exhibit greater sequence complexity and increased reliance on audition for maintaining their quality. We found that FoxP1 and FoxP2 expression in Bengalese finches is similar to that in zebra finches, including strong mRNA signals for both factors in multiple song control nuclei and enhancement of FoxP1 in these regions relative to surrounding brain tissue. As with zebra finches, when Bengalese finches sing, FoxP2 is behaviorally downregulated within basal ganglia Area X over a similar time course, and expression negatively correlates with the amount of singing. This study confirms that in multiple songbird species, FoxP1 expression highlights song control regions, and regulation of FoxP2 is associated with motor control of song.
The effect of substrate diameter and incline on locomotion in an arboreal frog
Authors: Herrel Anthony , Perrenoud Mats , Decamps Thierry , Abdala Virginia , Manzano Adriana , Pouydebat Emannuelle
Published: September 2013

Frogs are characterized by a unique morphology associated with their saltatory lifestyle. Yet, arboreal species show morphological specializations relative to other ecological specialists allowing them to hold on to narrow substrates. However, almost nothing is known about the effects of substrate characteristics on locomotion in frogs. Here, we quantified the 3D kinematics of forelimb movement for frogs moving across branches of different diameters (1 and 40 mm) and two different inclines (horizontal and 45 deg uphill). Our results show that grip types differ while moving across substrates of different diameters and inclines. The kinematics of the wrist, elbow and shoulder as well as the body position relative to the substrate also showed significant effects of individual, diameter and incline. Kinematic differences involved duration, velocity of movement and angular excursions. Differences were most pronounced for the proximal joints of the forelimb and effects for substrate diameter were greater than for incline. Interestingly, the effects of diameter and incline on both grip type and kinematics are similar to what has been observed for lizards and primates, suggesting that the mechanics of narrow substrate locomotion drive the kinematics of movement independent of morphology and phylogeny.
Dynamic biophotonics: female squid exhibit sexually dimorphic tunable leucophores and iridocytes
Authors: DeMartini Daniel G. , Ghoshal Amitabh , Pandolfi Erica , Weaver Aaron T. , Baum Mary , Morse Daniel E.
Published: September 2013

Loliginid squid use tunable multilayer reflectors to modulate the optical properties of their skin for camouflage and communication. Contained inside specialized cells called iridocytes, these photonic structures have been a model for investigations into bio-inspired adaptive optics. Here, we describe two distinct sexually dimorphic tunable biophotonic features in the commercially important species Doryteuthis opalescens: bright stripes of rainbow iridescence on the mantle just beneath each fin attachment and a bright white stripe centered on the dorsal surface of the mantle between the fins. Both of these cellular features are unique to the female; positioned in the same location as the conspicuously bright white testis in the male, they are completely switchable, transitioning between transparency and high reflectivity. The sexual dimorphism, location and tunability of these features suggest that they may function in mating or reproduction. These features provide advantageous new models for investigation of adaptive biophotonics. The intensely reflective cells of the iridescent stripes provide a greater signal-to-noise ratio than the adaptive iridocytes studied thus far, while the cells constituting the white stripe are adaptive leucophores – unique biological tunable broadband scatterers containing Mie-scattering organelles activated by acetylcholine, and a unique complement of reflectin proteins.
Synthesis of Novel Imidazo[1,2-a]pyrimidin-5(1H)-one Derivatives by Intramolecular Cycloisomerization of 2-Amino-3-alkynylpyrimidin-4(3H)-one in the Presence of Aqueous Base
Authors: Nagender P , Reddy G Malla , Rao P Sambasiva , Kurumurthy C , Rao P Shanthan , Narsaiah B
Published: September 2013

An efficient strategy has been developed for the synthesis of novel imidazo[1,2-a]pyrimidin-5(1H)-one derivatives 4 from 2-amino-3-alkynylpyrimidin-4(3H)-one 2 and alkyl halides in a single step by intramolecular cycloisomerization followed by N-alkylation in the presence of aqueous base.
The Causal Relationship between Energy Consumption and GDP in Turkey
Authors: Ozturk Ilhan , Kaplan Muhittin , Kalyoncu Huseyin
Published: September 2013

This paper attempts to investigate the short-run and long-run relationship and causality between energy consumption and economic growth during 1960–2006 period for Turkey. Johansen and Juselius cointegration method and vector error correction model (VECM) have been employed to examine this issue. After finding cointegration among variables, a VECM is estimated and the Granger causality tests were carried out based on a VECM. The results have shown that there is no short-run causality in both energy consumption and GDP models. The results also confirmed that there is unidirectional long-run causality among variables of interest and the direction of long-run causality is running from per capita GDP to per capita energy consumption. As a result, conservation hypothesis which postulates unidirectional causality from economic growth to energy consumption is confirmed for Turkey. Taken together, these empirical findings involve valuable information for policy makers.
Peat Production in High-Emission Level Peatlands — A Key to Reducing Climatic Impacts?
Authors: Väisänen Sanni E. , Silvan Niko R. , Ihalainen Antti V. J. , Soukka Risto M.
Published: September 2013

Both peat utilization and peatlands themselves contribute to increases in greenhouse gas (GHG) emissions. This article examines how peatlands with naturally high GHG emission levels affect net GHG emissions during the life cycle of peat. GHG emissions were measured from three drained peatland sites with high GHG emission levels. The impact of peatland type on the GHG emissions was considered when peat was assumed to replace coal in an energy production facility. The emission reduction levels achieved with the use of peat fuel originating from high-emission level peatlands stood at 35% compared to coal use and 30% compared to the average peat emission value. The findings indicate that GHG emissions can be reduced overall when peat from high-emission peatlands is utilized instead of coal. Lower emissions are primarily achieved because the harvesting of peat from high-emission level peatlands reduces the GHG emission levels of those lands.
Analyst Recommendations, Mutual Fund Herding, and Overreaction in Stock Prices
Authors: Brown Nerissa C. , Wei Kelsey D. , Wermers Russ
Published: September 2013

This paper documents that mutual funds “herd” (trade together) into stocks with consensus sell-side analyst upgrades, and herd out of stocks with consensus downgrades. This influence of analyst recommendation changes on fund herding is stronger for downgrades, and among managers with greater career concerns. These findings indicate that career-concerned managers are incentivized to follow analyst information, and that managers have a greater tendency to herd on negative stock information, given the greater reputational and litigation risk of holding losing stocks. Furthermore, starting in the mid-1990s (when aggregate mutual fund equity ownership is significantly higher), stocks traded by career-concerned herds of fund managers in response to analyst recommendation changes experience a significant same-quarter price impact, followed by a sharp subsequent price reversal. Our evidence suggests that analyst recommendation revisions induce herding by career-concerned fund managers, and that this type of trading has become price destabilizing with the increasing level of mutual fund ownership of stocks.

This paper was accepted by Wei Jiang, finance.
Corporate Risk Management: Integrating Liquidity, Hedging, and Operating Policies
Authors: Gamba Andrea , Triantis Alexander J.
Published: September 2013

We analyze the value created by a dynamic integrated risk management strategy involving liquidity management, derivatives hedging, and operating flexibility, in the presence of several frictions. We show that liquidity serves a critical and distinct role in risk management, justifying high levels of cash. We find that the marginal value associated with derivatives hedging is likely to be low, though we explain why some empirical studies find a higher value. We explore the complex interactions between operating flexibility and financial risk management, finding that substitution effects are nonmonotonic and are affected by operating leverage, the nature of operating flexibility, and the effectiveness of the hedging instrument.

This paper was accepted by Jerome Detemple, finance.
A Closer Look at the Short-Term Return Reversal
Authors: Da Zhi , Liu Qianqiu , Schaumburg Ernst
Published: September 2013

Stock returns unexplained by “fundamentals,” such as cash flow news, are more likely to reverse in the short run than those linked to fundamental news. Making novel use of analyst forecast revisions to measure cash flow news, a simple enhanced reversal strategy generates a risk-adjusted return four times the size of the standard reversal strategy. Importantly, isolating the component of past returns not driven by fundamentals provides a cleaner setting for testing existing theories of short-term reversals. Using this approach, we find that both liquidity shocks and investor sentiment contribute to the observed short-term reversal, but in different ways: Specifically, the reversal profit is attributable to liquidity shocks on the long side because fire sales more likely demand liquidity, and it is attributable to investor sentiment on the short side because short-sale constraints prevent the immediate elimination of overvaluation.

This paper was accepted by Brad Barber, finance.
OM Forum—Sustainable Operations Management: An Enduring Stream or a Passing Fancy?
Authors: Drake David F. , Spinler Stefan
Published: September 2013

Paul Kleindorfer was among the first to weigh in on and nurture the stream of sustainable operations management. The thoughts laid out here are based on conversations we had with Paul relating to the drivers underlying sustainability as a management issue: population and per capita consumption growth, the limited nature of resources and sinks, and the responsibility and exposure of firms to ensuing ecological risks and costs. We then discuss how an operations management lens contributes to the issue and criteria to help the sustainable operations management perspective endure. This paper relates to a presentation delivered by Morris Cohen for Paul's Manufacturing and Service Operations Management Distinguished Fellows Award, given at Columbia University, June 18, 2012. We wrote this paper at Paul's request.
Mechanical Drying of Senna leaves (Cassia angustifolia)
Authors: Ambrose Dawn , Naik Ravindra
Published: September 2013

Senna (Cassia angustifolia) is an important medicinal crop which is being exported from India. The present method of drying the leaves is under sun or shade which results in poor quality product. An attempt was made to dry senna in a forced flow type dryer at different temperatures. Sennoside concentrate which is an important quality aspect of Senna revealed that drying at 45 ºC was superior compared to other samples.
Colostrum - Its Composition, Benefits As A Nutraceutical : A Review
Authors: Godhia Meena , Patel Neesah
Published: September 2013

Colostrumis ‘the first milk secreted at the time of parturition, differing from the milk secreted later, by containing more lactalbumin and lactoprotein, and also being rich in antibodies that confer passive immunity to the newborn, also called “foremilk”. Human Colostrum (HC) and Bovine Colostrum (BC) are rich in protein, immunoglobulin, lactoferrin and growth factors. Recent studies suggest that colostrum components, immunoglobulin and growth factor benefits physically active personandin treatment of autoimmune disorders.It isused for the treatment of a wide variety of gastrointestinal conditions, including non-steroidalanti-inflammatory drug–induced gut injury, H pylori infection,immunedeficiency related diarrhea as well as infective diarrhea. This review explores the current knowledge on the beneficial effect of colostrum supplementation in the above condition.
Pitfalls of Using Body Mass Index (BMI) in Assessment of Obesity Risk
Authors: Bhurosy Trishnee , Jeewon Rajesh
Published: September 2013

This review focuses on the potential drawbacks of using body mass index (BMI) which are often overlooked in the assessment of overweight or obesity risk, with special emphasis on the use of other equally important anthropometric measurements such as waist circumference (WC), waist-hip-ratio (WHR) and skin-fold thicknesses. There have been inconsistencies in findings when using BMI as an indicator of obesity risk. These have arisen mainly due to gender, age and ethnic differences in body fat composition and distribution coupled with increased reliance on self-reported values of weight and height. Since BMI remains the most widely used tool to screen obesity risk in many studies, establishment of gender-, age- and ethnicity-based cut-offs of BMI, tailored to specific populations, will significantly enhance public health policies and increase the success rates of obesity intervention programs. The use of other anthropometric measures such as WC and WHR in conjunction with BMI is also highly recommended to assess abdominal obesity or other body-specific areas.
Effect of Potassium Carbonate (K2CO3) on the Viscosity and Related Physico – Chemical Properties of Genger (Bombax costatum) Powder during Storage
Authors: Gernah D , Gbakaan P
Published: September 2013

Effect of storage and concentration of potassium carbonate (K2CO3) on the viscosity and related physico – chemical properties of genger (Bombax costatum) powder was determined. Genger powder was stored for a period of four (4) months (May-August) at 30oc ± 5oc under varying concentrations of K2CO3: 0%, 5%, 10% and 15% in two containers (plastic, giving samples A – D and metal tins, giving samples A1 – D1). Thereafter, the moisture and crude fat contents, water absorption capacity, least gelation concentration, effect of K2CO3 concentration on gel strength and viscosity of the stored powders were determined, using standard methods of analysis, with fresh powder (analyzed before storage) as control. Moisture content decreased significantly (p < 0.05) from 8.37% to 3.04% and 2.00% in samples D and D1 respectively, while crude fat content increased significantly (p < 0.05) from 2.50% to 7.50% and 10.05% in the same samples. Water absorption capacity also increased significantly (p < 0.05) from 6.4g/g to 6.40g/g in the fresh sample to 7.30g/g and 8.30g/g in samples D and D1 respectively. Gelation capacity increased considerably, with 15% K2CO3 giving very strong gels at 1.50% concentration. The overall viscosity increased significantly (p < 0.05) with increase in concentration of (K2CO3) from 64.00FN to 110.00FN after storage. Generally, samples stored in metal tin gave better results than those in the plastic container.
Erythropoietic protoporhyria in first pregnancy
Authors: Elliott Karan D. , Mongelli Max
Published: September 2013

Erythropoietic protoporphyria is a rare, inherited disorder, mainly characterised by photosensitivity. Its accompanying vitamin D and iron deficiencies, as well as potential effects on the liver, make it an important condition to monitor in pregnancy. However, as discovered in our subject case, pregnancy and delivery appear to pose little additional burden to the woman or baby, and in fact, may lead to an improvement of symptoms.
Raceways-based Production of Algal Crude Oil
Authors: Chisti Yusuf
Published: September 2013

Raceway ponds, or “high-rate algal ponds”, of various configurations have been used to treat wastewater since the 1950s. They are also known as Oswald ponds after their inventor W. J. Oswald. Large-scale outdoor culture of microalgae and cyanobacteria in raceways is well established (Terry and Raymond 1985; Oswald 1988; Borowitzka and Borowitzka 1989; Becker 1994; Lee 1997; Molina Grima 1999; Pulz 2001; Borowitzka 2005; Spolaore et al. 2006). Raceway culture is used commercially in the United States, Thailand, China, Israel and elsewhere, mostly to produce algae for relatively highvalue applications. This chapter is focused on raceways typically used in the production of algal biomass and not in the treatment of wastewater. The engineering design, operation and performance characteristics of raceways are discussed. The biomass productivity of the raceways is assessed in relation to limits imposed by algal biology. The economics of algal oil production in raceways are discussed.
Taking Universality Seriously: A Functional Approach to Extraterritoriality in International Human Rights Law
Authors: Shany Yuval
Published: September 2013

International human rights law (IHRL) has struggled to define a standard for determining the extraterritorial applicability of its norms that would reconcile the ethos of universal entitlement, on the one hand, with the centrality of borders in delineating state powers and responsibilities under international law, on the other hand. The case law of the UN Human Rights Committee and the European Court of Human Rights (ECtHR) favors barring states from engaging in conduct outside their borders that would be impermissible if undertaken inside their borders. Still, attempts to demarcate the precise scope of extraterritorial application through allusion to degrees of control over individuals or areas, or by the nature of the obligation itself – have led to unsatisfactory, if not arbitrary results. This article opines a move to functionalism as the basis for extraterritorial applicability – requiring states to protect IHRL in situations they can do so. Under this approach, which takes universality seriously, borders lose much their normative significance. I suggest limiting the functional approach to extraterritorial applicability in accordance with two key notions: (1) the intensity of power relations – factual relations of power entailing direct, significant and foreseeable potential impact – should result in the application of IHRL obligations; or, alternatively, (2) special legal relations – relations of power that put the state in a unique legal position to afford IHRL protection would also justify the imposition of extraterritorial obligations.
Taxonomic revision of pikas Ochotona (Lagomorpha, Mammalia) at the species level
Authors: Lissovsky Andrey A.
Published: September 2013

I examined a sample comprising 1090 intact skulls, representing all recognized Palearctic species of pika (
Diameter, Length, Speed, and Conduction Delay of Callosal Axons in Macaque Monkeys and Humans: Comparing Data from Histology and Magnetic Resonance Imaging Diffusion Tractography
Authors: Caminiti Roberto , Carducci Filippo , Piervincenzi Claudia , Battaglia-Mayer Alexandra , Confalone Giuseppina , Visco-Comandini Federica , Pantano Patrizia , Innocenti Giorgio M.
Published: September 2013

Three macaque monkeys and 13 healthy human volunteers underwent diffusion tensor MRI with a 3 Tesla scanner for diffusion tract tracing (DTT) reconstruction of callosal bundles from different areas. In six macaque monkeys and three human subjects, the length of fiber tracts was obtained from histological data and combined with information on the distribution of axon diameter, so as to estimate callosal conduction delays from different areas. The results showed that in monkeys, the spectrum of tract lengths obtained with DTT closely matches that estimated from histological reconstruction of axons labeled with an anterogradely transported tracer. For each sector of the callosum, we obtained very similar conduction delays regardless of whether conduction distance was obtained from tractography or from histological analysis of labeled axons. This direct validation of DTT measurements by histological methods in monkeys was a prerequisite for the computation of the callosal conduction distances and delays in humans, which we had previously obtained by extrapolating the length of callosal axons from that of the monkey, proportionally to the brain volumes in the two species. For this analysis, we used the distribution of axon diameters from four different sectors of the corpus callosum. As in monkeys, in humans the shortest callosal conduction delays were those of motor, somatosensory, and premotor areas; the longer ones were those of temporal, parietal, and visual areas. These results provide the first histological validation of anatomical data about connection length in the primate brain based on DTT imaging.
Predictive Modeling by the Cerebellum Improves Proprioception
Authors: Bhanpuri Nasir H. , Okamura Allison M. , Bastian Amy J.
Published: September 2013

Because sensation is delayed, real-time movement control requires not just sensing, but also predicting limb position, a function hypothesized for the cerebellum. Such cerebellar predictions could contribute to perception of limb position (i.e., proprioception), particularly when a person actively moves the limb. Here we show that human cerebellar patients have proprioceptive deficits compared with controls during active movement, but not when the arm is moved passively. Furthermore, when healthy subjects move in a force field with unpredictable dynamics, they have active proprioceptive deficits similar to cerebellar patients. Therefore, muscle activity alone is likely insufficient to enhance proprioception and predictability (i.e., an internal model of the body and environment) is important for active movement to benefit proprioception. We conclude that cerebellar patients have an active proprioceptive deficit consistent with disrupted movement prediction rather than an inability to generally enhance peripheral proprioceptive signals during action and suggest that active proprioceptive deficits should be considered a fundamental cerebellar impairment of clinical importance.
Protein Tyrosine Phosphatase α in the Dorsomedial Striatum Promotes Excessive Ethanol-Drinking Behaviors
Authors: Ben Hamida Sami , Darcq Emmanuel , Wang Jun , Wu Su , Phamluong Khanhky , Kharazia Viktor , Ron Dorit
Published: September 2013

We previously found that excessive ethanol drinking activates Fyn in the dorsomedial striatum (DMS) (Wang et al., 2010; Gibb et al., 2011). Ethanol-mediated Fyn activation in the DMS leads to the phosphorylation of the GluN2B subunit of the NMDA receptor, to the enhancement of the channel's activity, and to the development and/or maintenance of ethanol drinking behaviors (Wang et al., 2007, 2010). Protein tyrosine phosphatase α (PTPα) is essential for Fyn kinase activation (Bhandari et al., 1998), and we showed that ethanol-mediated Fyn activation is facilitated by the recruitment of PTPα to synaptic membranes, the compartment where Fyn resides (Gibb et al., 2011). Here we tested the hypothesis that PTPα in the DMS is part of the Fyn/GluN2B pathway and is thus a major contributor to the neuroadaptations underlying excessive ethanol intake behaviors. We found that RNA interference (RNAi)-mediated PTPα knockdown in the DMS reduces excessive ethanol intake and preference in rodents. Importantly, no alterations in water, saccharine/sucrose, or quinine intake were observed. Furthermore, downregulation of PTPα in the DMS of mice significantly reduces ethanol-mediated Fyn activation, GluN2B phosphorylation, and ethanol withdrawal-induced long-term facilitation of NMDAR activity without altering the intrinsic features of DMS neurons. Together, these results position PTPα upstream of Fyn within the DMS and demonstrate the important contribution of the phosphatase to the maladaptive synaptic changes that lead to excessive ethanol intake.
Central Activation of the A1 Adenosine Receptor (A1AR) Induces a Hypothermic, Torpor-Like State in the Rat
Authors: Tupone Domenico , Madden Christopher J. , Morrison Shaun F.
Published: September 2013

Since central activation of A1 adenosine receptors (A1ARs) plays an important role in the induction of the hypothermic and hypometabolic torpid state in hibernating mammals, we investigated the potential for the A1AR agonist N6-cyclohexyladenosine to induce a hypothermic, torpor-like state in the (nonhibernating) rat. Core and brown adipose tissue temperatures, EEG, heart rate, and arterial pressure were recorded in free-behaving rats, and c-fos expression in the brain was analyzed, following central administration of N6-cyclohexyladenosine. Additionally, we recorded the sympathetic nerve activity to brown adipose tissue; expiratory CO2and skin, core, and brown adipose tissue temperatures; and shivering EMGs in anesthetized rats following central and localized, nucleus of the solitary tract, administration of N6-cyclohexyladenosine. In rats exposed to a cool (15°C) ambient temperature, central A1AR stimulation produced a torpor-like state similar to that in hibernating species and characterized by a marked fall in body temperature due to an inhibition of brown adipose tissue and shivering thermogenesis that is mediated by neurons in the nucleus of the solitary tract. During the induced hypothermia, EEG amplitude and heart rate were markedly reduced. Skipped heartbeats and transient bradycardias occurring during the hypothermia were vagally mediated since they were eliminated by systemic muscarinic receptor blockade. These findings demonstrate that a deeply hypothermic, torpor-like state can be pharmacologically induced in a nonhibernating mammal and that recovery of normothermic homeostasis ensues upon rewarming. These results support the potential for central activation of A1ARs to be used in the induction of a hypothermic, therapeutically beneficial state in humans.
NG2 Cells in White Matter But Not Gray Matter Proliferate in Response to PDGF
Authors: Hill Robert A. , Patel Kiran D. , Medved Jelena , Reiss Alex M. , Nishiyama Akiko
Published: September 2013

Glial cells that express the NG2 proteoglycan and the α receptor for PDGF (NG2 cells, polydendrocytes) make up the fifth major cell population that serves as oligodendrocyte progenitor cells in the postnatal CNS. Although recent studies have suggested differences in their proliferation and oligodendrocyte differentiation in gray and white matter, the mechanism underlying the observed differences has been unclear. Using organotypic slice cultures from the forebrain and cerebellum of early postnatal NG2creBAC:ZEG mice, we have compared basal and growth factor-induced proliferation of NG2 cells in gray and white matter. NG2 cells in white matter exhibited greater proliferative response to PDGF AA than those in gray matter. Heterotopic slice transplant and explant cultures suggested intrinsic mechanisms for the differential proliferative response of gray and white matter cells. Additionally, younger white matter NG2 cells showed a more robust proliferative response to PDGF. Basal and PDGF-induced proliferation of gray and white matter NG2 cells was largely dependent on Wnt/β-catenin and phosphatidylinositol 3-kinase acting through the mammalian target of rapamycin pathway and not through ERK. These data uncover a previously unrecognized divergence between gray and white matter NG2 cells in the developing brain in their proliferative response to PDGF.
An Anatomical Substrate for Integration among Functional Networks in Human Cortex
Authors: van den Heuvel Martijn P. , Sporns Olaf
Published: September 2013

The human brain shows several characteristics of an efficient communication network architecture, including short communication paths and the existence of modules interlinked by a small set of highly connected regions. Studies of structural networks comprising macroscopic white matter projections have shown that these putative hubs are densely interconnected, giving rise to a spatially distributed and topologically central collective called the “rich club.” In parallel, studies of intrinsic brain activity have consistently revealed distinct functional communities or resting-state networks (RSNs), indicative of specialized processing and segregation of neuronal information. However, the pattern of structural connectivity interconnecting these functional RSNs and how such inter-RSN structural connections might bring about functional integration between RSNs remain largely unknown. Combining high-resolution diffusion weighted imaging with resting-state fMRI, we present novel evidence suggesting that the rich club structure plays a central role in cross-linking macroscopic RSNs of the human brain. Rich club hub nodes were present in all functional networks, accounted for a large proportion of “connector nodes,” and were found to coincide with regions in which multiple networks overlap. In addition, a large proportion of all inter-RSN connections were found to involve rich club nodes, and these connections participated in a disproportionate number of communication paths linking nodes in different RSNs. Our findings suggest that the brain's rich club serves as a macroscopic anatomical substrate to cross-link functional networks and thus plays an important role in the integration of information between segregated functional domains of the human cortex.
A Circuit for Motor Cortical Modulation of Auditory Cortical Activity
Authors: Nelson Anders , Schneider David M. , Takatoh Jun , Sakurai Katsuyasu , Wang Fan , Mooney Richard
Published: September 2013

Normal hearing depends on the ability to distinguish self-generated sounds from other sounds, and this ability is thought to involve neural circuits that convey copies of motor command signals to various levels of the auditory system. Although such interactions at the cortical level are believed to facilitate auditory comprehension during movements and drive auditory hallucinations in pathological states, the synaptic organization and function of circuitry linking the motor and auditory cortices remain unclear. Here we describe experiments in the mouse that characterize circuitry well suited to transmit motor-related signals to the auditory cortex. Using retrograde viral tracing, we established that neurons in superficial and deep layers of the medial agranular motor cortex (M2) project directly to the auditory cortex and that the axons of some of these deep-layer cells also target brainstem motor regions. Usingin vitrowhole-cell physiology, optogenetics, and pharmacology, we determined that M2 axons make excitatory synapses in the auditory cortex but exert a primarily suppressive effect on auditory cortical neuron activity mediated in part by feedforward inhibition involving parvalbumin-positive interneurons. Usingin vivointracellular physiology, optogenetics, and sound playback, we also found that directly activating M2 axon terminals in the auditory cortex suppresses spontaneous and stimulus-evoked synaptic activity in auditory cortical neurons and that this effect depends on the relative timing of motor cortical activity and auditory stimulation. These experiments delineate the structural and functional properties of a corticocortical circuit that could enable movement-related suppression of auditory cortical activity.
Effects of Sleep and Wake on Oligodendrocytes and Their Precursors
Authors: Bellesi Michele , Pfister-Genskow Martha , Maret Stephanie , Keles Sunduz , Tononi Giulio , Cirelli Chiara
Published: September 2013

Previous studies of differential gene expression in sleep and wake pooled transcripts from all brain cells and showed that several genes expressed at higher levels during sleep are involved in the synthesis/maintenance of membranes in general and of myelin in particular, a surprising finding given the reported slow turnover of many myelin components. Other studies showed that oligodendrocyte precursor cells (OPCs) are responsible for the formation of new myelin in both the injured and the normal adult brain, and that glutamate released from neurons, via neuron–OPC synapses, can inhibit OPC proliferation and affect their differentiation into myelin-forming oligodendrocytes. Because glutamatergic transmission is higher in wake than in sleep, we asked whether sleep and wake can affect oligodendrocytes and OPCs. Using the translating ribosome affinity purification technology combined with microarray analysis in mice, we obtained a genome-wide profiling of oligodendrocytes after sleep, spontaneous wake, and forced wake (acute sleep deprivation). We found that hundreds of transcripts being translated in oligodendrocytes are differentially expressed in sleep and wake: genes involved in phospholipid synthesis and myelination or promoting OPC proliferation are transcribed preferentially during sleep, while genes implicated in apoptosis, cellular stress response, and OPC differentiation are enriched in wake. We then confirmed through BrdU and other experiments that OPC proliferation doubles during sleep and positively correlates with time spent in REM sleep, whereas OPC differentiation is higher during wake. Thus, OPC proliferation and differentiation are not perfectly matched at any given circadian time but preferentially occur during sleep and wake, respectively.
Model Order Reduction by Approximate Balanced Truncation: A Unifying Framework / Modellreduktion durch approximatives Balanciertes Abschneiden: eine vereinigende Formulierung
Authors: Wolf Thomas , Panzer Heiko K. F. , Lohmann Boris
Published: September 2013

A novel formulation of approximate truncated balanced realization (TBR) is introduced to unify three approaches: two iterative methods for solving the underlying Lyapunov equations - the alternating directions implicit (ADI) iteration and the rational Krylov subspace method (RKSM) - and a two-step procedure that performs a Krylov-based projection and subsequently direct TBR. The framework allows to compare the three methods with respect to solvability, fidelity, numerical effort, stability preservation and global error bounds, which suggests to merge ADI with the two-step procedure