bluuebunny/crossref_metadata_2025 huggingface dataset:
ADrosophilamodel for fetal alcohol syndrome disorders: role for the insulin pathway
Authors: McClure Kimberly D. , French Rachael L. , Heberlein Ulrike
Published: February 2011

Prenatal exposure to ethanol in humans results in a wide range of developmental abnormalities, including growth deficiency, developmental delay, reduced brain size, permanent neurobehavioral abnormalities and fetal death. Here we describe the use of Drosophila melanogaster as a model for exploring the effects of ethanol exposure on development and behavior. We show that developmental ethanol exposure causes reduced viability, developmental delay and reduced adult body size. We find that flies reared on ethanol-containing food have smaller brains and imaginal discs, which is due to reduced cell division rather than increased apoptosis. Additionally, we show that, as in mammals, flies reared on ethanol have altered responses to ethanol vapor exposure as adults, including increased locomotor activation, resistance to the sedating effects of the drug and reduced tolerance development upon repeated ethanol exposure. We have found that the developmental and behavioral defects are largely due to the effects of ethanol on insulin signaling; specifically, a reduction in Drosophila insulin-like peptide (Dilp) and insulin receptor expression. Transgenic expression of Dilp proteins in the larval brain suppressed both the developmental and behavioral abnormalities displayed by ethanol-reared adult flies. Our results thus establish Drosophila as a useful model system to uncover the complex etiology of fetal alcohol syndrome.
Differential endocytosis and signaling dynamics of insulin receptor variants IR-A and IR-B
Authors: Giudice Jimena , Leskow Federico Coluccio , Arndt-Jovin Donna J. , Jovin Thomas M. , Jares-Erijman Elizabeth A.
Published: February 2011

Insulin signaling comprises a complex cascade of events, playing a key role in the regulation of glucose metabolism and cellular growth. Impaired response to insulin is the hallmark of diabetes, whereas upregulated insulin activity occurs in many cancers. Two splice variants of the insulin receptor (IR) exist in mammals: IR-A, lacking exon 11, and full-length IR-B. Although considerable biochemical data exist on insulin binding and downstream signaling, little is known about the dynamics of the IR itself. We created functional IR transgenes fused with visible fluorescent proteins for use in combination with biotinamido-caproyl insulin and streptavidin quantum dots. Using confocal and structured illumination microscopy, we visualized the endocytosis of both isoforms in living and fixed cells and demonstrated a higher rate of endocytosis of IR-A than IR-B. These differences correlated with higher and sustained activation of IR-A in response to insulin and with distinctive ERK1/2 activation profiles and gene transcription regulation. In addition, cells expressing IR-B showed higher AKT phosphorylation after insulin stimulation than cells expressing IR-A. Taken together, these results suggest that IR signaling is dependent on localization; internalized IRs regulate mitogenic activity, whereas metabolic balance signaling occurs at the cell membrane.
The F-actin cortical network is a major factor influencing the organization of the secretory machinery in chromaffin cells
Authors: Torregrosa-Hetland Cristina J. , Villanueva José , Giner Daniel , Lopez-Font Inmaculada , Nadal Angel , Quesada Iván , Viniegra Salvador , Expósito-Romero Giovanna , Gil Amparo , Gonzalez-Velez Virginia , Segura Javier , M. Gutiérrez Luis
Published: February 2011

We have studied how the F-actin cytoskeleton is involved in establishing the heterogeneous intracellular Ca2+ levels ([Ca2+]i) and in the organization of the exocytotic machinery in cultured bovine chromaffin cells. Simultaneous confocal visualization of [Ca2+]i and transmitted light studies of the cytoskeleton showed that, following cell stimulation, the maximal signal from the Ca2+-sensitive fluorescent dye Fluo-3 was in the empty cytosolic spaces left by cytoskeletal cages. This was mostly due to the accumulation of the dye in spaces devoid of cytoskeletal components, as shown by the use of alternative Ca2+-insensitive fluorescent cytosolic markers. In addition to affecting the distribution of such compounds in the cytosol, the cytoskeleton influenced the location of L- and P-Q-type Ca2+ channel clusters, which were associated with the borders of cytoskeletal cages in resting and stimulated cells. Indeed, syntaxin-1 and synaptotagmin-1, which are components of the secretory machinery, were present in the same location. Furthermore, granule exocytosis took place at these sites, indicating that the organization of the F-actin cytoskeletal cortex shapes the preferential sites for secretion by associating the secretory machinery with preferential sites for Ca2+ entry. The influence of this cortical organization on the propagation of [Ca2+]i can be modelled, illustrating how it serves to define rapid exocytosis.
Twilight spectral dynamics and the coral reef invertebrate spawning response
Authors: Sweeney Alison M. , Boch Charles A. , Johnsen Sonke , Morse Daniel E.
Published: February 2011

There are dramatic and physiologically relevant changes in both skylight color and intensity during evening twilight as the pathlength of direct sunlight through the atmosphere increases, ozone increasingly absorbs long wavelengths and skylight becomes increasingly blue shifted. The moon is above the horizon at sunset during the waxing phase of the lunar cycle, on the horizon at sunset on the night of the full moon and below the horizon during the waning phase. Moonlight is red shifted compared with daylight, so the presence, phase and position of the moon in the sky could modulate the blue shifts during twilight. Therefore, the influence of the moon on twilight color is likely to differ somewhat each night of the lunar cycle, and to vary especially rapidly around the full moon, as the moon transitions from above to below the horizon during twilight. Many important light-mediated biological processes occur during twilight, and this lunar effect may play a role. One particularly intriguing biological event tightly correlated with these twilight processes is the occurrence of mass spawning events on coral reefs. Therefore, we measured downwelling underwater hyperspectral irradiance on a coral reef during twilight for several nights before and after the full moon. We demonstrate that shifts in twilight color and intensity on nights both within and between evenings, immediately before and after the full moon, are correlated with the observed times of synchronized mass spawning, and that these optical phenomena are a biologically plausible cue for the synchronization of these mass spawning events.
Multimodal signal variation in space and time: how important is matching a signal with its signaler?
Authors: Taylor Ryan C. , Klein Barrett A. , Stein Joey , Ryan Michael J.
Published: February 2011

Multimodal signals (acoustic+visual) are known to be used by many anuran amphibians during courtship displays. The relative degree to which each signal component influences female mate choice, however, remains poorly understood. In this study we used a robotic frog with an inflating vocal sac and acoustic playbacks to document responses of female túngara frogs to unimodal signal components (acoustic and visual). We then tested female responses to a synchronous multimodal signal. Finally, we tested the influence of spatial and temporal variation between signal components for female attraction. Females failed to approach the isolated visual cue of the robotic frog and they showed a significant preference for the call over the spatially separate robotic frog. When presented with a call that was temporally synchronous with the vocal sac inflation of the robotic frog, females did not show a significant preference for this over the call alone; when presented with a call that was temporally asynchronous with vocal sac inflation of the robotic frog, females discriminated strongly against the asynchronous multimodal signal in favor of the call alone. Our data suggest that although the visual cue is neither necessary nor sufficient for attraction, it can strongly modulate mate choice if females perceive a temporal disjunction relative to the primary acoustic signal.
Coping with novelty and stress in free-living house sparrows
Authors: Lendvai Ádám Z. , Bókony Veronika , Chastel Olivier
Published: February 2011

Individuals respond differently to stressors and it has been suggested that stress responses are related to coping styles (consistent individual differences in behavior and physiology). We studied behavioral responses to a novel object and corticosterone response to stress during chick rearing in free-living female house sparrows (Passer domesticus). To prevent mates from influencing each others' behavior, we removed the males temporarily from nests and tested the females the following day either with a novel object placed on the nest box or as control. The two groups differed only in behaviors that were a priori defined as responses to the novel object (latency to first feeding, time spent near the nest, and inspecting the novel object by hovering in front of it) indicating that mate-removal per se had no effect on female behavior. Based on these variables, females' coping behaviors were categorized as ‘bold’, ‘inquisitive’ or ‘shy’ by discriminant analysis. Baseline corticosterone, measured on the day following the novel-object or control test, was not related to any measure of coping. Stress-induced corticosterone, however, was negatively related to number of hoverings in front of the nest (a measure of explorativeness) and accordingly differed between the behavioral coping categories, with ‘inquisitive’ birds having the lowest stress response. We propose that the relationship between physiological stress response and behavioral response to novelty (a component of personality or coping style) may be more complex than previously suggested, and individuals cannot always be unambiguously categorized along a single personality axis.
Understanding the energetic costs of living in saline environments: effects of salinity on basal metabolic rate, body mass and daily energy consumption of a long-distance migratory shorebird
Authors: Gutiérrez Jorge S. , Masero José A. , Abad-Gómez José M. , Villegas Auxiliadora , Sánchez-Guzmán Juan M.
Published: February 2011

Many migratory vertebrates typically move between habitats with varying salinities during the annual cycle. These organisms clearly exhibit a remarkable phenotypic flexibility in their ‘osmoregulatory machinery’, but the metabolic consequences of salinity acclimatization are still not well understood. We investigated the effects of salinity on basal metabolic rate (BMR), body mass and daily energy consumption of a long-distance migratory shorebird, the dunlin (Calidris alpina), outside the breeding season. Mass-corrected BMR and daily energy consumption increased significantly by 17 and 20% between freshwater (0.3‰ NaCl) and saltwater (33.0–35.0‰ NaCl), respectively. Body mass in both captive and wild dunlins was lower (9–16%) in saline than in freshwater environments. These changes on BMR and body mass were quickly reversed by returning the birds to freshwater, suggesting that metabolic adjustment to saltwater and metabolic readjustment to freshwater are both processes that occur in a few days. Our findings support empirically that the processes of developing and maintaining an active osmoregulatory machinery are energetically expensive, and they could help to explain diet and/or habitat selection patterns along the flyway. Finally, we discuss whether body mass loss in saltwater may be a strategy to reduce maintenance cost in osmotically stressful conditions such as overwintering in marine habitats, and raise some methodological implications for studies of BMR-related outcomes using captive birds captured in saline environments.
Estimation of musculoskeletal models from in situ measurements of muscle action in the rat hindlimb
Authors: Yeo Sang Hoon , Mullens Christopher H. , Sandercock Thomas G. , Pai Dinesh K. , Tresch Matthew C.
Published: February 2011

Musculoskeletal models are often created by making detailed anatomical measurements of muscle properties. These measurements can then be used to determine the parameters of canonical models of muscle action. We describe here a complementary approach for developing and validating muscle models, using in situ measurements of muscle actions. We characterized the actions of two rat hindlimb muscles: the gracilis posticus (GRp) and the posterior head of biceps femoris (BFp; excluding the anterior head with vertebral origin). The GRp is a relatively simple muscle, with a circumscribed origin and insertion. The BFp is more complex, with an insertion distributed along the tibia. We measured the six-dimensional isometric forces and moments at the ankle evoked from stimulating each muscle at a range of limb configurations. The variation of forces and moments across the workspace provides a succinct characterization of muscle action. We then used this data to create a simple muscle model with a single point insertion and origin. The model parameters were optimized to best explain the observed force–moment data. This model explained the relatively simple muscle, GRp, very well (R2>0.85). Surprisingly, this simple model was also able to explain the action of the BFp, despite its greater complexity (R2>0.84). We then compared the actions observed here with those predicted using recently published anatomical measurements. Although the forces and moments predicted for the GRp were very similar to those observed here, the predictions for the BFp differed. These results show the potential utility of the approach described here for the development and refinement of musculoskeletal models based on in situ measurements of muscle actions.
The effects of salinity and temperature on the transparency of the grass shrimp Palaemonetes pugio
Authors: Bhandiwad Ashwin , Johnsen Sönke
Published: February 2011

Transparency is an effective form of camouflage, but it must be present throughout the entire volume of an animal to succeed. Certain environmental stressors may cause physiological responses that increase internal light scattering, making tissue less transparent and more conspicuous to predators. We tested this in the transparent grass shrimp, Palaemonetes pugio, which is found in shallow estuaries where both salinity and temperature change rapidly because of tidal cycles, evaporation and runoff. Animals originally kept at a salinity of 15 p.p.t. and a temperature of 20°C were placed into solutions with salinities of 0, 15, 25 or 30 p.p.t. and temperatures of 13, 20 or 27°C for 12 h (N=26 for each of 12 treatments). Under the control conditions of 15 p.p.t. at 20°C, the transparency of grass shrimp tails was 54±3% (mean ± s.e.). At higher salinities and at both higher and lower temperatures, transparency dropped significantly (P<0.001, two-way ANOVA), reaching 0.04±0.01% at 30 p.p.t. at 27°C. Confocal microscopy of P. pugio's tail suggested that the observed loss of transparency was due to the pooling of low refractive index hemolymph between the high index muscle fibers, creating many index boundaries that increased light scattering. Analysis of a year-long salinity and temperature record from a North Carolina estuary showed that changes of the order of those found in this study are relatively common, suggesting that P. pugio may undergo periods of reduced crypsis, potentially leading to increased predation.
Mechanical filtering for narrow-band hearing in the weta
Authors: Lomas Kathryn , Montealegre-Z Fernando , Parsons Stuart , Field Larry H. , Robert Daniel
Published: February 2011

This paper constitutes a major attempt to associate tympanic deflections with the mechanoreceptor organ location in an acoustic insect. The New Zealand tree weta (Hemideina thoracica) has tympanal ears located on each of the prothoracic tibiae. The tympana exhibit a sclerotized oval plate, membranous processes bulging out from the tibial cuticle and many loosely suspended ripples. We used microscanning laser Doppler vibrometry to determine how such a tympanal membrane vibrates in response to sound and whether the sclerotized region plays a role in hearing. The tympanum displays a single resonance at the calling frequency of the male, an unusual example of an insect tympana acting as a narrow bandpass filter. Both tympana resonate in phase with the stimulus and with each other. Histological sections show that the tympanal area is divided into two distinct regions, as in other ensiferans. An oval plate lies in the middle of a thickened region and is surrounded by a transparent and uniformly thin region. It is hinged dorsally to the tympanal rim and thus resembles the model of a ‘hinged flap’. The thickened region appears to act as a damping mass on the oscillation of the thin region, and vibration displacement is reduced in this area. The thinner area vibrates with higher amplitude, inducing mechanical pressure on the dorsal area adjacent to the crista acustica. We present a new model showing how the thickened region might confer a mechanical gain onto the activation of the crista acustica sensory neurons during the sound-induced oscillations.
Environmental complexity, seasonality and brain cell proliferation in a weakly electric fish, Brachyhypopomus gauderio
Authors: Dunlap Kent D. , Silva Ana C. , Chung Michael
Published: February 2011

Environmental complexity and season both influence brain cell proliferation in adult vertebrates, but their relative importance and interaction have not been directly assessed. We examined brain cell proliferation during both the breeding and non-breeding seasons in adult male electric fish, Brachyhypopomus gauderio, exposed to three environments that differed in complexity: (1) a complex natural habitat in northern Uruguay, (2) an enriched captive environment where fish were housed socially and (3) a simple laboratory setting where fish were isolated. We injected fish with BrdU 2.5 h before sacrifice to label newborn cells. We examined the hindbrain and midbrain and quantified the density of BrdU+ cells in whole transverse sections, proliferative zones and two brain nuclei in the electrocommunication circuitry (the pacemaker nucleus and the electrosensory lateral line lobe). Season had the largest effect on cell proliferation, with fish during the breeding season having three to seven times more BrdU+ cells than those during the non-breeding season. Although the effect was smaller, fish from a natural environment had greater rates of cell proliferation than fish in social or isolated captive environments. For most brain regions, fish in social and isolated captive environments had equivalent levels of cell proliferation. However, for brain regions in the electrocommunication circuitry, group-housed fish had more cell proliferation than isolated fish, but only during the breeding season (season × environment interaction). The regionally and seasonally specific effect of social environment on cell proliferation suggests that addition of new cells to these nuclei may contribute to seasonal changes in electrocommunication behavior.
Dynamics of gecko locomotion: a force-measuring array to measure 3D reaction forces
Authors: Dai Zhendong , Wang Zhouyi , Ji Aihong
Published: February 2011

Measuring the interaction between each foot of an animal and the substrate is one of the most effective ways to understand the dynamics of legged locomotion. Here, a new facility – the force-measuring array (FMA) – was developed and applied to measure 3D reaction forces of geckos on different slope surfaces. The FMA consists of 16 3D sensors with resolution to the mN level. At the same time the locomotion behaviour of geckos freely moving on the FMA was recorded by high speed camera. The reaction forces acting on the gecko's individual feet measured by the FMA and correlated with locomotion behaviour provided enough information to reveal the mechanical and dynamic secrets of gecko locomotion. Moreover, dynamic forces were also measured by a force platform and correlated with locomotion behaviour. The difference between the forces measured by the two methods is discussed. From the results we conclude that FMA is the best way to obtain true reaction forces acting on the gecko's individual feet.
Survival and energetic costs of repeated cold exposure in the Antarctic midge, Belgica antarctica: a comparison between frozen and supercooled larvae
Authors: Teets Nicholas M. , Kawarasaki Yuta , Lee Richard E. , Denlinger David L.
Published: February 2011

In this study, we examined the effects of repeated cold exposure (RCE) on the survival, energy content and stress protein expression of larvae of the Antarctic midge, Belgica antarctica (Diptera: Chironomidae). Additionally, we compared results between larvae that were frozen at –5°C in the presence of water during RCE and those that were supercooled at –5°C in a dry environment. Although >95% of larvae survived a single 12 h bout of freezing at –5°C, after five cycles of RCE survival of frozen larvae dropped below 70%. Meanwhile, the survival of control and supercooled larvae was unchanged, remaining around 90% for the duration of the study. At the tissue level, frozen larvae had higher rates of cell mortality in the midgut than control and supercooled larvae. Furthermore, larvae that were frozen during RCE experienced a dramatic reduction in energy reserves; after five cycles, frozen larvae had 25% less lipid, 30% less glycogen and nearly 40% less trehalose than supercooled larvae. Finally, larvae that were frozen during RCE had higher expression of hsp70 than those that were supercooled, indicating a higher degree of protein damage in the frozen group. Results were similar between larvae that had accumulated 60 h of freezing at –5°C over five cycles of RCE and those that were frozen continuously for 60 h, suggesting that the total time spent frozen determines the physiological response. Our results suggest that it is preferable, both from a survival and energetic standpoint, for larvae to seek dry microhabitats where they can avoid inoculative freezing and remain unfrozen during RCE.
Resting and action potentials under hypotonic conditions, unlike Na+ pump activity, depend only on the alteration of intracellular [Na+] and [K+] in frog skeletal muscle
Authors: Venosa Roque A.
Published: February 2011

It is well established that hypotonicity generates a marked and unexpected increase in active Na+ efflux in frog muscle fibers as well as in other cells like cardiac myocytes, astrocytes, brain synaptosomes and renal cells. The effect of hypotonicity on the electrical activity of skeletal muscle related to Na+ and K+ voltage-gated channels, however, has not been specifically addressed. The results of the present investigation show that the changes in resting and action potentials produced by hypotonicity can be fully explained by the reduction of intracellular [Na+] and [K+] due to the increase in cellular water content.
Development and validation of a quantitative assay based on tandem mass spectrometry
Authors: Honour John W
Published: February 2011

Many routine hospital and clinical research assays have relied upon immunoassay procedures to achieve sensitive measurements of a range of important analytes. Some of the methods have been developed in-house but increasingly commercial kits and automated analysers have become commonplace. The accuracies of these methods are under question in health care. Mass spectrometry (MS) is potentially a more accurate technique with the ability to demonstrate specificity. An introduction of the basic analytical aspects of liquid chromatography (LC)–MS/MS leads on to the validation of the method before general use. LC coupled with MS and tandem mass spectrometry (MSn) is being adopted in a number of hospital laboratories for the quantitative analysis of a number of analytes from physiological matrices, but standards for development and validation of such assays are not easily available. Most assays can be regarded as in-house methods and herein may lay the failure so far for mass spectrometric methods to improve quality of results between laboratories for an analyte using the same technology. Manufacturers are taking on board the experience of clinical laboratories with kits containing all or most of the disposable items and reagents. A number of documents and guidelines have been consulted. These documents are expensive to purchase, are often very long and not easy to read. This review highlights the specific requirements for introduction of a tandem mass spectrometric test for small molecules into a routine hospital laboratory. A number of experiments need to be planned and executed in order to describe a new quantitative method in terms of selectivity, accuracy, imprecision, sensitivity and stability. The introduction of a quantitative method based on tandem MS requires careful validation. This review has distilled out important points from a number of key documents in order to provide a working validation guideline for clinical laboratories. In a supplementary file a working document for assembling the assay validation is proposed.
Utility of the urine calcium-to-creatinine ratio to diagnose primary hyperparathyroidism in asymptomatic hypercalcaemic patients with vitamin D deficiency
Authors: Jayasena Channa N , Mahmud Mohammad , Palazzo Fausto , Donaldson Mandy , Meeran Karim , Dhillo Waljit S
Published: February 2011

Background

Primary hyperparathyroidism (PHP) is the most common cause of hypercalcaemia, and often requires surgical treatment. Familial hypocalciuric hypercalcaemia (FHH) has similar biochemical features to PHP, but requires no treatment. The most common biochemical method used to distinguish between PHP and FHH is the urine calcium-to-creatinine ratio (UCCR). Vitamin D deficiency may alter the renal excretion of calcium, but it is unclear how vitamin D deficiency affects the diagnostic performance of UCCR.

Aim

To examine the reliability of UCCR to detect PHP in patients presenting with asymptomatic hypercalcaemia, in the presence or absence of vitamin D deficiency.

Methods

One hundred and eighteen UCCR measurements from 97 asymptomatic hypercalcaemic patients diagnosed with PHP presenting to a single specialist endocrine unit were analysed retrospectively.

Results

A significantly higher proportion of UCCR measurements were <0.010 in patients with serum vitamin D <25 nmol/L when compared with patients with serum vitamin D >25 nmol/L, thus incorrectly suggesting the presence of FHH (proportion of measurements with UCCR >0.010: 11/48 [22.9%], vitamin D <25 nmol/L; 4/70 [5.7%], vitamin D >25 nmol/L; P < 0.001). Urine calcium concentration was 26% lower and serum parathyroid hormone (PTH) was 27% higher in patients with vitamin D deficiency when compared with patients without vitamin D deficiency.

Conclusions

These data suggest that the presence of vitamin D deficiency is associated with worsened PTH hypersecretion, impairment of urinary calcium excretion and reduced sensitivity of UCCR measurement with respect to the detection of PHP. These data have important clinical implications for the investigation and management of patients with asymptomatic hypercalcaemia.
Efficacy of major general surgery performed by non-physician clinicians at a central hospital in Malawi
Authors: Wilhelm Torsten J , Thawe Innocent K , Mwatibu Biswick , Mothes Henning , Post Stefan
Published: February 2011

In some sub-Saharan African countries non-physician clinicians have to perform major general surgery without medical officers and surgeons. The safety of this practice has not been established. The aim of this study was to evaluate the contribution of clinical officers (COs) to major general surgery at Zomba Central Hospital. We performed a retrospective five-year period study during 2003–2007. The perioperative outcome for three procedures was analysed. During the study 2931 major general surgical procedures were performed: 1437 (49%) by surgeons; 366 (12.5%) by COs assisted by surgeons; and 1128 (38.5%) by COs alone. COs performed 50% of prostatectomies, ventriculo-peritoneal-shuntings and strangulated hernia repairs with bowel resection alone. Baseline parameters and perioperative outcomes of the patients who underwent operations with surgeons present (as operator or assistant, ‘surgeon group’) or patients operated by COs alone (‘CO group’) were similar. COs can safely perform major general surgery when adequate training and supervision are provided.
Graphical Models for Economic Profit Maximization
Authors: Cobb Barry
Published: February 2011

Decision trees and influence diagrams are utilized to analyze and solve profit maximization problems from economics. As a complement to traditional analytical methods for solving these problems, use of these graphical representations allows students to learn about the effects of uncertainty on pricing and capacity choices. Decision trees are first used to model a firm's production capacity and pricing decisions when these choices are made simultaneously under certain and uncertain demand. The decision tree approach is next extended to a situation where the firm makes its capacity and price selections under different information constraints. The use of these problems as part of a case assignment in a writing-intensive managerial economics course is discussed. Influence diagrams are also presented as an alternative modeling technique that can easily accommodate more potential values for decision variables when solving these problems. By studying the effects of uncertainty on profit maximization problems, students can also learn to appreciate that dealing with uncertainty is important in many business decisions.
Clique Relaxations in Social Network Analysis: The Maximum k-Plex Problem
Authors: Balasundaram Balabhaskar , Butenko Sergiy , Hicks Illya V.
Published: February 2011

This paper introduces and studies the maximum k-plex problem, which arises in social network analysis and has wider applicability in several important areas employing graph-based data mining. After establishing NP-completeness of the decision version of the problem on arbitrary graphs, an integer programming formulation is presented, followed by a polyhedral study to identify combinatorial valid inequalities and facets. A branch-and-cut algorithm is implemented and tested on proposed benchmark instances. An algorithmic approach is developed exploiting the graph-theoretic properties of a k-plex that is effective in solving the problem to optimality on very large, sparse graphs such as the power law graphs frequently encountered in the applications of interest.
Optimal Inventory Policies when Purchase Price and Demand Are Stochastic
Authors: Berling Peter , Martínez-de-Albéniz Victor
Published: February 2011

In this paper we consider the problem of a firm that faces a stochastic (Poisson) demand and must replenish from a market in which prices fluctuate, such as a commodity market. We describe the price evolution as a continuous stochastic process and we focus on commonly used processes suggested by the financial literature, such as the geometric Brownian motion and the Ornstein-Uhlenbeck process. It is well known that under variable purchase price, a price-dependent base-stock policy is optimal. Using the single-unit decomposition approach, we explicitly characterize the optimal base-stock level using a series of threshold prices. We show that the base-stock level is first increasing and then decreasing in the current purchase price. We provide a procedure for calculating the thresholds, which yields closed-form solutions when price follows a geometric Brownian motion and implicit solutions under the Ornstein-Uhlenbeck price model. In addition, our numerical study shows that the optimal policy performs much better than inventory policies that ignore future price evolution, because it tends to place larger orders when prices are expected to increase.
Supply Chain Competition with Multiple Manufacturers and Retailers
Authors: Adida Elodie , DeMiguel Victor
Published: February 2011

We study competition in a supply chain where multiple manufacturers compete in quantities to supply a set of products to multiple risk-averse retailers who compete in quantities to satisfy the uncertain consumer demand. For the symmetric supply chain, we give closed-form expressions for the unique equilibrium. We find that, provided there is a sufficiently large number of manufacturers and retailers, the supply chain efficiency (the ratio of the aggregate utility in the decentralized and centralized chains) can be raised to 1 by inducing the right degree of retailer differentiation. Also, risk aversion results in triple marginalization: retailers require a strictly positive margin to distribute even when they are perfectly competitive, because otherwise they are unwilling to undertake the risk associated with the uncertainty in demand. For the asymmetric supply chain, we show how numerical optimization can be used to compute the equilibria, and we find that the supply chain efficiency may drop sharply with the asymmetry of either manufacturers or retailers. We also find that the introduction of asymmetric product assortment reduces the degree of competition among retailers and thus has an effect similar to that of reducing the number of retailers. We show that, unlike in the symmetric chain, the asymmetric chain efficiency depends on product differentiation and risk aversion because of the interaction between these features and the asymmetry of manufacturers and retailers.
On the Minimax Complexity of Pricing in a Changing Environment
Authors: Besbes Omar , Zeevi Assaf
Published: February 2011

We consider a pricing problem in an environment where the customers' willingness-to-pay (WtP) distribution may change at some point over the selling horizon. Customers arrive sequentially and make purchase decisions based on a quoted price and their private reservation price. The seller knows the WtP distribution pre- and postchange but does not know the time at which this change occurs. The performance of a pricing policy is measured in terms of regret: the loss in revenues relative to an oracle that knows the time of change prior to the start of the selling season. We derive lower bounds on the worst-case regret and develop pricing strategies that achieve the order of these bounds, thus establishing the complexity of the pricing problem. Our results shed light on the role of price experimentation and its necessity for optimal detection of changes in market response/WtP. Our formulation allows for essentially arbitrary consumer WtP distributions and purchase request patterns.
Routing and Staffing in Large-Scale Service Systems: The Case of Homogeneous Impatient Customers and Heterogeneous Servers
Authors: Armony Mor , Mandelbaum Avishai
Published: February 2011

Motivated by call centers, we study large-scale service systems with homogeneous impatient customers and heterogeneous servers; the servers differ with respect to their speed of service. For this model, we propose staffing and routing rules that are jointly asymptotically optimal in the heavy-traffic many-server QED, ED, and ED + QED regimes, respectively. For the QED regime, our proposed routing rule is FSF, that assigns customers to the fastest server available first. In the ED and ED + QED regimes, all work-conserving policies perform (asymptotically) equally well. In all these regimes, the form of the asymptotically optimal staffing is consistent with the asymptotically optimal staffing in the same regimes in the single-pool case, respectively. In particular, the total service capacity is (asymptotically) equal to a term that is proportional to the arrival rate plus, possibly, a term that is proportional to the square-root of the arrival rate, with both terms being regime dependent. Our specific proposed approximation for the optimal staffing vector is obtained via a straightforward solution to a deterministic optimization problem subject to a linear feasible region.
Finite Disjunctive Programming Characterizations for General Mixed-Integer Linear Programs
Authors: Chen Binyuan , Küçükyavuz Simge , Sen Suvrajeet
Published: February 2011

In this paper, we give a finite disjunctive programming procedure to obtain the convex hull of general mixed-integer linear programs (MILP) with bounded integer variables. We propose a finitely convergent convex hull tree algorithm that constructs a linear program that has the same optimal solution as the associated MILP. In addition, we combine the standard notion of sequential cutting planes with ideas underlying the convex hull tree algorithm to help guide the choice of disjunctions to use within a cutting plane method. This algorithm, which we refer to as the cutting plane tree algorithm, is shown to converge to an integral optimal solution in finitely many iterations. Finally, we illustrate the proposed algorithm on three well-known examples in the literature that require an infinite number of elementary or split disjunctions in a rudimentary cutting plane algorithm.
A Model of Instrumental Networks: The Roles of Socialized Charismatic Leadership and Group Behavior
Authors: Varella Paul , Javidan Mansour , Waldman David A.
Published: February 2011

This article introduces a model of the development of instrumental networks inside organizational groups. We provide a theoretical framework and empirically test a series of hypotheses pertaining to the relationships between socialized charismatic leadership (SCL) and its consequences in terms of cooperative and sanctioning group behavior. We then examine whether these behaviors predict the density of instrumental networks inside groups and, consequently, their performance. Our findings, based on assessments of 70 group leaders and their approximately 500 subordinates, colleagues, and supervisors, show that SCL is associated with heightened levels of cooperation and lower levels of sanctioning in groups. Cooperation, in turn, is associated with the instrumental network density of the group. Our findings also demonstrate that under conditions of physical proximity, instrumental network density predicts group performance. The study provides an understanding of group social psychological processes in relation to the development of instrumental networks inside organizational groups.
Organizing Ecologies of Complex Innovation
Authors: Dougherty Deborah , Dunne Danielle D.
Published: February 2011

For many sectors like health care, financial services, or renewable energy, new products and services are generated by an ecology of business firms, nonprofit foundations, public institutions, and other agents. Knowledge to innovate is dispersed across ecologies, so no single firm or small group of firms can innovate alone. Moreover, many new products and services in ecologies such as health care or energy are complex or comprise many parts with unknown interactions. New products, knowledge, business models, and applications all emerge unpredictably over considerable time periods, as various agents in the ecologies of innovation interact with and react to the actions of others. However, the existing organizing structure in these ecologies stifles emergence and precludes much innovation, simply because theory and practice do not adequately address how to organize for complex innovation. We develop a preliminary model for organizing ecologies of complex innovation. We suggest that innovations can continually emerge productively if people work locally in ecologies to set and solve problems of orchestrating knowledge capabilities across the ecology, strategizing across the ecology to create new businesses and applications, and developing public policies to embrace ambiguity. Using examples from biopharmaceuticals and alternative energy, we develop specific organizing ideas that can be examined and elaborated upon. This new direction for organization science integrates existing ideas around a new kind of organizing and shows how organization science can add real value in addressing major challenges of public welfare and safety in the 21st century.
Legitimating Nascent Collective Identities: Coordinating Cultural Entrepreneurship
Authors: Wry Tyler , Lounsbury Michael , Glynn Mary Ann
Published: February 2011

The concept of collective identity has gained prominence within organizational theory as researchers have studied how it consequentially shapes organizational behavior. However, much less attention has been paid to the question of how nascent collective identities become legitimated. Although it is conventionally argued that membership expansion leads to collective identity legitimacy, we draw on the notion of cultural entrepreneurship to argue that the relationship is more complex and is culturally mediated by the stories told by group members. We propose a theoretical framework about the conditions under which the collective identity of a nascent entrepreneurial group is more likely to be legitimated. Specifically, we posit that legitimacy is more likely to be achieved when members articulate a clear defining collective identity story that identifies the group's orienting purpose and core practices. Although membership expansion can undermine legitimation by introducing discrepant actors and practices to a collective identity, this potential downside is mitigated by growth stories, which help to coordinate expansion. Finally, we theorize how processes associated with collective identity membership expansion might affect the evolution of defining collective identity stories.
Genetic Mechanisms of Antimicrobial Resistance of Acinetobacter Baumannii
Authors: Esterly John S , Richardson Chad L , Eltoukhy Noha S , Qi Chao , Scheetz Marc H
Published: February 2011

OBJECTIVE:

To summarize published data identifying known genetic mechanisms of antibiotic resistance in Acinetobacter baumannii and the correlating phenotypic expression of antibiotic resistance.

DATA SOURCES:

MEDLINE databases (1966-July 15, 2010) were searched to identify original reports of genetic mechanisms of antibiotic resistance in A. baumannii.

DATA SYNTHESIS:

Numerous genetic mechanisms of resistance to multiple classes of antibiotics are known to exist in A. baumannii, a gram-negative bacterium increasingly implicated in nosocomial infections. Mechanisms may be constitutive or acquired via plasmids, integrons, and transposons. Methods of resistance include enzymatic modification of antibiotic molecules, modification of antibiotic target sites, expression of efflux pumps, and downregulation of cell membrane porin channel expression. Resistance to β-lactams appears to be primarily caused by β-lactamase production, including extended spectrum β-lactamases ( blaTEM, blaSHV, blaCTX-M. blaKPC), metallo-β-lactamases ( blaIMP, blaVIM, blaSIM), and most commonly, oxacillinases ( blaOXA). Antibiotic target site alterations confer resistance to fluoroquinolones ( gyrA, parC) and aminoglycosides ( arm, rmt), and to a much lesser extent, β-lactams. Efflux pumps ( tet, ade, abe) contribute to resistance against β-lactams, tetracyclines, fluoroquinolones, and aminoglycosides. Finally, porin channel deletion ( carO, oprD) appears to contribute to β-lactam resistance and may contribute to rarely seen polymyxin resistance. Of note, efflux pumps and porin deletions as solitary mechanisms may not render clinical resistance to A. baumannii.

CONCLUSIONS:

A. baumannii possesses copious genetic resistance mechanisms. Knowledge of local genotypes and expressed phenotypes for A. baumannii may aid clinicians more than phenotypic susceptibilities reported in large epidemiologic studies.
Strategies to Improve Medication Adherence Reported by Diabetes Patients and Caregivers: Results of a Taking Control of Your Diabetes Survey
Authors: Morello Candis M , Chynoweth Megan , Kim Hoim , Singh Renu F , Hirsch Jan D
Published: February 2011

BACKGROUND:

Published studies assessing specific methods that patients with diabetes and their caregivers perceive as helpful means of increasing medication adherence are lacking.

OBJECTIVE:

To determine methods that patients with diabetes and their caregivers have used to improve medication adherence, investigate the perceived helpfulness of these methods, and identify motivating factors and medication characteristics that may positively influence adherence.

METHODS:

A cross-sectional survey was distributed to patients with diabetes and caregivers of patients with diabetes at the 11th annual Taking Control of Your Diabetes conference in October 2005 at the San Diego Convention Center. Outcome measures were self-reported medication adherence, perceived helpfulness of methods employed to improve adherence, motivating factors that may improve adherence, and medication characteristics that may improve adherence.

RESULTS:

A total of 524 (40.5% response rate) questionnaires were included in the final analysis, 357 from patients with diabetes and 167 from caregivers. Taking medications as part of a daily routine and using pill boxes were the most frequently reported helpful methods for improving medication adherence. The 3 motivating factors most commonly identified as improving medication adherence were: knowing that diabetes medications work effectively to lower blood glucose, knowing how to manage medication adverse effects, and understanding medication benefits. Many participants thought that newer injectable diabetes medications resulting in weight loss or no additional blood glucose monitoring would be helpful in optimizing adherence.

CONCLUSIONS:

Participants in this study identified medication education as a key factor in improving adherence. To empower patients to overcome medication adherence barriers, pharmacists could perform more proactive and thorough counseling sessions that include education on indication, mechanism of action, and therapeutic effects of drugs. They could recommend that patients take medications concurrently with a daily routine and use a pill box, as these actions were reported to be likely to improve medication adherence. However, our results also remind us that motivating factors and tools that may improve adherence may be very patient specific and that pharmacists should incorporate an assessment of this variance in their counseling sessions.