bluuebunny/crossref_metadata_2025 huggingface dataset:
The Costs of Related Diversification: The Impact of the Core Business on the Productivity of Related Segments
Authors: Kumar M. V. Shyam
Published: February 2013

I develop the thesis that in related diversified firms, the core business (in my analysis, the largest business) may provide benefits such as scope economies to a related segment, but it may also exert power and constrain the segment to act in its interests in various internal and external transactions. This enables the core business to shift productivity gains toward itself from the segment, which could lead to various inefficiencies within the related diversified firm. Using input/output flow data and a multilevel model with the segment as the unit of analysis, I first show that a segment’s productivity is lower compared with a single-business firm when it shares backward and forward complementarity (i.e., when it shares transactions with common suppliers and customers) with the core business. Correspondingly, I show that as a mirror image, the core business’s productivity is enhanced when the business shares backward and forward complementarity with segments and when segments are backward integrated with it (i.e., when the core business provides outputs to segments). These shifts in productivity and the attendant inefficiencies do not seem to be destroying the entire value from related diversification. Overall, the findings support the argument that the power and influence exerted by the core business—and concomitantly, the subsidization of the core business by related segments—is an important source of costs borne by segments in a related diversified firm.
Open Door Disclosure in Civil Litigation
Authors: Higgins Andrew
Published: February 2013

This article offers a defence of broad disclosure in civil litigation given its value in helping parties enforce their legal rights or uphold the law. Nonetheless there is an inherent tension between accuracy, cost and time in determining disputes, and there are legitimate concerns that disclosure has become too costly. The article argues that the primary disclosure obligation in large cases should be to open one's door to the other party. It would then be incumbent on the party seeking disclosure to review an opponent's files for relevant documents. The party giving disclosure would have additional rights to protect privileged and private information, including guarantees against the use and further disclosure of such information. This model will promote efficiency because it puts the decision as to how much to invest in disclosure directly in the hands of the party seeking it. Recent proposals that would allow open door or ‘keys to the warehouse’ disclosure are welcome, and it would be desirable to formally recognise this disclosure model in the rules.
Regulatory polymorphisms in CYP2C19 affecting hepatic expression
Authors: Sanford Jonathan C. , Guo Yingying , Sadee Wolfgang , Wang Danxin
Published: February 2013

Background: Cytochrome P450 2C19 is responsible for the metabolism of many drugs, including the activation of clopidogrel. The allele CYP2C19*17 is associated with ultra-rapid metabolizer phenotypes by increasing gene transcription. This study tests to what extent CYP2C19*17 enhances CYP2C19 expression in human liver and whether additional regulatory variants contribute to variation in CYP2C19 expression.

Methods: CYP2C19 mRNA was measured with quantitative real-time PCR (qRT-PCR), enzyme activity as metabolic velocity with S-mephenytoin as the substrate and allelic mRNA expression ratio with SNaPshot in human livers. CYP2C19 transcribed exons and a 4kb promoter region were sequenced using IonTorrent PGM or Sanger sequencing and screened for polymorphisms associated with total hepatic CYP2C19 mRNA, enzyme activity and allelic mRNA ratios.

Results: Livers heterozygote and homozygous for CYP2C19*17 had mRNA levels 1.8-fold (p=0.028) and 2.9-fold (p=0.006), respectively, above homozygous reference allele livers. CYP2C19*17 heterozygotes were also associated with increased allelic mRNA expression (allelic ratio ~1.8-fold, SD±0.6, p<0.005), whereas CYP2C19 enzyme activity was elevated 2.3-fold, with borderline significance (p=0.06) in CYP2C19*17 carriers. One liver sample of African ancestry displayed a 2-fold allelic expression ratio, and another sample, a ~12-fold increase in metabolic velocity. Neither case was accounted for by *17, which indicates the presence of additional regulatory variants.

Conclusions: Our findings confirm *17 as a regulatory polymorphism enhancing hepatic CYP2C19 expression 2-fold with potential to compensate for the loss of function allele CYP2C19*2. Additional regulatory factors may also enhance CYP2C19 expression in African American populations.
An ethical framework for the disposal of autologous stem cells
Authors: Petrini Carlo
Published: February 2013

The disposal of haematopoietic stem cells stored for autologous transplantation purposes becomes a problem for hospitals when the conditions for their preservation cease to exist. When these cells have been stored for a considerable time the problem often becomes an ethical one involving informed consent and is linked to at least two simultaneous circumstances: (i) the indications regarding disposal contained in available informed consent papers are either absent or too generic; (ii) the person who provided the sample can no longer be traced. This article proposes and discusses some of the ethical criteria for addressing this problem on the basis of the so-called “principles” of North American bioethics, and compares them with some of the principles and values proposed in other models of bioethics.
Effects of aqueous extract of Musa paradisiaca root on testicular function parameters of male rats
Authors: Yakubu Musa Toyin , Oyeyipo Theo Oyetayo , Quadri Ayodeji Luqman , Akanji Musbau Adewumi
Published: February 2013

Background: There is an age-long claim that the Musa paradisiaca root is used to manage reproductive dysfunction, most especially sexual dysfunction (as an aphrodisiac), but there are no data in the open scientific literature that have refuted or supported this claim and the effects of M. paradisiaca root on the testes. Therefore, this study was aimed at investigating the effect of oral administration of the aqueous extract of M. paradisiaca root on the testicular function parameters of male rat testes.

Methods: Sexually matured male albino rats (138.67±5.29 g) were randomly assigned into four groups, A, B, C, and D, that respectively received 0.5 mL (3.6 mL/kg body weight) of distilled water and 25, 50, and 100 mg/kg body weight of the extract, orally, once daily, for 14 days.

Results: The extract significantly increased (p<0.05) the testes-body weight ratio, total protein, sialic acid, glycogen, cholesterol, activities of alkaline phosphatase, γ-glutamyltransferase, acid phosphatase, and the concentration of testicular testosterone. In contrast, the extract decreased the concentrations of both luteinizing and follicle-stimulating hormones in the serum of the animals. The results revealed that oral administration of M. paradisiaca root extract at doses of 25, 50, and 100 mg/kg body weight enhanced the testosterone-dependent normal functioning of the testes.

Conclusions: Overall, the aqueous extract of M. paradisiaca stimulated the normal functioning of the testes and exhibited both androgenic and anabolic properties. The results may explain the rationale behind the folkloric beneficial effect of the plant in the management of reproductive dysfunction.
A discrepancy principle for generalized local regularization
of linear inverse problems
Authors: Brooks Cara D. , Lamm Patricia K.
Published: February 2013

A modified version of the classical discrepancy principle
is formulated for use with generalized local regularization operators
of the form

ℛ
α

=

(

a
α

I
+

𝒜
α

)

-
1

T
α

${\mathcal {R}_\alpha = (a_\alpha I + \mathcal {A}_\alpha )^{-1}T_\alpha }$

for the approximate solution of linear inverse problems
in Banach space with deterministically modeled noise. The choice of the
local regularization parameter according to the a posteriori
parameter selection strategy is shown to result in a class of convergent
regularization methods and a general rate of convergence is
provided. As an example, the theory is applied to establish convergence
and convergence rates for approximations obtained using a zeroth-order
local regularization scheme with the modified principle for solving
Volterra convolution equations in

L
p

(
0
,
1
)

${{L^p(0,1)}}$

,

p
∈
(
1
,
∞
)

${{p \in (1,\infty )}}$

. A numerical example is provided to illustrate the practical use and
effectiveness of the method.
Selective Optogenetic Activation of Rostral Ventrolateral Medullary Catecholaminergic Neurons Produces Cardiorespiratory Stimulation in Conscious Mice
Authors: Abbott Stephen B. G. , DePuy Seth D. , Nguyen Thanh , Coates Melissa B. , Stornetta Ruth L. , Guyenet Patrice G.
Published: February 2013

Activation of rostral ventrolateral medullary catecholaminergic (RVLM-CA) neurons e.g., by hypoxia is thought to increase sympathetic outflow thereby raising blood pressure (BP). Here we test whether these neurons also regulate breathing and cardiovascular variables other than BP. Selective expression of ChR2-mCherry by RVLM-CA neurons was achieved by injecting Cre-dependent vector AAV2-EF1α-DIO-ChR2-mCherry unilaterally into the brainstem of dopamine-β-hydroxylaseCre/0mice. Photostimulation of RVLM-CA neurons increased breathing in anesthetized and conscious mice. In conscious mice, photostimulation primarily increased breathing frequency and this effect was fully occluded by hypoxia (10% O2). In contrast, the effects of photostimulation were largely unaffected by hypercapnia (3 and 6% CO2). The associated cardiovascular effects were complex (slight bradycardia and hypotension) and, using selective autonomic blockers, could be explained by coactivation of the sympathetic and cardiovagal outflows. ChR2-positive RVLM-CA neurons expressed VGLUT2 and their projections were mapped. Their complex cardiorespiratory effects are presumably mediated by their extensive projections to supraspinal sites such as the ventrolateral medulla, the dorsal vagal complex, the dorsolateral pons, and selected hypothalamic nuclei (dorsomedial, lateral, and paraventricular nuclei).

In sum, selective optogenetic activation of RVLM-CA neurons in conscious mice revealed two important novel functions of these neurons, namely breathing stimulation and cardiovagal outflow control, effects that are attenuated or absent under anesthesia and are presumably mediated by the numerous supraspinal projections of these neurons. The results also suggest that RVLM-CA neurons may underlie some of the acute respiratory response elicited by carotid body stimulation but contribute little to the central respiratory chemoreflex.
A Sensory-Labeled Line for Cold: TRPM8-Expressing Sensory Neurons Define the Cellular Basis for Cold, Cold Pain, and Cooling-Mediated Analgesia
Authors: Knowlton Wendy M. , Palkar Radhika , Lippoldt Erika K. , McCoy Daniel D. , Baluch Farhan , Chen Jessica , McKemy David D.
Published: February 2013

Many primary sensory neurons are polymodal, responding to multiple stimulus modalities (chemical, thermal, or mechanical), yet each modality is recognized differently. Although polymodality implies that stimulus encoding occurs in higher centers, such as the spinal cord or brain, recent sensory neuron ablation studies find that behavioral responses to different modalities require distinct subpopulations, suggesting the existence of modality-specific labeled lines at the level of the sensory afferent. Here we provide evidence that neurons expressing TRPM8, a cold- and menthol-gated channel required for normal cold responses in mammals, represents a labeled line solely for cold sensation. We examined the behavioral significance of conditionally ablating TRPM8-expressing neurons in adult mice, finding that, like animals lacking TRPM8 channels (Trpm8−/−), animals depleted of TRPM8 neurons (“ablated”) are insensitive to cool to painfully cold temperatures. Ablated animals showed little aversion to noxious cold and did not distinguish between cold and a preferred warm temperature, a phenotype more profound than that ofTrpm8−/−mice which exhibit only partial cold-avoidance and -preference behaviors. In addition to acute responses, cold pain associated with inflammation and nerve injury was significantly attenuated in ablated andTrpm8−/−mice. Moreover, cooling-induced analgesia after nerve injury was abolished in both genotypes. Last, heat, mechanical, and proprioceptive behaviors were normal in ablated mice, demonstrating that TRPM8 neurons are dispensable for other somatosensory modalities. Together, these data show that, although some limited cold sensitivity remains inTrpm8−/−mice, TRPM8 neurons are required for the breadth of behavioral responses evoked by cold temperatures.
Changes in the Spinal Segmental Motor Output for Stepping during Development from Infant to Adult
Authors: Ivanenko Yuri P. , Dominici Nadia , Cappellini Germana , Di Paolo Ambrogio , Giannini Carlo , Poppele Richard E. , Lacquaniti Francesco
Published: February 2013

Human stepping movements emergein uteroand show several milestones during development to independent walking. Recently, imaging has become an essential tool for investigating the development and function of pattern generation networks in the spinal cord. Here we examine the development of the spinal segmental output by mapping the distribution of motoneuron activity in the lumbosacral spinal cord during stepping in newborns, toddlers, preschoolers, and adults. Newborn stepping is characterized by an alternating bilateral motor output with only two major components that are active at all lumbosacral levels of the spinal cord. This feature was similar across different cycle durations of neonate stepping. The alternating spinal motor output is consistent with a simpler organization of neuronal networks in neonates. Furthermore, a remarkable feature of newborn stepping is a higher overall activation of lumbar versus sacral segments, consistent with a rostrocaudal excitability gradient. In toddlers, the stance-related motor pool activity migrates to the sacral cord segments, while the lumbar motoneurons are separately activated at touchdown. In the adult, the lumbar and sacral patterns become more dissociated with shorter activation times. We conclude that the development of human locomotion from the neonate to the adult starts from a rostrocaudal excitability gradient and involves a gradual functional reorganization of the pattern generation circuitry.
A Two-Layer Biophysical Model of Cholinergic Neuromodulation in Olfactory Bulb
Authors: Li Guoshi , Cleland Thomas A.
Published: February 2013

Cholinergic inputs from the basal forebrain regulate multiple olfactory bulb (OB) functions, including odor discrimination, perceptual learning, and short-term memory. Previous studies have shown that nicotinic cholinergic receptor activation sharpens mitral cell chemoreceptive fields, likely via intraglomerular circuitry. Muscarinic cholinergic activation is less well understood, though muscarinic receptors are implicated in olfactory learning and in the regulation of synchronized oscillatory dynamics in hippocampus and cortex. To understand the mechanisms underlying cholinergic neuromodulation in OB, we developed a biophysical model of the OB neuronal network including both glomerular layer and external plexiform layer (EPL) computations and incorporating both nicotinic and muscarinic neuromodulatory effects. Our simulations show how nicotinic activation within glomerular circuits sharpens mitral cell chemoreceptive fields, even in the absence of EPL circuitry, but does not facilitate intrinsic oscillations or spike synchronization. In contrast, muscarinic receptor activation increases mitral cell spike synchronization and field oscillatory power by potentiating granule cell excitability and lateral inhibitory interactions within the EPL, but it has little effect on mitral cell firing rates and hence does not sharpen olfactory representations under a rate metric. These results are consistent with the theory that EPL interactions regulate the timing, rather than the existence, of mitral cell action potentials and perform their computations with respect to a spike timing-based metric. This general model suggests that the roles of nicotinic and muscarinic receptors in olfactory bulb are both distinct and complementary to one another, together regulating the effects of ascending cholinergic inputs on olfactory bulb transformations.
Microscale Inhomogeneity of Brain Tissue Distorts Electrical Signal Propagation
Authors: Nelson Matthew J. , Bosch Clémentine , Venance Laurent , Pouget Pierre
Published: February 2013

Interpretations of local field potentials (LFPs) are typically shaped on an assumption that the brain is a homogenous conductive milieu. However, microscale inhomogeneities including cell bodies, dendritic structures, axonal fiber bundles and blood vessels are unequivocally present and have different conductivities and permittivities than brain extracellular fluid. To determine the extent to which these obstructions affect electrical signal propagation on a microscale, we delivered electrical stimuli intracellularly to individual cells while simultaneously recording the extracellular potentials at different locations in a rat brain slice. As compared with relatively unobstructed paths, signals were attenuated across frequencies when fiber bundles were in between the stimulated cell and the extracellular electrode. Across group of cell bodies, signals were attenuated at low frequencies, but facilitated at high frequencies. These results show that LFPs do not reflect a democratic representation of neuronal contributions, as certain neurons may contribute to the LFP more than others based on the local extracellular environment surrounding them.
Axons Giving Rise to the Palisade Endings of Feline Extraocular Muscles Display Motor Features
Authors: Zimmermann Lars , Morado-Díaz Camilo J. , Davis-López de Carrizosa María A. , de la Cruz Rosa R. , May Paul J. , Streicher Johannes , Pastor Ángel M. , Blumer Roland
Published: February 2013

Palisade endings are nerve specializations found in the extraocular muscles (EOMs) of mammals, including primates. They have long been postulated to be proprioceptors. It was recently demonstrated that palisade endings are cholinergic and that in monkeys they originate from the EOM motor nuclei. Nevertheless, there is considerable difference of opinion concerning the nature of palisade ending function.

Palisade endings in EOMs were examined in cats to test whether they display motor or sensory characteristics. We injected an anterograde tracer into the oculomotor or abducens nuclei and combined tracer visualization with immunohistochemistry and α-bungarotoxin staining. Employing immunohistochemistry, we performed molecular analyses of palisade endings and trigeminal ganglia to determine whether cat palisade endings are a cholinergic trigeminal projection.

We confirmed that palisade endings are cholinergic and showed, for the first time, that they, like extraocular motoneurons, are also immunoreactive for calcitonin gene-related peptide. Following tracer injection into the EOM nuclei, we observed tracer-positive palisade endings that exhibited choline acetyl transferase immunoreactivity. The tracer-positive nerve fibers supplying palisade endings also established motor terminals along the muscle fibers, as demonstrated by α-bungarotoxin. Neither the trigeminal ganglion nor the ophthalmic branch of the trigeminal nerve contained cholinergic elements.

This study confirms that palisade endings originate in the EOM motor nuclei and further indicates that they are extensions of the axons supplying the muscle fiber related to the palisade. The present work excludes the possibility that they receive cholinergic trigeminal projections. These findings call into doubt the proposed proprioceptive function of palisade endings.
Eye Movement Targets Are Released from Visual Crowding
Authors: Harrison William J. , Mattingley Jason B. , Remington Roger W.
Published: February 2013

Our ability to recognize objects in peripheral vision is impaired when other objects are nearby (Bouma, 1970). This phenomenon, known as crowding, is often linked to interactions in early visual processing that depend primarily on the retinal position of visual stimuli (Pelli, 2008; Pelli and Tillman, 2008). Here we tested a new account that suggests crowding is influenced by spatial information derived from an extraretinal signal involved in eye movement preparation. We had human observers execute eye movements to crowded targets and measured their ability to identify those targets just before the eyes began to move. Beginning ∼50 ms before a saccade toward a crowded object, we found that not only was there a dramatic reduction in the magnitude of crowding, but the spatial area within which crowding occurred was almost halved. These changes in crowding occurred despite no change in the retinal position of target or flanking stimuli. Contrary to the notion that crowding depends on retinal signals alone, our findings reveal an important role for eye movement signals. Eye movement preparation effectively enhances object discrimination in peripheral vision at the goal of the intended saccade. These presaccadic changes may enable enhanced recognition of visual objects in the periphery during active search of visually cluttered environments.
Structural-Functional Properties of Identified Excitatory and Inhibitory Interneurons within Pre-Bötzinger Complex Respiratory Microcircuits
Authors: Koizumi Hidehiko , Koshiya Naohiro , Chia Justine X. , Cao Fang , Nugent Joseph , Zhang Ruli , Smith Jeffrey C.
Published: February 2013

We comparatively analyzed cellular and circuit properties of identified rhythmic excitatory and inhibitory interneurons within respiratory microcircuits of the neonatal rodent pre-Bötzinger complex (pre-BötC), the structure generating inspiratory rhythm in the brainstem. We combined high-resolution structural–functional imaging, molecular assays for neurotransmitter phenotype identification in conjunction with electrophysiological property phenotyping, and morphological reconstruction of interneurons in neonatal rat and mouse slicesin vitro. This approach revealed previously undifferentiated structural–functional features that distinguish excitatory and inhibitory interneuronal populations. We identified distinct subpopulations of pre-BötC glutamatergic, glycinergic, GABAergic, and glycine-GABA coexpressing interneurons. Most commissural pre-BötC inspiratory interneurons were glutamatergic, with a substantial subset exhibiting intrinsic oscillatory bursting properties. Commissural excitatory interneurons projected with nearly planar trajectories to the contralateral pre-BötC, many also with axon collaterals to areas containing inspiratory hypoglossal (XII) premotoneurons and motoneurons. Inhibitory neurons as characterized in the present study did not exhibit intrinsic oscillatory bursting properties, but were electrophysiologically distinguished by more pronounced spike frequency adaptation properties. Axons of many inhibitory neurons projected ipsilaterally also to regions containing inspiratory XII premotoneurons and motoneurons, whereas a minority of inhibitory neurons had commissural axonal projections. Dendrites of both excitatory and inhibitory interneurons were arborized asymmetrically, primarily in the coronal plane. The dendritic fields of inhibitory neurons were more spatially compact than those of excitatory interneurons. Our results are consistent with the concepts of a compartmental circuit organization, a bilaterally coupled excitatory rhythmogenic kernel, and a role of pre-BötC inhibitory neurons in shaping inspiratory pattern as well as coordinating inspiratory and expiratory activity.
Murine basal cell carcinoma leads to tumor-mediated alterations in endocrine Igf1 signaling
Authors: Villani Rehan M , Waters Michael J , Wainwright Brandon J
Published: February 2013

The intrinsic properties underlying cancer development are extensively studied while the effect of a cancer on the host is often overlooked. Activation of the Hedgehog (Hh) signaling pathway underlies a number of types of common human cancers, yet little is known concerning endocrine signaling in such tumors. Here, we investigated endocrine signaling in a murine model of basal cell carcinoma (BCC) of the skin, the most common cancer. BCCs were generated by the activation of Hh signaling resulting from the specific deletion of thePtch1gene in the developing epidermis. Subsequently, a severe growth deficiency was observed in the murine BCC model, and we identified a deficiency of circulating IGF1 (Igf1). We demonstrate that Hh pathway activation in murine BCC induces IGF binding proteins, thereby regulating Igf1 sequestration into the skin and skewing Igf endocrine signaling. Significantly, these results show that Hh-induced tumors can have endocrine effects on normal tissues that in turn can greatly impact the host. This study not only identifies that Igf is important in Hh-associated skin tumors but also exemplifies the need to consider endocrine signaling when interpreting complexin vivotumor models.
MEK inhibition leads to lysosome-mediated Na+/I− symporter protein degradation in human breast cancer cells
Authors: Zhang Zhaoxia , Beyer Sasha , Jhiang Sissy M
Published: February 2013

The Na+/I−symporter (NIS (SLC5A5)) is a transmembrane glycoprotein that mediates active iodide uptake into thyroid follicular cells. NIS-mediated iodide uptake in thyroid cells is the basis for targeted radionuclide imaging and treatment of differentiated thyroid carcinomas and their metastases. Furthermore, NIS is expressed in many human breast tumors but not in normal non-lactating breast tissue, suggesting that NIS-mediated radionuclide uptake may also allow the imaging and targeted therapy of breast cancer. However, functional cell surface NIS expression is often low in breast cancer, making it important to uncover signaling pathways that modulate NIS expression at multiple levels, from gene transcription to posttranslational processing and cell surface trafficking. In this study, we investigated NIS regulation in breast cancer by MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK) signaling, an important cell signaling pathway involved in oncogenic transformation. We found that MEK inhibition decreased NIS protein levels in all-trans retinoic acid/hydrocortisone-treated MCF-7 cells as well as human breast cancer cells expressing exogenous NIS. The decrease in NIS protein levels by MEK inhibition was not accompanied by a decrease inNISmRNA or a decrease inNISmRNA export from the nucleus to the cytoplasm. NIS protein degradation upon MEK inhibition was prevented by lysosome inhibitors but not by proteasome inhibitors. Interestingly, NIS protein level was correlated with MEK/ERK activation in human breast tumors from a tissue microarray. Taken together, MEK activation appears to play an important role in maintaining NIS protein stability in human breast cancers.
Oocyte–cumulus cell interactions regulate free intracellular zinc in mouse oocytes
Authors: Lisle R S , Anthony K , Randall M A , Diaz F J
Published: February 2013

Zinc increases in the oocyte during maturation and is required for progression and completion of meiosis. The objective of this study was to determine whether cumulus cells regulate the levels of free intracellular zinc in the oocyte during maturation. In the cumulus–oocyte complex (COC) the relative level of free intracellular zinc was almost fourfold higher in cumulus cells compared with the resident germinal vesicle-stage oocyte. Removal of cumulus cells caused a fourfold increase in intracellular zinc in the oocyte by 1 h after cumulus cell removal, but subsequent coculture of denuded oocytes with COC decreased free intracellular zinc in the oocyte by 65%. Thus, cumulus cells suppress free intracellular zinc in the oocyte. The mRNA transcripts for the zinc transporter proteins Slc39a6, Slc39a8, Slc39a9, Slc39a10, Slc39a12, Slc30a2, Slc30a4, Slc30a5 and Slc30a8 mRNAs were higher in oocytes, while Slc39a1, Slc39a7, Slc39a13, Slc39a14, Slc30a6, Slc30a7 and Slc30a9 mRNAs were higher in cumulus cells. Thus a complex zinc transport network is present in the COC. Pretreatment with epidermal growth factor for 4 h abolished the ability of COCs to restrict free intracellular zinc in denuded oocytes. Coculture of denuded metaphase II oocytes with COC lowers free intracellular zinc in mature oocytes. Oocytes matured in vivo or oocytes from older mice had lower levels of free intracellular zinc than oocytes matured in vitro or from younger mice. Thus, a precise mechanism for regulating oocyte zinc homeostasis has been uncovered in the COC that is disrupted with increasing age or by removal of cumulus cells.
Effect of xenogenic cortical bone on fracture healing in a canine fracture model
Authors: Heo Suyoung , So Kyoungmin , Kim Sehoon , Kim Minsu , Lee Haebeom , Kim Namsoo
Published: February 2013

The purpose of this study was to investigate the effect of xenogenic cortical bone (XCB) on fracture repair in the canine ulna. The entire group of animals (n = 12) had a transverse resection of 5 mm length at the middle part of the right ulnar diaphysis. In Group A (eight beagles), the fracture was treated with XCB and metal bone screw. In Group B (four beagles), the fracture was treated with metal bone plate and screw. Radiological, micro-computed tomography (micro-CT), histological examination and mechanical testing were employed to evaluate bone healing and reaction of XCB in the host bone. In Group A, bone union was noticed in 6 out of 8 dogs (75%), starting from the 4th week onwards. Micro-CT and histological examinations showed that the XCB was absorbed and incorporated into the host bone. Incorporation of XCB was observed in 7 cases (88%); it started from the 10th week onwards and continued to week 32 after surgery. Biomechanical strength of the bone fracture site was higher in Group A than in Group B, and was similar to that of normal bone. XCB enhances the bone healing process and can be used as absorbable internal fixation for the management of long bone fractures in dogs.
Transmission of porcine circovirus type 2b (PCV2b) in Kunming mice
Authors: Deng Zhi , Yuan An , Luo Wei , Wang Nai , Gong Qian , Yu Xing , Xue Li
Published: February 2013

To investigate porcine circovirus type 2b (PCV2b) transmission by contact and vertical infection in Kunming mice (an outbred mouse stock deriving from Swiss albino mice with a high ratio of gene heterozygosis), four mice in cage 6 were inoculated with PCV2b and 25 mice without any treatment were placed into cages 1 to 5 (five mice in each cage). Seven days after being infected, the PCV2-binoculated mice were co-mingled with non-inoculated mice from cages 1 to 5 successively at 7, 14, 21, 28 and 35 days post infection (dpi), respectively, for 3 days. In addition, eleven pregnant mice were injected with PCV2b. Samples were collected from non-inoculated mice and three newborn mice from each litter for PCV2b detection by polymerase chain reaction (PCR) and immunohistochemistry (IHC). The PCR results showed that PCV2b transmission rate among mice in cages 1, 2, 3, 4 and 5 was 0/5, 2/5, 5/5, 5/5 and 1/5, respectively. PCV2b antigen signals generally appeared in most organs of the non-inoculated mice in which viruses were detected by PCR. PCV2b DNA was also detected in newborn mice of PCV2b-infected litters, and viral antigen signals were observed in their organs as well. PCV2b was transmitted in Kunming mice by contact, and it also caused vertical infection through the placenta.
Genetic diversity of acute bee paralysis virus in Slovenian honeybee samples
Authors: Jamnikar Ciglenečki Urška , Toplak Ivan
Published: February 2013

The genetic diversity of acute bee paralysis virus (ABPV) in honeybees was studied in Slovenia. A total of 248 honeybee samples obtained from 134 different apiaries in Slovenia were tested for the presence of ABPV by RT-PCR. Specific 398-base pair (bp) products were generated with primers amplifying the ORF2 region and 452-base pair (bp) products with primers amplifying the ORF1 region of the viral genome. To characterise the overall nucleotide diversity among the ABPV sequences, phylogenetic trees with 54 and 29 samples were constructed from 357 nucleotides from ORF2 and 408 nucleotides from ORF1, respectively. The nucleotide comparison of Slovenian ABPV strains revealed two distinct clusters in ORF2 and ORF1, showing 91.2–92.5% and 96.7–97.2% nucleotide identity, respectively. Comparison of data regarding the geographical location of the ABPV-positive samples with the constructed phylogenetic trees revealed the random distribution of the two clusters throughout Slovenia.
Adjuvant Therapy With Zoledronic Acid in Patients With Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Valachis Antonis , Polyzos Nikolaos P. , Coleman Robert E. , Gnant Michael , Eidtmann Holger , Brufsky Adam M. , Aft Rebecca , Tevaarwerk Amye J. , Swenson Karen , Lind Pehr , Mauri Davide
Published: February 2013

Background.

The purpose of the study was to estimate the impact on survival and fracture rates of the use of zoledronic acid versus no use (or delayed use) in the adjuvant treatment of patients with early-stage (stages I–III) breast cancer.

Materials and Methods.

We performed a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library, and major cancer scientific meeting searches. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with zoledronic acid versus nonuse, placebo, or delayed use of zoledronic acid as treatment to individuals who develop osteoporosis were considered eligible. Standard meta-analytic procedures were used to analyze the study outcomes.

Results.

Fifteen studies were considered eligible and were further analyzed. The use of zoledronic acid resulted in a statistically significant better overall survival outcome (five studies, 6,414 patients; hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.70–0.94). No significant differences were found for the disease-free survival outcome (seven studies, 7,541 patients; HR, 0.86; 95% CI, 0.70–1.06) or incidence of bone metastases (seven studies, 7,543 patients; odds ratio [OR], 0.94; 95% CI, 0.64–1.37). Treatment with zoledronic acid led to a significantly lower overall fracture rate (OR, 0.78; 95% CI, 0.63–0.96). Finally, the rate of osteonecrosis of the jaw was 0.52%.

Conclusion.

Zoledronic acid as adjuvant therapy in breast cancer patients appears to not only reduce the fracture risk but also offer a survival benefit over placebo or no treatment.
Factors Associated With Fatigue After Surgery in Women With Early-Stage Invasive Breast Cancer
Authors: Rotonda Christine , Guillemin Francis , Bonnetain Franck , Velten Michel , Conroy Thierry
Published: February 2013

Learning Objectives

Describe the effect of worsening fatigue after breast cancer surgery on physical functioning and psychological distress. Better identify women at risk for developing cancer-related fatigue. Direct target interventions to patients most in need.

Purpose.

Fatigue is one of the most frequent symptoms in patients with cancer. However, the precise determinants of fatigue are still unknown. This study was conducted to investigate factors correlated with cancer-related fatigue before surgery and just before subsequent adjuvant therapy.

Methods.

Patients completed the Multidimensional Fatigue Inventory (MFI-20), the European Organization for Research and Treatment of Cancer 30-item quality-of-life questionnaire before and after surgery, the Trait Anxiety Inventory and the Life Orientation Test before surgery, and the State Anxiety Inventory before the start of adjuvant therapy. Multiple regression analysis of determinants of change in MFI-20 total score after surgery was conducted.

Results.

A series of 466 eligible patients with stage I–III breast cancer with planned surgery were recruited. An increase in MFI-20 total score after surgery was significantly correlated with higher preoperative fatigue and lower role functioning before surgery; a decrease in role functioning, physical functioning, and cognitive functioning after surgery; an increase in insomnia after surgery; and a higher state anxiety after surgery. Disease stage, lymph node metastases, surgical procedure, and demographic characteristics (e.g., age, marital status, having children, educational level) were not correlated with fatigue in multivariate analysis.

Conclusion.

These results suggest that worsening fatigue after surgery for breast cancer is associated with a decrease in physical functioning and an increase in psychological distress rather than with the cancer characteristics. Therefore, screening measures should be implemented at the time of diagnosis—before starting treatment—to identify psychologically vulnerable patients and to offer them professional support.
Predicting the Optimal Basal Insulin Infusion Pattern in Children and Adolescents on Insulin Pumps
Authors: Holterhus Paul-Martin , Bokelmann Jessica , Riepe Felix , Heidtmann Bettina , Wagner Verena , Rami-Merhar Birgit , Kapellen Thomas , Raile Klemens , Quester Wulf , Holl Reinhard W. ,   the German/Austrian DPV-Initiative and the German Pediatric CSII Working Group
Published: February 2013

OBJECTIVE

We aimed at developing and cross-validating a mathematical prediction model for an optimal basal insulin infusion pattern for children with type 1 diabetes on continuous subcutaneous insulin infusion therapy (CSII).

RESEARCH DESIGN AND METHODS

We used the German/Austrian DPV-Wiss database for quality control and scientific surveys in pediatric diabetology and retrieved all CSII patients <20 years of age (November 2009). A total of 1,248 individuals from our previous study were excluded (dataset 1), resulting in 6,063 CSII patients (dataset 2) (mean age 10.6 ± 4.3 years). Only the most recent basal insulin infusion rates (BRs) were considered. BR patterns were identified and corresponding patients sorted by unsupervised clustering. Logistic regression analysis was applied to calculate the probabilities for each BR pattern. Equations were based on both independent datasets separately, and probabilities for BR patterns were cross-validated using typical test patients.

RESULTS

Of the 6,063 children, 5,903 clustered in one of four major circadian BR patterns, confirming our previous study. The oldest age-group (mean age 12.8 years) was represented by 2,490 patients (42.18%) with a biphasic dawn-dusk pattern (BC). A broad single insulin maximum at 9–10 p.m. (F) was unveiled by 853 patients (14.45%) (mean age 6.3 years). Logistic regression analysis revealed that age, to a lesser extent duration of diabetes, and partly sex predicted BR patterns. Cross-validation revealed almost identical probabilities for BR patterns BC and F in the two datasets but some variation in the remaining two BR patterns.

CONCLUSIONS

Reconfirmation of four key BR patterns in two very large independent cohorts supports that these patterns are realistic approximations of the circadian distribution of insulin needs in children with type 1 diabetes. Prediction of an optimal pattern a priori can improve initiation and clinical follow-up of CSII in children and adolescents. In addition, these BR patterns represent valuable information for insulin-infusion algorithms in closed-loop CSII.
Stability of Finite-difference Schemes for Semilinear Multidimensional Parabolic Equations
Authors: Jovanovic Bosko , Lapinska-Chrzczonowicz Magdalena , Matus Aleh , Matus Piotr
Published: February 2013

Abstract — We have studied the stability of finite-difference schemes approximating
initial-boundary value problem (IBVP) for multidimensional parabolic equations with
a nonlinear source of a power type. We have obtained simple sufficient input data
conditions, in which the solutions of differential and difference problems are globally
bounded for all t. It is shown that if these conditions are not satisfied, then
the solution can blow-up (go to infinity) in finite time. The lower bound of the blow-up
time has been determined. The stability of the difference solution has been proven. In
all cases, we used the method of energy inequalities based on the application of the
Chaplygin comparison theorem for nonlinear ODEs, Bihari-type inequalities and their
discrete analogs.
Efficient Halley-like Methods for the Inclusion of Multiple Zeros of Polynomials
Authors: Petković Miodrag S. , Milošević Mimica R.
Published: February 2013

Starting from suitable zero-relation, we derive higher-order iterative methods
for the simultaneous inclusion of polynomial multiple zeros in circular complex
interval arithmetic. The convergence rate is increased using a family of two-point
methods of the fourth order for solving nonlinear equations as a predictor. The methods
are more efficient compared to existing inclusion methods for multiple zeros, based
on fixed point relations. Using the concept of the R-order of convergence of mutually
dependent sequences, we present the convergence analysis of the total-step and the
single-step methods. The proposed self-validated methods possess a great computational
efficiency since the acceleration of the convergence rate from four to seven is
achieved only by a few additional calculations. To demonstrate convergence behavior
of the presented methods, two numerical examples are given.
Norms of Discrete Trace Functions of (Ω) and (Ω)
Authors: Xu Jinchao , Zhang Shuo
Published: February 2013

This paper discusses the constructive and computational presentations of several non-local norms of discrete trace functions
of H¹(Ω) and H²(Ω) defined on the boundary or interface of an unstructured grid. We transform the nonlocal norms
of trace functions to local norms of certain functions defined on the whole domain by constructing isomorphic extension operators.
A unified approach is used to explore several typical examples. Additionally, we also discuss exactly invertible Poincaré–Steklov
operators and their discretization.
Domain Decomposition Preconditioning for Problems with Highly Varying Coefficients
Authors: Matsokin Aleksandr , Nepomnyaschikh Sergei
Published: February 2013

In this paper we construct efficient domain decomposition methods for solving
scalar second-order elliptic boundary problems in bounded two-dimensional domains
with small holes, and present some results of numerical experiments, confirming the efficiency
and robustness of the proposed
domain decomposition methods.
An overview of some recent developments on the Invariant Subspace Problem
Authors: Chalendar Isabelle , Partington Jonathan R.
Published: February 2013

An overview of some recent developments on the Invariant Subspace Problem

This paper presents an account of some recent approaches to the Invariant Subspace Problem. It contains a brief historical account of the problem, and some more detailed discussions of specific topics, namely, universal operators, the Bishop operators, and Read’s Banach space counter-example involving a finitely strictly singular operator.
Intelligent financial time series forecasting: A complex neuro-fuzzy approach with multi-swarm intelligence
Authors: Li Chunshien , Chiang Tai-Wei
Published: February 2013

Financial investors often face an urgent need to predict the future. Accurate forecasting may allow investors to be aware of changes in financial markets in the future, so that they can reduce the risk of investment. In this paper, we present an intelligent computing paradigm, called the Complex Neuro-Fuzzy System (CNFS), applied to the problem of financial time series forecasting. The CNFS is an adaptive system, which is designed using Complex Fuzzy Sets (CFSs) whose membership functions are complex-valued and characterized within the unit disc of the complex plane. The application of CFSs to the CNFS can augment the adaptive capability of nonlinear functional mapping, which is valuable for nonlinear forecasting. Moreover, to optimize the CNFS for accurate forecasting, we devised a new hybrid learning method, called the HMSPSO-RLSE, which integrates in a hybrid way the so-called Hierarchical Multi-Swarm PSO (HMSPSO) and the wellknown Recursive Least Squares Estimator (RLSE). Three examples of financial time series are used to test the proposed approach, whose experimental results outperform those of other methods.
DFIS: A novel data filling approach for an incomplete soft set
Authors: Qin Hongwu , Ma Xiuqin , Herawan Tutut , Zain Jasni Mohamad
Published: February 2013

The research on incomplete soft sets is an integral part of the research on soft sets and has been initiated recently. However, the existing approach for dealing with incomplete soft sets is only applicable to decision making and has low forecasting accuracy. In order to solve these problems, in this paper we propose a novel data filling approach for incomplete soft sets. The missing data are filled in terms of the association degree between the parameters when a stronger association exists between the parameters or in terms of the distribution of other available objects when no stronger association exists between the parameters. Data filling converts an incomplete soft set into a complete soft set, which makes the soft set applicable not only to decision making but also to other areas. The comparison results elaborated between the two approaches through UCI benchmark datasets illustrate that our approach outperforms the existing one with respect to the forecasting accuracy.
Combined classifier based on feature space partitioning
Authors: Woźniak Michał , Krawczyk Bartosz
Published: February 2013

This paper presents a significant modification to the AdaSS (Adaptive Splitting and Selection) algorithm, which was developed several years ago. The method is based on the simultaneous partitioning of the feature space and an assignment of a compound classifier to each of the subsets. The original version of the algorithm uses a classifier committee and a majority voting rule to arrive at a decision. The proposed modification replaces the fairly simple fusion method with a combined classifier, which makes a decision based on a weighted combination of the discriminant functions of the individual classifiers selected for the committee. The weights mentioned above are dependent not only on the classifier identifier, but also on the class number. The proposed approach is based on the results of previous works, where it was proven that such a combined classifier method could achieve significantly better results than simple voting systems. The proposed modification was evaluated through computer experiments, carried out on diverse benchmark datasets. The results are very promising in that they show that, for most of the datasets, the proposed method outperforms similar techniques based on the clustering and selection approach.