bluuebunny/crossref_metadata_2025 huggingface dataset:
Distributed adaptive swarm for obstacle avoidance
Authors: Hettiarachchi Suranga , Spears William M.
Published: November 2009

Purpose

The purpose of this paper is to demonstrate a novel use of a generalized Lennard‐Jones (LJ) force law inPhysicomimetics, combined with offline evolutionary learning, for the control of swarms of robots moving through obstacle fields towards a goal. The paper then extends the paradigm to demonstrate the utility of a real‐time online adaptive approach named distributed agent evolution with dynamic adaptation to local unexpected scenarios (DAEDALUS).

Design/methodology/approach

To achieve the best performance, the parameters of the force law used in the Physicomimetics approach are optimized, using an evolutionary algorithm (EA) (offline learning). A weighted fitness function is utilized consisting of three components: a penalty for collisions, lack of swarm cohesion, and robots not reaching the goal. Each robot of the swarm is then given a slightly mutated copy of the optimized force law rule set found with offline learning and the robots are introduced to a more difficult environment. The online learning framework (DAEDALUS) is used for swarm adaptation in this more difficult environment.

Findings

The novel use of the generalized LJ force law combined with an EA surpasses the prior state‐of‐the‐art in the control of swarms of robots moving through obstacle fields. In addition, the DAEDALUS framework allows the swarms of robots to not only learn and share behavioral rules in changing environments (in real time), but also to learn the proper amount of behavioral exploration that is appropriate.

Research limitations/implications

There are significant issues that arise with respect to “wall following methods” and “local minimum trap” problems. “Local minimum trap” problems have been observed in this paper, but this issue is not addressed in detail. The intention is to explore other approaches to develop more robust adaptive algorithms for online learning. It is believed that the learning of the proper amount of behavioral exploration can be accelerated.

Practical implications

In order to provide meaningful comparisons, this paper provides a more complete set of metrics than prior papers in this area. The paper examines the number of collisions between robots and obstacles, the distribution in time of the number of robots that reach the goal, and the connectivity of the formation as it moves.

Originality/value

This paper addresses the difficult task of moving a large number of robots in formation through a large number of obstacles. The important real‐world constraint of “obstructed perception” is modeled. The obstacle density is approximately three times the norm in the literature. The paper shows how concepts from population genetics can be used with swarms of agents to provide fast online adaptive learning in these challenging environments. In addition, this paper also presents a more complete set of metrics of performance.
Model independence in swarm robotics
Authors: Kazadi S.
Published: November 2009

Purpose

The purpose of this paper is to examine and illustrate the development of a methodology for generating swarms using lossless flocking.

Design/methodology/approach

A general methodology for swarm design is described. Examples of this approach in the literature are examined. A general requirement for lossless flocking is developed. The requirement is used in developing two swarm behaviors.

Findings

It is possible to apply the approach to the lossless flocking and to use the swarm condition to develop two swarm behaviors which satisfy this condition in many situations.

Research limitations/implications

This paper illustrates the general swarm engineering method and demonstrates how it can be properly applied.

Originality/value

The swarm engineering method is used to develop the “quark” model, a new physicomimetic model.
Decentralized evolution of robotic behavior using finite state machines
Authors: König Lukas , Mostaghim Sanaz , Schmeck Hartmut
Published: November 2009

Purpose

In evolutionary robotics (ER), robotic control systems are subject to a developmental process inspired by natural evolution. The purpose of this paper is to utilize a control system representation based on finite state machines (FSMs) to build a decentralized online‐evolutionary framework for swarms of mobile robots.

Design/methodology/approach

A new recombination operator for multi‐parental generation of offspring is presented and a known mutation operator is extended to harden parts of genotypes involved in good behavior, thus narrowing down the dimensions of the search space. A storage called memory genome for archiving the best genomes of every robot introduces a decentralized elitist strategy. These operators are studied in a factorial set of experiments by evolving two different benchmark behaviors such as collision avoidance and gate passing on a simulated swarm of robots. A comparison with a related approach is provided.

Findings

The framework is capable of robustly evolving the benchmark behaviors. The memory genome and the number of parents for reproduction highly influence the quality of the results; the recombination operator leads to an improvement in certain parameter combinations only.

Research limitations/implications

Future studies should focus on further improving mutation and recombination. Generality statements should be made by studying more behaviors and there is a need for experimental studies with real robots.

Practical implications

The design of decentralized ER frameworks is improved.

Originality/value

The framework is robust and has the advantage that the resulting controllers are easier to analyze than in approaches based on artificial neural networks. The findings suggest improvements in the general design of decentralized ER frameworks.
Adaptive swarm behavior acquisition by a neuro‐fuzzy system and reinforcement learning algorithm
Authors: Kuremoto Takashi , Obayashi Masanao , Kobayashi Kunikazu
Published: November 2009

Purpose

The purpose of this paper is to present a neuro‐fuzzy system with a reinforcement learning algorithm (RL) for adaptive swarm behaviors acquisition. The basic idea is that each individual (agent) has the same internal model and the same learning procedure, and the adaptive behaviors are acquired only by the reward or punishment from the environment. The formation of the swarm is also designed by RL, e.g. temporal difference (TD)‐error learning algorithm, and it may bring out a faster exploration procedure comparing with the case of individual learning.

Design/methodology/approach

The internal model of each individual composes a part of input states classification by a fuzzy net, and a part of optimal behavior learning network which adopting a kind of RL methodology named actor‐critic method. The membership functions and fuzzy rules in the fuzzy net are adaptively formed online by the change of environment states observed in the trials of agent's behaviors. The weights of connections between the fuzzy net and the action‐value functions of actor which provides a stochastic policy of action selection, and critic which provides an evaluation to state transmission, are modified by TD‐error.

Findings

Simulation experiments of the proposed system with several goal‐directed navigation problems are accomplished and the results show that swarms are successfully formed and optimized routes are found by swarm learning faster than the case of individual learning.

Originality/value

Two techniques, i.e. fuzzy identification system and RL algorithm, are fused into an internal model of the individuals for swarm formation and adaptive behavior acquisition. The proposed model may be applied to multi‐agent systems, swarm robotics, metaheuristic optimization, and so on.
A review and implementation of swarm pattern formation and transformation models
Authors: Varghese Blesson , McKee Gerard
Published: November 2009

Purpose

The purpose of this paper is to address a classic problem – pattern formation identified by researchers in the area of swarm robotic systems – and is also motivated by the need for mathematical foundations in swarm systems.

Design/methodology/approach

The work is separated out as inspirations, applications, definitions, challenges and classifications of pattern formation in swarm systems based on recent literature. Further, the work proposes a mathematical model for swarm pattern formation and transformation.

Findings

A swarm pattern formation model based on mathematical foundations and macroscopic primitives is proposed. A formal definition for swarm pattern transformation and four special cases of transformation are introduced. Two general methods for transforming patterns are investigated and a comparison of the two methods is presented. The validity of the proposed models, and the feasibility of the methods investigated are confirmed on the Traer Physics and Processing environment.

Originality/value

This paper helps in understanding the limitations of existing research in pattern formation and the lack of mathematical foundations for swarm systems. The mathematical model and transformation methods introduce two key concepts, namely macroscopic primitives and a mathematical model. The exercise of implementing the proposed models on physics simulator is novel.
A swarm of robots using RFID tags for synchronization and cooperation
Authors: Zecca Giulio , Couderc Paul , Banâtre Michel , Beraldi Roberto
Published: November 2009

Purpose

The purpose of this paper is to show how a swarm of robots can cooperate to achieve a common task, in a totally distributed and autonomous way, by exploiting powerful clues contained in some devices that are distributed in the environment. This system exploits a coordination mechanism that is twofold, using radio frequency identification (RFID) tags for spatial coordination, and wireless robot‐to‐robot communication for the temporal and semantic synchronization.

Design/methodology/approach

Progress in the pervasive computing field has led to the distribution of knowledge and computational power in the environment, rather than condensing it in a single, powerful entity. This vision of ambient intelligence is supported by the interchange of information between physically sparse agents cooperating to achieve a common goal. An emerging method for this kind of collaboration considers the agents as insects in a swarm, having the possibility of communicating directly or indirectly with each other. The goal is to fulfill a common task, showing that a collaborative behavior can be useful in the real world. The paper focuses on a technique for the coordination of swarm‐robots with low capabilities, driven by instructions learned from RFID tags used as distributed pervasive memories. These robots exploit ubiquitous computing to regroup in a synchronization area, make a formation in space, coordinate with team‐mates in the same zone, and finally complete a cooperative task. The algorithm is validated through a simulation environment, showing its applicability and performance, before the real implementation on Roomba‐like robots.

Findings

The goal of the research is to prove the feasibility of such a novel approach. It is observed that a swarm of robots can achieve a good degree of autonomous cooperation without a central infrastructure or global network, carrying out a goal in a fair time.

Originality/value

The value is given by the benefits of splitting the synchronization semantics into two levels: space, by exploiting RFID landmarks; and time, by exploiting wireless short‐range communication. RFID tags are used to distribute computational power and actively interact with the surrounding areas, allowing to learn and modify the state of the environment. Robot‐to‐robot communication, instead, is used for providing timing and semantic information. In the proposal, this augmented environment is used to allow a good level of coordination among robots, both in time and space, with the aim of building a cooperative system.
Inhibition of MMP‐9 transcription and suppression of tumor metastasis by pyrrole‐imidazole polyamide
Authors: Wang Xiaofei , Nagase Hiroki , Watanabe Takayoshi , Nobusue Hiroyuki , Suzuki Tsukasa , Asami Yukihiro , Shinojima Yui , Kawashima Hiroyuki , Takagi Keiko , Mishra Rajeev , Igarashi Jun , Kimura Makoto , Takayama Tadatoshi , Fukuda Noboru , Sugiyama Hiroshi
Published: November 2009

(Cancer Sci 2010; 101: 759–766)

Matrix metalloproteinase (MMP)‐9, the 92‐kDa type IV collagenase, contributes to tumor invasion and metastases, and strategies to down‐regulate its expression could ultimately be of clinical utility. A pyrrole‐imidazole (PI) polyamide that targets the activator protein‐1 (AP‐1)‐binding site of the MMP‐9 promoter was designed and synthesized as a gene‐silencing agent for tumor metastases. The synthesized product showed selective DNA binding ability. The MMP‐9 PI polyamide significantly inhibited MMP‐9’s mRNA expression, protein level, and enzymatic activity in human breast adenocarcinoma cells (MDA‐MB‐231). Furthermore, the MMP‐9 PI polyamide inhibited migration and invasion by in vitro wound‐healing and matrigel‐invasion assay. The FITC‐labeled PI polyamide was localized in nuclei in 45 min of incubation with an MDA‐MB‐231 cell and remained in the nuclei for up to 96 h after incubation in vitro. It was also quickly localized in the mouse cellular nuclei of many tissues, including liver, kidney, and spleen, after intravenous injection without using any drug‐delivery system. Moreover, the polyamide treatment significantly decreased metastasis in a mouse model of liver metastasis. Our results suggest that this PI polyamide, which targets the MMP‐9 gene promoter, can be a novel MMP‐9 down‐regulating molecule for antimetastasis.
Role of tumor‐associated lymphatic endothelial cells in metastasis: A study of epithelial ovarian tumor in vitro
Authors: Yang Shouhua , Zhu Xiaowu , Cai Liqiong , Cheng Henghui , Zhao Rongwei , Wang Hongbo , Zhao Hong , Wang Zehua
Published: November 2009

(Cancer Sci 2010; 101: 679–685)

Tumor‐associated lymphatic endothelial cells (TLEC) could play a key role in the process of tumor metastasis. The aim of this study was to investigate the effect of TLECs that were isolated from human epithelial ovarian tumor (EOT) on ovarian cancer cell line CAOV‐3 in vitro. First, TLECs in EOT were detected by immunochemistry and flow cytometry, then marked by lymphatic endothelial cell (LEC) marker LYVE‐1, isolated by magnetic beads, and cultured in vitro. The cells were identified by immunostaining of LEC markers LYVE‐1, Prox‐1, Podoplanin, VEGFR‐3, and pan‐endothelial cell marker CD31. TLECs from EOT can be detected, cultured, and identified in vitro successfully. The effects of TLECs on invasion and migration of CAOV‐3 cells were investigated by 12‐well Boyden chamber; the proliferation effect was studied by counting the Trypan blue exclusion cell number. Furthermore, changes in MMP‐2/9 secreted by CAOV‐3 cells treated with TLEC were shown using real‐time PCR and zymography, and TIMP‐1/2 was detected by real‐time PCR. In vitro, TLECs can enhance invasion and migration of CAOV‐3 cells, but have no significant effect on proliferation. It was clear that the expression of MMP‐9 increased and TIMP‐2 decreased in CAOV‐3 cells treated by TLECs, and the increasing of MMP‐9 was confirmed by zymography. TLECs from EOT can enhance migration and invasion of human ovarian carcinoma cell line in vitro, and the possible mechanism was through activation of MMP‐9/TIMP‐2.
Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis
Authors: Wada Shun‐ichi , Usami Ihomi , Umezawa Yoji , Inoue Hiroyuki , Ohba Shun‐ichi , Someno Tetsuya , Kawada Manabu , Ikeda Daishiro
Published: November 2009

(Cancer Sci 2010; 101: 743–750)

Although cytostatin analog protein phosphatase 2A (PP2A)‐specific inhibitors are promising candidates of a new type of anticancer drug, their development has been hindered because of their liability. To find new classes of PP2A‐specific inhibitors, we conducted a screening with microbial metabolites and found that rubratoxin A, a classical mycotoxin, is a highly specific and potent inhibitor of the enzyme. While rubratoxin A inhibits PP2A at Ki = 28.7 nm, it hardly inhibited any other phosphatases examined. Rubratoxin B, a close analog, also specifically but weakly inhibits PP2A at Ki = 3.1 μm. The inhibition of intracellular PP2A in cultured cells is obviously observed with 20 μm rubratoxin A treatment for 3 h, inducing the overphosphorylation in PP2A substrate proteins. Although rubratoxins and cytostatin differ in the apparent structures, these compounds share similarities in the structures in detail and PP2A‐binding manners. Rubratoxin A showed higher suppression of tumor metastasis and reduction of the primary tumor volume than cytostatin in mouse experiments. As a successor of cytostatin analogs, rubratoxin A should be a good compound leading to the development of antitumor drugs targeting PP2A.
Impact of evidence‐based medicine on the treatment of patients with unresectable hepatocellular carcinoma
Authors: GIANNINI E. G. , BODINI G. , CORBO M. , SAVARINO V. , RISSO D. , DI NOLFO M. A. , DEL POGGIO P. , BENVEGNÙ L. , FARINATI F. , ZOLI M. , BORZIO F. , CATURELLI E. , CHIARAMONTE M. , TREVISANI F. ,   FOR THE ITALIAN LIVER CANCER (ITA.LI.CA.) GROUP
Published: November 2009

Aliment Pharmacol Ther 31, 493–501

Background  A randomized controlled trial performed by the Barcelona Clinic Liver Cancer (BCLC) published in 2002 demonstrated that transcatheter arterial chemoembolisation (TACE) is an effective treatment for well‐selected patients with unresectable hepatocellular carcinoma (HCC).

Aim  To access whether this information has modified the use of TACE in clinical practice.

Methods  From 2042 HCC patients included in the Italian Liver Cancer database, we selected 336 cases diagnosed over two 4‐year periods (1999–2002, n = 161 and 2003–2006, n = 175), fulfilling the inclusion criteria of the BCLC study. These groups were compared for TACE application rate, patient characteristics and survival.

Results  Patients undergoing TACE increased in the 2003–2006 period (from 62% to 73%, P = 0.035), with an increase in of Child‐Pugh class A (from 64% to 77%, P = 0.048) and advanced HCC patients (from 54% to 69%, P = 0.041). In the 1999–2002 period, there was no significant difference in survival between TACE‐treated and untreated patients, while in the 2003–2006 period, TACE‐treated patients survived longer (P < 0.0001).

Conclusions  Following the publication of studies providing evidence of a survival benefit of TACE in selected patients with unresectable HCC, significantly more patients with well‐compensated cirrhosis underwent TACE within this very homogenous population, leading to an increased survival despite a more advanced tumour stage.
Neurokinin 3 Receptor Immunoreactivity in the Septal Region, Preoptic Area and Hypothalamus of the Female Sheep: Colocalisation in Neurokinin B Cells of the Arcuate Nucleus but not in Gonadotrophin‐Releasing Hormone Neurones
Authors: Amstalden M. , Coolen L. M. , Hemmerle A. M. , Billings H. J. , Connors J. M. , Goodman R. L. , Lehman M. N.
Published: November 2009

Recent evidence has implicated neurokinin B (NKB) in the complex neuronal network mediating the effects of gonadal steroids on the regulation of gonadotrophin‐releasing hormone (GnRH) secretion. Because the neurokinin 3 receptor (NK3R) is considered to mediate the effects of NKB at the cellular level, we determined the distribution of immunoreactive NK3R in the septal region, preoptic area (POA) and hypothalamus of the ewe. NK3R cells and/or fibres were found in areas including the bed nucleus of the stria terminalis, POA, anterior hypothalamic and perifornical areas, dopaminergic A15 region, dorsomedial and lateral hypothalamus, arcuate nucleus (ARC) and the ventral premammillary nucleus. We also used dual‐label immunocytochemistry to determine whether a neuroanatomical basis for direct modulation of GnRH neurones by NKB was evident. No GnRH neurones at any rostral‐caudal level were observed to contain NK3R immunoreactivity, although GnRH neurones and fibres were in proximity to NK3R‐containing fibres. Because NKB fibres formed close contacts with NKB neurones in the ARC, we determined whether these NKB neurones also contained immunoreactive NK3R. In luteal‐phase ewes, 64% ± 11 of NKB neurones colocalised NK3R. In summary, NK3R is distributed in areas of the sheep POA and hypothalamus known to be involved in the control of reproductive neuroendocrine function. Colocalisation of NK3R in NKB neurones of the ARC suggests a potential mechanism for the autoregulation of this subpopulation; however, the lack of NK3R in GnRH neurones suggests that the actions of NKB on GnRH neurosecretory activity in the ewe are mediated indirectly via other neurones and/or neuropeptides.
Theoretical Consequences of Fluctuating Versus Constant Liganding of Oestrogen Receptor‐α in Neurones
Authors: Pfaff D. W. , Ribeiro A. C.
Published: November 2009

A theory is put forward that emphasises differences in neuronal responses to fluctuations in steroid hormone levels compared to constant hormone levels. We propose that neuronal functions that regulate gonadotrophin release from the anterior pituitary tend to be more sensitive to rapid increases in the levels of oestrogens than they are to constant oestrogen levels. By contrast, neurones that control certain behavioral functions are affected just as well by constant oestrogen levels as by positively accelerating levels of oestrogen. In addition to providing examples of data from recent experiments that examine actions of the long‐term effects of oestrogen on mouse behaviour, we illustrate the behavioural effects of microinjections of adeno‐associated viral vectors of small interfering RNA directed against the mRNA for oestrogen receptor‐α (ERα). This manipulation provides for a long‐term loss of ERα function in a neuranatomically specific manner. The theoretical distinction between temporal features of oestrogen sensitivity of neuroendocrine versus behavioural function is not absolute, but is intended to stimulate new experimentation that examines temporal features of oestrogen administration.
Central and Peripheral Effects of Thyroid Hormone Signalling in the Control of Energy Metabolism
Authors: Alkemade A.
Published: November 2009

Increasing evidence points towards a role for thyroid hormone signalling in the central nervous system with respect to the development of symptoms of thyroid disease, in addition to the well‐known peripheral effects of thyroid hormone. Thyroid hormone affects target tissues directly via thyroid hormone receptors, but also indirectly through effects on the integration of the sympathetic signal in target tissues. The present review discusses these pathways and the evidence for a third pathway, that is effects of thyroid hormone on the pre‐autonomic neurones in the central nervous system. The pre‐autonomic neurones reside in the hypothalamus in brain nuclei such as the paraventricular nucleus of the hypothalamus where thyroid hormone receptor isoforms are expressed. Recent data from studies in transgenic mice implicate a role for thyroid hormone receptor alpha 1 in the modulation of sympathetic signalling to target tissues, thereby affecting both glucose and lipid metabolism. Focal stimulation of hypothalamic nuclei expressing thyroid hormone receptors and selective liver denervation experiments in rats have provided further evidence indicating that the metabolic changes observed during hyperthyroidism are not only a result of increased thyroid hormone signalling in the periphery, but also, at least in part, result from altered signalling in thyroid hormone sensitive neurones.
The Medial Amygdala Modulates Body Weight but not Neuroendocrine Responses to Chronic Stress
Authors: Solomon M. B. , Jones K. , Packard B. A. , Herman J. P.
Published: November 2009

Stress pathologies such as depression and eating disorders (i.e. anorexia nervosa) are associated with amygdalar dysfunction, which are linked with hypothalamic‐pituitary‐adrenal axis (HPA) axis hyperactivity. The medial amygdaloid nucleus (MeA), a key output nucleus of the amygdaloid complex, promotes HPA axis activation to acute psychogenic stress and is in a prime position to mediate the deleterious effects of chronic stress on physiology and behaviour. The present study tests the hypothesis that the MeA is necessary for the development of maladaptive physiological changes caused by prolonged stress exposure. Male rats received bilateral ibotenate or sham lesions targeting the MeA and one half underwent 2 weeks of chronic variable stress (CVS) or served as home cage controls. Sixteen hours post CVS, all animals were exposed to an acute restraint challenge. CVS induced thymic involution, adrenal hypertrophy, and attenuated body weight gain and up‐regulation of hypothalamic corticotrophin‐releasing hormone mRNA expression. Consistent with previous literature, lesions of the MeA dampened stress‐induced increases in corticosterone after 30 min of exposure to acute restraint stress. However, this effect was independent of CVS exposure, suggesting that the MeA may not be critical for modulating neuroendocrine responses after chronic HPA axis drive. Interestingly, lesion of the MeA modestly exaggerated the stress‐induced attenuation of weight gain. Overall, the data obtained suggest that the MeA modulates the neuroendocrine responses to acute but not chronic stress. In addition, the data suggest that the MeA may be an important neural component for the control of body weight in the face of chronic stress.
The Role of Oestradiol in Sexually Dimorphic Hypothalamic‐Pituitary‐Adrena Axis Responses to Intracerebroventricular Ethanol Administration in the Rat
Authors: Larkin J. W. , Binks S. L. , Li Y. , Selvage D.
Published: November 2009

Systemic ethanol (EtOH) administration activates the hypothalamic‐pituitary‐adrenal (HPA) axis of rats in a sexually dimorphic manner. The present studies tested the role played by the central nervous system (CNS) in this phenomenon. To localise the effects of the drug to the brain, we utilised an experimental paradigm whereby a small, nontoxic amount of the drug was delivered via intracerebroventricular (i.c.v.) injection. EtoH administered i.c.v. rapidly diffuses throughout the cerebrospinal fluid and brain, and does not cause neuronal damage or have any long‐term physiological or behavioural effects. Experimental groups included intact males, intact cycling females, and ovariectomised (OVX) animals with or without replacement oestradiol (E2). Intracerebroventricular EtOH‐induced HPA hormonal activation was determined by measuring plasma adrenocorticotrophin (ACTH) levels. Activation of brain areas that both regulate HPA function and are responsive to gonadal hormones was determined using expression of the transcription factorc‐fos(Fos) as a marker of neuronal activity. We observed sex‐ and oestrous cycle‐ dependent differences in HPA activation by EtOH as measured by both these parameters. ACTH secretion was highest in females in pro‐oestrus or oestrus, just prior to or after the endogenous peak of E2, as was Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and the locus coreuleus (LC) of the brainstem. In OVX animals, E2replacement caused an increase in PVN and LC Fos expression in response to i.c.v. EtOH compared to OVX controls, but a decrease in ACTH secretion. Taken together, these results indicate that at the level of the CNS, EtOH stimulates HPA activity more robustly at times when the effects of E2are high, but that E2alone is not responsible for this effect. The data further suggest that the LC plays an important role in the circuitry, which appears to be different from that activated following the systemic administration of EtOH.
Participation of the Prolactin‐Releasing Peptide‐Containing Neurones in Caudal Medulla in Conveying Haemorrhagic Stress‐Induced Signals to the Paraventricular Nucleus of the Hypothalamus
Authors: Uchida K. , Kobayashi D. , Das G. , Onaka T. , Inoue K. , Itoi K.
Published: November 2009

The prolactin‐releasing peptide (PrRP) has been proposed to be a co‐transmitter or modulator of noradrenaline (NA) because it colocalises with NA in the A1 (in the ventrolateral reticular formation) and A2 (in the nucleus of the solitary tract; NTS) cell groups in the caudal medulla. The baroreceptor signals, originating from the great vessels, are transmitted primarily to the NTS, and then part of the signals is conveyed to the hypothalamic neuroendocrine neurones via the ascending NA neurones. The hypotensive haemorrhagic paradigm was employed to examine whether the PrRP‐containing neurones in the caudal medulla participate in conveying signals to the hypothalamic neuroendocrine neurones. Among the caudal medullary A1 or A2 neurones, the majority of the PrRP‐immunoreactive (‐ir) neurones became c‐Fos‐ir at 2 h after hypotensive haemorrhage. Hypothalamic corticotrophin‐releasing hormone‐ir neurones and vasopressin‐ir neurones became c‐Fos positive in parallel with the activation of medullary PrRP‐ir neurones. After delivery of retrograde tracer fluorogold (FG) to the paraventricular nucleus of the hypothalamus (PVN), part of the PrRP/FG double‐labelled neurones in the A1 and A2 became c‐Fos‐ir after haemorrhage, demonstrating that PrRP‐ir neurones participate in conveying the haemorrhagic stress‐induced signals from the medulla to the PVN. PrRP and/or NA were microinjected directly to the PVN of conscious rats, and they presented a synergistic action on arginine vasopressin release, whereas an additive action was observed for adrenocorticotrophin release. These results suggest that the PrRP‐containing NA neurones in the caudal medulla may relay the haemorrhagic stress‐induced medullary inputs to the hypothalamic neuroendocrine neurones.
Photoperiodic Control of TSH‐β Expression in the Mammalian Pars Tuberalis has Different Impacts on the Induction and Suppression of the Hypothalamo‐Hypopysial Gonadal Axis
Authors: Yasuo S. , Yoshimura T. , Ebihara S. , Korf H.‐W.
Published: November 2009

Seasonal reproduction depends on photoperiod‐regulated activation or suppression of the gonadal axis. Recent studies in quail have identified long‐day induced TSH‐β expression in the pars tuberalis (PT) as a rapid trigger of gonadal activation. Thyroid‐stimulating hormone (TSH) induces type 2 deiodinase (Dio2) in the ependymal cell layer (EC) of the infundibular recess to stimulate the gonadal axis. A similar mechanism is proposed in sheep and mice, but the experimental data on the temporal patterns of induction and suppression of TSH‐β and Dio2 expression are incomplete. In the present study, we examined the expression of TSH‐β and Dio2 in hamsters transferred from short‐ to long‐day conditions for 9 days, and demonstrate the induction of TSH‐β and Dio2 on day 8 after transition. These data demonstrate the close relationship between TSH‐β and Dio2 expression in the inductive pathway. The temporal expression of TSH‐β and Dio2 in the suppressive pathway was also examined by s.c. melatonin injection, which mimics the transition from long to short days. Importantly, Dio2 expression in the EC is suppressed on day 1 after the onset of injection, whereas TSH‐β expression in the PT was not suppressed until day 10. These data suggest that regulated transcription of TSH‐β is involved in the induction of the gonadal axis in mammals, whereas the suppression of this axis is mediated by different mechanisms.
Effect of Photoperiod on the Thyroid‐Stimulating Hormone Neuroendocrine System in the European Hamster (Cricetus cricetus)
Authors: Hanon E. A. , Routledge K. , Dardente H. , Masson‐Pévet M. , Morgan P. J. , Hazlerigg D. G.
Published: November 2009

Recent studies have characterised a retrograde mechanism whereby the pineal hormone melatonin acts in the pars tuberalis (PT) of the pituitary gland to control thyroid hormone action in the hypothalamus, leading to changes in seasonal reproductive function. This involves the release of thyroid‐stimulating hormone (TSH) from PT that activates type II deiodinase (DIO2) gene expression in hypothalamic ependymal cells, locally generating biologically active T3, and thus triggering a neuroendocrine cascade. In the present study, we investigated whether a similar regulatory mechanism operates in the European hamster. This species utilises both melatonin signalling and a circannual timer to time the seasonal reproductive cycle. We found that expression of βTSH RNA in the PT was markedly increased under long compared to short photoperiod, whereas TSH receptor expression was localised in the ependymal cells lining the third ventricle, and in the PT, where its expression varied with time and photoperiod. In the ependymal cells at the base of the third ventricle, DIO2 and type III deiodinase (DIO3) expression was reciprocally regulated, with DIO2 activated under long and repressed under short photoperiod, and the reverse case for DIO3. These data are consistent with recent observations in sheep, and suggest that the PT TSH third ventricle‐ependymal cell relay plays a conserved role in initiating the photoperiodic response in both long‐ and short‐day breeding mammals.
Degradation of cytokinins by maize cytokinin dehydrogenase is mediated by free radicals generated by enzymatic oxidation of natural benzoxazinones
Authors: Frébortová Jitka , Novák Ondřej , Frébort Ivo , Jorda Radek
Published: November 2009

Hydroxamic acid 2,4‐dihydroxy‐7‐methoxy‐1,4‐benzoxazin‐one (DIMBOA) was isolated from maize phloem sap as a compound enhancing the degradation of isopentenyl adenine by maize cytokinin dehydrogenase (CKX), after oxidative conversion by either laccase or peroxidase. Laccase and peroxidase catalyze oxidative cleavage of DIMBOA to 4‐nitrosoresorcinol‐1‐monomethyl ether (coniferron), which serves as a weak electron acceptor of CKX. The oxidation of DIMBOA and coniferron generates transitional free radicals that are used by CKX as effective electron acceptors. The function of free radicals in the CKX‐catalyzed reaction was also verified with a stable free radical of 2,2′‐azino‐bis‐3‐ethylbenzothiazoline‐6‐sulfonic acid. Application of exogenous cytokinin to maize seedlings resulted in an enhanced benzoxazinoid content in maize phloem sap. The results indicate a new function for DIMBOA in the metabolism of the cytokinin group of plant hormones.
Medicago truncatula Vapyrin is a novel protein required for arbuscular mycorrhizal symbiosis
Authors: Pumplin Nathan , Mondo Stephen J. , Topp Stephanie , Starker Colby G. , Gantt J. Stephen , Harrison Maria J.
Published: November 2009

Arbuscular mycorrhizal (AM) symbiosis is a widespread mutualism formed between vascular plants and fungi of the Glomeromycota. In this endosymbiosis, fungal hyphae enter the roots, growing through epidermal cells to the cortex where they establish differentiated hyphae called arbuscules in the cortical cells. Reprogramming of the plant epidermal and cortical cells occurs to enable intracellular growth of the fungal symbiont; however, the plant genes underlying this process are largely unknown. Here, through the use of RNAi, we demonstrate that the expression of a Medicago truncatula gene named Vapyrin is essential for arbuscule formation, and also for efficient epidermal penetration by AM fungi. Vapyrin is induced transiently in the epidermis coincident with hyphal penetration, and then in the cortex during arbuscule formation. The Vapyrin protein is cytoplasmic, and in cells containing AM fungal hyphae, the protein accumulates in small puncta that move through the cytoplasm. Vapyrin is a novel protein composed of two domains that mediate protein–protein interactions: an N‐terminal VAMP‐associated protein (VAP)/major sperm protein (MSP) domain and a C‐terminal ankyrin‐repeat domain. Putative Vapyrin orthologs exist widely in the plant kingdom, but not in Arabidopsis, or in non‐plant species. The data suggest a role for Vapyrin in cellular remodeling to support the intracellular development of fungal hyphae during AM symbiosis.
The Chloroplast Function Database: a large‐scale collection of Arabidopsis Ds/Spm‐ or T‐DNA‐tagged homozygous lines for nuclear‐encoded chloroplast proteins, and their systematic phenotype analysis
Authors: Myouga Fumiyoshi , Akiyama Kenji , Motohashi Reiko , Kuromori Takashi , Ito Takuya , Iizumi Haruko , Ryusui Rie , Sakurai Tetsuya , Shinozaki Kazuo
Published: November 2009

A majority of the proteins of the chloroplast are encoded by the nuclear genome, and are post‐translationally targeted to the chloroplast. From databases of tagged insertion lines at international seed stock centers and our own stock, we selected 3246 Ds/Spm (dissociator/suppressor–mutator) transposon‐ or T‐DNA‐tagged Arabidopsis lines for genes encoding 1369 chloroplast proteins (about 66% of the 2090 predicted chloroplast proteins) in which insertions disrupt the protein‐coding regions. We systematically observed 3‐week‐old seedlings grown on agar plates, identified mutants with abnormal phenotypes and collected homozygous lines with wild‐type phenotypes. We also identified insertion lines for which no homozygous plants were obtained. To date, we have identified 111 lines with reproducible seedling phenotypes, 122 lines for which we could not obtain homozygotes and 1290 homozygous lines without a visible phenotype. The Chloroplast Function Database presents the molecular and phenotypic information obtained from this resource. The database provides tools for searching for mutant lines using Arabidopsis Genome Initiative (AGI) locus numbers, tagged line numbers and phenotypes, and provides rapid access to detailed information on the tagged line resources. Moreover, our collection of insertion homozygotes provides a powerful tool to accelerate the functional analysis of nuclear‐encoded chloroplast proteins in Arabidopsis. The Chloroplast Function Database is freely available at http://rarge.psc.riken.jp/chloroplast/. The homozygous lines generated in this project are also available from the various Arabidopsis stock centers. We have donated the insertion homozygotes to their originating seed stock centers.
Regional differences in local recurrence rates after rectal cancer surgery
Authors: Kodeda K. , Holmberg E. , Steineck G. , Nordgren S.
Published: November 2009

Aim  To analyse a substantial regional difference in local failure rate after rectal cancer surgery focusing on management.

Method  National, population‐based, prospective registry data were used, including comprehensive 5‐year follow up of 3783 patients operated on in the period 1998–2000. Local recurrence rates were compared using crude rate, Kaplan–Meier estimates and competing risk methodology. Resected patients (651 regional and 3132 national) were analysed and subgroup comparisons of management were performed.

Results  The crude local recurrence rate was 13.7% in the regional cohort and 7.1% in the national cohort. The absolute difference of 6.6% may partly be explained by systematic errors of underreporting (≤ 1.4%), differences in patient populations and indications for surgery. A significant difference in the use of neoadjuvant radiotherapy (explaining ≤ 1.0%) and some aspects of surgical strategy were also observed.

Conclusions  We conclude that some of the difference in the registered incidence of local recurrence between the regional and the national cohorts remains unexplained and may depend on surgical technique in terms of lack of radicality in removing tumour tissue.
A randomized, prospective, double‐blind, placebo‐controlled trial of the effect of topical diltiazem on posthaemorrhoidectomy pain
Authors: Amoli H. A. , Notash A. Y. , Shahandashti F. J. , Kenari A. Y. , Ashraf H.
Published: November 2009

Aim  Spasm of the internal anal sphincter plays a role in haemorrhoidal disease and may be a source of anal pain after haemorrhoid surgery. In this study, we investigated the effect of topical diltiazem (DTZ) on postoperative pain following Milligan–Morgan haemorrhoidectomy.

Method  After haemorrhoidectomy, 33 patients were randomly assigned to receive DTZ ointment (2%; n = 16) or a placebo ointment (n = 17). Ointments were applied to the perianal region three times daily for 7 days. A Visual Analogue Scale was used to assess postoperative pain. The primary end‐point was reduction in postoperative pain.

Results  Patients using the DTZ cream had significantly less pain and greater benefit than those in the placebo group throughout the first postoperative week, and total and daily narcotic analgesic use was higher in the placebo group. There were no differences in morbidity between the two groups.

Conclusion  Perianal application of DTZ cream after haemorrhoidectomy significantly reduces postoperative pain and is perceived as beneficial, with no increase in associated morbidity.
Nanosized Iron Oxide Colloids Strongly Enhance Microbial Iron Reduction
Authors: Bosch Julian , Heister Katja , Hofmann Thilo , Meckenstock Rainer U.
Published: November 2009

Microbial iron reduction is considered to be a significant subsurface process. The rate-limiting bioavailability of the insoluble iron oxyhydroxides, however, is a topic for debate. Surface area and mineral structure are recognized as crucial parameters for microbial reduction rates of bulk, macroaggregate iron minerals. However, a significant fraction of iron oxide minerals in the subsurface is supposed to be present as nanosized colloids. We therefore studied the role of colloidal iron oxides in microbial iron reduction. In batch growth experiments with
Geobacter sulfurreducens
, colloids of ferrihydrite (hydrodynamic diameter, 336 nm), hematite (123 nm), goethite (157 nm), and akaganeite (64 nm) were added as electron acceptors. The colloidal iron oxides were reduced up to 2 orders of magnitude more rapidly (up to 1,255 pmol h
−
1
cell
−
1
) than bulk macroaggregates of the same iron phases (6 to 70 pmol h
−
1
cell
−
1
). The increased reactivity was not only due to the large surface areas of the colloidal aggregates but also was due to a higher reactivity per unit surface. We hypothesize that this can be attributed to the high bioavailability of the nanosized aggregates and their colloidal suspension. Furthermore, a strong enhancement of reduction rates of bulk ferrihydrite was observed when nanosized ferrihydrite aggregates were added.
Emergence of a Cell Wall Protease in the
Streptococcus thermophilus
Population
Authors: Delorme Christine , Bartholini Claire , Bolotine Alexander , Ehrlich S. Dusko , Renault Pierre
Published: November 2009

Streptococcus thermophilus
is perceived as a recently emerged food bacterium that evolved from a commensal ancestor by loss and gain of functions. Here, we provide data allowing a better understanding of this evolutionary scheme. A multilocus sequence typing approach that we developed showed that
S. thermophilus
diverges significantly from its potential ancestors of the salivarius group and displays a low level of allelic variability, confirming its likely recent emergence. An analysis of the origin and dissemination of the
prtS
gene was carried out within this evolutionary scheme. This gene encodes a protease that allows better growth in milk by facilitating casein breakdown to supply amino acids. The
S. thermophilus
protease exhibits 95% identity to the animal
Streptococcus suis
protein PrtS. Genomic analysis showed that
prtS
is part of an island flanked by two tandem insertion sequence elements and containing three other genes which present the best identities and synteny with the
S. suis
genome. These data indicate a potential origin for this “ecological” island in a species closely related to
S. suis
. The analysis of the distribution of the
prtS
gene in
S. thermophilus
showed that the gene is infrequent in historical collections but frequent in recent industrial ones. Moreover, this “ecological” island conferring an important metabolic trait for milk adaptation appears to have disseminated by lateral transfer in the
S. thermophilus
population. Taken together, these data support an evolutionary scheme of
S. thermophilus
where gene acquisition and selection by food producers are determining factors. The source and impact of genes acquired by horizontal gene transfer on the physiology and safety of strains should be addressed.
Involvement of Vacuolar Sequestration and Active Transport in Tolerance of
Saccharomyces
cerevisiae
to Hop Iso-α-Acids
Authors: Hazelwood Lucie A. , Walsh Michael C. , Pronk Jack T. , Daran Jean-Marc
Published: November 2009

The hop plant,
Humulus
lupulus
L., has an exceptionally high content of secondary metabolites, the hop α-acids, which possess a range of beneficial properties, including antiseptic action. Studies performed on the mode of action of hop iso-α-acids have hitherto been restricted to lactic acid bacteria. The present study investigated molecular mechanisms of hop iso-α-acid resistance in the model eukaryote
Saccharomyces
cerevisiae
. Growth inhibition occurred at concentrations of hop iso-α-acids that were an order of magnitude higher than those found with hop-tolerant prokaryotes. Chemostat-based transcriptome analysis and phenotype screening of the
S
.
cerevisiae
haploid gene deletion collection were used as complementary methods to screen for genes involved in hop iso-α-acid detoxification and tolerance. This screening and further analysis of deletion mutants confirmed that yeast tolerance to hop iso-α-acids involves three major processes, active proton pumping into the vacuole by the vacuolar-type ATPase to enable vacuolar sequestration of iso-α-acids and alteration of cell wall structure and, to a lesser extent, active export of iso-α-acids across the plasma membrane. Furthermore, iso-α-acids were shown to affect cellular metal homeostasis by acting as strong zinc and iron chelators.
Probabilistic Model of Microbial Cell Growth, Division, and Mortality
Authors: Horowitz Joseph , Normand Mark D. , Corradini Maria G. , Peleg Micha
Published: November 2009

After a short time interval of length δ
t
during microbial growth, an individual cell can be found to be divided with probability

P
d

(
t
)δ
t
, dead with probability

P
m

(
t
)δ
t
, or alive but undivided with the probability 1 − [

P
d

(
t
)

+ P
m

(
t
)]δ
t
, where
t
is time,

P
d

(
t
) expresses the probability of division for an individual cell per unit of time, and

P
m

(
t
) expresses the probability of mortality per unit of time. These probabilities may change with the state of the population and the habitat's properties and are therefore functions of time. This scenario translates into a model that is presented in stochastic and deterministic versions. The first, a stochastic process model, monitors the fates of individual cells and determines cell numbers. It is particularly suitable for small populations such as those that may exist in the case of casual contamination of a food by a pathogen. The second, which can be regarded as a large-population limit of the stochastic model, is a continuous mathematical expression that describes the population's size as a function of time. It is suitable for large microbial populations such as those present in unprocessed foods. Exponential or logistic growth with or without lag, inactivation with or without a “shoulder,” and transitions between growth and inactivation are all manifestations of the underlying probability structure of the model. With temperature-dependent parameters, the model can be used to simulate nonisothermal growth and inactivation patterns. The same concept applies to other factors that promote or inhibit microorganisms, such as pH and the presence of antimicrobials, etc. With

P
d

(
t
) and

P
m

(
t
) in the form of logistic functions, the model can simulate all commonly observed growth/mortality patterns. Estimates of the changing probability parameters can be obtained with both the stochastic and deterministic versions of the model, as demonstrated with simulated data.