bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatocyte growth factor (HGF) autocrine activation predicts sensitivity to MET inhibition in glioblastoma
Authors: Xie Qian , Bradley Robert , Kang Liang , Koeman Julie , Ascierto Maria Libera , Worschech Andrea , De Giorgi Valeria , Wang Ena , Kefene Lisa , Su Yanli , Essenburg Curt , Kaufman Dafna W. , DeKoning Tom , Enter Mark A. , O'Rourke Timothy J. , Marincola Francesco M. , Vande Woude George F.
Published: December 2011

Because oncogene MET and EGF receptor (EGFR) inhibitors are in clinical development against several types of cancer, including glioblastoma, it is important to identify predictive markers that indicate patient subgroups suitable for such therapies. We investigated in vivo glioblastoma models characterized by hepatocyte growth factor (HGF) autocrine or paracrine activation, or by
MET
or
EGFR
amplification, for their susceptibility to MET inhibitors. HGF autocrine expression correlated with high phospho-MET levels in HGF autocrine cell lines, and these lines showed high sensitivity to MET inhibition in vivo. An HGF paracrine environment may enhance glioblastoma growth in vivo but did not indicate sensitivity to MET inhibition. EGFRvIII amplification predicted sensitivity to EGFR inhibition, but in the same tumor, increased copies of
MET
from gains of chromosome 7 did not result in increased MET activity and did not predict sensitivity to MET inhibitors. Thus, HGF autocrine glioblastoma bears an activated MET signaling pathway that may predict sensitivity to MET inhibitors. Moreover, serum HGF levels may serve as a biomarker for the presence of autocrine tumors and their responsiveness to MET therapeutics.
Evolutionary conservation of the habenular nuclei and their circuitry controlling the dopamine and 5-hydroxytryptophan (5-HT) systems
Authors: Stephenson-Jones Marcus , Floros Orestis , Robertson Brita , Grillner Sten
Published: December 2011

The medial (MHb) and lateral (LHb) habenulae are a small group of nuclei that regulate the activity of monoaminergic neurons. Disruptions to these nuclei lead to deficits in a range of cognitive and motor functions from sleep to decision making. Interestingly, the habenular nuclei are present in all vertebrates, suggesting that they provide a common neural mechanism to influence these diverse functions. To unravel conserved habenula circuitry and approach an understanding of their basic function, we investigated the organization of these nuclei in the lamprey, one of the phylogenetically oldest vertebrates. Based on connectivity and molecular expression, we show that the MHb and LHb circuitry is conserved in the lamprey. As in mammals, separate populations of neurons in the LHb homolog project directly or indirectly to dopamine and serotonin neurons through a nucleus homologous to the GABAergic rostromedial mesopontine tegmental nucleus and directly to histamine neurons. The pallidal and hypothalamic inputs to the LHb homolog are also conserved. In contrast to other species, the habenula projecting pallidal nucleus is topographically distinct from the dorsal pallidum, the homolog of the globus pallidus interna. The efferents of the MHb homolog selectively target the interpeduncular nucleus. The MHb afferents arise from sensory (medial olfactory bulb, parapineal, and pretectum) and not limbic areas, as they do in mammals; consequently, the “context” in which this circuitry is recruited may have changed during evolution. Our results indicate that the habenular nuclei provide a common vertebrate circuitry to adapt behavior in response to rewards, stress, and other motivating factors.
Resistance in Maize Inbred Lines to Fusarium verticillioides and Fumonisin Accumulation in South Africa
Authors: Small I. M. , Flett B. C. , Marasas W. F. O. , McLeod A. , Stander M. A. , Viljoen A.
Published: December 2011

Fusarium ear rot of maize, caused by Fusarium verticillioides, is an important disease affecting maize production worldwide. Apart from reducing yield and grain quality, F. verticillioides produces fumonisins which have been associated with mycotoxicoses of animals and humans. Currently, no maize breeding lines are known with resistance to F. verticillioides in South Africa. The objective of this study, therefore, was to evaluate 24 genetically diverse maize inbred lines as potential sources of resistance to Fusarium ear rot and fumonisin accumulation in field trials at Potchefstroom and Vaalharts in South Africa. After artificial silk channel inoculation with F. verticillioides, Fusarium ear rot development was determined at harvest and fumonisins B1, B2, and B3 quantified. A significant inbred line by location effect was observed for Fusarium ear rot severity (P ≤ 0.001), although certain lines proved to be consistently resistant across both locations. The individual inbred lines also differed considerably in fumonisin accumulation between Potchefstroom and Vaalharts, with differentiation between susceptible and potentially resistant inbred lines only being possible at Vaalharts. A greenhouse inoculation trial was then also performed on a subset of potentially resistant and highly susceptible lines. The inbred lines CML 390, CML 444, CML 182, VO 617Y-2, and RO 549 W consistently showed a low Fusarium ear rot (<5%) incidence at both Potchefstroom and Vaalharts and in the greenhouse. Two of these inbred lines, CML 390 and CML 444, accumulated fumonisin levels <5 mg kg–1. These lines could potentially act as sources of resistance for use within a maize breeding program.
Pathogenic and Genetic Diversity of Xanthomonas translucens pv. undulosa in North Dakota
Authors: Adhikari Tika B. , Gurung Suraj , Hansen Jana M. , Bonman J. Michael
Published: December 2011

Bacterial leaf streak (BLS), caused by Xanthomonas translucens pv. undulosa, has become more prevalent recently in North Dakota and neighboring states. From five locations in North Dakota, 226 strains of X. translucens pv. undulosa were collected and evaluated for pathogenicity and then selected strains were inoculated on a set of 12 wheat cultivars and other cereal hosts. The genetic diversity of all strains was determined using repetitive sequence-based polymerase chain reaction (rep-PCR) and insertion sequence-based (IS)-PCR. Bacterial strains were pathogenic on wheat and barley but symptom severity was greatest on wheat. Strains varied greatly in aggressiveness, and wheat cultivars also showed differential responses to several strains. The 16S ribosomal DNA sequences of the strains were identical, and distinct from those of the other Xanthomonas pathovars. Combined rep-PCR and IS-PCR data produced 213 haplotypes. Similar haplotypes were detected in more than one location. Although diversity was greatest (≈92%) among individuals within a location, statistically significant (P ≤ 0.001 or 0.05) genetic differentiation among locations was estimated, indicating geographic differentiation between pathogen populations. The results of this study provide information on the pathogen diversity in North Dakota, which will be useful to better identify and characterize resistant germplasm.
Immunology in the clinic review series; focus on type 1 diabetes and viruses: how viral infections modulate beta cell function
Authors: Grieco F A , Sebastiani G , Spagnuolo I , Patti A , Dotta F
Published: December 2011

OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES

Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy.

Type 1 diabetes mellitus (T1DM) is a multi-factorial immune-mediated disease characterized by the autoimmune destruction of insulin-producing pancreatic islet beta cells in genetically susceptible individuals. Epidemiological evidence has also documented the constant rise in the incidence of T1DM worldwide, with viral infections representing one of the candidate environmental risk factors identified by several independent studies. In fact, epidemiological data showed that T1DM incidence increases after epidemics due to enteroviruses and that enteroviral RNA can be detected in the blood of >50% of T1DM patients at the time of disease onset. Furthermore, both in-vitro and ex-vivo studies have shown that viruses can infect pancreatic beta cells with consequent effects ranging from functional damage to cell death.
Heritability estimates for racing performance in Japanese Thoroughbred racehorses using linear and non‐linear model analyses
Authors: Tozaki T. , Miyake T. , Kakoi H. , Gawahara H. , Hirota K. , Nakano Y. , Kurosawa M.
Published: December 2011

This study evaluated the differences between linear and non‐linear modelled heritability estimates of racing performance based on lifetime earnings (LE) and lifetime ranking (LR) in Japanese Thoroughbred racehorses. The heritability estimate (h2 = 0.25) obtained from a non‐linear model based on formal Japan Racing Association ranking was much higher than that obtained from a linear model based on the original trait phenotype (h2 = 0.11). The linear models showed slightly higher heritability estimates under the trait categorizations than under the original phenotypes, while the non‐linear categorical trait models showed much higher heritability estimates than the linear models, especially for binary trait categorizations (h2 = 0.34) with non‐winning and winning horses. The binary trait categorizations were consistent with the case and control classifications in the previous genome‐wide association study (GWAS), which identified possible sequence variants on ECA18 that affect racing performance in Japanese Thoroughbred racehorses. Those findings suggested that the different heritability estimates obtained from several trait categorizations would reflect the possible presence of susceptibility gene segregations in the analyzed population, indicating that heritability estimates from non‐linear models are useful for the selection of case and control populations in GWAS.
Work of breathing and respiratory drive in obesity
Authors: LIN CHING‐KAI , LIN CHING‐CHI
Published: December 2011

Obesity, particularly severe central obesity, affects respiratory physiology both at rest and during exercise. Reductions in expiratory reserve volume, functional residual capacity, respiratory system compliance and impaired respiratory system mechanics produce a restrictive ventilatory defect. Low functional residual capacity and reductions in expiratory reserve volume increase the risk of expiratory flow limitation and airway closure during quiet breathing. Consequently, obesity may cause expiratory flow limitation and the development of intrinsic positive end expiratory pressure, especially in the supine position. This increases the work of breathing by imposing a threshold load on the respiratory muscles leading to dyspnoea. Marked reductions in expiratory reserve volume may lead to ventilation distribution abnormalities, with closure of airways in the dependent zones of the lungs, inducing ventilation perfusion mismatch and gas exchange abnormalities. Obesity may also impair upper airway mechanical function and neuromuscular strength, and increase oxygen consumption, which in turn, increase the work of breathing and impair ventilatory drive. The combination of ventilatory impairment, excess CO2 production and reduced ventilatory drive predisposes obese individuals to obesity hypoventilation syndrome.
Botulinum toxin A modulates afferent fibers in neurogenic detrusor overactivity
Authors: Conte A. , Giannantoni A. , Proietti S. , Giovannozzi S. , Fabbrini G. , Rossi A. , Porena M. , Berardelli A.
Published: December 2011

Background:  Although botulinum toxin (BoNT/A) injected into the detrusor muscle improves overactive bladder symptoms in patients with neurogenic detrusor overactivity, how it does so remains unclear. In this study, we investigated whether BoNT/A improves detrusor overactivity by modulating bladder afferent activity.

Methods:  To do so, during urodynamic assessment, we tested the soleus muscle Hoffmann (H) reflex during bladder filling before and after intradetrusor BoNT/A in patients with Parkinson’s disease (PD) and in patients with complete chronic spinal cord lesion (SCI) and detrusor overactivity refractory to conventional therapy. Healthy subjects underwent H reflex studies during urodynamic assessment and acted as controls.

Results:  Our findings show that BoNT/A injected into the detrusor muscle effectively reduces clinical overactive bladder symptoms in patients with PD and SCI. In healthy subjects and patients with PD, bladder filling [at maximum cystometric capacity, (MCC)] significantly decreased the H reflex size, whereas in patients with SCI, it slightly facilitated the H reflex size. At MCC, in patients with PD, BoNT/A significantly reduced the expected H reflex inhibition, whereas in those with SCI, BoNT/A turned the H reflex facilitation at maximum bladder filling into a slight inhibition.

Conclusions:  These findings show that BoNT/A injected into the detrusor muscle in patients with PD and SCI modulates bladder afferent activity. Modulation of bladder afferents possibly explains why BoNT/A improves detrusor overactivity.
Physical Training Improves Motor Performance in People with Dementia: A Randomized Controlled Trial
Authors: Hauer Klaus , Schwenk Michael , Zieschang Tania , Essig Marco , Becker Clemens , Oster Peter
Published: December 2011

Objectives

To determine whether a specific, standardized training regimen can improve muscle strength and physical functioning in people with dementia.

Design

Double‐blinded, randomized, controlled trial with 3‐month intervention and 3‐month follow‐up period in 2006 to 2009.

Setting

Outpatient geriatric rehabilitation.

Participants

Individuals with confirmed mild to moderate dementia, no severe somatic or psychological disease, and ability to walk 10 m. Most participants were still living independently with or without supportive care.

Intervention

Supervised, progressive resistance and functional group training for 3 months specifically developed for people with dementia (intervention, n = 62) compared with a low‐intensity motor placebo activity (control, n = 60).

Measurements

Primary outcome measures were one‐repetition maximum in a leg press device for maximal strength and duration of the five‐chair‐stand test for functional performance. Secondary outcome measures were assessed for a number of established parameters for maximal strength, physical function, and physical activity.

Results

Training significantly improved both primary outcomes (percentage change from baseline: maximal strength, intervention group (IG): +51.5 ± 41.5 kg vs control group (CG): –1.0 ± 28.9 kg, P < .001; functional performance, IG: –25.9 ± 15.1 seconds vs CG: +11.3 ± 60.4 seconds, P < .001). Secondary analysis confirmed effects for all strength and functional parameters. Training gains were partly sustained during follow‐up. Low baseline performance on motor tasks but not cognitive impairment predicted positive training response. Physical activity increased significantly during the intervention (P < .001).

Conclusion

The intensive, dementia‐adjusted training was feasible and substantially improved motor performance in frail, older people with dementia and may represent a model for structured rehabilitation or outpatient training.
Maximum Occlusal Force and Physical Performance in the Oldest Old: The Tokyo Oldest Old Survey on Total Health
Authors: Iinuma Toshimitsu , Arai Yasumichi , Fukumoto Motoko , Takayama Michiyo , Abe Yukiko , Asakura Keiko , Nishiwaki Yuji , Takebayashi Toru , Iwase Takashi , Komiyama Kazuo , Gionhaku Nobuhito , Hirose Nobuyoshi
Published: December 2011

Objectives

To elucidate the independent relationship between masticatory and physical performance in community‐living oldest old people (mean age ± standard deviation 87.8 ± 2.2, range 85–102).

Design

Cross‐sectional analysis.

Setting

University research center or home‐based examination.

Participants

Four hundred eighty‐nine community‐living individuals (219 men, 270 women) aged 85 and older.

Measurements

Maximum occlusal force (MOF) was measured using an occlusal force measuring device. Sociodemographic and functional factors, oral health, comorbidities, blood chemistry, lower extremity performance, and handgrip strength were assessed. Blood chemistry analyses included serum albumin, C‐reactive protein, interleukin (IL)‐6, and total and free testosterone.

Results

MOF was significantly associated with age, body mass index, and cognitive impairment in men but not in women. Comorbidities and blood chemistry were not associated with MOF except for a significant association with IL‐6 concentration in women. In a multivariate model adjusted for various confounders, lower MOF was associated with greater risk for poor performance on the timed up and go (TUG) test in men and women (men: odds ratio (OR)=2.34, 95% confidence interval (CI)=1.02–5.38; women: OR=2.44, 95% CI=1.12–5.33). MOF was similarly associated with performance in chair standing, one‐leg standing, and handgrip strength only in men. These associations remained after adjustment for number of natural teeth.

Conclusion

MOF was strongly and independently associated with all measures of physical performance in men and with the TUG test in women after adjustment for various confounders, suggesting that age‐related declines in masticatory and skeletal muscle functions share common mechanistic pathways in older age, particularly in men.
Developmental Validation of RSID™‐Semen: A Lateral Flow Immunochromatographic Strip Test for the Forensic Detection of Human Semen*
Authors: Old Jennifer , Schweers Brett A. , Boonlayangoor Pravat W. , Fischer Brian , Miller Kevin W. P. , Reich Karl
Published: December 2011

Abstract:  Tests for the identification of semen commonly involve the microscopic visualization of spermatozoa or assays for the presence of seminal markers such as acid phosphatase (AP) or prostate‐specific antigen (PSA). Here, we describe the rapid stain identification kit for the identification of semen (RSID™‐Semen), a lateral flow immunochromatographic strip test that uses two antihuman semenogelin monoclonal antibodies to detect the presence of semenogelin. The RSID™‐Semen strip is specific for human semen, detecting <2.5 nL of semen, and does not cross‐react with other human or nonhuman tissues tested. RSID™‐Semen is more sensitive with certain forensic evidence samples containing mixtures of vaginal secretions and semen than either of the commercially available PSA‐based forensic semen detection tests or tests that measure AP activity that were tested in parallel. The RSID™‐Semen kit also allows sampling a fraction of a questioned stain while retaining the majority of the sample for further processing through short tandem repeat analysis.
Lymphangiosarcoma arising after 33 years within a background of chronic filariasis: a case report with review of literature
Authors: Krishnamoorthy Naveen , Viswanathan Seethalakshmi , Rekhi Bharat , Jambhekar Nirmala A.
Published: December 2011

Cutaneous angiosarcoma or lymphangiosarcoma represents an uncommon aggressive tumor known to arise on a background of chronic lymphedema secondary to various etiologies, principally following surgery or irradiation. There have been rarely reported cases of angiosarcoma following infective conditions that eventuate with lymphatic stasis. We report a case of angiosarcoma arising after 33 years within a background of filariasis. Awareness of this association can lead to early diagnosis and appropriate treatment of this potentially fatal malignant tumor.

Krishnamoorthy N, Viswanathan S, Rekhi B, Jambhekar NA. Lymphangiosarcoma arising after 33 years within a background of chronic filariasis: a case report with review of literature.
COMPUTED TOMOGRAPHIC APPEARANCE OF EQUINE SINONASAL NEOPLASIA
Authors: Cissell Derek D. , Wisner Erik R. , Textor Jamie , Mohr F. Charles , Scrivani Peter V. , Théon Alain P.
Published: December 2011

The computed tomography (CT) features of tumors involving the nasal cavity and/or paranasal sinuses of 15 horses were reviewed. The 15 tumors included five neuroendocrine tumors/neuroblastomas, two undifferentiated carcinomas, two myxosarcomas, and one each of nasal adenocarcinoma, hemangiosarcoma, chondroblastic osteosarcoma, anaplastic sarcoma, myxoma, and ossifying fibroma. All tumors except the ossifying fibroma were iso‐ or hypoattenuating relative to masseter muscle. Thirteen of the fifteen tumors exhibited moderate or marked osteolysis of adjacent cortical bone and 14/15 were characterized by destructive changes of the nasal turbinates, nasal septum, and/or infraorbital canal. Ten horses had moderate or marked involvement of the cribriform plate and six had clear intracranial extension of the mass.CTfeatures were compared to radiographic findings for 10 horses. A mass was observed in 10/10 radiographic studies and mass within the caudal maxillary sinus (7/8) and rostral maxillary sinus (6/7) was identified correctly in most horses. The radiographs were least sensitive for identifying masses within the sphenopalatine sinus (0/5), cranium (0/4), and retrobulbar space (1/7) compared toCT. The radiographs also underestimated potential features of malignancy, such as severity of osteolysis or osseous production. While radiographs are a useful screening tool for identification of sinonasal masses,CTprovides greater information regarding mass extent, features of malignancy, and important prognostic indicators.
Major and Trace Element Characteristics of Apatites in Granitoids from Central Kazakhstan: Implications for Petrogenesis and Mineralization
Authors: CAO Mingjian , LI Guangming , QIN Kezhang , SEITMURATOVA Eleonora Yusupovha , LIU Yongsheng
Published: December 2011

This paper presents abundances of major and trace elements of apatites in granitic rocks associated with different types of ore deposits in Central Kazakhstan on the basis of electron probe microanalysis and laser ablation inductively coupled plasma mass spectrometry. Our results demonstrate that the concentrations and ratios of elements in apatites from different granitoid rocks show distinct features, and are sensitive to magma evolution, petrogenetic and metallogenetic processes. Apatites in the rocks associated with Mo‐W deposits have high content of F and MnO, low content of Cl, which may be indicative of sedimentary sources, while apatites from a Pb‐Zn deposit show relatively high content of Cl and low F content, which possibly suggest a high water content. In these apatites, Sr contents decrease, while Mn and Y contents increase with magma evolution. This relationship reflects that these elements in apatites are related with the degree of magmatic differentiation. Four types of REE patterns in apatites are identified. Type 1 character of highest (La/Yb)N in apatites of Aktogai porphyry Cu‐Mo deposit, Sayak‐I skarn Cu deposit and Akzhal skarn Pb‐Zn depposit is likely produced by the crystallization of heavy REE‐enriched minerals. Type 2 character of upward‐convex light REE in apatite of Aktogai porphyries likely results from La‐enriched mineral crystallization. Type 3 feature of Nd depletion in apatites of East Kounrad and Zhanet deposits both from Mo‐W deposits primarily inherits the character of host‐rock. Type 4 apatites of Aktogai deposit and Akshatau W‐Mo deposit with wide range of REE contents may suggest that apatites crystallize under a wide temperature range. Three types of apatite with distinct redox states are identified based on Eu anomaly. The Aktogai apatite with slight negative Eu anomaly displays the most oxidized state of the magma, and the apatites of other samples at Aktogai, East Kounrad and Akzhal with moderate negative Eu anomaly show moderate oxidizing condition of these rocks, while the remaining apatites with strong En anomaly indicate a moderate reductive state of these rocks.
Time-Varying Meshing Stiffness Calculation and Vibration Analysis for a 16DOF Dynamic Model With Linear Crack Growth in a Pinion
Authors: Zhou Xiaojun , Shao Yimin , Lei Yaguo , Zuo Mingjian
Published: December 2011

A modified mathematical model for simulating gear crack from root with linear growth path in a pinion is developed, in which an improved potential energy method is used to calculate the time-varying meshing stiffnesses of the meshing gear pair while we also take the deformation of gear-body into consideration. The formulas for the meshing stiffness are deduced when the crack grows as the linear growth path in the pinion. A 16DOF dynamic model of a one-stage spur gear system is used to study the response from the system considering time-varying meshing stiffnesses and different levels of crack growing in the pinion. As vibration signals induced by the tooth crack are buried in normal vibration signals which are induced by the normal gear pair in meshing at the early stage of crack growth, the algorithm combined autoregressive modeling method and demodulation method is proposed to process the signals to investigate the response characteristics as the crack grows, and the comparison of the relationship between indicators and the crack levels from different simulation methods are given.
In Vitro
Characterization of the Activity of PF-05095808, a Novel Biological Agent for Hepatitis C Virus Therapy
Authors: Lavender Helen , Brady Kevin , Burden Frances , Delpuech-Adams Oona , Denise Hubert , Palmer Amy , Perkins Hannah , Savic Boris , Scott Sarah , Smith-Burchnell Caroline , Troke Phil , Wright J. Fraser , Suhy David , Corbau Romu
Published: December 2011

PF-05095808 is a novel biological agent for chronic hepatitis C virus (HCV) therapy. It comprises a recombinant adeno-associated virus (AAV) DNA vector packaged into an AAV serotype 8 capsid. The vector directs expression of three short hairpin RNAs (shRNAs) targeted to conserved regions of the HCV genome. These shRNAs are processed by the host cell into the small interfering RNAs which mediate sequence-specific cleavage of target regions. For small-molecule inhibitors the key screens needed to assess
in vitro
activity are well defined; we developed new assays to assess this RNA interference agent and so to understand its therapeutic potential. Following administration of PF-05095808 or corresponding synthetic shRNAs, sequence-specific antiviral activity was observed in HCV replicon and infectious virus systems. To quantify the numbers of shRNA molecules required for antiviral activity
in vitro
and potentially also
in vivo
, a universal quantitative PCR (qPCR) assay was developed. The number of shRNA molecules needed to drive antiviral activity proved to be independent of the vector delivery system used for PF-05095808 administration. The emergence of resistant variants at the target site of one shRNA was characterized. A novel RNA cleavage assay was developed to confirm the spectrum of activity of PF-05095808 against common HCV clinical isolates. In summary, our data both support antiviral activity consistent with an RNA interference mechanism and demonstrate the potential of PF-05095808 as a therapeutic agent for chronic HCV infection.
A Novel Agent Effective against Clostridium difficile Infection
Authors: Dvoskin Sofya , Xu Wei-Chu , Brown Neal C. , Yanachkov Ivan B. , Yanachkova Milka , Wright George E.
Published: December 2011

N
2
-(3,4-Dichlorobenzyl)-7-(2-[1-morpholinyl]ethyl)guanine (MorE-DCBG, 362E) is a synthetic purine that selectively inhibits the replication-specific DNA polymerase of
Clostridium difficile
. MorE-DCBG and its analogs strongly inhibited the growth of a wide variety of
C. difficile
strains. When administered orally in a hamster model of
C. difficile
-specific colitis, 362E was as effective as oral vancomycin, the current agent of choice for treating severe forms of the human disease.
Sur7 Promotes Plasma Membrane Organization and Is Needed for Resistance to Stressful Conditions and to the Invasive Growth and Virulence of Candida albicans
Authors: Douglas Lois M. , Wang Hong X. , Keppler-Ross Sabine , Dean Neta , Konopka James B.
Published: December 2011

The human fungal pathogen
Candida albicans
causes lethal systemic infections because of its ability to grow and disseminate in a host. The
C. albicans
plasma membrane is essential for virulence by acting as a protective barrier and through its key roles in interfacing with the environment, secretion of virulence factors, morphogenesis, and cell wall synthesis. Difficulties in studying hydrophobic membranes have limited the understanding of how plasma membrane organization contributes to its function and to the actions of antifungal drugs. Therefore, the role of the recently discovered plasma membrane subdomains termed the membrane compartment containing Can1 (MCC) was analyzed by assessing the virulence of a
sur7
Δ mutant. Sur7 is an integral membrane protein component of the MCC that is needed for proper localization of actin, morphogenesis, cell wall synthesis, and responding to cell wall stress. MCC domains are stable 300-nm-sized punctate patches that associate with a complex of cytoplasmic proteins known as an eisosome. Analysis of virulence-related properties of a
sur7
Δ mutant revealed defects in intraphagosomal growth in macrophages that correlate with increased sensitivity to oxidation and copper. The
sur7
Δ mutant was also strongly defective in pathogenesis in a mouse model of systemic candidiasis. The mutant cells showed a decreased ability to initiate an infection and greatly diminished invasive growth into kidney tissues. These studies on Sur7 demonstrate that the plasma membrane MCC domains are critical for virulence and represent an important new target for the development of novel therapeutic strategies.

IMPORTANCE
Candida albicans
, the most common human fungal pathogen, causes lethal systemic infections by growing and disseminating in a host. The plasma membrane plays key roles in enabling
C. albicans
to grow
in vivo
, and it is also the target of the most commonly used antifungal drugs. However, plasma membrane organization is poorly understood because of the experimental difficulties in studying hydrophobic components. Interestingly, recent studies have identified a novel type of plasma membrane subdomain in fungi known as the membrane compartment containing Can1 (MCC). Cells lacking the MCC-localized protein Sur7 display broad defects in cellular organization and response to stress
in vitro
. Consistent with this,
C. albicans
cells lacking the
SUR7
gene were more susceptible to attack by macrophages than cells with the gene and showed greatly reduced virulence in a mouse model of systemic infection. Thus, Sur7 and other MCC components represent novel targets for antifungal therapy.
ON THE GENERAL ONE-DIMENSIONAL XY MODEL: POSITIVE AND ZERO TEMPERATURE, SELECTION AND NON-SELECTION
Authors: BARAVIERA A. T. , CIOLETTI L. M. , LOPES A. O. , MOHR JOANA , SOUZA RAFAEL RIGAO
Published: December 2011

We consider (M, d) a connected and compact manifold and we denote by [Formula: see text] the Bernoulli space Mℤ. The analogous problem on the half-line ℕ is also considered. Let [Formula: see text] be an observable. Given a temperature T, we analyze the main properties of the Gibbs state [Formula: see text].

In order to do our analysis, we consider the Ruelle operator associated to [Formula: see text], and we get in this procedure the main eigenfunction [Formula: see text]. Later, we analyze selection problems when the temperature goes to zero: (a) existence, or not, of the limit [Formula: see text], a question about selection of subactions, and, (b) existence, or not, of the limit [Formula: see text], a question about selection of measures.

The existence of subactions and other properties of Ergodic Optimization are also considered.

The case where the potential depends just on the coordinates (x0, x1) is carefully analyzed. We show, in this case, and under suitable hypotheses, a Large Deviation Principle, when T → 0, graph properties, etc. Finally, we will present in detail a result due to van Enter and Ruszel, where the authors show, for a particular example of potential A, that the selection of measure [Formula: see text] in this case, does not happen.
AUTOMATIC COLLISION DETECTION FOR ASSEMBLY SEQUENCE PLANNING USING A THREE-DIMENSIONAL SOLID MODEL
Authors: ALFADHLANI  , SAMADHI T. M. A. ARI , MA'RUF ANAS , TOHA ISA SETIASYAH
Published: December 2011

Assembly sequence planning of a product involves several steps, including generation of precedence constraints, generation of assembly sequences, and selection of assembly sequences. Generation and selection of assembly sequences should be able to guarantee the feasibility of assembly. Assembly will be feasible if there is no collision between components when assembled. Detection of collision-free path of assembly can be done in an automated way. There are a number of collision detection methods that have been developed, but the method requires a complicated process of data geometry analysis. This paper proposes a method for detecting a collision-free path of the assembly component in a more simple way. Geometrical data required, taken from the three-dimensional (3D) solid drawing in the form of stacked drawing in computer-aided design (CAD) systems. Retrieval of geometrical data of components and detection of the collision-free path of an assembly were done in an automated way, directly from the CAD system.
A Multihypothesis Sequential Probability Test for Fault Detection and Identification of Vehicles' Ultrasonic Parking Sensors
Authors: Abdel-Hafez Mamoun F.
Published: December 2011

This paper presents a sequential fault detection and identification algorithm for detecting a fault in a vehicle's ultrasonic parking sensors. The algorithm identifies a bias fault in any of the ultrasonic sensors by computing the probability of having that bias fault given a carefully constructed measurement residual that is only a function of the measurement noise and the possible measurement fault. A set of bias hypotheses is assumed and initially given equal alarm probability. It is assumed that only one sensor will acquire a bias at any given time. Once the probability of a hypothesis approaches 1, that hypothesis is declared as the correct hypothesis and the bias associated with the hypothesis is removed from the sensors' reading. The accuracy and convergence characteristics of the proposed algorithm are verified using experimental results. This study is essential to ensure accurate operation of vehicle's ultrasonic parking sensors.
Water-Cooled Radiofrequency: A Neuroablative or a Neuromodulatory Modality with Broader Applications?
Authors: Malik Khalid , Benzon Honorio T. , Walega David
Published: December 2011

We report the successful use of water-cooled radiofrequency where more traditional forms of neuroablation—conventional and pulsed radiofrequency—had failed to achieve adequate pain relief. We also discuss the mechanism of neural damage with water cooled radiofrequency and discuss why this technique may have a broader role in the management of a wide array of pain syndromes.
Intelligent Control of a Novel Hydraulic Forging Manipulator
Authors: Wang J. , Gao F. , Zhang Y.
Published: December 2011

The increased demand for large-size forgings has led to developments and innovations of heavy-duty forging manipulators. Besides the huge carrying capacity, some robot features such as force perception, delicacy and flexibility, forging manipulators should also possess. The aim of the work is to develop a heavy-duty forging manipulator with robot features by means of combination of methods in mechanical, hydraulic, and control field. In this paper, through kinematic analysis of a novel forging manipulator, control strategy of the manipulator is proposed considering the function and motion of forging manipulators. Hybrid pressure/position control of hydraulic actuators in forging manipulator is realized. The feasibility of the control method has been verified by the experiments on a real prototype of the novel hydraulic forging manipulator in our institute. The intelligent control of the forging manipulator is performed with programmable logic controller which is suitable for industrial applications.
Amanita bisporigera-Induced Hepatic Failure: A Fatal Case of Mushroom Ingestion
Authors: Nici Anthony , Kim Sang
Published: December 2011

Wild mushroom poisoning from the genus Amanita is a medical emergency, with Amanita phalloides being the most common offender. Patients may complain of nausea, vomiting, diarrhea and/or abdominal pain. If not aggressively treated, fulminant hepatic failure may develop within several days of ingestion. In this case report, a patient poisoned withAmanita bisporigerais described, along with the typical clinical presentation, patient outcomes, and treatment options for dealing with an Amanita mushroom poisoning.
Protective Role of Cytotoxic T Lymphocytes in Filovirus Hemorrhagic Fever
Authors: Warfield Kelly Lyn , Olinger Gene Garrard
Published: December 2011

Infection with many emerging viruses, such as the hemorrhagic fever disease caused by the filoviruses, Marburg (MARV), and Ebola virus (EBOV), leaves the host with a short timeframe in which to mouse a protective immune response. In lethal cases, uncontrolled viral replication and virus‐induced immune dysregulation are too severe to overcome, and mortality is generally associated with a lack of notable immune responses. Vaccination studies in animals have demonstrated an association of IgG and neutralizing antibody responses against the protective glycoprotein antigen with survival from lethal challenge. More recently, studies in animal models of filovirus hemorrhagic fever have established that induction of a strong filovirus‐specific cytotoxic T lymphocyte (CTL) response can facilitate complete viral clearance. In this review, we describe assays used to discover CTL responses after vaccination or live filovirus infection in both animal models and human clinical trials. Unfortunately, little data regarding CTL responses have been collected from infected human survivors, primarily due to the low frequency of disease and the inability to perform these studies in the field. Advancements in assays and technologies may allow these studies to occur during future outbreaks.
Local Context Influence, Activity Space, and Foodscape Exposure in Two Canadian Metropolitan Settings: Is Daily Mobility Exposure Associated with Overweight?
Authors: Lebel Alexandre , Kestens Yan , Pampalon Robert , Thériault Marius , Daniel Mark , Subramanian S. V.
Published: December 2011

It has become increasingly common to attribute part of the obesity epidemic to changes in the environment. Identification of a clear and obvious role for contextual risk factors has not yet been demonstrated. The objectives of this study were to explain differences in local overweight risk in two different urban settings and to explore sex-specific associations with estimated mobility patterns. Overweight was modeled within a multilevel framework using built environmental and socioeconomic contextual indicators and individual-level estimates of activity space exposure to fast-food restaurants (or exposure to visited places). Significant variations in local levels in overweight risk were observed. Physical and socioeconomic contexts explained more area-level differences in overweight among men than among women and among inhabitants of Montreal than among inhabitants of Quebec City. Estimated activity space exposure to fast-food outlets was significantly associated with overweight for men in Montreal. Local-level analyses are required to improve our understanding of contextual influences on obesity, including multiple influences in people's daily geographies.
Disturbed Cytokine Production at the Systemic Level in Difficult-to-Control Atopic Asthma: Evidence for Raised Interleukin-4 and Decreased Interferon-γ Release following Lipopolysaccharide Stimulation
Authors: Manise M. , Schleich F. , Quaedvlieg V. , Moermans C. , Henket M. , Sele J. , Corhay J.L. , Louis R.
Published: December 2011

Background: Disturbed cytokine production is thought to govern inflammation in asthma, which, in its turn, may lead to uncontrolled disease. The aim of this study was to assess the relationship between cytokine production from blood leucocytes and the level of asthma control. Methods: We compared the production of interleukin (IL)-4, IL-6, IL-10, interferon (IFN)-γ and tumour necrosis factor-α from peripheral blood leucocytes in non-atopic healthy subjects (n = 22), atopic non-asthmatics (n = 10), well-controlled asthmatics [Juniper asthma control questionnaire (ACQ) score <1.5; n = 20] and patients with uncontrolled asthma despite inhaled or oral corticoids (ACQ score ≧1.5; n = 20). Fifty microlitres of peripheral blood was incubated for 24 h with RPMIc, lipopolysaccharide (LPS; 1 ng/ml) or phytohaemagglutinin (1 µg/ml), and cytokines were measured by immunotrapping (ELISA). Results: Both controlled and uncontrolled asthmatics as well as atopic non-asthmatics spontaneously produced more IL-4 than non-atopic healthy subjects (p < 0.001). IL-4 production induced by LPS was significantly greater (p < 0.05) in both asthma groups compared to atopic non-asthmatics and non-atopic healthy subjects. By contrast, IFN-γ release induced by LPS was lower in uncontrolled asthmatics than in non-atopic healthy subjects (p < 0.05) and controlled asthmatics (p < 0.05). IL-10 release after LPS was greater in uncontrolled asthmatics than in atopic non-asthmatics (p < 0.05). No difference was observed regarding other cytokines. Conclusion: Blood cells from patients with difficult-to-control atopic asthma display highly skewed Th2 cytokine release following LPS stimulation.
Bifidobacterium bifidum NCC 453 Promotes Tolerance Induction in Murine Models of Sublingual Immunotherapy
Authors: Moussu Hélène , Van Overtvelt Laurence , Horiot Stéphane , Tourdot Sophie , Airouche Sabi , Zuercher Adrian , Holvoet Sébastien , Prioult Guénolée , Nutten Sophie , Mercenier Annick , Mascarell Laurent , Moingeon Philippe
Published: December 2011

Background:Enhancing clinical efficacy remains a major goal in allergen-specific immunotherapy. In this study, we tested three strains of bifidobacteria as candidate adjuvants for sublingual allergy vaccines. Methods:Probiotic candidates were evaluated in human monocyte-derived dendritic cell (h-DC) maturation and CD4+ T-cell polarization in vitro models and further tested in murine models of sublingual immunotherapy in BALB/c mice sensitized to either ovalbumin or birch pollen. Results:Bifidobacterium adolescentis, B. bifidum and B. longum induced h-DC maturation and polarized naïve CD4+ T cells toward interferon-γ and interleukin-10 production. B. bifidum increased CD25high, Foxp3+ cells within CD4+ T lymphocytes and was the most potent inducer of interferon-γ in Th2-skewed peripheral blood mononuclear cells and h-DC T-cell cocultures. It also induced a significant decrease in airway hyperresponsiveness in BALB/c mice sensitized to ovalbumin. Sublingual administration of B. bifidum together with recombinant Bet v 1 enhanced tolerance induction in BALB/c mice sensitized to birch pollen, with a downregulation of both airway hyperresponsiveness, lung inflammation and Bet v 1-specific Th2 responses. Conclusions: Due to its capacity to reorient established Th2 responses toward Th1/regulatory T-cell profiles, B. bifidum represents a valid candidate adjuvant for specific immunotherapy of type I allergies.
Identifying Depression in South Asian Patients with End-Stage Renal Disease: Considerations for Practice
Authors: Sharma Shivani , Bhui Kamaldeep , Chilcot Joseph , Wellsted David , Farrington Ken
Published: December 2011

Depression is a prevalent burden for patients with end-stage renal disease (ESRD) and one that is under-recognized and consequently under-treated. Although several studies have explored the association between depression symptoms, treatment adherence and outcomes in Euro-American patient groups, quantitative and qualitative exploration of these issues in patients from different cultural and ethnic backgrounds has been lacking. This review discusses the methodological issues associated with measuring depression in patients of South Asian origin who have a 3- to 5-fold greater risk of developing ESRD. There is a need to advance research into the development of accurate screening practices for this patient group, with an emphasis on studies utilizing rigorous approaches to evaluating the use of both emic (culture-specific) and etic (universal or culture-general) screening instruments.
Fractures as an Independent Predictor of Functional Decline in Older People: A Population-Based Study with an 8-Year Follow-Up
Authors: Piirtola Maarit , Löppönen Minna , Vahlberg Tero , Isoaho Raimo , Kivelä Sirkka-Liisa , Räihä Ismo
Published: December 2011

Background: Fractures among older people are common, but there is scant evidence about the impact of fractures on functional decline in an unselected older population. Objective: The objective of this study was to analyze the impact of lower and upper body fractures on functional performance among older adults during an 8-year follow-up. Methods: A population-based cohort of 616 Finnish persons aged 65 and over was followed for up to 8 years, and the association between fractures and the risk of short-term (0–2 years) and long-term (up to 8 years) functional decline was analyzed. Fractures were categorized according their functional influence on mobility and activities of daily living (ADL) into lower and upper body fractures. Multivariate cumulative logistic regression model was used in the analyses. Results: During the 8-year follow-up, 112 (18%) persons sustained at least one fracture. In the multivariate analyses, lower body fractures predicted both short-term and long-term decline in mobility [cumulative odds ratio (COR) 4.7, 95% confidence interval (95% CI) 1.9–11.7 and COR 2.6, 95% CI 1.1–6.2, respectively] and in ADL performance (COR 3.1, 95% CI 1.3–7.6 and COR 4.7, 95% CI 2.0–11.4, respectively). Upper body fractures predicted decline in ADL performance during the long-term follow-up (COR 2.5, 95% CI 1.3–4.8). Pre-fracture functional decline and inactivity in leisure time physical exercise were independently associated with the risk of decline in extensive activities. Conclusion: Fractures have an independent influence on the development of functional decline in older persons regardless of the pre-fracture health. Prevention of falls and fractures and improvement of treatment, rehabilitation and follow-up process after fractures are needed.
A Case of Spontaneous Intra-Amniotic Hemorrhage in an Asymptomatic Patient at Near Term Pregnancy
Authors: Gilboa Yinon , Duvdevani Nir , Yinon Yoav , Achiron Reuven
Published: December 2011

A spontaneous intra-amniotic hemorrhage is a very rare condition, which has been previously described in symptomatic patients. We report a case of an asymptomatic spontaneous intra-amniotic hemorrhage at 38 weeks of gestation, resulting in a favorable maternal and neonatal outcome following sonographic antenatal detection of an intra-amniotic blood clot. This pathology should be acknowledged, since a good clinical outcome depends on early diagnosis.