bluuebunny/crossref_metadata_2025 huggingface dataset:
The Economics of Urban-Rural Space
Authors: Irwin Elena G. , Bell Kathleen P. , Bockstael Nancy E. , Newburn David A. , Partridge Mark D. , Wu JunJie
Published: June 2009

The emergence of urban-rural space, as evidenced by the expansion of low-density exurban areas and growth of amenity-based rural areas, is characterized by the merging of a rural landscape form with urban economic function. Changing economic conditions, including waning transportation and communication costs, technological change and economic restructuring, rising real incomes, and changing tastes for natural amenities, have led to this new form of urban-rural interdependence. We review the recent research on the causes and consequences of this growth at regional and metropolitan scales, discuss advances in empirical and theoretical economic models of urban land-use patterns at spatially disaggregate scales, and highlight research on environmental impacts and the efficacy of growth controls and land conservation programs that seek to manage this growth. The paper concludes with future research questions and needs. These include spatially disaggregate and accurate data, improved causal inference and structural modeling, and dynamic models that incorporate multiple sources of spatial and agent heterogeneity and interactions.
Inhibition of CDKS by roscovitine suppressed LPS-induced·NO production through inhibiting NFκB activation and BH4biosynthesis in macrophages
Authors: Du Jianhai , Wei Na , Guan Tongju , Xu Hao , An Jianzhong , Pritchard Kirkwood A. , Shi Yang
Published: June 2009

In inflammatory diseases, tissue damage is critically associated with nitric oxide (·NO) and cytokines, which are overproduced in response to cellular release of endotoxins. Here we investigated the inhibitory effect of roscovitine, a selective inhibitor of cyclin-dependent kinases (CDKs) on·NO production in mouse macrophages. In RAW264.7 cells, we found that roscovitine abolished the production of·NO induced by lipopolysaccharide (LPS). Moreover, roscovitine significantly inhibited LPS-induced inducible nitric oxide synthase (iNOS) mRNA and protein expression. Our data also showed that roscovitine attenuated LPS-induced phosphorylation of IκB kinase β (IKKβ), IκB, and p65 but enhanced the phosphorylation of ERK, p38, and c-Jun NH2-terminal kinase (JNK). In addition, roscovitine dose dependently inhibited LPS-induced expression of cyclooxygenase-2 (COX)-2, IL-1β, and IL-6 but not tumor necrosis factor (TNF)-α. Tetrahydrobiopterin (BH4), an essential cofactor for iNOS, is easily oxidized to 7,8-dihydrobiopterin (BH2). Roscovitine significantly inhibited LPS-induced BH4biosynthesis and decreased BH4-to-BH2ratio. Furthermore, roscovitine greatly reduced the upregulation of GTP cyclohydrolase-1 (GCH-1), the rate-limiting enzyme for BH4biosynthesis. Using other CDK inhibitors, we found that CDK1, CDK5, and CDK7, but not CDK2, significantly inhibited LPS-induced·NO production in macrophages. Similarly, in isolated peritoneal macrophages, roscovitine strongly inhibited·NO production, iNOS, and COX-2 upregulation, activation of NFκB, and induction of GCH-1 by LPS. Together, our data indicate that roscovitine abolishes LPS-induced·NO production in macrophages by suppressing nuclear factor-κB activation and BH4biosynthesis, which might be mediated by CDK1, CDK5, and CDK7. Our results also suggest that roscovitine may inhibit inflammation and that CDKs may play important roles in the mechanisms by which roscovitine attenuates inflammation.
EnterohemorrhagicEscherichia colisuppresses inflammatory response to cytokines and its own toxin
Authors: Bellmeyer Amy , Cotton Cynthia , Kanteti Rajani , Koutsouris Athanasia , Viswanathan V. K. , Hecht Gail
Published: June 2009

Infection with the enteric pathogen enterohemorrhagic Escherichia coli (EHEC) causes a variety of symptoms ranging from nonbloody diarrhea to more severe sequelae including hemorrhagic colitis, altered sensorium and seizures, and even life-threatening complications, such as hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. The more severe consequences of EHEC infection are attributable to the production of Shiga toxin (Stx) and its subsequent effects on the vasculature, which expresses high levels of the Stx receptor, Gb3. Interestingly, the intestinal epithelium does not express Gb3. Despite the lack of Gb3 receptor expression, intestinal epithelial cells translocate Stx. The effect of Stx on intestinal epithelial cells is controversial with some studies demonstrating induction of inflammation and others not. This may be difficult to resolve because EHEC expresses both proinflammatory molecules, such as flagellin, and factor(s) that dampen the inflammatory response of epithelial cells. The goal of our study was to define the effect of Stx on the inflammatory response of intestinal epithelial cells and to determine whether infection by EHEC modulates this response. Here we show that Stx is a potent inducer of the inflammatory response in intestinal epithelial cells and confirm that EHEC attenuates the induction of IL-8 by host-derived proinflammatory cytokines. More importantly, however, we show that infection with EHEC attenuates the inflammatory response by intestinal epithelial cells to its own toxin. We speculate that the ability of EHEC to dampen epithelial cell inflammatory responses to Stx and cytokines facilitates intestinal colonization.
The Influence of Neuroactive Steroid Lipophilicity on GABAAReceptor Modulation: Evidence for a Low-Affinity Interaction
Authors: Chisari Mariangela , Eisenman Lawrence N. , Krishnan Kathiresan , Bandyopadhyaya Achintya K. , Wang Cunde , Taylor Amanda , Benz Ann , Covey Douglas F. , Zorumski Charles F. , Mennerick Steven
Published: June 2009

Anesthetic steroids with actions at γ-aminobutyric acid type A receptors (GABAARs) may access transmembrane domain binding site(s) directly from the plasma cell membrane. Accordingly, the effective concentration in lipid phase and the ability of the steroid to meet pharmacophore requirements for activity will both contribute to observed steady-state potency. Furthermore, onset and offset of receptor effects may be rate limited by lipid partitioning. Here we show that several GABA-active steroids, including naturally occurring neurosteroids, of different lipophilicity differ in kinetics and potency at GABAARs. The hydrophobicity ranking predicted relative potency of GABAAR potentiation and predicted current offset kinetics. Kinetic offset differences among steroids were largely eliminated by γ-cyclodextrin, a scavenger of unbound steroid, suggesting that affinity differences among the analogues are dwarfed by the contributions of nonspecific accumulation. A 7-nitrobenz-2-oxa-1,3-diazole (NBD)–tagged fluorescent analogue of the low-lipophilicity alphaxalone (C17-NBD-alphaxalone) exhibited faster nonspecific accumulation and departitioning than those of a fluorescent analogue of the high-lipophilicity (3α,5α)-3-hydroxypregnan-20-one (C17-NBD-3α5αA). These differences were paralleled by differences in potentiation of GABAAR function. The enantiomer of C17-NBD-3α5αA, which does not satisfy pharmacophore requirements for steroid potentiation, exhibited identical fluorescence kinetics and distribution to C17-NBD-3α5αA, but was inactive at GABAARs. Simple simulations supported our major findings, which suggest that neurosteroid binding affinity is low. Therefore both specific (e.g., fulfilling pharmacophore requirements) and nonspecific (e.g., lipid solubility) properties contribute to the potency and longevity of anesthetic steroid action.
Chemosensory Responses to CO2 in Multiple Brain Stem Nuclei Determined Using a Voltage-Sensitive Dye in Brain Slices From Rats
Authors: Erlichman Joseph S. , Boyer Andrew C. , Reagan Patrick , Putnam Robert W. , Ritucci Nick A. , Leiter J. C.
Published: June 2009

We used epifluorescence microscopy and a voltage-sensitive dye, di-8-ANEPPS, to study changes in membrane potential during hypercapnia with or without synaptic blockade in chemosensory brain stem nuclei: the locus coeruleus (LC), the nucleus of the solitary tract, lateral paragigantocellularis nucleus, raphé pallidus, and raphé obscurus and, in putative nonchemosensitive nuclei, the gigantocellularis reticular nucleus and the spinotrigeminal nucleus. We studied the response to hypercapnia in LC cells to evaluate the performance characteristics of the voltage-sensitive dye. Hypercapnia depolarized many LC cells and the voltage responses to hypercapnia were diminished, but not eradicated, by synaptic blockade (there were intrinsically CO2-sensitive cells in the LC). The voltage response to hypercapnia was substantially diminished after inhibiting fast Na+ channels with tetrodotoxin. Thus action potential–related activity was responsible for most of the optical signal that we detected. We systematically examined CO2 sensitivity among cells in brain stem nuclei to test the hypothesis that CO2 sensitivity is a ubiquitous phenomenon, not restricted to nominally CO2 chemosensory nuclei. We found intrinsically CO2 sensitive neurons in all the nuclei that we examined; even the nonchemosensory nuclei had small numbers of intrinsically CO2 sensitive neurons. However, synaptic blockade significantly altered the distribution of CO2-sensitive cells in all of the nuclei so that the cellular response to CO2 in more intact preparations may be difficult to predict based on studies of intrinsic neuronal activity. Thus CO2-sensitive neurons are widely distributed in chemosensory and nonchemosensory nuclei and CO2 sensitivity is dependent on inhibitory and excitatory synaptic activity even within brain slices. Neuronal CO2 sensitivity important for the behavioral response to CO2 in intact animals will thus be determined as much by synaptic mechanisms and patterns of connectivity throughout the brain as by intrinsic CO2 sensitivity.
Right Porto-Ovarian H-Shunt for the Surgical Treatment of Symptomatic Portal Biliopathy: A Case Report and Literature Review
Authors: Vasiliadis Konstantinos , Engelmann Guido , Sauer Peter , Weitz Jürgen , Schmidt Jan
Published: June 2009

Portal hypertension, especially when it is caused by extrahepatic portal vein thrombosis, is commonly followed by the development of an abnormal periportal and pericholedochal variceal network, which form a portal cavernoma. This may exert extrinsic pressure on the adjacent biliary ducts and gallblader, causing morphologic abnormalities, termed portal biliopathy, which is usually leading to asymptomatic cholestasis, while less frequently it can be associated with obstructive jaundice, gallstone formation, and cholangitis. Endoscopic stone extraction can effectively treat portal biliopathy when cholangitis is associated with common bile duct stones. Portosystemic shunts are indicated in cases of disease recurrence as they can achieve regression of portal cavernoma and usually relieve symptomatic portal biliopathy. This case describes an alternative partial portosystemic shunt that utilizes the right ovarian vein as an autologous conduit for the surgical treatment of symptomatic portal biliopathy.
On the Relation between Bursts and Dynamic Synapse Properties: A Modulation‐Based Ansatz
Authors: Mayr Christian , Partzsch Johannes , Schüffny Rene
Published: June 2009

When entering a synapse, presynaptic pulse trains are filtered according to the recent pulse history at the synapse and also with respect to their own pulse time course. Various behavioral models have tried to reproduce these complex filtering properties. In particular, the quantal model of neurotransmitter release has been shown to be highly
selective for particular presynaptic pulse patterns. However, since the original, pulse‐iterative quantal model does not lend itself to mathematical analysis, investigations have only been carried out via simulations. In contrast, we derive a comprehensive explicit expression for the quantal model. We show the correlation between the parameters of this explicit
expression and the preferred spike train pattern of the synapse. In particular, our analysis of the transmission of modulated pulse trains across a dynamic synapse links the original parameters of the quantal model to the transmission efficacy of two major spiking regimes, that is, bursting and constant‐rate ones.
Worldwide Guidelines for the Preparation and Quality Management of Dialysis Fluid and Their Implementation
Authors: Ward Richard A.
Published: June 2009

Quality standards for dialysis water have existed for more than 25 years. Current standards generally agree concerning the maximum allowable levels of chemical contaminants; however, significant differences exist concerning the maximum allowable levels of microbiological contaminants and the methods used to measure them. While quality standards for dialysis water are common, there are relatively few standards or recommendations for dialysis fluid quality and these also differ markedly in the maximum allowable level for microbiological contaminants. Compliance with quality standards for dialysis water and dialysis fluid appears to have improved over the past 20 years, although the actual extent of compliance is difficult to assess. A universal standard for fluid quality might be of benefit to the wider dialysis community; however, progress towards that goal will depend on resolution of important issues, including how the standard is to be applied, if it should be limited to substances with documented toxicity for hemodialysis patients, and how to address microbiological contaminants.
Purification of Dialysis Fluid: Historical Background and Perspective
Authors: Ledebo Ingrid
Published: June 2009

When dialysis became a chronic therapy, certain clinical symptoms could be connected to the fluid quality and some form of water treatment had to be introduced. The required equipment was empirically developed and consisted of sedimentation filters, carbon filters and softeners. In the mid-1970s the toxic effect of aluminum accumulation was discovered and led to the introduction of reverse osmosis modules. When these components – prefilters, softeners and RO modules – are properly maintained, they produce water of a quality that should meet modern standards. However, the water quality could be ruined by bacterial contamination from the distribution pipes, unless the entire flow path is hygienically designed and frequently disinfected. The quality of the concentrate is also important, especially the bicarbonate component which is prone to bacterial growth. The extent of the microbiological burden in water and dialysis fluid has been brought to the attention of the dialysis community through new and sensitive detection and quantification methods for bacteria and endotoxin.
Clinical Effect of Purification of Dialysis Fluids, Evidence and Experience
Authors: Schindler Ralf
Published: June 2009

Microinflammation in renal failure has been the subject of numerous contributions to the literature. The bacterial contamination of dialysate and subsequent transfer of bacterial products onto the blood side is an important cause for microinflammation in hemodialysis patients. It has been suggested that the inflammatory process may not merely be an epiphenomenon but rather a pathogenetic factor in the genesis of atherosclerosis [1,2,3]. Thus, by promoting microinflammation, dialysate contamination may contribute directly to cardiovascular morbidity and mortality.
Current Situation of Endotoxin Retentive Filter
Authors: Tsuchida Kenji , Nakamura Masayuki , Yoshikawa Kazuhiro , Minakuchi Jun , Takesawa Shingo
Published: June 2009

Most Japanese facilities use central dialysis fluid delivery systems (CDDS). In addition, since high-performance dialysis membranes are frequently used in Japan, the standard recommends that ultrapure dialysis fluid (UPD) should be used for all dialysis modalities at all dialysis facilities. RO produces and endotoxin retentive filters (ETRFs) occupy the most important position for UPD in this CDDS process. But ETRF is not accepted as medical equipment now in Japan. Since the logarithm reduction value (LRV) of ETRFs widely used today may be a desirable 3 for endotoxin (ET) and 7 for bacteria, UPD could be theoretically obtained through the use of ETRFs. However, we have no data of the LRV for ET and bacteria with a both new and used ETRF now. So we must study whether ETRF has this performance by doing an ET and bacterial challenge test in the near future. Also, ETRF will have to be accepted as medical equipment indicating the safety of CDDS.
Structural Analyses of Chromosomes and Their Constituent Proteins
Authors: Fukui K.
Published: June 2009

The importance of chromosome structural study is first described. Then an overview of historical imaging methods that enable us to quantitatively understand chromosome images and structure is given with special reference to the identification of small plant chromosomes and development of their quantitative chromosome maps. A three-dimensional understanding of chromosome distribution within a nucleus answers why the gene-rich regions localize at both ends of chromosomes, especially in the case of species with Rabl orientation. Not only imaging methods but also proteomic approaches are effective in understanding chromosome structure. Over 200 proteins have been identified by proteome analysis of human metaphase chromosomes, and are categorized into four distinct groups according to their nature and localization on chromosomes. These are chromosome coating proteins (CCPs), chromosome peripheral proteins (CPPs), chromosome structural proteins (CSPs), and chromosome fibrous proteins (CFPs). A chromosome four layer model has been developed accordingly. Case studies on individual identified proteins are further described, and the functional similarities of CPPs are exemplified. In addition the controversial roles of CSPs (topoisomerase and condensin), especially for development of higher-order chromosome structure, are discussed. Finally, it is concluded that further advances in chromosome research are necessary to solve an enigma lasting nearly two centuries, that is, why chromosomes retain the same shape in plants and animals.
Extrachromosomal Double Minutes and Chromosomal Homogeneously Staining Regions as Probes for Chromosome Research
Authors: Shimizu N.
Published: June 2009

Gene amplification in human cancer cells generates two cytogenetically identifiable structures: extrachromosomal double minutes (DMs) and the chromosomal homogeneously staining region (HSR). DMs are composed of autonomously replicating circular DNA of genomic origin, and they tell us about how the extrachromosomal elements may behave in the cells, how they were entrapped by the micronuclei and how they were eliminated from the cells. On the other hand, the episome model predicts that extrachromosomal elements excised from the chromosome arm might generate DMs, and the breakage-fusion-bridge (BFB) cycle model explains the generation of the HSR. In accordance with this, a plasmid bearing a mammalian replication initiation region (IR) and a matrix attachment region (MAR) mimics gene amplification and generates DMs and HSRs de novo. The IR/MAR gene amplification system extends our understanding on the mechanism of gene amplification and the behavior of amplified genes. Furthermore, the system may suggest the way how extrachromosomal elements in general may alter the chromosome architecture and function.
A Technical Note on Quantum Dots for Multi-Color Fluorescence in situ Hybridization
Authors: Müller S. , Cremer M. , Neusser M. , Grasser F. , Cremer T.
Published: June 2009

Quantum dots (Qdots) are semiconductor nanocrystals, which are photo-stable, show bright fluorescence with narrow, symmetric emission spectra and are available in multiple resolvable colors. We established a FISH protocol for the simultaneous visualization of up to 6 different DNA probes differentially labeled with Qdots and with conventional organic fluorochromes. Using a Leica SP5 laser scanning confocal microscope for image capture, we tested various combinations of hapten-labeled probes detected with streptavidin-Qdot525, sheep anti-digoxigenin-Qdot605, rat anti-dinitrophenyl-Qdot655 and goat anti-mouse-Qdot655, respectively, together with FITC-dUTP-, Cy3-dUTP- and Texas Red-dUTP-labeled probes. We further demonstrate that Qdots are suitable for imaging of FISH probes using 4Pi microscopy, which promises to push the resolution limits of light microscopy to 100 nanometers or less when applying a deconvolution algorithm, but requires the use of highly photo-stable fluors.
Endothelial Function in Lacunar Infarction: A Comparison of Lacunar Infarction, Cerebral Atherosclerosis and Control Group
Authors: Kim Jin-Seok , Lee Hak-Seung , Park Hyun-Young , Kim Soo-Seong , Kang Hyun-Goo , Kim Nam-Ho , Park Jong-Seong , Kim Yosik
Published: June 2009

Background: There are conflicting evidences on endothelial function in lacunar infarction. This may be attributed to the effects of risk factors on the vascular smooth muscle. To test endothelial function only in patients with lacunar infarction, we evaluated the endothelium-dependent and -independent vasodilatation of the brachial artery. Methods: We enrolled consecutive patients with lacunar infarction defined by clinical characteristics and MRI findings. The control group included age- and sex-matched patients with hypertension who do not have any history of clinical stroke, coronary artery disease or peripheral vascular disease. Endothelial function was evaluated using flow-mediated dilatation (FMD) and nitrogen-mediated dilatation (NMD) of the brachial artery. FMD and NMD were examined by an experienced vascular sonographer using a high-resolution ultrasound. Intracranial stenosis was defined as flow gap or >50% reduction in vessel diameter on MRA. Results: FMD was 6.6 ± 4.5% in the lacunar infarction group and 12.2 ± 4.6% in the control group (p = 0.000). NMD was 14.3 ± 4.9% in the lacunar infarction group and 13.8 ± 4.9% in the control group (p = 0.37). FMD in patients with lacunar infarction and intracranial arterial stenosis was 6.4 ± 3.9%, and FMD in patients with lacunar infarction was only 6.9 ± 5.5%. In the control group, it was 12.2 ± 4.6%. Conclusion: FMD was low in patients with lacunar infarction. NMD was similar between the lacunar infarction group and the control group. These results are suggestive of pure endothelial dysfunction in lacunar infarction. Endothelial dysfunction was as severe in lacunar infarction as in intracranial arterial stenosis.
Genistein in the Presence of 17β-Estradiol Inhibits Proliferation of ERβ Breast Cancer Cells
Authors: Rajah Talitha T. , Du Nga , Drews Neil , Cohn Rachel
Published: June 2009

Background/Aim:Genistein, a soy component, has been shown to have a biphasic proliferative effect in breast cancer cells, inhibiting in vitro cell proliferation at high concentrations (>10 μmol/l), while stimulating cell proliferation at lower concentrations (<10 μmol/l). However, epidemiological studies have shown an inverse correlation between the intake of genistein and the incidence of breast cancer. One of the possible reasons for this discrepancy could be the differing status of the estrogen receptor (ERα and/or ERβ). Genistein selectively binds to ERβ with strong affinity and thereby could be a potential chemotherapeutic agent against breast cancer of the ERα-negative and ERβ-positive type. Therefore, the objective of the present study was to determine whether the proliferative effects of genistein were caused by its activity as a selective ERβ agonist or merely as an antiestrogen. Method: This study was carried out in MDA-MB-231 (ERβ) and T47D (ERα and ERβ) human breast cancer cells. Cell proliferation was determined by the MTT (3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) assay. The cells were grown in estrogen-starved media and exposed to genistein at different concentrations for 72 h, either in the presence or absence of 17β-estradiol. Results: A significant decrease in cell proliferation was seen in MDA-MB-231 cells at low concentrations of genistein in the presence of 17β-estradiol, as compared to genistein alone. In T47D cells, which are known to have a predominance of ERα over ERβ, genistein showed a biphasic cell proliferative response both in the presence and absence of 17β-estradiol. Conclusions:Our results suggest that in cells with a predominance of ERα, genistein acts as an agonist to ERα, and in cells with ERβ alone, genistein most likely acts as an antiestrogen. Our results also suggest that genistein could be useful as a chemotherapeutic agent in premenopausal women with breast cancer of the ERα-negative and ERβ-positive type.
Occurrence of Depression in Families with Frontotemporal Dementia: A Family History Study
Authors: Horstmann V. , Gräsbeck A.
Published: June 2009

Background: There are clinical similarities between frontotemporal dementia (FTD) and depression. The aim is to study co-aggregation of depression in families with FTD, indicating the existence of common aetiological factors. Methods: The study included 74 index patients with FTD and their 540 first-degree relatives above the age of 15 years. Occurrence of depression was studied at 3 different levels. Results: The incidence of depression in first-degree relatives of FTD patients was not higher than that of a general population. Occurrence of depression was not higher in families where parents had FTD compared to families with parents having no indications of FTD. Individuals with FTD had not suffered from depression to a greater extent than those without FTD. Conclusions: The hypothesis of a common aetiological factor of FTD and depression was not supported.
Surgical Salvage of Bleeding Peptic Ulcers after Failed Therapeutic Endoscopy
Authors: Chiu Philip Wai Yan , Ng Enders Kwok Wai , Wong Simon Kin Hung , Teoh Anthony Yuen Bun , Cheung Frances Ka Yin , Yung Man-yee , Sung Joseph Jao Yiu , Lau James Yun Wong
Published: June 2009

Background: The approach to salvage surgery after failed endoscopic therapy for a bleeding peptic ulcer is controversial. We aimed to compare the outcomes of salvage surgery after failed endoscopic therapy for bleeding peptic ulcers over a 10-year period. Methods: Patients receiving salvage surgery for bleeding peptic ulcers were divided into 2 cohorts, the 1st from 1993 to 1998 and the 2nd from 1999 to 2004. The type of salvage surgery was defined as minimal if ulcer plication or an ulcerectomy was performed, and definitive if the patient received a vagotomy or gastrectomy. Results: One hundred and twenty-three patients received salvage surgery in the 1st cohort, while 42 patients received surgical hemostasis for the bleeding peptic ulcer in the 2nd cohort. Patients in the 2nd cohort consisted of a larger proportion of in-hospital bleeders (cohort 1: 12.2%, cohort 2: 42.9%; p < 0.005) and had a significantly higher proportion of comorbidities. A larger number of patients received minimal surgery in cohort 2 (cohort 1: 42.3%, cohort 2: 73.8%; p < 0.005). Conclusions: With advances in therapeutic endoscopy, patients who developed failed endoscopic hemostasis are likely to be poor surgical candidates with multiple comorbidities. The approach to salvage surgery has inclined towards minimal surgery to hasten surgical hemostasis among these fragile patients.
How to Prevent Lateral Thermal Damage to Tissue Using the Harmonic Scalpel: Experimental Study on Pig Small Intestine and Abdominal Wall
Authors: Pogorelić Z. , Perko Z. , Družijanić N. , Tomić S. , Mrklić I.
Published: June 2009

Introduction: When using a harmonic scalpel, the lower amount of energy that is transduced to the tissue reduces the chance of lateral thermal damage. Methods: Pigs (weight: 40 kg) were used as the experimental model. After anesthesia, tissue was coagulated using different application regimens for each group. The width of tissue necrosis was measured from the point of incision by the harmonic scalpel. Results: The pig abdominal tissues suffered mean thermal damage of 0.0825 (output power 3) and 0.2969 mm (output power 5) when used for 5 s; at 10 s these values were 0.3850 and 0.4793 mm, respectively. In a third experimental condition, with 10 s of application broken down into 2 parts of 5 s with a 5-second pause in-between, these values were 0.1876 and 0.2013 mm, respectively. The small intestine tissues suffered mean thermal damage of 0.1302 (output power 3) and 0.1771 mm (output power 5) at a duration of 5 s. After 10 s of application, these values changed to 0.2655 (output power 3) and 0.2983 mm (output power 5). In the third condition (activity for 5 s, pause for 5 s, activity for 5 s), they were 0.2011 and 0.2258 mm, respectively. Conclusion: Coagulation necrosis is bigger if the usage is continuous rather than if it is disconnected/reconnected.
A Pilot Beta-Thalassaemia Screening Program in the Albanian Population for a Health Planning Program
Authors: Baghernajad-Salehi Leila , D’Apice Maria Rosaria , Babameto-Laku Anila , Biancolella Michela , Mitre Anila , Russo Silvia , Di Daniele Nicola , Sangiuolo Federica , Mokini Vahe , Novelli Giuseppe
Published: June 2009

In Albania, no definite national screening programme of β-thalassaemia has yet been developed for carrier detection. Only limited information about the occurrence and the types of haemoglobin abnormalities is available. Thus, an educational and screening programme was carried out in one high school with a total of 217 young students from the coastal province of Lushnja in Albania. The pilot programme included a systematic sampling of whole saliva, DNA genomic extraction and the determination of defective β-thalassaemia genes by reverse dot-blot hybridization with 22 probes specific for the Mediterranean populations.Of the 201 subjects tested, 17 (8.4%) students turned out to be carriers of β-thalassaemia mutations and haemoglobin variants. The most common mutation is HbS (c.20A→T) with a frequency of 3.2%, followed by IVS-I-110 (G→A) (c.93-21G→A) substitution identified in 4 out of 402 chromosomes (1%). In the province of Lushnja, the frequency of β-thalassaemia carriers was high. As expected, the results show that identified mutations in this population are similar to those found in the east Mediterranean area, suggesting the same origin for mutant alleles during migratory streams. Implementation of a routine carrier-screening programme is significantly facilitated by the presence of only two mutations and would be a wise approach to prevent β-thalassaemia in the region.
A New Perspective on Therapeutic Inhibition of Advanced Glycation in Diabetic Microvascular Complications: Common Downstream Endpoints Achieved Through Disparate Therapeutic Approaches?
Authors: Sourris Karly C. , Harcourt Brooke E. , Forbes Josephine M.
Published: June 2009

A commonality among the chemically disparate compounds that inhibit the formation and accumulation of advanced glycation end products (AGEs) or their signalling pathways is their end organ protection in experimental models of diabetes complications. Although this group of therapeutics are structurally and functionally distinct with numerous mechanisms of action, the most important factor governing their therapeutic capability is clearly their ability to alleviate the tissue burden of advanced glycation, rather than the biochemical mechanism by which this is achieved. However, it remains to be determined if it is the reduction in tissue AGE levels per se or inhibition of downstream signal pathways which is ultimately required for end organ protection. For example, a number of these agents stimulate antioxidant defences, modify lipid profiles and inhibit low-grade inflammation. These novel actions emphasise the importance of further examination of the advanced glycation pathway and in particular the diverse action of these agents in ameliorating the development of diabetic complications such as nephropathy.
Applications of Nucleic Acid Chaperone Activity of CspA and Its Homologues
Authors: Phadtare Sangita , Zhu Ling , Uemori Takashi , Mukai Hiroyuki , Kato Ikunoshin , Inouye Masayori
Published: June 2009

In Escherichia coli, the cold shock response is exerted upon temperature change from 37 to 15°C and is characterized by induction of several cold shock proteins including its major cold shock protein, CspA. E. coli CspA family consists of nine members, CspA to CspI. CspA and some of its homologues play a critical role in cold acclimation of cells as RNA chaperones by destabilizing secondary structures in RNAs. Here, we showed that the nucleic acid melting activity of Csp proteins can be used to facilitate reactions, such as RT-PCR or RNA cleavage reactions by endoribonucleases, which are hindered by presence of secondary structures in the DNA/RNA substrate used. The low substrate specificity of Csps together with their compatibility with various enzymes and their stability and activity over a broad temperature range makes them ideal candidates to be used for a variety of processes.
Population Screening for Genetic Disorders in the 21st Century: Evidence, Economics, and Ethics
Authors: Grosse S.D. , Rogowski W.H. , Ross L.F. , Cornel M.C. , Dondorp W.J. , Khoury M.J.
Published: June 2009

Background: Proposals for population screening for genetic diseases require careful scrutiny by decision makers because of the potential for harms and the need to demonstrate benefits commensurate with the opportunity cost of resources expended. Methods: We review current evidence-based processes used in the United States, the United Kingdom, and the Netherlands to assess genetic screening programs, including newborn screening programs, carrier screening, and organized cascade testing of relatives of patients with genetic syndromes. In particular, we address critical evidentiary, economic, and ethical issues that arise in the appraisal of screening tests offered to the population. Specific case studies include newborn screening for congenital adrenal hyperplasia and cystic fibrosis and adult screening for hereditary hemochromatosis. Results: Organizations and countries often reach different conclusions about the suitability of screening tests for implementation on a population basis. Deciding when and how to introduce pilot screening programs is challenging. In certain cases, e.g., hereditary hemochromatosis, a consensus does not support general screening although cascade screening may be cost-effective. Conclusion: Genetic screening policies have often been determined by technological capability, advocacy, and medical opinion rather than through a rigorous evidence-based review process. Decision making should take into account principles of ethics and opportunity costs.
Cadmium Is a Novel and Independent Risk Factor for Early Atherosclerosis Mechanisms and In Vivo Relevance
Authors: Messner Barbara , Knoflach Michael , Seubert Andreas , Ritsch Andreas , Pfaller Kristian , Henderson Blair , Shen Ying H. , Zeller Iris , Willeit Johann , Laufer Günther , Wick Georg , Kiechl Stefan , Bernhard David
Published: June 2009

Objectives—

Although cadmium (Cd) is an important and common environmental pollutant and has been linked to cardiovascular diseases, little is known about its effects in initial stages of atherosclerosis.

Methods and Results—

In the 195 young healthy women of the Atherosclerosis Risk Factors in Female Youngsters (ARFY) study, cadmium (Cd) level was independently associated with early atherosclerotic vessel wall thickening (intima-media thickness exceeding the 90th percentile of the distribution; multivariable OR 1.6[1.1.–2.3],
P
=0.016). In line, Cd-fed ApoE knockout mice yielded a significantly increased aortic plaque surface compared to controls (9.5 versus 26.0 mm
2
,
P
<0.004). In vitro results indicate that physiological doses of Cd increase vascular endothelial permeability up to 6-fold by (1) inhibition of endothelial cell proliferation, and (2) induction of a caspase-independent but Bcl-xL-inhibitable form of cell death more than 72 hours after Cd addition. Both phenomena are preceded by Cd-induced DNA strand breaks and a cellular DNA damage response. Zinc showed a potent protective effect against deleterious effects of Cd both in the in vitro and human studies.

Conclusion—

Our research suggests Cd has promoting effects on early human and murine atherosclerosis, which were partly offset by high Zn concentrations.
Palmitoylation of ATP-Binding Cassette Transporter A1 Is Essential for Its Trafficking and Function
Authors: Singaraja Roshni R. , Kang Martin H. , Vaid Kuljeet , Sanders Shaun S. , Vilas Gonzalo L. , Arstikaitis Pamela , Coutinho Jonathan , Drisdel Renaldo C. , El-Husseini Alaa El Din , Green William N. , Berthiaume Luc , Hayden Michael R.
Published: June 2009

ATP-binding cassette transporter (ABC)A1 lipidates apolipoprotein A-I both directly at the plasma membrane and also uses lipids from the late endosomal or lysosomal compartment in the internal lipidation of apolipoprotein A-I. However, how ABCA1 targeting to these specific membranes is regulated remains unknown. Palmitoylation is a dynamically regulated lipid modification that targets many proteins to specific membrane domains. We hypothesized that palmitoylation may also regulate ABCA1 transport and function. Indeed, ABCA1 is robustly palmitoylated at cysteines 3, -23, -1110, and -1111. Abrogation of palmitoylation of ABCA1 by mutation of the cysteines results in a reduction of ABCA1 localization at the plasma membranes and a reduction in the ability of ABCA1 to efflux lipids to apolipoprotein A-I. ABCA1 is palmitoylated by the palmitoyl transferase DHHC8, and increasing DHHC8 protein results in increased ABCA1-mediated lipid efflux. Thus, palmitoylation regulates ABCA1 localization at the plasma membrane, and regulates its lipid efflux ability.
Novel Pharmacophores of Connexin43 Based on the “RXP” Series of Cx43-Binding Peptides
Authors: Verma Vandana , Larsen Bjarne Due , Coombs Wanda , Lin Xianming , Spagnol Gaelle , Sorgen Paul L. , Taffet Steven M. , Delmar Mario
Published: June 2009

Gap junction pharmacology is a nascent field. Previous studies have identified molecules that enhance intercellular communication, and may offer potential for innovative antiarrhythmic therapy. However, their specific molecular target(s) and mechanism(s) of action remain unknown. Previously, we identified a 34-aa peptide (RXP-E) that binds the carboxyl terminal domain of Cx43 (Cx43CT) and prevents cardiac gap junction closure and action potential propagation block. These results supported the feasibility of a peptide-based pharmacology to Cx43, but the structure of the core active element in RXP-E, an essential step for pharmacological development, remained undefined. Here, we used a combination of molecular modeling, surface plasmon resonance, nuclear magnetic resonance and patch-clamp strategies to define, for the first time, a unique ensemble of pharmacophores that bind Cx43CT and prevent closure of Cx43 channels. Two particular molecules are best representatives of this family: a cyclized heptapeptide (called CyRP-71) and a linear octapeptide of sequence RRNYRRNY. These 2 small compounds offer the first structural platform for the design of Cx43-interacting gap junction openers. Moreover, the structure of these compounds offers an imprint of a region of Cx43CT that is fundamental to gap junction channel function.
A Model for Learning Topographically Organized Parts-Based Representations of Objects in Visual Cortex: Topographic Nonnegative Matrix Factorization
Authors: Hosoda Kenji , Watanabe Masataka , Wersing Heiko , Körner Edgar , Tsujino Hiroshi , Tamura Hiroshi , Fujita Ichiro
Published: June 2009

Object representation in the inferior temporal cortex (IT), an area of visual cortex critical for object recognition in the primate, exhibits two prominent properties: (1) objects are represented by the combined activity of columnar clusters of neurons, with each cluster representing component features or parts of objects, and (2) closely related features are continuously represented along the tangential direction of individual columnar clusters. Here we propose a learning model that reflects these properties of parts-based representation and topographic organization in a unified framework. This model is based on a nonnegative matrix factorization (NMF) basis decomposition method. NMF alone provides a parts-based representation where nonnegative inputs are approximated by additive combinations of nonnegative basis functions. Our proposed model of topographic NMF (TNMF) incorporates neighborhood connections between NMF basis functions arranged on a topographic map and attains the topographic property without losing the parts-based property of the NMF. The TNMF represents an input by multiple activity peaks to describe diverse information, whereas conventional topographic models, such as the self-organizing map (SOM), represent an input by a single activity peak in a topographic map. We demonstrate the parts-based and topographic properties of the TNMF by constructing a hierarchical model for object recognition where the TNMF is at the top tier for learning high-level object features. The TNMF showed better generalization performance over NMF for a data set of continuous view change of an image and more robustly preserving the continuity of the view change in its object representation. Comparison of the outputs of our model with actual neural responses recorded in the IT indicates that the TNMF reconstructs the neuronal responses better than the SOM, giving plausibility to the parts-based learning of the model.
Democratic Elitism Reappraised
Authors: Higley John , Best Heinrich
Published: June 2009

During the postwar decades following Joseph Schumpeter's seminal Capitalism, Socialism and Democracy, democratic elitism struck many as an apt and insightful description of how representative democracy works – even though convinced democrats detected an "elitist" thrust they found disturbing. But during the last several decades political elites and leaders have wielded more power and influence in Western democracies than Schumpeter and his early adherents acknowledged. If it is to retain relevance and utility, democratic elitism must incorporate the now more evident roles elites and leaders play.
Teachers’ Perception of Satisfaction, Skill Development, and Skill Application After Instructional Consultation Services
Authors: Kaiser Lauren , Rosenfield Sylvia , Gravois Todd
Published: June 2009

A primary hypothesized outcome of consultee-centered consultation, including instructional consultation (IC), is that consultees will become more skilled. However, these claims have not been well researched. Data from 274 teachers implementing IC were analyzed to investigate perceptions of satisfaction and skill development. Results indicated that teachers were highly satisfied, perceived outcomes to meet or exceed their expectations, and felt confident about handling similar problems in the future. The majority reported learning one or more skills or strategies from participating and indicated generalization of skills learned from IC to other students. Relationships between satisfaction, generalization, and perceived outcomes are also presented. Although based on descriptive methodology, this analysis of teachers’ perceptions of IC provides a window into their experiences.
Communicating Depth
Authors: Haysom Keith
Published: June 2009

This essay takes as its task the critical comparison of two thinkers who are rarely matched or studied in tandem: Jürgen Habermas and Maurice Merleau-Ponty. It stages a (largely) speculative dialogue between the two thinkers, considering not only the points of convergence but their likely objections to each other’s accounts of communication and language. I will argue that Merleau-Ponty, whose own concerns significantly overlap with Habermas’s, while simultaneously pulling in a different direction, serves as a useful counter-point to Habermas. This is so because Merleau-Ponty offers us an intersubjectivist account of praxis, from which can be extrapolated an ethics of communicative engagement between self, other, and world. Such a phenomenological and/or existential rereading of the central Habermasian problematic not only compensates for the notorious abstraction of Discourse Ethics, but better underscores possibilities for social transformation inherent in intersubjectivity and the lifeworld than are acknowledged by Habermas.
Thermal, Chemical, and Morphological Characterization of Microcellular Polyurethane Elastomers
Authors: Pacheco Marcos F.M. , Bianchi Otávio , Fiorio Rudinei , Zattera Ademir J. , Zeni Mara , Giovanela Marcelo , Crespo Janaina S.
Published: June 2009

In this study, three different microcellular polyurethane elastomers (MPUE) based on 4,4'-diphenylmethane diisocyanate with different rigid segment contents are prepared (Formulations 1, 2, and 3 with 32, 35, and 42% of rigid segment content, respectively). The MPUE are obtained through a two-step method using a prepolymer system. The samples are analyzed to determine their thermal, morphological, and chemical properties. The thermogravimetric analysis indicates the presence of two degradation stages, referring to the rigid and flexible phases, respectively. The differential scanning calorimetry tests indicate that for the MPUE there was an increase in the glass transition temperature of the flexible phase with an increase in the percent of the rigid phase. An increase in the quantity of the rigid phase present in the MPUE results in greater values for the crosslink density, which in turn results in an increase in the rigidity of the material. The scanning electron microscopy micrographs indicated a large number of closed cells and that a higher rigid segment content give a better cell homogeneity of the samples.
Networked Silica with Exceptional Reinforcing Performance for SBR Compounds: Interconnected by Methylene Diphenyl Diisocyanate
Authors: Dong Shin Jeong  , Chang Kook Hong  , Gyun Taek Lim  , Seo Gon , Chang Seok Ryu
Published: June 2009

A networked silica (NS) prepared by interconnecting silica particles with polymeric methylene diphenyl diisocyanate (MDI) was developed for use as a highly effective reinforcing material for rubber compounds without the need to add silane coupling agents. MDI incorporated onto the silica surface formed networks among neighboring silica particles with urethane linkages and produced NS at low cost. The TEM photographs illustrated the improved dispersion and formation of openings among the silica particles, which could allow easy intrusion of rubber molecules. The NS showed a high reinforcing performance for styrene—butadiene rubber (SBR) compounds, suggesting the possibility of replacing the silica reinforcing systems with coupling agents. Due to the absence of any silane-containing coupling agents, the NS does not suffer the disadvantages associated with coupling agents. Since the NS reinforces rubber compounds by the physical entanglement between rubber molecules and the MDI chains, high loading of the NS is more effective in enhancing the mechanical properties of rubber compounds.
Morphology Development and Melt Linear Viscoelastic Properties of (PA6/PP/PS) Ternary Blend Systems
Authors: Mohammadigoushki Hadi , Nazockdast Hossein , Mostofi Nima
Published: June 2009

The morphology development and melt linear viscoelastic properties of PA6/PP/PS (70/15/15) ternary blends were studied. An attempt was also made to predict the morphology development of these blends using the dynamic interfacial tension of the blend components evaluated from the Palierne's viscoelastic model in conjunction with spreading coefficient approach. The blend samples were prepared by melt blending in an internal mixer at temperature of 260°C and rotor speed of 60 rpm. The ternary blend samples exhibited a pronounced low-frequency nonterminal storage modulus whose values were much greater than those predicted for elastic response of the binary blend samples. This was attributed to strong elastic resistance of a core-shell composite droplet formed in the ternary blend samples that was evidenced by the SEM micrographs of these samples. The results predicted based on spreading coefficient concept also suggested a core-shell type morphology in which PP core was encapsulated by PS shell as a composite minor phase dispersed in PA6 matrix. It was demonstrated that there is a close relationship between melt viscoelastic properties and morphology of ternary blends.