bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying the treatment efficacy of reverse transcriptase inhibitors: new analyses of clinical data based on within-host modeling
Authors: Breban Romulus , Napravnik Sonia , Kahn James , Blower Sally
Published: November 2009

Background

Current measures of the clinical efficacy of antiretroviral therapy (ART) in the treatment of HIV include the change in HIV RNA in the plasma and the gain in CD4 cells.

Methods

We propose new measures for evaluating the efficacy of treatment that is based upon combinations of non-nucleoside and nucleoside reverse transcriptase inhibitors. Our efficacy measures are: theCD4 gain per virion eliminated, thepotential of CD4 count restoration and the viral reproduction number (R0). These efficacy measures are based upon a theoretical understanding of the impact of treatment on both viral dynamics and the immune reconstitution. Patient data were obtained from longitudinal HIV clinical cohorts.

Results

We found that theCD4 cell gain per virion eliminatedranged from 10-2to 600 CD4 cells/virion, thepotential of CD4 count restorationranged from 60 to 1520 CD4 cells/μl, and the basic reproduction number was reduced from an average of 5.1 before therapy to an average of 1.2 after one year of therapy. There was substantial heterogeneity in these efficacy measures among patients with detectable viral replication. We found that many patients who achieved viral suppression did not have high CD4 cell recovery profiles. Our efficacy measures also enabled us to identify a subgroup of patients who were not virally suppressed but had the potential to reach a high CD4 count and/or achieve viral suppression if they had been switched to a more potent regimen.

Conclusion

We show that our new efficacy measures are useful for analyzing the long-term treatment efficacy of combination reverse transcriptase inhibitors and argue that achieving a lowR0does not imply achieving viral suppression.
The expression of Gli3, regulated by HOXD13, may play a role in idiopathic congenital talipes equinovarus
Authors: Cao DongHua , Jin ChunLian , Ren MeiHong , Lin ChangKun , Zhang Xuan , Zhao Ning
Published: November 2009

Background

Idiopathic congenital talipes equinovarus (ICTEV) is a congenital limb deformity. Based on extended transmission disequilibrium testing, Gli-Kruppel family member 3 (Gli3) has been identified as a candidate gene for ICTEV. Here, we verify the role of Gli3 in ICTEV development.

Methods

Using the rat ICTEV model, we analyzed the differences in Gli3 expression levels between model rats and normal control rats. We used luciferase reporter gene assays and ChIP/EMSA assays to analyze the regulatory elements of Gli3.

Results

Gli3 showed higher expression levels in ICTEV model rats compared to controls (P < 0.05). We identified repressor and activator regions in the rat Gli3 promoter. The Gli3 promoter also contains two putative Hoxd13 binding sites. Using EMSA, the Hoxd13 binding site 2 was found to directly interact with Hoxd13 in vitro. ChIP assays of the Hoxd13-Gli3 promoter complex from a developing limb confirmed that endogenous Hoxd13 interacts with this region in vivo.

Conclusion

Our findings suggest that HoxD13 directly interacts with the promoter of Gli3. The increase of Gli3 expression in ICTEV model animal might result from the low expression of HoxD13.
High-level HIV-1 Nef transient expression in Nicotiana benthamiana using the P19 gene silencing suppressor protein of Artichoke Mottled Crinckle Virus
Authors: Lombardi Raffaele , Circelli Patrizia , Villani Maria Elena , Buriani Giampaolo , Nardi Luca , Coppola Valentina , Bianco Linda , Benvenuto Eugenio , Donini Marcello , Marusic Carla
Published: November 2009

Background

In recent years, different HIV antigens have been successfully expressed in plants by either stable transformation or transient expression systems. Among HIV proteins, Nef is considered a promising target for the formulation of a multi-component vaccine due to its implication in the first steps of viral infection. Attempts to express Nef as a single protein product (not fused to a stabilizing protein) in transgenic plants resulted in disappointingly low yields (about 0.5% of total soluble protein). In this work we describe a transient expression system based on co-agroinfiltration of plant virus gene silencing suppressor proteins in Nicotiana benthamiana, followed by a two-step affinity purification protocol of plant-derived Nef.

Results

The effect of three gene silencing viral suppressor proteins (P25 of Potato Virus X, P19 of either Artichoke Mottled Crinckle virus and Tomato Bushy Stunt virus) on Nef transient expression yield was evaluated. The P19 protein of Artichoke Mottled Crinckle virus (AMCV-P19) gave the highest expression yield in vacuum co-agroinfiltration experiments reaching 1.3% of total soluble protein, a level almost three times higher than that previously reported in stable transgenic plants. The high yield observed in the co-agroinfiltrated plants was correlated to a remarkable decrease of Nef-specific small interfering RNAs (siRNAs) indicating an effective modulation of RNA silencing mechanisms by AMCV-P19. Interestingly, we also showed that expression levels in top leaves of vacuum co-agroinfiltrated plants were noticeably reduced compared to bottom leaves. Moreover, purification of Nef from agroinfiltrated tissue was achieved by a two-step immobilized metal ion affinity chromatography protocol with yields of 250 ng/g of fresh tissue.

Conclusion

We demonstrated that expression level of HIV-1 Nef in plant can be improved using a transient expression system enhanced by the AMCV-P19 gene silencing suppressor protein. Moreover, plant-derived Nef was purified, with enhanced yield, exploiting a two-step purification protocol. These results represent a first step towards the development of a plant-derived HIV vaccine.
Cytotoxic and antibacterial activities of endophytic fungi isolated from plants at the National Park, Pahang, Malaysia
Authors: Hazalin Nurul AMN , Ramasamy Kalavathy , Lim Siong Siong Meng , Wahab Ibtisam Abdul , Cole Anthony LJ , Abdul Majeed Abu Bakar
Published: November 2009

Background

Endophytes, microorganisms which reside in plant tissues, have potential in producing novel metabolites for exploitation in medicine. Cytotoxic and antibacterial activities of a total of 300 endophytic fungi were investigated.

Methods

Endophytic fungi were isolated from various parts of 43 plants from the National Park Pahang, Malaysia. Extracts from solid state culture were tested for cytotoxicity against a number of cancer cell lines using the MTT assay. Antibacterial activity was determined using the disc diffusion method.

Results

A total of 300 endophytes were isolated from various parts of plants from the National Park, Pahang. 3.3% of extracts showed potent (IC50 < 0.01 μg/ml) cytotoxic activity against the murine leukemic P388 cell line and 1.7% against a human chronic myeloid leukemic cell line K562. Sporothrix sp. (KK29FL1) isolated from Costus speciosus showed strong cytotoxicity against colorectal carcinoma (HCT116) and human breast adenocarcinoma (MCF7) cell lines with IC50 values of 0.05 μg/ml and 0.02 μg/ml, respectively. Antibacterial activity was demonstrated for 8% of the extracts.

Conclusion

Results indicate the potential for production of bioactive agents from endophytes of the tropical rainforest flora.
Health care utilisation amongst Shenzhen migrant workers: does being insured make a difference?
Authors: Mou Jin , Cheng Jinquan , Zhang Dan , Jiang Hanping , Lin Liangqiang , Griffiths Sian M
Published: November 2009

Background

As one of the most populous metropolitan areas in the Pearl River Delta of South China, Shenzhen attracts millions of migrant workers annually. The objectives of this study were to compare health needs, self-reported health and healthcare utilisation of insured and uninsured migrant workers in Shenzhen, China, where a new health insurance scheme targeting at migrant workers was initiated.

Methods

A cross-sectional survey using multi-staged sampling was conducted to collect data from migrant factory workers. Statistical tests included logistic regression analysis were used.

Results

Among 4634 subjects (96.54%) who responded to the survey, 55.11% were uninsured. Disease patterns were similar irrespective of insurance status. The uninsured were more likely to be female, single, younger and less educated unskilled labourers with a lower monthly income compared with the insured. Out of 1136 who reported illness in the previous two weeks, 62.15% did not visit a doctor. Of the 296 who were referred for inpatient care, 48.65% did not attend because of inability to pay. Amongst those who reported sickness, 548 were insured and 588 were uninsured.

Those that were insured, and had easier access to care were more likely to make doctor visits than those who were uninsured.

Conclusion

Health care utilisation patterns differ between insured and uninsured workers and insurance status appears to be a significant factor. The health insurance system is inequitably distributed amongst migrant workers. Younger less educated women who are paid less are more likely to be uninsured and therefore to pay out of pocket for their care. For greater equity this group need to be included in the insurance schemes as they develop.
Oxaliplatin-Induced Loss of Phosphorylated Heavy Neurofilament Subunit Neuronal Immunoreactivity in Rat Drg Tissue
Authors: Jamieson Stephen MF , Subramaniam Joshuan , Liu Johnson J , Jong Nancy N , Ip Virginia , Connor Bronwen , McKeage Mark J
Published: November 2009

Background

Oxaliplatin and related chemotherapeutic drugs cause painful chronic peripheral neuropathies in cancer patients. We investigated changes in neuronal size profiles and neurofilament immunoreactivity in L5 dorsal root ganglion (DRG) tissue of adult female Wistar rats after multiple-dose treatment with oxaliplatin, cisplatin, carboplatin or paclitaxel.

Results

After treatment with oxaliplatin, phosphorylated neurofilament heavy subunit (pNF-H) immunoreactivity was reduced in neuronal cell bodies, but unchanged in nerve fibres, of the L5 DRG. Morphometric analysis confirmed significant changes in the number (-75%; P < 0.0002) and size (-45%; P < 0.0001) of pNF-H-immunoreactive neurons after oxaliplatin treatment. pNF-H-immunoreactive neurons had overlapping size profiles and co-localisation with neurons displaying cell body immunoreactivity for parvalbumin, non-phospho-specific neurofilament medium subunit (NF-M) and non-phospho-specific neurofilament heavy subunit (NF-H), in control DRG. However, there were no significant changes in the numbers of neurons with immunoreactivity for parvalbumin (4.6%, P = 0.82), NF-M (-1%, P = 0.96) or NF-H (0%; P = 0.93) after oxaliplatin treatment, although the sizes of parvalbumin (-29%, P = 0.047), NF-M (-11%, P = 0.038) and NF-H (-28%; P = 0.0033) immunoreactive neurons were reduced. In an independent comparison of different chemotherapeutic agents, the number of pNF-H-immunoreactive neurons was significantly altered by oxaliplatin (-77.2%; P < 0.0001) and cisplatin (-35.2%; P = 0.03) but not by carboplatin or paclitaxel, and their mean cell body area was significantly changed by oxaliplatin (-31.1%; P = 0.008) but not by cisplatin, carboplatin or paclitaxel.

Conclusion

This study has demonstrated a specific pattern of loss of pNF-H immunoreactivity in rat DRG tissue that corresponds with the relative neurotoxicity of oxaliplatin, cisplatin and carboplatin. Loss of pNF-H may be mechanistically linked to oxaliplatin-induced neuronal atrophy, and serves as a readily measureable endpoint of its neurotoxicity in the rat model.
[68Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning
Authors: Gehler Barbara , Paulsen Frank , Öksüz Mehmet Ö , Hauser Till-Karsten , Eschmann Susanne M , Bares Roland , Pfannenberg Christina , Bamberg Michael , Bartenstein Peter , Belka Claus , Ganswindt Ute
Published: November 2009

Purpose

The observation that human meningioma cells strongly express somatostatin receptor (SSTR 2) was the rationale to analyze retrospectively in how far DOTATOC PET/CT is helpful to improve target volume delineation for intensity modulated radiotherapy (IMRT).

Patients and Methods

In 26 consecutive patients with preferentially skull base meningioma, diagnostic magnetic resonance imaging (MRI) and planning-computed tomography (CT) was complemented with data from [68Ga]-DOTA-D Phe1-Tyr3-Octreotide (DOTATOC)-PET/CT. Image fusion of PET/CT, diagnostic computed tomography, MRI and radiotherapy planning CT as well as target volume delineation was performed with OTP-Masterplan®. Initial gross tumor volume (GTV) definition was based on MRI data only and was secondarily complemented with DOTATOC-PET information. Irradiation was performed as EUD based IMRT, using the Hyperion Software package.

Results

The integration of the DOTATOC data led to additional information concerning tumor extension in 17 of 26 patients (65%). There were major changes of the clinical target volume (CTV) which modify the PTV in 14 patients, minor changes were realized in 3 patients. Overall the GTV-MRI/CT was larger than the GTV-PET in 10 patients (38%), smaller in 13 patients (50%) and almost the same in 3 patients (12%). Most of the adaptations were performed in close vicinity to bony skull base structures or after complex surgery. Median GTV based on MRI was 18.1 cc, based on PET 25.3 cc and subsequently the CTV was 37.4 cc. Radiation planning and treatment of the DOTATOC-adapted volumes was feasible.

Conclusion

DOTATOC-PET/CT information may strongly complement patho-anatomical data from MRI and CT in cases with complex meningioma and is thus helpful for improved target volume delineation especially for skull base manifestations and recurrent disease after surgery.
Cecum perforation due to tuberculosis in a renal transplant recipient: a case report
Authors: Carkman Sinan , Ozben Volkan , Aytac Erman
Published: November 2009

Introduction

Tuberculosis can present in many varied clinical situations in immunosuppressed patients. It has been reported that the sigmoid colon is the most common site for colonic perforation in renal transplant recipients and diverticulitis is its most common cause. Cecal perforation because of tuberculosis is extremely rare in a renal transplant recipient. We present the case of a renal transplant patient with cecal perforation due to tuberculosis, 10 years after renal transplantation.

Case presentation

A 39-year-old Caucasian man, who was a renal transplant recipient, was admitted to our emergency surgery unit with an acute abdomen. A cecal perforation was found at exploratory laparotomy, and a right hemicolectomy with an end ileostomy and transverse colonic mucous fistula were performed. Necrotizing granulomatous colitis due to tuberculosis was reported in the histopathologic examination.

Conclusion

Colonic perforations in immunosuppressed patients may have unusual presentations and unusual causes. Tuberculosis infection should be considered in the differential diagnosis during the histopathologic evaluation in immunocompromised patients such as renal transplant recipients.
CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features
Authors: Essien Kobby , Vigneau Sebastien , Apreleva Sofia , Singh Larry N , Bartolomei Marisa S , Hannenhalli Sridhar
Published: November 2009

Background

CTCF (CCCTC-binding factor) is an evolutionarily conserved zinc finger protein involved in diverse functions ranging from negative regulation of MYC, to chromatin insulation of the beta-globin gene cluster, to imprinting of the Igf2 locus. The 11 zinc fingers of CTCF are known to differentially contribute to the CTCF-DNA interaction at different binding sites. It is possible that the differences in CTCF-DNA conformation at different binding sites underlie CTCF's functional diversity. If so, the CTCF binding sites may belong to distinct classes, each compatible with a specific functional role.

Results

We have classified approximately 26,000 CTCF binding sites in CD4+ T cells into three classes based on their similarity to the well-characterized CTCF DNA-binding motif. We have comprehensively characterized these three classes of CTCF sites with respect to several evolutionary, genomic, epigenomic, transcriptomic and functional features. We find that the low-occupancy sites tend to be cell type specific. Furthermore, while the high-occupancy sites associate with repressive histone marks and greater gene co-expression within a CTCF-flanked block, the low-occupancy sites associate with active histone marks and higher gene expression. We found that the low-occupancy sites have greater conservation in their flanking regions compared to high-occupancy sites. Interestingly, based on a novel class-conservation metric, we observed that human low-occupancy sites tend to be conserved as low-occupancy sites in mouse (and vice versa) more frequently than expected.

Conclusions

Our work reveals several key differences among CTCF occupancy-based classes and suggests a critical, yet distinct functional role played by low-occupancy sites.
Scott's Stoic Characters: Ethics, Sentiment, and Irony in The Antiquary, Guy Mannering, and “the Author of Waverley”
Authors: Baker Samuel
Published: November 2009

It is well known that Walter Scott adapted the forms of sentimental fiction for his initial trilogy of novels on Scottish manners and that he drew on philosophical theories of sympathy when conceiving of his characters and placing them in historical relation to one another and to his readership. Scott's adaptations of sentimentalism and of theories of sympathy come into sharper focus, however, once one takes seriously his claim that Stoicism is his proper philosophy and traces his ironic treatment of the figure of the sympathetic Stoic undermined by sentiment back to its eighteenth-century antecedents in Joseph Addison and Adam Smith. Like two of his early protagonists, Guy Mannering the astrologer and Jonathan Oldbuck the antiquary, “the Author of Waverley” is himself a compromised Stoic, yet Scott's narratives demonstrate repeatedly how, while it may fail on its own terms, the ancient philosophy of apathy creates the conditions of possibility for modern romance.
Islam, Nation-State, and the Military: A Discussion of Secularism in Turkey
Authors: Gürbey Sinem
Published: November 2009

In comparative and theoretical discussions, Turkey—where secularism is imposed from above as one of the irrevocable founding principles of the constitution—is criticized for being religiously hostile, aiming to repress religion in the public sphere in a coercive manner. This view is faulty on two grounds. First, it essentializes religion by assuming that religion is an objectively identifiable concept and that as such it can be separated from the realm of the secular and become an object of state power. The separation between the secular and the religious, as this article argues, is premised on particular definitions of religion, the roots of which are historically contingent and intimately linked to the rise of the modern nation-state. As the article argues, a particular conception of Islam is integrated into the nation-state's projects of rationalization, homogenization, and disciplinization, and as such it is turned into a disciplinary tool through which new citizens are created. Second, the claim that the state represses “religion” relies exclusively on legal and constitutional machinery that restricts the use of religion for political purposes and consequently misses how a particular conception of religion is disseminated by state institutions in the private realms of culture and education in order to form new Islamic selves that agree to put the nation's “sacred” interests above all “particular” interests. The article problematizes the way military service is normalized in defending the secular constitution through an appeal to the Islamic conception of martyrdom, wherein “good” citizens are promised to be rewarded not in the secular time but in the hereafter.
The Urban Dynamism of Islamic Hegemony: Absorbing Squatter Creativity in Istanbul
Authors: Tugal Cihan
Published: November 2009

The transformation of urban space constitutes one of the most dynamic aspects of the Islamist movement. Prevalent models have accounted for this phenomenon by referring to the rural immigrants' capacity for autonomous network building or their creative subjectivities. This article analyzes Islamization by studying the interactions between Islamists and the residents in a poor district in Istanbul. It demonstrates not only that the urban poor are indeed active in forming communities and subjectivities but also that their agency is shaped (and ultimately absorbed) by the Islamist project. It is Islamism as political practice and not solely the dynamism of civil society that lies at the root of the city's religious transformation. Nevertheless, Islamism becomes influential because it is able to link civil society and urban subjectivity to its project. These arguments are based on a two-year-long ethnography and fifty interviews.
The Synergy between Neoliberalism and Communitarianism: “Erdoğan's Third Way”
Authors: Patton Marcie J.
Published: November 2009

What distinguishes the Adalet ve Kalkınma Partisi (AKP) from previous Islam-oriented parties is its ability to create a comfortable fit between neoliberal economic policies and conservative communitarian ideas. This article explains this convergence by exploring how a certain articulation of communitarianism by the AKP government lends itself to deepening neoliberalism and by drawing comparisons to experiments in Third Way politics elsewhere by modernizing social democrats. It suggests that the government of Recep Tayyip Erdoğan has formulated a Turkish variant of the Third Way that accommodates Islamist values while privileging the neoliberal capitalist economic order.
Ipl1-dependent phosphorylation of Dam1 is reduced by tension applied on kinetochores
Authors: Keating Patrick , Rachidi Najma , Tanaka Tomoyuki U. , Stark Michael J. R.
Published: November 2009

The conserved Aurora B protein kinase (Ipl1 in Saccharomyces cerevisiae) is essential for ensuring that sister kinetochores become attached to microtubules from opposite spindle poles (bi-orientation) before anaphase onset. When sister chromatids become attached to microtubules from a single pole, Aurora B/Ipl1 facilitates turnover of kinetochore-microtubule attachments. This process requires phosphorylation by Aurora B/Ipl1 of kinetochore components such as Dam1 in yeast. Once bi-orientation is established and tension is applied on kinetochores, Aurora B/Ipl1 must stop promoting this turnover, otherwise correct attachment would never be stabilised. How this is achieved remains elusive: it might be due to dephosphorylation of Aurora B/Ipl1 substrates at kinetochores, or might take place independently, for example because of conformational changes in kinetochores. Here, we show that Ipl1-dependent phosphorylation at crucial sites on Dam1 is maximal during S phase and minimal during metaphase, matching the cell cycle window when chromosome bi-orientation occurs. Intriguingly, when we reduced tension at kinetochores through failure to establish sister chromatid cohesion, Dam1 phosphorylation persisted in metaphase-arrested cells. We propose that Aurora B/Ipl1-facilitated bi-orientation is stabilised in response to tension at kinetochores by dephosphorylation of Dam1, resulting in termination of kinetochore-microtubule attachment turnover.
Development of a middle-range six-degrees-of-freedom system
Authors: Jywe W , Jeng Y-R , Liu C-H , Teng Y-F , Wu C-H , Hsieh T-H , Duan L-L
Published: November 2009

This paper describes the successful development of a middle-range six-degrees-of-freedom stage, using the features of a flexible structure. The system includes two parts: a middle-range positioning X— Y stage and a four-degrees-of-freedom stage. The flexible structure of the four-degrees-of-freedom stage is built from two kinds of flexible bodies: circular hinges and a new two-degrees-of-freedom flexible body. The four-degrees-of-freedom stage was designed to compensate movement errors including linear displacement, pitch, and roll errors. The linear displacement reaches 20 mm along the X-axis, 20 mm along the Y-axis, and 5 μm along the Z-axis. The rotation angle around the X-axis (θ x), Y-axis (θ y), and Z-axis (θ z) were all 10 arcsec. A novel six-degrees-of-freedom measuring system was also designed. Precision feedback control is demonstrated in a series of experiments performed using the proposed measurement system.
Investigation of force-controlled friction stir welding for manufacturing and automation
Authors: Longhurst W R , Strauss A M , Cook G E , Cox C D , Hendricks C E , Gibson B T , Dawant Y S
Published: November 2009

Friction stir welding (FSW) is a solid-state joining process for materials with low melting points. The process uses a rotating tool that consists of a shoulder and a pin. The tool plastically deforms the material with its pin and then forges together the parent materials underneath the shoulder. Past research has established that the axial force on the tool that creates the forging pressure is a function of plunge depth, traverse speed, and rotation speed. Historically, force control of FSW has been accomplished by varying the plunge depth of the tool.

The research presented in this paper examines the force control of FSW by varying each of the process parameters separately. A force controller was implemented on a retrofitted milling machine. The closed-loop proportional—integral—derivative (PID) control architecture was tuned using the Ziegler—Nichols method. Welding experiments were conducted by butt welding ¼ inch (6.35 mm) × 1½ inch (38.1 mm) × 8 inch (203.2 mm) samples of aluminium 6061-T6511 with a ¼ inch (6.35 mm) FSW tool.

The results indicate that force control via traverse speed is the most accurate and, as a by-product, heat distribution control along the weld seam occurs. Force control via plunge depth is the least accurate but it compensates for machine and robot deflection. Tensile test data show that greater strength can be obtained through force control via rotation speed.

It is concluded that force is maintained by keeping the amount of tool surface area in contract with the workpiece constant throughout the welding process when plunge depth is used as the controlling variable. Force is maintained by varying the rate of heat generation when rotation speed is used as the controlling variable. Lastly, force is maintained by changing the amount of heat deposited per unit length along the weld seam when traverse speed is used as the controlling variable. Successful robotic FSW requires to be selected the appropriate controlling variable and the sensitivity of the interaction between the tool and the workpiece to be reduced.
On-machine fabrication of high-aspect-ratio micro-electrodes and application in vibration-assisted micro-electrodischarge drilling of tungsten carbide
Authors: Jahan M P , Rahman M , Wong Y S , Fuhua L
Published: November 2009

The concept of fabricating on-machine high-aspect-ratio micro-electrodes arises from the need to fabricate small and deep micro-holes in micro-electrical discharge machining (micro-EDM). In the present study, investigations are conducted on the fabrication of high-aspect-ratio micro-electrodes using two simple and cost-effective micro-EDM-based processes: the ‘turning-μEDM’ hybrid process and the ‘moving-electrode-block-μEDM’ process. Process descriptions and important aspects for successful fabrication of high-aspect-ratio micro-electrodes are discussed. In addition, the application of these micro-electrodes in the fabrication of deep micro-holes in tungsten carbide using normal micro-EDM and vibration-assisted micro-EDM is presented. It is found that the turning-μEDM process can generate finer micro-electrodes for easily machinable materials such as brass, but its application to the machining of deep micro-holes in tungsten Carbide is limited by the extreme tool wear of the brass electrode. The block-μEDM process can generate microelectrodes with hard, difficult-to-cut, and high-melting-point materials such as copper tungsten (alloy) and tungsten with much higher aspect ratios. However, the taper angle of the fabricated micro-electrodes is a common problem in the stationary block-μEDM process. This problem is reduced to a great extent by using block-μEDM with a moving electrode. Micro-holes with an aspect ratio of 16.7 are achieved using vibration-assisted micro-EDM with the fabricated tungsten micro-electrode machined by the moving-electrode-block-μEDM process.
Computer-aided process planning based on automatic fuzzy comprehensive evaluation
Authors: Tang W , Gu L Z , Guo H
Published: November 2009

There is strong contradiction in the traditional evaluation of processes in terms of diversity of manufactured goods, discreteness of manufacturing processes, complexity of the environment of manufacture, and variability of the market. It is essential to meet the need for an automatic, time-saving, accurate, and optimal evaluation of processes. The current study was aimed at fuzzy auto-evaluation, taking the processes for the parts as (a) subject investigated, (b) structuring evaluation system, and (c) method of processes in computer-aided production planning (CAPP) based on fuzzy mathematics. On analysis and comparison, the automatic fuzzy comprehensive evaluation system was built based on the following factors: set, the weight set and assessment set, and the single factor: proposed comprehensive fuzzy evaluation. The membership degree was determined with fuzzy statistics, and the weight of various factors was determined by the fuzzy consistent matrix. A combination of theoretical analysis, practical experience, goals of evaluation, and factors set for processes was accomplished by extracting the factors that impacted evaluation of processes; weight set was established based on different weights that each factor impacting on the extent of technology programs gave; the assessment set was gained with a factor matrix which the expert group provided for every factor; the fuzzy evaluation matrix was obtained with a matrix calculation according to the model M (∧, ∨). The process grade was determined according to the principle of maximum membership degree. The process evaluation would automatically be realized through the evaluation system with the VC++ program after weights of various factors from the experts in the field were added. The optimum process was eventually obtained by comparing the grades of these processes. Three feasible processes of a disc-like component, as an example, were evaluated through this evaluation system, realizing the automatic evaluation of processes and obtaining the best process.
Influence of surface remelting on distribution of residual stresses in medium alloy—medium carbon steel gas tungsten arc weldment
Authors: Venkata Ramana P , Madhusudhan Reddy G
Published: November 2009

The influence of surface remelting on the residual stress distribution in the fusion weld of a medium alloy—medium carbon steel was investigated using X-ray diffraction. It was observed that the sense of residual stresses changes from tensile stresses in the as-welded condition to compressive stresses after surface remelting. The microstructure of the remelted region exhibited fine martensitic microstructure compared with the as-welded microstructure. The observed residual stress distribution was found to be in agreement with hardness data. This study is of significance as this is the first report of surface remelting of a fusion zone to alter residual stresses.
Rapid prototyping medical models for dysplastic hip orthopaedic surgery
Authors: Dhakshyani R , Nukman Y , Osman N A Abu , Merican A M , George J
Published: November 2009

This research was carried out to show the usefulness of rapid prototyping (RP) medical models in dysplastic hip orthopaedic surgery. There is a lack of published information on the use of RP medical models in planning of dysplastic hip orthopaedic surgery, so this research was conducted to provide such information. Computed tomography (CT) of a patient with a dysplastic hip was used. Special medical software was used to prepare the three-dimensional model of the patient, which was then used to produce the RP medical models. These models were then given to the orthopaedic surgeons to plan for the dysplastic hip surgeries. Measurements on the CT scan data were taken before surgery. Finally, surgeons’ comments on their experience of planning dysplastic hip surgery with the use of RP medical models were obtained. The CT scan measurements taken before surgery indicated the severity of the dysplastic hip in each patient. Surgeons found the RP medical models to be very useful in planning of surgery, as they helped them to make decisions, increased their confidence, and also reduced surgery time. The results obtained show the effectiveness of using RP medical models in planning of dysplastic hip orthopaedic surgery. This research provides an understanding of the use of RP medical models in planning of dysplastic hip orthopaedic surgery. Surgeons had fresh experience of using models that greatly influenced the success of the surgery.
Recursive trigonometric interpolation algorithms
Authors: Stotsky A A
Published: November 2009

Two new recursive algorithms for the calculation of the coefficients of the trigonometric polynomial that is fitted to measured data in the least-squares sense in a window of a sufficiently large size that is moving in time are proposed. Both algorithms use the strictly diagonally dominant property of the information matrix for a sufficiently large window size. The first one is based on a recursive inversion of the information matrix and the second one uses a priori estimate of the coefficients of the polynomial obtained from the Kaczmarz projection method. The algorithms are computationally suitable for selection of the order of a trigonometric polynomial in each step of a moving window in real-time applications. The results are verified by simulations.
Pregnancy in peri- and postmenopausal women: challenges in management
Authors: Tower Clare
Published: November 2009

Pregnancy in peri- and postmenopausal women is associated with an increased risk of complications and represents several challenges in terms of clinical management. Women in these age groups typically fall into one of two distinct groups, those who have conceived following assisted reproductive techniques, using ovum donation and those who have conceived spontaneously. While both have age in common, they differ in terms of additional risk factors. Recipients of assisted reproductive technologies have pregnancy risks associated with that treatment, but are at lower risks of a fetus affected by aneuploidy. Furthermore, they have been rigorously screened for medical complications, but are more likely to be primiparous and have multiple pregnancies. In contrast, women conceiving spontaneously are more likely to be of high parity and have additional medical complications such as obesity, hypertension or diabetes. In addition to the increased risk of antenatal complications such as miscarriage, ectopic pregnancies, gestational diabetes and hypertension, these women have a high risk of unexplained stillbirth. They also have a very high rate of Caesarean section. All these risk factors interact to modify clinical management. However, there are no randomized trials available to guide clinical management, thus decisions must be made on a case-by-case basis.
Multigenic combination of estrogen-related genes is associated with age at natural menopause in a Spanish population
Authors: Mendoza Nicolás , Sánchez-Borrego Rafael , Galiano Daniela , Salamanca Alberto , Mozas Juan , Quereda Francisco , Vázquez Francisco , Martínez-Astorquiza Txantón , Moron Francisco
Published: November 2009

Objective

Age at natural menopause (ANM) can be considered a complex parameter that depends on the interaction of multiple factors. In the present study, the role of interaction between genetic variants within estrogen synthesis and signalling pathways in the ANM in Spanish women is studied.

Material and methods

Nine single nucleotide polymorphisms (SNPs) located at different candidate genes related to the estrogen signalling pathway were analysed in 1980 Spanish postmenopausal women.

Results

Independently, none of the nine markers were significantly associated with early ANM. Only heterozygosis at the NRIP rs2229741 locus could be associated with early menopause; however, this marker does not maintain statistical significance. In contrast, linear regression analysis suggests several epistatic interactions including these markers in relation to ANM, especially between ESR2, NRIP1 and BMP15. The genetic variant that appears most in these interactions is that of the BMP15 rs3897937. It was observed that AA-TC combined genotype for NRIP-BMP15 (rs3897937), respectively, appears to be associated with a lower ANM than other possible combinations of these SNP (46.1±5.9 versus 50.4±3.3; P = 0.002). In the multilocus analysis, the multigenic interaction formed by ESR2 (AA), BMP15 rs3897937 (TC) and NRIP1 (AA) has the lower ANM (45.37±6.8 versus 48.69±5; P = 0.038).

Conclusions

The results suggest that epistatic interactions of estrogen-related alleles may contribute to variance in ANM in Spanish women. Moreover, BMP15 and NRIP1 also appear as attractive candidate genes for premature menopause but require further investigation to confirm them.
Pilot Study of Linking Web-Based Supplemental Interpretive Information to Laboratory Test Reports
Authors: Shirts Brian H. , Gundlapalli Adi V. , Jackson Brian
Published: November 2009

Electronic medical records have the ability to link to reference material, providing clinicians with immediate access to information relevant to patient care. Adding relevant links to laboratory test results could add value while minimizing the volume of ancillary text presented.

We provided Web-based universal resource locator (URL) links with all results of 7 laboratory tests ordered at ARUP Laboratories (Salt Lake City, UT). URL links provided were modified 7 months later, and use between initial and subsequent URLs was tracked to establish frequency and duration of access to supplemental Web information.

Monthly Web-site hit rates for individual tests varied from 0.00% to 3.00% (median, 0.12%). Rare and specialty tests averaged higher hit rates. There was no decay in hit rate 9 months after URLs were removed from test reports.

We conclude that links to reference material are accessed by clinicians. The use of Web links months after links were no longer published raises an important issue of long-term maintenance and the resources required to support these features.
Proactivity with image in mind: How employee and manager characteristics affect evaluations of proactive behaviours
Authors: de Stobbeleir Katleen E. M. , Ashford Susan J. , de Luque Mary F. Sully
Published: November 2009

This paper investigates image cost as a potential downside of proactivity. Drawing on attribution theory, we examine how people construct subjective evaluations of one manifestation of proactivity, feedback‐seeking behaviour. Using a scenario methodology, we examined how employees' performance history, their manager's implicit person theory (IPT), and the frequency of their feedback‐seeking affect how managers evaluate employees' feedback seeking. Results indicate that manager attribute average performers' feedback seeking significantly less to performance‐enhancement motives than superior performers' seeking. Results further show that the frequency of feedback seeking and a manager's IPT interact in influencing managers' attributions for feedback seeking, with more entity oriented managers attributing frequent feedback seeking significantly more to impression‐management motives than infrequent feedback requests. These results highlight the importance of not only the instrumental benefits of employee proactivity, but also its potential costs.
Disruption of the Ether-à-go-go K+Channel Gene BEC1/KCNH3 Enhances Cognitive Function
Authors: Miyake Akira , Takahashi Shinji , Nakamura Yukihiro , Inamura Kohei , Matsumoto Shun-ichiro , Mochizuki Shinobu , Katou Masao
Published: November 2009

The K+channel, one of the determinants for neuronal excitability, is genetically heterogeneous, and various K+channel genes are expressed in the CNS. The therapeutic potential of K+channel blockers for cognitive enhancement has been discussed, but the contribution each K+channel gene makes to cognitive function remains obscure. BEC1 (KCNH3) is a member of the K+channel superfamily that shows forebrain-preferential distribution. Here, we show the critical involvement of BEC1 in cognitive function. BEC1 knock-out mice performed behavioral tasks related to working memory, reference memory, and attention better than their wild-type littermates. Enhanced performance was also observed in heterozygous mutants. The knock-out mice had neither the seizures nor the motor dysfunction that are often observed in K+channel-deficient mice. In contrast to when it is disrupted, overexpression of BEC1 in the forebrain caused the impaired performance of those tasks. It was also found that altering BEC1 expression could change hippocampal neuronal excitability and synaptic plasticity. The results indicate that BEC1 may represent the first K+channel that contributes preferentially and bidirectionally to cognitive function.
Disruption of the Head Direction Cell Signal after Occlusion of the Semicircular Canals in the Freely Moving Chinchilla
Authors: Muir Gary M. , Brown Joel E. , Carey John P. , Hirvonen Timo P. , Della Santina Charles C. , Minor Lloyd B. , Taube Jeffrey S.
Published: November 2009

Head direction (HD) cells in the rat anterodorsal thalamic nucleus (ADN) fire relative to the animal's directional heading. Lesions of the entire vestibular labyrinth have been shown to severely alter VIIIth nerve input and disrupt these HD signals. To assess the specific contributions of the semicircular canals without altering tonic VIIIth nerve input, ADN cells were recorded from chinchillas after bilateral semicircular canal occlusion. Although ADN HD cells (and also hippocampal place cells and theta cells) were identified in intact chinchillas, no direction-specific activity was seen after canal occlusions. Instead, “bursty” cells were observed that exhibited burst-firing patterns similar to normal HD cells but with firing unrelated to the animal's actual head direction. Importantly, when pairs of bursty cells were recorded, the temporal order of their firing was dependent on the animal's turning direction, as is the case for pairs of normal HD cells. These results suggest that bursty cells are actually disrupted HD cells. The present findings further suggest that the HD cell network is still able to generate spiking activity after canal occlusions, but the semicircular canal input is critical for updating the network activity in register with changes in the animal's HD.
Divergent Pathways Mediate Spine Alterations and Cell Death Induced by Amyloid-β, Wild-Type Tau, and R406W Tau
Authors: Tackenberg Christian , Brandt Roland
Published: November 2009

Alzheimer's disease is characterized by synaptic alterations and neurodegeneration. Histopathological hallmarks represent amyloid plaques composed of amyloid-β (Aβ) and neurofibrillary tangles containing hyperphosphorylated tau. To determine whether synaptic changes and neurodegeneration share common pathways, we established anex vivomodel using organotypic hippocampal slice cultures from amyloid precursor protein transgenic mice combined with virus-mediated expression of EGFP-tagged tau constructs. Confocal high-resolution imaging, algorithm-based evaluation of spines, and live imaging were used to determine spine changes and neurodegeneration. We report that Aβ but not tau induces spine loss and shifts spine shape from mushroom to stubby through a mechanism involving NMDA receptor (NMDAR), calcineurin, and GSK-3β activation. In contrast, Aβ alone does not cause neurodegeneration but induces toxicity through phosphorylation of wild-type (wt) tau in an NMDAR-dependent pathway. We show that GSK-3β levels are elevated in APP transgenic cultures and that inhibiting GSK-3β activity or use of phosphorylation-blocking tau mutations prevented Aβ-induced toxicity of tau. FTDP-17 tau mutants are differentially affected by Aβ. While R406W tau shows increased toxicity in the presence of Aβ, no change is observed with P301L tau. While blocking NMDAR activity abolishes toxicity of both wt and R406W tau, the inhibition of GSK-3β only protects against toxicity of wt tau but not of R406W tau induced by Aβ. Tau aggregation does not correlate with toxicity. We propose that Aβ-induced spine pathology and tau-dependent neurodegeneration are mediated by divergent pathways downstream of NMDAR activation and suggest that Aβ affects wt and R406W tau toxicity by different pathways downstream of NMDAR activity.
Dissociating Response Conflict and Error Likelihood in Anterior Cingulate Cortex
Authors: Yeung Nick , Nieuwenhuis Sander
Published: November 2009

Neuroimaging studies consistently report activity in anterior cingulate cortex (ACC) in conditions of high cognitive demand, leading to the view that ACC plays a crucial role in the control of cognitive processes. According to one prominent theory, the sensitivity of ACC to task difficulty reflects its role in monitoring for the occurrence of competition, or “conflict,” between responses to signal the need for increased cognitive control. However, a contrasting theory proposes that ACC is the recipient rather than source of monitoring signals, and that ACC activity observed in relation to task demand reflects the role of this region in learning about the likelihood of errors. Response conflict and error likelihood are typically confounded, making the theories difficult to distinguish empirically. The present research therefore used detailed computational simulations to derive contrasting predictions regarding ACC activity and error rate as a function of response speed. The simulations demonstrated a clear dissociation between conflict and error likelihood: fast response trials are associated with low conflict but high error likelihood, whereas slow response trials show the opposite pattern. Using the N2 component as an index of ACC activity, an EEG study demonstrated that when conflict and error likelihood are dissociated in this way, ACC activity tracks conflict and is negatively correlated with error likelihood. These findings support the conflict-monitoring theory and suggest that, in speeded decision tasks, ACC activity reflects current task demands rather than the retrospective coding of past performance.
Saúde mental na atenção básica: um estudo epidemiológico baseado no enfoque de risco
Authors: Andrade Fábia Barbosa de , Bezerra Alessandra Isis Cirne , Pontes Ana Lúcia Félix de , Filha Maria Oliveira Ferreira , Vianna Rodrigo Pinheiro de Toledo , Dias Maria Djair , Silva Antônia Oliveira
Published: November 2009

As transformações de cunho social-político e econômico ocorrido nas últimas décadas repercutem em todos os setores da sociedade. Fato que traz transformações para a saúde mental da população. Teve como objetivo realizar a população com risco para adoecimento mental. Trata-se de um estudo epidemiológico de corte transversal realizado em uma comunidade de João Pessoa-PB, utilizando-se Self Report Questionnaire-20 (SRQ-20). Observou-se associação do Risco para Depressão e Ansiedade com o sexo feminino (59,40%), faixa etária de 40 a 65 anos (66%), ocupação de serviços domésticos (65,5%). Somos levados a reconhecer que o sofrimento mental tem crescido relativamente na amostra estudada e a partir dessa constatação faz-se necessário uma atenção imediata aos problemas de saúde mental nas pessoas da comunidade.