bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of Lotus Fibre Spinning Machine
Authors: Nguyen Van-Tinh , Nguyen Ngoc-Kien , Bui Ngoc-Tam
Published: March 2024

Lotus thread is usually collected to make a lotus silk and is high-quality material in fashion field. Lotus is commonly planted in Southeast Asian countries such as Vietnam, Cambodia, Myanmar, and some parts of India. Up to now, the lotus fibre is still gathered manually and this process takes at least two months to collect thread enough for making a scarf. As a result, the products made by lotus silk are usually expensive. Besides, the quality of fibre in lotus stalk will decreases after 24 hours of cutting down and is easily broken, thus, lotus fibre spinning process needs implementing quickly. To promote the development of traditional products made by lotus silk and enhance effectiveness of the lotus fibre spinning process, this paper introduced the first design of lotus fibre spinning machine which solves all shortcomings of manually spinning process.
The Impact of Cloud Manufacturing on RAMI 4.0
Authors: Ciortea M. E.
Published: March 2024

The paper deals with an empirical way of approaching the cloud manufacturing system on Reference Architectural Model Industry 4.0 (RAMI 4.0). The complex system wants to provide an overview of the advantage offered by cloud manufacturing through direct interaction with RAMI 4.0. For modeling the empirical system, we used the Visual Object Net++ package, which is simple to implement, offers the possibility of optimizing the system right from the design and analysis stage. It provides real-time information on the various activities in the nodes under analysis. The diagrams thus obtained are clear and relatively easy to analyze and interpret by qualified persons. This system is easy to implement and comes to the aid of company managers with the necessary information provided in real time with the actions carried out through RAMI 4.0.
Repairing the Harm of Digital Design Using a Trauma-informed Approach
Authors: Eggleston Melissa , Noel Lesley-Ann
Published: March 2024

With increased awareness and mindful decisions, digital designers can repair the harm caused by digital design and improve the online experience of individuals who have been previously marginalized. This repair of poor design decisions, well-intentioned or out of ignorance, is necessary in a world where technology, exclusion, and trauma are pervasive. This article provides examples of digital harm that designers must acknowledge, understand, and avoid recreating. The concept of trauma-informed design is explained along with two practical approaches for designers to use to become more trauma-informed, and repair harm when creating websites, apps, and other digital experiences.
In vitro Wound Healing Effect of a Siddha Formulation: Gandhaga Thailam
Authors: Adithya R. Sathish , Manikgantan E. M. , Kabilan N. , Kanimozhi S.
Published: March 2024

Introduction: Wound is defined as disruption in the integrity of skin. Wound healing is a physiological process primarily initiated by vasoconstriction and platelet aggregation. Wound closure is completed by release of inflammatory markers and aggregation of fibroblasts which causes reepitheliazation. Gandhaga thailam (Medicated oil), a siddha formulation prepared from Gandhagam (sulphur), Vediuppu (Potassium nitrate), Manosilai (Arsenic disulphide), Navacharam (Ammonium Chloride), and Veeram (Mercuric per chloride) triturated with cow ghee is used in a variety of skin diseases. Scientific validation of the wound healing efficacy of Gandhaga thailam remains unveiled.
Aim: The main aim of this research is to validate the wound healing efficacy of Gandhaga thailam through in vitro studies in L929 (Mouse fibroblast) cell line.
Materials and Methods: L929 (Mouse fibroblast) cell line was cultured in a 25 cm 2 tissue culture flask with DMEM supplemented with 10% FBS, L-glutamine, sodium bicarbonate, and antibiotic solution containing: Penicillin (100 U/ml), Streptomycin (100 µg/ml), and Amphoteracin B (2.5 µg/ml). The scratch wounds were made by a sterile 1 mL pipette tip through a pre-marked line. The sample was checked for 0 hours, 24 hours, 48 hours, and 72 hours’.
Results: The results of the study shows that Gandhaga thailam is efficient in wound healing and the wound is closed by about 48th hour after the scratch. The faster wound healing efficacy of Gandhaga thailam might be due to its potency to initiate Re- epithelialization.
Conclusion: Thus it is evidenced that Gandhaga thailam has a potential wound healing activity.
Chitin Bodies Vs Teeth of Hookworm
Authors: Siagian Forman Erwin
Published: March 2024

Aims: To differentiate morphologically and functionality of chitin bodies belong to Necator americanus (old world hook worm) vs. 2 pair of teeth belong to Ancylostoma duodenale (new world hook worm)

Discussion: Anemia due to hookworms caused by persistent blood loss. Those micro-bleeding occurs due to the attachment to the villi of the host’s small intestine in order to facilitate feed on their host’s blood. Hookworms use their two pairs of teeth (A. duodenale) or cutting plates called chitin bodies (N. americanus) to fasten their attachment onto the mucosa and submucosa, where at the same time they secrete a series of biochemically active polypeptides that prevent blood from clotting and supress the host inflammatory response. Differences in the shape of teeth or similar apparatus in the two species of hookworms that infect humans play a role in the occurrence of persistent minor bleeding that causes anemia and this also depend on the number of hookworms invaded the host.

Conclusion: chitin bodies of N. americanus causes less bleeding than two pairs of teeth belongs to A. duodenale
Exploring Climate Patterns in Karnataka, India: A Comprehensive Examination of Rainfall and Temperature Variability Over Time and Space
Authors: Chowhan Vikas , Chandargi D. M. , Goudappa S. B. , Kammar S. K. , Koppalakar B. G. , Lokesh G. B.
Published: March 2024

Examining the manifestations and effects of climate change is critically dependent on the spatiotemporal analysis of meteorological variables, particularly in areas where agriculture depends on rainfall. The present study analyzes the change in temperature and rainfall using Mann-Kendall and Sen's slope estimator and also identifies the variations in rainfall by using the Rainfall Anomaly Index (RAI). The main purpose of this study is to assess the variation in climatic variables (temperature and rainfall) among four taluks of Karnataka over 42 years (1981–2022), which might help identify strategies that can aid in addressing the consequences of extreme climate events in the future and in formulating appropriate taluk-specific strategies. The trend analysis of the temperature series revealed a significant increasing trend for the minimum temperature for both seasons, whereas the maximum temperature in the Kharif season shows a decreasing trend. However, there is a significant increasing trend in kharif season rainfall and a nonsignificant increasing trend for rabi season rainfall. The RAI value indicates a relatively greater number of dry periods in Gurmitkal taluk in comparison to Chittapur, Sedam and Yadgigi taluks. The findings of the study can be useful in developing plans to manage water resources effectively and reduce the adverse impacts of droughts, mainly in the study area taluks.
Prevalence and Factors Associated with Teenage Pregnancy at Paynesville, Monrovia, Liberia: Facility Based Cross Section Study
Authors: Sinnatwah James D. , Carter Boye B. , Femi-Adepoju Abiola Grace
Published: March 2024

Introduction: In Liberia, teenage pregnancy is a serious public health issue that causes social and economic hardship. Adolescent birth rates are among the highest in sub-Saharan Africa, according to statistics. There are significant differences in the prevalence of teenage pregnancy between and within nations. Most teenage pregnancies occur in places with poorer incomes and lower levels of education. The purpose of this research is to determine the prevalence of teenage pregnancy in Liberia and to investigate the risk factors related to it, particularly in the Paynesville city community of Duport Road cow field block "B.".

Methods: The research that was done using the Duport Road Clinic as a resource center provided the data for this study.  Fifty girls between the ages of 15 and 19 who visited the hospital and lived in the community throughout the study period were recruited as participants. Total population sampling was used to interview all 50 of the females. A population-based cross-sectional survey is used in this quantitative study to gather data, and IBM 20.0 SPSS was used for analysis.

Results: According to the report, 50.2% of adolescent girls between the ages of 15 and 19 had started having children at the time of the survey. Teenage pregnancy in the community was significantly correlated with age (OR = 6.9; 95% CI: 4.647, 10.366, p – value 0.001), teenagers living with their parents (OR = 1.057; p > 0.001), non-use of contraception (OR = 2.53; 95% CI: 1.739, 3.683), and teenage girls who were aware of contraceptive methods (OR = 2.86, 95% CI = 0.443, 18.463).

Conclusion: In conclusion, a number of factors, including early sexual initiation, cohabitation, lack of education, and contraceptive non-use, contribute to the high rate of teenage pregnancy in Liberia. Interventions including encouraging the use of contraception, discouraging early sexual beginning, and setting up family planning clinics are advised in order to lessen its prevalence.
Prediction of Soil Expansivity with Direct and Indirect Method in Banten Region, Indonesia
Authors: Cikmit Arlyn Aristo , Sudisman Rangga Adiprima , Damayanti Aprika , Rizki Burhani
Published: March 2024

Expansive soils are widespread in Indonesia, particularly in Banten Province, causing extensive road damages. The study aimed to predict the soil expansivity of soil subgrade along the damaged road segments in Malingping, Cikeusik-Cibaliung, and Labuan districts. Indirect and direct expansivity predictions were employed to determine soil swelling potential. Indirect expansivity prediction was conducted based on various criteria using the Atterberg limit and grain size distribution. Direct expansivity prediction was conducted using an oedometer apparatus to measure the expansion index according to ASTM D-4829. A dynamic cone penetration test was also conducted to measure CBR values. Various indirect methods showed inconclusive results of swelling potentials, low to very high. The direct method provided more conclusive results, Expansivity Index = 100-167 and swelling values = 9%-18%, thus, categorized as expansive clay (high to very high swelling potential). CBR values were 1.49%-5% which is lower than minimum provisioned CBR (6%).
Evaluation of Shear-Flexure Interaction Behavior of Reinforced Concrete Wall
Authors: Chandra Jimmy , Milla Gata , Tambuna Jonathan Aurelius
Published: March 2024

Reinforced concrete (RC) wall is a critical structural member that resists lateral loadings, such as earthquake and wind. RC wall having moderate height to length ratio, 1.50-2.50, has the altered shear-flexure interaction (SFI) behavior, so shear and flexural failure mechanisms occur almost concurrently. Therefore, an experimental study of a moderate RC wall was conducted as a comprehensive study of the wall’s coupled nonlinear shear-flexure behavior under cyclic loading. The experimental results show that the RC wall failed in flexure mechanism, indicated by crushing of the flexural compression zone, and followed by immediate shear failure, notified by the occurrence of web crushing. In addition to the experiment, an analytical model using SFI-MVLEM element in OpenSees software was performed to verify the experimental results. The analytical results show that the model is able to simulate reasonably well the coupled nonlinear shear-flexure behavior of the RC wall subjected to cyclic loading.
T‐genes and limb bud development
Authors: King Mary , Arnold Jelena S. , Shanske Alan , Morrow Bernice E.
Published: May 2006

The T‐box family of transcriptional factors is ancient and highly conserved among most species of animals. Haploinsufficiency of multiple T‐box proteins results in severe human congenital malformation syndromes, involving craniofacial, cardiovascular, and skeletal structures. These genes have major roles in embryogenesis, including the development of the limbs. Formation of the limbs begins with a limb bud and its morphogenesis requires complex epithelial–mesenchymal interactions. Recent studies have shown that T, Tbx2, Tbx3, Tbx4, Tbx5, Tbx15, and Tbx18 are all expressed in the limb buds, and many have developmental functions. The study of these genes is clinically relevant as mutations in several of them cause human congenital malformation syndromes. Furthermore, understanding the function and biology of these genes is important in understanding normal embryogenesis. © 2006 Wiley‐Liss, Inc.
Real‐time generation of augmented video sequences by background tracking
Authors: Douze Matthijs , Charvillat Vincent
Published: May 2006

We present a real‐time system that outputs a multi‐layer augmented video from a normal video stream. The input sequence is captured in a known environment: a panoramic image (the reference background) is provided before shooting. We use background tracking to register each input frame with this reference, and background subtraction to segment the foreground objects. Our background tracking method is a coarse‐to‐fine integration of three state‐of‐the‐art algorithms that we make resistant to occlusions. In particular, we introduce an algebraic technique to properly adapt the Jurie and Dhome (JD) tracker (the most robust of them). We report experimental results on real and synthetic data which validate our approach. We generate our augmented video sequences by compositing layers: a natural or synthetic background and several natural or synthetic foregrounds. Copyright © 2006 John Wiley & Sons, Ltd.
An Efficient Method for the Synthesis of Peptide Aldehyde Libraries Employed in the Discovery of Reversible SARS Coronavirus Main Protease (SARS‐CoV Mpro) Inhibitors
Authors: Al‐Gharabli Samer I. , Shah Syed T. Ali , Weik Steffen , Schmidt Marco F. , Mesters Jeroen R. , Kuhn Daniel , Klebe Gerhard , Hilgenfeld Rolf , Rademann Jörg
Published: May 2006

A method for the parallel solid‐phase synthesis of peptide aldehydes has been developed. Protected amino acid aldehydes obtained by the racemization‐free oxidation of amino alcohols with Dess–Martin periodinane were immobilized on threonyl resins as oxazolidines. Following Boc protection of the ring nitrogen to yield the N‐protected oxazolidine linker, peptide synthesis was performed efficiently on this resin. A peptide aldehyde library was designed for targeting the SARS coronavirus main protease, SARS‐CoV Mpro(also known as 3CLpro), on the basis of three different reported binding modes and supported by virtual screening. A set of 25 peptide aldehydes was prepared by this method and investigated in inhibition assays against SARS‐CoV Mpro. Several potent inhibitors were found with IC50values in the low micromolar range. An IC50of 7.5 μMwas found for AcNSTSQ‐H and AcESTLQ‐H. Interestingly, the most potent inhibitors seem to bind to SARS‐CoV Mproin a noncanonical binding mode.
PNC‐28, a p53‐derived peptide that is cytotoxic to cancer cells, blocks pancreatic cancer cell growth in vivo
Authors: Michl Josef , Scharf Bruce , Schmidt Anna , Huynh Chan , Hannan Raquibul , von Gizycki Hans , Friedman Fred K , Brandt‐Rauf Paul , Fine Robert L. , Pincus Matthew R.
Published: May 2006

PNC‐28 is a p53 peptide from its mdm‐2‐binding domain (residues 17–26), which contains the penetratin sequence enabling cell penetration on its carboxyl terminal end. We have found that this peptide induces necrosis, but not apoptosis, of a variety of human tumor cell lines, including several with homozygous deletion of p53, and a ras‐transformed rat acinar pancreatic carcinoma cell line, BMRPA1. Tuc3. On the other hand, PNC‐28 has no effect on untransformed cells, such as rat pancreatic acinar cells, BMRPA1, and human breast epithelial cells and no effect on the differentiation of human stem cells. In this study, we now test PNC‐28 in vivo for its ability to block the growth of BMRPA1. Tuc3 cells. When administered over a 2‐week period in the peritoneal cavities of nude mice containing simultaneously transplanted tumors, PNC‐28 causes complete destruction of these tumors. When delivered concurrently with tumor explantation at a remote site, PNC‐28 causes a complete blockade of any tumor growth during its 2‐week period of administration and 2 weeks posttreatment, followed by weak tumor growth that plateaus at low tumor sizes compared with tumor growth in the presence of a control peptide. When administered after tumor growth has occurred at a site remote from the tumor, PNC‐28 causes a decrease in tumor size followed by a slow increase in tumor growth that is significantly slower than growth in the presence of control peptide. These results suggest that PNC‐28 may be effective in treating cancers especially if delivered directly to the tumor. © 2006 Wiley‐Liss, Inc.
Verification of the profile of mood states‐brief: Cross‐cultural analysis
Authors: Yeun Eun Ja , Shin‐Park Kay KongBum
Published: May 2006

This international study investigated whether the mood states of adults can be compared between different settings and cultures using the same instrument, namely, by comparing the psychometric properties of the Profile of Mood States‐Brief (POMS‐B) using data gathered in the United States and Korea. The Korean research instrument was a translation of the original POMS‐B, and was evaluated psychometrically for each country separately as well as for the two countries combined, based on a convenience sample of 184 adults: The POMS‐B was administered to 69 native English speakers and the Korean version (K‐POMS‐B) was administered to 115 native Korean speakers. The mean total mood disturbance (TMD) score was 23.59 (SD = 16.7): 26.11 (SD = 15.9) for the Americans and 21.06 (SD = 17.5) for the Koreans. Cronbach's alpha coefficient was high for both versions. The content validity index was 96% in the K‐POMS‐B. The Korean version of the POMS‐B seems to be ready for use in research. © 2006 Wiley Periodicals, Inc. J Clin Psychol 62: 1173–1180, 2006.
The association between depressive personality and treatment outcome for depression following a group cognitive–behavioral intervention
Authors: Saulsman Lisa M. , Coall David A. , Nathan Paula R.
Published: May 2006

The present study investigated the association of depressive personality traits to treatment outcome for depression. One hundred and nineteen patients with a primary diagnosis of major depression were divided into high‐ and low‐depressive personality groups, and depression symptomatology was assessed pre‐ and postparticipation in a standardized group cognitive–behavioral intervention. Analyses revealed poorer pre‐state and end‐state functioning for the high‐depressive personality group. However, rate of improvement pre‐ to posttreatment was comparable between the two groups. Subsequent multiple regression analyses revealed that when controlling for pretreatment depression severity, depressive personality was not a predictor of depression treatment outcome. Within the methodological parameters of the current study, depressive personality traits were not associated with a poorer response to cognitive–behavioral treatment for depression. © 2006 Wiley Periodicals, Inc. J Clin Psychol 62: 1181–1196, 2006.
Calcium sources used by post‐natal human myoblasts during initial differentiation
Authors: Arnaudeau Serge , Holzer Nicolas , König Stéphane , Bader Charles R. , Bernheim Laurent
Published: May 2006

Increases in cytoplasmic Ca2+ are crucial for inducing the initial steps of myoblast differentiation that ultimately lead to fusion; yet the mechanisms that produce this elevated Ca2+ have not been fully resolved. For example, it is still unclear whether the increase comes exclusively from membrane Ca2+ influx or also from Ca2+ release from internal stores. To address this, we investigated early differentiation of myoblast clones each derived from single post‐natal human satellite cells. Initial differentiation was assayed by immunostaining myonuclei for the transcription factor MEF2. When Ca2+ influx was eliminated by using low external Ca2+ media, we found that approximately half the clones could still differentiate. Of the clones that required influx of external Ca2+, most clones used T‐type Ca2+ channels, but others used store‐operated channels as influx‐generating mechanisms. On the other hand, clones that differentiated in low external Ca2+ relied on Ca2+ release from internal stores through IP3 receptors. Interestingly, by following clones over time, we observed that some switched their preferred Ca2+ source: clones that initially used calcium release from internal stores to differentiate later required Ca2+ influx and inversely. In conclusion, we show that human myoblasts can use three alternative mechanisms to increase cytoplasmic Ca2+ at the onset of the differentiation process: influx through T‐types Ca2+ channels, influx through store operated channels and release from internal stores through IP3 receptors. In addition, we suggest that, probably because Ca2+ elevation is essential during initial differentiation, myoblasts may be able to select between these alternate Ca2+ pathways. J. Cell. Physiol. 208: 435–445, 2006. © 2006 Wiley‐Liss, Inc.
Surrogate threshold effect: an alternative measure for meta‐analytic surrogate endpoint validation
Authors: Burzykowski Tomasz , Buyse Marc
Published: May 2006

In many therapeutic areas, the identification and validation of surrogate endpoints is of prime interest to reduce the duration and/or size of clinical trials. Buyse et al. [Biostatistics 2000; 1:49–67] proposed a meta‐analytic approach to the validation. In this approach, the validity of a surrogate is quantified by the coefficient of determination R obtained from a model, which allows for prediction of the treatment effect on the endpoint of interest (‘true’ endpoint) from the effect on the surrogate. One problem related to the use of R is the difficulty in interpreting its value. To address this difficulty, in this paper we introduce a new concept, the so‐called surrogate threshold effect (STE), defined as the minimum treatment effect on the surrogate necessary to predict a non‐zero effect on the true endpoint. One of its interesting features, apart from providing information relevant to the practical use of a surrogate endpoint, is its natural interpretation from a clinical point of view. Copyright © 2006 John Wiley & Sons, Ltd.
Cellular mechanisms of Cu-tolerance in the epilithic lichen Lecanora polytropa growing at a copper mine
Authors: PAWLIK-SKOWROŃSKA Barbara , PURVIS O. William , PIRSZEL Jacek , SKOWROŃSKI Tadeusz
Published: May 2006

Cellular responses to copper stress were investigated for the first time in a saxicolous lichen species, Lecanora polytropa (Hoffm.) Rabenh. Bright blue-green apothecia accumulated up to 1·3% Cu on a dry weight basis (205 μ mol Cu g−1), c. 50% in an exchangeable form. A bright turquoise-blue layer extended beneath the hymenium into the medulla, above and between a dentate photobiont layer. Oxalic (1·88 μ mol g−1), citric (0·83 μ mol g−1) and lower concentrations of malic (0·45 μ mol g−1) acids were determined by GC/MS analysis. Short-term exposure to high Cu2+ concentrations (40 and 400 μ mol g−1) under non-complexing conditions caused a dose-dependent decrease in chlorophyll a content; chlorophyll b and total carotenoid contents remained constant. The phaeophytinization quotient remained unchanged during Cu2+ exposure. Analysis of thiol peptides confirmed glutathione was reduced (GSH) in native L. polytropa (0·538 μ mol g−1), and phytochelatins (PC2 and PC3) oxidised. Short-term exposure to 40 μ mol g−1 Cu2+ oxidised c. 28% of the glutathione pool; oxidised phytochelatin concentrations remained unchanged. This is the first report of phytochelatin production and thiol peptide status in a crustose lichen. These represent two possible detoxification mechanisms in this Cu-tolerant species. Copper complexation by low molecular mass organic acids and non-protein thiols do not entirely account for its tolerance.
A new species of Pertusaria from Valdivian rainforest, Argentina
Authors: MESSUTI María Inés , ARCHER Alan W. , DE LA ROSA Iris Nadia
Published: May 2006

The new species, Pertusaria huanicola Messuti & A. W. Archer (Pertusariaceae, Ascomycota), is described. It is distinguished from Pertusaria phlyctaenula Nyl., P. subambigens Dibben and P. suboculata Brodo & Dibben by the chemistry and the number of ascospores per ascus. The new species is known only from Valdivian rainforest in south-western Argentina.
Marked from the outset: season of birth and health during early life in Spain during the demographic transition
Authors: REHER DAVID SVEN , SANZ GIMENO ALBERTO
Published: May 2006

In this article implications of season of birth for child health in Spain during the demographic transition are explored. Making use of the Aranjuez data base, the authors look at the seasonality of births and its heterogeneities, finding a nearly universal prevalence of late spring and early summer conceptions that is most evident with last-born children. Levels and causes of childhood mortality are strongly related to the season of birth, with those born between April and October showing lower likelihood of survival. These findings can be explained by the way infant feeding, age and season intersect. These results have implications for the relative efficiency of different demographic regimes.
Local knowledge and attitudes about onchocerciasis in Oji-River local government area of Enugu State, Nigeria
Authors: MANAFA O. U. , ISAMAH A. N.
Published: May 2006

A total of 556 individuals in Agbalenyi Community of Oji-River local government area of Enugu State, Nigeria were studied using questionnaires, focus group discussions and key informant interviews to determine the socio-cultural factors affecting the transmission of onchocerciasis. The result revealed a low level of knowledge about the cause, prevention and complications of onchocerciasis. Respondents have developed a cultural system around the disease due to long exposure. The majority are aware of the disease which they recognize once their body starts itching or musculoskeletal pain develops but only 64·4, 34·0, 1·4 and 3·6%, respectively attributed chronic itching, nodules, bad vision and leopard skin to blackfly bite. Other perceived causes mentioned include ageing, the type of food eaten, farm work and ‘bad blood’. Only 0·8% knew diagnosis could be made through skin snips. Neither Oji-River nor any of the river systems were associated with any of the complications of onchocerciasis. Significant differences in most socio-demographic characteristics were associated with differences in the level of knowledge about the disease.
The role of solar ultraviolet irradiation in zoster
Authors: ZAK-PRELICH M. , BORKOWSKI J. L. , ALEXANDER F. , NORVAL M.
Published: May 2006

Ultraviolet radiation (UVR) suppresses many aspects of cell-mediated immunity but it is uncertain whether solar UV exposure alters resistance to human infectious diseases. Varicella-zoster virus (VZV) causes varicella (chickenpox) and can reactivate from latency to cause zoster (shingles). The monthly incidence of chickenpox and zoster in a defined Polish population over 2 years was recorded and ground level solar UV was measured daily. There was a significant seasonality of UVR. Evidence of seasonal variation was found for all zoster cases and for zoster in males, with the lowest number of cases in the winter. The number of zoster cases with lesions occurring on exposed body sites (the face) demonstrated highly significant seasonality with a peak in July/August. Seasonal models for UVR and zoster cases showed similar temporal patterns. By contrast, for varicella, the maximum number of cases was found in March and the minimum in August/September, probably explained by the respiratory spread of VZV. It is tempting to speculate that the increase in solar UVR in the summer could induce suppression of cellular immunity, thus contributing to the corresponding rise in the incidence of zoster.
Colloid deposition on non‐ideal porous media: The influences of collector shape and roughness on the single‐collector efficiency
Authors: Saiers James E. , Ryan J. N.
Published: May 2006

The transport of groundwater colloids (e.g., bacteria, viruses, clay particles) is governed, in part, by the rate at which the colloids strike and adhere to aquifer mineral grains. We report results of coupled flow and transport simulations that reveal how changes in mineral‐grain shape and surface roughness influence the single‐collector contact efficiency (ηT) – a parameter of colloid‐filtration theory that quantifies the frequency of colloid collisions with the surface of a mineral grain (collector). Our analyses indicate that the sensitivity of ηT to variations in collector shape and roughness depends on colloid size and suggests that quantitative descriptions of colloid transport through real aquifers will, in some cases, require nontraditional approaches that are not limited by the simplifying assumptions of smooth, spherical collectors.
Anticrack inclusion model for compaction bands in sandstone
Authors: Sternlof Kurt R. , Rudnicki John W. , Pollard David D.
Published: May 2006

Detailed observations of compaction bands exposed in the Aztec Sandstone of southeastern Nevada indicate that these thin, tabular, bounded features of localized porosity loss initiated at pervasive grain‐scale flaws, which collapsed in response to compressive tectonic loading. From many of these Griffith‐type flaws, an apparently self‐sustaining progression of collapse propagated outward to form bands of compacted grains a few centimeters thick and tens of meters in planar extent. These compaction bands can be idealized as highly eccentric ellipsoidal bodies that have accommodated uniform uniaxial plastic strain parallel to their short dimension within a surrounding elastic material. They thus can be represented mechanically as contractile Eshelby inclusions, which generate near‐tip compressive stress concentrations consistent with self‐sustaining, in‐plane propagation. The combination of extreme aspect ratio (∼10−4) and significant uniaxial plastic strain (∼10%) also justifies an approximation of the bands as anticracks: sharp boundaries across which a continuous distribution of closing mode displacement discontinuity has been accommodated. This anticrack interpretation of compaction bands is analogous to that of pressure solution surfaces, except that porosity loss takes the place of material dissolution. We find that displacement discontinuity boundary element modeling of compaction bands as anticracks within a two‐dimensional linear elastic continuum can accurately represent the perturbed external stress fields they induce.
Infarct Prediction and Treatment Assessment with MRI-based Algorithms in Experimental Stroke Models
Authors: Wu Ona , Sumii Toshihisa , Asahi Minoru , Sasamata Masao , Østergaard Leif , Rosen Bruce R , Lo Eng H , Dijkhuizen Rick M
Published: May 2006

There is increasing interest in using algorithms combining multiple magnetic resonance imaging (MRI) modalities to predict tissue infarction in acute human stroke. We developed and tested a voxel-based generalized linear model (GLM) algorithm to predict tissue infarction in an animal stroke model in order to directly compare predicted outcome with the tissue's histologic outcome, and to evaluate the potential for assessing therapeutic efficacy using these multiparametric algorithms. With acute MRI acquired after unilateral embolic stroke in rats ( n = 8), a GLM was developed and used to predict infarction on a voxel-wise basis for saline ( n = 6) and recombinant tissue plasminogen activator (rt-PA) treatment ( n = 7) arms of a trial of delayed thrombolytic therapy in rats. Pretreatment predicted outcome compared with post-treatment histology was highly accurate in saline-treated rats (0.92±0.05). Accuracy was significantly reduced ( P=0.04) in rt-PA-treated animals (0.86±0.08), although no significant difference was detected when comparing histologic lesion volumes. Animals that reperfused had significantly lower ( P < 0.01) GLM-predicted infarction risk (0.73±0.03) than nonreperfused animals (0.81 ± 0.05), possibly reflecting less severe initial ischemic injury and therefore tissue likely more amenable to therapy. Our results show that acute MRI-based algorithms can predict tissue infarction with high accuracy in animals not receiving thrombolytic therapy. Furthermore, alterations in disease progression due to treatment were more sensitively monitored with our voxel-based analysis techniques than with volumetric approaches. Our study shows that predictive algorithms are promising metrics for diagnosis, prognosis and therapeutic evaluation after acute stroke that can translate readily from preclinical to clinical settings.
HIV-1 gp120 Compromises Blood–Brain Barrier Integrity and Enhance Monocyte Migration across Blood–Brain Barrier: Implication for Viral Neuropathogenesis
Authors: Kanmogne Georgette D , Schall Kathy , Leibhart Jessica , Knipe Bryan , Gendelman Howard E , Persidsky Yuri
Published: May 2006

Human immunodeficiency virus-1 (HIV-1) encephalitis is characterized by brain infiltration of virus-infected monocytes and macrophages. Cellular products and viral proteins secreted by infected cells likely play an important role in blood–brain barrier (BBB) impairment and the development of HIV-1-associated dementia (HAD). We previously demonstrated that HIV-1 envelope glycoprotein gp120 induces toxicity and alters expression of tight junction proteins in human brain microvascular endothelial cells (HBMECs). Here, we delineate the mechanisms of gp120-induced BBB dysfunction. Human brain microvascular endothelial cells expressed HIV-1 co-receptors (CCR5 and CXCR4). Exposure of HBMECs to gp120 derived from macrophage (CCR5) or lymphocyte (CXCR4)-tropic viruses decreased BBB tightness, increased permeability, and enhanced monocyte migration across in vitro BBB models. Blood–brain barrier integrity was restored after gp120 removal. CCR5 antibodies and inhibitors of myosin light chain kinase or protein kinase C (PKC) blocked gp120-enhanced monocyte migration and permeability of BBB in vitro. Exposure of HBMECs to gp120 induced release of intracellular calcium ([Ca2+]i) that was prevented by CCR5 antibody and partially blocked by CXCR4 antagonist. Human immunodeficiency virus-1 gp120 activated three PKC isoforms in HBMECs [PKC-α/βII, PKC(pan)-βII and PKC-ζλ]. Furthermore, specific PKC inhibitors (acting at the ATP-binding and calcium release site) blocked gp120-induced PKC activation and prevented increase in BBB permeability, supporting the biologic significance of these results. Thus, gp120 can cause dysfunction of BBB via PKC pathways and receptor mediated [Ca2+]i release leading to cytoskeletal alterations and increased monocyte migration.
Transgenic Overexpression of Adenosine Kinase Aggravates Cell Death in Ischemia
Authors: Pignataro Giuseppe , Simon Roger P , Boison Detlev
Published: May 2006

Adenosine is an endogenous neuromodulator with anticonvulsive and neuroprotective activity. Adenosine levels are normally kept in the range of 20 to 200 nmol/L by low basal expression of its main metabolic enzyme, adenosine kinase (ADK). Dysfunction of the adenosinergic system has been demonstrated to contribute to epileptogenesis. To investigate whether upregulation of ADK may render the brain more susceptible to ischemic cell death, mutant mice overexpressing an Adk transgene in brain were subjected to middle cerebral artery occlusion (MCAO). One day after either 15 or 60 mins of MCAO, wild-type (WT) animals had infarct areas encompassing about 5% and 50% of their ischemic hemisphere, respectively. In marked contrast, the volume of the infarcts increased three-fold in Adk transgenic mutants after 15 mins of MCAO, and after 60 mins of MCAO all mutants died within 24 h. Pretreatment of the mutants with the ADK inhibitor 5-iodotubercidin led to lesions similar to those in WT mice. Thus, low levels of ADK are essential to maintain adenosine-mediated neuroprotection. We conclude that pathologic overexpression of ADK as in epilepsy may also render the brain more susceptible to injury from ischemia. Consequently, ADK emerges as a rational therapeutic target to enhance neuroprotection.
Multiphoton Imaging of Ultrasound/Optison Mediated Cerebrovascular Effects in vivo
Authors: Raymond Scott B , Skoch Jesse , Hynynen Kullervo , Bacskai Brian J
Published: May 2006

Ultrasound (US) enhanced with microbubble contrast agents may transiently disrupt the blood–brain barrier (BBB) with minimal damage, providing a technique for noninvasive, localized drug-delivery deep within the brain. The mechanism and temporal profile of disruption are not understood, owing to the limitations of imaging modalities used previously. In this study, we monitored US-induced BBB disruption with multiphoton microscopy, providing high-resolution temporal and spatial information about the permeabilization mechanism and immediate effects of US exposure. Anesthetized C57 mice were prepared with a craniotomy and injected intravenously with fluorescent dyes to permit visualization of the vasculature and BBB integrity. The animals were imaged through a cranial window while exposed to low-intensity US ( f =1.029 MHz, power = 0.2 W) with a coincident intravenous injection of Optison (a microbubble contrast agent). We observed arteriolar vasoconstriction on US exposure that disrupted blood flow and lasted up to 5 mins; BBB disruption occurred via two characteristically distinct processes—perivascular fluorescence gradually increased (over minutes) along the length of the affected vessel without apparent rupture of the vessel wall or rapidly (seconds) increased in select, focal regions. These data corroborated previous studies suggesting increased endothelial transcytosis and breached tight junctions and demonstrated vasoconstriction, which might alter BBB permeability by modifying cerebral blood flow.
Allosteric action in real time: Time-resolved crystallographic studies of a cooperative dimeric hemoglobin
Authors: Knapp James E. , Pahl Reinhard , Šrajer Vukica , Royer William E.
Published: May 2006

Protein allostery provides mechanisms for regulation of biological function at the molecular level. We present here an investigation of global, ligand-induced allosteric transition in a protein by time-resolved x-ray diffraction. The study provides a view of structural changes in single crystals of
Scapharca
dimeric hemoglobin as they proceed in real time, from 5 ns to 80 μs after ligand photodissociation. A tertiary intermediate structure forms rapidly (<5 ns) as the protein responds to the presence of an unliganded heme within each R-state protein subunit, with key structural changes observed in the heme groups, neighboring residues, and interface water molecules. This intermediate lays a foundation for the concerted tertiary and quaternary structural changes that occur on a microsecond time scale and are associated with the transition to a low-affinity T-state structure. Reversal of these changes shows a considerable lag as a T-like structure persists well after ligand rebinding, suggesting a slow T-to-R transition.
The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs
Authors: Kavanagh Kathryn L. , Guo Kunde , Dunford James E. , Wu Xiaoqiu , Knapp Stefan , Ebetino Frank H. , Rogers Michael J. , Russell R. Graham G. , Oppermann Udo
Published: May 2006

Osteoporosis and low bone mass are currently estimated to be a major public health risk affecting >50% of the female population over the age of 50. Because of their bone-selective pharmacokinetics, nitrogen-containing bisphosphonates (N-BPs), currently used as clinical inhibitors of bone-resorption diseases, target osteoclast farnesyl pyrophosphate synthase (FPPS) and inhibit protein prenylation. FPPS, a key branchpoint of the mevalonate pathway, catalyzes the successive condensation of isopentenyl pyrophosphate with dimethylallyl pyrophosphate and geranyl pyrophosphate. To understand the molecular events involved in inhibition of FPPS by N-BPs, we used protein crystallography, enzyme kinetics, and isothermal titration calorimetry. We report here high-resolution x-ray structures of the human enzyme in complexes with risedronate and zoledronate, two of the leading N-BPs in clinical use. These agents bind to the dimethylallyl/geranyl pyrophosphate ligand pocket and induce a conformational change. The interactions of the N-BP cyclic nitrogen with Thr-201 and Lys-200 suggest that these inhibitors achieve potency by positioning their nitrogen in the proposed carbocation-binding site. Kinetic analyses reveal that inhibition is competitive with geranyl pyrophosphate and is of a slow, tight binding character, indicating that isomerization of an initial enzyme–inhibitor complex occurs with inhibitor binding. Isothermal titration calorimetry indicates that binding of N-BPs to the apoenzyme is entropy-driven, presumably through desolvation entropy effects. These experiments reveal the molecular binding characteristics of an important pharmacological target and provide a route for further optimization of these important drugs.
Genetic variation in putative regulatory loci controlling gene expression in breast cancer
Authors: Kristensen Vessela N. , Edvardsen Hege , Tsalenko Anya , Nordgard Silje H. , Sørlie Therese , Sharan Roded , Vailaya Aditya , Ben-Dor Amir , Lønning Per Eystein , Lien Sigbjørn , Omholt Stig , Syvänen Ann-Christine , Yakhini Zohar , Børresen-Dale Anne-Lise
Published: May 2006

Candidate single-nucleotide polymorphisms (SNPs) were analyzed for associations to an unselected whole genome pool of tumor mRNA transcripts in 50 unrelated patients with breast cancer. SNPs were selected from 203 candidate genes of the reactive oxygen species pathway. We describe a general statistical framework for the simultaneous analysis of gene expression data and SNP genotype data measured for the same cohort, which revealed significant associations between subsets of SNPs and transcripts, shedding light on the underlying biology. We identified SNPs inEGF,IL1A,MAPK8,XPC,SOD2, andALOX12that are associated with the expression patterns of a significant number of transcripts, indicating the presence of regulatory SNPs in these genes. SNPs were found to act in trans in a total of 115 genes. SNPs in 43 of these 115 genes were found to act both in cis and in trans. Finally, subsets of SNPs that share significantly many common associations with a set of transcripts (biclusters) were identified. The subsets of transcripts that are significantly associated with the same set of SNPs or to a single SNP were shown to be functionally coherent in Gene Ontology and pathway analyses and coexpressed in other independent data sets, suggesting that many of the observed associations are within the same functional pathways. To our knowledge, this article is the first study to correlate SNP genotype data in the germ line with somatic gene expression data in breast tumors. It provides the statistical framework for further genotype expression correlation studies in cancer data sets.
Helicobacter pylori isolated from patients who later failed H. pylori eradication triple therapy readily develop resistance to clarithromycin
Authors: Kobayashi Intetsu , Saika Takeshi , Muraoka Hiroe , Murakami Kazunari , Fujioka Toshio
Published: May 2006

In this study, the ease of selection of clarithromycin resistance was investigated in clarithromycin-susceptible Helicobacter pylori strains isolated from patients with H. pylori infection prior to the administration of triple-combination eradication therapy (clarithromycin plus amoxicillin plus a proton pump inhibitor). Clarithromycin-susceptible strains isolated from ten patients in whom the eradication therapy was successful and from six patients in whom the eradication therapy was unsuccessful were exposed serially to subinhibitory concentrations of clarithromycin. The number of transfers required for the MICs of the strains to increase by 8- and 32-fold were 6.6 and 7.2, respectively, in the successful eradication group, and as few as 2.4 and 1.5, respectively, in the unsuccessful eradication group. The number of transfers required for the A2142G or A2143G point mutation of the 23S rRNA gene to be detected in the strains were 5 and 8, respectively, for the strains in the successful eradication group, and 1 and 2, respectively, for the strains in the unsuccessful eradication group. These results suggest that patients in the unsuccessful eradication group were infected with strains of H. pylori that readily became resistant to clarithromycin on exposure to the drug.
Airborne transmission of lyssaviruses
Authors: Johnson N. , Phillpotts R. , Fooks A. R.
Published: May 2006

In 2002, a Scottish bat conservationist developed a rabies-like disease and subsequently died. This was caused by infection with European bat lyssavirus 2 (EBLV-2), a virus closely related to Rabies virus (RABV). The source of this infection and the means of transmission have not yet been confirmed. In this study, the hypothesis that lyssaviruses, particularly RABV and the bat variant EBLV-2, might be transmitted via the airborne route was tested. Mice were challenged via direct introduction of lyssavirus into the nasal passages. Two hours after intranasal challenge with a mouse-adapted strain of RABV (Challenge Virus Standard), viral RNA was detectable in the tongue, lungs and stomach. All of the mice challenged by direct intranasal inoculation developed disease signs by 7 days post-infection. Two out of five mice challenged by direct intranasal inoculation of EBLV-2 developed disease between 16 and 19 days post-infection. In addition, a simple apparatus was evaluated in which mice could be exposed experimentally to infectious doses of lyssavirus from an aerosol. Using this approach, mice challenged with RABV, but not those challenged with EBLV-2, were highly susceptible to infection by inhalation. These data support the hypothesis that lyssaviruses, and RABV in particular, can be spread by airborne transmission in a dose-dependent manner. This could present a particular hazard to personnel exposed to aerosols of infectious RABV following accidental release in a laboratory environment.
Escherichia coli interactions with Acanthamoeba: a symbiosis with environmental and clinical implications
Authors: Alsam Selwa , Jeong Seok Ryoul , Sissons James , Dudley Ricky , Kim Kwang Sik , Khan Naveed Ahmed
Published: May 2006

The ability of Acanthamoeba to feed on Gram-negative bacteria, as well as to harbour potential pathogens, such as Legionella pneumophila, Coxiella burnetii, Pseudomonas aeruginosa, Vibrio cholerae, Helicobacter pylori, Listeria monocytogenes and Mycobacterium avium, suggest that both amoebae and bacteria are involved in complex interactions, which may play important roles in the environment and in human health. In this study, Acanthamoeba castellanii (a keratitis isolate belonging to the T4 genotype) was used and its interactions with Escherichia coli (strain K1, a cerebrospinal fluid isolate from a meningitis patient, O18 : K1 : H7, and a K-12 laboratory strain, HB101) were studied. The invasive K1 isolate exhibited a significantly higher association with A. castellanii than the non-invasive K-12 isolate. Similarly, K1 showed significantly increased invasion and/or uptake by A. castellanii in gentamicin protection assays than the non-invasive K-12. Using several mutants derived from K1, it was observed that outer-membrane protein A (OmpA) and LPS were crucial bacterial determinants responsible for E. coli K1 interactions with A. castellanii. Once inside the cell, E. coli K1 remained viable and multiplied within A. castellanii, while E. coli K-12 was killed. Again, OmpA and LPS were crucial for E. coli K1 intracellular survival in A. castellanii. In conclusion, these findings suggest that E. coli K1 interactions with A. castellanii are carefully regulated by the virulence of E. coli.