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Islam means submission to the will of God. Therefore Muslims put primary emphasis on obeying God as prescribed in Islamic law. Islam’s worldview is a vision of individual and communal moral responsibility; Muslims must strive or struggle (jihad) in the path (shariah) of God in order to implement God’s will on earth, expand and defend the Muslim community, and establish a just society. The purpose of Islamic law is to provide the guidelines and requirements for two types of interactions: those between human beings and God, or worship, and those between human beings, or social transactions. Both have private and public dimensions, and both give Islam a prominent public role in Muslim community life.

Since the terrorist attacks of September 11th, there has been an overwhelming demand for information about Islam, and recent events - the war in Iraq, terrorist attacks both failed and successful, debates throughout Europe over Islamic dress, and many others - have raised new questions in the minds of policymakers and the general public. This newly updated edition of What Everyone Needs to Know about Islam is the best single source for clearly presented, objective information about these new developments, and for answers to questions about the origin and traditions of Islam. Editor of The Oxford Encyclopedia of Modern Islam and The Oxford History of Islam, and author of The Future of Islambits and many other acclaimed works, John L. Esposito is one of America's leading authorities on Islam. This brief and readable book remains the first place to look for up-to-date information on the faith, customs, and political beliefs of the more than one billion people who call themselves Muslims.

This special issue of the American Journal of Islamic Social Sciences on Ismail al Faruqi is prepared to honor the memory and contribution of Professor Ismail al Faruqi to the academia, the history of Islamic thought, and the development of the Muslim community (Ummah). Providing a perspective twenty-five years after Professor al Faruqi’s death, it provides thought-provoking papers relating of the person, mission, and intellectual jihad initiated by Professor al Faruqi. Ismail Raji al Faruqi (1921–1986) was a great scholar of Islam in modern times. His scholarship covered a broad spectrum of Islamic studies: the study of religion, Islamic thought, approaches to knowledge, history, culture, education, interfaith dialogue, aesthetics, ethics, politics, economics, science, and gender issues. He had indeed an encyclopedic knowledge, a rare person among contemporary Muslim scholars. Ismail al-Faruqi laid the foundation for a new interpretation and analysis of the quintessence of tawhid and its relevance in various dimensions of human life and thought. He also made unique contributions to the study of Islam and its relevance to the contemporary age. In fact, many of his unique contributions to Islamic scholarship remain especially relevant today and have been carried on and extended by many of his former. Professor al Faruqi was a founder of “the school of Islamization of knowledge,” which has been incorporated at several international Islamic universities. His school of thought, academic approach, and practice is also being applied by hundreds of his students who are teaching and doing research at different universities in all continents. This special issue of the American Journal of Islamic Social Sciences, revisits the intellectual legacy and continuing influence of Professor Ismail al Faruqi since his death ...

Persistent diarrhea is commonly observed after solid organ transplantation (SOT). A few cases of mycophenolate mofetil (MMF)-induced duodenal villous atrophy (DVA) have been previously reported in kidney-transplant patients with chronic diarrhea. Herein, we report on the incidence and characteristics of DVA in SOT patients with chronic diarrhea. One hundred thirty-two SOT patients with chronic diarrhea underwent an oesophago-gastroduodenoscopy (OGD) and a duodenal biopsy after classical causes of diarrhea have been ruled out. DVA was diagnosed in 21 patients (15.9%). It was attributed to mycophenolic acid (MPA) therapy in 18 patients (85.7%) (MMF [n = 14] and enteric-coated mycophenolate sodium [n = 4]). MPA withdrawal or dose reduction resulted in diarrhea cessation. The incidence of DVA was significantly higher in patients with chronic diarrhea receiving MPA compared to those who did not (24.6% vs. 5.1%, p = 0.003). DVA was attributed to a Giardia lamblia parasitic infection in two patients (9.5%) and the remaining case was attributed to azathioprine. In these three patients, diarrhea ceased after metronidazole therapy or azathioprine dose reduction. In conclusion, DVA is a frequent cause of chronic diarrhea in SOT recipients. MPA therapy is the most frequent cause of DVA. An OGD should be proposed to all transplant recipients who present with persistent diarrhea.

Rare-earth doped yttrium aluminum garnet (YAG) ceramics are among the most widely produced transparent ceramics for laser applications. Yb:YAG ceramics are an interesting IR laser material [1], which allows significantly higher doping compared to the generally more used Nd:YAG [2, 3]. This work presents the preparation of polycrystalline Yb:YAG ceramics with dopant concentration from 0 up to 20 at.% via solid state reactive sintering. Samples were prepared via cold isostatic pressing of spray dried mixture of pure oxide powders with TEOS as a sintering aid. Sintering was conducted under high vacuum and clean atmosphere. Samples with optical transmittance higher than 80 % were prepared (see Fig. 1) and their laser performance was examined. The effect of Yb on both the optical properties (transmittance) and mechanical properties (tensile modulus and hardness) was studied. The crucial factor affecting the optical properties of transparent ceramics is the potential presence of other phases or pores [4]. Final microstructure of prepared samples was thus analyzed via optical and scanning electron microscopy and EDS. In addition, high-temperature behavior was studied, so that the important and critical preparation steps, which affect the final microstructure, and thus the optical as well as laser properties, could be selected and optimized.

Nell'ambito del progetto, a seguito dello sviluppo sul "Sistema di accumulo e scambio termico con mezzo granulare fluidizzato" (Task 1.3) si è reso necessario un approfondimento sull'applicazione dei materiali ceramici nei prototipi previsti dal progetto. Tale approfondimento riguarda essen-zialmente l'individuazione delle caratteristiche composizionali e funzionali dei materiali ceramici e soluzioni tecnologiche per: -Tubi in carburo di silicio (risers); -Involucro di contenimento della cavità; -Giunzioni tubi di SiC-blocchi di ricircolo; -Blocchi di ricircolo; -Griglia di fluidizzazione; -Isolamento refrattario.

An exhaustive hardness characterization and comparative evaluation of the dry wear performance of three different wear-resistant coating systems (alumina-titania, WC-Co, and Ni-Cr on a carbon steel substrate) mated against a normalized 0.3% carbon steel are presented. The WC-Co coating was found to be the most wear resistant, followed by the alumina-titania and NiCr-based coatings.

Carotid artery stenosis is a leading, treatable risk factor for stroke. Until recently, risk prediction has, for the main part, been based on the degree of lumen narrowing which does not reflect our actual insight into the etiology of arterio-embolic stroke. The risk of carotid artery stenosis is in fact defined by the texture and morphology of the atherosclerotic lesion. Both B-mode ultrasound and MRI can depict these features and have considerable potential for detection of vulnerable plaques.

Background Plaque imaging based on magnetic resonance imaging (MRI) represents a new modality for risk assessment in atherosclerosis. It allows classification of carotid plaques in high-risk and low-risk lesion types (I-VIII). Type 2 diabetes mellitus (DM 2) represents a known risk factor for atherosclerosis, but its specific influence on plaque vulnerability is not fully understood. This study investigates whether MRI-plaque imaging can reveal differences in carotid plaque features of diabetic patients compared to nondiabetics. Methods 191 patients with moderate to high-grade carotid artery stenosis were enrolled after written informed consent was obtained. Each patient underwent MRI-plaque imaging using a 1.5-T scanner with phased-array carotid coils. The carotid plaques were classified as lesion types I-VIII according to the MRI-modified AHA criteria. For 36 patients histology data was available. Results Eleven patients were excluded because of insufficient MR-image quality. DM 2 was diagnosed in 51 patients (28.3%). Concordance between histology and MRI-classification was 91.7% (33/36) and showed a Cohen's kappa value of 0.81 with a 95% CI of 0.98-1.15. MRI-defined high-risk lesion types were overrepresented in diabetic patients (n = 29; 56.8%). Multiple logistic regression analysis revealed association between DM 2 and MRI-defined high-risk lesion types (OR 2.59; 95% CI [1.15-5.81]), independent of the degree of stenosis. Conclusion DM 2 seems to represent a predictor for the development of vulnerable carotid plaques irrespective of the degree of stenosis and other risk factors. MRI-plaque imaging represents a new tool for risk stratification of diabetic patients. See Commentary: http://www.biomedcentral.com/1741-7015/8/78/abstract

The swine-origin influenza A (H1N1) virus is mainly responsible for flu. No hepatitis attributable to H1N1 virus has been previously documented. Herein, we report on a kidney transplant patient who developed influenza H1N1 virus-induced hepatocellular injury. The patient's body temperature was only somewhat elevated, and pulmonary and flu symptoms were mild. H1N1 virus was detected by polymerase chain reaction assay in nasopharyngeal and bronchoalveolar swabs, as well as in the serum. The hepatocellular injury episode resolved after the patient had been placed on oseltamivir therapy. This observation suggests that acute hepatocellular injury could be linked to the influenza H1N1 virus.

Introduction Section 1: Iraq 1. Religion, Sect, Ethnicity and Tribe: The Uncertainties of Identity Politics in the New Society Faleh Abdul-Jabbar 2. Lessons from Iraq Laith Kubba 3. Kurdistan: Democracy and Future of Iraq Salah Aziz 4. Forging a Third Way: Sistani's Marjaiyya between Quietism and Wilayat al-Faqih Abbas Kadhim Section 2: 5. Humble Democracy? On the Need for New Thinking about an Aging Ideal John Keane 6. Islamic Democracy: A Valid Concept of an Oxymoron? Ali Paya 7. Promoting Democracy Bhikhu Parekh 8. The Democratic Freedom Deficit in the Middle East Beverley Milton-Edwards Section 3: The Future of the Muslim World 9. World of Islam, Historical Perspectives and Modern Political Discources Seyyed Mohammad Khatami 10. The Saga of Islam and Democracy in the Middle East John Esposito 11. Islam's Future Imperfect: Fighting over Camels at the End of History Abdelwahab El-Affendi 12. Triumph through Destabilization: The Future of Politcal Islam Mohammad Samiei 13. Reason and revelation in Islamic Political Ethics Abdulaziz Sachedina

Background Transient ischemic attack (TIA) patients are at a high vascular risk. Recently the ABCD2 score was validated for evaluating short-term stroke risk after TIA. We assessed the value of this score to predict the vascular outcome after TIA during medium- to long-term follow-up. Methods The ABCD2 score of 176 TIA patients consecutively admitted to the Stroke Unit was retrospectively calculated and stratified into three categories. TIA was defined as an acute transient focal neurological deficit caused by vascular disease and being completely reversible within 24 hours. All patients had to undergo cerebral MRI within 5 days after onset of symptoms as well as extracranial and transcranial Doppler and duplex ultrasonography. At a median follow-up of 27 months, new vascular events were recorded. Multivariate Cox regression adjusted for EDC findings and heart failure was performed for the combined endpoint of cerebral ischemic events, cardiac ischemic events and death of vascular or unknown cause. Results Fifty-five patients (32.0%) had an ABCD2 score ≤ 3, 80 patients (46.5%) had an ABCD2 score of 4-5 points and 37 patients (21.5%) had an ABCD2 score of 6-7 points. Follow-up data were available in 173 (98.3%) patients. Twenty-two patients (13.8%) experienced an ischemic stroke or TIA; 5 (3.0%) a myocardial infarction or acute coronary syndrome; 10 (5.7%) died of vascular or unknown cause; and 5 (3.0%) patients underwent arterial revascularization. An ABCD2 score > 3 was significantly associated with the combined endpoint of cerebral or cardiovascular ischemic events, and death of vascular or unknown cause (hazard ratio (HR) 4.01, 95% confidence interval (CI) 1.21 to 13.27). After adjustment for extracranial ultrasonographic findings and heart failure, there was still a strong trend (HR 3.13, 95% CI 0.94 to 10.49). Whereas new cardiovascular ischemic events occurred in 9 (8.3%) patients with an ABCD2 score > 3, this happened in none of the 53 patients with a score ≤ 3. Conclusions An ABCD2 score > 3 is associated with an increased general risk for vascular events in the medium- to long-term follow-up after TIA.

Preemptive kidney transplantation is the treatment of choice for end-stage renal disease. Compared with nonpreemptive transplantation, preemptive transplantation is significantly associated with improved kidney allograft survival in recipients of either cadaver or living-donor transplants. This seems to be related to better patient survival. It can be proposed to all patients, but still needs to be evaluated for repeat transplantation. The main barriers are organ-allocation policies and late referral of patients to transplantation centers.

Despite numerous studies suggesting a relationship between paradoxical embolism from a patent foramen ovale (PFO) and stroke, the role of PFO as a risk factor for cerebral ischaemia remains controversial. We therefore sought to determine the association between a RLS detected by contrast-enhanced transcranial Doppler ultrasonography (c-TCD) and recurrent stroke in an unselected population sample.We analyzed the records of 763 patients with diagnosis of cerebral ischaemia at our institution. All patients had undergone TCD-based detection of RLS. Embolic signals have been measured both under resting conditions and after performing a Valsalva maneuver. For follow-up, all patients were contacted by mail, which included a standardized questionnaire. Endpoints of follow-up were defined as recurrence of cerebral ischaemia, occurrence of myocardial infarction or death from any cause.Follow-up data were available in 639 patients (83.7%). At baseline, a RLS was detected in 140 (28%) men and in 114 (42%) women. Ten shunt-carriers (1.6%) and 32 patients (5.0%) without RLS had suffered a recurrent stroke. After adjustment for age, sex, and atrial fibrillation, the hazard ratio of RLS for stroke recurrence was 0.86 (95% CI 0.41-1.79). The condition of RLS at rest adjusted for age, sex, stroke subtype, and cardiovascular risk factors was not found to increase the risk of stroke substantially (HR 1.16 [95% CI 0.41-3.29])Our data suggest that the risk of recurrent stroke in subjects with PFO is not significantly increased in comparison with subject without it.

We previously described a lyophilized supernatant from germinated Candida albicans that blocks human neutrophil (PMN) O2- production and degranulation stimulated by several PMN agonists but does not block stimulation by PMA. In studies to further characterize this Candida hyphal inhibitory product (CHIP), we noted several physicochemical parallels with the purine nucleoside adenosine (Ado). A Sephadex G-10 semipurified fraction of CHIP had an absorption peak near 260 nm, an apparent m.w. of less than 400, and was resistant to boiling and proteases. Maximally effective doses of CHIP (100 micrograms/ml) and Ado (100 microM) blocked 0.1 microM FMLP-stimulated O2- production by 76.8 +/- 4.1 and 81.7 +/- 4.8%, respectively. Ado deaminase, known to inactivate Ado, reversed inhibition by both Ado and CHIP. Results were comparable for the effect of CHIP and Ado on FMLP-stimulated beta-glucuronidase and lactoferrin release. Activation of the respiratory burst by opsonized C. albicans yeast was also inhibited by CHIP and Ado, but the extent of inhibition was less than for FMLP. At yeast:PMN ratios of 4:1, 10:1, and 40:1, CHIP inhibited O2- by -3.8%, 14.3%, and 12.8%, respectively; Ado blocked production by 32.9%, 24.2%, and 11.5%, respectively. The effect of CHIP and Ado on Candida killing by PMN was compared using two viability assays in each of four experiments. Ado (100 microM) had no effect on killing, although CHIP (100 micrograms/ml) inhibited killing in the MTT assay at 15 and 45 min by 81.6 +/- 6.3 and 24.7 +/- 6.2%, respectively; as assayed by CFU, CHIP inhibited killing by 34.1 +/- 6.2 and 10.3 +/- 2.5%, respectively. The ability of CHIP to inhibit killing was not affected by adding Ado deaminase, providing additional evidence that an Ado-like effect by CHIP is not essential for killing inhibition. Killing of opsonized Streptococcus pneumoniae was also inhibited in a concentration-dependent manner. Reverse-phase HPLC of the semipurified fraction revealed a peak, eluting identically to authentic Ado, which was eliminated by adding Ado deaminase. Ado content of the G-10 fraction was sufficient to account fully for the FMLP-inhibitory activity. The antikilling activity was resistant to boiling and proteases but was eliminated by mild periodation. Fractions eluting from a Sephadex CL6B column between 0.8 and 2.0 x 10(6) m.w. had increased sp. act. for killing inhibition. Sp. act. increased as carbohydrate content increased, but killing inhibition by various Candida cell wall constituents was absent to modest compared to inhibition induced by CHIP.(ABSTRACT TRUNCATED AT 400 WORDS)

The risk of humans acquiring pneumonia as a result of their occupation appears to have declined during the twentieth century in developed countries, such as the United States. Thus, some conditions that are traditionally associated with the workplace, such as woolsorters' disease, represent illnesses that are of historical interest only. Nevertheless, the problem of occupation-associated pneumonia remains substantial. First, large outbreaks of zoonotic infections continue to occur, especially psittacosis among poultry farmers and abattoir workers. Second, clusters of illnesses caused by recently recognized pathogens are now being reported, including legionnaires' disease in industrial workers and Chlamydia pneumoniae infections in military personnel. Finally, epidemics of old conditions are appearing in new settings, such as tuberculosis among nursing home workers. Thus, the transmission, control, and treatment of pneumonias acquired in the workplace represent intriguing and challenging areas of concern to the epidemiologist and clinician.

Multi-modal registration is the task of aligning images from an object acquired with different imaging systems, sensors or parameters. The current gold standard for medical images is the maximization of mutual information by computing the joint intensity distribution. However intensities are highly sensitive to various kinds of noise and denoising is a very challenging task often involving a priori knowledge and parameter tuning. We propose to perform registration on a novel robust information support: the wavelet energy map, giving a measure of local energy for each pixel. This spatial feature is derived from local spectral components computed with a redundant wavelet transform. The multi-frequential aspect of our method is particularly adapted to robust registration of images showing ambiguities such as tissues, complex textures and multiple interfaces. We show the benefits of the wavelet energy map approach in comparison to the classical framework in 2D and 3D rigid registration experiments on synthetic and real data.

Background and Purpose Few studies investigated the neuropsychological outcome after carotid angioplasty with stent placement (CAS), yielding partially inconsistent results. The present investigation evaluated the effect of CAS in patients with high-grade stenosis and assessed the predictive value of ischemic lesion number for postinterventional cognitive deterioration. Methods 22 patients were tested neuropsychologically before and six weeks after CAS. Cerebral ischemic changes were assessed with diffusion weighted imaging (DWI) prior to and after angioplasty. Results Pre- to postinterventional cognitive performance improved significantly in terms of verbal memory (t = −2.30; p

Background Transient ischemic attack (TIA) patients are at high vascular risk. We assessed the value of extracranial (ECD) and transcranial (TCD) Doppler and duplex ultrasonography to predict clinical outcome after TIA. Methods 176 consecutive TIA patients admitted to the Stroke Unit were recruited in the study. All patients received diffusion-weighted imaging, standardized ECD and TCD. At a median follow-up of 27 months, new vascular events were recorded. Results 22 (13.8%) patients experienced an ischemic stroke or TIA, 5 (3.1%) a myocardial infarction or acute coronary syndrome, and 5 (3.1%) underwent arterial revascularization. ECD revealed extracranial ≥ 50% stenosis or occlusions in 34 (19.3%) patients, TCD showed intracranial stenosis in 15 (9.2%) and collateral flow patterns due to extracranial stenosis in 5 (3.1%) cases. Multivariate analysis identified these abnormal ECD and TCD findings as predictors of new cerebral ischemic events (ECD: hazard ratio (HR) 4.30, 95% confidence interval (CI) 1.75 to 10.57, P = 0.01; TCD: HR 4.73, 95% CI 1.86 to 12.04, P = 0.01). Abnormal TCD findings were also predictive of cardiovascular ischemic events (HR 18.51, 95% CI 3.49 to 98.24, P = 0.001). Conclusion TIA patients with abnormal TCD findings are at high risk to develop further cerebral and cardiovascular ischemic events.

Foreword, J.L.Esposito Aftershocks P.Yancey PART I: ISLAM AND 9/11 An Altered Terrain: Engaging Islam in the Post-9/11 Public Sphere A.Afsaruddin A Struggle for the Soul of a Faith: Spiritual Islam versus Political Islam M.Zuhdi Jasser & S.Shahid How Does the U.S. Government Look at Islam since 9/11? L.Danan & A.E.Hunt PART II: OTHER RELIGIOUS PERSPECTIVES Prodigal Nation: September 11 and the American Jeremiad A.Murphy Geopolitical Theology J.Milbank September 11 and the Jewish Vocabulary of Tragedy Rabbi J.Moline Dialogue and Disagreement after 9/11 J.Spiegel & R.Pflum Truth and Falsehood in Religion and Politics J.B.Cobb, Jr. SECTION III: 9/11 AND PHILOSOPHY AND EFFECTS Reconciliatory Praxis: The Face of Justice after 9/11 A.M.Isasi-Diaz Known Unknowns: How Current Philosophy Addresses Fear of the Post-9/11 World L.Harte Power, Terror, and the Good for Humans J.Secada On Moral Alchemy: A Critical Examination of Post-9/11 U.S. Military Policy T.Brewer The Day the World Changed? Reflections on 9/11 and U.S. National Security Strategy M.L.Cook SECTION IV: THE JUST WAR THEORY AFTER 9/11 Just War in the Shadow of 9/11 J.B.Elshtain Understanding Terrorism and the Limits of Just War Theory M.McKenna The Just War Tradition Faces the Remnants of War M.Douglas Catholic Just War Theory: The Conversation since 9/11 L.Johnston Pacifism and Just War Theory after 9/11 A.Fiala To Debate or Not to Debate: Philosophy and Torture after 9/11 P.Kaurin

The calculated energy dissipation associated with the pull‐back signal amplitude in plate impact experiment is usually larger than that obtained by accounting the contributions of the estimated plastic work at continuum scale and that due to ductile damage. As a possible explanation, it is proposed that the drop in the stress triaxiality, due to the formation of free surfaces as a result of the first appearance of the damage in form of voids, allows the matrix material to exhibit much larger plastic deformation. In order to verify this proposition, a numerical investigation based on the use of cohesive finite elements has been performed. The proposed numerical model has been used to predict the damage development and the rear pressure profile in a flyer plate impact test on 99.99% Cu and 316 L SS under flat top and triangular pressure wave profile.

In the framework of CDM, the evolution of the plastic strain, at which damage processes initiates, as a function of stress triaxiality, making the assumption of constant damage dissipated work is derived. Based on this, the CDM model proposed by Bonora (Eng. Frac. Mech., 58, 1‐2, 1997) has been used to predict the occurrence of ductile failure at different stress triaxiality conditions, under both quasi‐static and dynamic loading conditions. This solution allows the possibility to correctly predict the conditions for which ductile damage can initiate under uniaxial strain (such as that for the flyer plate impact test) and mixed conditions such as those in the Taylor impact test. The solution offers the possibility to correlate continuum damage model parameters to micro structural features such as grain size and purity grade.

Aims To examine the prevalence of cryoglobulinemia (Cryo) and autoimmune markers in renal-transplant recipients in a stable condition, and to determine its risk factors and impact upon allograft function. Patients and methods In May, 2006, 117 kidney-transplant (KT) recipients, aged 31 â 76 years, were tested for cryoglobulinemia, hepatitis B and C, complement C3, C4, CH50, antinuclear (ANAs), anticytoplasmic nuclear (ANCAs) and anticardiolipid antibodies, rheumatoid factor (RF), and lymphocyte subpopulations. Renal, liver, and hematological tests were also performed. Immunosuppressive regimens were based on calcineurin inhibitors (82%). Results Cryo was positive in 47 patients (Cryo(+): 40.2%), of whom 13 were HCV+ (27.7%), with characteristics of Type II in 21.2% and Type III in 78.8%. Cryo was positive in 13/16 (81.2%) of HCV+/RNA+ patients vs. 34/101 (33.6%, p = 0.0003) of HCV-negative patients. Cryo(+) RT patients had been recipients of a graft for longer (142 months) than Cryo(-) patients, i.e., 95 months (p = 0.02). Creatinine clearances were similar in the two groups (56 vs. 50 ml/mn, p = 0.5), as were microalbuminuria and albuminemia. There was no difference between Cryo(-) and Cryo(+) patients in terms of age, sex, HLA mismatch, daily steroid doses, liver and hematological tests, ANAs, anticardiolipid antibodies, serum complement, and lymphocyte subpopulations. RF occurred in all Cryo(+) patients and in 82.8% of Cryo(-) patients, with higher titers in the Cryo(+) group (23 vs. 9 UI/ml, p = 0.012). ANCA occurred in nine Cryo(-) but in no Cryo(+) patients (p = 0.013). Finally, a multivariate analysis was not able to determine any predictive factor associated with cryoglobulinemia. Conclusion Cryoglobulinemia is frequent after KT, and is associated with HCV markers, RF, and absence of ANCA.

The inherent toxicity of many metal compounds, together with their widespread environmental distribution, raises concerns of potential health hazards. Little is known about the impact of these important environmental toxicants on adult stem/progenitor cells, necessary for tissue homeostasis and repair. We recently reported that autophagy is implicated in the response of hematopoietic stem/progenitor cells to toxic concentrations of hexavalent chromium (Cr[VI]) and cadmium (Cd), two well known carcinogenic heavy metal cations. Autophagy may lead to cell death if carried out too extensively, but also acts as a survival pathway in cells under stress. In stem/progenitor cells, an autophagic phenotype could mitigate metal-induced toxicity, contributing to the conservation of tissue renewal capability. Given the key role of toxic damage to adult stem/progenitor cells in cancer, it is necessary to investigate whether autophagic responses modulate the carcinogenic potential of exposure to heavy metals during stem/progenitor cell differentiation.

The phenomenon of post-indentation subcritical (slow) crack growth in silicon carbide whisker-reinforced silicon nitride ceramic matrix composites has been investigated under inert and humid ambient atmospheres. The {open_quotes}residual{close_quotes} component of the stress field of the {open_quotes}sharp{close_quotes} Vickers indentation has been shown to have a little effect on crack extension after unloading. However, the humid atmosphere plays a significant role, due to {open_quotes}Stress Corrosion-Assisted Crack Propagation{close_quotes} (SCACP) at the crack tip. The so-called {open_quotes}well-developed{close_quotes} crack, [i.e. c>>b or c/a>2, where c is the crack length measured from the centre of indentation diagonal and a and b are the half-diagonal length and the radius of the plastic zone as defined by Lawn, Evans and Marshall], is an inappropriate term used to define the type of the crack developed after indentation process. It is recommended that a thorough and systematic analysis is required to correlate the microstructural features of the {open_quotes}specific{close_quotes} material to the shape and evolution of the crack during and after indentation, after excluding the environmental effects on crack growth, which dominate the {open_quotes}equilibrium{close_quotes} shape and the type of the crack.

Introduction A number of studies has addressed the possible association between patent foramen ovale (PFO) and stroke. However, the role of PFO in the pathogenesis of cerebral ischemia has remained controversial and most studies did not analyze patient subgroups stratified for gender, age and origin of stroke. Methods To address the role of PFO for the occurrence of cerebral ischemia, we investigated the prevalence of right-to-left shunt in a large group of patients with acute stroke or TIA. 763 consecutive patients admitted to our hospital with cerebral ischemia were analyzed. All patients were screened for the presence of PFO by contrast-enhanced transcranial Doppler sonography at rest and during Valsalva maneuver. Subgroup analyses were performed in patients stratified for gender, age and origin of stroke. Results A right-to-left shunt was detected in 140 (28%) male and in 114 (42%) female patients during Valsalva maneuver, and in 66 (13%) and 44 (16%) at rest respectively. Patients with right-to-left shunt were younger than those without (P < 0.001). PFO was associated with stroke of unknown origin in male (P = 0.001) but not female patients (P > 0.05). After adjusting for age no significant association between PFO and stroke of unknown origin was found in either group. Conclusion Our findings argue against paradoxical embolization as a major cause of cerebral ischemia in patients with right-to-left shunt. Our data demonstrate substantial gender-and age-related differences that should be taken into account in future studies.

In this work, an embedded cohesive elements (ECE) approach has been developed in order to account for the energy dissipated in the separation of the fracture surfaces during spall in flyer plate impact test. The ECE method consists in embedding cohesive elements capable to sustain only normal and shear forces into standard isoparametric 2D or 3D FEM continuum elements. The cohesive elements remain silent and inactive until the underlying continuum elements fail. At failure, the continuum elements are removed while the embedded cohesive elements become active until the energy of fracture separation is fully dissipated. In this work, the methodology is presented and applied to simulate soft spall in ductile metals such as 99.99% copper.

To assess the effects of advanced age on the ability of circulating neutrophils to respond to biologically relevant chemoattractants, cells were isolated from the peripheral blood of pathogen and disease-free C57BL/6 mice and evaluated in a microchemotaxis chamber. The responses of granulocytes obtained from senescent mice (26-28 months) to the chemotactic peptide, FMLP, and to leukotriene B4 were similar to those found with cells from the younger animals (8-10 months). In contrast, the migration of neutrophils in response to sonicated type 3 Streptococcus pneumoniae was significantly greater with cells from the older animals. Similarly, the chemotactic response of neutrophils to zymosan-activated serum was greater with cells and serum from the senescent animals; however, the enhanced chemotaxis exhibited by granulocytes from the aged mice was a consequence of serum factors. Following the deposition of viable type 3 S. pneumoniae into the lower respiratory tract, the neutrophil influx at 24 h after challenge was significantly greater in the senescent mice; however, age-related differences in survival rates and LD50 were not detected. Thus, in the C57BL/6 mouse, senescence is not associated with deficiencies in the response of neutrophils in vitro to chemoattractants that contribute to lung host defense against the pneumococcus; further, in this murine strain, advanced age does not result in an attenuation of the pulmonary inflammatory reaction to infection with type 3 S. pneumoniae.

To characterize the factors that contribute to the killing of type 3 S. pneumoniae, human neutrophils were obtained from healthy donors and incubated with viable organisms. In contrast to prior observations with other pneumococcal serotypes, killing was not detected when 10(6) colony forming units (cfu) were incubated at 37 degrees C for 2-4 hours with 10(6) neutrophils in the presence of 20-80% fresh autologous serum; further, pneumococcidal activity was not found when preopsonized bacteria and primed neutrophils were employed in the standard assay. However, when the bacterium to cell ratio was reduced to 1:100 and 1:1000, microbicidal action was detected; a 10-fold reduction in the number of viable bacteria was observed when 2 x 10(3) cfu were incubated with 2 x 10(6) neutrophils and 80% autologous serum at 37 degrees C for 4 hours. To assess the effects of serum factors on killing, bactericidal assays were performed in the presence of normal human serum (NHS), heat-inactivated human serum (HIHS) and absorbed human serum (AHS); heating reduced and absorption eliminated the capacity of serum to support killing. Studies performed with mutanolysin, an enzyme that lyses type 3 pneumococci, demonstrated that the effects of HIHS and AHS on bactericidal activity were highly correlated with alterations in the ability of the sera to support phagocytosis. Studies of neutrophil activation revealed changes in the production of superoxide anion that correlated well with phagocytosis and killing; however, the results of assays of leukotriene B4 generation and degranulation (beta-glucuronidase and lactoferrin release) were more variable. In mixing experiments, the capacity of HIHS to support killing was normalized with NHS; however, the ability of AHS to promote killing was not restored with HIHS or NHS. Thus, these studies demonstrate the relatively limited capacity of human serum to support the killing of type 3 pneumococci, and they emphasize the importance of killing assays in assessing interactions between the bacterium and neutrophils.

Stem cells are a key target of environmental toxicants, but little is known about their toxicological responses. We aimed at developing an in-vitro model based on adult human stem cells to identify biomarkers of heavy metal exposure. To this end we investigated the responses of human CD34+ hematopoietic progenitor cells to hexavalent chromium (Cr[VI]) and cadmium (Cd). Parallel cultures of CD34+ cells isolated from umbilical cord blood were exposed for 48 h to 0.1 microM and 10 microM Cr(VI) or Cd. Cultures treated with 10 microM Cr(VI) or Cd showed marked cell loss. Ultrastructural analysis of surviving cells revealed prominent autophagosomes/autophagolysosomes, which is diagnostic of autophagy, associated with mitochondrial damage and replication, dilatation of the rough endoplasmic reticulum and Golgi complex, cytoplasmic lipid droplets and chromatin condensation. Treated cells did not show the morphologic hallmarks of apoptosis. Treatment with 0.1 microM Cr(VI) or Cd did not result in cell loss, but at the ultrastructural level cells showed dilated endoplasmic reticulum and evidence of mitochondrial damage. We conclude that autophagy is implicated in the response of human hematopoietic stem cells to toxic concentrations of Cr(VI) and Cd. Autophagy, which mediates cell survival and death under stress, deserves further evaluation to be established as biomarker of metal exposure.