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Lockdown measures were taken since February 2020 in Lebanon, a country already going through a socio-economic crisis, to fight the new coronavirus pandemic. The aim of this study is to evaluate the psychological impact of the lockdown in Lebanon. A cross-sectional, online survey was conducted during the lockdown period in order to punctually assess depression, anxiety symptoms as well as eating and substance use disorders using self-rating scales (the DASS-21, SCOFF and CAGE-AID respectively), while identifying factors that might affect those outcomes. Overall, 1133 participants completed the questionnaire. The DASS-21 score was positively correlated with the impact of lockdown on participants' lifestyle and lockdown duration. A highest effect on DASS-21 score was related to the intensity of other stressful life events that have happened during the last 3 months. Linear regression analysis also showed that age, monthly income, professional status, the SCOFF and CAGE-AID scores, the intensity of the lockdown's impact on lifestyle and having been through other stressful life events unrelated to the lockdown per se, were risk factors affecting significantly the DASS-21 score. Lockdown, as well as other stressful life event that have happened during the last 3 months, were therefore associated with higher depression, anxiety, and stress symptoms. These findings may guide future policy making strategies in order to prevent mental health problems in case of a pandemic concomitant with other critical stressors., Author(s): Rami Bou Khalil [sup.1] [sup.2] , Ramez Dagher [sup.1] [sup.2] , Myriam Zarzour [sup.1] [sup.2] , Ghassan Sleilaty [sup.2] [sup.3] , Hanna Abi Akl [sup.4] , Maya Kallab [sup.2] [...]

The Mediterranean region is identified as one of the world's 36 biodiversity hotspots, with the Earth's most biologically rich yet threatened areas. Lebanon is a hub for Eastern Mediterranean Region (EMR) biodiversity with 9116 characterized plant and animal species (4486 fauna and 4630 flora). Using DNA barcoding as a tool has become crucial in the accurate identification of species in multiple contexts. It can also complement species morphological descriptions, which will add to our understanding of the biodiversity and richness of ecosystems and benefit conservation projects for endangered and endemic species. In this study, we create the first reference library of standard DNA markers for mammals and plants in the EMR, with a focus on endemic and endangered species. Plant leaves were collected from different nature reserves in Mount Lebanon, and mammal samples were obtained from taxidermized museum specimens or road kills. We generated the 12S rRNA sequences of 18 mammal species from 6 orders and 13 different families. We also obtained the trnL and rbcL barcode sequences of 52 plant species from 24 different families. Twenty-five plant species and two mammal species included in this study were sequenced for the first time using these markers. Key words: Lebanon, biodiversity, Mediterranean basin, conservation, ancient DNA, DNA barcoding. La region mediterraneenne est l'une des 36 zones riches en biodiversite dans le monde ; ces regions de la terre etant parmi les plus riches biologiquement mais en meme temps les plus menacees. Le Liban constitue un point chaud pour la biodiversite dans la Mediterranee orientale avec ses 9116 especes vegetales et animales repertoriees, dont la faune compte 4486 especes et la flore4630especes. Lecodage a barres del'ADN est devenu un outil essentiel pour l'identification juste des especes dans de nombreux contextes. Il peut aussi s'averer complementaire aux descriptions morphologiques des especes, ce qui contribuera a notre connaissance de la biodiversite et de la richesse de ces ecosystemes tout en etant utile pour des projets de protection des especes menacees ou indigenes. Dans cette etude, les auteurs ont cree une premiere banque de reference pour des marqueurs de l'ADN standard chez les especes de mammiferes et de plantes de la Mediterranee orientale, l'emphase etant placee sur les especes indigenes ou menacees. Des feuilles ont ete prelevees dans differentes reserves naturelles de la region du Mont Liban, tandis que des echantillons de mammiferes ont ete obtenus a partir de specimens taxidermises dans des musees ou d'animaux tues sur la route. Les auteurs ont genere des sequences pour l'ARNr 12S chez 18 especes de mammiferes appartenant a 6 ordres et 13 familles differentes. Ils ont egalement obtenu des sequences pour les codes a barres trnL et rbcL apartir de 52 especes vegetales appartenant a 24 familles. Vingt-cinq especes vegetales et deux especes de mammiferes incluses dans ce travail ont ete sequencees pour la premiere fois a l'aide de ces marqueurs. [Traduit par la Redaction] Mots-cle's : Liban, biodiversite, bassin mediterraneen, conservation, ADN ancien, codage a barres de l'ADN., Introduction The Mediterranean region is identified as one of the world's 36 biodiversity hotspots, with the Earth's most biologically rich yet threatened areas (Myers 1990; Mittermeier et al. 1999, 2004; [...]

Arterial cardiovascular events are the leading cause of death in patients with [JAK2.sup.V617F] myeloproliferative neoplasms (MPNs). However, their mechanisms are poorly understood. The high prevalence of myocardial infarction without significant coronary stenosis or atherosclerosis in patients with MPNs suggests that vascular function is altered. The consequences of [JAK2.sup.V617F] mutation on vascular reactivity are unknown. We observe here increased responses to vasoconstrictors in arteries from [Jak2.sup.V617F] mice resulting from a disturbed endothelial NO pathway and increased endothelial oxidative stress. This response was reproduced in WT mice by circulating microvesicles isolated from patients carrying [JAK2.sup.V617F] and by erythrocyte-derived microvesicles from transgenic mice. Microvesicles of other cellular origins had no effect. This effect was observed ex vivo on isolated aortas, but also in vivo on femoral arteries. Proteomic analysis of microvesicles derived from [JAK2.sup.V617F] erythrocytes identified increased expression of myeloperoxidase as the likely mechanism accounting for their effect. Myeloperoxidase inhibition in microvesicles derived from [JAK2.sup.V617F] erythrocytes suppressed their effect on oxidative stress. Antioxidants such as simvastatin and W-acetyl cysteine improved arterial dysfunction in [Jak2.sup.V617F] mice. In conclusion, [JAK2.sup.V617F] MPNs are characterized by exacerbated vasoconstrictor responses resulting from increased endothelial oxidative stress caused by circulating erythrocyte-derived microvesicles. Simvastatin appears to be a promising therapeutic strategy in this setting., Introduction Bcr/Abl-negative myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the proliferation of particular hematopoietic lineages without blockage in cell maturation. They include polycythemia vera, essential thrombocythemia, [...]

The antimicrobial stewardship program (ASP) at Saint Georges Hospital University Medical Center (SGHUMC), a 400-bed tertiary-care center in Beirut, Lebanon, requires an infectious disease (ID) specialist to preauthorize use of [...]

Tularemia, also known as rabbit fever, is a zoonotic disease caused by the gram-negative bacterium Francisella tularensis. Natural transmission to humans occurs through a variety of routes, including tick and [...]

In response to viral pathogens, the host upregulates antiviral genes that suppress translation of viral mRNAs. However, induction of such antiviral responses may not be exclusive to viruses, as the pathways lie at the intersection of broad inflammatory networks that can also be induced by bacterial pathogens. Using a model of Gram-negative sepsis, we show that propagation of kidney damage initiated by a bacterial origin ultimately involves antiviral responses that result in host translation shutdown. We determined that activation of the eukaryotic translation initiation factor 2-[alpha] kinase 2/ eukaryotic translation initiation factor 2[alpha] (Eif2ak2/Eif2[alpha]) axis is the key mediator of translation initiation block in late-phase sepsis. Reversal of this axis mitigated kidney injury. Furthermore, temporal profiling of the kidney translatome revealed that multiple genes involved in formation of the initiation complex were translationally altered during bacterial sepsis. Collectively, our findings imply that translation shutdown is indifferent to the specific initiating pathogen and is an important determinant of tissue injury in sepsis., IntroductionBacterial sepsis remains the leading cause of death in intensive care units. It is a highly dynamic pathological state in which a wide array of pro- and antiinflammatory pathways are [...]

Background: Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. Methods: We used high-resolution positron emission tomography with [[sup.18]F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence. Results: Twelve individuals participated in our study. Among participants reporting a craving response (9 of 12), exposure to the cocaine cues significantly decreased [[sup.18]F]fallypride binding potential ([BP.sub.ND]) values in the medial orbitofrontal cortex and striatum. In all 12 participants, individual differences in the magnitude of craving correlated with [BP.sub.ND] changes in the medial orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate, and striatum. Consistent with the presence of autoreceptors on mesostriatal but not mesocortical DA cell bodies, midbrain [BP.sub.ND] values were significantly correlated with changes in [BP.sub.ND] within the striatum but not the cortex. The lower the midbrain D2 receptor levels, the greater the striatal change in [BP.sub.ND] and self-reported craving. Limitations: Limitations of this study include its modest sample size, with only 2 female participants. Newer tracers might have greater sensitivity to cortical DA release. Conclusion: In people with cocaine use disorders, the presentation of drug-related cues induces DA release within cortical and striatal regions. Both effects are associated with craving, but only the latter is regulated by midbrain autoreceptors. Together, the results suggest that cortical and subcortical DA responses might both influence drug-focused incentive motivational states, but with separate regulatory mechanisms., Introduction The prefrontal cortex (PFC) integrates and interprets sensory information, processing value, directing attention, and planning actions based on experience. (1,2) In cocaine-dependent individuals, these regions and processes are engaged [...]

Data from the dot-com boom-bust episode suggest that growth opportunities played an important role in explaining firms ' financing strategy during this understudied episode. The low leverage of this sector [...]

Background Previous studies have suggested that the prevalence of BRCA1 and 2 mutations in the Lebanese population is low despite the observation that the median age of breast cancer diagnosis is significantly lower than European and North American populations. We aimed at reviewing the rates and patterns of BRCA1/2 mutations found in individuals referred to the medical genetics unit at the American University of Beirut. We also evaluated the performance of clinical prediction tools. Methods We retrospectively reviewed the cases of all individuals undergoing BRCA mutation testing from April 2011 to May 2016. To put our findings in to context, we conducted a literature review of the most recently published data from the region. Results Two-hundred eighty one individuals were referred for testing. The prevalence of mutated BRCA1 or 2 genes were 6 and 1.4% respectively. Three mutations accounted for 54% of the pathogenic mutations found. The BRCA1 c.131G > T mutation was found among 5/17 (29%) unrelated subjects with BRCA1 mutation and is unique to the Lebanese and Palestinian populations. For patients tested between 2014 and 2016, all patients positive for mutations fit the NCCN guidelines for BRCA mutation screening. The Manchester Score failed to predict pathogenic mutations. Conclusion The BRCA1 c.131G > T mutation can be considered a founder mutation in the Lebanese population detected among 5/17 (29%) of individuals diagnosed with a mutation in BRCA1 and among 7/269 families in this cohort. On review of recently published data regarding the landscape of BRCA mutations in the Middle East and North Africa, each region appears to have a unique spectrum of mutations. Keywords: BRCA1, BRCA2, Manchester score, Familial, Lebanon, Author(s): Chantal Farra[sup.1] , Christelle Dagher[sup.2] , Rebecca Badra[sup.1] , Miza Salim Hammoud[sup.2] , Raafat Alameddine[sup.2] , Johnny Awwad[sup.3] , Muhieddine Seoud[sup.3] , Jaber Abbas[sup.4] , Fouad Boulos[sup.1] , Nagi [...]

Many empirical exercises estimating demand functions, whether in energy economics or other fields, are concerned with estimating dynamic effects of price and income changes over time. This paper first reviews a number of commonly used dynamic demand specifications to highlight the implausible a priori restrictions that they place on short and long-run elasticities. Such problems are easily avoided by adopting a general-to-specific modeling methodology. Second, it discusses functional forms and estimation issues for getting point estimates and associated standard errors for both short and long-run elasticities--key information that is missing from many published studies. Third, our proposed approach is illustrated using a dataset on Minnesota residential electricity demand. Keywords: SR elasticity, LR elasticity, Demand function, ADL, INTRODUCTION Many empirical exercises estimating demand and supply functions are concerned with estimating dynamic effects of price and income changes over time. (1) Researchers are typically interested in estimating both [...]

Centrosome amplification has long been recognized as a feature of human tumours; however, its role in tumorigenesis remains unclear (1). Centrosome amplification is poorly tolerated by non-transformed cells and, in the absence of selection, extra centrosomes are spontaneously lost (2). Thus, the high frequency of centrosome amplification, particularly in more aggressive tumours (3), raises the possibility that extra centrosomes could, in some contexts, confer advantageous characteristics that promote tumour progression. Using a three-dimensional model system and other approaches to culture human mammary epithelial cells, we find that centrosome amplification triggers cell invasion. This invasive behaviour is similar to that induced by overexpression of the breast cancer oncogene ERBB2 (ref. 4) and indeed enhances invasiveness triggered by ERBB2. Our data indicate that, through increased centrosomal microtubule nucleation, centrosome amplification increases Rac1 activity, which disrupts normal cell-cell adhesion and promotes invasion. These findings demonstrate that centrosome amplification, a structural alteration of the cytoskeleton, can promote features of malignant transformation., The centrosome is the major microtubule-organizing centre in mammalian cells and comprises of a pair of centrioles surrounded by the pericentriolar material (5). Centrosome abnormalities, usually increased numbers, are common [...]

X-linked Alport syndrome is a form of progressive renal failure caused by pathogenic variants in the COL4A5 gene. More than 700 variants have been described and a further 400 are estimated to be known to individual laboratories but are unpublished. The major genetic testing laboratories for X-linked Alport syndrome worldwide have established a Web-based database for published and unpublished COL4A5 variants (https://grenada.lumc.nl/ LOVD2/COL4A/home.php?select_db=COL4A5). This conforms with the recommendations of the Human Variome Project: it uses the Leiden Open Variation Database (LOVD) format, describes variants according to the human reference sequence with standardized nomenclature, indicates likely pathogenicity and associated clinical features, and credits the submitting laboratory. The database includes non-pathogenic and recurrent variants, and is linked to another COL4A5 mutation database and relevant bioinformatics sites. Access is free. Increasing the number of COL4A5 variants in the public domain helps patients, diagnostic laboratories, clinicians, and researchers. The database improves the accuracy and efficiency of genetic testing because its variants are already categorized for pathogenicity. The description of further COL4A5 variants and clinical associations will improve our ability to predict phenotype and our understanding of collagen IV biochemistry. The database for X-linked Alport syndrome represents a model for databases in other inherited renal diseases. Keywords Alport syndrome * Gene variant * DNA database * Genetic testing * Inherited renal disease, Alport syndrome Alport syndrome is an inherited cause of renal failure that affects at least one in 50,000 individuals [1]. Eighty-five percent of families have X-linked disease (MIM 301050) [2], [...]

Background This study determined the family history and clinical features that suggested autosomal recessive rather than X-linked Alport syndrome. Methods All patients had the diagnosis of Alport syndrome and the mode of inheritance confirmed by genetic testing, and underwent examination at a single centre. Results Patients comprised 9 males and 6 females with autosomal recessive Alport syndrome, and 18 males and 22 females with X-linked disease. Fourteen (93%) individuals with autosomal recessive Alport syndrome developed early end-stage renal failure, all 15 had hearing loss, and most had lenticonus (12, 80%), and a central (13, 87%) or peripheral (13, 87%) retinopathy. These features occurred as often as in males with X-linked disease. Females with autosomal recessive inheritance were less likely to have an affected family member in another generation (p =0.01) than females with X-linked disease. They were more likely to have renal failure (p = 0.003), hearing loss (p =0.02) and lenticonus (p < 0.001). Fifty percent had a central retinopathy compared with 18% with X-linked disease (p = 0.14), but peripheral retinopathy prevalence was not different (p = 0.64). Nonsense mutations accounted for 67% (8/12) of these disease-causing mutations. Conclusions Autosomal recessive inheritance is increased in females with Alport syndrome and early onset renal failure, hearing loss, lenticonus, and, possibly, central retinopathy. Keywords Alport syndrome * Retinopathy * Nonsense mutations, Introduction Alport syndrome is characterised by hematuria, progressive renal failure, hearing loss, lenticonus, perimacular flecks and a peripheral coalescing retinopathy [1, 2]. X-linked inheritance accounts for 85% of patients [3] [...]

Byline: Antoine. Lutfallah, Christine. Dagher, Nicole. Naccache, Patricia. Yazbeck Sir, Progressive supranuclear palsy (PSP), also known as Steele-Richardson-Olszewski disease, is a neurodegenerative disorder affecting the basal ganglia and characterised by [...]

The involvement of whole-chromosome aneuploidy in tumorigenesis is the subject of debate, in large part because of the lack of insight into underlying mechanisms. Here we identify a mechanism by which errors in mitotic chromosome segregation generate DNA breaks via the formation of structures called micronuclei. Whole-chromosome-containing micronuclei form when mitotic errors produce lagging chromosomes. We tracked the fate of newly generated micronuclei and found that they undergo defective and asynchronous DNA replication, resulting in DNA damage and often extensive fragmentation of the chromosome in the micronucleus. Micronuclei can persist in cells over several generations but the chromosome in the micronucleus can also be distributed to daughter nuclei. Thus, chromosome segregation errors potentially lead to mutations and chromosome rearrangements that can integrate into the genome. Pulverization of chromosomes in micronuclei may also be one explanation for 'chromothripsis' in cancer and developmental disorders, where isolated chromosomes or chromosome arms undergo massive local DNA breakage and rearrangement., Whole-chromosome aneuploidy is a major feature of cancer genomes, yet its role in tumour development remains controversial (1,2). This contrasts with chromosome breaks and rearrangements, which are known to produce [...]

This paper describes the structural performance of an innovative wood plastic composite (WPC) sheet piling. Tensile coupon tests were performed to determine tensile strength and modulus over a range of strain rates for both WPC and specimens cut from commercially available vinyl sheet piles. Full scale four-point bending tests were conducted up to failure on 20 sets of joined pairs of WPC Z-piles with four different span lengths. For comparison, bending and coupon-level tension tests were also conducted on commercially available vinyl Z-piles and coupons cut from them. The coupon-level tests indicated that WPC had on average a 14% greater modulus than the vinyl specimens in the initial linear range, defined as between 10 and 40% of the respective material's ultimate tensile strength. However, if the modulus is computed over the same stress range of 10-40% of the WPC ultimate tensile strength, both materials have a similar modulus. The vinyl had a tensile strength 3.6 times that of the WPC. During the bending tests, the hollow cross section WPC Z-piles failed primarily in bending-induced tension, while the solid vinyl Z-piles exhibited buckling of the compression flange. Creep rupture testing was conducted for pair of WPC Z-piles in a four-point bending setup to determine long-term load- carrying capacity. No loss of load-carrying capacity was observed during the 90-day test and creep rates generally decreased during the test. However, creep deflections were larger than what would normally be exhibited by wood structural members. While additional studies are needed to address the effects of water absorption on WPC properties, the findings show promise for wood plastic composite light duty sheet piling retaining wall structures. DOI: 10.1061/(ASCE)MT.1943-5533.0000132 CE Database subject headings: Composite materials; Composite structures; Sheet piles; Stiffness; Creep. Author keywords: Composite materials; Composite structures; Sheet piles; Stiffness; Creep.

Background: In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic-pituitary-adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. Methods: In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Results: Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Limitations: Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. Conclusion: We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group., Introduction The hypothalamic-pituitary-adrenal (HPA) axis is one of the most important neuroendocrine stress systems. (1) Dysregulations of the HPA axis are implicated in the pathophysiology of stress-related disorders, such as [...]

Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) and is characterized by widespread tubular and microvascular damage. The tumor suppressor p53 is upregulated after IRI and contributes to renal injury in part by promoting apoptosis. Acute, short-term inhibition of p53 with pifithrin-[alpha] conveys significant protection after IRI. The hypoxia-inducible factor-1 (HIF-1) pathway is also activated after IRI and has opposing effects to those promoted by p53. The balance between the HIF-1 and p53 responses can determine the outcome of IRI. In this manuscript, we investigate whether p53 regulates the HIF-1 pathway in a rodent model of IRI. HIF-1[alpha] is principally expressed in the collecting tubules (CT) and thick ascending limbs (TAL) under physiological conditions. However, inhibition of p53 with pifithrin-[alpha] increases the faint expression of HIF-1[alpha] in proximal tubules (PT) under physiological conditions. Twenty-four hours after IRI, HIF-1[alpha] expression is decreased in both CT and TAL. HIF-1[alpha] expression in the PT is not significantly altered after IRI. Acute inhibition of p53 significantly increases HIF-1[alpha] expression in the PT after IRI. Additionally, pifithrin-[alpha] prevents the IRI-induced decrease in HIF-1[alpha] in the CT and TAL. Parallel changes are observed in the HIF-1[alpha] transcriptive target, carbonic anhydrase-9. Finally, inhibition of p53 prevents the dramatic changes in Von Hippel-Lindau protein morphology and expression after IRI. We conclude that activation of p53 after IRI mitigates the concomitant activation of the protective HIF-1 pathway. Modulating the interactions between the p53 and HIF-1 pathway can provide novel options in the treatment of AKI. acute kidney injury; acute renal failure; hypoxia-inducible factor-1[alpha]; Von Hippel-Lindau protein

Tamm-Horsfall protein (THP) is a glycoprotein with unclear functions expressed exclusively in thick ascending limbs (TAL) of the kidney. Its role in ischemic acute kidney injury is uncertain, with previous data suggesting a possible negative effect by enhancing cast formation and promoting inflammation. Using a recently characterized THP knockout mouse (THP-/-), we investigated the role of THP in renal ischemia-reperfusion injury (IRI). In wild-type mice (THP+/+), THP expression was increased by injury. THP-/- mice developed more functional and histological renal damage after IRI compared with THP+/+. THP-/- kidneys showed more inflammation and tubular necrosis. Cast formation correlated with the severity of injury and was independent of THP presence. THP absence was associated with a more necrotic, rather than apoptotic, phenotype of cell death. The outer medulla was predominantly affected, where signifcant interstitial neutrophil infiltration was detected in proximity to injured S3 proximal tubular segments and TAL. This coincided with an enhanced expression of the innate immunity receptor Toll-like receptor 4 (TLR4) in S3 segments of THP-/- compared with THP+/+ mice. Specifically, a basolateral S3 expression of TLR4 was more evident in THP-/- kidneys compared with a more apical distribution in THP+/+. Such basolateral location for TLR4 allows a greater interaction with proinflammatory ligands present in the interstitium during ischemia. In conclusion, we are showing a completely novel role for a very old protein in the setting of renal injury. Our data suggest that THP stabilizes the outer medulla in the face of injury by decreasing inflammation, possibly through an effect on TLR4. acute kidney injury; Toll-like receptors; uromodulin; ischemia-reperfusion

Cyclooxygenase-2 (Cox-2) is an inducible enzyme responsible for the formation of inflammatory prostanoids such as prostaglandins and thromboxane. Its role in the pathophysiology of inflammatory states like sepsis is increasingly recognized. Recently, we demonstrated that sepsis up-regulates the endotoxin receptor Toll-like receptor 4 (TLR4) in rat kidney. Because Cox-2 is one of the downstream products of TLR4 activation, we hypothesized that sepsis-induced changes in renal Cox-2 expression are TLR4 dependent. Indeed, we show that in Sprague-Dawley rats, cecal ligation and puncture (a sepsis model) increases Cox-2 expression in cortical and medullary thick ascending loops (cTAL and mTAL, respectively) as well as inner medullary collecting ducts. These are all sites of increased TLR4 expression during sepsis. To determine the actual dependence on TLR4, we measured Cox-2 expression in wild-type and mutant mice which harbor a TLR4 gene deletion (TLR4-/-). In wild-type mice, sepsis increased Cox-2 expression in proximal tubules, cTAL, and mTAL. In contrast, septic TLR4-/- mice showed no significant increase in cTAL or mTAL Cox-2 expression. Furthermore, renin was absent from juxtaglomerular cells of TLR4-/- mice. We conclude that the dependence of sepsis-induced renal Cox-2 expression on TLR4 is tubule specific. The TLR4-dependent Cox-2 expression is mostly restricted to cortical and medullary thick ascending loops of Henle that characteristically express and secrete Tamm-Horsfall protein. Toll-like receptors; renin; Tamm-Horsfall protein; macula densa; cyclooxygenase

ABSTRACT Field studies were used in 1999/2000 and 2000/2001 to investigate 'Black Plastic', 'Weed Barrier' and 'Pine Bark Nugget' (treatments) for purple nutsedge (Cyperus rotundus) control in field-grown feverfew (Tanacetum [...]

An important issue in wireless sensor networks is the limited energy and bandwidth resources. A novel theory is developed here for maximizing the lifetime of unicast multihop wireless sensor networks. An optimal centralized solution is presented in the form of an iterative algorithm. The algorithm attempts to find a Pareto-optimal (PO) solution. In the first iteration, the minimum lifetime of the network is maximized. If the solution is not PO, a second iteration is performed which maximizes the second minimum lifetime, subject to the minimum lifetime being maximum. At the nth iteration, the algorithm maximizes the nth minimum lifetime subject to the (n - 1)th minimum lifetime being maximum, subject to the (n - 2)th minimum lifetime being maximum, etc. The algorithm can be stopped at any iteration n. The presented solution assumes static network conditions. Index Terms--Communication system routing, routing, sensor networks.

The objective of this study was to characterize the pharmacokinetics (PK) of intravenous busulfan in pediatric patients and provide dosing recommendations. Twenty-four pediatric patients were treated with intravenous busulfan, 1.0 [...]

We consider a network of imaging sensors. We address the problem of energy-efficient communication of the measurements of the sensors. A novel algorithm is presented for the purpose of exploiting intersensor and intrasensor correlation, which is inherent in a network of imaging sensors. The collaborative algorithm is used in conjunction with a cooperative multihop routing strategy to maximize the lifetime of the network. The algorithm is demonstrated to achieve an average gain in the lifetime as high as 3.2 over previous methods. OCIS codes: 100.0100, 200.3050.

The continuous reduction in size of devices, such as integrated circuits or microelectro-mechanical systems (MEMS), results in the need to control with better and better resolution the materials involved, and in particular the electrical properties of the insulating and semiconducting parts. In this paper we propose an approach applicable to space charge measurement methods for improving the resolution to the nanometer range by using femtosecond laser pulses. It is shown that a resolution of about 60 nm in Si[O.sub.2] can be achieved with thermal and pressure wave propagation methods. Concerning the pulsed electro-acoustic method, the interfacial displacement as small as 100 fm can be measured at THz rate. Index Terms--Space charge, nanometer resolution, femtosecond laser, thermal method, pressure wave propagation method, pulsed electro-acoustic method.

An algorithm is presented that efficiently exploits inter- and intrasensor correlation for the purpose of power-constrained distributed transmission of sensor-network imagery. Results demonstrate that gains in network lifetime up to 114e obtained when using the suggested algorithm with lossless compression, and much larger gains are achieved when lossy compression is employed.

In this paper, a fast incremental principal non-Gaussian directions analysis algorithm, called IPCA-ICA, is introduced. This algorithm computes the principal components of a sequence of image vectors incrementally without estimating the covariance matrix (so covariance-free) and at the same time transforming these principal components to the independent directions that maximize the non-Gaussianity of the source. Two major techniques are used sequentially in a real-time fashion in order to obtain the most efficient and independent components that describe a whole set of human faces database. This procedure is done by merging the runs of two algorithms based on principal component analysis (PCA) and independent component analysis (ICA) running sequentially. This algorithm is applied to face recognition problem. Simulation results on different databases showed high average success rate of this algorithm compared to others. Index Terms--IPCA-ICA, Principal component analysis (PCA), independent component analysis (ICA), principal non-Gaussian directions, image processing, blind source separation.

Toll-like receptors (TLRs) are now recognized as the major receptors for microbial pathogens on cells of the innate immune system. Recently, TLRs were also identified in many organs including the kidney. However, the cellular distribution and role of these renal TLRs remain largely unknown. In this paper, we investigated the expression of TLR4 in a cecal ligation and puncture (CLP) model of sepsis in Sprague-Dawley rats utilizing fluorescence microscopy. In sham animals, TLR4 was expressed predominantly in Tamm-Horsfall protein (THP)-positive tubules. In CLP animals, TLR4 expression increased markedly in all tubules (proximal and distal), glomeruli, and the renal vasculature. The staining showed a strong apical distribution in all tubules. A moderately less intense cellular signal colocalized partially with the Golgi apparatus. In addition, kidneys from septic rats showed increased expression of CD14 and THP. They each colocalized strongly with TLR4, albeit in different tubular segments. We also imaged the kidneys of live septic animals with two-photon microscopy after fluorescent lipopolysaccharide (LPS) injection. Within 10 min, LPS was seen at the brush border of some proximal tubules. Within 60 min, LPS was fully cytoplasmic in proximal tubules. Conversely, distal tubules showed no LPS uptake. We conclude that TLR4, CD14, and THP have specific renal cellular and tubular expression patterns that are markedly affected by sepsis. Systemic endotoxin can freely access the tubular and cellular sites where these proteins are present. Therefore, locally expressed TLRs and other interacting proteins could potentially modulate the renal response to systemic sepsis. TLR4; CD14; Tamm-Horsfall protein; cecal ligation and puncture: lipopolysaccharide

This study addresses the development and structural testing of a hybrid sheathing panel designed to improve the lateral resistance of light wood-frame shear walls. The panel consists of thin outer sheets of oriented-strand board (OSB) bonded to strips of fiber-reinforced polymer (FRP) that are sandwiched between the OSB panels at the edges. The FRP-reinforced panel material selection and fabrication are summarized. Monotonic and cyclic tests were conducted to assess the performance of single-connector sheathing-to-framing connections using both OSB and FRP-reinforced OSB. Twenty-four full-scale shear walls were tested under monotonic and cyclic racking loads to determine the benefits of FRP-reinforced OSB to wall lateral load resistance. For a 102 mm perimeter nail spacing, FRP-reinforced OSB-sheathed walls exhibited increases in peak capacity and energy dissipation under cyclic loading of 27 and 73%, respectively, compared to walls sheathed with conventional OSB. Based on these experimental results, FRP-reinforced OSB panels appear to have significant potential for increasing the energy dissipation capacity and lateral load resistance of wood-frame structures subjected to extreme lateral loads. However, their full utilization will require higher strengths for critical shear wall components such as tension ties and framing interconnections, as well as improvements in sheathing-to-framing fastener performance. DOI: 10.1061/(ASCE)0733-9445(2006)132:1(153) CE Database subject headings: Timber construction; Fiber reinforced polymers; Shear walls; Seismic design; Panels; Wooden structures.

Obstruction of the upper urinary tract induces a progressive loss in renal mass through apoptotic renal cell death. Although TNF-[alpha] has been implicated in ischemia-reperfusion-induced apoptotic renal cell death, its role in obstructive renal cell apoptosis remains unknown. To study this, male Sprague-Dawley rats were subjected to left unilateral ureteral obstruction vs. sham operation. Twenty-four hours before surgery and every 84 h thereafter, rats received either vehicle or a pegylated form of soluble TNF receptor type 1 (PEG-sTNFR1). The kidneys were harvested 1, 3, or 7 days postoperatively, and tissue samples were subsequently analyzed for TNF-[alpha] (ELISA, RT-PCR), Fas ligand (RT-PCR), apoptosis (TUNEL, ELISA), and caspase 8 and 3 activity (Western blot). Renal obstruction induced increased tissue TNF-[alpha] and Fas ligand mRNA levels, TNF-[alpha] protein production, apoptotic renal tubular cell death, and elevated caspase 8 and 3 activity, whereas treatment with PEG-sTNFR1 significantly reduced obstruction-induced TNF-[alpha] production, renal tubular cell apoptosis, and caspase activity. PEG-sTNFR1 did not significantly alter Fas ligand expression. These results demonstrate that TNF-[alpha] mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling and identify TNF-[alpha] neutralization as a potential therapeutic option for the amelioration of obstruction-induced renal injury. inflammation; tumor necrosis factor receptor 1; kidney; cytokine

Tetracyclines exhibit significant anti-inflammatory properties, inhibit matrix metalloproteinases (MMPs), and are protective in models of ischemiareperfusion injury (IRI). Both inflammatory cascades and MMP activation have been demonstrated to modulate microvascular permeability. Because increased microvascular permeability occurs during IRI in a variety of organ systems including the kidney, we hypothesized that minocycline, a semisynthetic tetracycline, would diminish microvascular leakage during renal IRI. To test this hypothesis, we used intravital 2-photon microscopy to examine leakage of fluorescent dextrans from the vasculature in a rodent model of IRI. Minocycline significantly reduced the extent of dextran (500 kDa) leakage from the renal microvasculature 24 h after ischemia. Although minocycline diminished leukocyte accumulation in the kidney following ischemia, areas of leukocyte accumulation did not correlate with areas of microvascular permeability in either the saline- or minocycline-pretreated animals. Minocycline diminished the perivascular increase in MMP-2 and MMP-9, as well as the increase in MMP-2 activity 24 h after ischemia. ABT-518, a specific inhibitor of MMP-2 and MMP-9, also significantly reduced the extent of dextran (500 kDa) leakage from the renal microvasculature 24 h after ischemia. Our results indicate that minocycline mitigates the renal microvascular permeability defect following IRI. This effect is spatially distinct from the effect of minocycline on leukocyte accumulation and may be related to diminished activity of MMPs on the integrity of the perivascular matrix. kidney; tetracycline; vascular permeability; matrix metalloproteinase

Minocycline inhibits apoptosis and inflammation in a rat model of ischemic renal injury. Am J Physiol Renal Physiol 287: F760-F766, 2004. First published June 1, 2004; 10.1152/ajprenal.00050.2004.--Tetracyclines exhibit significant anti-inflammatory properties in a variety of rheumatologic and dermatologic conditions. They have also been shown to inhibit apoptosis in certain neurodegenerative disorders. Because ischemic renal injury is characterized by both apoptosis and inflammation, we investigated the therapeutic potential of tetracyclines in a rat model of renal ischemiareperfusion. Male Sprague-Dawley rats underwent bilateral renal artery clamp for 30 min followed by reperfusion and received either minocycline or saline for 36 h before ischemia. Minocycline reduced tubular cell apoptosis 24 h after ischemia as determined by terminal transferase-mediated dUTP nick end-labeling staining and nuclear morphology. It also decreased cytochrome c release into the cytoplasm and reduced upregulation of p53 and Bax after ischemia. The minocycline-treated group showed a significant reduction in tubular injury and cast formation. In addition, minocycline reduced the number of infiltrating leukocytes, decreased leukocyte chemotaxis both in vitro and ex vivo, and downregulated the expression of ICAM-1. Serum creatinine 24-h postischemia was significantly reduced in the minocycline-treated group. We conclude that minocycline has potent antiapoptotic and anti-inflammatory properties and protects renal function in this model of ischemia-reperfusion. Tetracyclines are among the safest and best-studied antibiotics. They are thus attractive candidates for the therapy of human ischemic acute renal failure. tetracyclines; acute renal failure; cytochrome c; p53

We develop novel methods for compressing volumetric imagery that has been generated by single-platform (mobile) range sensors. We exploit the correlation structure inherent in multiple views in order to improve compression efficiency. We show that, for lossless compression, three-dimensional volumes compress more efficiently than two-dimensional (2D) images by a factor of 60%. Furthermore, our error metric for lossy compression suggests that accumulating more than nine range images in one volume before compression yields as much as a 99% improvement in compression performance over 2D compression. OCIS codes: 100.6890, 100.200, 110.6880, 200.3050, 200.4560.

Two leaky- bucket rate allocation methods that provide constant quality video under buffer constraint are proposed. The goal is to allocate the capacity of the channel between sequences to achieve constant quality across all sequences and the results demonstrate substantial benefits from the use of Motion JPEG2000.

Rho GTPases are critical for actin cytoskeletal regulation, and alterations in their activity may contribute to altered cytoskeletal organization that characterizes many pathological conditions, including ischemia. G protein activity is a function of the ratio of GTP-bound (active) to GDP-bound (inactive) protein, but the effect of altered energy metabolism on Rho protein activity has not been determined. We used antimycin A and substrate depletion to induce depletion of intracellular ATP and GTP in the kidney proximal tubule cell line LLC-P[K.sub.10] and measured the activity of RhoA, Rac1, and Cdc42 with GTPase effector binding domains fused to glutathione S-transferase. RhoA activity decreased in parallel with the concentration of ATP and GTP during depletion, so that by 60 min there was no detectable RhoA-GTP, and recovered rapidly when cells were returned to normal culture conditions. Dissociation of the membrane-actin linker ezrin, a target of RhoA signaling, from the cytoskeletal fraction paralleled the decrease in RhoA activity and was augmented by treatment with the Rho kinase inhibitor Y27632. The activity of Cdc42 did not decrease significantly during depletion or recovery. Rac1 activity decreased moderately to a minimum at 30 min of depletion but then increased from 30 to 90 min of depletion, even as ATP and GTP levels continued to fall. Our data are consistent with a principal role for RhoA in cytoskeletal reorganization during ischemia and demonstrate that the activity of Rho GTPases can be maintained even at low GTP concentrations. Rac; Cdc42; actin; ezrin; adenosine 5'-triphosphate; guanosine 5'-triphosphate

Apoptosis is an important mode of cell death under both physiological and pathophysiological conditions. Numerous techniques are available for the study and quantitation of apoptosis in cell culture, but only few are useful when applied to complex tissues. Among these, the terminal transferase-mediated dUTP nick end-labeling (TUNEL) assay remains the most widely used technique. However, its specificity and sensitivity for the detection of apoptosis remain controversial. We developed a technique consisting of staining live cells and tissues with Hoechst 33342 and the vital dye propidium iodide (PI), followed by fixation and the TUNEL reaction. We demonstrate excellent retention of PI in necrotic cells after fixation. We also examined the distribution of TUNEL staining among necrotic and apoptotic cells in various models of cell injury in vitro and in vivo. We show that the sensitivity of the TUNEL varied between 61 and 90% in the models examined. The specificity exceeded 87% in all models but fell to 70% when a predominantly necrotic injury was induced. This novel and simple method will permit the determination of indices of sensitivity and specificity for the TUNEL assay in other tissues and experimental conditions. necrosis; propidium iodide; two-photon microscopy; ischemia

Echinacea species grown as medicinal plants are a potential economic crop for farmers in Mississippi. Field experiment was used to compare the survival, growth, and mineral composition of E. angustifolia, [...]

Optical microscopy, when applied to living animals, provides a powerful means of studying cell biology in the most physiologically relevant setting. The ability of two-photon microscopy to collect optical sections deep into biological tissues has opened up the field of intravital microscopy to high-resolution studies of the brain, lens, skin, and tumors. Here we present examples of the way in which two-photon microscopy can be applied to intravital studies of kidney physiology. Because the kidney is easily externalized without compromising its function, microscopy can be used to evaluate various aspects of renal function in vivo. These include cell vitality and apoptosis, fluid transport, receptor-mediated endocytosis, blood flow, and leukocyte trafficking. Efficient two-photon excitation of multiple fluorophores permits comparison of multiple probes and simultaneous characterization of multiple parameters and yields spectral information that is crucial to the interpretation of images containing uncharacterized autofluorescence. The studies described here demonstrate the way in which two-photon microscopy can provide a level of resolution previously unattainable in intravital microscopy, enabling kinetic analyses and physiological studies of the organs of living animals with subcellular resolution. fluorescence; multiphoton; in vivo

Results reveal that the GTP-bound Rac proteins sustain the phagocytic NADPH oxidase activity, while membrane-bound GTPase activating proteins mediate the deactivation of NADPH oxidase. Data suggest that the deactivation causes termination of the production of the superoxide.

Liver regeneration after partial hepatectomy results primarily from the simple division of mature hepatocytes. However, during embryonic and fetal development or in circumstances under which postnatal hepatocytes are injured, organ regeneration is believed to occur from a compartment of epithelial liver stem or progenitor cells with biliary and hepatocytic bipotentiality. The ability to identify, isolate, and transplant epithelial liver stem cells from fetal liver would greatly facilitate the treatment of hepatic diseases currently requiring orthotopic liver transplantation. Here we report the identification and immortalization by retrovirus-mediated transfer of the simian virus 40 large T antigen gene of primate fetal epithelial liver cells with a dual hepatocytic biliary phenotype. These cells grow indefinitely in vitro and express the liver epithelial cell markers cytokeratins 8/18, the hepatocyte-specific markers albumin and [alpha]-fetoprotein, and the biliary-specific markers cytokeratins 7 and 19. Bipotentiality of gene expression was confirmed by clonal analysis initiated from single cells. Endogenous telomerase also is expressed constitutively. After orthotopic transplantation via the portal vein, [approximately equal to] 50% of the injected cells integrated into the liver parenchyma of athymic mice without tumorigenicity. Three weeks after transplantation, cells having seeded in the liver parenchyma expressed both albumin and a-fetoprotein but had lost expression of cytokeratin 19. These results provide strong evidence for the existence of a bipotent epithelial liver stem cell in nonhuman primates. This unlimited source of donor cells also should enable the establishment of a model of allogenic liver cell transplantation in a large animal closely related to humans and shed light on important questions related to liver organogenesis and differentiation.