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Introduction:BMPR2mutation is the most common genetic cause of pulmonary arterial hypertension (PAH). Loss of BMPR2causes pulmonary arterial (PA) endothelial cell (EC) dysfunction and impairs EC-mediated suppression of smooth muscle cells proliferation. These are characteristic features of PAH vascular cells as is the presence of DNA damage that can be induced by oxidative stress. We previously showed that EC-Bmpr2-/-mice have persistent pulmonary hypertension (PH) with reoxygenation after hypoxia. However, the role of DNA damage in causing persistent PH related to loss of BMPR2 and oxidative stress is unknown.Hypothesis:We hypothesize that loss of BMPR2 causes unrepaired DNA damage and persistent PH by altering the expression of genes that maintain EC homeostasis.Methods and Results:DNA damage assessed by γH2AX foci was observed in PAEC of EC-Bmpr2-/-mice in room air, that was more extensive after reoxygenation (10% hypoxia for 3 weeks followed by recovery in room-air for 4 weeks). Deletion of the DNA damage sensor ataxia-telangiectasia mutated (ATM) in EC of mice (EC-Atm-/-) also resulted in persistent DNA damage and PH. RNA sequencing of PAEC after reoxygenation in EC-Bmpr2-/-and EC-Atm-/-mice vs. controls showed downregulated EC differentiation and development genes enriched in biding motifs for Foxf1, atranscription factor associated with DNA repair and angiogenesis. Foxf1expression was reduced in PAEC with loss of BMPR2 or ATM. Loss of Foxf1decreased angiogenic genes Cldn5and Vegfr2, and DNA damage response genes Atmand p53, and impaired PAEC migration and tube formation. Foxf1overexpression increased these genes in PAEC. Immunohistochemistry showed decreased FOXF1 in PAEC of human pulmonary vascular lesions. Delivery of Foxf1to EC-Bmpr2-/-mice with an AAV2-peptide targeting the PA endothelium attenuated DNA damage in PAEC, restored angiogenesis genes and completely reversed persistent PH returning right ventricular systolic pressure to normal levels.Conclusions:We link loss of BMPR2 and DNA damage sensing in PAEC to persistent DNA damage and PAH and show that both are mediated by reduced FOXF1. In EC-Bmpr2-/-mice, Foxf1gene therapy attenuated DNA damage restored angiogenesis genes, and prevented persistent PH.

Current polysaccharide conjugate vaccine manufacturing process involves conjugation of polysaccharide with protein followed by separation/purification of the conjugate from reaction components and free polysaccharide/protein, by preparative Size-Exclusion Chromatography (SEC). Each SEC fraction is analyzed and pooled the conjugate based on its molar mass and absence of free polysaccharide. In the present work, we have evaluated in-line Multi Angle Light Scattering (MALS) as a Process Analytical Technology (PAT) tool to eliminate the need for offline analysis of individual fractions after purification. The preparatory SEC unit is coupled to a MALS detector, i.e. preparatory SEC-MALS. In SEC, the molecules are separated based on size, where polysaccharide-protein conjugate elutes first followed by free polysaccharide and then free protein. The MALS detector monitors in-line weight-average molar mass (Mw) during SEC-fractionation. Except the first fraction, the molar mass distribution data from in-line MALS enables decision on preparative SEC fractions to be pooled. We found that offline analysis of preparative fractions using analytical SEC-MALS was in good agreement with the >2000 kDa cutoff criterion. Thus in-line process analysis is effective, time-saving, and simple to implement in manufacturing processes of conjugate vaccines.

Gamma glutamyl transferase (GGT) is emerging as a promising marker for assessing cardiovascular risk. GGT predicts cardiovascular mortality in the population and is positively associated with traditional risk factors for coronary artery disease (CAD). This study was undertaken on 200 north Indian CAD patients diagnosed with coronary angiography to study relation of GGT with risk factors for CAD and severity of CAD. GGT values ranged from 5 to 69U/L and were divided in 4 quartiles. GGT was positively associated with triglyceride (p=0.008) and VLDL cholesterol (p=0.002) in our subjects. Also an increase in total cholesterol from GGT quartile I to quartile IV (p=0.28) was noted.

In this paper, an implicit scheme is presented for a meshless compressible Euler solver based on the Least Square Kinetic Upwind Method (LSKUM). The Jameson and Yoon's split flux Jacobians formulation is very popular in finite volume methodology, which leads to a scalar diagonal dominant matrix for an efficient implicit procedure (Jameson & Yoon, 1987). However, this approach leads to a block diagonal matrix when applied to the LSKUM meshless method. The above split flux Jacobian formulation, along with a matrix-free approach, has been adopted to obtain a diagonally dominant, robust and cheap implicit time integration scheme. The efficacy of the scheme is demonstrated by computing 2D flow past a NACA 0012 airfoil under subsonic, transonic and supersonic flow conditions. The results obtained are compared with available experiments and other reliable computational fluid dynamics (CFD) results. The present implicit formulation shows good convergence acceleration over the RK4 explicit procedure. Further, the accuracy and robustness of the scheme in 3D is demonstrated by computing the flow past an ONERA M6 wing and a clipped delta wing with aileron deflection. The computed results show good agreement with wind tunnel experiments and other CFD computations.

The association of fungus in allergic fungal rhino sinusitis has been around 200 times in the world literature. As per the available literature, the most common agent identified so far appears to be ASPERGILLUS, though the condition is increasingly associated with Dematiaceous fungi. Here we report for the first time the presence of unusual fungus in allergic rhino sinusitis, which has not been reported so far.

Normal stem cells from a variety of tissues display unique metabolic properties compared to their more differentiated progeny. However, relatively little is known about metabolic properties of cancer stem cells, also called tumor initiating cells (TICs). In this study we show that, analogous to some normal stem cells, breast TICs have distinct metabolic properties compared to nontumorigenic cancer cells (NTCs). Transcriptome profiling using RNA‐Seq revealed TICs underexpress genes involved in mitochondrial biology and mitochondrial oxidative phosphorylation, and metabolic analyses revealed TICs preferentially perform glycolysis over oxidative phosphorylation compared to NTCs. Mechanistic analyses demonstrated that decreased expression and activity of pyruvate dehydrogenase (Pdh), a key regulator of oxidative phosphorylation, plays a critical role in promoting the proglycolytic phenotype of TICs. Metabolic reprogramming via forced activation of Pdh preferentially eliminated TICs both in vitro and in vivo. Our findings reveal unique metabolic properties of TICs and demonstrate that metabolic reprogramming represents a potential therapeutic strategy for targeting these cells. StemCells2014;32:1734–1745

In India, many state reference centres for sexually transmitted infections perform only a single screening assay for syphilis diagnosis. In this study, Treponema pallidumhaemagglutination (TPHA) was performed on 1115 Venereal Disease Research Laboratory (VDRL)/rapid plasma regain (RPR) non-reactive and 107 reactive sera out of 10,489 tested by VDRL/RPR according to the National AIDS Control Organisation syphilis testing protocol. A total of 47 Specimens reactive in TPHA and non-reactive with VDRL test were subjected to fluorescent treponemal antibody absorption and enzyme-immunoassay. Seroprevalence considering both VDRL and TPHA positivity was highest (4.4%) in sexually transmitted diseases clinic attendees than in other subject groups. Positivity by two treponemal tests in 24 (2.2%) cases non-reactive by VDRL/RPR was representative of the fully treated patients or latent or late syphilis cases. The findings highlight that a suitable treponemal confirmatory test should be performed in all the diagnostic laboratories.

Follicular lymphoma (FL) is currently incurable using conventional chemotherapy or immunotherapy regimes, compelling new strategies. Advances in high-throughput sequencing technologies that can reveal oncogenic pathways have stimulated interest in tailoring therapies toward actionable somatic mutations. However, for mutation-directed therapies to be most effective, the mutations must be uniformly present in evolved tumor cells as well as in the self-renewing tumor-cell precursors. Here, we show striking intratumoral clonal diversity within FL tumors in the representation of mutations in the majority of genes as revealed by whole exome sequencing of subpopulations. This diversity captures a clonal hierarchy, resolved using immunoglobulin somatic mutations and IGH-BCL2 translocations as a frame of reference and by comparing diagnosis and relapse tumor pairs, allowing us to distinguish early versus late genetic eventsduring lymphomagenesis. We provide evidence that IGH-BCL2 translocations and CREBBP mutations are early events, whereas MLL2 and TNFRSF14 mutations probably represent late events during disease evolution. These observations provide insight into which of the genetic lesions represent suitable candidates for targeted therapies.

Delegating the responsibility of safe driving on an autonomous vehicle needs the autonomous system to be extremely robust. In an attempt to design a robust guidance system for the autonomous vehicle we decided to go refer the most complex system designed which is “humans”. In humans we peculiarly observe that there exists an array of senses we possess that provide the required robustness and efficiency in chores that we perform. It clearly displays that in human beings the various senses we possess precisely complement each other to support a process. On this basis we propose an introduction to optimization of lane detection and tracking. Also the scalability of computation for smart vehicles such as auto park assist, cruise mode or auto lane keep assist continue to grow for driverless manoeuvre thus removing the possibility of manual or judgmental error in driving. We model a ground vehicle in a turning manoeuvre, such as a step lane-change where modeling process follows that of a vehicle undergoing translational as well as rotational motion. We shall be using this to design the control algorithm for executing a lane change maneuver under a safety set of rules using Dynamic Matrix Control which is a subset of the Model Predictive Control. This requires that we transform the vehicle lateral variable into the fixed coordinates. The application depends on recursively obtained sensor readings in a feedback loop mode for processing and deploying a corrective action tot exploits non-linear functions of the state and finds control inputs such as state of system, position, acceleration, peer movement to recursively estimate and improve the quality of resulting estimation for collision avoidance and target localization.

Lsr2 protein of Mycobacterium leprae was shown earlier to elicit B and T cell responses in leprosy patients (20, 28). Lymphoproliferation to M. leprae and Lsr2 antigens was observed in >70% of tuberculoid (T) patients and in 16 and 34% of lepromatous (L) patients, respectively. We focused on the M. leprae nonresponders in the lepromatous group using 22 synthetic Lsr2 peptides (end-to-end peptides A to F and overlapping peptides p1 to p16) in in vitro T cell responses. A total of 125 leprosy and 13 tuberculosis patients and 19 healthy controls from the area of endemicity (here, healthy controls, or HC) were investigated. The highest responses were observed (67 to 100%) in HC for all peptides except p1 to p3, and the lowest was observed in tuberculosis patients. Significant differences in lymphoproliferation were observed in T, L, and HC groups (analysis of variance [ANOVA], P = 0.000 to 0.015) for all end-to-end peptides except B and for p5 and p7 to p10. Hierarchical recognition between lepromatous and tuberculoid leprosy was noted for p8 (P < 0.05) and between the HC and L groups for p7 to p10, p15, and p16 (P < 0.005 to P < 0.02). Significant lymphoproliferation was observed to peptides A to F and p1 to p9, p11, p12, p15, p16 (P = 0.000 to 0.001) with 40% responding to peptides C and p16 in L patients. Lepromatous patients also showed significantly higher levels of a gamma interferon (IFN-γ) response to peptide C than to other peptides (P < 0.05). Major histocompatibility complex (MHC) class II bias for peptide recognition was not observed. These studies indicate that Lsr2 has multiple T cell epitopes that induce in vitro T cell responses in the highly infective lepromatous leprosy patients.

ABSTRACTLsr2 protein of Mycobacterium lepraewas shown earlier to elicit B and T cell responses in leprosy patients (20, 28). Lymphoproliferation to M. lepraeand Lsr2 antigens was observed in >70% of tuberculoid (T) patients and in 16 and 34% of lepromatous (L) patients, respectively. We focused on the M. lepraenonresponders in the lepromatous group using 22 synthetic Lsr2 peptides (end-to-end peptides A to F and overlapping peptides p1 to p16) in in vitroT cell responses. A total of 125 leprosy and 13 tuberculosis patients and 19 healthy controls from the area of endemicity (here, healthy controls, or HC) were investigated. The highest responses were observed (67 to 100%) in HC for all peptides except p1 to p3, and the lowest was observed in tuberculosis patients. Significant differences in lymphoproliferation were observed in T, L, and HC groups (analysis of variance [ANOVA], P= 0.000 to 0.015) for all end-to-end peptides except B and for p5 and p7 to p10. Hierarchical recognition between lepromatous and tuberculoid leprosy was noted for p8 (P< 0.05) and between the HC and L groups for p7 to p10, p15, and p16 (P< 0.005 to P< 0.02). Significant lymphoproliferation was observed to peptides A to F and p1 to p9, p11, p12, p15, p16 (P= 0.000 to 0.001) with 40% responding to peptides C and p16 in L patients. Lepromatous patients also showed significantly higher levels of a gamma interferon (IFN-γ) response to peptide C than to other peptides (P< 0.05). Major histocompatibility complex (MHC) class II bias for peptide recognition was not observed. These studies indicate that Lsr2 has multiple T cell epitopes that induce in vitroT cell responses in the highly infective lepromatous leprosy patients.

Objective Ti define the clinical role of intravenous N-acetylcysteine for prophylaxis of contrast-induced nephropathy (CIN).Data Sources: Randomized controlled clinical trials were identified using a search of MEDLINE (1990-September 2010) with the search terms acetylcysteine, N-acetylcysteine, NAC, intravenous, IV, nephropathy, nephrotoxic, radiocontrast, contrast, and media. The search was limited to studies published in English. Additional pertinent literature was retrieved by reviewing references of the articles obtained in the initial search.Data Synthesis: N-Acetylcysteine is a vasodilator and antioxidant that has been investigated for the prevention of CIN. In the majority of clinical trials, neither oral nor intravenous N-acetyIcysteine has demonstrated clinical benefits at preventing CIN. The pharmacodynamic and pharmacokinetic profiles of intravenous N-acetylcysteine are significantly different from those of the oral product in that intravenous administration bypasses extensive first-pass metabolism. Studies have suggested that N-acetylcysteine directly affects serum creatinine levels in a way that is not associated with improvement of kidney function. Only intravenous N-acetylcysteine doses that were higher than the oral doses showed potential benefits, but they were associated with significant adverse events. Furthermore, the study populations were heterogeneous, including patients with various levels of kidney function and other risk factors, and the clinical definition of CIN was not well established.Conclusions: NO conclusive evidence has shown that intravenous N-acetyl-cysteine is safe and effective in preventing CIN. Further clinical trials to define its role are warranted.

Two new series of BocNα,δδ,α and β,δδ,βhybrid peptides containing repeats of LAlaδ5Caaδ5CaaLAla and β3Caaδ5Caaδ5Caaβ3Caa LAla Lalanine, Caa Clinked carbo amino acid derived from Dxylose have been differentiated by both positive and negative ion electrospray ionization ESI ion trap tandem mass spectrometry MSMS. MSnspectra of protonated isomeric peptides produce characteristic fragmentation involving the peptide backbone, the Bocgroup, and the side chain. The dipeptide positional isomers are differentiated by the collisioninduced dissociation CID of the protonated peptides. The loss of 2methylprop1ene is more pronounced for BocNHLAlaδCaaOCH31, whereas it is totally absent for its positional isomer BocNHδCaaLAlaOCH37, instead it shows significant loss of tbutanol. On the other hand, second isomeric pair shows significant loss of tbutanol and loss of acetone for BocNHδCaaβCaaOCH318, whereas these are insignificant for its positional isomer BocNHβCaaδCaaOCH313. The tetra and hexapeptide positional isomers also show significant differences in MS2and MS3CID spectra. It is observed that ‘b’ ions are abundant when oxazolone structures are formed through fivemembered cyclic transition state and cyclization process for larger ‘b’ ions led to its insignificant abundance. However, b1ion is formed in case of δ,αdipeptide that may have a sixmembered substituted piperidone ion structure. Furthermore, ESI negative ion MSMS has also been found to be useful for differentiating these isomeric peptide acids. Thus, the results of MSMS of pairs of di, tetra, and hexapeptide positional isomers provide peptide sequencing information and distinguish the positional isomers. Copyright © 2010 John Wiley & Sons, Ltd.

This article presents DSQL, a conservative extension of SQL, as an ad-hoc query language for XML. The development of DSQL follows the theoretical foundations of first order logic, and uses common query semantics already accepted for SQL. DSQL represents a core subset of XQuery that lends well to optimization techniques, while at the same time allows easy integration into current databases and applications that useSQL. The intent of DSQL is not to replace XQuery, the current W3C recommended XML query language, but to serve as an ad-hoc querying frontend to XQuery. Further, the authors present proofs for important query language properties such as complexity and closure. An empirical study comparing DSQL and XQuery for the purpose of ad-hoc querying demonstrates that users perform better with DSQL for both flat and tree structures, in terms of both accuracy and efficiency.

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A new series of BocNβ3, γ4γ4, β3isomeric hybrid peptides containing repeats of β3Caa and γ4Caas, Caa Clinked carbo β3γ4amino acids derived from Dxylose have been differentiated by both positive and negative ion electrospray ionization ESI iontrap and high resolution quadrupole timeofflighttandem mass spectrometry QTOF MSMS. MSnof protonated isomeric peptides and M H − Boc Hproduce characteristic fragmentation involving the peptide backbone, the Bocgroup, and the side chain. The positional isomers are differentiated from one another by the presence of yn, bn, and other fragment ions of different mzvalues. It is observed that the peptides with βCaa at the Nterminus produce extensive fragmentation, whereas γCaa gave rise to much less fragmentation. Peptides with γCaa at the Nterminus lose NH3, whereas this process is absent for the carbopeptides with βCaa at the Nterminus. Two pairs of dipeptide diastereomers are clearly differentiated by the collisioninduced dissociation CID of their protonated molecules. The loss of 2methylprop1ene is more pronounced for BocNHRβCaaRγCaaOCH36 and BocNHRγCaaRβCaaOCH312, whereas it is insignificant or totally absent for its protonated diastereomeric pair BocNHSβCaaSγCaaOCH31 and BocNHSγCaaSβCaaOCH37. Further, ESI negative ion tandem mass spectrometry has also been found to be useful for differentiating these isomeric peptide acids. Copyright © 2008 John Wiley & Sons, Ltd.

Alfisol soils of rainfed semi-arid tropics (SAT) are degrading due to several physical, chemical, and biological constraints. Appropriate soil-nutrient management practices may help to check further soil degradation. A long-term experiment comprising tillage and conjunctive nutrient use treatments under a sorghum (Sorghum bicolor (L.) Moench)?mung bean (Vigna radiata (L.) Wilkzec) system was conducted during 1998?05 on SAT Alfisols (Typic Haplustalf) at the Central Research Institute for Dryland Agriculture, Hyderabad. The study evaluated soil and nutrient management treatments for their long-term influence on soil quality using key indicators and soil quality indices (SQI). Of the 21 soil quality parameters considered for study, easily oxidisable N (KMnO4 oxidisable-N), DTPA extractable Zn and Cu, microbial biomass carbon (MBC), mean weight diameter (MWD) of soil aggregates, and hydraulic conductivity (HC) played a major role in influencing the soil quality and were designated as the key indicators of ?soil quality' for this system. The SQI obtained by the integration of key indicators varied from 0.66 (unamended control) to 0.83 (4Mg compost+20kg N as urea) under conventional tillage (CT), and from 0.66 (control) to 0.89 (4Mg compost+2Mg gliricidia loppings) under reduced tillage (RT). Tillage did not influence the SQI, whereas the conjunctive nutrient-use treatments had a significant effect. On an average, under both CT and RT, the sole organic treatment improved the soil quality by 31.8% over the control. The conjunctive nutrient-use treatments improved soil quality by 24.2?27.2%, and the sole inorganic treatment by 18.2% over the control. Statistically, the treatments improved soil quality in the following order: 4Mg compost+2Mg gliricidia loppings > 2Mg Gliricidia loppings+20kg N as urea=4Mg compost+20kg N as urea > 40kg N as urea. The percentage contribution of the key indicators towards the SQI was: MBC (28.5%), available N (28.6%), DTPA-Zn (25.3%), DTPA-Cu (8.6%), HC (6.1%), and MWD (2.9%). The functions predicting the changes in yield and sustainability yield index with a given change in SQI were also determined.

In clinical practice, mitochondrial disease is seldom considered until a variable combination of seizures, alteration in tone, muscle weakness, and developmental problems is evident. However, it is not uncommon for one symptom to occur in isolation and dominate the clinical phenotype. We report six patients from two families where dystonia was the principal clinical manifestation. A mitochondrial etiology was considered in each case because of the association of dystonia with other less prominent clinical features such as epilepsy.

A 4-day-old female neonate with raised cord blood thyroid-stimulating hormone (127 μIU/mL) underwent 99mTc thyroid scan to rule out thyroid dysgenesis. The images revealed midline focus of lingual thyroid as the only functioning thyroid tissue. In addition, bilateral focal and symmetrical breast uptake was seen without clinically palpable breast nodule on either side. Transplacental transfer of maternal hormones leading to stimulation of neonatal breasts explains this unusual scan finding. One should be aware of this rare pattern of focal breast uptake in 99mTc-pertechnetate scan in neonates with congenital hypothyroidism to avoid scan misinterpretation.

The utility of the air-jet and ring combination has been known in the last decade, on its ability to reduce the yarn hairiness. However, it still offers enough scope for further work, with respect to its application in cotton spinning. In the recent past, it has been proved by the textile researchers that with the employment of air-jet nozzle in ring spinning the yam hairiness could be reduced. This paper examines the effect of employing twin air-jet nozzle in ring spinning. In this study an attempt has been made to combine the advantage of air-jet spinning system, with conventional ring spinning system. Two types of air-jet nozzle similar in all dimensions but differing in the direction of inclination of orifice, namely, 'S' nozzle and a suitable air chamber to house these two nozzles in tandem have been designed and fabricated. This twin air-jet nozzle assembly has been positioned in between the front roller nip and lappet hook without altering the pinning angle The yarn emerging from the front roller nip has been guided to pass through the twin air-jet nozzle and subjected to the action of opposing swirling air current created by air vortex inside the nozzles. Trial have been conducted in mill condition on 30's carded count on conventional ring. Tinning machine without and with twin air-jet nozzle under four different combinations of air pressure ie, 0.25/0.25 bar, 0.25/0.50 bar, 0.50 /0.50 bar and 0.5/1.0 bar in the S' and Z' nozzles, respectively. the yarn samples thus produced have been tested for their properties like tenacity, elongation, evenness, imperfections, hairiness, diameter and twist. From the results it has been observed that the introduction of twin air-jet nozzle system; in ring spinning has lead to better compaction of yarn with improvement in yarn quality index, yarn tenacity and packing factor. The twin air-jet nozzle system under 0.25/0.50 bar pressure combination in the 'S' and 'Z' nozzles has produced the best results with 17.5% increased tenacity, 18.8% improvement in Yarn Quality Index and 15% increased Packing Factor, when compared to regular ring spun yam. This paper proves that the twin air-jet nozzle technology could beneficially employed for the improvement of yarn quality by the spinning industry. [ABSTRACT FROM AUTHOR]

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Mutations in the gene coding for the catalytic subunit of the mitochondrial DNA (mtDNA) polymerase γ (POLG1) have recently been described in patients with diverse clinical presentations, revealing a complex relationship between genotype and phenotype in patients and their families. POLG1 was sequenced in patients from different European diagnostic and research centres to define the phenotypic spectrum and advance understanding of the recurrence risks. Mutations were identified in 38 cases, with the majority being sporadic compound heterozygotes. Eighty-nine DNA sequence changes were identified, including 2 predicted to alter a splice site, 1 predicted to cause a premature stop codon and 13 predicted to cause novel amino acid substitutions. The majority of children had a mutation in the linker region, often 1399G→A (A467T), and a mutation affecting the polymerase domain. Others had mutations throughout the gene, and 11 had 3 or more substitutions. The clinical presentation ranged from the neonatal period to late adult life, with an overlapping phenotypic spectrum from severe encephalopathy and liver failure to late-onset external ophthalmoplegia, ataxia, myopathy and isolated muscle pain or epilepsy. There was a strong gender bias in children, with evidence of an environmental interaction with sodium valproate. POLG1 mutations cause an overlapping clinical spectrum of disease with both dominant and recessive modes of inheritance. 1399G→A (A467T) is common in children, but complete POLG1 sequencing is required to identify multiple mutations that can have complex implications for genetic counselling.

Alexander disease is most commonly associated with macrocephaly and, on MRI, a leukoencephalopathy with frontal preponderance. The disease is caused by mutation of the GFAPgene. Clinical and MRI phenotypic variation have been increasingly recognized.

Presence is a leading service enabler that permits the leveraging of existing unused dynamic network and user‐specified states to enhance the end‐user experience regardless of network type. This letter explores the evolution of presence standards, discusses the converged architecture and value‐added components of presence, and provides a simple application example to illustrate how presence works. © 2006 Lucent Technologies Inc.

Knowledge management (KM) has gained increasing attention since the mid-1990s. A KM strategy involves consciously helping people share and put knowledge into action. However, before an organization can realize the promise of KM, a fundamental question needs to be asked: What performance goal(s) is the organization trying to achieve? In this paper, we develop and offer a framework that provides a holistic view of the performance environment surrounding organizational knowledge work. We illustrate the KM framework using two organizational case studies. Then, based on the KM framework and further insights drawn from our case studies, we offer a series of steps that may guide and assist organizations and practitioners as they undertake KM initiatives. We further demonstrate the applicability of these steps by examining KM initiatives within a global software development company. We conclude with a discussion of implications for organizational practice and directions for future research.

A temperature-dependent magneto-optical study of three different temperature-sensitive fluids was carried out. The changes in transmitted intensity as a function of applied magnetic field and temperature are recorded. The study provides an alternative technique for determining the Curie temperature of such fluids, and it is also feasible for the monitoring of temperature changes of such fluids optically within a limited time span.

Ensuring the genetic purity of parental lines and hybrids is a prerequisite to realize their full potential. The cytoplasmic male sterile (CMS) lines that are utilized for developing the popular “three‐line” hybrids, often get contaminated with their isonuclear maintainer lines during CMS line multiplication. Use of such CMS lines in hybrid seed production results in the production of genetically impure hybrid seed. We report the identification of a DNA sequence that is homologous to rice mitochondrial DNA but unique to the Wild Abortive (WA) cytoplasmic male sterile lines of rice (Oryza sativaL.). In a polymerase chain reaction (PCR) using total genomic DNA as a template, oligonucleotide primers based on this unique DNA sequence could amplify a fragment from CMS lines of rice and their hybrids but not from their cognate maintainer lines. In tests on mixed samples of plants containing both CMS and Maintainer lines, this PCR assay was used to correctly predict the genotypes of these plants indicating that it can be used to detect the mixture of maintainer lines in the seed stocks of the CMS line.

The quality of brackish water pond cultured shrimp purchased from wholesale markets and retail sale points at the time of sale in Hyderabad city was studied. The various hygienic practices followed during the chain of commercial operations were also studied. All the samples collected from either markets had heavy filth. Out of 35 samples collected from the wholesale markets, light filth ranged from 2% to 28%, and it ranged from 8 to 22% in retail market samples. All the shrimp samples purchased from either source contained Staphylococcus spp, and 51% of the shrimp from wholesale markets were found to be contaminated with coliforms, 11% with Salmonella sppand 5% with Vibrio sppwhereas 48% of the retail market samples contained coliforms, 11%Salmonella sppand 25% had Proteus spp. None of the samples collected from either source were contaminated with Listeria spp.The extent of bacterial contamination (cfu/g) was more for the samples purchased from the retail sale points than that of the wholesale markets.

Tuberous sclerosis complex (TSC), an autosomal dominant disease caused by mutations in either TSC1 or TSC2, is characterized by the development of hamartomas in a variety of organs. Concordant with the tumour-suppressor model, loss of heterozygosity (LOH) is known to occur in these hamartomas at both TSC1 and TSC2 loci. LOH has been documented in renal angiomyolipomas, but loss of the wild-type allele in cortical tubers appears very uncommon. We analysed 24 hamartomas from 10 patients for second-hit mutations by several methods, and found no evidence for the inactivation of the second allele in many of the central nervous system (CNS) lesions, including tumours that appear to be clonally derived. We believe that somatic mutations in TSC1 and TSC2 resulting in the loss of wild-type alleles may not be necessary in some tumour types, and other mechanisms may contribute to tumorigenesis in this setting. We have shown that hamartin interacts with neurofilament light chain (NF-L) and could integrate the neuronal cytoskeleton through its direct interaction with NF-L and ERM (ezrin/radixin/moeisin) proteins. Our unpublished work further documents the binding of tuberin with Pam, a protein associated with c-Myc, which is enriched in brain. All these observations suggest that the tuberin–hamartin complex is likely to have distinct functions in the CNS.

This paper describes the theory and application of a grid‐free kinetic upwind scheme known as LSKUM. The basic principle in LSKUM is the determination of derivatives occurring in the conservation laws using the least squares method. The grid‐free nature of the scheme is obtained because the least squares method can be used on an arbitrary distribution of nodes, i.e. the nodes need not form a structured/unstructured grid. Copyright © 2002 John Wiley & Sons, Ltd.

Hormonal approaches to male contraception that are based on the suppression of LH secretion require androgen replacement treatment to maintain sexual behaviour and secondary sexual characteristics. Androgen supplementation not only involves large and frequent doses of testosterone esters but also results in undesirable effects on the prostate gland. In an attempt to avoid such problems, a synthetic androgen, 7alpha-methyl-19-nortestosterone (MENT), which is much more potent than testosterone, has been developed. In the present study, MENT was administered at different doses (25, 50, 100, 300 and 1000 microg day(-1)) either alone or in combination with oestradiol via Silastic implants for a specified period to adult male bonnet monkeys (Macaca radiata). Blood and semen samples were collected at specific intervals and analysed for serum testosterone and seminal parameters, respectively. The results of the present study clearly indicate that administration of MENT at all doses tested results in suppression of the nocturnal surge of testosterone (by day 3), as well as a decrease in the number of spermatozoa (by day 45). Co-administration of oestradiol resulted in a reduction in the dose of MENT required to suppress the nocturnal surge. None of the male bonnet monkeys treated with MENT were able to impregnate females, clearly demonstrating the efficacy of MENT in blocking fertility in male bonnet monkeys.

The estimation of hybrid rice seed purity is done conventionally by the grow out test (GOT), which is based on the assessment of morphological and floral characteristics in plants grown to maturity. For seed companies, large amounts of capital are locked up in the form of hybrid seed stock while awaiting the results of the GOT. With the objective of replacing the GOT with DNA based assays, cytoplasmic male sterile (CMS), restorer, and hybrid lines have been screened by means of microsatellite and sequence tagged site (STS) polymorphisms. A simple procedure for detecting heterozygosity and purity has been standardized and uses 6‐d‐old rice (Oryza sativaL.) seedlings, which could be used for detection of off‐types in hybrid seed lots. The extent of heterozygosity within parental lines of rice hybrids was assessed and the results suggest that a single, appropriately chosen microsatellite marker should be sufficient for assessing hybrid seed purity.

Excitation energy transfer in PS I particles from the green alga Chlamydomonas reinhardtii CC 2696 was studied at 10 K by femtosecond transient absorption spectroscopy. Five-nm wide excitation pulses at 670, 680, 695, and 700 nm were applied to selectively excite different spectral forms contributing to the wide QY transition band of chlorophyll a. Absorbance changes between 630 and 770 nm, up to 100 ps after excitation, were collected with a time step of 54 fs during the first 5 ps. Excitation at 700 nm leads to a structured initial absorbance difference spectra with four positive bands clearly resolved at 634, 645, 652, and 661 nm, and four negative bands at 667, 675, 684, and 695 nm. These spectra are interpreted in terms of excitonic coupling between the six electron-transfer chlorophyll a molecules:  a special pair, two accessory and two A0 chlorophylls. The negative bands were ascribed to photobleaching of the four one-exciton states in line with theoretical predictions (Beddard, G. S. J. Phys. Chem. B. 1998, 102, 10 966), and the positive ones to excited-state absorption. The significance of the broad absorbance changes is proposed to be the introduction of spectral overlap between the reaction center and different spectral forms of the antenna chlorophylls that is expected to increase the efficiency of energy flow to the reaction center. Excitation at different wavelengths shows indeed that trapping can occur from different spectral pools of chlorophylls with similar efficiency (trapping time 29−44 ps). Following the excitation at 670 and 680 nm, trapping was shown to occur from the same pool as at room temperature centered at 682−685 nm, containing apparently only a minority of antenna molecules located close to the reaction center. The trapping time was found to be only slightly longer compared to that at room temperature (20−23 ps at RT). At 10 K, a significant amount of chlorophylls cannot exchange excitation energy with their neighbors. Our results are consistent with previous reports that at cryogenic temperatures, charge separation is possible in ~50% of PS I particles and that excitation quenching by the oxidized and reduced primary donor is equally effective. As was observed at room temperature, there is no indication of red chlorophylls absorbing above 700 nm. This lack of red chlorophylls makes it possible to directly excite reaction center chlorophylls and study interaction between them in wild type and, in future, mutant PS I from Chlamydomonas.

Background and aims: Microgravity has adverse effects on the immune system. We examined the effects of supplemental dietary nucleotides on immune function in ground-based in vivo anti-orthostatic tail-suspended (AOS) mice and in vitro (bioreactor—BIO) analogs of microgravity. Methods: BALB/c mice were divided into the following three groups: group housed, single isolation, and AOS. Mice were fed either control chow or chow supplemented with RNA or uracil. Immune function was assessed by in vivo popliteal lymph node proliferation (PLN), in vitro PHA-stimulated proliferation of splenocytes and cytokine production. BIO splenocytes were cultured in vitro with/without PHA, a nucleoside-nucleotide mixture (NS/NT) or uridine. The cell proliferation and scanning electron microscopic examination for cells were carried out. Results: PLN response was significantly suppressed in AOS mice (P&lt;0.05) and was restored by RNA and uracil diets. Splenocytes from AOS mice had decreased phytohemagglutinin (PHA)-stimulated proliferation, decreased IL-2 and IFN- γ cytokine levels (P&lt;0.05). These responses were restored by RNA and uracil diets. In BIO cultures, PHA response was suppressed significantly, and uridine and NS/NT restored the proliferative responses. Scanning electron microscopic analysis of cells cultured in BIO revealed cells with pinched, distorted and eroded membranes. Nucleotide supplementation especially uridine restored normal activated cell surface appearance and ruffling. Conclusion: In the microgravity analog environment of AOS and BIO, supplemental nucleotides and especially uracil/uridine have up-regulating and immunoprotective effects with potential as a countermeasure to the observed immune dysfunction in true microgravity. Copyright 2002 Elsevier Science Ltd. All rights reserved.