AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenom...AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonicadenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a signif icant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.展开更多
A novel upper gastrointestinal bleeding risk stratification score(AIMS65) has recently been developed and validated. It has advantages over existing risk scores including being easy to remember and lack of subjectivit...A novel upper gastrointestinal bleeding risk stratification score(AIMS65) has recently been developed and validated. It has advantages over existing risk scores including being easy to remember and lack of subjectivity in calculation. We comment on a recent study that has cast doubt on the applicability of AIMS65 in the peptic ulcer disease population. Although promising, further studies are required to evaluate the validity of AIMS65 in various populations.展开更多
Objective: This study examined the antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava against methicillin-resistant Staphylococcus aureus (MRSA) and used a standardized purification pro...Objective: This study examined the antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava against methicillin-resistant Staphylococcus aureus (MRSA) and used a standardized purification protocol to determine the presence and abundance of bioactive compounds in the leaf extracts. Methods: In vitro antimicrobial activities of the ethanolic extracts of C sativa, T. orientalis and P. guajava were tested against MRSA. The presence of bioactive molecules in these three leaves was evaluated using biochemical assays and high-performance thin-layer chromatography (HPTLC). Results: Resistance to methicillin, penicillin, oxacillin and cefoxitin was observed in each of the clinical and nonclinical MRSA isolates. However, they were still vulnerable to vancomydn. Used individually, the 50% extract of each plant leaf inhibited MRSA growth. A profound synergism was observed when C sativa was used in combination with T. orientalis (1:1 ) and when P. guajava was used in combination with T. orientalis (1:1 ). This was shown by larger zones of inhibition. This synergism was probably due to the combined inhibitory effect of phenolics present in the leaf extracts (i.e., quercetin and gallic acid) and catechin, as detected by HPTLC. Conclusion: The leaf extracts of C sativa, T. orientalis and P. guajava had potential for the control of both hospital- and community-acquired MRSA. Moreover, the inhibitory effect was enhanced when extracts were used in combination.展开更多
Seven different, but highly conserved 14-3-3 proteins are involved in diverse signaling pathways in human cells. It isunclear how the 14-3-3σ isoform, a transcriptional target of p53, exerts its inhibitory effect on ...Seven different, but highly conserved 14-3-3 proteins are involved in diverse signaling pathways in human cells. It isunclear how the 14-3-3σ isoform, a transcriptional target of p53, exerts its inhibitory effect on the cell cycle in thepresence of other 14-3-3 isoforms, which are constitutively expressed at high levels. In order to identify structuraldifferences between the 14-3-3 isoforms, we solved the crystal structure of the human 14-3-3σ protein at a resolutionof 2.8 ? and compared it to the known structures of 14-3-3ζ and 14-3-3τ. The global architecture of the 14-3-3σ foldis similar to the previously determined structures of 14-3-3ζ and 14-3-3τ: two 14-3-3σ molecules form a cup-shapeddimer. Significant differences between these 14-3-3 isoforms were detected adjacent to the amphipathic groove, whichmediates the binding to phosphorylated consensus motifs in 14-3-3-ligands. Another specificity determining region islocalized between amino-acids 203 to 215. These differences presumably select for the interaction with specific ligands,which may explain the different biological functions of the respective 14-3-3 isoforms. Furthermore, the two 14-3-3σmolecules forming a dimer differ by the spatial position of the ninth helix, which is shifted to the inside of the ligandinteraction surface, thus indicating adaptability of this part of the molecule. In addition, 5 non-conserved residues arelocated at the interface between two 14-3-3σ proteins forming a dimer and represent candidate determinants of homo-and hetero-dimerization specificity. The structural differences among the 14-3-3 isoforms described here presumablycontribute to isoform-specific interactions and functions.展开更多
Interaction between bovine serum albumin(BSA) and phosphorus heterocycles(PHs) was studied using multispectroscopic techniques. The results indicated the high binding affinity of PHs to BSA as it quenches the intrinsi...Interaction between bovine serum albumin(BSA) and phosphorus heterocycles(PHs) was studied using multispectroscopic techniques. The results indicated the high binding affinity of PHs to BSA as it quenches the intrinsic fluorescence of BSA. The experimental data suggested the fluorescence quenching mechanism between PHs and BSA as a dynamic quenching. From the UV–vis studies, the apparent association constant(K_(app)) was found to be 9.25×10~2, 1.27×10~4and 9.01×10~2L/mol for the interaction of BSA with PH-1, PH-2 and PH-3,respectively. According to the F?rster's non-radiation energy transfer(FRET) theory, the binding distances between BSA and PHs were calculated. The binding distances(r) of PH-1, PH-2 and PH-3 were found to be2.86, 3.03, and 5.12 nm, respectively, indicating energy transfer occurs between BSA and PHs. The binding constants of the PHs obtained from the fluorescence quenching data were found to be decreased with increase of temperature. The negative values of the thermodynamic parameters ΔH, ΔS and ΔG at different temperatures revealed that the binding process is spontaneous; hydrogen bonds and van der Waals interaction were the main force to stabilize the complex. The microenvironment of the protein-binding site was studied by synchronous fluorescence and circular dichroism(CD) techniques and data indicated that the conformation of BSA changed in the presence of PHs. Finally, we studied the BSA-PHs docking using Auto Dock and results suggest that PHs is located in the cleft between the domains of BSA.展开更多
Background: The present study was designed to evaluate load carriage performance at extremely high altitudes with different loads and walking speeds in terms of physiological evaluation. The degree of maximum oxygen c...Background: The present study was designed to evaluate load carriage performance at extremely high altitudes with different loads and walking speeds in terms of physiological evaluation. The degree of maximum oxygen consumption changes at high altitudes was also examined.Methods: Twelve Indian Army soldiers were acclimatized at altitudes of 3,505 m and 4,300 m. They walked for 10 minutes on a motorized treadmill at 2.5km/h and 3.5km/h speeds during carrying no loads and three magnitudes of load(10.7kg, 21.4kg, 30kg) at both altitudes. Physiological parameters such as oxygen consumption, energy expenditure, heart rate, and ventilation were recorded for each breath using a gas analyzer. The rating of perceived exertion was also noted after each load carriage session. Maximal oxygen consumption(VO2max) was measured at sea level and the two high altitudes, and respective relative workloads(% of VO2max) were calculated from oxygen consumption. Repeated measure ANOVA was applied to reveal the significant effects of the independent variables.Results: The participants had significant reductions in VO2 max with rising altitude. Marked increases in almost all physiological parameters were observed with increasing load, altitude, and speed. The soldiers expressed heavy perceived exertion levels with higher loads at 3.5km/h at the two high altitudes.Conclusions: Considering the physiological responses, expressions of perceived exertion and changes in relative work load at both of the high altitudes. Indian soldiers are advised to walk slowly with adequate rest in between their schedules and to carry not more than 32% of their body weight.展开更多
The growing demand for air travel has led to the saturation of air traffic networks.Conventional methods of adding routes to alleviate congestion and reduce delays may not achieve the desired effect and even degrade s...The growing demand for air travel has led to the saturation of air traffic networks.Conventional methods of adding routes to alleviate congestion and reduce delays may not achieve the desired effect and even degrade system performance.In this paper,we explore the application of Braess’s Paradox in the reduction of air traffic networks.This counterintuitive phenomenon shows that adding new connections to a network can actually increase the overall network pressure.This study uses Hidden Markov methods and the Viterbi algorithm to match air traffic flow with routes,a machine learning approach and a mathematical method to construct cost functions for flight time and traffic volume,and finally uses genetic algorithm and the A*algorithm to detect Braess’s Paradox edges.We uses ADS-B data from the busy month of July 2019 for a case study of the air traffic network over the UK airspace.The results show that Braess’s Paradox is also applicable to multi-flight level air route networks.Removing such network edges can improve system performance.In one day’s case,the total flight time of the day’s traffic volume decreased from 11509.24 minutes to 10459.97 minutes.This equates to an average savings of 4.99 minutes of flight time per flight,which is significant in controlling delay performance.展开更多
Diamond anvil cell techniques have been improved to allow access to the multimegabar ultrahigh-pressure region for exploring novel phenomena in condensedmatter.However,the onlyway to determine crystal structures of ma...Diamond anvil cell techniques have been improved to allow access to the multimegabar ultrahigh-pressure region for exploring novel phenomena in condensedmatter.However,the onlyway to determine crystal structures of materials above 100 GPa,namely,X-ray diffraction(XRD),especially for lowZ materials,remains nontrivial in the ultrahigh-pressure region,even with the availability of brilliant synchrotron X-ray sources.In thiswork,we performa systematic study,choosing hydrogen(the lowest X-ray scatterer)as the subject,to understand how to better perform XRD measurements of low Z materials at multimegabar pressures.The techniques that we have developed have been proved to be effective in measuring the crystal structure of solid hydrogen up to 254GPa at room temperature[C.Ji et al.,Nature 573,558–562(2019)].Wepresent our discoveries and experienceswith regard to several aspects of thiswork,namely,diamond anvil selection,sample configuration for ultrahigh-pressure XRDstudies,XRDdiagnostics for low Z materials,and related issues in data interpretation and pressure calibration.Webelieve that these methods can be readily extended to other low Z materials and can pave the way for studying the crystal structure of hydrogen at higher pressures,eventually testing structural models of metallic hydrogen.展开更多
Field experiments were conducted in oil and edible sunflower to study the effects of potassium(K) fertilization on achene yield and quality, and to estimate the nutrient internal efficiency(IE) and nutrient requiremen...Field experiments were conducted in oil and edible sunflower to study the effects of potassium(K) fertilization on achene yield and quality, and to estimate the nutrient internal efficiency(IE) and nutrient requirement in sunflower production. All trials in edible sunflower and 75% trials in oil sunflower showed positive yield responses to K fertilization. Compared with control without K fertilization, the application of K increased achene yield by an average of 406 kg ha–1for oil sunflower and 294 kg ha–1for edible sunflower. K application also increased 1 000-achene weight and kernel rate of both oil and edible sunflower. K fertilization improved the contents of oil, oleic acid, linoleic acid and linolenic acid in achenes of oil sunflower, and increased contents of oil, total unsaturated fatty acid and protein in achenes of edible sunflower. The average agronomic efficiency of K fertilizer was 4.0 for oil sunflower and 3.0 kg achene kg–1K2O for edible sunflower. The average IE of N, P and K under balanced NPK fertilization was 22.9, 82.8, and 9.9 kg kg–1for oil sunflower, and 27.3, 138.9, and 14.3 kg kg–1for edible sunflower. These values were equivalent to 45.5, 14.1, and 108.1 kg, and 39.0, 8.0, and 71.7 kg of N, P and K, respectively, in above-ground dry matter required for production per ton of achenes. The average harvest index of N, P and K was 0.47, 0.56 and 0.05 kg kg–1in oil sunflower, and 0.58, 0.58 and 0.14 kg kg–1in edible sunflower.展开更多
Tree species diversity and population structure at different community types were described and analyzed for primary and secondary lowland moist deciduous forests in Tripura. Overall 10,957 individual trees belonging ...Tree species diversity and population structure at different community types were described and analyzed for primary and secondary lowland moist deciduous forests in Tripura. Overall 10,957 individual trees belonging to 46 family, 103 genera and 144 species were counted at ≥30 cm DBH (diameter at breast height) using 28 permanent belt transects with a size of 1 ha (10 m × 1000 m). Four different tree communities were identified. The primary forests was dominated by Shorea robusta (mean density 464.77 trees.ha^-1, 105 species) and Schima wallichii (336.25 trees.ha^-1, 82 species), while the secondary forests was dominated by Tectona grandis (333.88 trees.ha^-1, 105 species) and Hevea brasiliensis (299.67 trees.ha^-1, 82 species). Overall mean basal area in this study was 18.01m2.ha^-1; the maximum value was recorded in primary Shorea forest (26.21 m2.ha^-1). Mean density and diversity indices were differed significantly within four different communities. No significant differences were observed in number of species, genera, family and tree basal cover area. Significant relationships were found between the species richness and different tree population groups across the communities. Results revealed that species diversity and density were increased in those forests due to past disturbances which resulted in slow accumu- lation of native oligarchic small tree species. Seventeen species were recorded with 〈2 individuals of which Saraca asoka (Roxb.) de Wilde and Entada phaseoloides (L.) Men'. etc. extensively used in local ethnomedicinal formulations. The present S. robusta Gaertn dominated forest was recorded richer (105 species) than other reported studies. Moraceae was found more speciose family instead of Papilionaceae and Euphorbiaceae than other Indian moist deciduous forests. Seasonal phenological gap in such moist deciduous forests influenced the population of Trachypithecus pileatus and capped langur. The analysis of FIV suggested a slow trend of shifting the po展开更多
Bone resorption requires the formation of complex, actin-rich cytoskeletal structures. During the early phase of sealing ring formation by osteoclasts, L-plastin regulates actin-bundling to form the nascent sealing zo...Bone resorption requires the formation of complex, actin-rich cytoskeletal structures. During the early phase of sealing ring formation by osteoclasts, L-plastin regulates actin-bundling to form the nascent sealing zones(NSZ). Here, we show that L-plastin knockout mice produce osteoclasts that are deficient in the formation of NSZs, are hyporesorptive, and make superficial resorption pits in vitro. Transduction of TAT-fused full-length L-plastin peptide into osteoclasts from L-plastin knockout mice rescued the formation of nascent sealing zones and sealing rings in a time-dependent manner. This response was not observed with mutated full-length L-plastin(Ser-5 and-7 to Ala-5 and-7) peptide. In contrast to the observed defect in the NSZ, L-plastin deficiency did not affect podosome formation or adhesion of osteoclasts in vitro or in vivo. Histomorphometry analyses in 8-and 12-week-old female L-plastin knockout mice demonstrated a decrease in eroded perimeters and an increase in trabecular bone density, without a change in bone formation by osteoblasts. This decrease in eroded perimeters supports that osteoclast function is attenuated in L-plastin knockouts. Micro-CT analyses confirmed a marked increase in trabecular bone mass. In conclusion, female L-plastin knockout mice had increased trabecular bone density due to impaired bone resorption by osteoclasts. L-plastin could be a potential target for therapeutic interventions to treat trabecular bone loss.展开更多
The present study concerns understanding the effect of process parameters on the characteristics and flowability of nanocrystalline CoNiCrAlY powder synthesized by mechanical milling.Mechanical milling has been conduc...The present study concerns understanding the effect of process parameters on the characteristics and flowability of nanocrystalline CoNiCrAlY powder synthesized by mechanical milling.Mechanical milling has been conducted in a planetary ball mill with tungsten carbide(WC)ball,with ball to powder ratio of 10:1 at 300 rpm speed,using 1%stearic acid and toluene as process control agent(PCA)with time varying from 10 h to 36 h.The synthesized nanocrystalline powder were characterized by Scanning Electron Microscopy,X-ray Diffraction technique,X-ray Photoelectron Spectroscopy,and Differential Scanning Calorimetry.Subsequently,flowability in terms of Hausner ratio was assessed by Tap Density Tester.Average particle size of the powder was found to decrease from 33μm to 22μm after 10 h of milling and further increases to 43μm and 38μm after 25 and 36 h of milling,respectively,in stearic acid medium.However,in toluene medium particle size continuously decreases from 33μm to 9.7μm with increasing milling time.The particle morphology changes from spherical to platelet shape at low milling hours in both of the media.After 25 h of milling,the shape of the particles is nearly spherical for stearic acid and irregular for toluene used as a PCA.Crystallize size was found to decrease with increasing milling time from 147 nm to 7.7 nm and to 6.4 nm in stearic acid and toluene media,respectively.There was presence ofγ,γʹ,β,hcp-Co,Al_(2)O_(3)and AlOOH phases on the powder particles milled in both the medium.The measured Hausner ratio of the powders was found to vary from 1.18 to 1.32 in stearic acid medium,and was found to increase with increasing milling time.On the other hand,in toluene media flowability decreases(Hausner ratio increases from 1.33 to 1.44)with increasing milling time.展开更多
Members of the receptor tyrosine kinase family, that include EGFR, ErbB-2/HER-2, ErbB-3/HER-3 and ErbB-4/ HER-4, are frequently implicated in experimental models of epithelial cell neoplasia as well as in human cancer...Members of the receptor tyrosine kinase family, that include EGFR, ErbB-2/HER-2, ErbB-3/HER-3 and ErbB-4/ HER-4, are frequently implicated in experimental models of epithelial cell neoplasia as well as in human cancers. Therefore, interference with the activation of these growth factor receptors represents a promising strategy for de- velopment of novel and selective anticancer therapies. Indeed, a number of inhibitors that target either EGFR or HER-2, with the exception of a few that target both; have been developed for treatment of epithelial cancers. Since most solid tumors express different ErbB receptors and/or their ligands, identification of inhibitor(s), targeting multiple EGFR family members may provide a therapeutic benefit to a broader patient population. Here we describe the significance of an ErbB family of receptors in epithelial cancers, and summarize different available therapeutics targeting these receptors. It also emphasizes the need to develop pan-ErbB inhibitors and discusses EGF-Receptor Related Protein, a recently isolated negative regulator of EGFR as a potential pan-ErbB therapeutic for a wide vari- ety of epithelial cancers.展开更多
To estimate woody plant biomass stocks in different patches of forest ecosystems, total 20, 500 × 10 m (0.5 ha) sized line transects were laid in a protected area of Tripura, Northeast India. Overall, 9160 indivi...To estimate woody plant biomass stocks in different patches of forest ecosystems, total 20, 500 × 10 m (0.5 ha) sized line transects were laid in a protected area of Tripura, Northeast India. Overall, 9160 individuals were measured at ≥10 cm diameter at breast height (dbh) in 10 ha sampled area. Estimation of biomass suggested that highest coefficient for allometric relationships between density and biomass in 10 dbh classes was observed in bamboo brakes (R<sup>2</sup> = 0.90) than lowest for semi evergreen patch (R<sup>2</sup> = 0.48). The stock of carbon (C) was differ significantly along the forest patches (F = 7.01, df = 3.19;p < 0.01). Most of biomass stock (69.38%) was accumulated in lower dbh class (<30 cm) and only 23% of biomass was estimated at higher dbh classes (> 70 cm). Range of biomass stock (37.85 - 85.58 Mg ha<sup>-</sup><sup>1</sup>) was low, compared to other tropical forest ecosystems in India, which implies that the proper management is required to monitor regional ecosystem C pool.展开更多
Optical metasurfaces are currently an important research area all around the world because of their wide application opportunities in imaging,wavefront engineering,nonlinear optics,quantum information processing,just ...Optical metasurfaces are currently an important research area all around the world because of their wide application opportunities in imaging,wavefront engineering,nonlinear optics,quantum information processing,just to name a few.The feature issue“Optical Metasurfaces:Fundamentals and Applications”in Photonics Research allows for archival publication of the most recent works in optical metasurface and provides for broad dissemination in the photonics community.展开更多
Aim:To investigate the status of seminal plasma reduced glutathione(GSH)and vitamin E in three different condi-tions of spermatogenesis:azoospermia,oligozoospermia and nonnospennia.Methods:Reduced glutathione wasmeasu...Aim:To investigate the status of seminal plasma reduced glutathione(GSH)and vitamin E in three different condi-tions of spermatogenesis:azoospermia,oligozoospermia and nonnospennia.Methods:Reduced glutathione wasmeasured in the seminal plasma by the method of Moron et al(1979),and vitamin E estimation was performed by themethod of Taylor et al(1976).Results:Vitamin E levels in seminal plasma of oligospermic and azoospennic sam-ples were significantly decreased to 65.54%and 66.04%respectively as compared to the normospermic group.Levelsof reduced glutathione were also significantly decreased in oligospermic and azoospennic group,and the reduction inazoospermic group(76.73%)was more pronounced than oligozoospermic group(62.07%).Conclusion.The de-crease in reduced glutathione,an endogenous antioxidant,levels in azoospermic and oligozoospermic conditions maycause dismption in the membrane integrity of spermatozoa as a consequence of increased oxidative stress.展开更多
A middle aged, non-addict male presented with right upper abdominal pain and swelling with respiratory distress. Examination revealed central cyanosis, bipedal pitting edema with prominent epigastric and back veins. L...A middle aged, non-addict male presented with right upper abdominal pain and swelling with respiratory distress. Examination revealed central cyanosis, bipedal pitting edema with prominent epigastric and back veins. Liver was enlarged, tender, spanned 20 cm without any splenomegaly or ascites. Other systems were clinically normal. Laboratory investigations showed polymorphonuclear leucocytosis with slightly deranged liver function. Abdominal ultrasonography showed an abscess in the right lobe of the liver with compressed inferior vena cava (IVC), middle and left hepatic veins. Arterial blood gas (ABG) documented hypoxia with orthodeoxia and air-contrast echocardiography was suggestive of an intrapulmonary shunt. A diagnosis of hepato-pulmonary syndrome (HPS) was made with near normal liver function secondary to amebic liver abscess. It reversed completely following successful treatment of the liver abscess.展开更多
Recurrence of colon cancer still remains a major issue which affects nearly 50% of patients treated by conventional therapeutics. Although the underlying causative factor(s) is not fully understood, development of dr... Recurrence of colon cancer still remains a major issue which affects nearly 50% of patients treated by conventional therapeutics. Although the underlying causative factor(s) is not fully understood, development of drug-resistance has been associated with induction of cancer stem or stem-like cells (CSCs) which constitute a small sub-population of tumor cells known to be highly resistant to chemotherapy. In fact, the discovery of CSCs in a variety of tumors (including colon cancer) has changed the view of carcinogenesis and therapeutic strategies. Emerging reports have indicated that to improve patient outcomes, conventional anticancer therapies should be replaced with specifi c approaches targeting CSCs. Thus, therapeutic strategies that specifically target CSCs are being sought to reduce the risk of relapse and metastasis. In order to specifi cally target colon CSCs (while sparing somatic intestinal stem cells), it is critical to identify unique deregulated pathways responsible for self-renewal of CSCs and colon cancer recurrence. Colon CSCs present a unique opportunity to better understand the biology of solid tumors. Thus, a better understanding of the clinical signs and symptoms of colon cancer patients (under-going surgery or chemotherapy) during perioperative periods, along with the underlying regulatory events affecting the stem/progenitor cell self-renewal and differentiation of colon epithelial cells, is of immense importance. In this review we discuss the implication of clinical factors and the emerging role of CSCs during recurrence of colon cancer along with the development of new therapeutic strategies involving the use of natural agents.展开更多
The air traffic management system(ATM)has the task of ensuring safe,orderly and expeditious flow of air traffic.The ATM system architecture is very much dependent on the concept of operations(ConOps).Over the years th...The air traffic management system(ATM)has the task of ensuring safe,orderly and expeditious flow of air traffic.The ATM system architecture is very much dependent on the concept of operations(ConOps).Over the years the evolution in ConOps has resulted in changes in the ATM′s physical architecture,improving its physical infrastructure,increasing the levels of automation and making operational changes to improve air traffic flow,to cope with increasing demand for air travel.However,what is less clear is the impact of such changes in ConOps on the ATM′s functional architecture.This is vital for ensuring optimality in the implementation of the physical architecture components to support the ATM functions.This paper reviews the changes in the ConOps over the years,proposes a temporally invariant ATM functional model,and discusses some of the main key technologies expected to make significant improvements to the ATM system.展开更多
In order to achieve holistic urban plans incorporating transport infrastructure,public space and the behavior of people in these spaces,integration of urban design and computer modeling is a promising way to provide b...In order to achieve holistic urban plans incorporating transport infrastructure,public space and the behavior of people in these spaces,integration of urban design and computer modeling is a promising way to provide both qualitative and quantitative support to decisionmakers.This paper describes a systematic literature review following a four-part framework.Firstly,to understand the relationship of elements of transport,spaces,and humans,w e review policy and urban design strategies for promoting positive interactions.Secondly,we present an overview of the integration methods and strategies used in urban design and policy discourses.Afterward,metrics and approaches for evaluating the effectiveness of integrated plan alternatives are reviewed.Finally,this paper gives a review of state-of-the-art tools with a focus on seven com puter simulation paradigms.This article explores mechanisms underlying the complex system of transport,spaces,and humans from a multidisciplinary perspective to provide an integrated toolkit for designers,planners,modelers and decision-m akers with the current methods and their challenges.展开更多
文摘AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonicadenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a signif icant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.
文摘A novel upper gastrointestinal bleeding risk stratification score(AIMS65) has recently been developed and validated. It has advantages over existing risk scores including being easy to remember and lack of subjectivity in calculation. We comment on a recent study that has cast doubt on the applicability of AIMS65 in the peptic ulcer disease population. Although promising, further studies are required to evaluate the validity of AIMS65 in various populations.
基金Saaii Educational Foundation, Kanpur-209203,India,for their financial assistance
文摘Objective: This study examined the antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava against methicillin-resistant Staphylococcus aureus (MRSA) and used a standardized purification protocol to determine the presence and abundance of bioactive compounds in the leaf extracts. Methods: In vitro antimicrobial activities of the ethanolic extracts of C sativa, T. orientalis and P. guajava were tested against MRSA. The presence of bioactive molecules in these three leaves was evaluated using biochemical assays and high-performance thin-layer chromatography (HPTLC). Results: Resistance to methicillin, penicillin, oxacillin and cefoxitin was observed in each of the clinical and nonclinical MRSA isolates. However, they were still vulnerable to vancomydn. Used individually, the 50% extract of each plant leaf inhibited MRSA growth. A profound synergism was observed when C sativa was used in combination with T. orientalis (1:1 ) and when P. guajava was used in combination with T. orientalis (1:1 ). This was shown by larger zones of inhibition. This synergism was probably due to the combined inhibitory effect of phenolics present in the leaf extracts (i.e., quercetin and gallic acid) and catechin, as detected by HPTLC. Conclusion: The leaf extracts of C sativa, T. orientalis and P. guajava had potential for the control of both hospital- and community-acquired MRSA. Moreover, the inhibitory effect was enhanced when extracts were used in combination.
文摘Seven different, but highly conserved 14-3-3 proteins are involved in diverse signaling pathways in human cells. It isunclear how the 14-3-3σ isoform, a transcriptional target of p53, exerts its inhibitory effect on the cell cycle in thepresence of other 14-3-3 isoforms, which are constitutively expressed at high levels. In order to identify structuraldifferences between the 14-3-3 isoforms, we solved the crystal structure of the human 14-3-3σ protein at a resolutionof 2.8 ? and compared it to the known structures of 14-3-3ζ and 14-3-3τ. The global architecture of the 14-3-3σ foldis similar to the previously determined structures of 14-3-3ζ and 14-3-3τ: two 14-3-3σ molecules form a cup-shapeddimer. Significant differences between these 14-3-3 isoforms were detected adjacent to the amphipathic groove, whichmediates the binding to phosphorylated consensus motifs in 14-3-3-ligands. Another specificity determining region islocalized between amino-acids 203 to 215. These differences presumably select for the interaction with specific ligands,which may explain the different biological functions of the respective 14-3-3 isoforms. Furthermore, the two 14-3-3σmolecules forming a dimer differ by the spatial position of the ninth helix, which is shifted to the inside of the ligandinteraction surface, thus indicating adaptability of this part of the molecule. In addition, 5 non-conserved residues arelocated at the interface between two 14-3-3σ proteins forming a dimer and represent candidate determinants of homo-and hetero-dimerization specificity. The structural differences among the 14-3-3 isoforms described here presumablycontribute to isoform-specific interactions and functions.
文摘Interaction between bovine serum albumin(BSA) and phosphorus heterocycles(PHs) was studied using multispectroscopic techniques. The results indicated the high binding affinity of PHs to BSA as it quenches the intrinsic fluorescence of BSA. The experimental data suggested the fluorescence quenching mechanism between PHs and BSA as a dynamic quenching. From the UV–vis studies, the apparent association constant(K_(app)) was found to be 9.25×10~2, 1.27×10~4and 9.01×10~2L/mol for the interaction of BSA with PH-1, PH-2 and PH-3,respectively. According to the F?rster's non-radiation energy transfer(FRET) theory, the binding distances between BSA and PHs were calculated. The binding distances(r) of PH-1, PH-2 and PH-3 were found to be2.86, 3.03, and 5.12 nm, respectively, indicating energy transfer occurs between BSA and PHs. The binding constants of the PHs obtained from the fluorescence quenching data were found to be decreased with increase of temperature. The negative values of the thermodynamic parameters ΔH, ΔS and ΔG at different temperatures revealed that the binding process is spontaneous; hydrogen bonds and van der Waals interaction were the main force to stabilize the complex. The microenvironment of the protein-binding site was studied by synchronous fluorescence and circular dichroism(CD) techniques and data indicated that the conformation of BSA changed in the presence of PHs. Finally, we studied the BSA-PHs docking using Auto Dock and results suggest that PHs is located in the cleft between the domains of BSA.
基金funded through Project No.S&T-09/DIP-251,C3.0 from the Defence Research and Development Organization(DRDO),Ministry of Defence,Government of India
文摘Background: The present study was designed to evaluate load carriage performance at extremely high altitudes with different loads and walking speeds in terms of physiological evaluation. The degree of maximum oxygen consumption changes at high altitudes was also examined.Methods: Twelve Indian Army soldiers were acclimatized at altitudes of 3,505 m and 4,300 m. They walked for 10 minutes on a motorized treadmill at 2.5km/h and 3.5km/h speeds during carrying no loads and three magnitudes of load(10.7kg, 21.4kg, 30kg) at both altitudes. Physiological parameters such as oxygen consumption, energy expenditure, heart rate, and ventilation were recorded for each breath using a gas analyzer. The rating of perceived exertion was also noted after each load carriage session. Maximal oxygen consumption(VO2max) was measured at sea level and the two high altitudes, and respective relative workloads(% of VO2max) were calculated from oxygen consumption. Repeated measure ANOVA was applied to reveal the significant effects of the independent variables.Results: The participants had significant reductions in VO2 max with rising altitude. Marked increases in almost all physiological parameters were observed with increasing load, altitude, and speed. The soldiers expressed heavy perceived exertion levels with higher loads at 3.5km/h at the two high altitudes.Conclusions: Considering the physiological responses, expressions of perceived exertion and changes in relative work load at both of the high altitudes. Indian soldiers are advised to walk slowly with adequate rest in between their schedules and to carry not more than 32% of their body weight.
文摘The growing demand for air travel has led to the saturation of air traffic networks.Conventional methods of adding routes to alleviate congestion and reduce delays may not achieve the desired effect and even degrade system performance.In this paper,we explore the application of Braess’s Paradox in the reduction of air traffic networks.This counterintuitive phenomenon shows that adding new connections to a network can actually increase the overall network pressure.This study uses Hidden Markov methods and the Viterbi algorithm to match air traffic flow with routes,a machine learning approach and a mathematical method to construct cost functions for flight time and traffic volume,and finally uses genetic algorithm and the A*algorithm to detect Braess’s Paradox edges.We uses ADS-B data from the busy month of July 2019 for a case study of the air traffic network over the UK airspace.The results show that Braess’s Paradox is also applicable to multi-flight level air route networks.Removing such network edges can improve system performance.In one day’s case,the total flight time of the day’s traffic volume decreased from 11509.24 minutes to 10459.97 minutes.This equates to an average savings of 4.99 minutes of flight time per flight,which is significant in controlling delay performance.
基金This research was supported by the National Natural Science Foundation of China under Award No.U1930401the Department of Energy(DOE),Office of Basic Energy Science,Division of Materials Sciences and Engineering under Award No.DE-FG02-99ER45775
文摘Diamond anvil cell techniques have been improved to allow access to the multimegabar ultrahigh-pressure region for exploring novel phenomena in condensedmatter.However,the onlyway to determine crystal structures of materials above 100 GPa,namely,X-ray diffraction(XRD),especially for lowZ materials,remains nontrivial in the ultrahigh-pressure region,even with the availability of brilliant synchrotron X-ray sources.In thiswork,we performa systematic study,choosing hydrogen(the lowest X-ray scatterer)as the subject,to understand how to better perform XRD measurements of low Z materials at multimegabar pressures.The techniques that we have developed have been proved to be effective in measuring the crystal structure of solid hydrogen up to 254GPa at room temperature[C.Ji et al.,Nature 573,558–562(2019)].Wepresent our discoveries and experienceswith regard to several aspects of thiswork,namely,diamond anvil selection,sample configuration for ultrahigh-pressure XRDstudies,XRDdiagnostics for low Z materials,and related issues in data interpretation and pressure calibration.Webelieve that these methods can be readily extended to other low Z materials and can pave the way for studying the crystal structure of hydrogen at higher pressures,eventually testing structural models of metallic hydrogen.
基金financial support from the International Plant Nutrition Institute of USA (IPNI-2015-CHN-C14)the earmarked fund for China Agriculture Research System (CARS-14)
文摘Field experiments were conducted in oil and edible sunflower to study the effects of potassium(K) fertilization on achene yield and quality, and to estimate the nutrient internal efficiency(IE) and nutrient requirement in sunflower production. All trials in edible sunflower and 75% trials in oil sunflower showed positive yield responses to K fertilization. Compared with control without K fertilization, the application of K increased achene yield by an average of 406 kg ha–1for oil sunflower and 294 kg ha–1for edible sunflower. K application also increased 1 000-achene weight and kernel rate of both oil and edible sunflower. K fertilization improved the contents of oil, oleic acid, linoleic acid and linolenic acid in achenes of oil sunflower, and increased contents of oil, total unsaturated fatty acid and protein in achenes of edible sunflower. The average agronomic efficiency of K fertilizer was 4.0 for oil sunflower and 3.0 kg achene kg–1K2O for edible sunflower. The average IE of N, P and K under balanced NPK fertilization was 22.9, 82.8, and 9.9 kg kg–1for oil sunflower, and 27.3, 138.9, and 14.3 kg kg–1for edible sunflower. These values were equivalent to 45.5, 14.1, and 108.1 kg, and 39.0, 8.0, and 71.7 kg of N, P and K, respectively, in above-ground dry matter required for production per ton of achenes. The average harvest index of N, P and K was 0.47, 0.56 and 0.05 kg kg–1in oil sunflower, and 0.58, 0.58 and 0.14 kg kg–1in edible sunflower.
基金supported by DBT Network Project (BT/PR7928/NDB/52/9/2006)Department of Biotechnology(DBT),Govt. of India
文摘Tree species diversity and population structure at different community types were described and analyzed for primary and secondary lowland moist deciduous forests in Tripura. Overall 10,957 individual trees belonging to 46 family, 103 genera and 144 species were counted at ≥30 cm DBH (diameter at breast height) using 28 permanent belt transects with a size of 1 ha (10 m × 1000 m). Four different tree communities were identified. The primary forests was dominated by Shorea robusta (mean density 464.77 trees.ha^-1, 105 species) and Schima wallichii (336.25 trees.ha^-1, 82 species), while the secondary forests was dominated by Tectona grandis (333.88 trees.ha^-1, 105 species) and Hevea brasiliensis (299.67 trees.ha^-1, 82 species). Overall mean basal area in this study was 18.01m2.ha^-1; the maximum value was recorded in primary Shorea forest (26.21 m2.ha^-1). Mean density and diversity indices were differed significantly within four different communities. No significant differences were observed in number of species, genera, family and tree basal cover area. Significant relationships were found between the species richness and different tree population groups across the communities. Results revealed that species diversity and density were increased in those forests due to past disturbances which resulted in slow accumu- lation of native oligarchic small tree species. Seventeen species were recorded with 〈2 individuals of which Saraca asoka (Roxb.) de Wilde and Entada phaseoloides (L.) Men'. etc. extensively used in local ethnomedicinal formulations. The present S. robusta Gaertn dominated forest was recorded richer (105 species) than other reported studies. Moraceae was found more speciose family instead of Papilionaceae and Euphorbiaceae than other Indian moist deciduous forests. Seasonal phenological gap in such moist deciduous forests influenced the population of Trachypithecus pileatus and capped langur. The analysis of FIV suggested a slow trend of shifting the po
基金supported by the National Institutes of Health (NIH) grants under Award Number R01 AR066044 to MAC R01 AR063631 and AR071614 to JPS R01-AI104732 to SCM
文摘Bone resorption requires the formation of complex, actin-rich cytoskeletal structures. During the early phase of sealing ring formation by osteoclasts, L-plastin regulates actin-bundling to form the nascent sealing zones(NSZ). Here, we show that L-plastin knockout mice produce osteoclasts that are deficient in the formation of NSZs, are hyporesorptive, and make superficial resorption pits in vitro. Transduction of TAT-fused full-length L-plastin peptide into osteoclasts from L-plastin knockout mice rescued the formation of nascent sealing zones and sealing rings in a time-dependent manner. This response was not observed with mutated full-length L-plastin(Ser-5 and-7 to Ala-5 and-7) peptide. In contrast to the observed defect in the NSZ, L-plastin deficiency did not affect podosome formation or adhesion of osteoclasts in vitro or in vivo. Histomorphometry analyses in 8-and 12-week-old female L-plastin knockout mice demonstrated a decrease in eroded perimeters and an increase in trabecular bone density, without a change in bone formation by osteoblasts. This decrease in eroded perimeters supports that osteoclast function is attenuated in L-plastin knockouts. Micro-CT analyses confirmed a marked increase in trabecular bone mass. In conclusion, female L-plastin knockout mice had increased trabecular bone density due to impaired bone resorption by osteoclasts. L-plastin could be a potential target for therapeutic interventions to treat trabecular bone loss.
基金the Indian Space Research Organization(ISRO),India,Science and Engineering Research Board,N.Delhi(POWER Fellowship,SPF/2021/000073,Dt.11-03-2021),Ministry of Human Resource Development(MHRD)Government of India(under IMPRINT-2,sanction letter IMP/2018/001162,Dt.02-01-2019)+1 种基金Department of Science and Technology(DST),N.Delhi(DST/TSG/AMT/2015/636/G,Dt.18-06-2018,DST/TDT/AMT/2017/074(G),Dt.12-09-2018)Alexander von Humboldt Foundation。
文摘The present study concerns understanding the effect of process parameters on the characteristics and flowability of nanocrystalline CoNiCrAlY powder synthesized by mechanical milling.Mechanical milling has been conducted in a planetary ball mill with tungsten carbide(WC)ball,with ball to powder ratio of 10:1 at 300 rpm speed,using 1%stearic acid and toluene as process control agent(PCA)with time varying from 10 h to 36 h.The synthesized nanocrystalline powder were characterized by Scanning Electron Microscopy,X-ray Diffraction technique,X-ray Photoelectron Spectroscopy,and Differential Scanning Calorimetry.Subsequently,flowability in terms of Hausner ratio was assessed by Tap Density Tester.Average particle size of the powder was found to decrease from 33μm to 22μm after 10 h of milling and further increases to 43μm and 38μm after 25 and 36 h of milling,respectively,in stearic acid medium.However,in toluene medium particle size continuously decreases from 33μm to 9.7μm with increasing milling time.The particle morphology changes from spherical to platelet shape at low milling hours in both of the media.After 25 h of milling,the shape of the particles is nearly spherical for stearic acid and irregular for toluene used as a PCA.Crystallize size was found to decrease with increasing milling time from 147 nm to 7.7 nm and to 6.4 nm in stearic acid and toluene media,respectively.There was presence ofγ,γʹ,β,hcp-Co,Al_(2)O_(3)and AlOOH phases on the powder particles milled in both the medium.The measured Hausner ratio of the powders was found to vary from 1.18 to 1.32 in stearic acid medium,and was found to increase with increasing milling time.On the other hand,in toluene media flowability decreases(Hausner ratio increases from 1.33 to 1.44)with increasing milling time.
基金Supported by grants from the National Institute of Aging (5RO1 AG14343) (APNM) and the Department of Veterans Affairs(APNM and AKR) and from The Susan G. Komen Foundation forBreast Cancer Research (AKR)
文摘Members of the receptor tyrosine kinase family, that include EGFR, ErbB-2/HER-2, ErbB-3/HER-3 and ErbB-4/ HER-4, are frequently implicated in experimental models of epithelial cell neoplasia as well as in human cancers. Therefore, interference with the activation of these growth factor receptors represents a promising strategy for de- velopment of novel and selective anticancer therapies. Indeed, a number of inhibitors that target either EGFR or HER-2, with the exception of a few that target both; have been developed for treatment of epithelial cancers. Since most solid tumors express different ErbB receptors and/or their ligands, identification of inhibitor(s), targeting multiple EGFR family members may provide a therapeutic benefit to a broader patient population. Here we describe the significance of an ErbB family of receptors in epithelial cancers, and summarize different available therapeutics targeting these receptors. It also emphasizes the need to develop pan-ErbB inhibitors and discusses EGF-Receptor Related Protein, a recently isolated negative regulator of EGFR as a potential pan-ErbB therapeutic for a wide vari- ety of epithelial cancers.
文摘To estimate woody plant biomass stocks in different patches of forest ecosystems, total 20, 500 × 10 m (0.5 ha) sized line transects were laid in a protected area of Tripura, Northeast India. Overall, 9160 individuals were measured at ≥10 cm diameter at breast height (dbh) in 10 ha sampled area. Estimation of biomass suggested that highest coefficient for allometric relationships between density and biomass in 10 dbh classes was observed in bamboo brakes (R<sup>2</sup> = 0.90) than lowest for semi evergreen patch (R<sup>2</sup> = 0.48). The stock of carbon (C) was differ significantly along the forest patches (F = 7.01, df = 3.19;p < 0.01). Most of biomass stock (69.38%) was accumulated in lower dbh class (<30 cm) and only 23% of biomass was estimated at higher dbh classes (> 70 cm). Range of biomass stock (37.85 - 85.58 Mg ha<sup>-</sup><sup>1</sup>) was low, compared to other tropical forest ecosystems in India, which implies that the proper management is required to monitor regional ecosystem C pool.
文摘Optical metasurfaces are currently an important research area all around the world because of their wide application opportunities in imaging,wavefront engineering,nonlinear optics,quantum information processing,just to name a few.The feature issue“Optical Metasurfaces:Fundamentals and Applications”in Photonics Research allows for archival publication of the most recent works in optical metasurface and provides for broad dissemination in the photonics community.
文摘Aim:To investigate the status of seminal plasma reduced glutathione(GSH)and vitamin E in three different condi-tions of spermatogenesis:azoospermia,oligozoospermia and nonnospennia.Methods:Reduced glutathione wasmeasured in the seminal plasma by the method of Moron et al(1979),and vitamin E estimation was performed by themethod of Taylor et al(1976).Results:Vitamin E levels in seminal plasma of oligospermic and azoospennic sam-ples were significantly decreased to 65.54%and 66.04%respectively as compared to the normospermic group.Levelsof reduced glutathione were also significantly decreased in oligospermic and azoospennic group,and the reduction inazoospermic group(76.73%)was more pronounced than oligozoospermic group(62.07%).Conclusion.The de-crease in reduced glutathione,an endogenous antioxidant,levels in azoospermic and oligozoospermic conditions maycause dismption in the membrane integrity of spermatozoa as a consequence of increased oxidative stress.
文摘A middle aged, non-addict male presented with right upper abdominal pain and swelling with respiratory distress. Examination revealed central cyanosis, bipedal pitting edema with prominent epigastric and back veins. Liver was enlarged, tender, spanned 20 cm without any splenomegaly or ascites. Other systems were clinically normal. Laboratory investigations showed polymorphonuclear leucocytosis with slightly deranged liver function. Abdominal ultrasonography showed an abscess in the right lobe of the liver with compressed inferior vena cava (IVC), middle and left hepatic veins. Arterial blood gas (ABG) documented hypoxia with orthodeoxia and air-contrast echocardiography was suggestive of an intrapulmonary shunt. A diagnosis of hepato-pulmonary syndrome (HPS) was made with near normal liver function secondary to amebic liver abscess. It reversed completely following successful treatment of the liver abscess.
基金Supported by The National Institutes of Health/National Institute on Aging, AG014343the Department of Veterans Affairs, to Adhip PN Majumdar
文摘 Recurrence of colon cancer still remains a major issue which affects nearly 50% of patients treated by conventional therapeutics. Although the underlying causative factor(s) is not fully understood, development of drug-resistance has been associated with induction of cancer stem or stem-like cells (CSCs) which constitute a small sub-population of tumor cells known to be highly resistant to chemotherapy. In fact, the discovery of CSCs in a variety of tumors (including colon cancer) has changed the view of carcinogenesis and therapeutic strategies. Emerging reports have indicated that to improve patient outcomes, conventional anticancer therapies should be replaced with specifi c approaches targeting CSCs. Thus, therapeutic strategies that specifically target CSCs are being sought to reduce the risk of relapse and metastasis. In order to specifi cally target colon CSCs (while sparing somatic intestinal stem cells), it is critical to identify unique deregulated pathways responsible for self-renewal of CSCs and colon cancer recurrence. Colon CSCs present a unique opportunity to better understand the biology of solid tumors. Thus, a better understanding of the clinical signs and symptoms of colon cancer patients (under-going surgery or chemotherapy) during perioperative periods, along with the underlying regulatory events affecting the stem/progenitor cell self-renewal and differentiation of colon epithelial cells, is of immense importance. In this review we discuss the implication of clinical factors and the emerging role of CSCs during recurrence of colon cancer along with the development of new therapeutic strategies involving the use of natural agents.
文摘The air traffic management system(ATM)has the task of ensuring safe,orderly and expeditious flow of air traffic.The ATM system architecture is very much dependent on the concept of operations(ConOps).Over the years the evolution in ConOps has resulted in changes in the ATM′s physical architecture,improving its physical infrastructure,increasing the levels of automation and making operational changes to improve air traffic flow,to cope with increasing demand for air travel.However,what is less clear is the impact of such changes in ConOps on the ATM′s functional architecture.This is vital for ensuring optimality in the implementation of the physical architecture components to support the ATM functions.This paper reviews the changes in the ConOps over the years,proposes a temporally invariant ATM functional model,and discusses some of the main key technologies expected to make significant improvements to the ATM system.
文摘In order to achieve holistic urban plans incorporating transport infrastructure,public space and the behavior of people in these spaces,integration of urban design and computer modeling is a promising way to provide both qualitative and quantitative support to decisionmakers.This paper describes a systematic literature review following a four-part framework.Firstly,to understand the relationship of elements of transport,spaces,and humans,w e review policy and urban design strategies for promoting positive interactions.Secondly,we present an overview of the integration methods and strategies used in urban design and policy discourses.Afterward,metrics and approaches for evaluating the effectiveness of integrated plan alternatives are reviewed.Finally,this paper gives a review of state-of-the-art tools with a focus on seven com puter simulation paradigms.This article explores mechanisms underlying the complex system of transport,spaces,and humans from a multidisciplinary perspective to provide an integrated toolkit for designers,planners,modelers and decision-m akers with the current methods and their challenges.