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Abstract The production cross sections of D0, D+, and Λ c + $$ {\Lambda}_{\textrm{c}}^{+} $$ hadrons originating from beauty-hadron decays (i.e. non-prompt) were measured for the first time at midrapidity in proton–lead (p–Pb) collisions at the center-of-mass energy per nucleon pair of s NN $$ \sqrt{s_{\textrm{NN}}} $$ = 5.02 TeV. Nuclear modification factors (R pPb) of non-prompt D0, D+, and Λ c + $$ {\Lambda}_{\textrm{c}}^{+} $$ are calculated as a function of the transverse momentum (p T) to investigate the modification of the momentum spectra measured in p–Pb collisions with respect to those measured in proton–proton (pp) collisions at the same energy. The R pPb measurements are compatible with unity and with the measurements in the prompt charm sector, and do not show a significant p T dependence. The p T-integrated cross sections and p T-integrated R pPb of non-prompt D0 and D+ mesons are also computed by extrapolating the visible cross sections down to p T = 0. The non-prompt D-meson R pPb integrated over p T is compatible with unity and with model calculations implementing modification of the parton distribution functions of nucleons bound in nuclei with respect to free nucleons. The non-prompt Λ c + $$ {\Lambda}_{\textrm{c}}^{+} $$ /D0 and D+ /D0 production ratios are computed to investigate hadronisation mechanisms of beauty quarks into mesons and baryons. The measured ratios as a function of p T display a similar trend to that measured for charm hadrons in the same collision system.

Emulators of Earth system models (ESMs) are statistical models that approximate selected outputs of ESMs. Owing to their runtime efficiency, emulators are especially useful when large amounts of data are required, for example, for in-depth exploration of the emission space, for investigating high-impact low-probability events, or for estimating uncertainties and variability. This paper introduces an emulation framework that allows us to emulate gridded monthly mean precipitation fields using gridded monthly mean temperature fields as forcing. The emulator is designed as an extension of the Modular Earth System Model Emulator (MESMER) framework, and its core relies on the concepts of generalised linear models (GLMs). Precipitation at each (land) grid point and for each month is approximated as a multiplicative model with two factors. The first factor entails the temperature-driven precipitation response and is assumed to follow a gamma distribution with a logarithmic link function. The second factor is the residual variability in the precipitation field, which is assumed to be independent of temperature but may still possess spatial precipitation correlations. Therefore, the monthly residual field is decomposed into independent principal components and subsequently approximated and sampled using a kernel density estimation with a Gaussian kernel. The emulation framework is tested and validated using 24 ESMs from the sixth phase of the Coupled Model Intercomparison Project (CMIP6). For each ESM, we train on a single-ensemble member across scenarios and evaluate the emulator performance using simulations with historical and Shared Socioeconomic Pathways (SSP5-8.5) forcing. We show that the framework captures grid-point-specific precipitation characteristics, such as variability, trend, and temporal auto-correlations. In addition, we find that emulated spatial (cross-variable) characteristics are consistent with those of ESMs. The framework is also able to capture compound hot–dry and cold–wet extremes, although it systematically underestimates their occurrence probabilities. The emulation of spatially explicit coherent monthly temperature and precipitation time series is a major step towards a computationally efficient representation of impact-relevant variables of the climate system.

Abstract Background Epidermolysis Bullosa (EB) is a genetic condition with fragility of the skin and oral mucosal lining requiring appropriate care and management by dental health professionals. The objective of this scoping review was to comprehensively examine the specialised dental needs of children with Epidermolysis Bullosa and map evidence towards the type, availability, and accessibility of specialised dental care services within various health care systems. Methods This scoping review was conducted using the JBI Methodology framework for scoping reviews. Five databases were used to source relevant literature: MEDLINE, Embase, Dentistry & Oral Sciences Source, Scopus, and Web of Science during the period 1963–2022. Results Thirty three published case reports were identified reporting on 45 participants encompassing the dental care and management of children diagnosed with EB aged between 0–12 years of age from an Australian and international health care context. The findings reveal the need for greater awareness amongst health professionals in the management and specialised dental care needs of children and the need for further research, and care pathways for children with EB. Conclusion There is a dearth of evidence which examines the dental needs of children, in particular referral pathways and timely access to dental health services and professionals. Dentists play an important role in monitoring and providing individualised and specialised oral care and treatment to the child with EB. It is vital that dentists as well as the wider multidisciplinary team have knowledge and understanding of the EB condition in meeting the specialised needs and management of these children.

Land cover changes have been proposed to play a significant role, alongside emission reductions, in achieving the temperature goals agreed upon under the Paris Agreement. Such changes carry both global implications, pertaining to the biogeochemical effects of land cover change and thus the global carbon budget, and regional or local implications, pertaining to the biogeophysical effects arising within the immediate area of land cover change. Biogeophysical effects of land cover change are of high relevance to national policy and decision makers, and accounting for them is essential for effective deployment of land cover practices that optimise between global and regional impacts. To this end, Earth system model (ESM) outputs that isolate the biogeophysical responses of climate to land cover changes are key in informing impact assessments and supporting scenario development exercises. However, generating multiple such ESM outputs in a manner that allows comprehensive exploration of all plausible land cover scenarios is computationally untenable. This study proposes a framework to explore in an agile manner the local biogeophysical responses of climate under customised tree cover change scenarios by means of a computationally inexpensive emulator, the Tree cover change clIMate Biophysical responses EmulatoR (TIMBER) v0.1. The emulator is novel in that it solely represents the biogeophysical responses of climate to tree cover changes, and it can be used as either a standalone device or as a supplement to existing climate model emulators that represent the climate responses from greenhouse gas (GHG) or global mean temperature (GMT) forcings. We start off by modelling local minimum, mean, and maximum surface temperature responses to tree cover changes by means of a month- and Earth system model (ESM)-specific generalised additive model (GAM) trained over the whole globe; 2 m air temperature responses are then diagnosed from the modelled minimum and maximum surface temperature responses using observationally derived relationships. Such a two-step procedure accounts for the different physical representations of surface temperature responses to tree cover changes under different ESMs whilst respecting a definition of 2 m air temperature that is more consistent across ESMs and with observational datasets. In exploring new tree cover change scenarios, we employ a parametric bootstrap sampling method to generate multiple possible temperature responses, such that the parametric uncertainty within the GAM is also quantified. The output of the final emulator is demonstrated for the Shared Socioeconomic Pathway (SSP) 1-2.6 and 3-7.0 scenarios. Relevant temperature responses are identified as those displaying a clear signal in relation to their surrounding parametric uncertainty, calculated as the signal-to-noise ratio between the sample set mean and sample set variability. The emulator framework developed in this study thus provides a first step towards bridging the information gap surrounding biogeophysical implications of land cover changes, allowing for smarter land use decision making.

The degree of trust placed in climate model projections is commensurate with how well their uncertainty can be quantified, particularly at timescales relevant to climate policy makers. On inter-annual to decadal timescales, model projection uncertainty due to natural variability dominates at the local level and is imperative to describing near-term and seasonal climate events but difficult to quantify owing to the computational constraints of producing large ensembles. To this extent, emulators are valuable tools for approximating climate model runs, allowing for the exploration of the uncertainty space surrounding selected climate variables at a substantially reduced computational cost. Most emulators, however, operate at annual to seasonal timescales, leaving out monthly information that may be essential to assessing climate impacts. This study extends the framework of an existing spatially resolved, annual-scale Earth system model (ESM) emulator (MESMER, Beusch et al., 2020) by a monthly downscaling module (MESMER-M), thus providing local monthly temperatures from local yearly temperatures. We first linearly represent the mean response of the monthly temperature cycle to yearly temperatures using a simple harmonic model, thus maintaining month-to-month correlations and capturing changes in intra-annual variability. We then construct a month-specific local variability module which generates spatio-temporally correlated residuals with yearly temperature- and month-dependent skewness incorporated within. The emulator's ability to capture the yearly temperature-induced monthly temperature response and its surrounding uncertainty due to natural variability is demonstrated for 38 different ESMs from the sixth phase of the Coupled Model Intercomparison Project (CMIP6). The emulator is furthermore benchmarked using a simple gradient-boosting-regressor-based model trained on biophysical information. We find that while regional-scale, biophysical feedbacks may induce non-uniformities in the yearly to monthly temperature downscaling relationship, statistical emulation of regional effects shows comparable skill to the more physically informed approach. Thus, MESMER-M is able to statistically generate ESM-like, large initial-condition ensembles of spatially explicit monthly temperature fields, providing monthly temperature probability distributions which are of critical value to impact assessments.

Tropical cyclones are among the most damaging extreme weather events. An increase in Atlantic tropical cyclone activity has been observed, but attribution to global warming remains challenging due to large inter-annual variability and modeling challenges. Here we show that the increase in Atlantic tropical cyclone activity since the 1980s can be robustly ascribed to variations in atmospheric circulation as well as sea surface temperature (SST) increase. Based on a novel weather-pattern-based statistical model, we find that the forced warming trend in Atlantic SSTs over the 1982–2020 period has doubled the probability of extremely active tropical cyclone seasons. For the year 2020, our results suggest that such an exceptionally intense season might have been made twice as likely by ocean surface warming. In our statistical model, seasonal atmospheric circulation remains the dominant factor explaining the inter-annual variability and the occurrence of very active seasons. However, our study underscores the importance of rising SSTs that lead to more extreme outcomes in terms of cyclone intensity for the same seasonal atmospheric patterns. Our findings provide a new perspective on the contribution of ocean warming to the increase in recent hurricane activity and illustrate how anthropogenic climate change has contributed to a decisive increase in Atlantic tropical cyclone season activity over the observational period.

The impact of noise pollution in urban healthy livings are not well documented and is seen often get less attention than it should. The increasing noise in urban settings must be studied further due to its site-specific nature for adoption of appropriate control measures or for better zoning of city's land uses. The present study assessed and evaluated the spatiotemporal variability of noise level and noise pollution indices for Chattogram City Corporation (CCC) in Bangladesh as study area. A total of 123 selected points were uniformly distributed to 41 wards under CCC has been taken as measuring sites. An ArcGIS 10.4 software is used to develop and evaluate the variations in noise descriptor and pollution indices in a graphical format. The study found that irrespective of sources, in general, city dwellers experienced moderately high noise with an average noise level of 75 dBA exceeding the limit values set by the Department of Environment (DoE), Bangladesh, World Health Organization (WHO), American Association of State Highway and Transportation Official (AASHTO) for different land uses individually or in combination. With an exception of few wards located far from major roads and with less population and industries, the city dwellers at 14 wards located in the north west, central and few parts of south belt experienced as high as 80 to 90 dBA based on noise equivalent (Leq), noise climate (NC) and noise pollution level (NPL) indices. The higher NPL of its standard value of 88 dBA is found at 14 wards align with the higher Leq and NC located close to major and urban road networks in CCC, while other 12 wards located in the central belt of the city are also with upper bound of limit values. Based on the results and reviewing the recommendations and standards, only three (3) out of the 41 wards or areas considered are under normally acceptable situation, while 12 wards are under normally unacceptable and the noise levels of the rest locations are clearly unacceptable. An immediate zoning of city's land uses and urban settings are to be taken in the identified wards. The outcomes of this study may assist policy makers, regulatory bodies and local council to adopt appropriate measures to ensure healthy living environment for city dwellers.

A hydroelastic model is developed to study the interaction of linear long gravity waves with a very large floating flexible plate resting on a viscoelastic foundation, which is based on the Kelvin–Voigt model. Flexural gravity wave blocking occurs for specific values of the compressive force in the absence of viscous damping. During wave blocking, the group velocity vanishes, and mode swapping occurs. Within wave blocking and plate buckling limit in the presence of compressive force, three distinct propagating modes occur in the absence of viscous damping. Moreover, the study reveals that irrespective of the values of viscous damping constant, the blocking/buckling points shift to a higher wavenumber with an increase in the value of elastic foundation constant. On the other hand, the flexural gravity wave modes become complex in the presence of a viscoelastic foundation. The complex wave modes are classified as predominant progressive wave modes and rapidly decaying modes. In the presence of viscous damping, wave blocking does not happen before the buckling limit of the compressive force. However, the phase velocity vanishes, and the group velocity becomes continuous irrespective of the value of non-zero viscous damping at the buckling limit for the compressive force. The detailed behavior of the roots of the dispersion equation and the mode shapes are illustrated through contour plots and by analyzing the roots’ loci. Furthermore, plate deflections are exhibited for different wave and structural parameters.

A statistical model description of heavy ion induced fusion–fission reactions is presented where shell effects, collective enhancement of level density, tilting away effect of compound nuclear spin and dissipation are included. It is shown that the inclusion of all these effects provides a consistent picture of fission where fission hindrance is required to explain the experimental values of both pre-scission neutron multiplicities and evaporation residue cross-sections in contrast to some of the earlier works where a fission hindrance is required for pre-scission neutrons but a fission enhancement for evaporation residue cross-sections.

The aim is to bring together the new anthropological techniques and knowledge about populations that are least known. The present study was performed on 901 healthy Gujarati volunteers (676 males, 225 females) within the age group of 21–50 years with the aim to examine whether any correlation exists between cephalofacial measures naming maximum head length, maximum head breadth, bizygomatic breadth, bigonial diameter, morphological facial length, physiognomic facial length, biocular breadth and total cephalofacial height and sex determination. Also, discriminant function and logistic regression methods were verified to check the best accuracy level for sex determination. Mean values of cephalofacial dimensions were higher in males than in females. Best reliable results were obtained by using logistic regression equations in males (92%) and discriminant function in females (80.9%). Our study conclusively establishes the existence of a definite statistically significant sexual dimorphism in Gujarati population using cephalo-facial dimensions.

The present work focuses on the anti-neoplastic role of non steroidal anti-inflammatory drugs (NSAIDs) in modulating the biophysical parameters of the colonic membranes in 1,2-dimethylhydrazine dihydrochloride (DMH) induced carcinogenesis. The steady-state fluorescence polarization technique was applied to assess membrane fluidity, membrane polarity and lipid phase states. The decline in cholesterol content, biosynthesis and cholesterol: phospholipids ratio with DMH treatment indicates more fluidity associated with carcinogenesis. The DMH group had shown lower order parameter indicating more fluidity whereas NSAIDs resulted in increasing the membrane lipid order. The converging effects of these changes were more in membrane phase separations and membrane phase state. In DMH treatment membrane shows lesser phase separation or high polarity, and more liquid crystalline state while for NSAID groups membranes have higher phase separations or low polarity, and more of the gel phase. Further, NSAIDs induced anti-proliferative effects were evidently observed by apoptosis in the colonocytes by using acridine orange-ethidium bromide fluorescent staining and Terminal de-oxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The results suggest that NSAIDs induced alteration in the membrane biophysical parameters may be an important initiating event for the chemopreventive action.Este trabajo se centra en el papel antineoplásico de los fármacos antiinflamatorios no esteroideos (AINE) en la modulación de los parámetros biofísicos de las membranas colónicas en la carcinogénesis inducida por 1,2-dihidrocloruro de dimetilhidracina (DMH). Se aplicó la técnica de polarización de la fluorescencia en estado de equilibrio para evaluar la fluidez de la membrana, su polaridad y los estados de fase lipídica. El declive del contenido de colesterol, la biosíntesis y el cociente colesterol: fosfolípidos con el tratamiento con DMH indica más fluidez asociada con la carcinogénesis. El grupo DMH mostraba un parámetro de menor orden, lo que indica más fluidez, mientras que los AINE produjeron un aumento del orden de lípidos de membrana. Los efectos convergentes de estos cambios fueron más notables en las separaciones de la fase de membrana y en el estado de fase de membrana. Con el tratamiento con DMH, la membrana muestra menor separación de fase o polaridad elevada, y un estado cristalino más líquido o polaridad elevada mientras que los grupos de AINE tienen mayores separaciones de membrana o polaridad baja y más fase en estado gel. Además, los efectos antiproliferativos inducidos por los AINE se observaron de forma evidente utilizando tinción fluorescente con naranja de acridinabromuro de etidio y el ensayo de marcado final de la dUTP transferasa desoxinucleotidil terminal (TUNEL). Los resultados sugieren que los AINE inducían una alteración de los parámetros biofísicos de la membrana, lo cual podría ser un acontecimiento inicial importante para la acción quimiopreventiva.

Non steroidal anti inflammatory drugs (NSAIDs) are efficacious in chemoprevention of colorectal cancer. Therefore, the potential ability of Etoricoxib, a selective cycloxygenase-2(COX-2) inhibitor and Diclofenac, a preferential COX-2 inhibitor are considered in the chemoprevention of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rat model. DMH was injected s.c. for six weeks while Etoricoxib and Diclofenac were fed daily orally alone and also in combination with an weekly subcutaneous injection of 1,2-dimethylhydrazine dihydrochloride (DMH) to the rats. After the treatment period of 6 weeks the animals were sacrificed by an overdose of ether anesthesia and the colonic tissues were removed and studied by the FTIR and NMR Spectroscopic techniques to evaluate the changes occurring in the lipid bilayer of colonic membrane lipids. The alterations in wave number of FTIR spectra as well as the chemical shifts of NMR spectra were recorded which signify the modulation of membrane lipids during colon carcinogenesis and possible cancer prevention by the oral administration of NSAIDs in an experimental model of chemical induced colon carcinogenesis.Los fármacos antiinflamatorios no esteroideos (AINE) son eficaces en la prevención del cáncer colorrectal. Por lo tanto, la capacidad potencial de Etoricoxib, un inhibidor selectivo de la ciclooxigenasa-2(COX-2), y de Diclofenaco, un inhibidor preferencial de la COX-2, se considera en la quimioprevención de la carcinogénesis de colon inducida por 1, 2-dimetilhidracina (DMH) en el modelo murino. Se inyectó s.c. DMH durante 6 semanas a la vez que se administraban diariamente por vía oral Etoricoxib y Diclofenaco solos y en combinación con una inyección s.c. semanal de dihidrocloruro de 1,2-dimetilhidracina (DMH) a las ratas. Después del período de tratamiento de 6 semanas, se sacrificó a los animales mediante una sobredosis de anestesia con éter y se extirpó el tejido colónico para estudio con las técnicas espectroscópicas FTIR y NMR para evaluar los cambios que ocurrieron en la bicapa lipídica de las membranas lipídicas colónicas. Se registraron las alteraciones en el número de onda del espectro FTIR así como las desviaciones químicas del espectro NMR, lo que significa la modulación de los lípidos de membrana durante la carcinogénesis colónica y la posible prevención del cáncer mediante la administración de AINE por vía oral en un modelo experimental de carcinogénesis colónica inducida por un agente químico.

In this paper, we present the effect of total solar eclipse on surface O3, NO, NO2, NH3, CO mixing ratio and the meteorological parameters on 15 January 2010 at Thiruvanathapuram, India. On the day of total solar eclipse (i.e., 15 January 2010), the decrease in mixing ratio of surface O3 and NO2 is observed after the beginning of the solar eclipse events (11:15 to 15:30). Decrease in surface O3 may be due to decreased efficiency of the photochemical ozone formation, whereas, mixing ratio of NO and NH3 have been changed following the night time chemistry. Surface O3 reduced to 20.3 ppb after 22 min of full phase of the eclipse. During the solar eclipse period, the ambient temperature and wind speed have decreased, whereas, relative humidity has increased as expected.

The direct aerosol radiative forcing (DARF) has been estimated for the clear-sky conditions over Delhi from January 2006 to January 2007 using Santa Barbara DISORT Atmospheric Radiative Transfer model (SBDART) in the wavelength range 300–3000 nanometer. The single scattering albedo (SSA) and the asymmetry parameter used in this model were estimated using the Optical Properties of Aerosol and Cloud (OPAC) model. The annual average AOD observed at 500 nm was ~0.86±0.42 with an average Angstrom exponent ~0.68±0.35. The average monthly AOD throughout the year over Delhi was found to be in the range 0.56 to 1.22 with the Angstrom exponent in the range 0.38 to 0.96. A high monthly average BC concentration in the range 4–15 μg m−3 led to monthly average SSA in the range 0.90±0.4 to 0.74±0.3 during the year. Consequently, the monthly average clear-sky DARF at the surface was found to vary in the range −46±8 W m−2 to −110±20 W m−2, at TOA in the range −1.4±0.4 to 21±2 W m−2, whereas in the atmosphere it was in the range 46±9 W m−2 to 115±19 W m−2 throughout the year. As the dust concentration in the atmosphere was highest (May–June) the SSA showed an increase with wavelength however when dust concentration was low the SSA decreased with the wavelength.

Aspirin at a dose of 50 mg/kg body weight was found to decrease the activity of the rat intestinal brush border membrane (BBM) - associated enzymes such as the sucrase, lactase, maltase and alkaline phosphatase. Aspirin treatment also led to a decrease in the microviscosity in the native as well as the benzyl alcohol treated membrane which might be due to the lipid peroxidative damage in the membrane. Physical correlation of the membrane oxidative damage was evident as the Fourier Transformation Infra Red (FTIR) study of the Aspirin treated membrane, which include an increased proportion of gauche to trans conformer, shift in the methylene C-H asymmetric and symmetric stretching frequencies, C = O double bond stretching, NH bending, antisymmetric (N)-CH3 bending, C-N stretching and antisymmetric CNC stretching while there was no change in the CH2 wagging and twisting as well as in NH-bending amide bond I and II. Aspirin treatment also caused an alteration in the glucose and histidine transport, as evident by a decreased Vmax value while the apparent Km remaining unchanged in the control and Aspirin-treated animals confirming that there was no change in the substrate affinity constant of the membrane transport proteins for the glucose and the basic amino acid, although the rate of transport decreased considerably. There was a decrease noted in the energy of activation of glucose and histidine transport when studied at different temperature but no change in the temperature of phase transition in the BBM with Aspirin treatment, thus implying that perhaps the thermotropic phase transition in the membrane may have relatively little effect on the transport processes. The result suggests an underlying molecular mechanism indicating the implied membrane damage by Aspirin, an important member of the non-steroidal antiinflammatory drug (NSAID) family which could possibly through an oxidative damage may lead to an altered molecular structure, physical state and biological functions of the intestinal membrane.Se encontró que la aspirina a una dosis de 50 mg/kg de peso corporal disminuye la actividad de las enzimas asociadas a la membrana con borde en cepillo (MBC) del intestino de la rata como la sucrasa, lactasa, maltasa y fosfata alcalina. El tratamiento con aspirina también produjo una disminución de la microviscosidad en la membrana nativa así como en la membrana tratada con alcohol bencílico, lo que podría deberse a la lesión de peroxidación lipídica de la membrana. La correlación física de la lesión oxidativa de la membrana fue evidente como mostró el estudio Fourier Transformation Infra Red (FTIR) de la membrana tratada con aspirina, que incluía un aumento en la proporción de la conformación levo a trans, un cambio en las frecuencias de estiramiento metileno C-H asimétrico y simétrico, el estiramiento de los dobles enlaces C = O, la curvatura NH, la curvatura anti-simétrica (N)-CH3, el estiramiento C-N y el estiramiento anti-simétrico CNC, mientras que no hubo cambios en el movimiento y retorcimiento CH2 ni en la curvatura NH del enlace amida I y II. El tratamiento con aspirina también produjo una alteración en el transporte de glucosa e histidina, como se evidenció por una disminución del valor de la Vmax mientras que la Km aparente permaneció inalterada en los animales control y tratados con aspirina, lo que confirma que no hubo cambios en la constante de afinidad por el sustrato de las proteínas transportadoras de membrana para la glucosa y el aminoácido básico, si bien la tasa de transporte disminuyó considerablemente. Se apreció un descenso en la energía de activación del transporte de glucosa e histidina cuando se estudiaron a temperaturas distintas, pero no hubo cambios en la temperatura de la fase de transición de la MBC con el tratamiento con aspirina, lo que implica que quizás la fase de transición termotrópica en la membrana pudiera tener un efecto relativamente pequeño sobre los procesos de transporte. El resultado sugiere un mecanismo molecular subyacente lo que indica el daño implícito de la membrana por la aspirina, un miembro importante de la familia de fármacos antiinflamatorios no esteroideos (AINE), que posiblemente a través de un daño oxidativo podría producir una alteración de la estructura molecular, del estado físico y de las funcionesbiológicas de la membrana intestinal.

The chemopreventive response was evaluated of nonsteroidal anti-inflammatory drug, Diclofenac, a preferential cyclooxygenase-2 (COX-2) inhibitor in 1,2-dimethyhydrazine (DMH)-induced colon cancer in rat model. The signs of neoplasm were evident in the animals receiving 30mg of DMH per kg body weight in a weekly s.c injection for six weeks. The putative biomarker of carcinogenesis was visible in the form of multiple plaque lesions in DMH treatment and then regression seen in those animals which also received an oral dose of Diclofenac, 8 mg/kg body weight whereas no such macroscopic neoplastic lesions were seen in the animals receiving Diclofenac only or the control animals receiving the vehicle of the drug. Histopathological results showed the presence of early aberrant changes in the form of severe dysplasia and also numerous crypt fissions in the apical surface of the colonic mucosa. A very high expression of COX-2 was seen in the colonic epithelium of DMH-treated rats, as analyzed by immunohistochemistry. Also, the apoptotic events were assessed by terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) assay, where the DMH group shows few number of TUNEL positive cells which dramatically increased in the Diclofenac treatment. The results suggest that Diclofenac could be an effective chemopreventive agent in colon cancer, where perhaps apoptosis plays a very dominant end effect in cancer cell killings.Se evaluó la respuesta quimiopreventiva del fármaco antiinflamatorio no esteroideo, diclofenaco, un inhibidor preferente de la ciclooxigenasa-2 (Cox-2), en el cáncer de colon inducido por 1,2-dimetilhidracina (DMH) en un modelo de rata. Los signos de neoplasia fueron evidentes en los animales que recibieron 30 mg de DMH por kg de peso corporal mediante inyecciones s.c. semanales durante 6 semanas. El biomarcador putativo de la carcinogénesis fue visible en la forma de múltiples lesiones en placas con el tratamiento de DMH y la posterior regresión apreciada en los animales que también recibieron una dosis oral de diclofenaco, 8 mg/kg de peso corporal, mientras que no se vieron tales lesiones neoplásicas macroscópicas en los animales que recibieron solamente el diclofenaco o en los animales control que recibieron el vehículo del fármaco. Los resultados histopatológicos mostraron la presencia de cambios aberrantes precoces en la forma de una displasia intensa y también numerosas fisiones de las criptas en la superficie apical de la mucosa colónica. Se vio una expresión muy elevada de Cox-2 en el epitelio colónico de las ratas tratadas con DMH, al analizarlo por inmunohistoquímica. También se evaluaron los eventos apoptóticos mediante el ensayo terminal deoxynucleotidyl dutp nick end labeling (TUNEL), en el que el grupo DMH mostró un pequeño número de células TUNEL positivas, que se incrementó notablemente en el grupo de tratamiento con diclofenaco. Estos resultados sugieren que podría existir un agente quimiopreventivo eficaz para el cáncer de colon en el que, quizás, la apoptosis desempeñe un efecto terminal muy dominante en la muerte de las células cancerosas.

The present study was designed to evaluate the effects of three non-steroidal anti-inflammatory drugs (NSAIDs) with varying cycloxygenase selectivities on the small intestinal biochemical composition, function and histology during 1, 2-dimethylhydrazine (DMH) administration. Sprague Dawley male rats were divided into five different groups viz: Group 1 (control, vehicle treated), Group 2 (DMH-treated, 30 mg/kg body weight/week in 1 mM EDTA-saline, subcutaneously), Group 3 (DMH + aspirin-60 mg/kg body weight), Group 4 (DMH + celecoxib-6 mg/kg body weight), Group 5 (DMH + etoricoxib-0.64 mg/kg body weight). After six weeks of treatment, brush border membrane was isolated from the jejunum segment of all the groups and changes in the associated enzymes such as sucrase, lactase, maltase, alkaline phosphatase, membrane lipid composition, fluorescence polarizations of diphenylhexatriene, pyrene excimer formation, histological changes and surface characteristics were studied. The results indicated a significant alteration in the enzyme activity as well as changes in the structure and function of the intestine in the presence of the pro-carcinogen, DMH, which suggests the possible chemopreventive efficacy of NSAIDs against the intestinal cancer.El presente estudio se diseñó para evaluar los efectos de tres fármacos antiinflamatorios no esteroideos (AINE) con diferente selectividad por la ciclooxigenasa sobre la composición bioquímica, la función y la histología del intestino delgado durante la administración de 1,2-dimetilhidracina (DMH). Se distribuyó a ratas macho Sprague Dawley en grupos distintos: Grupo 1 (control, tratado con vehículo), Grupo 2 (tratado con DMH, 30 mg/kg de peso /semana en 1 mM de EDTA-salino, subcutáneo), Grupo 3 (DMH + aspirina-60 mg/kg de peso), Grupo 4 (DMH + celecoxib-6 mg/kg de peso), Grupo 5 (DMH + etoricoxib-0,64 mg/kg de peso). Tras seis semanas de tratamiento, se aisló la membrana en cepillo de un segmento del yeyuno en todos los grupos y se estudiaron los cambios en las enzimas asociadas tales como sucrasa, lactasa, maltasa, fosfatasa alcalina, en la composición lipídica de la membrana, las polarizaciones de fluorescencia del difenilhexatrieno, la formación del excímero pireno, los cambios histológicos y las características de la superficie. Los resultados indican una alteración significativa de la actividad enzimática así como cambios en la estructura y función del intestino en presencia del procarcinógeno DMH, lo que sugiere la posible eficacia quimio-preventiva de los AINE frente al cáncer de intestino.

The present study was designed to investigate the gastrointestinal side effects of cycloxygenase (COX) inhibitor with varying selectivity, called the non-steroidal antiinflammatory drugs (NSAIDs) viz., non-selective COX-1 & 2 inhibitor -aspirin, prefentially selective COX-2 inhibitor- nimesulide and highly selective COX-2 inhibitor- celecoxib. Treatment with NSAIDs exhibited a decrease in the activity of rat intestinal brush border membrane associated enzymes such as sucrase, lactase, maltase and alkaline phosphatase as compared to the control in the duodenum, jejunum and ileum. The uptake of D-glucose and L-histidine in the everted intestinal sac was found to be decreased. Also the decease of glucose and histidine uptake was found to be dependent on the substrate concentration, temperature and the time interval of incubation. The physical state and composition of brush border membrane was found to be altered as evident in the FTIR spectrum, by appearance of new peaks while disappearance of certain peaks occurred which were characteristics of the control membrane. The changes in wave number as well as peaks height were also noticed. Alterations in protein profile of the membrane were demonstrated using SDS-PAGE analysis where disappearance of few bands and change in the relative intensities of the bands were noticed and correlated with the alterations that have taken place at the molecular level. Histological studies have depicted a marked decrease in the absorption surface area such as the villi height of the intestinal segment. In addition, crypt number also deceased in the treated animals, an indication that such changes also correlate well with the changes in the transport of the end product nutrients.Se diseñó este estudio para investigar los efectos adversos gastrointestinales de los inhibidores de la ciclooxigenasa (COX) con selectividad variable, denominados fármacos antiinflamatorios no esteroideos (AINE), inhibidores no selectivos de la COX-1 y la COX-2 -aspirina, los inhibidores predominantemente selectivos de la COX-2- nimesulida, y los inhibidores muy selectivos de la COX-2 -celecoxib. El tratamiento con AINE mostró un descenso de la actividad de las enzimas asociadas a la membrana en cepillo intestinal de la rata, tales como sucrasa, lactasa, maltasa y fosfatasa alcalina, en comparación con el control, en el duodeno, yeyuno e íleon. Se halló que la captación de D-glucosa y L-histidina en el saco intestinal revertido estaba disminuida. También se encontró que la captación de glucosa e histidina dependía de la concentración de sustrato, la temperatura y el intervalo de tiempo de incubación. El estado físico y la composición de la membrana en borde en cepillo estaban alterados como se evidenció en el espectro FTIR, con aparición de nuevas picos y desaparición de ciertos picos característicos de la membrana control. También se apreciaron cambios en el número de ondas así como la altura de los picos. Se demostraron cambios en el perfil de proteínas de membrana mediante el análisis SDSPAGE, apreciándose desaparición de algunas pocas bandas y cambio en las intensidades relativas de las bandas, correlacionándose con las alteraciones que ocurrían a nivel molecular. Los estudios histológicos han mostrado un descenso marcado de la superficie de absorción, como por ejemplo la altura de las vellosidades del segmento intestinal. Además, el número de criptas también disminuyó en los animales tratados, un indicador de que tales cambios también se correlacionan bien con los cambios en el transporte de los nutrientes finales.

In the present study the effects of two cycloxygenase-2 (COX-2) selective inhibitors, celecoxib and nimesulide as compared to a non-selective COX inhibitor, aspirin was studied in the rat intestine. Female Wistar rats weighing between 150-175 g were divided into four groups having 8 animals each as follows: Group 1(Control), Group 2- Aspirin (40 mg/kg), Group 3- Nimesulide (10 mg/kg) and Group 4- Celecoxib (10 mg/kg). After 35 days of treatment the animals were sacrificed, intestine removed and the effects on the antioxidant defense system, membrane composition and functions along with the membrane specific enzymes were studied in different regions of the intestine. The study showed a significant increase in the lipid peroxide levels as TBA-reactive substance as well as the conjugated dienes, except for celecoxib treated group which showed a decrease. Significant decrease was also observed in the level of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-s-transferase and catalase activities for aspirin and nimesulide group while Celecoxib caused an increase in glutathione reductase (GR). Aspirin and nimesulide exhibited an increase in the brush border membrane (BBM) bound enzyme activities like sucrase, lactase, maltase and alkaline phosphatase in the small intestine while celecoxib showed decrease in lactase, maltase and alkaline phosphatase. The phospholipid content increased only for aspirin treated group while cholesterol decreased in all the treatment groups. Also celecoxib treatment brought about an increase in glycolipid content. The membrane fluidity was studied by the rotational diffusion of 1, 6, diphenyl, 1, 3, 5 hexatriene (DPH) incorporated in the membrane and the fluorescence polarization (p), fluorescence anisotropy(r), anisotropy parameter [r0/r -1]-1 and order parameter [S² = (4/3r - 0.1)/ r0] were recorded. No significant change in the fluorescence parameters were observed in the BBM and the liposomes made from the BBM lipids for the treatment groups. These results indicate that celecoxib may be accepted as a safer drug in terms of overall gastro-intestinal toxicity as compared to the aspirin and nimesulide.En el presente estudio se comparaban los efectos de dos inhibidores selectivos de la ciclo-oxigenasa-2 (COX-2), celecoxib y nimesulide, con los de un inhibidor no selectivo de la COX, la aspirina, en el intestino de la rata. Se escogieron ratas Wistar hembra, con un peso de 150-175 g, y se las dividió en 4 grupos, con 8 animales cada uno, como sigue: Grupo 1 (Control), Grupo 2 - Aspirina (40 mg/kg), Grupo 3 - Nimesulide (10 mg/kg), y Grupo 4 - Celecoxib (10 mg/kg). Tras 35 días de tratamiento, se sacrificó a los animales, se extirpó el intestino, y se estudiaron los efectos sobre el sistema de defensa antioxidante, la composición de la membrana y sus funciones, además de las enzimas de membrana específicas, en diferentes regiones del intestino. El estudio mostró un aumento significativo de las concentraciones de peróxido lipídico como sustancia TBA reactiva así como de dienos conjugados, excepto para el grupo tratado con celecoxib que mostró un descenso. También se observó un descenso significativo en las actividades de glutatión reducido (GSH), de superóxido dismutasa (SOD), de glutatión-s-transferasa y de catalasa en los grupos tratados con aspirina y con nimesulide, mientras que el grupo tratado con celecoxib tuvo un aumento de la glutatión reductasa (GR). La aspirina y el nimesulide mostraron un aumento de las actividades de las enzimas ligadas a la membrana de borde en cepillo (BBM) como la sucrasa, lactasa, maltasa y fosfatasa alcalina. El contenido en fosfolípidos aumentó sólo en el grupo tratado con aspirina mientras que el colesterol disminuyó en todos los grupos de tratamiento. En el grupo de celecoxib también se objetivó un aumento en el contenido en glucolípidos. Se estudió la fluidez de la membrana mediante difusión rotacional del 1,6-difenil-1,3,5-hexatrieno (DPH) incorporado a la membrana y se registraron la polarización de fluorescencia (p), la anisotropía de fluorescencia (r), el parámetro de anisotropía [r0/r -1]-1 y el parámetro de orden [S² =(4/3 r - 0,1)/ r0]. No se observaron cambios significativos en los parámetros de fluorescencia en la BBM ni de los liposomas formados a partir de los lípidos de la BBM en ninguno de los grupos tratados. Estos resultados indican que se puede considerar al celecoxib como un fármaco más seguro en cuanto a toxicidad gastrointestinal general en comparación con el nimesulide y la aspirina.

Nanostructured molybdenum disulfide thin films were deposited on various substrates by direct current (DC) electrolysis form aqueous electrolyte containing molybdate and sulfide ions. Post deposition annealing at higher temperatures in the range 450–700°C transformed the as-deposited amorphous films to nanocrystalline structure. High temperature X-ray diffraction studies clearly recorded the crystal structure transformations associated with grain growth with increase in annealing temperature. Surface morphology investigations revealed featureless structure in case of as-deposited surface; upon annealing it converts into a surface with protruding nanotubes, nanorods, or dumbbell shape nanofeatures. UV-visible and FTIR spectra confirmed about the presence of Mo-S bonding in the deposited films. Transmission electron microscopic examination showed that the annealed MoS2 films consist of nanoballs, nanoribbons, and multiple wall nanotubes.

The second axis of the dual-axis radiography of hydrodynamic testing (DARHT) facility produces up to four radiographs within an interval of 1.6 μs. It does this by slicing four micropulses out of a 2-μs long electron beam pulse and focusing them onto a bremsstrahlung converter target. The 1.8-kA beam pulse is created by a dispenser cathode diode and accelerated to more than 16 MeV by the unique DARHT Axis-II linear induction accelerator (LIA). Beam motion in the accelerator would be a problem for multipulse flash radiography. High-frequency motion, such as from beam-breakup (BBU) instability, would blur the individual spots. Low-frequency motion, such as produced by pulsed-power variation, would produce spot-to-spot differences. In this article, we describe these sources of beam motion, and the measures we have taken to minimize it. Using the methods discussed, we have reduced beam motion at the accelerator exit to less than 2% of the beam envelope radius for the high-frequency BBU, and less than 1/3 of the envelope radius for the low-frequency sweep.

A halo generation mechanism in the nonperiodic lattices such as the SNS (Spallation Neutron Source) linac MEBT [medium-energy beam transport between radio-frequency quadrupole and DTL (drift tube linac)] is reported. We find that the nonlinear space charge force resulting from large transverse beam eccentricity ∼2:1 in the ∼1.6 m-long MEBT chopper section is responsible for halo formation. As a result, the beam distribution, based on the front end emittance measurements and multiparticle simulation studies, develops halo that leads to beam loss and radioactivation of the SNS linac. Designing lattices with transverse beam eccentricity close to 1:1 suppresses this kind of halo generation. Modifying the MEBT optics and introducing adjustable collimators in the MEBT significantly reduced beam losses in the coupled cavity linac, which is a preferred scheme for mitigating halo. It turns out that the DTL collimation does not effectively remove halo and presents a risk of overheating drift tubes.