Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)

The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the India-based Neutrino Observatory (INO) is designed to study the atmospheric neutrinos and antineutrinos separately over a wide range of energies and path lengths. The primary focus of this experiment is to explore the Earth matter effects by observing the energy and zenith angle dependence of the atmospheric neutrinos in the multi-GeV range. This study will be crucial to address some of the outstanding issues in neutrino oscillation physics, including the fundamental issue of neutrino mass hierarchy. In this document, we present the physics potential of the detector as obtained from realistic detector simulations. We describe the simulation framework, the neutrino interactions in the detector, and the expected response of the detector to particles traversing it. The ICAL detector can determine the energy and direction of the muons to a high precision, and in addition, its sensitivity to multi-GeV hadrons increases its physics reach substantially. Its charge identification capability, and hence its ability to distinguish neutrinos from antineutrinos, makes it an efficient detector for determining the neutrino mass hierarchy. In this report, we outline the analyses carried out for the determination of neutrino mass hierarchy and precision measurements of atmospheric neutrino mixing parameters at ICAL, and give the expected physics reach of the detector with 10 years of runtime. We also explore the potential of ICAL for probing new physics scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration, Contents identical with the version published in Pramana - J. Physic

First simulation study of trackless events in the INO-ICAL detector to probe the sensitivity to atmospheric neutrinos oscillation parameters

The proposed India-based Neutrino Observatory will host a 50 kton magnetized iron calorimeter (ICAL) with resistive plate chambers as its active detector element. Its primary focus is to study charged-current interactions of atmospheric muon neutrinos via the reconstruction of muons in the detector. We present the first study of the energy and direction reconstruction of the final state lepton and hadrons produced in charged current interactions of atmospheric electron neutrinos at ICAL and the sensitivity of these events to neutrino oscillation parameters $\theta_{23}$ and $\Delta m_{32}^2$. However, the signatures of these events are similar to those from neutral-current interactions and charged-current muon neutrino events in which the muon track is not reconstructed. On including the entire set of events that do not produce a muon track, we find that reasonably good sensitivity to $\theta_{23}$ is obtained, with a relative $1\sigma$ precision of 15% on the mixing parameter $\sin^2\theta_{23}$, which decreases to 21%, when systematic uncertainties are considered

A COMPARATIVE EVALUATION ON THE EFFECT OF ZINC-PROBIOTIC AND PROBIOTIC THERAPY IN PAEDIATRIC ACUTE DIARRHOEA AND THE IMPACT OF COUNSELLING OF MOTHERS

Objective: To compare the efficacy of zinc-probiotic combination therapy and probiotic therapy alone in the treatment of acute paediatric diarrhoea and to assess the knowledge, attitude and practice (KAP) of the mothers of affected children and the impact of counselling on diarrhoea management.Methods: A prospective observational comparative study was conducted from October 2014 to March 2015 in the paediatric department of Cosmopolitan Hospitals Pvt. Ltd., Thiruvananthapuram, Kerala, South India. The study was carried out on 150 patients between the ages of 3 mo to 12 y. The selected patients were divided into 2 groups of 75 members each. Initially, demographic data, details of socioeconomic status, severity, duration and frequency of diarrhoea and the presence of other associated symptoms and KAP of mothers before and after counselling was collected by using specially designed proforma. Group 1 patients received zinc and probiotic and Group 2 received probiotic only by oral administration. All children in both groups received sufficient quantity of oral rehydration solution (ORS). The requirement of other medications and adverse effects were also monitored.Results: The study revealed that, in group 1, 54.6% of patients were males and in group 2, 58.6% were females. The mean age of affected children was 5.14±3.53. In both groups, the majority of patients were from outpatient (OP) departments. In group 1, majority of patients, 49.3% were resting in upper lower economic class followed by 30.7% were lower middle class. In the case of group 2, 34.6% patients were from lower middle and 28% were from upper middle class. Other medications such as antiemetic and antipyretic were administered to 127and 110 patients respectively. Antisecretory and antibiotic were administered to 31 and 26 patients respectively. Totally 8 patients were affected with adverse drug reactions such as rashes and swelling of lips. In both groups severity of diarrhoea was high before treatment and it was changed after effective treatment with drugs. Comparing with group 2, the duration and severity of diarrhoea and other associated symptoms in group 1 patients were significantly reduced after treatment. Before counseling, the majority of mothers had very poor knowledge about the diarrhoeal disease and its management. Evaluation after counselling showed a significant improvement.Conclusion: Low socioeconomic life is a risk factor for diarrhoea. A combination of zinc and probiotic therapy is more effective than probiotic therapy alone in the treatment of acute diarrhoea and vomiting in children. The emergence and severity of the diarrhoeal disease can be reduced by effective clinical pharmacist interventions, and a great emphasis is needed in the counselling and education of mothers about this disease and its management.Keywords: Paediatric diarrhoea, Zinc, Probiotic, KAP, Counselling and educatio

The Engine Is the Message: Videogame Infrastructure and the Future of Digital Platforms

On January 18, Microsoft revealed its $68.7 billion deal to acquire videogame publisher Activision Blizzard. The acquisition was pitched as an investment towards “metaverse platforms” that gaming would play a key role in developing. Journalists speculated about the increasing consolidation of the videogame industry and whether blockbuster franchises would be locked into Microsoft’s platforms and subscription services. Commentary on the metaverse weighed in on how toxicity and harassment in game industry workplaces such as Activision Blizzard might relate to issues of trust and safety in virtual worlds such as Meta’s Horizon Worlds. Seemingly above the fray of platform strategy, market speculation, and corporate scandal, New Yorker writer Kyle Chayka (2022) tweeted as a matter of fact: “video game infrastructure and tools are increasingly going to take over all digital platforms”. This panel contextualizes discussions about the business and aesthetics of 3D platforms in the infrastructural work of game engines, which routinely integrate databases, file formats, web protocols, and translational algorithms. We trace public debates and corporate statements over representation and governance, equity and inclusion (Bosworth 2021) to the techniques, technologies, and practices that enable massive real-time 3D digital spaces to flow and transact. We also highlight the growing intertwinement between game engine development companies and related content ecosystems, such as the Epic Games Store and the Unreal Engine, and Epic’s and Unity’s Asset Stores. This panel investigates how digital systems are designed to regulate technical interoperability and its implications for creative practice and cultural production. Together, these papers map how power and capital become centralized and distributed throughout the back end of the metaverse, and politicize how social practices and subjectivities are negotiated through technological architecture

High Pulse Pressure Impairs Cerebral Artery Endothelial Function in Young, but Not Old, Mice

One of the hallmarks of vascular aging is increased pulse pressure. This elevated pulse pressure is associated with deleterious effects on cerebral vascular function; however, it is unknown if age modulates the susceptibility to high pulse pressure. To examine the effects of age on the cerebral artery response to pulse pressure, we studied isolated cerebral arteries collected from young (6.1 ± 0.2 mo) and old (26.7 ± 0.5 mo) male C57BL/6 mice. Isolated cerebral arteries were exposed ex vivo to static pressure, low pulse pressure (25 mmHg), and high pulse pressure (50 mmHg). In cerebral arteries from young mice, endothelium-dependent dilation was similar between the static and low pulse pressure conditions. Exposure to high pulse pressure impaired endothelium-dependent dilation in cerebral arteries from young mice, mediated by less nitric oxide bioavailability and greater oxidative stress. Cerebral arteries from old mice had impaired cerebral artery endothelium-dependent dilation at static pressure compared with young cerebral arteries. However, exposure to low or high pulse pressure did not cause any further impairments to endothelium-dependent dilation in old cerebral arteries compared with static pressure. The old cerebral arteries had less distension during exposure to high pulse pressure and greater stiffness compared with young cerebral arteries. These results indicate that acute exposure to high pulse pressure impairs endothelium-dependent dilation in young, but not old, cerebral arteries. The greater stiffness of cerebral arteries from old mice potentially protects against the negative consequences of high pulse pressure

Pyridoxamine Treatment Ameliorates Large Artery Stiffening and Cerebral Artery Endothelial Dysfunction in Old Mice

Age-related increases in large artery stiffness are associated with cerebrovascular dysfunction and cognitive impairment. Pyridoxamine treatment prevents large artery stiffening with advancing age, but the effects of pyridoxamine treatment on the cerebral vasculature or cognition is unknown. The purpose of this study was to investigate the effects of pyridoxamine on blood pressure, large artery stiffness, cerebral artery function, and cognitive function in old mice. Old male C57BL/6 mice consumed either pyridoxamine (2 g/L) or vehicle control in drinking water for ∼7.5 months and were compared with young male C57BL/6 mice. From pre- to post-treatment, systolic blood pressure increased in old control mice, but was maintained in pyridoxamine treated mice. Large artery stiffness decreased in pyridoxamine-treated mice but was unaffected in control mice. Pyridoxamine-treated mice had greater cerebral artery endothelium-dependent dilation compared with old control mice, and not different from young mice. Old control mice had impaired cognitive function; however, pyridoxamine only partially preserved cognitive function in old mice. In summary, pyridoxamine treatment in old mice prevented age-related increases in blood pressure, reduced large artery stiffness, preserved cerebral artery endothelial function, and partially preserved cognitive function. Taken together, these results suggest that pyridoxamine treatment may limit vascular aging

Concurrent epigenetic silencing of wnt/β-catenin pathway inhibitor genes in B cell chronic lymphocytic leukaemia

Background The Wnt/β-catenin signalling is aberrantly activated in primary B cell chronic lymphocytic leukaemia (CLL). Epigenetic silencing of pathway inhibitor genes may be a mechanism for its activation. In this study, we investigated systematically and quantitatively the methylation status of 12 Wnt/β-catenin pathway inhibitor genes – CDH1, DACT1, DKK1, DKK2, DKK3, DKK4, SFRP1, SFRP2, SFRP3, SFRP4, SFRP5 and WIF1 – in the cell lines EHEB and MEC-1 as well as patient samples. Methods Quantification of DNA methylation was performed by means of bisulphite pyrosequencing and confirmed by bisulphite Sanger sequencing. Gene expression was analysed by qPCR using GAPDH as internal control. E-cadherin and β-catenin protein quantification was carried out by microsphere-based immunoassays. Methylation differences observed between the patient and control groups were tested using generalised least squares models. Results For 10 genes, a higher methylation level was observed in tumour material. Only DKK4 exhibited similarly high methylation levels in both tumour and normal specimens, while DACT1 was always essentially unmethylated. However, also for these inhibitors, treatment of cells with the demethylating agent 5-aza-2´-deoxycytidine resulted in an induction of their expression, as shown by quantitative PCR, suggesting an indirect epigenetic control of activity. While the degree of demethylation and its transcriptional consequences differed between the genes, there was an overall high correlation of demethylation and increased activity. Protein expression studies revealed that no constitutive Wnt/β-catenin signalling occurred in the cell lines, which is in discrepancy with results from primary CLL. However, treatment with 5-aza-2´-deoxycytidine caused accumulation of β-catenin. Simultaneously, E-cadherin expression was strongly induced, leading to the formation of a complex with β-catenin and thus demonstrating its epigenetically regulated inhibition effect. Conclusions The results suggest an epigenetic silencing mechanism of the Wnt/β-catenin pathway inhibitor genes in CLL. Hypermethylation and silencing of functionally related genes may not be completely stochastic but result from the tumour epigenome reprogramming orchestrated by Polycomb-group repressive complexes. The data are of interest in the context of epigenetic-based therapy

Advancements in bacteria based self-healing concrete and the promise of modelling

In the last two decades self-healing of concrete through microbial based carbonate precipitation has emerged as a promising technology for making concrete structures more resilient and sustainable. Currently, progress in the field is achieved mainly through physical experiments, but their duration and cost are barriers to innovation and keep the number of large scale applications still very limited. Modelling and simulation of the phenomena underlying microbial based healing of concrete may provide a key to complement the experimental efforts, but their development is still in its infancy. In this review, we briefly present the field, introduce some key aspects emerged from the experiments, present the main ongoing developments in modelling and simulation of mineral and microbial systems, and discuss how their synergy may be accomplished to speed up progress in the near future