KUTIPRAVESHIK RASAYANA- A REVIEW

The Vedas have seriously considered the problem of aging and its prevention. It has been the cherished wish of human race to achieve long life and to live at least 100 year in perfect health; probably this idea at a later stage necessitated the development of complete clinical discipline like Rasayana to deal with the problem of aging, its prevention, and rejuvenation of body. In Sushruta Samhita being a text preliminarily dealing with surgical discipline has discussed different problem of Rasayana therapy in a different way. The most important contribution of Sushruta and Dalhana to development of Rasayana tantra is the classification of Rasayana measures and made Rasayana therapy more practical, applied and useful. One distinct observation made by Sushruta regarding the age factor in selection of the subject for Rasayana therapy is the indication in younger and middle age groups. At the same time, the main aim of Geriatrics is to study the changes in the tissue during the aging process and attempt to make the lives of old persons comfortable. If we compare Rasayana with gerontology we can find the major difference between them. In addition to prevention of ageing, Rasayana is aimed for longevity; maintenance of positive health; the improvement in mental faculties like intelligence, perseverance and memory; and resistance against disease. Rasayana essentially refers to the acceleration of the process of nutrition for the correct condition of the body tissue

A comparative evaluation of frictional resistance and surface roughness of silver coated and uncoated stainless-steel bracket wire assembly- An in-vitro study

Silver ions act as potent antimicrobial agents. Silver coating of brackets and the archwires can help reduce the formation of white spot lesions and caries which is commonly seen with fixed orthodontic treatment. However, this may affect the friction and surface roughness of the bracket-wire assembly which in turn affects the biological tooth movement. MATERIAL AND METHODS: A total of 60 samples were included in the study which was divided into four groups. Group-1: * 15 silver coated 0.022 x 0.028" slot MBT prescription maxillary central incisor brackets * 15 silver coated 0.019 x 0.025" stainless-steel wires; Group-2: * 15 uncoated 0.022 x 0.028" slot MBT prescription maxillary central incisor brackets * 15 silver coated 0.019 x 0.025" stainless-steel wires; Group-3: * 15 silver coated 0.022 x 0.028" slot MBT prescription maxillary central incisor brackets * 15 uncoated 0.019 x 0.025" stainless-steel wires; Group-4: * 15 uncoated 0.022x0.028" slot MBT prescription maxillary central incisor brackets * 15 uncoated 0.019 x 0.025" stainless-steel wires. All brackets and wires used were of American Orthodontics, St. Paul, USA. Surface modification of wires and brackets was carried out using the Vacuum Coating Unit model by Thermal Vacuum Evaporation method with silver nanoparticles (10 nm size). The frictional resistance of all brackets and wires was checked using Universal Testing Machine. RESULTS: On comparison of maximum load, it was found that friction was highest in group 3, followed by group 1, group 4 and group 2. The mean difference between all groups was found to be statistically significant with a P value Group 1> Group 2> Group 3 *Wire roughness: Group 4> Group 1> Group 2> Group 3. CONCLUSIONS: This study concluded that friction was least when only the wire was coated with silver and the bracket was uncoated and it was the most when the bracket was coated and the wire was uncoated. The surface roughness after the friction test was the least when the wire was uncoated. Key words:Silver nanoparticles, Frictional Resistance, Surface Roughness

ARE INVESTORS INTENTIONALLY MAKING INVESTMENTS IN RISKY DERIVATIVES OR ARE THEY BEEN DEPRIVED OF GETTING APPROPRIATE AND PROPORTIONATE KNOWLEDGE? IN REFERENCE TO SOCIAL INFRASTRUCTURE IN INDIA

ABSTRACT Present study attempts to provide a deep understanding about the soft infrastructure and how soft infrastracture play the vital role in the competative market. We also discuss about the types of Soft-Infrastructure and mainly focuss to the social infrastructure. An overview about derivative market are risky investments only for those young and new businesses which don't have a sufficient amount of knowledge in D-Markets scenerio in India. This paper emphasis how the investor not getting actual benifits out of the investment done in Derivative Market ; this may be due to improper knowledge of soft infrastructure

Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy

RAS oncogenes (collectively NRAS, HRAS and especially KRAS) are among the most frequently mutated genes in cancer, with common driver mutations occurring at codons 12, 13 and 611. Small molecule inhibitors of the KRAS(G12C) oncoprotein have demonstrated clinical efficacy in patients with multiple cancer types and have led to regulatory approvals for the treatment of non-small cell lung cancer2,3. Nevertheless, KRASG12C mutations account for only around 15% of KRAS-mutated cancers4,5, and there are no approved KRAS inhibitors for the majority of patients with tumours containing other common KRAS mutations. Here we describe RMC-7977, a reversible, tri-complex RAS inhibitor with broad-spectrum activity for the active state of both mutant and wild-type KRAS, NRAS and HRAS variants (a RAS(ON) multi-selective inhibitor). Preclinically, RMC-7977 demonstrated potent activity against RAS-addicted tumours carrying various RAS genotypes, particularly against cancer models with KRAS codon 12 mutations (KRASG12X). Treatment with RMC-7977 led to tumour regression and was well tolerated in diverse RAS-addicted preclinical cancer models. Additionally, RMC-7977 inhibited the growth of KRASG12C cancer models that are resistant to KRAS(G12C) inhibitors owing to restoration of RAS pathway signalling. Thus, RAS(ON) multi-selective inhibitors can target multiple oncogenic and wild-type RAS isoforms and have the potential to treat a wide range of RAS-addicted cancers with high unmet clinical need. A related RAS(ON) multi-selective inhibitor, RMC-6236, is currently under clinical evaluation in patients with KRAS-mutant solid tumours (ClinicalTrials.gov identifier: NCT05379985).J.E. Klomp is funded by National Cancer Institute grants T32CA009156, F32CA239328 and K99CA276700, and American Cancer Society grant PF-20-069. P.L. is supported in part by the NIH/NCI (1R01CA23074501, 1R01CA23026701A1 and 1R01CA279264-01), The Pew Charitable Trusts, the Damon Runyon Cancer Research Foundation, and the Pershing Square Sohn Cancer Research Alliance. P.L. is also supported by the Josie Robertson Investigator Program and the Support Grant-Core Grant program (P30 CA008748) at Memorial Sloan Kettering Cancer Center. D.S. is funded by AECC Excellence Program 2022 (EPAEC222641CICS). A.J.A. has research funding from Bristol Myers Squibb, Deerfield, Eli Lilly, Mirati Therapeutics, Novartis, Novo Ventures, Revolution Medicines and Syros Pharmaceuticals. A.M.W. was supported by a grant from the NCI (K22CA276632-01). C.J.D. has received research funding support from Deciphera Pharmaceuticals, Mirati Therapeutics, Reactive Biosciences, Revolution Medicines, and SpringWorks Therapeutics, the National Cancer Institute (P50CA257911 and R35CA232113), Department of Defense (W81XWH2110692), and Pancreatic Cancer Action Network (22-WG-DERB). C.A. is funded by grants from the Giovanni Armenise–Harvard Foundation, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 101001288) and AIRC under IG 2021–ID. 25737 project.Peer reviewe

A BRIEF REVIEW OF TREATMENT MODALITIES FOR NON-MELANOMA SKIN CANCER

NMSC (Non-melanoma skin cancer) is the most commonly occurring malignancy in Caucasians. Out of all diagnosed NMSC cases, 95% of the cases are of basal cell carcinoma and squamous cell carcinoma. The therapeutic approaches to cure or ultimately rescue the skin area affected by NMSC include surgical methods, photodynamic therapy, radiation therapy, immunotherapy, and chemotherapy. This article aims to provide a brief overview of the preliminary mechanism of action, clinical studies, advantages, and disadvantages of currently available treatment modalities

Determination of Growth Inhibitory Effect of Iminodibenzyl Against Breast Cancer

Breast cancer arises from the culmination of complex process enclosing multiple gene modifications such as cyclooxygenase-2 (COX-2). It catalyzes arachidonic acid (AA, downstream ω-6 polyunsaturated fatty acid (ω-6 PUFA)) metabolism to cancer-promoting prostaglandin E2 (PGE2). Hence, COX-2 inhibition was considered an ideal strategy to inhibit the cancer progression. However, COX-2 inhibitors are no longer advised for cancer management due to life threatening cardiovascular adverse events. Recently, we found that inhibition of delta-5-desaturase (D5D, enzyme catalyzing di homo-gamma-linolenic acid (DGLA) metabolism to AA) in breast cancer cells by siRNA/shRNA caused the diversion of DGLA metabolism from PGE2 to anticancer metabolite 8-hydroxyoctanoic acid (8-HOA). But, the approach of using siRNA/shRNA was limited by endonucleases mediated physiological degradation and inability to cross the cell membrane. Therefore, to overcome the limitation and to stimulate DGLA metabolism towards anti-cancer activity, small molecule D5D activity inhibitor Iminodibenzyl was identified. Here, we have hypothesized that Iminodibenzyl could inhibit the DGLA metabolism by inhibiting the D5D activity, and simultaneously overexpressed COX-2 in breast cancer cells would peroxidize the accumulated DGLA to an anti-cancer metabolite 8-HOA. To achieve the research goal, we have performed various in vitro and in vivo studies (orthotopic breast cancer model). From these studies, we noted that Iminodibenzyl could alter DGLA metabolism to anti-cancer metabolite 8-HOA in 4T1 and MDA-MB-231 breast cancer cells. After treating cancer cells with the combination of Iminodibenzyl and DGLA, a significant increase in apoptosis was observed through the caspasedependent mechanism, which was validated by pretreating cells with nonspecific caspase inhibitor Z-VAD-FMK. Additionally, a significant reduction in HDAC activity and β-Catenin was observed, which might have reduced cancer cell survival fraction and proliferation. We believe that all the above mechanisms affected by the combination might have reduced the cancer growth resulting in significant reduction in tumor size. Additionally, combination treatment also reduced lamellipodia and filopodia, and EMT markers resulting in reduction in cancer cell migration as visible from larger wound size and less number of metastatic nodules. Hence, all the above findings provide evidence about the efficacy of Iminodibenzyl to shift the DGLA metabolism producing anti-cancer activity in breast cancer cells

Towards Emotion- and Time-Aware Classification of Tweets to Assist Human Moderation for Suicide Prevention

Social media platforms are already engaged in leveraging existing online socio-technical systems to employ just-in-time interventions for suicide prevention to the public. These efforts primarily rely on self-reports of potential self-harm content that is reviewed by moderators. Most recently, platforms have employed automated models to identify self-harm content, but acknowledge that these automated models still struggle to understand the nuance of human language (e.g., sarcasm). By explicitly focusing on Twitter posts that could easily be misidentified by a model as expressing suicidal intent (i.e., they contain similar phrases such as ``wanting to die''), our work examines the temporal differences in historical expressions of general and emotional language prior to a clear expression of suicidal intent. Additionally, we analyze time-aware neural models that build on these language variants and factors in the historical, emotional spectrum of a user's tweeting activity. The strongest model achieves high (statistically significant) performance (macro F1=0.804, recall=0.813) to identify social media indicative of suicidal intent. Using three use cases of tweets with phrases common to suicidal intent, we qualitatively analyze and interpret how such models decided if suicidal intent was present and discuss how these analyses may be used to alleviate the burden on human moderators within the known constraints of how moderation is performed (e.g., no access to the user's timeline). Finally, we discuss the ethical implications of such data-driven models and inferences about suicidal intent from social media. Content warning: this article discusses self-harm and suicide

Study of Driver’s Behavior at Passive Railroad‐Highway Grade Crossings

Railway highway grade crossing safety has always been a concern for railroads, state DOTs, and the driving population. This paper presents an overview of drivers’ behavior at different passive warning sign systems present at a selected number of Kansas railroad-highway grade crossings. Emphasis in this study was on drivers’ stopping behavior at the STOP signs, as that has been a major concern of Kansas DOT (KDOT). A field study was conducted on nine grade crossings with selected warning devices to determine driver’s approach behavior, particularly stopping behavior at STOP signs. Various statistical analysis and comparisons are done for stopping of heavy trucks, school buses and other vehicles at crossings with both poor and good sight distance on their approaches. Based on the field tests conducted it was found that the majority of drivers did not stop at the STOP signs at the grade crossings. A higher percentage of drivers actually stopped at crossings with poor sight distance on the approach than on approaches with good sight distance. The use of the STOP sign at passive grade crossings has been controversial for several decades. This paper presents a brief history of their use and the controversy. Based on this limited study, the authors recommended that a STOP sign should not be used at grade crossings without a valid engineering study that includes an evaluation of the sight distance