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Chaperone-assisted E3 ligase CHIP:A double agent in cancer

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Genes & Diseases 2022年第6期9卷 1521-1555页

作者： sunny kumar Malini Basu Mrinal K.Ghosh Cancer Biology and Inflammatory Disorder Division Council of Scientific and Industrial Research-Indian Institute of Chemical Biology(CSIR-IICB)TRUE CampusCN-6SectoreVSalt LakeKolkata-700091&4Raja S.C.Mullick RoadJadavpurKolkata 700032India Department of Microbiology Dhruba Chand Halder CollegeDakshin BarasatSouth 24 ParaganasWest Bengal 743372India

The carboxy-terminus of Hsp70-interacting protein(CHIP)is a ubiquitin ligase and co-chaperone belonging to Ubox family that plays a crucial role in the maintenance of cellular homeostasis by switching the equilibrium of the folding-refolding mechanism towards the proteasomal or lysosomal degradation *** links molecular chaperones ***70,HSP70 and HSP90 with ubiquitin proteasome system(UPS),acting as a quality control *** contains charged domain in between N-terminal tetratricopeptide repeat(TPR)and C-terminal Ubox *** domain interacts with the aberrant client proteins via chaperones while Ubox domain facilitates the ubiquitin transfer to the client proteins for ***,CHIP is a classic molecule that executes ubiquitination for degradation of client ***,CHIP has been found to be indulged in cellular differentiation,proliferation,metastasis and ***,CHIP can play its dual role as a tumor suppressor as well as an oncogene in numerous malignancies,thus acting as a double ***,in this review,we have reported almost all substrates of CHIP established till date and classified them according to the hallmarks of *** addition,we discussed about its architectural alignment,tissue specific expression,sub-cellular localization,folding-refolding mechanisms of client proteins,E4 ligase activity,normal physiological roles,as well as involvement in various diseases and tumor ***,we aim to discuss its importance in HSP90 inhibitors mediated cancer ***,this report concludes that CHIP may be a promising and worthy drug target towards pharmaceutical industry for drug development.

关键词： Chaperones(HSC70/HSP70&HSP90) CHIP Oncogene Therapy Tumor suppressor Ubiquitin proteasome system(UPS)

COVID-19 therapeutics:Clinical application of repurposed drugs and futuristic strategies for target-based drug discovery

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Genes & Diseases 2023年第4期10卷 1402-1428页

作者： sunny kumar Malini Basu Pratyasha Ghosh Uttam Pal Mrinal K.Ghosh Cancer Biology and Inflammatory Disorder Division Council of Scientific and Industrial Research-Indian Institute of Chemical Biology(CSIR-IICB)TRUE CampusCN-6SectoreVSalt LakeKolkata-700091&4Raja S.C.Mullick RoadJadavpurKolkata 700032India Department of Microbiology Dhruba Chand Halder CollegeDakshin BarasatWest Bengal 743372India Department of Economics Bethune CollegeUniversity of CalcuttaKolkata 700006India

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)causes the compli-cated disease *** are continuously facing huge problems in the treatment of patients,as COVID-19-specific drugs are not available,hence the principle of drug repurpos-ing serves as a one-and-only ***,the repurposing of many drugs is underway;few of them are already approved by the regulatory bodies for their clinical use and most of them are in different phases of clinical *** in this review,our main aim is to discuss in detail the up-to-date information on the target-based pharmacological classification of repurposed drugs,the potential mechanism of actions,and the current clinical trial status of various drugs which are under repurposing since early *** last,we briefly proposed the probable phar-macological and therapeutic drug targets that may be preferred as a futuristic drug discovery approach in the development of effective medicines.

关键词： Clinical trials COVID-19 Drug discovery Pharmacology Repurposing of drugs SARS-CoV-2

Targeting PD-1/PD-L1 in cancer immunotherapy:An effective strategy for treatment of triple-negative breast cancer(TNBC)patients

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Genes & Diseases 2023年第4期10卷 1318-1350页

作者： sunny kumar Mouli Chatterjee Pratyasha Ghosh Kirat K.Ganguly Malini Basu Mrinal K.Ghosh Cancer Biology and Inflammatory Disorder Division Council of Scientific and Industrial Research-Indian Institute of Chemical Biology(CSIR-IICB)TRUE CampusCN-6SectoreVSalt LakeKolkata 700091JadavpurKolkataPIN 700032India Department of Economics Bethune CollegeUniversity of CalcuttaKolkataPIN 700006India Department of Microbiology Michael Madhusudan Memorial CollegeDurgapurPIN 713216India Department of Microbiology Dhruba Chand Halder CollegeUniversity of CalcuttaKolkataPIN 743372India

Maintaining the balance between eliciting immune responses against foreign pro-teins and tolerating self-proteins is crucial for maintenance of *** functions of programmed death protein 1(PD-1)and its ligand programmed death ligand 1(PD-L1)are to inhibit immune responses so that over-reacting immune cells does not cause any damage to its own body ***,cancer cells hijack this mechanism to attenuate immune cells functions and create an immunosuppressive environment that fuel their continuous growth and *** the past few years’rapid development in cancer immunotherapy has opened a new avenue in cancer *** of PD-1 and PD-L1 has become a potential strategy that rescue the functions of immune cells to fight against cancer with high ***,immune checkpoint monotherapies were not very successful,making breast cancer less ***,recent reports support the presence of tumor infiltrating lympho-cytes(TILs)in breast cancer that make it favorable for PD-1/PD-L1 mediated immunotherapy,which is effective in PD-L1 positive ***,anti-PD-1(pembrolizumab)and anti-PD-L1(atezolizumab)gets FDA approval for breast cancer treatment and make PD-1/PD-L1 immunotherapy is meaningful for further ***,this article gathered understand-ing of PD-1 and PD-L1 in recent years,their signaling networks,interaction with other mole-cules,regulations of their expressions and functions in both normal and tumor tissue microenvironments are crucial to find and design therapeutic agents that block this pathway and improve the treatment ***,authors collected and highlighted most of the important clinical trial reports on monotherapy and combination therapy.

关键词： Breast cancer Cancer Clinical trial Immunotherapy PD-1/PD-L1 TNBC

Effect of cooling media on bead geometry,microstructure,and mechanical properties of wire arc additive manufactured IN718 alloy

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Advances in Manufacturing 2024年第1期12卷 124-149页

作者： Parveen kumar Satish kumar Sharma Ratnesh kumar Raj Singh Department of Mechanical Engineering Thapar Institute of Engineering and TechnologyPatialaPunjab147004India

This work aims to present and explore thermal management techniques for the wire arc additive manufacturing(WAAM)of IN718 *** heat can be mitigated via air or water *** this study,the material was deposited under four different heat-input conditions with air or water *** air cooling,the layer is deposited in a normal atmospheric air environment,whereas with water cooling,the material is deposited inside a water tank by varying the water *** validate the air and water cooling thermal management techniques,IN718 single-pass and multilayer linear walls were deposited using the bidirectional gas metal arc welding based WAAM setup under four different heat input *** the deposition of single layers,the temperature profiles were recorded,and the geometric and microstructural features were *** multilayer wall structures,the mechanical properties(hardness,tensile strength,and elongation)were determined and assessed using the corresponding microstructural features explored through scanning electron microscopy(SEM),energy dispersive spectroscopy(EDS),and electron backscatter diffraction(EBSD)*** microstructure observed through SEM analysis in the building direction was found to be nonhomogenous compared with that in the deposition ***,water cooling was found to govern bead characteristics,such as wall width and *** grain size and anisotropy of the mechanical properties also decreased in the water-cooled ***,water cooling is an economical and efficient method to mitigate excessive heat accumulation in WAAM-deposited IN718.

关键词： Air cooling Water cooling IN718 Bead characteristics Microstructure Electron backscatter diffraction(EBSD)

Study of damage behavior and repair effectiveness of patch repaired carbon fiber laminate under quasi-static indentation loading

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Defence Technology（防务技术） 2024年第4期34卷 29-41页

作者： Alok kumar Chinmaya kumar Sahoo A.Arockiarajan Department of Applied Mechanics Indian Institute of Technology MadrasChennai 600036India

Damage caused due to low-velocity impacts in composites leads to substantial deterioration in their residual strength and eventually provokes structural *** work presents an experimental investigation on the effects of different patch and parent laminate stacking sequences on the enhancement of impact strength of Carbon Fiber Reinforced Polymers(CFRP)composites by utilising the adhesively bonded external patch repair *** evolution study is also performed with the aid of Acoustic Emission(AE).Two different quasi-isotropic configurations were selected for the parent laminate,viz.,[45°/45°/0°/0°]s and[45°/0°/45°/0°]*** Static Indentation(QSI)test was performed on both the pristine laminates,and damage areas were detected by using the C-scan inspection *** laminates were repaired by using a single-sided patch of two different configurations,viz.,[45°/45°/45°/45°]and[45°/0°/0°/45°],and employing a circular plug to fill the damaged *** different combinations of repaired laminates with two configurations of each parent and patch laminate were produced,which were further subjected to the QSI *** results reveal the effectiveness of the repair method,as all the repaired laminates show higher impact resistance compared to the respective pristine *** of[45°/0°/0°/45°]configuration when repaired by taking[45°/45°/0°/0°]s and[45°/0°/45°/0°]s as parents exhibited 68%and 73%higher peak loads,respectively,than the respective pristine ***,parent and patch of configuration[45°/0°/45°/0°]s and[45°/0°/0°/45°],respectively,attain the highest peak load,whereas[45°/45°/0°/0°]s and[45°/45°/45°/45°]combinations possess the most gradual decrease in the load.

关键词： Carbon fiber reinforced polymers(CFRP) Quasi-isotropic laminate Quasi static indentation(QSI) Acoustic emission(AE) Composite repair

Surface Modification Aspects for Improving Biomedical Properties in Implants:A Review

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Acta Metallurgica Sinica(English Letters) 2024年第2期37卷 213-241页

作者： J.Sharath kumar Rakesh kumar Rajeev Verma Industrial and Production Department Dr B R Ambedkar National Institute of Technology JalandharJalandharPunjab144008India

The primary focus during surgery is to ensure successful implantation by achieving long-term and stable fixation of *** surgery is now more focused on the development of novel biomaterials intended to improve implant *** obtain a better understanding of metal implants,this article investigated the causes of material failures in certain cases and analysed a few case *** interaction between the implant and bone tissue was a crucial aspect of successful implantation,and this study explored the factors influencing this interaction as well as ways to improve *** modern approaches used for modifying implant surfaces were systematically illustrated and briefly *** spray coatings were often favoured because of their wide range of coating materials,but other substantial surface modifications(such as friction stir processing and laser surface texturing)were also used for a selection of ***,implant surfaces with desirable features,such as biocompatibility,antibacterial properties,corrosion resistance,and wear resistance,were essential for optimising implant *** systematic review's main aim is to provide exhaustive reference information and a broad overview to advance the production and design of orthopaedic implants.

关键词： Biomaterials Surface treatments Thermal spray coatings Antibacterial Biocompatibility Corrosion resistance Wear resistance

Identification of earthquake induced structural damage based on synchroextracting transform

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Earthquake Engineering and Engineering Vibration 2024年第2期23卷 475-487页

作者： Roshan kumar Gaurav kumar Wei Zhao Arvind R Yadav Gang Yu Jayendra kumar Evans Amponsah Department of Electronic and Information Technology Miami College of Henan UniversityHenan 475004China Alliance University Alliance College of Engineering and DesignBanglore 562106India Department of Electronics and Comm Parul UniversityVadodra 391760India School of Electrical Engineering University of JinanJinan 250022China Department of Electronics and Comm NIT JamshedpurJamshedpur 831014India Department of Civil engineering Kwame Nkrumah University of Science and TechnologyKumasi 10959Ghana

Several popular time-frequency techniques,including the Wigner-Ville distribution,smoothed pseudo-Wigner-Ville distribution,wavelet transform,synchrosqueezing transform,Hilbert-Huang transform,and Gabor-Wigner transform,are investigated to determine how well they can identify damage to *** this work,a synchroextracting transform(SET)based on the short-time Fourier transform is proposed for estimating post-earthquake structural *** performance of SET for artificially generated signals and actual earthquake signals is examined with existing *** other tested techniques,SET improves frequency resolution to a great extent by lowering the influence of smearing along the time-frequency ***,interpretation and readability with the proposed method are improved,and small changes in the time-varying frequency characteristics of the damaged buildings are easily detected through the SET method.

关键词： cross-term damage detection earthquake signal synchroextracting transform time-frequency

Study of Type-B QPOs Observed in Black Hole X-Ray Binary Swift J1728.9-3613

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Research in Astronomy and Astrophysics 2024年第3期24卷 1-9页

作者： Raj kumar Astrophysical Sciences Division Bhabha Atomic Research CentreMumbai 400085India Homi Bhabha National Institute Mumbai 400094India

We report the detection of type-B quasi-periodic oscillation(QPO)of the black hole X-ray binary Swift J1728.9-3613 observed by NICER during the 2019 outburst.A type-B QPO was observed for the first two days and it disappeared as flux increased,but again appeared at∼7.70 Hz when flux was dramatically *** source was found in the soft intermediate state during these *** further studied the energy dependence of the *** found that QPO was observed only for a higher energy range implying that the origin of QPO is possibly due to the corona emitting higher energy photons by the inverse Compton *** variation of spectral parameters can be explained with the disk truncation *** fractional rms was found to be monotonically increased with *** phase lag spectrum followed the“U-shaped”*** rms and phase lag spectrum are modeled and explained with the single-component Comptonization model vkompthdk.

关键词： X-rays binaries-accretion-accretion disks-X-rays individual (Swift J1728.9-3613)

AI/ML Enabled Automation System for Software Defined Disaggregated Open Radio Access Networks:Transforming Telecommunication Business

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Big Data Mining and Analytics 2024年第2期7卷 271-293页

作者： Sunil kumar Institute for Communication Systems University of SurreyGuildfordGU27XHUK

Open Air Interface(OAI)alliance recently introduced a new disaggregated Open Radio Access Networks(O-RAN)framework for next generation telecommunications and *** disaggregated architecture is open,automated,software defined,virtual,and supports the latest advanced technologies like Artificial Intelligence(AI)Machine Learning(AI/ML).This novel intelligent architecture enables programmers to design and customize automated applications according to the business needs and to improve quality of service in fifth generation(5G)and Beyond 5G(B5G).Its disaggregated and multivendor nature gives the opportunity to new startups and small vendors to participate and provide cheap hardware software solutions to keep the market *** paper presents the disaggregated and programmable O-RAN architecture focused on automation,AI/ML services,and applications with Flexible Radio access network Intelligent Controller(FRIC).We schematically demonstrate the reinforcement learning,external applications(xApps),and automation steps to implement this disaggregated O-RAN *** idea of this research paper is to implement an AI/ML enabled automation system for software defined disaggregated O-RAN,which monitors,manages,and performs AI/ML-related services,including the model deployment,optimization,inference,and training.

关键词： Artificial Intelligence(AI) Reinforcement Learning(RL) Open Radio Access Networks(O-RAN) Flexible Radio access network Intelligent Controller(FRIC) external Applications(xApps) Machine Learning(ML),sixth generation(6G)