Heat shock proteins (HSPs) are a large family of chaperones that are involved in protein folding and maturation of a variety of "client" proteins protecting them from degradation, oxidative stress, ...hypoxia, and thermal stress. Hence, they are significant regulators of cellular proliferation, differentiation and strongly implicated in the molecular orchestration of cancer development and progression as many of their clients are well established oncoproteins in multiple tumor types. Interestingly, tumor cells are more HSP chaperonage-dependent than normal cells for proliferation and survival because the oncoproteins in cancer cells are often misfolded and require augmented chaperonage activity for correction. This led to the development of several inhibitors of HSP90 and other HSPs that have shown promise both preclinically and clinically in the treatment of cancer. In this article, we comprehensively review the roles of some of the important HSPs in cancer, and how targeting them could be efficacious, especially when traditional cancer therapies fail.
Jets with electrons from boosted top quarks Chatterjee, Suman; Godbole, Rohini; Roy, Tuhin S.
The journal of high energy physics,
01/2020, Letnik:
2020, Številka:
1
Journal Article
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A
bstract
We propose a method to identify jets consisting of all the visible remnants of a boosted top quark decaying semileptonically with an electron in the final state. An overlap of electron ...shower with the
b
quark initiated shower, and the large nontrivial energy-momentum carried by the invisible neutrino in the top quark decay are the two obstacles to achieving this aim. Our method uses the distribution of energy in different parts of the detector to identify a jet containing an energetic electron, involves use of substructure of the jet to determine the momentum associated with the electron and then completes the identification of top jet with the construction of new variables which would reflect the top quark decay kinematics. The last part involves an ansatz of the existence of a massless, invisible four-momentum
roughly
collimated with the electron, whose four- momentum when combined with that of the the electron and the full jet, reconstructs to the
W
boson and the top quark respectively. We demonstrate the efficacy of this proposal using simulated data and show that our method not only reduces the backgrounds from light flavor jets,
b
jets from QCD, and hadronic top jets, it can also tell apart jets rich in electrons but not due to top quark decays.
Laser beam welding (LBW) has found wide applications in several fields, including electronics, aerospace, and automobile industries, owing to its inherent capabilities over existing welding ...techniques. Dissimilar laser welding is one of the challenging fabrication processes. However, joining of different materials poses challenging issues because material properties of each material interacts to give rise to hybrid system performance. In present study weld of Al-Cu and Cu-Al has been performed using Ytterbium pulsed fibre laser with a maximum laser power of 300 W. The scanning electron microscope (SEM), and energy dispersive x-ray spectroscopy (EDS) has been employed to investigate the microstructural and chemical composition of the welded joints. The EDS analysis showed the presence of possible intermetallic compounds (IMCs) like AlCu and Cu2Al in the fusion zone. The Al-Cu and Cu-Al welded joints had maximum shear strength of 295 N and 84 N, respectively. The results showed the efficacy of Al-Cu joints over Cu-Al joints. The study further demonstrated that the Al-Cu weld had a better microstructure with fewer pores and cracks than the Cu-Al welds by varying the laser powers.
Effective suppression of dye aggregation on the photoanode surface of dye sensitized solar cells plays a key role in improving solar cell efficiency. Chenodeoxycholic acid (CDCA) is a very popular ...anti dye aggregation material used in dye sensitized solar cells (DSSC). However, the selection of an improper concentration of CDCA may lead to decreased solar cell efficiency by lowering the open circuit voltage and short circuit current as a consequence of reduced dye loading. The influence of CDCA as a dye co-adsorbent on the performance of DSSCs fabricated using Rose Bengal dye was studied in this paper. The concentration of the CDCA solution was varied to identify the optimum value for the best device performance. Aside from this, the effect of a very thin and compact ZnO blocking layer was also investigated to reduce the charge recombination. With photovoltaic parameters such as short circuit current density (J
sc
) = 1.98 mA/cm
2
, open circuit voltage (V
oc
) = 0.58 V, and fill factor (FF) = 0.43, the traditional cell displayed an overall conversion efficiency of 0.49%, while the power conversion efficiency was found to be increased to 1.00% (Jsc = 2.80 mA/cm
2
, V
oc
= 0.64, FF = 0.58) when CDCA was added at optimised concentration of 8 mM. Reduced dye aggregation and increased electron injection in the presence of CDCA may be accounted for the DSSC's remarkable improvement in the efficiency. Moreover, the combined effect of 8 mM CDCA and the compact ZnO blocking layer dramatically enhanced the efficiency further to 1.22% (J
sc
= 3.09 mA/cm
2
, V
oc
= 0.66, FF = 60). Electrochemical impedance spectroscopic (EIS) analysis revealed that the addition of CDCA as a co-adsorbent in the dye solution and addition of ZnO blocking layer resulted in significantly improved electron lifetime and reduced electron recombination yielding improved J
sc
, V
oc
and η.
Patients with EGFR-mutant non-small-cell lung cancer (NSCLC) have significantly benefited from the use of EGFR tyrosine kinase inhibitors (TKIs). However, long-term efficacy of these therapies is ...limited due to de novo resistance (~30%) as well as acquired resistance. Epithelial-mesenchymal transition transcription factors (EMT-TFs), have been identified as drivers of EMT-mediated resistance to EGFR TKIs, however, strategies to target EMT-TFs are lacking. As the third generation EGFR TKI, osimertinib, has now been adopted in the first-line setting, the frequency of T790M mutations will significantly decrease in the acquired resistance setting. Previously less common mechanisms of acquired resistance to first generation EGFR TKIs including EMT are now being observed at an increased frequency after osimertinib. Importantly, there are no other FDA approved targeted therapies after progression on osimertinib. Here, we investigated a novel strategy to overcome EGFR TKI resistance through targeting the EMT-TF, TWIST1, in EGFR-mutant NSCLC. We demonstrated that genetic silencing of TWIST1 or treatment with the TWIST1 inhibitor, harmine, resulted in growth inhibition and apoptosis in EGFR-mutant NSCLC. TWIST1 overexpression resulted in erlotinib and osimertinib resistance in EGFR-mutant NSCLC cells. Conversely, genetic and pharmacological inhibition of TWIST1 in EGFR TKI-resistant EGFR-mutant cells increased sensitivity to EGFR TKIs. TWIST1-mediated EGFR TKI resistance was due in part to TWIST1 suppression of transcription of the pro-apoptotic BH3-only gene, BCL2L11 (BIM), by directly binding to BCL2L11 intronic regions and promoter. As such, pan-BCL2 inhibitor treatment overcame TWIST1-mediated EGFR TKI resistance and were more effective in the setting of TWIST1 overexpression. Finally, in a mouse model of autochthonous EGFR-mutant lung cancer, Twist1 overexpression resulted in erlotinib resistance and suppression of erlotinib-induced apoptosis. These studies establish TWIST1 as a driver of resistance to EGFR TKIs and provide rationale for use of TWIST1 inhibitors or BCL2 inhibitors as means to overcome EMT-mediated resistance to EGFR TKIs.
Superbugs such as infectious bacteria pose a great threat to humanity due to an increase in bacterial mortality leading to clinical treatment failure, lengthy hospital stay, intravenous therapy and ...accretion of bacteraemia. These disease-causing bacteria gain resistance to drugs over time which further complicates the treatment. Monitoring of antibiotic resistance is therefore necessary so that bacterial infectious diseases can be diagnosed rapidly. Antimicrobial susceptibility testing (AST) provides valuable information on the efficacy of antibiotic agents and their dosages for treatment against bacterial infections. In clinical laboratories, most widely used AST methods are disk diffusion, gradient diffusion, broth dilution, or commercially available semi-automated systems. Though these methods are cost-effective and accurate, they are time-consuming, labour-intensive, and require skilled manpower. Recently much attention has been on developing rapid AST techniques to avoid misuse of antibiotics and provide effective treatment. In this review, we have discussed emerging engineering AST techniques with special emphasis on phenotypic AST. These techniques include fluorescence imaging along with computational image processing, surface plasmon resonance, Raman spectra, and laser tweezer as well as micro/nanotechnology-based device such as microfluidics, microdroplets, and microchamber. The mechanical and electrical behaviour of single bacterial cell and bacterial suspension for the study of AST is also discussed.
•Emerging engineering AST technologies with emphasis on phenotypic AST.•Microfluidics-based technologies with different sensing modalities.•Advantages and limitations with various techniques with respect to its translational value.•Constraints and challenges in scaling to point-of-care platforms.
Background: Fungal infections are predominantly opportunistic infections in immunocompromised patients and in immunocompetent adults with a history of trauma. Recently, there is an increase in trends ...of fungal infections in immunocompetent individuals also without any history of trauma. Pigmented fungi are a group of fungi that have pigment in their cell wall and also known as dematiaceous fungi. These pigmented fungi include phaeohyphomycosis with a differential diagnosis of chromoblastomycosis, cryptococcosis, mycetoma, and aspergillus. Phaeohyphomycosis is a subcutaneous or systemic infection characterized histologically by dark-colored fungal hyphae and yeast forms (black yeast). Aims and Objectives: The aim of the present study is to analyze the clinicopathological features of pigmented fungal infections in biopsy specimen based on their histomorphology. Materials and Methods: This was a prospective study in which we have analyzed the dematiaceous fungal species by their histomorphological characteristics in biopsy specimens. Results: A total of 21 cases of biopsy specimens (with the clinical presentation of cutaneous/subcutaneous lesions) were studied histologically which showed 13 cases of phaeohyp homycosis, seven cases of eumycotic mycetoma, and one case of chromoblastomycosis. There was male predominance (17, 80.95%) and the majority of the patients were >60 years (16, 76.19%). Most common site of infection was foot with predominant clinical presentation as subcutaneous mass lesion. Conclusion: All the cases of dematiaceous fungal infections were diagnosed by histopathological examination. Melanin in the cell wall of dematiaceous fungi is the pathogenic factor. Phaeohyphomycosis is no longer considered as a rare infection rather there is an increasingly incidence of recognized infection. Although culture and histopathological study remain important tools for final diagnosis, various molecular studies might be helpful for accurate diagnosis.
Abstract
Excitonic states trapped in harmonic moiré wells of twisted heterobilayers is an intriguing testbed for exploring many-body physics. However, the moiré potential is primarily governed by the ...twist angle, and its dynamic tuning remains a challenge. Here we demonstrate anharmonic tuning of moiré potential in a WS
2
/WSe
2
heterobilayer through gate voltage and optical power. A gate voltage can result in a local in-plane perturbing field with odd parity around the high-symmetry points. This allows us to simultaneously observe the first (linear) and second (parabolic) order Stark shift for the ground state and first excited state, respectively, of the moiré trapped exciton - an effect opposite to conventional quantum-confined Stark shift. Depending on the degree of confinement, these excitons exhibit up to twenty-fold gate-tunability in the lifetime (100 to 5 ns). Also, exciton localization dependent dipolar repulsion leads to an optical power-induced blueshift of ~ 1 meV/μW - a five-fold enhancement over previous reports.
Dissimilar metal welding leads to the development of brittleness in the welded joints due to incompatibility in mechanical and physical properties of the metals to be joined. To overcome such ...brittleness, suppressing the formation of intermetallic compound is the key factor for attaining reliable welded joints. The present study attempts to find the possibility of obtaining joints of crack-free surface in laser butt welding of Ti6Al4V with AISI 304 stainless steel sheets using intermetallic layer through electroplating process. Laser welding on Ti6Al4V titanium alloy with AISI 304 stainless steel sheets of 5 mm thickness has been performed providing copper as an intermetallic layer using electroplating process. Electroplating of the welding edges of two different materials was carried out with and without adding sulphuric acid in the electrolyte solution. The electroplating results indicate that addition of sulphuric acid in the solution increases the thickness of the coating. Presence of copper at the welding edges provides compatibility between Ti6Al4V and AISI 304 during the laser welding process and reduces brittleness. Laser welding was conducted using 3.5-kW CO
2
laser with 3-m/min welding speed. The quality of weldment was characterized by macrostructure analysis by scanning electron microscope (SEM), analysis of composition of weldment by energy dispersive spectroscopy (EDS), phase analysis by X-ray diffraction (XRD), microhardness across the weldment by Vickers hardness tester and estimation of welding strength by dynamic mechanical analyser. Welding strength of around 34 MPa has been obtained and it is quite acceptable.
Introduction: Hypothyroidism, one of the most common thyroid gland disorders, can cause electrolyte disturbances in the body. Hypothyroidism can alter mineral metabolism by changing the levels of ...serum calcium and magnesium. Therefore, it is essential to study any abnormalities in calcium and magnesium metabolism in patients with hypothyroidism. Aim: The aim of this study was to assess the levels of calcium and magnesium in patients with hypothyroidism and to study the correlation between Thyroid Stimulating Hormone (TSH), fT3, and fT4 with calcium and magnesium in subclinical and Overt Hypothyroidism (OH). Materials and Methods: This cross-sectional study was held from August 2019 to January 2020 in the Department of Biochemistry, BS Medical College, Bankura. A total of 150 subjects were included in the study, distributed equally among three groups: euthyroidism, subclinical hypothyroidism, and OH. Serum TSH, fT3, fT4, calcium, and magnesium levels were determined in the laboratory, and the data obtained were statistically analysed using ANOVA test and Pearson’s correlation test. Results: Out of a total of 150 subjects, 61 were female, among whom 23 had subclinical hypothyroidism and 21 had OH. There were significant differences in the mean levels of TSH, fT3, fT4, calcium, and magnesium between the SCH, OH, and euthyroid groups. The study showed that the mean serum calcium level was significantly lower in SCH and OH compared to euthyroids, while the level of serum magnesium was significantly increased in SCH and OH compared to euthyroid. There was a statistically significant negative correlation between TSH and serum calcium in both OH and SCH, while a statistically significant positive correlation was observed between TSH and serum magnesium levels in both groups. Conclusion: The present study revealed that serum magnesium levels were high while serum calcium levels were low in both subclinical hypothyroidism and OH when compared to euthyroid subjects. Additionally, calcium levels negatively correlated with TSH, while magnesium levels positively correlated with TSH levels.
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