Search

Cks1, a small protein whose expression is strongly associated with aggressive breast tumors, is a component of cyclin-cdk complexes, as well as the SCFSkp2 ubiquitin ligase. In these studies, we explored its roles in estrogen receptor–positive breast tumor cells. When exposed to the antiestrogen ICI 182780, these cells accumulate in G1 by reducing the expression of Cks1, and increasing the levels of p130/Rb2, a cdk2 inhibitor and SCFSkp2 target. Heregulin β1 or estradiol abrogate antiestrogen effects by increasing Cks1 expression, down-regulating p130/Rb2 and inducing S phase entry. Depletion of Cks1 in these cells by RNA interference concomitantly decreased Skp2 and up-regulated p130/Rb2 and another SCFSkp2 target, p27Kip1. Remarkably, however, Cks1-depleted cells not only exhibit slowed G1 progression, but also accumulate in G2-M due to blocked mitotic entry. Notably, we show that cdk1 expression, which is crucial for M phase entry, is drastically diminished by Cks1 depletion, and that restoration of cdk1 reduces G2-M accumulation in Cks1-depleted cells. cdk1 reduction in Cks1-depleted cells is a consequence of a marked decrease in its mRNA and not due to alteration in its proteolytic turnover. Both heregulin β1 and estradiol could neither restore cdk1 nor sustain cycling in Cks1-depleted cells, although classical estrogen receptor function remained unaltered. Cks1 depletion also decreased Skp2 in human mammary epithelial cells without altering cell cycle progression. Thus, the indispensability of Cks1 to the breast cancer cell cycle, versus its redundancy in normal cells, suggests that Cks1 abrogation could be an effective interventional strategy in breast cancer. [Cancer Res 2007;67(23):11393–401]

Supplementary Figure 2 from Cks1 Regulates cdk1 Expression: A Novel Role during Mitotic Entry in Breast Cancer Cells

Supplementary Figure 4 from Cks1 Regulates cdk1 Expression: A Novel Role during Mitotic Entry in Breast Cancer Cells

Supplementary Table 1 from Cks1 Regulates cdk1 Expression: A Novel Role during Mitotic Entry in Breast Cancer Cells

Supplementary Figure 1 from Cks1 Regulates cdk1 Expression: A Novel Role during Mitotic Entry in Breast Cancer Cells

Supplementary Figure Legends 1-4 from Cks1 Regulates cdk1 Expression: A Novel Role during Mitotic Entry in Breast Cancer Cells

Supplementary Figure 3 from Cks1 Regulates cdk1 Expression: A Novel Role during Mitotic Entry in Breast Cancer Cells

A luminescent spectroscopy probe is an effective tool to ascertain the precise status of Eu(iii) coordination in the ionic liquid phase. Many of the unrevealed facts in IL based solvent extraction results have been explored by luminescence spectroscopy.

Consumer behavior is often unpredictable. It includes the actions that consumers take or do not take due to some internal or external influences. The fast pace of life, daily changes in desires and needs, as well as the appearance of new technologies and opportunities on the market, significantly affect consumer behavior. Natural disasters, wars, and pandemics also have a big impact, which significantly change the awareness and behavior of consumers. Consumers become irrational and behave impulsively, while their habits change completely. This paper will research consumer behavior due to the COVID-19 pandemic and the ways in which it has changed over time. A sample of consumer behavior due to the COVID-19 pandemic and other global crises will also be presented.

The existence of unique ON⋯π pnicogen bonding in combination with C-H⋯π/C-H⋯O hydrogen bonding interactions has been experimentally affirmed in the heterodimers of nitromethane with aliphatic (acetylene; NMAc) and aromatic (benzene; NMBz) π-electron donors at low temperatures under isolated conditions. The potential energy surfaces of NMAc and NMBz dimers have been probed for stationary points using

In the present communication, we have explored the feasibility of the dissolution of U–Zr alloy in an acid-saturated amide-based organic ligand, N,N-dihexyloctanamide (DHOA) in the context of the preparation of the spent metallic fuel dissolver solution. The diverse experimental parameters such as temperature, the concentration of nitric acid, dissolution time, volume of DHOA, etc. were optimized for accomplishing the dissolution process. The present methodology requires less amount of nitric acid for the dissolution of the metalloy as compared to that of direct dissolution in nitric acid medium, and in particular, DHOA strongly influences the dissolution time and the temperature demand for the dissolution process. These added advantages certainly have the edge over the conventional dissolution process. Stripping of the loaded metal ion in DHOA phase and the recycling of DHOA were also ascertained and reported in the paper. Dissolution of U–Zr pellet in the acid-saturated DHOA phase leads to quantitative dissolution of uranium leaving zirconium as the pasty black residue with poor dissolution performance.

E-learning is a planned effort towards providing interactive and experiential learning having flexibility in terms of time, place, pace, participation and accessibility. Globalization has set the stage for a social transformation of the world economy driven by technological innovation, emphasizing knowledge-based processes. While the tertiary education enrolments in wealthy nations have gone up incrementally, the same cannot be said to be right about developing economies. E-Learning can streamline enrolments to higher education, in developing nations by being a cost-effective and flexible alternative. The objective of this paper is to draw attention to the similarities in the national culture of these two countries and compare students’ perception on e-learning in India and Sri Lanka along eight dimensions viz., viability, dependability, flexibility, inclusivity, power, pertinence, challenge and equitability. The results reveal that e-learning is equally popular among students from both countries, and they have a high perception score towards e-learning on each of the measured eight dimensions. Hence results are indicative of an opportunity of tapping the potential of e-learning in reaching out to a broader audience of underprivileged students and onboarding them into the knowledge economy.

The role of nitrogen, the first member of the pnicogen group, as an electron donor in hypervalent non-covalent interactions has been established long ago, while observation of its electron accepting capability is still elusive experimentally, and remains quite intriguing, conceptually. In the light of minimal computational exploration of this novel class of pnicogen bonding so far, the present work provides experimental proof with unprecedented clarity, for the existence of N(acceptor)⋯N(donor) interaction using the model nitromethane (NM) molecule with ammonia (AM) as a Lewis base in NM–AM aggregates. The NM–AM dimer, in which the nitrogen atom of NM (as a unique pnicogen) accepts electrons from AM (the traditional electron donor), was synthesized at low temperatures under isolated conditions within inert gas matrixes and was characterized using infrared spectroscopy. The experimental generation of the NM–AM dimer stabilized via N⋯N interaction has strong corroboration from ab initio calculations. Furthermore, confirmation regarding the directional prevalence of this N⋯N interaction over C–H⋯N and N–H⋯O hydrogen bonding is elucidated quantitatively by quantum theory of atoms in molecules (QTAIM), electrostatic potential mapping (ESP), natural bond orbital (NBO), non-covalent interaction (NCI) and energy decomposition (ED) analyses. The present study also allows the extension of σ-hole/π-hole driven interactions to the atoms of the second period, in spite of their low polarizability.

Owing to the fact that σ stacking is as important as π stacking in determining the structural motifs of aliphatic saturated cyclic hydrocarbons, in this work we have provided the first unambiguous spectroscopic evidence for the existence of σ stacking interactions in cyclohexane dimers at low temperatures. Molecular beam experiments performed using effusive nozzle and supersonic jet sources on cyclohexane in an N2 matrix generated cyclohexane dimers stabilized through σ stacking and the dimers were characterized by infrared spectroscopy. The ab initio computations carried out on cyclohexane dimers identified eclipsed (face-to-face), parallel displaced and T-shaped structures, which are predominantly stabilized by σ stacking interactions. While natural bond orbital analysis substantiated a significant amount of σ → σ* interactions involved in the stabilization, the Atoms in Molecules analysis indicated that the stacking is induced by a plausible 'dihydrogen bonding' interaction. Energy decomposition analysis disclosed that a large measure of dispersion interactions effectively contributes for the overall stability of cyclohexane dimers.

Methyl imidazole (M-Imid)⋯HCl (1 : 1) complexes were studied using matrix isolation infrared spectroscopy and ab initio computations. Computations using the MP2 level of theory with the aug-cc-pVDZ basis set predicted three complexes, where the global minimum had a strong hydrogen-bonded N⋯H⋯Cl interaction with a binding energy of ∼12 kcal mol−1 (complex A). The first local minimum had an H⋯π interaction (complex B) and the second local minimum (complex C) was stabilized through combined hydrogen, halogen and pnicogen bonding (with a nitrogen atom as the pnicogen) interactions. Of the three complexes, the hydrogen-bonded complex A alone possesses experimental significance. Experiments were performed by co-depositing M-Imid and HCl separately in an N2 matrix at a low temperature of ∼12 K. The annealing of the low temperature matrix encouraged the formation of M-Imid–HCl complex A, which was subsequently probed using infrared spectroscopy. Experimentally, the vibrational shift of ∼1720 cm−1 was observed for the N2 matrix, while harmonic frequency calculations indicated a shift of 1063 cm−1 in the H–Cl stretching region of the strong hydrogen-bonded complex A. The inclusion of anharmonicity in the calculations red-shifted the H–Cl stretching frequency further down to 1650 cm−1, which was almost close to the experimental value. It is inferred from this large experimental red-shift of the stretching frequency of the proton donor that proton-shared hydrogen bonding is facilitated in the M-Imid–HCl system experimentally. Using atoms in molecules, energy decomposition and natural bond orbital analyses, the uniqueness of this strong proton-shared hydrogen bonding is established with respect to conventional hydrogen bonding.

One of the major prerequisites for effective operations of a manufacturing plant depends on the sufficiency of a good facility layout. A well-planned facility layout enables better utilization of resources and thereby better production control. The purpose of this research was to analyse the effectiveness of the layout improvement through systematic plant layout planning (SLP) method. Factors like relationship diagram/affinity chart, material flow, space requirements etc. were studied to propose a modified layout according to the SLP method. The study found that the improved plant layout not only optimised the material flow and space requirements but in addition it enormously reduced the material handling cost of the plant thereby bringing better operational efficiency.

Bacterial virulence factors or effectors are proteins targeted into host cells to coopt or interfere with cellular proteins and pathways. Viruses often coopt the same cellular proteins and pathways to support their replication in infected cells. Therefore, we screened the Legionella pneumophila effectors to probe virus-host interactions and identify factors that modulate tomato bushy stunt virus (TBSV) replication in yeast surrogate host. Among 302 Legionella effectors tested, 28 effectors affected TBSV replication. To unravel a coopted cellular pathway in TBSV replication, the identified DrrA effector from Legionella was further exploited. We find that expression of DrrA in yeast or plants blocks TBSV replication through inhibiting the recruitment of Rab1 small GTPase and endoplasmic reticulum-derived COPII vesicles into the viral replication compartment. TBSV hijacks Rab1 and COPII vesicles to create enlarged membrane surfaces and optimal lipid composition within the viral replication compartment. To further validate our Legionella effector screen, we used the Legionella effector LepB lipid kinase to confirm the critical proviral function of PI(3)P phosphoinositide and the early endosomal compartment in TBSV replication. We demonstrate the direct inhibitory activity of LegC8 effector on TBSV replication using a cell-free replicase reconstitution assay. LegC8 inhibits the function of eEF1A, a coopted proviral host factor. Altogether, the identified bacterial effectors with anti-TBSV activity could be powerful reagents in cell biology and virus-host interaction studies. This study provides important proof of concept that bacterial effector proteins can be a useful toolbox to identify host factors and cellular pathways coopted by (+)RNA viruses.

Luminescence of Eu(III) with furan monocarboxylates (FCA) ligands namely, 2 furoate (2FCA) and 3 furoate (3FCA) have been studied in aqueous medium. Both the ligands sensitized the luminescence of Eu(III) to a different extent. The magnitude of luminescence intensity was higher for the Eu(III)-2FCA than Eu(III)-3FCA complex due to the higher absorbance of 2FCA ligand as corroborated by UV–Vis spectroscopy. The formation of 1:1 Eu(III) complexes with both the ligands was confirmed through luminescence lifetime measurements. Stability constants of these complexes, calculated using HypSpec computation program were found to increase with temperature. The coordination mode of both the ligands was found to be monodentate. Van't Hoff equation was used to calculate enthalpy of formation of Eu(III) complexes using stability constants at different temperatures (283, 298, 313, 328, 343 K). The enthalpy of complex formation of 2FCA and 3FCA with Eu(III) was endothermic. Density functional theory (DFT) and time dependent (TD)-DFT calculations were performed to corroborate experimental observations.

Over the years, a number of performance indicators have been developed and used to assess the performance of mutual funds. The choice of these performance measures completely rests on the perception of the investor as to which measure conveys the information sought after by the investor and which information the investor considers would be meaningful in deciding the fate of his investments. Objective & Methodology: To evaluate the risk and return of selected technology sector mutual funds and to analyse the composite information conveyed by Sharpe’s ratio, Treynor’s ratio, upside and downside capture ratios. Results & Discussion: When the funds were analysed using Sharpe ratio, Treynor’s ratio upside capture ratio and downside capture ratio, the funds that performed the best in consideration to a particular measure may not be termed best when analysed with another performance gauges stressing on the fact that all the ratios should be analysed with an integrated perspective to derive any underlying information on the performance of the fund and that the choice of the benchmark which stands as a basis to assess performance of the fund is crucial.

The purpose of the article is to recognize the moderating effect of customer knowledge on perceived service quality and customer satisfaction through customer value evaluation in the Indian banking sector. This knowledge can considerably streamline the effort banks invest in acquiring the right kind of customers. The results of the study indicated that perceptions of service quality positively impacted customer value evaluation. Moreover, customer knowledge strengthened the relationship that the empathy and responsiveness dimensions of service quality had with customer value evaluation and moderated the relationship that reliability and tangibility dimensions had with customer value evaluation.

The thermal decomposition behaviour of tris(2-methyl butyl) phosphate (T2MBP), a higher branched homologue of tri-n-butyl phosphate (TBP), which possesses the vital characteristics of a potential extractant for the processing of nuclear materials is the subject of the present work. The thermal stability of neat T2MBP and 1.1 M T2MBP/n-dodecane (in the presence and absence of HNO3) has been determined using adiabatic calorimeter. The results have been compared with the corresponding tri-n-amyl phosphate (TAP) and TBP based systems. From the calorimetric experiments, the thermo-kinetic parameters have been deduced and the resulting end products have been analysed. The data show lower magnitude of exothermicity for T2MBP compared to TAP based systems. The present work thereby highlights the influence of alkyl group chain length and branching on the thermal decomposition behaviour of trialkyl phophates, which in turn will help to identify an alternate to TBP to avoid the potential runaway explosion hazards.

This paper analyses the relationship between the teacher technology competence and their use of technology under the mediating influence of ease of use. The paper presents a set of results that are empirically tested on a sample of 387 high school and higher secondary school teachers from across 14 districts in Kerala, a southern state in India. A majority of these respondents had a teaching experience of more than eleven years and had been using computers for more than five years. The results reveal that technology competence among these teachers was moderately but positively correlated to their actual use of technology and this relationship was found to be mediated by ease of use of technology. The paper discusses the implications of these findings and makes recommendations to leverage these relationships so as to achieve greater technology integration.

The coronavirus disease 2019 (COVID-19) caused by a novel coronavirus, turned into a pandemic and raised a serious concern to the global healthcare system. The reverse transcription polymerase chain reaction (RT-PCR) is the most widely used diagnostic tool to detect COVID-19. However, this test is time consuming and subject to availability of the test kits during a crisis. An automated method of screening chest x-ray images using convolutional neural network (CNN) Transfer Learning approach has been proposed as a relatively fast and cost-effective, decision support tool to detect pulmonary pathology due to COVID-19. In this study we have used Kaggle dataset with chest x-ray images of normal and pneumonia cases. We have added COVID-19 x-ray images from 5 different open-source datasets. The images were pre-processed based on the position of radiography images and greyscale was applied and subsequently the images were used for training. After consolidation, COVID-19 images comprised only 5% of the dataset. To address the class imbalance, we have used dynamic image augmentation technique to reduce the bias. We have then explored custom CNN and VGG-16, InceptionNet-V3, MobileNet-V2, ResNet-50, and DarkNet-53 transfer learning approaches to classify COVID-19, other pneumonia and normal x-ray images and compared their performances. So far, we have achieved the best score of F1 score 0.95, sensitivity 95% and specificity 95% for COVID-19 class with Darknet-53 feature extractor. Darknet-53 classifier is part of the state-of-the-art object detection algorithm named Yolo-v3. We have also done a McNemar-Bowker post-hoc test to compare Darknet-53 performance with the next best ResNet-50. This test suggests that Darknet-53 is significantly better skilled than ResNet-50 in differentiating COVID-19 from other pneumonia in chest x-ray images.

Heterodimers of POCl

The branching of a methyl group in a linear chain has a profound influence on the conformational morphology as it wields a strong control in reducing a large number of conformations. To unravel the effect of branching on the second non-hyperconjugative carbon atom on the conformational landscape, the conformations of tris(2-methylbutyl)phosphate (T2MBP) were studied using Density Functional Theory (DFT) computations and matrix isolation infrared spectroscopy. Experimentally, T2MBP along with N2/Ar/Kr/Xe gases was effusively expanded and deposited at a low temperature of 12 K, which was subsequently probed using infrared spectroscopy. The computations of all the conformations were accomplished using the B3LYP level of theory with the 6-311++G(d,p) basis set. A dimethyl(2-methylbutyl) phosphate (DM2MBP) prototype, a molecule containing a single 2-methylbutyl moiety, was examined for its conformations. Computations predicted 18 and 9 conformations each for the ‘gauche’ and ‘trans’ families, respectively, in which the third branched carbon completely influences the orientation of the fourth carbon, which simplifies the conformational problem of DM2MBP. Of the 18 and 9 bunches each in the ‘gauche’ and ‘trans’ families, only 7 and 3 conformations, respectively, became energetically important, which when extrapolated to T2MBP resulted in 343 and 147 conformational possibilities. The factor of degeneracy further reduced these numbers and a total of 168 conformations effectively contribute to the conformational composition of T2MBP in the gas phase. The role of stereo electronic and steric factors prevalent in the conformational clusters of T2MBP was unravelled respectively using natural bond orbital and non-covalent interaction analyses.