Using a Cold Radiometer to Measure Heat Loads and Survey Heat Leaks

We have developed an inexpensive cold radiometer for use in thermal/vacuum chambers to measure heat loads, characterize emissivity and specularity of surfaces and to survey areas to evaluate stray heat loads. We report here the results of two such tests for the James Webb Space Telescope to measure heat loads and effective emissivities of 2 major pieces of optical ground support equipment that will be used in upcoming thermal vacuum testing of the Telescope

"Price Barriers" and the Dynamics of Asset Prices in Equilibrium

In a variety of realistic scenarios, some investors trade infrequently rather than continuously, basing their buy or sell decisions on current price levels. A “price barrier” is a price level at which a large number of investors either buy or sell securities. We analyze the dynamics of asset prices in an economy with infrequent traders and price barriers. Our analysis predicts that when price barriers exist, both asset prices and price volatility can jump at the time the price barrier is reached, even if the trade is rationally anticipated. Moreover, the direction of the price jump may very well be the opposite of what one would expect. A price-triggered purchase may generate a downward jump in stock prices and, vice versa, a price-triggered sale may induce stock prices to jump above the price barrier. This is because trades affect prices before they are implemented: the anticipation of a stock purchase inflates stock prices, while the anticipation of a stock sale depresses stock prices. In the case of repeated trades, before-trade prices anticipate not only the next trade, but also the following ones. This may lead to the counterintuitive result that stock prices are inflated rather than depressed, in the proximity of a stock sale

"Price Barriers" and the Dynamics of Asset Prices in Equilibrium

In a variety of realistic scenarios, some investors trade infrequently rather than continuously, basing their buy or sell decisions on current price levels. A “price barrier” is a price level at which a large number of investors either buy or sell securities. We analyze the dynamics of asset prices in an economy with infrequent traders and price barriers. Our analysis predicts that when price barriers exist, both asset prices and price volatility can jump at the time the price barrier is reached, even if the trade is rationally anticipated. Moreover, the direction of the price jump may very well be the opposite of what one would expect. A price-triggered purchase may generate a downward jump in stock prices and, vice versa, a price-triggered sale may induce stock prices to jump above the price barrier. This is because trades affect prices before they are implemented: the anticipation of a stock purchase inflates stock prices, while the anticipation of a stock sale depresses stock prices. In the case of repeated trades, before-trade prices anticipate not only the next trade, but also the following ones. This may lead to the counterintuitive result that stock prices are inflated rather than depressed, in the proximity of a stock sale

Accurate prediction of core-level spectra of radicals at density functional theory cost via square gradient minimization and recoupling of mixed configurations

State-specific orbital optimized approaches are more accurate at predicting core-level spectra than traditional linear-response protocols, but their utility had been restricted on account of the risk of `variational collapse' down to the ground state. We employ the recently developed square gradient minimization (SGM, J. Chem. Theory Comput. 16, 1699-1710, 2020) algorithm to reliably avoid variational collapse and study the effectiveness of orbital optimized density functional theory (DFT) at predicting second period element 1s core-level spectra of open-shell systems. Several density functionals (including SCAN, B3LYP and $\omega$B97X-D3) are found to predict excitation energies from the core to singly occupied levels to high accuracy ($\le 0.3$ eV RMS error), against available experimental data. Higher excited states are however more challenging by virtue of being intrinsically multiconfigurational. We thus present a CI inspired route to self-consistently recouple single determinant mixed configurations obtained from DFT, in order to obtain approximate doublet states. This recoupling scheme is used to predict the C K-edge spectra of the allyl radical, the O K-edge spectra of CO$^+$ and the N K-edge of NO$_2$ to high accuracy relative to experiment, indicating substantial promise in using this approach for computation of core-level spectra for doublet species (vs more traditional time dependent DFT, EOM-CCSD or using unrecoupled mixed configurations). We also present general guidelines for computing core-excited states from orbital optimized DFT.Comment: Added more dat

Leaching of Korean monazite for the recovery of rare earth metals

The technological innovations resulted in various applications using rare earth metals (REM), which lead to a steep increase in their demand. Monazite is the second most essential naturally occurring phosphate mineral containing REM. The present work reports the recovery of REM from Korean monazite which contained mainly 50.12% rare earth oxide and 29.4% phosphate. For the recovery of REM from monazite, the hydrometallurgical process consisting of alkaline leaching of phosphate followed by acid dissolution of REM has been reported. As the presence of phosphate decreases the leaching efficiency of REM from monazite, the studies were carried out initially for hot digestion of phosphate present in the monazite in an autoclave using sodium hydroxide, which resulted in the formation of RE oxide and soluble sodium phosphate. To get the optimum condition for phosphate decomposition by alkaline leaching, the various process parameters such as concentration of sodium hydroxide, temperature, mixing time and pulp density were studied. The obtained slurry was washed with hot water and filtered to get sodium phosphate in the solution. A maximum of 99% phosphate was removed from monazite concentrate using 50% sodium hydroxide solutions (wt./vol.) at 170oC in 4 h mixing time maintaining the pulp density of 100 g/L. From the phosphate free monazite sample, REM was leached out using hydrochloric acid. More than 95% of REM was found to be leached out using 6M HCl at constant pulp density 100 g/L, temperature 90oC and mixing time 2 h. Further studies are in progress to obtain pure solution and salts of REM from chloride leach liquor using recipitation/ solvent extraction/ ion-exchange techniques

Povećanje letalnog učinka bleomicina na stanice HeLa i V79 s pomoću pčelinjeg otrova

This study investigated possible growth-inhibiting effects of bee venom applied alone or in combination with a cytotoxic drug bleomycin on HeLa and V79 cells in vitro based on clone formation, cell counting, and apoptosis. Melittin, the key component of bee venom, is a potent inhibitor of calmodulin activity, and also a potent inhibitor cell growth and clonogenicity. Intracellular accumulation of melittin correlates with the cytotoxicity of antitumour agents. Previous studies indicated that some calcium antagonists and calmodulin inhibitors enhanced intracellular levels of antitumor agents by inhibiting their outward transport. In this study, treatment of exponentially growing HeLa and V79 cells with bleomycin caused a dose-dependent decrease in cell survival due to DNA damage. This lethal effect was potentiated by adding a non-lethal dose of the bee venom. By preventing repair of damaged DNA, bee venom inhibited recovery from potentially lethal damage induced by bleomycin in V79 and HeLa cells. Apoptosis, necrosis, and lysis were presumed as possible mechanisms by which bee venom inhibited growth and clonogenicity of V79 cells. HeLa cells, on the other hand, showed greater resistance to bee venom. Our findings suggest that bee venom might find a therapeutic use in enhancing cytotoxicity of antitumour agent bleomycin.U uvjetima in vitro istražen je inhibitorni učinak pčelinjeg otrova, samog ili združenog s citostatikom bleomicinom, na rast stanica HeLa i V79. Rabljene su sljedeće metode: brojenje stanica, metoda klonskog rasta i apoptoza. Poznato je da neki antagonisti kalcija i kalmodulinski inhibitori povisuju unutarstaničnu razinu protutumorskih lijekova inhibirajući njihov prijenos iz stanice. Unutarstanična akumulacija melitina izravno povećava citotoksični učinak protutumorskog lijeka. Obrada stanica HeLa i V79 u eksponencijalnoj fazi rasta bleomicinom uzrokuje oštećenje DNA ovisno o dozi te smanjenje broja živih stanica. Uočeno je da se letalni učinak bleomicina može pojačati dodatkom neletalne doze pčelinjeg otrova. Pčelinji otrov pritom inhibira popravak nastalih oštećenja u stanicama HeLa i V79 te sprječava oporavak stanica tretiranih bleomicinom. Apoptoza, nekroza i liza mogući su mehanizmi kojima pčelinji otrov inhibira rast i stvaranje kolonija stanica V79, dok HeLa-stanice pokazuju pojačanu otpornost na pčelinji otrov. Istraživanje također potvrđuje mogućnost uporabe pčelinjeg otrova u povećanju citotoksičnosti bleomicina

The phosphorylated prodrug FTY720 is a histone deacetylase inhibitor that reactivates ERα expression and enhances hormonal therapy for breast cancer

Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and does not respond to conventional hormonal therapies. Strategies that lead to re-expression of ERα could sensitize ERα-negative breast cancers to selective ER modulators. FTY720 (fingolimod, Gilenya), a sphingosine analog, is the Food and Drug Administration (FDA)-approved prodrug for treatment of multiple sclerosis that also has anticancer actions that are not yet well understood. We found that FTY720 is phosphorylated in breast cancer cells by nuclear sphingosine kinase 2 and accumulates there. Nuclear FTY720-P is a potent inhibitor of class I histone deacetylases (HDACs) that enhances histone acetylations and regulates expression of a restricted set of genes independently of its known effects on canonical signaling through sphingosine-1-phosphate receptors. High-fat diet (HFD) and obesity, which is now endemic, increase breast cancer risk and have been associated with worse prognosis. HFD accelerated the onset of tumors with more advanced lesions and increased triple-negative spontaneous breast tumors and HDAC activity in MMTV-PyMT transgenic mice. Oral administration of clinically relevant doses of FTY720 suppressed development, progression and aggressiveness of spontaneous breast tumors in these mice, reduced HDAC activity and strikingly reversed HFD-induced loss of estrogen and progesterone receptors in advanced carcinoma. In ERα-negative human and murine breast cancer cells, FTY720 reactivated expression of silenced ERα and sensitized them to tamoxifen. Moreover, treatment with FTY720 also re-expressed ERα and increased therapeutic sensitivity of ERα-negative syngeneic breast tumors to tamoxifen in vivo more potently than a known HDAC inhibitor. Our work suggests that a multipronged attack with FTY720 is a novel combination approach for effective treatment of both conventional hormonal therapy-resistant breast cancer and triple-negative breast cancer

Role of Sphingosine Kinase 1 and Sphingosine-1-Phosphate Axis in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is primarily diagnosed in the latter stages of disease progression and is the third leading cause of cancer deaths worldwide. Thus, there is a need to find biomarkers of early HCC as well as the development of more effective treatments for the disease. Sphingosine-1-phosphate (S1P) is a pleiotropic lipid signaling molecule produced by two isoforms of sphingosine kinase (SphK1 and SphK2) that is involved in regulation of many aspects of mammalian physiology and pathophysiology, including inflammation, epithelial and endothelial barrier function, cancer, and metastasis, among many others. Abundant evidence indicates that SphK1 and S1P promote cancer progression and metastasis in multiple types of cancers. However, the role of SphK/S1P in HCC is less well studied. Here, we review the current state of knowledge of SphKs and S1P in HCC, including evidence for the correlation of SphK1 expression and S1P levels with progression of HCC and negative outcomes, and discuss how this information could lead to the design of more effective diagnostic and treatment modalities for HCC

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections.

Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a trispecific antibody (Ab), N6/αCD3-αCD28, that targets three independent proteins: (1) the HIV envelope via the broadly reactive CD4-binding site Ab, N6; (2) the T cell antigen CD3; and (3) the co-stimulatory molecule CD28. We find that the trispecific significantly increases antigen-specific T-cell activation and cytokine release in both CD4 <sup>+</sup> and CD8 <sup>+</sup> T cells. Co-culturing CD4 <sup>+</sup> with autologous CD8 <sup>+</sup> T cells from ART-suppressed HIV <sup>+</sup> donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8 <sup>+</sup> T cells. This trispecific antibody mediates CD4 <sup>+</sup> and CD8 <sup>+</sup> T-cell activation in non-human primates and is well tolerated in vivo. This HIV-directed antibody therefore merits further development as a potential intervention for the eradication of latent HIV infection