Purpose: To assess the clinical safety and possible effectiveness of Vasoactive Intestinal Peptide in the treatment of Acute Respiratory Distress Syndrome (ARDS) related to sepsis. Methods: Under FDA Investigational New Drug clearance, 8 patients with ARDS related to sepsis were treated with 50 pmole/kg/hr – 100 pmole/kg/hr of Vasoactive Intestinal Peptide by intravenous infusion for 12 hours. All patients were on mechanical ventilation and full telemetery. Results: No drug-related serious adverse events were seen. Hypotension was seen in association with two infusions and diarrhea in association with one, but did not necessitate cessation of therapy. Bigeminy was seen in association with one infusion without sequelae. Seven of eight patients demonstrated a successful course during intensive care and were successfully removed from mechanical ventilation and discharged from intensive care. The eighth patient succumbed to purulent secretions in the lungs. Of those who were discharged from the ICU, six demonstrated successful 30 day survival. The seventh died from a cerebral infract at day 30, deemed unrelated to treatment with VIP. Serum levels of Tumor Necrosis Factor α were obtained in 6 patients at baseline and 24 hours and were seen to decrease with treatment in five patients. Conclusions: Initial clinical results of treatment with VIP in patients with ARDS demonstrated a safety profile consistent with previous studies in normal volunteers. The successful clinical course seen in 7 of 8 patients in the setting of an expected 50% survival may suggest that VIP shows promise in the treatment of other infectious conditions that damage the pulmonary epithelium, particularly COVID-19.

This paper models and estimates the volatility of nonfinancial, innovative and hi-tech focused stock index, the Nasdaq-100, using univariate symmetric and asymmetric GARCH models. We employ GARCH, EGARCH and GJR-GARCH using daily data over the period January 4, 2000 through March 19, 2019. We find that the volatility shocks on the index returns are quite persistent. Furthermore, our findings show that the index has leverage effect, and the impact of shocks is asymmetric, whereby the impacts of negative shocks on volatility are higher than those of positive shocks of the same magnitude.

BOLD-100, a ruthenium-based complex, sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (also known as IT-139, NKP1339 or KP1339), is a novel small molecule drug that demonstrated a manageable safety profile at the maximum tolerated dose and modest antitumor activity in a phase I clinical trial. BOLD-100 has been reported to inhibit the upregulation of the endoplasmic reticulum stress sensing protein GRP78. However, response to BOLD-100 varies in different cancer models and the precise mechanism of action in high-response versus low-response cancer cells remains unclear. In vitro studies have indicated that BOLD-100 induces cytostatic rather than cytotoxic effects as a monotherapy. To understand BOLD-100 mediated signaling mechanism in breast cancer cells, we used estrogen receptor positive (ER+) MCF7 breast cancer cells to obtain gene-metabolite integrated models. Particularly, BOLD-100 significantly reduced expression of genes involved in the DNA repair pathway. BOLD-100 also induced reactive oxygen species (ROS) and phosphorylation of histone H2AX, gH2AX (Ser139), suggesting disruption of proper DNA surveillance. In estrogen receptor negative (ER-) breast cancer cells, combination of BOLD-100 with a PARP inhibitor, olaparib, induced significant inhibition of cell growth and xenografts and increased gH2AX. Thus, BOLD-100 is a novel DNA repair pathway targeting agent and can be used with other chemotherapies in ER- breast cancer.

Experimental and clinical data indicates that the initiation and progress of atherosclerosis, and its clinical manifestations, are caused first by circulating apoB-100 lipoproteins that enter and are retained in the arterial intima. Extracellular sulfated proteoglycans (PGs) of the intima are the retention agents. The PGs also initiate physical and biochemical lipoprotein degradation with the production of bioactive, lipid products that trigger an inflammatory response that leads to atherosclerosis. There are many simple methods for measuring abnormalities of circulating lipoproteins and their relation to atherosclerotic cardiovascular disease (ACVD). However, limited research has been aimed to evaluate procedures that could report quantitatively about the contribution of the apo-100 lipoprotein-arterial intima PGs interaction to clinical manifestation of ACVD. In the present review we will discuss observations indicating that simple ex vivo evaluation of the affinity of apoB-100 lipoproteins for arterial PGs and glycosaminoglycans (GAGs) can give indication of its association with clinical manifestations of atherosclerosis. In addition, we will discuss molecular and cellular aspect of the apoB-100 lipoproteins association with arterial PGs that are related to atherogenesis and that support the experimental framework behind the current “Response-to-Retention” hypothesis of atherosclerosis

Ultra-short 230 fs laser pulses of 515 nm wavelength were tightly focused into 700 nm focal spots and utilised in opening ~ 400 nm nano-holes in a Cr etch mask that was tens-of-nm thick. Nano-holes ablated at slightly above the threshold of ablation irradiance became nano-disks and nano-rings at slightly lower pulse energies. Subtle sub-1 nJ pulse energy control was harnessed to pattern large surface areas with controlled nano-alloying of Si and Cr. This technique is extendable to vacuum-free large area patterning of nanolayers by alloying them at distinct locations with sub-diffraction resolution. Such metal masks with nano-hole opening can be used for formation of random patterns of nano-needles with sub-100 nm separation when applied to dry etching of Si.

This study will investigate different signals and events/news that determined the stock market's movements. As we know, many factors affect the stock market on a daily, weekly, and monthly basis, e.g., rate of interest, exchange rate, and oil prices, etc. Our research will investigate the impact of daily events/news in the KSE-100 index due to several policies announced and events/news in the country because the daily movements in the stock market can be determined only by different signals and events/news. Time series data is collected daily for particular reasons from "The News" (Daily Newspaper, Sunday edition) from 2010 to 2019. The results of this study show that political and global news affects the stock market index ferociously. For investors, the investment in blue chips is not less than a safe haven. When day-to-day transactions are concerned, there is always a higher panic attack than the herd behaviour in the stock exchange. Investors tend to make prompt responses to negative rather than positive news, which makes them risk averters. Our finding also confirmed that the ARCH/GARCH model is better than the simple OLS method concerning stock market upheaval.

The energy transition requires integration of different energy carriers, including electricity, heat, and transport sectors. Energy modeling methods and tools are essential to provide a clear insight into the energy transition. However, the methodologies often overlook the details of small-scale energy systems. The study states an innovative approach to facilitate sub-national energy systems with 100% renewable penetration and sectoral integration. An optimization model, OSeEM-SN, is developed under the Oemof framework. The model is validated using the case study of Schleswig-Holstein. The study assumes three scenarios representing 25%, 50%, and 100% of the total available biomass potentials. OSeEM-SN reaches feasible solutions without additional offshore wind investment, indicating that they can be reserved for supplying other states’ energy demand. The annual investment cost varies between 1.02 bn – 1.44 bn €/yr for the three scenarios. The electricity generation decreases by 17%, indicating that with high biomass-based combined heat and power plants, the curtailment from other renewable plants can be decreased. Ground source heat pumps dominate the heat mix; however, their installation decreases by 28% as the biomass penetrates fully into the energy mix. The validation confirms OSeEM-SN as a beneficial tool to examine different scenarios for sub-national energy systems.

Many Caribbean island nations have historically been heavily dependent on imported fossil fuels for both power and transportation, while at the same time being at an enhanced risk from the impacts of climate change, although their emissions represent a very tiny fraction of the global total responsible for climate change. Small island developing states (SIDS) are among the leaders in advocating for the ambitious 1.5°C Paris Agreement target and the transition to 100% sustainable, renewable energy systems. In this work we present three central results. First, we show through GIS mapping of all Caribbean islands the potential for near-coastal deep-water as a resource for Ocean Thermal Energy Conversion (OTEC) and couple these results with an estimate of the countries for which OTEC would be most advantageous due to a lack of other dispatchable renewable power options. Second, hourly data have been utilized to explicitly show the trade-offs between battery storage needs and dispatchable renewable sources such as OTEC in 100% renewable electricity systems, both in technological and economic terms. Finally, the utility of near-shore, open-cycle OTEC with accompanying desalination is shown to enable a higher penetration of renewable energy and lead to lower system levelized costs than those of a conventional fossil fuel system.