Design Principles of FRET‐Based Dye‐Sensitized Solar Cells with Buried Quantum Dot Donors

In this article, the physics of FRET is demonstrated for an architecture of dye‐sensitized solar cells, in which the quantum dot “antennas” that serve as donors are incorporated into the solid titania electrode, providing isolation from electrolyte quenching, and potentially increased photostability. The energy transferred to the dye acceptor from the quantum dot donor, in addition to the direct light absorption by the dye, finally induce dye excitation and electron injection to the metal oxide semiconductor electrode. We use time‐resolved photoluminescence measurements to directly show achievement of FRET efficiencies of up to 70%, corresponding to over 80% internal quantum efficiency when considering radiative energy transfer as well. The various parameters governing the FRET efficiency and the requirements for high efficiency FRET‐based cells are discussed. Since both buried donors inside the electrode and donors solubilized in the electrolyte have both been shown to achieve high energy transfer efficiencies, and as the two methods take advantage of different available volumes of the electrode to introduce donors providing the excess absorption, synergy of the two methods is highly promising for achieving panchromatic absorption within a thin electrode.     

Knock-down of plasminogen-activator inhibitor-1 enhances expression of E-cadherin and promotes epithelial differentiation of human pancreatic adenocarcinoma cells

High levels of plasminogen activator inhibitor-1 (PAI-1), which is produced by stromal, endothelial, and cancer cells and has multiple complex effects on cancers, correlate with poor cancer prognosis. To more definitively study the role of endogenously produced PAI-1 in human pancreatic adenocarcinoma (PAC) PANC-1 cell line biology, we used anti-PAI-1 shRNA to create stable PAI-1 deficient cells (PD-PANC-1s). PD-PANC-1s exhibited a heterogeneous morphology. While the majority of cells exhibited a cuboidal shape similar to the parental PANC-1 or the vector-infected control cells, numerous large cells with long filopodia and a neuronal-like appearance were observed. Although both Vector-control cells and PD-PANC-1s expressed mRNAs that are characteristic of mesenchymal, neural, and epithelial phenotypes, epithelial marker RNAs were up-regulated (e.g., E-cadherin, 32-fold) whereas mesenchymal marker RNAs were down-regulated (e.g., Thy1, ninefold) in PD-PANC-1s, suggesting mesenchymal-to-epithelial transition. Neural markers exhibited both up- and down-regulation. Immunocytochemistry indicated that epithelial-like PD-PANC-1s expressed E-cadherin and β-catenin in significantly more cells, while neural-like cells exhibited robust expression of organized β-3-tubulin. PAI-1 and E-cadherin were rarely co-expressed in the same cells. Indeed, examination of PAI-1 and E-cadherin mRNAs expression in additional cell lines yielded clear inverse correlation. Indeed, infection of Colo357 PAC cells (that exhibit high expression of E-cadherin) with PAI-1-expressing adenovirus led to a marked decrease in E-cadherin expression and to enhanced migration of cells from clusters. Our results suggest that endogenous PAI-1 suppresses expression of E-cadherin and differentiation in PAC cells in vitro, supporting its negative impact on tumor prognosis.     

INDI: a computational framework for inferring drug interactions and their associated recommendations

Inferring drug–drug interactions (DDIs) is an essential step in drug development and drug administration. Most computational inference methods focus on modeling drug pharmacokinetics, aiming at interactions that result from a common metabolizing enzyme (CYP). Here, we introduce a novel prediction method, INDI (INferring Drug Interactions), allowing the inference of both pharmacokinetic, CYP‐related DDIs (along with their associated CYPs) and pharmacodynamic, non‐CYP associated ones. On cross validation, it obtains high specificity and sensitivity levels (AUC (area under the receiver‐operating characteristic curve)?0.93). In application to the FDA adverse event reporting system, 53% of the drug events could potentially be connected to known (41%) or predicted (12%) DDIs. Additionally, INDI predicts the severity level of each DDI upon co‐administration of the involved drugs, suggesting that severe interactions are abundant in the clinical practice. Examining regularly taken medications by hospitalized patients, 18% of the patients receive known or predicted severely interacting drugs and are hospitalized more frequently. Access to INDI and its predictions is provided via a web tool at http://www.cs.tau.ac.il/～bnet/software/INDI , facilitating the inference and exploration of drug interactions and providing important leads for physicians and pharmaceutical companies alike.     

Covasim: An agent-based model of COVID-19 dynamics and interventions

The COVID-19 pandemic has created an urgent need for models that can project epidemic trends, explore intervention scenarios, and estimate resource needs. Here we describe the methodology of Covasim (COVID-19 Agent-based Simulator), an open-source model developed to help address these questions. Covasim includes country-specific demographic information on age structure and population size; realistic transmission networks in different social layers, including households, schools, workplaces, long-term care facilities, and communities; age-specific disease outcomes; and intrahost viral dynamics, including viral-load-based transmissibility. Covasim also supports an extensive set of interventions, including non-pharmaceutical interventions, such as physical distancing and protective equipment; pharmaceutical interventions, including vaccination; and testing interventions, such as symptomatic and asymptomatic testing, isolation, contact tracing, and quarantine. These interventions can incorporate the effects of delays, loss-to-follow-up, micro-targeting, and other factors. Implemented in pure Python, Covasim has been designed with equal emphasis on performance, ease of use, and flexibility: realistic and highly customized scenarios can be run on a standard laptop in under a minute. In collaboration with local health agencies and policymakers, Covasim has already been applied to examine epidemic dynamics and inform policy decisions in more than a dozen countries in Africa, Asia-Pacific, Europe, and North America.     

REGULATION OF PROTEIN SYNTHESIS IN THE VENOM GLAND OF VIPERID SNAKES

Morphological changes in the venom gland of V. ammodytes were studied after the removal of the venom from the gland lumina (milking) It was found that the height of the secretory cells was changed during the secretory cycle. The patterns of the rough endoplasmic reticulum and of the Golgi complex were changed as well Milking induced an increased incorporation of [¹⁴C]amino acids into total and venom proteins In V ammodytes, during the first day after milking, 25% of the total counts in protein were precipitable by anti-venom serum, while at 8 days, 80% of the proteins synthesized were venom proteins At this stage, the incorporation was 10- and 20-fold that of unmilked glands for total and venom proteins, respectively. Venom was accumulated (secreted) in the gland lumina of V. ammodytes at a relatively high rate up to 2 wk after milking and leveled off afterwards. Intact glands and gland slices of V ammodytes and V palaestinae, taken from snakes a few days after milking, incorporated [¹⁴C]amino acids into proteins in vitro at a rate higher than that of unmilked glands. The activity of two exportable enzymes (phosphodiesterase and benzoyl arginyl ethyl esterase) was assayed in gland homogenates of V. ammodytes. It was found that 2–3 wk after milking, the intracellular level of these enzymes was up to 2-fold that of unmilked glands.     

Insulin action in intact mouse diaphragm II.

Summary Incubation of intact mouse diaphragms with insulin in the absence of glucose resulted in a rapid inhibition of the subsequent cell-free phosphorylation of endogenous protein substrates in tissue extracts. The phosphorylation of added histone was inhibited to a lesser extent. The inhibition was observed both in the absence and in the presence of added cyclic 35 adenosine monophosphate. Acrylamide gel electrophoresis of phosphorylation products revealed a number of major phosphorylated polypeptides. The phosphorylation of several polypeptides was inhibited following short treatment with insulin. These results represent a novel experimental approach to the elucidation of the mechanism of the action of insulin and are consistent with our hypothesis that the inhibition of protein kinase activities in the tissue may be the first step in this mechanism.Abbreviations Tricine N-tris(hydroxymethyl)methyl glycine - EDTA ethylenediamine tetraacetic acid - EGTA ethyleneglycol-bis-(-amino ethyl ether) N,N¹-tetraacetic acid - Mes 2(N-morpholino)ethane sulfonic acid J. Larner is an established investigator of the American Diabetes Association.     

Algae/Bacteria Ratio in High-Rate Ponds Used for Waste Treatment

Algae, bacteria, and zooplankton were counted in samples drawn from 120- and 150-m² high-rate algae ponds (those used for wastewater treatment). The fraction of nondegraded organic matter was estimated by comparing the ratio of biological and chemical oxygen demands and the bacterial, algal, and zooplankton counts to volatile suspended solids. With pond effluent quality at an acceptable level (around 18 mg of dissolved biological oxygen demand), the algae/bacteria ratio was around 1:100 or even higher, the zooplankton count was negligible, and the bacterial concentration was approximately 10¹¹ cells per liter by direct count. The data for bacteria exceeded those of earlier studies by one to three orders of magnitude.     

Growth of Spirulina maxima on cow-manure wastes

Experiments were carried out on culturing the blue-green alga Spirulina maxima on raw cow-manure wastes in an outdoor pond. Improved growth was obtained at pH above 9.2 and temperature above 32°C, with half the radiation intensity required for other green algal species. A yield of 3 g/liter, in terms of total suspended matter, was achieved. The main advantage of this method is that S. maxima removes nutrients and thus serves as an alternative protein source.     

Whole-body-vibration-induced increase in leg muscle activity during different squat exercises

This study analyzed leg muscle activity during whole-body vibration (WBV) training. Subjects performed standard unloaded isometric exercises on a vibrating platform (Power Plate): high squat (HS), low squat (LS), and 1-legged squat (OL). Muscle activity of the rectus femoris, vastus lateralis, vastus medialis, and gastrocnemius was recorded in 15 men (age 21.2 +/- 0.8 years) through use of surface electromyography (EMG). The exercises were performed in 2 conditions: with WBV and without (control [CO]) a vibratory stimulus of 35 Hz. Muscle activation during WBV was compared with CO and with muscle activation during isolated maximal voluntary contractions (MVCs). Whole-body vibration resulted in a significantly higher (p < 0.05) EMG root-mean-square compared with CO in all muscle groups and all exercises (between +39.9 +/- 17.5% and +360.6 +/- 57.5%). The increase in muscle activity caused by WBV was significantly higher (p < 0.05) in OL compared with HS and LS. In conclusion, WBV resulted in an increased activation of the leg muscles. During WBV, leg muscle activity varied between 12.6 and 82.4% of MVC values.     

Response to lysophosphatidic acid in Xenopus oocytes and its rapid desensitization: the role of Gq and Go G-protein families

Native Xenopus oocytes exhibit dose‐dependent depolarizing current responses to lysophosphatidic acid (LPA), with EC50 = 0.18 μM. Responses to LPA were subject to pronounced rapid desensitization. When oocytes were challenged with 5 nM LPA, the response was <10% of the maximal. Subsequent addition of 0.5 μM LPA resulted in 50–70% desensitization, when compared to naïve controls. Injection of antisense oligodeoxyoligonucleotides (ASODNs) targeted at either of the two endogenous LPA receptors inhibited the LPA response by approximately 50%, but did not alter the degree of rapid desensitization. To study the involvement of G‐proteins in rapid homologous desensitization of responses to LPA, we selectively depleted native G‐proteins by injection of specific ASDONs. Injection of ASDONs targeted at Gαq family mRNAs (mainly Gα11) reduced the response to 0.5 μM LPA by 50%. ASDONs targeted at either Gαo or Gαo1 caused a large decrease in the amount of their cognate mRNAs and the Gαo family proteins, while the response to LPA was inhibited by up to 30%. Injection of ASDONs targeted at Gαo1 mRNA decreased rapid desensitization from 69 to 23%, while pertussis toxin (PTX) completely abolished it. Expression of two dominant negative mutants of the human Gαo family homologs either decreased or virtually abolished rapid desensitization. Microinjection of CaCl₂ demonstrated that 50% of rapid desensitization could be attributed to inhibition of Ca²⁺ activation of chloride channels. We propose that the apparent degenerate coupling of different G‐proteins to LPA receptors in Xenopus oocytes actually serves both the generation of the response (by Gq and Go G‐protein families) and its desensitization (mostly by Go G‐protein family). © 2004 Wiley‐Liss, Inc.