Lessons from Israel's COVID-19 Green Pass program

As of the beginning of March 2021, Israeli law requires the presentation of a Green Pass as a precondition for entering certain businesses and public spheres. Entitlement for a Green Pass is granted to Israelis who have been vaccinated with two doses of COVID-19 vaccine, who have recovered from COVID-19, or who are participating in a clinical trial for vaccine development in Israel. The Green Pass is essential for retaining immune individuals' freedom of movement and for promoting the public interest in reopening the economic, educational, and cultural spheres of activity. Nonetheless, and as the Green Pass imposes restrictions on the movement of individuals who had not been vaccinated or who had not recovered, it is not consonant with solidarity and trust building. Implementing the Green Pass provision while advancing its effectiveness on the one hand, and safeguarding equality, proportionality, and fairness on the other hand may imbue this measure with ethical legitimacy despite involving a potential breach of trust and solidarity.

Synthesis of N-[3-(2,3-dimethyl-1H-indol-1-yl)-4-hydroxyphenyl]arylsulfon(aroyl)amides

Indole derivatives are an essential elements of many natural and synthetic compounds having significant biological activity. New derivatives of 2,3-dimethylindole were synthesized in this work by the reaction of N-(4-oxocyclohexa-2,5-dien-1-ylidene)arylsulfon(aroyl)amides and 4-methyl-N-(4-oxonaphthalen-1(4H)-ylidene)benzene-1-sulfonamide with 2,3-dimethylindole. The possibility of these reactions is determined by the redox potential of the starting amides and steric factor. If there is a free C=C bond in the quinoid ring of the starting arylsulfonamides, the reaction proceeds under the 1,4-addition scheme with the formation of corresponding N-[3-(2,3-dimethyl-1H-indol-1-yl)-4-hydroxyphenyl(naphthyl-1)]arylsulfonamides which are potentially biologically active compounds. N-(4-Oxocyclohexa-2,5-diene-1-ylidene)aroylamides have a high redox potential as compared with similar arylsulfonamides and naphthalene derivatives; therefore, two processes proceed in their reaction with 2,3-dimethylindole: reduction and 1,4-addition. The 1,4-addition product was obtained only for the 2,3-dimethyl derivative, which has the lowest redox potential among the investigated aroylamides. Analysis of the potential biological activity of the synthesized compounds by using the PASS program showed that the synthesized products can exhibit the following activities: para amino benzoic acid antagonist, glutamyl endopeptidase II inhibitor, CYP3A2 substrate, insulysin inhibitor, membrane integrity agonist and phobic disorders treatment.

Elements of Successful Universal Student Transit Pass Programs from Planning to Implementation: A Benchmark Study

Key elements in developing a successful universal college student transit pass program (U-Pass program) are investigated from the perspectives of three involved parties of interest: transit agencies, university administrations, and students. By collecting information from online surveys, case examples, literature, and other useful online resources, a generalized procedure of a U-Pass program is proposed, broken down into three phases: planning, launching, and implementation. In each phase, key elements and actions that lead to successful programs are investigated from the perspectives of the three involved parties. The roles of the three parties as well as how they interact with each other are also examined. Furthermore, some of the underlying factors that lead to program success are explored in the context of different built environment settings. As a benchmark study, this paper extends work from a Transit Cooperative Research Program synthesis to gain insight into how U-Pass programs have been planned, launched, and implemented. The research findings could assist responsible transit agencies and educational institutions in enhancing their current U-Pass programs or launching new programs in the future.

Etoposide-Induced Apoptosis in Cancer Cells Can Be Reinforced by an Uncoupled Link between Hsp70 and Caspase-3

The Hsp70 chaperone binds and inhibits proteins implicated in apoptotic signaling including Caspase-3. Induction of apoptosis is an important mechanism of anti-cancer drugs, therefore Hsp70 can act as a protective system in tumor cells against therapeutic agents. In this study we present an assessment of candidate compounds that are able to dissociate the complex of Hsp70 with Caspase-3, and thus sensitize cells to drug-induced apoptosis. Using the PASS program for prediction of biological activity we selected a derivative of benzodioxol (BT44) that is known to affect molecular chaperones and caspases. Drug affinity responsive target stability and microscale thermophoresis assays indicated that BT44 bound to Hsp70 and reduced the chaperone activity. When etoposide was administered, heat shock accompanied with an accumulation of Hsp70 led to an inhibition of etoposide-induced apoptosis. The number of apoptotic cells increased following BT44 administration, and forced Caspase-3 processing. Competitive protein–protein interaction and immunoprecipitation assays showed that BT44 caused dissociation of the Hsp70–Caspase-3 complex, thus augmenting the anti-tumor activity of etoposide and highlighting the potential role of molecular separators in cancer therapy.