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A new low, with a glow: novel NIR-emitting, deep-LUMO (−5.0 eV) nitro-aromatic terrylene diimides are reported.

The year 2023 marks professional social work’s quasquicentennial: the 125th anniversary of our profession since the first social work classes were offered in the summer of 1898 at Columbia University. The profession has grown in its reach across many human service sectors over all these years creating opportunities for those who want to serve their communities in myriad and impactful ways. As we observe disruptions in the higher education sector, with profound implications to the mission of the social work profession, we are also witnessing many cross-sector opportunities for the future of the social work profession. Given our changing environment, the time is right for us to re-envision social work education and practice in ways that center our professions’ commitment to social justice and the well-being of individuals, families, and communities. In our efforts to meet the needs of the people and communities we serve, we have seen several innovative and impactful expansions into areas that have augmented our original “scope of practice.” Some have occurred to meet the needs of the time; others have morphed due to market conditions for jobs that have been encroached on by other professions/disciplines. And as we see more complex and vexing societal issues in our current environment, it is time for us to collectively discern our purpose, adjust our mindset, and be prepared to meet future challenges and opportunities. This special issue on “re-envisioning social work” provides a space for thought leaders to showcase meaningful and purpose-filled advances for the profession.

Since gaining approval for the treatment of chronic lymphocytic leukemia (CLL), the BCL-2 inhibitor venetoclax has transformed the treatment of this and other blood-related cancers. Reflecting the large and hydrophobic BH3-binding groove within BCL-2, venetoclax has significantly higher molecular weight and lipophilicity than most orally administered drugs, along with negligible water solubility. Although a technology-enabled formulation successfully achieves oral absorption in humans, venetoclax tablets have limited drug loading and therefore can present a substantial pill burden for patients in high-dose indications. We therefore generated a phosphate prodrug (3, ABBV-167) that confers significantly increased water solubility to venetoclax and, upon oral administration to healthy volunteers either as a solution or high drug-load immediate release tablet, extensively converts to the parent drug. Additionally, ABBV-167 demonstrated a lower food effect with respect to venetoclax tablets. These data indicate that beyond-rule-of-5 molecules can be successfully delivered to humans via a solubility-enhancing prodrug moiety to afford robust exposures of the parent drug following oral dosing.

1. Measured pKa values of ABBV-167 (Table S1. Ionization constants of ABBV-167) 2. Preparation of ABBV-167 on large scale (Scheme S1: Synopsis of GMP synthesis of ABBV-167) 3. Preparation of clinical ABBV-167 drug supply 4. Animal pharmacokinetics (Table S2. Single dose pharmacokinetics of prodrug 3 and parent venetoclax in mouse and dog after IV dosing of prodrug 3. Table S3. Single dose pharmacokinetics of 3 after oral dosing in mouse and dog. Table S4. Single dose pharmacokinetics of parent venetoclax in mouse and dog after oral dosing of 3.) 5. Clinical study (Study design, Pharmacokinetic and statistical analysis, Safety and tolerability assessments, Clinical pharmacokinetic results, Table S5. Effect of prodrug and food on venetoclax bioavailability, Safety results) 6. Crystallography methods (Protein preparation. BCL-2 ABBV-167 complex crystallization. X-ray structure determination. Table S6. Diffraction data collection and refinement statistics for BCL-2 in complex with ABBV-167 (PDB code 7LHB))

This work describes the discovery of a bead-bound membrane-active peptide (MAP), LBF127, that selectively binds fungal giant unilamellar vesicles (GUVs) over mammalian GUVs. LBF127 was re-synthesized in solution form and demonstrated to have antifungal activity with limited hemolytic activity and cytotoxicity against mammalian cells. Through systematic structure-activity relationship studies, including N- and C-terminal truncation, alanine-walk, and d-amino acid substitution, an optimized peptide, K-oLBF127, with higher potency, less hemolytic activity, and cytotoxicity emerged. Compared to the parent peptide, K-oLBF127 is shorter by three amino acids and has a lysine at the N-terminus to confer an additional positive charge. K-oLBF127 was found to have improved selectivity toward the fungal membrane over mammalian membranes by 2-fold compared to LBF127. Further characterizations revealed that, while K-oLBF127 exhibits a spectrum of antifungal activity similar to that of the original peptide, it has lower hemolytic activity and cytotoxicity against mammalian cells. Mice infected with

To ascertain the degree and causes of visual disability, clinical and demographic data of UDID card applicants at RIO MOH Karnataka South India.It is a cross-sectional observation study, data collected from the UDID PORTAL where applicants applied between July 2019 to March 2020. Totally 551 applicants details were collected. Degree of visual disability and its causes, demographic details like age, gender, education, marital and employment status, annual income along with that other clinical details were ascertained. Among the 551 applications, 368 were men and 183 were women highlighting a significant gender bias. Almost 2/3 of applications were in the age group 20 to 50. 60% of applicants were married. 95% of applicants were in the blind category while only 4.3% were certified as having low vision. 47% of applicants were BPL Card holders and were dependent on the family member for livelihood. 47% of the applicants had completed basic education (10 std/SSLC). Retinitis pigmentosa was the top cause of blindness. Retinal pathologies constitute the leading cause among them majority had Retinitis pigmentosa. Genetic counseling plays a significant proactive role in the prevention of the disease. Creating awareness among employers to provide adequate protective equipment could help in reducing the disease burden of phthisis bulbi. Government and NGOs should prepare appropriate plans and implement them to rehabilitate individuals with visual disabilities. There is a need to create better awareness about the benefits of UDID CARDS in the community in general and among people with blindness and low vision in particular.

A broad effort is underway to understand and harness the interaction between superconductors and spin-active color centers with an eye on the realization of hybrid quantum devices and novel imaging modalities of superconducting materials. Most work, however, overlooks the complex interplay between either system and the environment created by the color center host. Here we use an all-diamond scanning probe to investigate the spin dynamics of a single nitrogen-vacancy (NV) center proximal to a high-critical-temperature superconducting film in the presence of a weak magnetic field. We find that the presence of the superconductor increases the NV spin coherence lifetime, a phenomenon we tentatively rationalize as a change in the electric noise due to a superconductor-induced redistribution of charge carriers near the NV site. We build on these findings to demonstrate transverse-relaxation-time-weighted imaging of the superconductor film. These results shed light on the complex surface dynamics governing the spin coherence of shallow NVs while simultaneously paving the route to new forms of noise spectroscopy and imaging of superconductors.

Within intellectual traditions in the Global South, there have been reflections on notions of self, community, and governance for several hundred years preceding the growth of a Euro-American conceptual vocabulary forged in the crucible of empire and Europe's self-appointed role in the world. Recovering these categories of thought is not merely an act of sentimentality, it is rather, a stepping out beyond the glare of an ignorance created by Euro-American categories. It is an attempt to think societies and polities in their own terms and from within their concepts. Some of these may be translatable into categories familiar to existing social science theory; some may sit beside known concepts as markers of alterity; and yet others may be distinctive to a locale of life and thought. Not all conceptions are translatable across cultures and this gives us occasion to think about the hubris of the universal assumptions of the social sciences.

A novel organic light emitting device intentionally couples emitter energy to the plasmon mode for increased device stability and converts plasmons to photons to improve device efficiency.

Intracellular adhesion molecule 1 (ICAM-1) is one of the most extensively studied inducible cell adhesion molecules which is responsible for several immune functions like T cell activation, extravasation, inflammation, etc. The molecule is constitutively expressed over the cell surface and is regulated up / down in response to inflammatory mediators like cellular stress, proinflammatory cytokines, viral infection. These stimuli modulate the expression of ICAM-1 primarily through regulating the ICAM-1 gene transcription. On account of the presence of various binding sites for NF-κB, AP-1, SP-1, and many other transcription factors, the architecture of the ICAM-1 promoter become complex. Transcription factors in union with other transcription factors, coactivators, and suppressors promote their assembly in a stereospecific manner on ICAM-1 promoter which mediates ICAM-1 regulation in response to different stimuli. Along with transcriptional regulation, epigenetic modifications also play a pivotal role in controlling ICAM-1 expression on different cell types. In this review, we summarize the regulation of ICAM-1 expression both at the transcriptional as well as post-transcriptional level with an emphasis on transcription factors and signaling pathways involved.

This work presents an end‐to‐end approach for assessing the absolute bioavailability of highly hydrophobic, poorly water‐soluble compounds that exhibit high nonspecific binding using venetoclax as a model drug. The approach utilizes a stable labeled i.v. microdose and requires fewer resources compared with traditional approaches that use radioactive 14C‐labeled compounds. The stable labeled venetoclax and internal standard were synthesized, then an i.v. formulation was developed. In the clinical study, female subjects received a single oral dose of venetoclax 100 mg followed by a 100‐µg i.v. dose of cold‐labeled 13C‐venetoclax at the oral time of maximum concentration (Tmax). The i.v. microdose was prepared as an extemporaneous, sterile compounded solution on the dosing day by pharmacists at the clinical site. Several measures were taken to ensure the sterility and safety of the i.v. preparation. A sensitive liquid chromatography‐tandem mass spectrometry method was developed to allow the detection of plasma levels from the i.v. microdose. Plasma samples were collected through 72 h, and pharmacokinetic parameters were estimated using noncompartmental methods. Postdosing sample analysis demonstrated the consistency of the preparations and allowed the precise calculation of the pharmacokinetic parameters based on the actual injected dose. The absolute bioavailability of venetoclax was estimated at 5.4% under fasting conditions. Venetoclax extraction ratio was estimated to be 0.06 suggesting that the fraction transferred from the enterocytes into the liver is limiting venetoclax bioavailability. The proposed framework can be applied to other highly hydrophobic, poorly water‐soluble compounds that exhibit high nonspecific binding to support the understanding of their absorption and disposition mechanisms and guide formulation development.

The immunosuppressive agents sirolimus and everolimus are sensitive CYP3A4 substrates with narrow therapeutic index. Ritonavir is a strong CYP3A inhibitor. A phase 1 study was conducted to evaluate the pharmacokinetics, safety, and tolerability of the co-administration of sirolimus or everolimus with the ritonavir-containing 3D regimen of the direct-acting antiviral agents ombitasvir, ritonavir-boosted paritaprevir, and dasabuvir in healthy subjects. This study had two independent arms, each with a two-period, single-sequence, crossover study design. A single dose of sirolimus 2 mg (N = 12) or everolimus 0.75 mg (N = 12) was administered in Period 1. In Period 2, multiple doses of the 3D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily and dasabuvir 250 mg twice daily) were administered for 34 or 28 days, with a single dose of sirolimus 0.5 mg or everolimus 0.75 mg co-administered on Day 15. Following co-administration with the 3D regimen, the sirolimus dose-normalized maximum observed blood concentration (C