Symmetry Breaking and Spin-Orbit Coupling for Individual Vacancy-Induced In-Gap States in MoS2 Monolayers.

Spins confined to point defects in atomically thin semiconductors constitute well-defined atomic-scale quantum systems that are being explored as single-photon emitters and spin qubits. Here, we investigate the in-gap electronic structure of individual sulfur vacancies in molybdenum disulfide (MoS2) monolayers using resonant tunneling scanning probe spectroscopy in the Coulomb blockade regime. Spectroscopic mapping of defect wave functions reveals an interplay of local symmetry breaking by a charge-state-dependent Jahn-Teller lattice distortion that, when combined with strong (≃100 meV) spin-orbit coupling, leads to a locking of an unpaired spin-1/2 magnetic moment to the lattice at low temperature, susceptible to lattice strain. Our results provide new insights into the spin and electronic structure of vacancy-induced in-gap states toward their application as electrically and optically addressable quantum systems.

Spin-Valley Locking for In-Gap Quantum Dots in a MoS2 Transistor.

Spins confined to atomically thin semiconductors are being actively explored as quantum information carriers. In transition metal dichalcogenides (TMDCs), the hexagonal crystal lattice gives rise to an additional valley degree of freedom with spin-valley locking and potentially enhanced spin life and coherence times. However, realizing well-separated single-particle levels and achieving transparent electrical contact to address them has remained challenging. Here, we report well-defined spin states in a few-layer MoS2 transistor, characterized with a spectral resolution of ∼50 µeV at Tel = 150 mK. Ground state magnetospectroscopy confirms a finite Berry-curvature induced coupling of spin and valley, reflected in a pronounced Zeeman anisotropy, with a large out-of-plane g-factor of g⊥ ≃ 8. A finite in-plane g-factor (g∥ ≃ 0.55-0.8) allows us to quantify spin-valley locking and estimate the spin-orbit splitting 2ΔSO ∼ 100 µeV. The demonstration of spin-valley locking is an important milestone toward realizing spin-valley quantum bits.

Indirect Clinical Validation of a Programmed Death-Ligand 1 Laboratory-Developed Test for Gastric/Gastroesophageal Junction Adenocarcinoma with 22C3 Antibody Concentrate.

BACKGROUND: The PD-L1 IHC 22C3 pharmDx used on the Dako Autostainer Link 48 (ASL48) staining platform is an established method for assessing programmed death-ligand 1 (PD-L1) expression in tumor tissue and determining patient eligibility for pembrolizumab treatment; however, the availability of this platform is limited in Europe and Asia. OBJECTIVES: The aims of this study were to develop and optimize protocols for the PD-L1 22C3 antibody concentrate with multiple immunohistochemistry staining platforms and to validate these protocols using PD-L1 combined positive score (CPS) with a cut-off of ≥ 1 in gastric or gastroesophageal junction adenocarcinoma. DESIGN: The 22C3 antibody concentrate was tested and optimized protocols were developed for use with three staining platforms: Dako ASL48, Ventana BenchMark ULTRA, and Leica BOND-MAX. Tumor specimens (N = 120) from patients with gastric or gastroesophageal junction adenocarcinoma were used for the validation study; these specimens were evaluated independently by three pathologists for PD-L1 CPS as a continuous variable and using a cut-off of ≥ 1. PD-L1 IHC 22C3 pharmDx used on the Dako ASL48 platform served as the reference or gold standard. RESULTS: The intraclass correlation coefficient of CPS as a continuous variable between the gold standard and each staining platform assessed was 0.910-0.989. When CPS was dichotomized based on a cut-off of ≥ 1, depending on the pathologist and the platform used, positive percentage agreement was 81-99% and negative percentage agreement was 90-100%. Interobserver agreement using the gold standard showed substantial agreement (κ = 0.779). CONCLUSION: The PD-L1 22C3 antibody concentrate can potentially be used with the laboratory-developed test on three commercially available immunohistochemistry staining platforms to determine PD-L1 expression in tumor samples from patients with gastric or gastroesophageal junction adenocarcinoma.

Structure-Activity Relationships of a Series of Echinocandins and the Discovery of CD101, a Highly Stable and Soluble Echinocandin with Distinctive Pharmacokinetic Properties.

Echinocandins are a first-line therapy for candidemia and invasive candidiasis. They are generally safe with few drug interactions, but the stability and pharmacokinetic properties of currently approved echinocandins are such that each was developed for daily intravenous infusion. We sought to discover a novel echinocandin with properties that would enable more flexible dosing regimens, alternate routes of delivery, and expanded utility. Derivatives of known echinocandin scaffolds were generated, and an iterative process of design and screening led to the discovery of CD101, a novel echinocandin that has since demonstrated improved chemical stability and pharmacokinetics. Here, we report the structure-activity relationships (including preclinical efficacy and pharmacokinetic data) for the series of echinocandin analogs from which CD101 was selected. In a mouse model of disseminated candidiasis, the test compounds displayed clear dose responses and were generally associated with lower fungal burdens than that of anidulafungin. Single-dose pharmacokinetic studies in beagle dogs revealed a wide disparity in the half-lives and volumes of distribution, with one compound (now known as CD101) displaying a half-life that is nearly 5-fold longer than that of anidulafungin (53.1 h versus 11.6 h, respectively). In vitro activity data against panels of Candida spp. and Aspergillus spp. demonstrated that CD101 behaved similarly to approved echinocandins in terms of potency and spectrum of activity, suggesting that the improved efficacy observed in vivo for CD101 is a result of features beyond the antifungal potency inherent to the molecule. Factors that potentially contribute to the improved in vivo efficacy of CD101 are discussed.

The fate and transport of the SiO2 nanoparticles in a granular activated carbon bed and their impact on the removal of VOCs.

Adsorption isotherm, adsorption kinetics and column breakthrough experiments evaluating trichloroethylene (TCE) adsorption onto granular activated carbon (GAC) were conducted in the presence and absence of silica nanoparticles (SiO(2) NPs). Zeta potentials of the SiO(2) NPs and the GAC were measured. Particle size distribution (PSD) of SiO(2) NPs dispersions was analyzed with time to evaluate the extent of aggregation. TEM analysis was conducted. The specific surface area and the pore size distribution of the virgin and the spent GAC were obtained. The fate and transport of the SiO(2) NPs in the GAC fixed bed and their impact on TCE adsorption were found to be a function of their zeta potential, concentration and PSD. The interaction of the SiO(2) NPs and the GAC is of an electrokinetic nature. A weak electrostatic attraction was observed between the SiO(2) NPs and the GAC. This attraction favors SiO(2) NPs attachment on the surface of GAC. SiO(2) NPs attachment onto GAC is manifested by a reduction in the amount of TCE adsorbed during the column breakthrough experiments suggesting a preloading pore blockage phenomenon. However, no effect of SiO(2) NPs was observed on the isotherm and the kinetic studies, this is mainly due to the fast kinetics of TCE adsorption.

Evaluating a composite cartridge for small system drinking water treatment.

A pilot-scale evaluation was conducted at the U.S. Environmental Protection Agency (EPA) Test & Evaluation (T&E) Facility in Cincinnati, Ohio, on a multi-layer, cartridge-based system that combines physical filtration with carbon adsorption and ultraviolet (UV) light disinfection to serve as a home-base water treatment security device against accidental or intentional contaminant events. The system was challenged with different levels of turbidity, a number of biological contaminants including Bacillus subtilis, Escherichia coli, MS2 bacteriophage and Polystyrene Latex (PSL) beads as a surrogate for Cryptosporidium and a number of chemical contaminants including super-chlorination, methyl tertiary butyl ether (MTBE), water chlorination disinfection byproducts (DBPs) and diazinon. The results demonstrated that the performance of the system varies as a function of the specific contaminant or surrogate. The overall performance indicated the potential of the system to improve the quality and safety of household water and to serve as an additional treatment barrier in circumstances where there is little or no treatment or where the quality of treated water may have deteriorated during distribution. The results also demonstrated that B. subtilis spore can serve as a more conservative surrogate for Cryptosporidium than PSL beads.

Successful pregnancy outcome following maternal intravenous immunoglobulin treatment in a woman with recurrent perinatal haemochromatosis.

OBJECTIVE: We report a case of successful pregnancy outcome following maternal intravenous immunoglobulin treatment in a woman with previous history of recurrent fetal hydrops secondary to perinatal haemochromatosis. METHODS: A 32-year old woman had two successive pregnancies complicated by fetal hydrops and perinatal deaths. Pathological examination of the fetus showed severe liver destruction with siderosis of hepatocytes at extrahepatic sites, but sparing of the reticulo-endothelial elements, consistent with the diagnosis of perinatal haemochromatosis. In the subsequent pregnancy, maternal intravenous immunoglobulin was administered weekly from the 18th week of gestation until delivery by elective caesarean section at 38 weeks. The infant was treated with desferrioxamine, N-acetylcysteine, vitamins K and E. RESULTS: The infant was born in good health, but had high serum ferritin levels, markedly elevated percent transferrin saturation, and mild transient derangement of liver and coagulation function. The infant made an excellent recovery and the treatment was stopped at 7 weeks of age. The liver and coagulation parameters and the serum ferritin levels returned to normal values. CONCLUSIONS: Haemochromatosis should be considered in the differential diagnosis of hydrops fetalis. The recurrence risk is high, and immunomodulation with intravenous immunoglobulin treatment appears to alter the course of the disease with better infant survival.

Amphiphilic conjugates of human brain natriuretic peptide designed for oral delivery: in vitro activity screening.

Congestive heart failure (CHF) is a complex syndrome involving altered neurohormonal levels and impaired cardiac and renal function. In recent years, intravenous administration of exogenous human brain-type natriuretic peptide (hBNP) has become an important therapy in treating patients with acutely decompensated CHF. However, reports during the past year suggest that hBNP could play a prominent role in the chronic treatment of CHF patients as well. We are currently developing conjugates of hBNP suitable for oral delivery to provide a patient-friendly treatment option for chronic heart failure patients. In this report, we present in vitro activity results obtained from hBNP conjugates featuring a variety of rationally designed amphiphilic oligomers. Mapping studies revealed that the hydrophobic/hydrophilic balance of the oligomer impacted the regioselectivity of conjugation. Additionally, the regiochemistry and extent of conjugation had a significant impact on activity. Many monoconjugates retained activity comparable to native peptide and are currently under evaluation in subsequent in vivo screens.