Substituted Pentacenes and Electronic Devices Made with Substituted Pentacenes

Novel substituted pentacenes and electronic devices made with those substituted pentacenes are disclosed

Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition.

Acquired drug resistance prevents cancer therapies from achieving stable and complete responses. Emerging evidence implicates a key role for non-mutational drug resistance mechanisms underlying the survival of residual cancer 'persister' cells. The persister cell pool constitutes a reservoir from which drug-resistant tumours may emerge. Targeting persister cells therefore presents a therapeutic opportunity to impede tumour relapse. We previously found that cancer cells in a high mesenchymal therapy-resistant cell state are dependent on the lipid hydroperoxidase GPX4 for survival. Here we show that a similar therapy-resistant cell state underlies the behaviour of persister cells derived from a wide range of cancers and drug treatments. Consequently, we demonstrate that persister cells acquire a dependency on GPX4. Loss of GPX4 function results in selective persister cell ferroptotic death in vitro and prevents tumour relapse in mice. These findings suggest that targeting of GPX4 may represent a therapeutic strategy to prevent acquired drug resistance

Aeronautic Instruments. Section V : Power Plant Instruments

Part 1 gives a general discussion of the uses, principles, construction, and operation of airplane tachometers. Detailed description of all available instruments, both foreign and domestic, are given. Part 2 describes methods of tests and effect of various conditions encountered in airplane flight such as change of temperature, vibration, tilting, and reduced air pressure. Part 3 describes the principal types of distance reading thermometers for aircraft engines, including an explanation of the physical principles involved in the functioning of the instruments and proper filling of the bulbs. Performance requirements and testing methods are given and a discussion of the source of error and results of tests. Part 4 gives methods of tests and calibration, also requirements of gauges of this type for the pressure measurement of the air pressure in gasoline tanks and the engine oil pressure on airplanes. Part 5 describes two types of gasoline gauges, the float type and the pressure type. Methods of testing and calibrating gasoline depth gauges are given. The Schroeder, R. A. E., and the Mark II flowmeters are described

Defining and evaluating a novel outcome measure representing end-stage knee osteoarthritis: data from the Osteoarthritis Initiative.

We described a definition of end-stage knee osteoarthritis (esKOA) and evaluated its association with health outcomes and osteoarthritis risk factors. We included Osteoarthritis Initiative participants with or at risk for knee osteoarthritis who had complete baseline data. We defined esKOA by adapting a validated appropriateness algorithm for total knee replacement based on data from baseline and the first four follow-up visits. We performed person-based analyses, including both knees from all participants. Participants met the definition of esKOA at the visit at which ≥1 knee reached the esKOA criteria. We assessed differences in individual characteristics between groups at baseline and over time and tested if incident esKOA (outcome) was associated with osteoarthritis risk factors (e.g., age, maximum adult weight, and quadriceps strength). The cohort consisted of 3916 participants with mean age of 61 (SD = 9) years and mean body mass index of 28.4 (4.7) kg/m(2); 59 % were female and 9.7 % developed incident esKOA. Those with incident esKOA had poorer health outcomes at baseline and greater declines in health outcomes, with the exception of SF-12 mental health score. Five out of nine tested risk factors were associated with incident esKOA in unadjusted analyses, with older age (≥65 years; odds ratio = 1.44, 95 % confidence interval = 1.19 to 1.83) and quadriceps weakness (odds ratio = 0.78, 95 % confidence interval = 0.71 to 0.86) remaining significant in adjusted models. Older age and quadriceps weakness predicted esKOA. esKOA is also characterized by poor health-related outcomes. This definition of esKOA could be a new clinically relevant outcome measure for osteoarthritis research

Evaluation of bone marrow lesion volume as a knee osteoarthritis biomarker - longitudinal relationships with pain and structural changes: data from the Osteoarthritis Initiative

Abstract Introduction Bone marrow lesion (BML) size may be an important imaging biomarker for osteoarthritis-related clinical trials and reducing BML size may be an important therapeutic goal. However, data on the interrelationships between BML size, pain, and structural progression are inconsistent and rarely examined in the same cohort. Therefore, we evaluated the cross-sectional and longitudinal associations of BML volume with knee pain and joint space narrowing (JSN). Methods A BML volume assessment was performed on magnetic resonance images of the knee collected at the 24- and 48-month Osteoarthritis Initiative visits from a convenience sample of 404 participants in the progression cohort. During the same visits, knee pain was assessed with WOMAC pain scores and knee radiographs were acquired and scored for JSN. BML volume was summed to generate a total knee volume and an index tibiofemoral compartment volume (compartment with greater baseline JSN). Primary analyses included multiple linear regressions (outcome = pain, predictor = total knee BML volume) and logistic regressions (outcome = JSN, predictor = index tibiofemoral compartment BML volume). Results This sample was 49% female with a mean age of 63 (9.2 standard deviation (SD)) years, and 71% had radiographic osteoarthritis in the study knee. Larger baseline BMLs were associated with greater baseline knee pain (P = 0.01), the presence of JSN at baseline (odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.23 to 1.83), and JSN progression (OR = 1.27, 95%CI = 1.11 to 1.46). Changes in total knee BML volume had a positive association with changes in knee pain severity (P = 0.004) and this association may be driven by knees that were progressing from no or small baseline BMLs to larger BMLs. In contrast, we found no linear positive relationship between BML volume change and JSN progression. Instead, regression of medial tibiofemoral BML volume was associated with JSN progression compared to knees with no or minimal changes in BML volume (OR = 3.36, 95%CI = 1.55 to 7.28). However, follow-up analyses indicated that the association between JSN progression and BML volume change may primarily be influenced by baseline BML volume. Conclusion Large baseline BMLs are associated with greater baseline knee pain, the presence of JSN at baseline, and disease progression. Additionally, BML regression is associated with decreased knee pain but not a reduced risk of concurrent JSN progression

The NASA-UC Eta-Earth Program: III. A Super-Earth orbiting HD 97658 and a Neptune-mass planet orbiting Gl 785

We report the discovery of planets orbiting two bright, nearby early K dwarf stars, HD 97658 and Gl 785. These planets were detected by Keplerian modelling of radial velocities measured with Keck-HIRES for the NASA-UC Eta-Earth Survey. HD 97658 b is a close-in super-Earth with minimum mass Msini = 8.2 +/- 1.2 M_Earth, orbital period P = 9.494 +/- 0.005 d, and an orbit that is consistent with circular. Gl 785 b is a Neptune-mass planet with Msini = 21.6 +/- 2.0 M_Earth, P = 74.39 +/- 0.12 d, and orbital eccentricity 0.30 +/- 0.09. Photometric observations with the T12 0.8 m automatic photometric telescope at Fairborn Observatory show that HD 97658 is photometrically constant at the radial velocity period to 0.09 mmag, supporting the existence of the planet.Comment: Submitted to ApJ, 7 pages, 6 figures, 5 table

Evidence of the Generation of Isosaccharinic Acids and Their Subsequent Degradation by Local Microbial Consortia within Hyper-Alkaline Contaminated Soils, with Relevance to Intermediate Level Radioactive Waste Disposal

The contamination of surface environments with hydroxide rich wastes leads to the formation of high pH (>11.0) soil profiles. One such site is a legacy lime works at Harpur Hill, Derbyshire where soil profile indicated in-situ pH values up to pH 12. Soil and porewater profiles around the site indicated clear evidence of the presence of the α and β stereoisomers of isosaccharinic acid (ISA) resulting from the anoxic, alkaline degradation of cellulosic material. ISAs are of particular interest with regards to the disposal of cellulosic materials contained within the intermediate level waste (ILW) inventory of the United Kingdom, where they may influence radionuclide mobility via complexation events occurring within a geological disposal facility (GDF) concept. The mixing of uncontaminated soils with the alkaline leachate of the site resulted in ISA generation, where the rate of generation in-situ is likely to be dependent upon the prevailing temperature of the soil. Microbial consortia present in the uncontaminated soil were capable of surviving conditions imposed by the alkaline leachate and demonstrated the ability to utilise ISAs as a carbon source. Leachate-contaminated soil was sub-cultured in a cellulose degradation product driven microcosm operating at pH 11, the consortia present were capable of the degradation of ISAs and the generation of methane from the resultant H2/CO2 produced from fermentation processes. Following microbial community analysis, fermentation processes appear to be predominated by Clostridia from the genus Alkaliphilus sp, with methanogenesis being attributed to Methanobacterium and Methanomassiliicoccus sp. The study is the first to identify the generation of ISA within an anthropogenic environment and advocates the notion that microbial activity within an ILW-GDF is likely to influence the impact of ISAs upon radionuclide migration

Quantum micro–nano devices fabricated in diamond by femtosecond laser and ion irradiation

Diamond has attracted great interest as a quantum technology platform thanks to its optically active nitrogen vacancy (NV) center. The NV's ground state spin can be read out optically, exhibiting long spin coherence times of ≈1 ms even at ambient temperatures. In addition, the energy levels of the NV are sensitive to external fields. These properties make NVs attractive as a scalable platform for efficient nanoscale resolution sensing based on electron spins and for quantum information systems. Diamond photonics enhance optical interactions with NVs, beneficial for both quantum sensing and information. Diamond is also compelling for microfluidic applications due to its outstanding biocompatibility, with sensing functionality provided by NVs. However, it remains a significant challenge to fabricate photonics, NVs, and microfluidics in diamond. In this Progress Report, an overview is provided of ion irradiation and femtosecond laser writing, two promising fabrication methods for diamond‐based quantum technological devices. The unique capabilities of both techniques are described, and the most important fabrication results of color center, optical waveguide, and microfluidics in diamond are reported, with an emphasis on integrated devices aiming toward high performance quantum sensors and quantum information systems of tomorrow