Block copolymers (BCPs) and their directed self‐assembly (DSA) has emerged as a realizable complementary tool to aid optical patterning of device elements for future integrated circuit advancements. ...Methods to enhance BCP etch contrast for DSA application and further potential applications of inorganic nanomaterial features (e.g., semiconductor, dielectric, metal and metal oxide) are examined. Strategies to modify, infiltrate and controllably deposit inorganic materials by utilizing neat self‐assembled BCP thin films open a rich design space to fabricate functional features in the nanoscale regime. An understanding and overview on innovative ways for the selective inclusion/infiltration or deposition of inorganic moieties in microphase separated BCP nanopatterns is provided. Early initial inclusion methods in the field and exciting contemporary reports to further augment etch contrast in BCPs for pattern transfer application are described. Specifically, the use of evaporation and sputtering methods, atomic layer deposition, sequential infiltration synthesis, metal‐salt inclusion and aqueous metal reduction methodologies forming isolated nanofeatures are highlighted in di‐BCP systems. Functionalities and newly reported uses for electronic and non‐electronic technologies based on the inherent properties of incorporated inorganic nanostructures using di‐BCP templates are highlighted. We outline the potential for extension of incorporation methods to triblock copolymer features for more diverse applications. Challenges and emerging areas of interest for inorganic infiltration of BCPs are also discussed.
Innovative strategies for the inorganic infiltration of “neat” block copolymer thin films for functional application are highlighted. A range of diverse routes for precisely incorporating inorganic material in self‐assembled block copolymer patterns are detailed. Both electronic and non‐electronic applications based on the incorporated inorganic features are discussed.
The mammalian Phospholipase D MitoPLD facilitates mitochondrial fusion by generating the signaling lipid phosphatidic acid (PA). The
Drosophila MitoPLD homolog Zucchini (Zuc), a proposed cytoplasmic ...nuclease, is required for piRNA generation, a critical event in germline development. We show that Zuc localizes to mitochondria and has MitoPLD-like activity. Conversely,
MitoPLD
−/− mice exhibit the meiotic arrest, DNA damage, and male sterility characteristic of mice lacking piRNAs. The primary function of MitoPLD seems to be the generation of mitochondrial-surface PA. This PA in turn recruits the phosphatase Lipin 1, which converts PA to diacylglycerol and promotes mitochondrial fission, suggesting a mechanism for mitochondrial morphology homeostasis. MitoPLD and Lipin 1 have opposing effects on mitochondria length and on intermitochondrial cement (nuage), a structure found between aggregated mitochondria that is implicated in piRNA generation. We propose that mitochondrial-surface PA generated by MitoPLD/Zuc recruits or activates nuage components critical for piRNA production.
► MitoPLD/Zuc generate the lipid phosphatidic acid (PA) on the mitochondrial surface ► This PA recruits the phosphatase Lipin 1, which converts the PA to diacylglycerol ► MitoPLD and Lipin 1 exert opposing effects on mitochondria and on germline nuage ►
MitoPLD
−/− spermatocytes exhibit disaggregated mitochondria and meiotic arrest
Creating inorganic nanostructures for development of nanoelectronic device components is a highly active research area. The ability for manipulation of the chemistry of materials, as well as their ...shape, size and placement enables scientists and engineers to propose technologically advanced devices. Recent techniques can now realize astounding control of metallic and oxide structures by insertion of metal molecules from gas phase or solution mediated processes into self-assembled block copolymer templates targeting distinct nanodomains as infiltration sites. Inorganic nanofeatures such as metals, oxides including a range of functional perovskites and related structures, have broad energy, photonic, catalytic and environmental nanotechnology applications; however, the objective in this perspective is to highlight salient achievements that block copolymers possess as infiltration sites specifically for nanoelectronic device manufacture. We briefly outline background semiconductor patterning followed by the basic theory of block copolymers for general readers. The subsequent section of this piece highlights gas/vapor and wet chemical approaches for the selective inclusion of functional inorganic materials in block copolymer nanodomains. The piece concisely describes advanced experimental achievements in the early part, while discussion then centres on the barriers that may prevent translation of such research in an industrial manufacturing environment. These barriers comprise both commercial and technical aspects. We present evaluations on each barrier in a forward-looking manner to accelerate overall progression. Finally, we discuss nanoelectronic opportunities that are possible from the synergy of block copolymers and infiltration techniques for future research endeavours. We envisage that this perspective serves to highlight the excellent progress in the field and allows readers to comprehend the hurdles for integration in high volume manufacturing and, thus, may lead to new studies to translate discovery to manufacturing.
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•Perspective focuses on infiltration methods to precisely position metals, oxides, and perovskites in block copolymer thin films.•Article highlights potential use of infiltrated nanofeatures for nanoelectronic manufacture.•Provides reader with concise overview of block copolymer fundamentals for nanolithography application.•Discussion on critical barriers of infiltration methods to overcome to bring research forward for devices is provided.•Potential solutions of issues are addressed and opportunities of infiltration methods in block copolymers are highlighted.
In multiple cancer types, high tumor mutational burden (TMB) is associated with longer survival after treatment with immune checkpoint inhibitors (ICIs). The association of TMB with survival outside ...of the immunotherapy context is poorly understood. We analyzed 10,233 patients (80% non-ICI-treated, 20% ICI-treated) with 17 cancer types before/without ICI treatment or after ICI treatment. In non-ICI-treated patients, higher TMB (higher percentile within cancer type) was not associated with better prognosis; in fact, in many cancer types, higher TMB was associated with poorer survival, in contrast to ICI-treated patients in whom higher TMB was associated with longer survival.
Au nanoparticles with diameters ranging between 15 and 170 nm have been synthesised in aqueous solution using a seed-mediated growth method, employing hydroxylamine hydrochloride as a reducing agent. ...Thiolated polyethylene glycol (mPEG-SH) polymers, with molecular weights ranging from 2100 to 51 000 g mol super(-1), were used as efficient particle stabilising ligands. Dynamic light scattering and zeta potential measurements confirmed that the overall mean diameter and zeta potential of the capped nanoparticles increased in a non-linear way with increasing molecular weight of the mPEG-SH ligand. Electron microscopy and thermal gravimetric analysis of the polymer-capped nanoparticles, with a mean gold core diameter of 15 nm, revealed that the grafting density of the mPEG-SH ligands decreased from 3.93 to 0.31 PEG nm super(-2) as the molecular weight of the ligands increased from 2100 to 51 400 g mol super(-1) respectively, due to increased steric hindrance and polymer conformational entropy with increase in the PEG chain length. Additionally, the number of bound mPEG-SH ligands, with a molecular weight of 10 800 g mol super(-1), was found to increase in a non-linear way from 278 ( sigma = 42) to approximately 12 960 PEG ( sigma = 1227) when the mean Au core diameter increased from 15 to 115 nm respectively. However, the grafting density of mPEG sub(10 000)-SH ligands was higher on 15 nm Au nanoparticles and decreased slightly from 1.57 to 0.8 PEG nm super(-2) when the diameter increased; this effect can be attributed to the fact that smaller particles offer higher surface curvature, therefore allowing increased polymer loading per nm super(2). Au nanoparticles were also shown to interact with CT-26 cells without causing noticeable toxicity.
Evolving treatments, disease phenotypes, and biology, together with a changing drug development environment, have created the need to revise castration-resistant prostate cancer (CRPC) clinical trial ...recommendations to succeed those from prior Prostate Cancer Clinical Trials Working Groups.
An international expert committee of prostate cancer clinical investigators (the Prostate Cancer Clinical Trials Working Group 3 PCWG3) was reconvened and expanded and met in 2012-2015 to formulate updated criteria on the basis of emerging trial data and validation studies of the Prostate Cancer Clinical Trials Working Group 2 recommendations.
PCWG3 recommends that baseline patient assessment include tumor histology, detailed records of prior systemic treatments and responses, and a detailed reporting of disease subtypes based on an anatomic pattern of metastatic spread. New recommendations for trial outcome measures include the time to event end point of symptomatic skeletal events, as well as time to first metastasis and time to progression for trials in the nonmetastatic CRPC state. PCWG3 introduces the concept of no longer clinically benefiting to underscore the distinction between first evidence of progression and the clinical need to terminate or change treatment, and the importance of documenting progression in existing lesions as distinct from the development of new lesions. Serial biologic profiling using tumor samples from biopsies, blood-based diagnostics, and/or imaging is also recommended to gain insight into mechanisms of resistance and to identify predictive biomarkers of sensitivity for use in prospective trials.
PCWG3 moves drug development closer to unmet needs in clinical practice by focusing on disease manifestations most likely to affect prognosis adversely for therapeutics tested in both nonmetastatic and metastatic CRPC populations. Consultation with regulatory authorities is recommended if a trial is intended to seek support for drug approval.
Herein, we demonstrate the fabrication of sub-20 nm MoS
2
horizontal nanowire arrays on silicon substrates using a self-assembled block copolymer assisted
in situ
inclusion approach. Microphase ...separated long-range ordered polystyrene-b-polyethylene oxide (PS-b-PEO) block copolymer (BCP) line-space nanopatterns were achieved through thermo-solvent annealing. The patterns produced had long-range order and domain sizes > 1 µm. The BCP structures were lightly etched and modified by anhydrous ethanol to facilitate insertion of molybdenum precursor within the film maintaining the parent BCP arrangements. Horizontal ordered molybdenum oxide nanowire arrays were then fabricated by ultraviolet (UV)/ozone treatment at room temperature. The oxides were converted to sulphides by thermal evaporation at different temperatures in Ar/H
2
environment. X-ray photoelectron spectroscopy revealed the composition and phases of the molybdenum oxide and sulphide nanowires. Elemental mapping was performed to investigate the interfaces between the oxide and sulphide nanowires with the substrate surface. The formation and stability of the sulphide nanowires were studied at different temperatures. The photoluminescence and Raman properties were studied at different formation temperatures to investigate defects and estimate the number of layers.
Abstract Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian disorder. Abnormal tau inclusions, in selected regions of the brain, are a hallmark of the disease and the H1 ...haplotype of MAPT , the gene encoding tau, is the major risk factor in PSP. A 3-repeat and 4-repeat (4R) tau isoform ratio imbalance has been strongly implicated as a cause of disease. Thus, understanding tau isoform regional expression in disease and pathology-free states is crucial to elucidating the mechanisms involved in PSP and other tauopathies. We used a tau isoform-specific fluorescent assay to investigate relative 4R-tau expression in 6 different brain regions in PSP cases and healthy control samples. We identified a marked difference in 4R-tau relative expression, across brain regions and between MAPT haplotypes. Highest 4R-tau expression levels were identified in the globus pallidus compared with pons, cerebellum, and frontal cortex. 4R-tau expression levels were related to the MAPT H1 and H1c haplotypes. Similar regional variation was seen in PSP case and in control samples.
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