Pump-Enhanced Continuous-Wave Magnetometry using Nitrogen-Vacancy Ensembles

Ensembles of nitrogen-vacancy centers in diamond are a highly promising platform for high-sensitivity magnetometry, whose efficacy is often based on efficiently generating and monitoring magnetic-field dependent infrared fluorescence. Here we report on an increased sensing efficiency with the use of a 532-nm resonant confocal cavity and a microwave resonator antenna for measuring the local magnetic noise density using the intrinsic nitrogen-vacancy concentration of a chemical-vapor deposited single-crystal diamond. We measure a near-shot-noise-limited magnetic noise floor of 200 pT/$\sqrt{\text{Hz}}$ spanning a bandwidth up to 159 Hz, and an extracted sensitivity of approximately 3 nT/$\sqrt{\text{Hz}}$, with further enhancement limited by the noise floor of the lock-in amplifier and the laser damage threshold of the optical components. Exploration of the microwave and optical pump-rate parameter space demonstrates a linewidth-narrowing regime reached by virtue of using the optical cavity, allowing an enhanced sensitivity to be achieved, despite an unoptimized collection efficiency of <2 %, and a low nitrogen-vacancy concentration of about 0.2 ppb.Comment: 10 pages and 5 figure

Nitrogen-Vacancy Ensemble Magnetometry Based on Pump Absorption

We demonstrate magnetic field sensing using an ensemble of nitrogen-vacancy centers by recording the variation in the pump-light absorption due to the spin-polarization dependence of the total ground state population. Using a 532 nm pump laser, we measure the absorption of native nitrogen-vacancy centers in a chemical vapor deposited diamond placed in a resonant optical cavity. For a laser pump power of 0.4 W and a cavity finesse of 45, we obtain a noise floor of $\sim$ 100 nT/$\sqrt{\textrm{Hz}}$ spanning a bandwidth up to 125 Hz. We project a photon shot-noise-limited sensitivity of $\sim$ 1 pT/$\sqrt{\textrm{Hz}}$ by optimizing the nitrogen-vacancy concentration and the detection method.Comment: 7 pages and 5 figure

Hydrogels for RNA delivery

Funding Information: This work was supported by the US National Institutes of Health grants R01CA200900, R01HL156362, R01HL159012 and R01HL162367 (to J.S.), the Lung Cancer Discovery Award from the American Lung Association (to J.S.), the Innovation Discovery Grants award from the Mass General Brigham (to J.S.), the European Research Council Starting Grant (ERC-StG-2019-848325 to J.C. and B.B.M.) and the Fundação para a Ciência e a Tecnologia FCT Grant (PTDC/BTM-MAT/4738/2020 to J.C.). Publisher Copyright: © 2023, Springer Nature Limited.RNA-based therapeutics have shown tremendous promise in disease intervention at the genetic level, and some have been approved for clinical use, including the recent COVID-19 messenger RNA vaccines. The clinical success of RNA therapy is largely dependent on the use of chemical modification, ligand conjugation or non-viral nanoparticles to improve RNA stability and facilitate intracellular delivery. Unlike molecular-level or nanoscale approaches, macroscopic hydrogels are soft, water-swollen three-dimensional structures that possess remarkable features such as biodegradability, tunable physiochemical properties and injectability, and recently they have attracted enormous attention for use in RNA therapy. Specifically, hydrogels can be engineered to exert precise spatiotemporal control over the release of RNA therapeutics, potentially minimizing systemic toxicity and enhancing in vivo efficacy. This Review provides a comprehensive overview of hydrogel loading of RNAs and hydrogel design for controlled release, highlights their biomedical applications and offers our perspectives on the opportunities and challenges in this exciting field of RNA delivery.publishersversionepub_ahead_of_prin

The impact of neuroscience on society: cognitive enhancement in neuropsychiatric disorders and in healthy people.

In addition to causing distress and disability to the individual, neuropsychiatric disorders are also extremely expensive to society and governments. These disorders are both common and debilitating and impact on cognition, functionality and wellbeing. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used to treat cognitive dysfunction in Alzheimer's disease and attention deficit hyperactivity disorder, respectively. Other cognitive enhancers include specific computerized cognitive training and devices. An example of a novel form of cognitive enhancement using the technological advancement of a game on an iPad that also acts to increase motivation is presented. Cognitive enhancing drugs, such as methylphenidate and modafinil, which were developed as treatments, are increasingly being used by healthy people. Modafinil not only affects 'cold' cognition, but also improves 'hot' cognition, such as emotion recognition and task-related motivation. The lifestyle use of 'smart drugs' raises both safety concerns as well as ethical issues, including coercion and increasing disparity in society. As a society, we need to consider which forms of cognitive enhancement (e.g. pharmacological, exercise, lifelong learning) are acceptable and for which groups (e.g. military, doctors) under what conditions (e.g. war, shift work) and by what methods we would wish to improve and flourish.All cited psychopharmacological work from Professor Sahakian laboratory was funded by a Wellcome Trust Grant (089589/Z/09/Z) awarded to T.W. Robbins, B.J. Everitt, A.C. Roberts, J.W. Dalley, and B.J. Sahakian, and it was conducted at the Behavioural and Clinical Neuroscience Institute, which is supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354). B.J. Sahakian receives funding from the Human Brain Project. We thank Janssen/J&J for funding the study on cognitive training in schizophrenia.This is the final version of the article. It first appeared from RSC via http://dx.doi.org/10.1098/rstb.2014.021

Surface preparation of powder metallurgical tool steels by means of wire electrical discharge machining

The surface of two types of powder metallurgical (PM) tool steels (i.e., with and without nitrogen) was prepared using wire electrical discharge machining (WEDM). From each grade of tool steel, seven surfaces corresponding to one to seven passes of WEDM were prepared. The WEDM process was carried out using a brass wire as electrode and deionized water as dielectric. After eachWEDM pass the surface of the tool steels was thoroughly examined. Surface residual stresses were measured by the X-ray diffraction (XRD) technique. The measured stresses were found to be of tensile nature. The surface roughness of the WEDM specimens was measured using interference microscopy. The surface roughness as well as the residual stress measurements indicated an insignificant improvement of these parameters after four passes of WEDM. In addition, the formed recast layer was characterized by means of scanning electron microscopy (SEM), XRD, and X-ray photoelectron spectroscopy (XPS). The characterization investigation clearly shows diffusion of copper and zinc from the wire electrode into the work material, even after the final WEDM step. Finally, the importance of eliminating excessive WEDM steps is thoroughly discussed

Micromechanical modeling of tension stiffening in FRP-strengthened concrete elements

This article presents a micromodeling computational framework for simulating the tensile response and tension-stiffening behavior of fiber reinforced polymer–strengthened reinforced concrete elements. The total response of strengthened elements is computed based on the local stress transfer mechanisms at the crack plane including concrete bridging stress, reinforcing bars stress, FRP stress, and the bond stresses at the bars-to-concrete and fiber reinforced polymer-to-concrete interfaces. The developed model provides the possibility of calculating the average response of fiber reinforced polymer, reinforcing bars, and concrete as well as the crack spacing and crack widths. The model, after validation with experimental results, is used for a systematic parameter study and development of micromechanics-based relations for calculating the crack spacing, fiber reinforced polymer critical ratio, debonding strength, and effective bond length. Constitutive models are also proposed for concrete tension stiffening and average response of steel reinforcing bars in fiber reinforced polymer–strengthened members as the main inputs of smeared crack modeling approaches

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Maximising retention in a longitudinal study of genital Chlamydia trachomatis among young women in Australia

<p>Abstract</p> <p>Background</p> <p>Cohort studies are an important study design however they are difficult to implement, often suffer from poor retention, low participation and bias. The aims of this paper are to describe the methods used to recruit and retain young women in a longitudinal study and to explore factors associated with loss to follow up.</p> <p>Methods</p> <p>The Chlamydia Incidence and Re-infection Rates Study (CIRIS) was a longitudinal study of Australian women aged 16 to 25 years recruited from primary health care clinics. They were followed up via the post at three-monthly intervals and required to return questionnaires and self collected vaginal swabs for chlamydia testing. The protocol was designed to maximise retention in the study and included using recruiting staff independent of the clinic staff, recruiting in private, regular communication with study staff, making the follow up as straightforward as possible and providing incentives and small gifts to engender good will.</p> <p>Results</p> <p>The study recruited 66% of eligible women. Despite the nature of the study (sexual health) and the mobility of the women (35% moved address at least once), 79% of the women completed the final stage of the study after 12 months. Loss to follow up bias was associated with lower education level [adjusted hazard ratio (AHR): 0.7 (95% Confidence Interval (CI): 0.5, 1.0)], recruitment from a sexual health centre as opposed to a general practice clinic [AHR: 1.6 (95% CI: 1.0, 2.7)] and previously testing positive for chlamydia [AHR: 0.8 (95% CI: 0.5, 1.0)]. No other factors such as age, numbers of sexual partners were associated with loss to follow up.</p> <p>Conclusions</p> <p>The methods used were considered effective for recruiting and retaining women in the study. Further research is needed to improve participation from less well-educated women.</p

Maximising retention in a longitudinal study of genital Chlamydia trachomatis among young women in Australia

<p>Abstract</p> <p>Background</p> <p>Cohort studies are an important study design however they are difficult to implement, often suffer from poor retention, low participation and bias. The aims of this paper are to describe the methods used to recruit and retain young women in a longitudinal study and to explore factors associated with loss to follow up.</p> <p>Methods</p> <p>The Chlamydia Incidence and Re-infection Rates Study (CIRIS) was a longitudinal study of Australian women aged 16 to 25 years recruited from primary health care clinics. They were followed up via the post at three-monthly intervals and required to return questionnaires and self collected vaginal swabs for chlamydia testing. The protocol was designed to maximise retention in the study and included using recruiting staff independent of the clinic staff, recruiting in private, regular communication with study staff, making the follow up as straightforward as possible and providing incentives and small gifts to engender good will.</p> <p>Results</p> <p>The study recruited 66% of eligible women. Despite the nature of the study (sexual health) and the mobility of the women (35% moved address at least once), 79% of the women completed the final stage of the study after 12 months. Loss to follow up bias was associated with lower education level [adjusted hazard ratio (AHR): 0.7 (95% Confidence Interval (CI): 0.5, 1.0)], recruitment from a sexual health centre as opposed to a general practice clinic [AHR: 1.6 (95% CI: 1.0, 2.7)] and previously testing positive for chlamydia [AHR: 0.8 (95% CI: 0.5, 1.0)]. No other factors such as age, numbers of sexual partners were associated with loss to follow up.</p> <p>Conclusions</p> <p>The methods used were considered effective for recruiting and retaining women in the study. Further research is needed to improve participation from less well-educated women.</p