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X-ray free-electron lasers (XFELs) deliver pulses of coherent X-rays on the femtosecond time scale, with potentially high repetition rates. While XFELs provide high peak intensities, both the intensity and the centroid of the beam fluctuate strongly on a pulse-to-pulse basis, motivating high-rate beam diagnostics that operate over a large dynamic range. The fast drift velocity, low X-ray absorption and high radiation tolerance properties of chemical vapour deposition diamonds make these crystals a promising candidate material for developing a fast (multi-GHz) pass-through diagnostic for the next generation of XFELs. A new approach to the design of a diamond sensor signal path is presented, along with associated characterization studies performed in the XPP endstation of the LINAC Coherent Light Source (LCLS) at SLAC. Qualitative charge collection profiles (collected charge versus time) are presented and compared with those from a commercially available detector. Quantitative results on the charge collection efficiency and signal collection times are presented over a range of approximately four orders of magnitude in the generated electron-hole plasma density.

Previous studies of the correlates of depression among women have not generally been based on adequate midlife samples or precision in the specification of marital status categories. The present analysis is designed to address these deficiencies and is based on data from the Health and Retirement Survey-Wave 1 (i.e., respondents 51 to 60 years old). Results indicate that married women are less likely to report symptoms of depression than their unmarried counterparts. The mental health benefits of marriage are greater for men than for women. Moreover, other variables, such as marital satisfaction, self-rated health, and employment status are more powerful predictors of emotional well-being than marital status per se. The quality of marriage affects depressive symptoms more strongly than women than for men. [ABSTRACT FROM AUTHOR]

A comprehensive analysis and simulation of two memristor-based neuromorphic architectures for nuclear radiation detection is presented. Both scalable architectures retrofit a locally competitive algorithm to solve overcomplete sparse approximation problems by harnessing memristor crossbar execution of vector-matrix multiplications. The proposed systems demonstrate excellent accuracy and throughput while consuming minimal energy for radionuclide detection. To ensure that the simulation results of our proposed hardware are realistic, the memristor parameters are chosen from our own fabricated memristor devices. Based on these results, we conclude that memristor-based computing is the preeminent technology for a radiation detection platform.

Monoclonal antibodies (mAbs) have transformed therapeutic strategies for various diseases. Their high specificity to target antigens makes them ideal therapeutic agents for certain diseases. However, a challenge to their application in clinical practice is their potential risk to induce unwanted immune response, termed immunogenicity. This challenge drives the continued efforts to deimmunize these protein therapeutics while maintaining their pharmacokinetic properties and therapeutic efficacy. Because mAbs hold a central position in therapeutic strategies against an array of diseases, the importance of conducting comprehensive immunogenicity risk assessment during the drug development process cannot be overstated. Such assessment necessitates the employment of in silico, in vitro, and in vivo strategies to evaluate the immunogenicity risk of mAbs. Understanding the intricacies of the mechanisms that drive mAb immunogenicity is crucial to improving their therapeutic efficacy and safety and developing the most effective strategies to determine and mitigate their immunogenic risk. This review highlights recent advances in immunogenicity prediction strategies, with a focus on protein engineering strategies used throughout development to reduce immunogenicity., (© 2024. The Author(s).)

Gradient-recalled echo (GRE) echo-planar imaging (EPI) is an efficient MRI pulse sequence that is commonly used for several enticing applications, including functional MRI (fMRI), susceptibility-weighted imaging (SWI), and proton resonance frequency (PRF) thermometry. These applications are typically not performed in the mid-field (<1 T) as longer T 2 * and lower polarization present significant challenges. However, recent developments of mid-field scanners equipped with high-performance gradient sets offer the possibility to re-evaluate the feasibility of these applications. The paper introduces a metric "T 2 * contrast efficiency" for this evaluation, which minimizes dead time in the EPI sequence while maximizing T 2 * contrast so that the temporal and pseudo signal-to-noise ratios (SNRs) can be attained, which could be used to quantify experimental parameters for future fMRI experiments in the mid-field. To guide the optimization, T 2 * measurements of the cortical gray matter are conducted, focusing on specific regions of interest (ROIs). Temporal and pseudo SNR are calculated with the measured time-series EPI data to observe the echo times at which the maximum T 2 * contrast efficiency is achieved. T 2 * for a specific cortical ROI is reported at 0.5 T. The results suggest the optimized echo time for the EPI protocols is shorter than the effective T 2 * of that region. The effective reduction of dead time prior to the echo train is feasible with an optimized EPI protocol, which will increase the overall scan efficiency for several EPI-based applications at 0.5 T.

Background: Although increased attention has been placed on the potential deleterious consequences of paternal incarceration on maternal health, little empirical research has attempted to understand the physiological processes that might underlie this relationship. Moreover, exposure to incarceration and access to resources that shape family incarceration patterns are unequally distributed across racial and ethnic lines, yet few studies utilize analytic frameworks that account for this social reality. Using a within race/ethnicity analytic framework, the present study addresses these gaps by examining relationships between paternal incarceration and telomere length for Black, Latina/o, and White mothers., Methods: Data were drawn from the Fragile Families and Child Wellbeing Study, a longitudinal, stratified multistage probability sample of couples and children in 20 large U.S. cities. The final analytic sample consisted of 2174 mothers that were followed from pregnancy to age 9 of the focal child., Results: Findings revealed exposure to paternal incarceration was negatively associated with telomere length for Black mothers, but not for Latina/o and White mothers. Mediation analysis also showed paternal incarceration-telomere length relationships did not operate through secondary stressors, such as economic instability, poor mental health, and parenting stress., Conclusion: Overall, results demonstrated that the detrimental physiological consequences of paternal incarceration for mothers depended on racial and ethnic background. Findings from this study can provide a foundation upon which health scholars and criminal justice stakeholders may better understand whether and how paternal incarceration shapes deleterious health patterns for the mothers who remain to care for the children of those incarcerated., (© 2022. W. Montague Cobb-NMA Health Institute.)

For Plasmodium falciparum, the most widespread and virulent malaria parasite that infects humans, persistence depends on continuous asexual replication in red blood cells, while transmission to their mosquito vector requires asexual blood-stage parasites to differentiate into non-replicating gametocytes. This decision is controlled by stochastic derepression of a heterochromatin-silenced locus encoding AP2-G, the master transcription factor of sexual differentiation. The frequency of ap2-g derepression was shown to be responsive to extracellular phospholipid precursors but the mechanism linking these metabolites to epigenetic regulation of ap2-g was unknown. Through a combination of molecular genetics, metabolomics and chromatin profiling, we show that this response is mediated by metabolic competition for the methyl donor S-adenosylmethionine between histone methyltransferases and phosphoethanolamine methyltransferase, a critical enzyme in the parasite's pathway for de novo phosphatidylcholine synthesis. When phosphatidylcholine precursors are scarce, increased consumption of SAM for de novo phosphatidylcholine synthesis impairs maintenance of the histone methylation responsible for silencing ap2-g, increasing the frequency of derepression and sexual differentiation. This provides a key mechanistic link that explains how LysoPC and choline availability can alter the chromatin status of the ap2-g locus controlling sexual differentiation., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Acute hemorrhage commonly leads to coagulopathy and organ dysfunction or failure. Recent evidence suggests that damage to the endothelial glycocalyx contributes to these adverse outcomes. The physiological events mediating acute glycocalyx shedding are undefined, however. Here, we show that succinate accumulation within endothelial cells drives glycocalyx degradation through a membrane reorganization-mediated mechanism. We investigated this mechanism in a cultured endothelial cell hypoxia-reoxygenation model, in a rat model of hemorrhage, and in trauma patient plasma samples. We found that succinate metabolism by succinate dehydrogenase mediates glycocalyx damage through lipid oxidation and phospholipase A2-mediated membrane reorganization, promoting the interaction of matrix metalloproteinase 24 (MMP24) and MMP25 with glycocalyx constituents. In a rat hemorrhage model, inhibiting succinate metabolism or membrane reorganization prevented glycocalyx damage and coagulopathy. In patients with trauma, succinate levels were associated with glycocalyx damage and the development of coagulopathy, and the interaction of MMP24 and syndecan-1 was elevated compared to healthy controls.

We present a spectrally selective, passively cooled mid-wave infrared bolometric absorber engineered to spatially and spectrally decouple infrared absorption and thermal emission. The structure leverages an antenna-coupled metal-insulator-metal resonance for mid-wave infrared normal incidence photon absorption and a long-wave infrared optical phonon absorption feature, aligned closer to peak room temperature thermal emission. The phonon-mediated resonant absorption enables a strong long-wave infrared thermal emission feature limited to grazing angles, leaving the mid-wave infrared absorption feature undisturbed. The two independently controlled absorption/emission phenomena demonstrate decoupling of the photon detection mechanism from radiative cooling and offer a new design approach enabling ultra-thin, passively cooled mid-wave infrared bolometers.

Background: ATLS suggests simple thoracostomy (ST) after failure of needle thoracostomy (NT) in thoracic trauma. Some EMS agencies have adopted ST into their practice. We sought to describe our experience implementing ST in the prehospital setting, hypothesizing that prehospital ST would reduce failure rates and improve outcomes compared to NT., Methods: This was a retrospective review of adult trauma patients who received prehospital ST or NT from 2017 to 2020., Results: There were 48 patients with 64 procedures included. 83.7% were male and 65.8% injured by penetrating mechanism and of median (IQR) age of 31 (25-46) years. 28 (43.8%) procedures were NT and 36 (56.3%) were ST. Rates of improved patient response ( P = .15), noted return of blood/air ( P = .19), and return of spontaneous circulation ( P = .62) did not differ. On-scene times were higher for ST (16.8 vs 11.5 minutes; P < .02). Overall mortality did not differ between ST and NT (68.2% vs 46.4%, respectively; P = .125). For patients that survived beyond the ED, procedure-related complication rates were 2 of 21 patients (9.5%) in ST and 1 of 12 (8.3%) in NT. In penetrating trauma, simple thoracostomy had longer on-scene time and total prehospital time., Discussion: ST did not improve success rates of ROSC and was associated with prolonged prehospital times, especially in penetrating trauma patients. Given the benefit of "scoop and run" in urban penetrating trauma, consideration should be given to direct transport in lieu of ST. Use of ST in blunt trauma should be evaluated prospectively.

The primary antigenic and virulence determinant of the human malaria parasite Plasmodium falciparum is a variant surface protein called PfEMP1. Different forms of PfEMP1 are encoded by a multicopy gene family called var , and switching between active genes enables the parasites to evade the antibody response of their human hosts. var gene switching is key for the maintenance of chronic infections; however, what controls switching is unknown, although it has been suggested to occur at a constant frequency with little or no environmental influence. var gene transcription is controlled epigenetically through the activity of histone methyltransferases (HMTs). Studies in model systems have shown that metabolism and epigenetic control of gene expression are linked through the availability of intracellular S-adenosylmethionine (SAM), the principal methyl donor in biological methylation modifications, which can fluctuate based on nutrient availability. To determine whether environmental conditions and changes in metabolism can influence var gene expression, P . falciparum was cultured in media with altered concentrations of nutrients involved in SAM metabolism. We found that conditions that influence lipid metabolism induce var gene switching, indicating that parasites can respond to changes in their environment by altering var gene expression patterns. Genetic modifications that directly modified expression of the enzymes that control SAM levels similarly led to profound changes in var gene expression, confirming that changes in SAM availability modulate var gene switching. These observations directly challenge the paradigm that antigenic variation in P. falciparum follows an intrinsic, programed switching rate, which operates independently of any external stimuli.

COVID-19 variants continue to create public health danger impacting mortality and morbidity across the United States. The spillover effects of COVID-19 on the economy and social institutions pose a significant threat to broader wellbeing, including the food security of millions across the country. We aim to explore whether the context of place matters above and beyond individual and social vulnerabilities for food insecurity. To do so, we employ a multi-level framework using data from a survey of over 10,000 U.S. adults from March 2020 with American Community Survey (ACS) and John Hopkins COVID Dashboard county-level data. We find nearly two in five respondents were food insecure by March of 2020 with disparities across race, nativity, the presence of children in the home, unemployment, and age. Furthermore, we note that individuals living in more disadvantaged communities were more likely to report food insecurity above and beyond individual and social vulnerabilities. Overall, food insecurity is driven by complex, multi-level dynamics that remain a pressing public health concern for the current-but also future-public health crisis.

Eukaryotes have canonical pathways for responding to amino acid (AA) availability. Under AA-limiting conditions, the TOR complex is repressed, whereas the sensor kinase GCN2 is activated. While these pathways have been highly conserved throughout evolution, malaria parasites are a rare exception. Despite auxotrophic for most AA, Plasmodium does not have either a TOR complex nor the GCN2-downstream transcription factors. While Ile starvation has been shown to trigger eIF2α phosphorylation and a hibernation-like response, the overall mechanisms mediating detection and response to AA fluctuation in the absence of such pathways has remained elusive. Here we show that Plasmodium parasites rely on an efficient sensing pathway to respond to AA fluctuations. A phenotypic screen of kinase knockout mutant parasites identified nek4, eIK1 and eIK2-the last two clustering with the eukaryotic eIF2α kinases-as critical for Plasmodium to sense and respond to distinct AA-limiting conditions. Such AA-sensing pathway is temporally regulated at distinct life cycle stages, allowing parasites to actively fine-tune replication and development in response to AA availability. Collectively, our data disclose a set of heterogeneous responses to AA depletion in malaria parasites, mediated by a complex mechanism that is critical for modulating parasite growth and survival., (© 2023. The Author(s).)

The effect of terahertz (THz) pulse generation has revolutionized broadband coherent spectroscopy and imaging at THz frequencies. However, THz pulses typically lack spatial structure, whereas structured beams are becoming essential for advanced spectroscopy applications. Nonlinear optical metasurfaces with nanoscale THz emitters can provide a solution by defining the beam structure at the generation stage. We develop a nonlinear InAs metasurface consisting of nanoscale optical resonators for simultaneous generation and structuring of THz beams. We find that THz pulse generation in the resonators is governed by optical rectification. It is more efficient than in ZnTe crystals, and it allows us to control the pulse polarity and amplitude, offering a platform for realizing binary-phase THz metasurfaces. To illustrate this capability, we demonstrate an InAs metalens, which simultaneously generates and focuses THz pulses. The control of spatiotemporal structure using nanoscale emitters opens doors for THz beam engineering and advanced spectroscopy and imaging applications.

We recently adapted a CUT&RUN protocol for genome-wide profiling of chromatin modifications in the human malaria parasite Plasmodium Using the step-by-step protocol described below, we were able to generate high-quality profiles of multiple histone modifications using only a small fraction of the cells required for ChIP-seq. Using antibodies against two commonly profiled histone modifications, H3K4me3 and H3K9me3, we show here that CUT&RUN profiling is highly reproducible and closely recapitulates previously published ChIP-seq-based abundance profiles of histone marks. Finally, we show that CUT&RUN requires substantially lower sequencing coverage for accurate profiling compared with ChIP-seq., (© 2022 Morillo et al.)

The United States' response to the COVID-19 pandemic has relied heavily on personal mitigation behaviors versus centralized governmental prevention strategies, especially early in the virus's outbreak. This study examines how family structure shapes mitigation, focusing on the intersectional effects of gender, marital status, and the presence of children while accounting for differences in worry about infection from the virus. Using data from a national survey of 10,368 United States adults early in the pandemic (March 2020), survey-weighted logistic regression models show important differences in the likelihood of personal mitigation adoption across family structures. Unmarried women with children were most likely to report personal mitigation behaviors, including washing hands more frequently and avoiding social gatherings. Our findings highlight the differential impacts of the pandemic on those living in specific family circumstances., Competing Interests: Conflict of interest: All authors declare no conflicts of interest in this paper., (© 2022 the Author(s), licensee AIMS Press.)

Thin film platinum resistive thermometers are conventionally applied for resistance thermometry techniques due to their stability and proven measurement accuracy. Depending upon the required thermometer thickness and temperature measurement, however, performance benefits can be realized through the application of alternative nanometallic thin films. Herein, a comparative experimental analysis is provided on the performance of nanometallic thin film thermometers most relevant to microelectronics and thermal sensing applications: Al, Au, Cu, and Pt. Sensitivity is assessed through the temperature coefficient of resistance, measured over a range of 10-300 K for thicknesses nominally spanning 25-200 nm. The interplay of electron scattering sources, which give rise to the temperature-dependent TCR properties for each metal, are analyzed in the framework of a Mayadas-Shatzkes based model. Despite the prevalence of evaporated Pt thin film thermometers, Au and Cu films fabricated in a similar manner may provide enhanced sensitivity depending upon thickness. These results may serve as a guide as the movement toward smaller measurement platforms necessitates the use of smaller, thinner metallic resistance thermometers., (© 2022 IOP Publishing Ltd.)

Highly flexible, electrically conductive freestanding graphene membranes hold great promise for vibration-based applications. This study focuses on their integration into mainstream semiconductor manufacturing methods. We designed a two-mask lithography process that creates an array of freestanding graphene-based variable capacitors on 100 mm silicon wafers. The first mask forms long trenches terminated by square wells featuring cone-shaped tips at their centers. The second mask fabricates metal traces from each tip to its contact pad along the trench and a second contact pad opposite the square well. A graphene membrane is then suspended over the square well to form a variable capacitor. The same capacitor structures were also built on 5 mm by 5 mm bare dies containing an integrated circuit underneath. We used atomic force microscopy, optical microscopy, and capacitance measurements in time to characterize the samples.

An in situ counted ion implantation experiment improving the error on the number of ions required to form a single optically active silicon vacancy (SiV) defect in diamond 7-fold compared to timed implantation is presented. Traditional timed implantation relies on a beam current measurement followed by implantation with a preset pulse duration. It is dominated by Poisson statistics, resulting in large errors for low ion numbers. Instead, our in situ detection, measuring the ion number arriving at the substrate, results in a 2-fold improvement of the error on the ion number required to generate a single SiV compared to timed implantation. Through postimplantation analysis, the error is improved 7-fold compared to timed implantation. SiVs are detected by photoluminescence spectroscopy, and the yield of 2.98% is calculated through the photoluminescence count rate. Hanbury-Brown-Twiss interferometry is performed on locations potentially hosting single-photon emitters, confirming that 82% of the locations exhibit single photon emission statistics.

Ultrafast optical excitation of select materials gives rise to the generation of broadband terahertz (THz) pulses. This effect has enabled the field of THz time-domain spectroscopy and led to the discovery of many physical mechanisms behind THz generation. However, only a few materials possess the required properties to generate THz radiation efficiently. Optical metasurfaces can relax stringent material requirements by shifting the focus onto the engineering of local electromagnetic fields to boost THz generation. Here we demonstrate the generation of THz pulses in a 160 nm thick nanostructured GaAs metasurface. Despite the drastically reduced volume, the metasurface emits THz radiation with efficiency comparable to that of a thick GaAs crystal. We reveal that along with classical second-order volume nonlinearity, an additional mechanism contributes strongly to THz generation in the metasurface, which we attribute to surface nonlinearity. Our results lay the foundation for engineering of semiconductor metasurfaces for efficient and versatile THz radiation emitters., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society.)

The novel coronavirus (Covid-19) pandemic has had a significant impact on the mental health of the general U.S. population. Extant literature has increasingly linked social vulnerabilities, risky behavior, and limited social and psychological resources to the growing mental health crisis during the virus's spread. The purpose of this study was to examine the impact of pertinent social vulnerabilities and subjective risk factors for both men and women on mental health (i.e., depression, anxiety, isolation) with a closer examination of the influence of pregnancy during the pandemic on mental health. The sample included 740,640 respondents participating in the U.S. Covid-19 Trends and Impact Survey that was deployed between February and March 2021. Descriptive statistics and ordinary least squares regression models are presented with a focus on the factors that shape negative mental health outcomes, particularly on the disparities between pregnant and non-pregnant women relative to men, but also subjective/perception factors (e.g., fear/worry) and social vulnerabilities. Results show that pregnant women were at significantly greater risk of negative mental health outcomes at this stage of the pandemic than either men or non-pregnant women. Overall, respondents who were younger, without children in the household, unemployed, worried generally about infection or their finances, or had ever tested positive for Covid were also more likely to report feelings of anxiety, isolation, and depression than their counterparts. Pregnant women may be especially vulnerable to depression, anxiety, and isolation during the pandemic and our findings suggest the importance of developing targeted mental health support for this sub-population., Competing Interests: Conflict of interests: All authors declare no conflicts of interest in this paper., (© 2022 the Author(s), licensee AIMS Press.)

A demonstration of 2D hole gases in GeSn/Ge heterostructures with a mobility as high as 20 000 cm 2 V -1 s -1 is given. Both the Shubnikov-de Haas oscillations and integer quantum Hall effect are observed, indicating high sample quality. The Rashba spin-orbit coupling (SOC) is investigated via magneto-transport. Further, a transition from weak localization to weak anti-localization is observed, which shows the tunability of the SOC strength by gating. The magneto-transport data are fitted to the Hikami-Larkin-Nagaoka formula. The phase-coherence and spin-relaxation times, as well as spin-splitting energy and Rashba coefficient of the k-cubic term, are extracted. The analysis reveals that the effects of strain and confinement potential at a high fraction of Sn suppress the Rashba SOC caused by the GeSn/Ge heterostructures., (© 2021 Wiley-VCH GmbH.)

Despite their wide use in terahertz (THz) research and technology, the application spectra of photoconductive antenna (PCA) THz detectors are severely limited due to the relatively high optical gating power requirement. This originates from poor conversion efficiency of optical gate beam photons to photocurrent in materials with sub-picosecond carrier lifetimes. Here we show that using an ultra-thin (160 nm), perfectly absorbing low-temperature grown GaAs metasurface as the photoconductive channel drastically improves the efficiency of THz PCA detectors. This is achieved through perfect absorption of the gate beam in a significantly reduced photoconductive volume, enabled by the metasurface. This Letter demonstrates that sensitive THz PCA detection is possible using optical gate powers as low as 5 µW-three orders of magnitude lower than gating powers used for conventional PCA detectors. We show that significantly higher optical gate powers are not necessary for optimal operation, as they do not improve the sensitivity to the THz field. This class of efficient PCA THz detectors opens doors for THz applications with low gate power requirements.

Resistance thermometry is a widely employed technique for general-purpose temperature measurements, with applications ranging from basic thermal physics experiments to industrial use in the automotive, aerospace, and microelectronics industries. Platinum is one of the most commonly used materials for resistance thermometry in microfabricated devices due to its broad range of temperature coverage, ease of fabrication, and compatibility with numerous microfabrication processes. For cryogenic applications below 10 K, transition metal oxynitrides and negative temperature coefficient alloys are the dominant choice owing to their superior temperature sensitivity in this range compared to pure metallic thin films. However, these materials often require arduous process development to optimize their sensitivity and may be constrained by a diminutive thermal budget. In this paper, we present a PtNiGe thermometer that has both the fabrication simplicity and thermal stability traits of a Pt thin film. We characterize this PtNiGe material system for a series of annealing temperatures and analyze its sensitivity and temperature coefficient of resistance. We find that this thermometer maintains a performance similar to Pt thin films at 40 K with a sensitivity just one order of magnitude below that of a high performance, commercial thermometer at 380 mK. This PtNiGe thermometer represents a middle ground between Pt thin films and commercial devices.

Perfect optical absorption occurs in a metasurface that supports two degenerate and critically-coupled modes of opposite symmetry. The challenge in designing a perfectly absorbing metasurface for a desired wavelength and material stems from the fact that satisfying these conditions requires multi-dimensional optimization often with parameters affecting optical resonances in non-trivial ways. This problem comes to the fore in semiconductor metasurfaces operating near the bandgap wavelength, where intrinsic material absorption varies significantly. Here we devise and demonstrate a systematic process by which one can achieve perfect absorption in GaAs metasurfaces for a desired wavelength at different levels of intrinsic material absorption, eliminating the need for trial and error in the design process. Using this method, we show that perfect absorption can be achieved not only at wavelengths where GaAs exhibits high absorption, but also at wavelengths near the bandgap edge. In this region, absorption is enhanced by over one order of magnitude compared a layer of unstructured GaAs of the same thickness.

A gradient coil with integrated second and third order shims has been designed and constructed for use inside an actively shielded 310 mm horizontal bore 9.4 T small animal MRI. An extension of the boundary element method, to minimise the power deposited in conducting surfaces, was used to design the gradients, and a boundary element method with a constraint on mutual inductance was used to design the shims. The gradient coil allows for improved imaging performance and was optimized for an imaging region appropriate for marmoset imaging studies. Efficiencies of 1.5 mT m -1 A -1 were achieved in a 15 cm wide bore while maintaining gradient uniformity ≤5% over the 8 cm region of interest. Two new cooling methods were implemented which allowed the gradient coil to operate at 100 A RMS, 25 % of max current with a temperature rise below 30 C.

Malaria parasites have a complex life cycle that includes specialized stages for transmission between their mosquito and human hosts. These stages are an understudied part of the lifecycle yet targeting them is an essential component of the effort to shrink the malaria map. The human parasite Plasmodium falciparum is responsible for the majority of deaths due to malaria. Our goal was to generate transgenic P. falciparum lines that could complete the lifecycle and produce fluorescent transmission stages for more in-depth and high-throughput studies. Using zinc-finger nuclease technology to engineer an integration site, we generated three transgenic P. falciparum lines in which tdtomato or gfp were stably integrated into the genome. Expression was driven by either stage-specific peg4 and csp promoters or the constitutive ef1a promoter. Phenotypic characterization of these lines demonstrates that they complete the life cycle with high infection rates and give rise to fluorescent mosquito stages. The transmission stages are sufficiently bright for intra-vital imaging, flow cytometry and scalable screening of chemical inhibitors and inhibitory antibodies.

Even as today's most prominent spin-based qubit technologies are maturing in terms of capability and sophistication, there is growing interest in exploring alternate material platforms that may provide advantages, such as enhanced qubit control, longer coherence times, and improved extensibility. Recent advances in heterostructure material growth have opened new possibilities for employing hole spins in semiconductors for qubit applications. Undoped, strained Ge/SiGe quantum wells are promising candidate hosts for hole spin-based qubits due to their low disorder, large intrinsic spin-orbit coupling strength, and absence of valley states. Here, we use a simple one-layer gated device structure to demonstrate both a single quantum dot as well as coupling between two adjacent quantum dots. The hole effective mass in these undoped structures, m* ∼ 0.08 m 0 , is significantly lower than for electrons in Si/SiGe, pointing to the possibility of enhanced tunnel couplings in quantum dots and favorable qubit-qubit interactions in an industry-compatible semiconductor platform.

This paper reports on plastic recovery and self-healing behavior in longitudinally-twinned and [112] orientated SiGe nanowire (NW) beams when they are subjected to large bending strains. The NW alloys are comprised of lamellar nanotwin platelet(s) sandwiched between two semi-cylindrical twins. The loading curves, which are acquired from atomic force microscope (AFM) based three-point bending tests, reveal the onset of plastic deformation at a characteristic stress threshold, followed by further straining of the NWs. This ductility is attributed to dislocation activity within the semi-cylindrical crystal portions of the NW, which are hypothesized to undergo a combination of elastic and plastic straining. On the other hand, the lamellar nanoplatelets undergo purely elastic stretching. During the unloading process, the release of internal elastic stresses enables dislocation backflow and escape at the surface. As a result, the dislocations are predominantly annihilated and the NW samples evidenced self-healing via plastic recovery even at ultra-large strains, which are estimated using finite-element models at 16.3% in one of the tested devices. Finite element analysis also establishes the independence of the observed nanomechanical behavior on the relative orientation of the load with respect to the nanoplatelet. This first observation of reversible plasticity in the SiGe material system, which is aided by a concurrent evolution of segmented elastic and plastic deformation within its grains during the loading process, presents an important new pathway for mechanical stabilization of technologically important group-IV semiconductor nanomaterials.

Terahertz (THz) photoconductive devices are used for generation, detection, and modulation of THz waves, and they rely on the ability to switch electrical conductivity on a subpicosecond time scale using optical pulses. However, fast and efficient conductivity switching with high contrast has been a challenge, because the majority of photoexcited charge carriers in the switch do not contribute to the photocurrent due to fast recombination. Here, we improve efficiency of electrical conductivity switching using a network of electrically connected nanoscale GaAs resonators, which form a perfectly absorbing photoconductive metasurface. We achieve perfect absorption without incorporating metallic elements, by breaking the symmetry of cubic Mie resonators. As a result, the metasurface can be switched between conductive and resistive states with extremely high contrast using an unprecedentedly low level of optical excitation. We integrate this metasurface with a THz antenna to produce an efficient photoconductive THz detector. The perfectly absorbing photoconductive metasurface opens paths for developing a wide range of efficient optoelectronic devices, where required optical and electronic properties are achieved through nanostructuring the resonator network.

Background: Recent articles have suggested regionalization of some emergency general surgery (EGS) problems to tertiary referral centers. We sought to characterize the clinical and cost burden of such transfers to our tertiary referral center., Materials and Methods: Data were collected retrospectively for nine EGS diagnoses for patients admitted to the EGS service during calendar years 2015 and 2016. Patients were grouped as inpatient transfers (IPTs), Emergency Department transfers (EDTs), or local admissions (LAs). Demographic data, length of stay at originating site, insurance status, Charlson Comorbidity Index, and all relevant financial data were obtained., Results: Six hundred sixty-three patients were reviewed: 93 IPTs, 343 EDTs, and 227 LAs. IPTs required longer lengths of stay (7.0 d compared to 4.0 d for EDTs and 3.0 d for LAs), higher median direct costs, and higher case mix index, which produced a higher median revenue but averaged a median net loss (-$264 compared to +$2436 for EDTs and +$3125 for LAs). The IPTs had higher median comorbidities (Charlson Comorbidity Index 3.5 versus 2.9 for EDTs and 2.0 for LAs), age (62 y versus 58 for EDTs and 52 for LAs), and mortality rate (7.5% versus 2.3% for EDTs and 0.4% for LAs)., Conclusions: Patients who present to a tertiary care EGS service as an IPT from another hospital have more comorbidities, higher mortality rate, and result in a financial loss. These data suggest the need for adequate risk adjustment in quality assessment of tertiary referral center outcomes and the need for increased financial reimbursement for the care of these patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Uncrossmatched packed red blood cell (PRBC) transfusion is fundamental in resuscitation of hemorrhagic shock. Ready availability of uncrossmatched blood can be achieved by storing uncrossmatched blood in a blood bank refrigerator in the emergency department (ED), but could theoretically lead to inappropriate uncrossmatched use., Methods: This retrospective study was performed at a level I trauma center from January 2013 to March 2014. Possibly inappropriate transfusion was defined as patients who received at least one unit of blood from the ED refrigerator and no more than two units of PRBC in the first 24 hours. Deaths within the first 24 hours were excluded. Patients who received blood from the ED refrigerator who received ≤2 units total in 24 hours were compared with those who received >2 units., Results: 158 adults received blood from the ED refrigerator. 140 (88.6%) were trauma patients. 37 (23.4%) received massive transfusion (MT). 42 (26.6%) deaths were excluded. 29 patients received ≤2 units and 87 received >2 units in the first 24  hours. The ≤2 units group had a higher systolic blood pressure (116  mm Hg vs. 102  mm Hg, p=0.042), lower base deficit (6.4 mEq/L vs. 9.4 mEq/L, p=0.032), higher hematocrit (34% vs. 30%, p=0.024), lower rate of MT protocol activation (27.6% vs. 58.6%, p=0.005), and lower rates of transfusion of fresh frozen plasma (17.2% vs. 54.0%, p=0.001) and platelets (13.8% vs. 39.1%, p=0.012). Appropriately transfused patients were more likely to have evidence of shock with active, non-compressible hemorrhage. Potentially inappropriate uses were more likely in patients either without evidence of hemorrhage or without signs of shock., Discussion: Storing uncrossmatched blood in the ED is an effective way to get PRBCs transfused quickly in hemorrhaging patients and is associated with a low rate of unnecessary uncrossmatched transfusion. Provider education and good clinical judgment are imperative to prevent unnecessary use., Level of Evidence: Level III, therapeutic., Competing Interests: Competing interests: None declared.

Outside several notable exceptions, few studies have examined variations in bias crime occurrences across American communities, and how community-level factors may differentially shape violent and non-violent bias crimes across victim groups. Drawing from ecological theories of crime, this study asks, (1) what are the structural predictors of the likelihood of bias homicide occurrences? and (2) how do structural predictors differ across bias victim groups? To answer these questions, data on bias homicide are derived from the United States Extremist Crime Database (ECDB) for the years 1990 through 2014 and paired with socio- structural variables from the United States Census Bureau. Results are discussed relative to the goals of understanding where fatal bias crimes are more likely to occur as a means of informing law enforcement and policymakers interested in preventing and responding to this specific form of crime., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Early initiation of a high ratio massive transfusion can lower trauma patient mortality by 80%. Long transport times from rural Level IV trauma centers therefore require that damage control resuscitation begin before patient transfer. This study evaluates the current use of fresh frozen plasma (FFP) at Level IV trauma centers and the feasibility of implementing trauma transfusion protocols at these centers. Demographic and clinical data were collected for trauma patients at all state Level IV trauma centers who would have met criteria for massive transfusion protocol (MTP) activation based on the Assessment of Blood Consumption (ABC) score. All state Level IV trauma centers were also surveyed to determine availability of blood bank plasma resources. A total of 760 adult trauma patients presented to a Level IV trauma center during the study period. Three hundred sixty-eight patients (48.4%) were transferred to a higher level of care. Because FAST (Focused Assessment with Sonography for Trauma) results were not available in the state registry data, we included all blunt trauma patients with an ABC score of 1 as "potential ABC-positive patients." Forty-two (5.5%) patients were potentially ABC positive. Fifteen of 22 Level IV centers responded to our survey. Seventy-three percent of respondents have FFP available. Mean time to FFP availability was 63.1 min. Median total length of stay from registration to emergency department discharge for potentially ABC-positive patients was 2 hr. Because most Level IV trauma centers have FFP and thaw times are such that administration would not delay transport to a higher level of care, we recommend implementation of MTPs at Level IV trauma centers to reduce hemorrhage-associated mortality.

This study quantified the spin-lattice relaxation rate (R 1 ) dispersion of murine tissues from 0.24 mT to 3 T. A combination of ex vivo and in vivo spin-lattice relaxation rate measurements were acquired for murine tissue. Selected brain, liver, kidney, muscle, and fat tissues were excised and R 1 dispersion profiles were acquired from 0.24 mT to 1.0 T at 37 °C, using a fast field-cycling MR (FFC-MR) relaxometer. In vivo R 1 dispersion profiles of mice were acquired from 1.26 T to 1.74 T at 37 °C, using FFC-MRI on a 1.5 T scanner outfitted with a field-cycling insert electromagnet to dynamically control B 0 prior to imaging. Images at five field strengths (1.26, 1.39, 1.5, 1.61, 1.74 T) were acquired using a field-cycling pulse sequence, where B 0 was modulated for varying relaxation durations prior to imaging. R 1 maps and R 1 dispersion (ΔR 1 /ΔB 0 ) were calculated at 1.5 T on a pixel-by-pixel basis. In addition, in vivo R 1 maps of mice were acquired at 3 T. At fields less than 1 T, a large R 1 magnetic field dependence was observed for tissues. ROI analysis of the tissues showed little relaxation dispersion for magnetic fields from 1.26 T to 3 T. Our tissue measurements show strong R 1 dispersion at field strengths less than 1 T and limited R 1 dispersion at field strengths greater than 1 T. These findings emphasize the inherent weak R 1 magnetic field dependence of healthy tissues at clinical field strengths. This characteristic of tissues can be exploited by a combination of FFC-MRI and T 1 contrast agents that exhibit strong relaxivity magnetic field dependences (inherent or by binding to a protein), thereby increasing the agents' specificity and sensitivity. This development can provide potential insights into protein-based biomarkers using FFC-MRI to assess early changes in tumour development, which are not easily measureable with conventional MRI., (Copyright © 2017 John Wiley & Sons, Ltd.)

We investigate carrier transport in silicon-germanium nanowires with an axial p-n junction doping profile by fabricating these wires into transistors that feature separate top gates over each doping segment. By independently biasing each gate, carrier concentrations in the n- and p-side of the wire can be modulated. For these devices, which were fabricated with nickel source-drain electrical contacts, holes are the dominant charge carrier, with more favorable hole injection occurring on the p-side contact. Channel current exhibits greater sensitivity to the n-side gate, and in the reverse biased source-drain configuration, current is limited by the nickel/n-side Schottky contact.

Pathogens have to balance transmission with persistence. For Plasmodium falciparum, the most widespread and virulent malaria parasite, persistence within its human host requires continuous asexual replication within red blood cells, while its mosquito-borne transmission depends on intra-erythrocytic differentiation into non-replicating sexual stages called gametocytes. Commitment to either fate is determined during the preceding cell cycle that begins with invasion by a single, asexually committed merozoite and ends, 48 hours later, with a schizont releasing newly formed merozoites, all committed to either continued asexual replication or differentiation into gametocytes. Sexual commitment requires the transcriptional activation of ap2-g (PF3D7&#95;1222600), the master regulator of sexual development, from an epigenetically silenced state during asexual replication. AP2-G expression during this 'commitment cycle' prepares gene expression in nascent merozoites to initiate sexual development through a hitherto unknown mechanism. To maintain a persistent infection, the expression of ap2-g is limited to a sub-population of parasites (1-30%, depending on genetic background and growth conditions). As sexually committed schizonts comprise only a sub-population and are morphologically indistinguishable from their asexually committed counterparts, defining their characteristic gene expression has been difficult using traditional, bulk transcriptome profiling. Here we use highly parallel, single-cell RNA sequencing of malaria cultures undergoing sexual commitment to determine the transcriptional changes induced by AP2-G within this sub-population. By analysing more than 18,000 single parasite transcriptomes from a conditional AP2-G knockdown line and NF54 wild-type parasites at multiple stages of development, we show that sexually committed, AP2-G + mature schizonts specifically upregulate additional regulators of gene expression, including other AP2 transcription factors, histone-modifying enzymes, and regulators of nucleosome positioning. These epigenetic regulators may act to facilitate the expression and/or repression of genes that are necessary for the initiation of gametocyte development in the subsequent cell cycle.

Battery cycle life is directly influenced by the microstructural changes occurring in the electrodes during charge and discharge cycles. Here, we image in situ the nanoscale phase evolution in negative electrode materials for Li-ion batteries using a fully enclosed liquid cell in a transmission electron microscope (TEM) to reveal early degradation that is not evident in the charge-discharge curves. To compare the electrochemical phase transformation behavior between three model materials, thin films of amorphous Si, crystalline Al, and crystalline Au were lithiated and delithiated at controlled rates while immersed in a commercial liquid electrolyte. This method allowed for the direct observation of lithiation mechanisms in nanoscale negative electrodes, revealing that a simplistic model of a surface-to-interior lithiation front is insufficient. For the crystalline films, a lithiation front spread laterally from a few initial nucleation points, with continued grain nucleation along the growing interface. The intermediate lithiated phases were identified using electron diffraction, and high-resolution postmortem imaging revealed the details of the final microstructure. Our results show that electrochemically induced solid-solid phase transformations can lead to highly concentrated stresses at the laterally propagating phase boundary which should be considered for future designs of nanostructured electrodes for Li-ion batteries.

Purpose: To optimize the design of radiofrequency (RF) shielding of transmit coils at 7T and reduce eddy currents generated on the RF shielding when imaging with rapid gradient waveforms., Methods: One set of a four-element, 2 × 2 Tic-Tac-Toe head coil structure was selected and constructed to study eddy currents on the RF coil shielding. The generated eddy currents were quantitatively studied in the time and frequency domains. The RF characteristics were studied using the finite difference time domain method. Five different kinds of RF shielding were tested on a 7T MRI scanner with phantoms and in vivo human subjects., Results: The eddy current simulation method was verified by the measurement results. Eddy currents induced by solid/intact and simple-structured slotted RF shielding significantly distorted the gradient fields. Echo-planar images, B1+ maps, and S matrix measurements verified that the proposed slot pattern suppressed the eddy currents while maintaining the RF characteristics of the transmit coil., Conclusion: The presented dual-optimization method could be used to design RF shielding and reduce the gradient field-induced eddy currents while maintaining the RF characteristics of the transmit coil., (© 2014 Wiley Periodicals, Inc.)

A growing body of research indicates that immigration to the U.S. has crime-reducing effects on aggregate levels of violence, which researchers have often attributed to the protective and revitalizing effects of immigrants settling in spatially concentrated neighborhoods. However, recent scholarship suggests that growing shares of the foreign-born population are bypassing these segregated immigrant enclaves and are dispersing more widely to other urban neighborhoods. Moreover, some scholars suggest that spatially isolating immigrant populations may not always be protective, but could actually contribute to social problems like crime, particularly in disadvantaged contexts. The current study offers one of the first analyses exploring the way that segregation of immigrant populations (relative to the U.S.-born) is related to year 2000 violent crime rates for nearly 500 census places in California and New York. Results of our analysis reveal no direct link between immigrant segregation and macro-level violence, but instead show that these effects are highly contextualized and depend on the resources present in locales. Specifically, immigrant segregation contributes to violence in highly disadvantaged places but is linked to lower violence in areas with greater resources., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Electrodeposited metallic lithium is an ideal negative battery electrode, but nonuniform microstructure evolution during cycling leads to degradation and safety issues. A better understanding of the Li plating and stripping processes is needed to enable practical Li-metal batteries. Here we use a custom microfabricated, sealed liquid cell for in situ scanning transmission electron microscopy (STEM) to image the first few cycles of lithium electrodeposition/dissolution in liquid aprotic electrolyte at submicron resolution. Cycling at current densities from 1 to 25 mA/cm(2) leads to variations in grain structure, with higher current densities giving a more needle-like, higher surface area deposit. The effect of the electron beam was explored, and it was found that, even with minimal beam exposure, beam-induced surface film formation could alter the Li microstructure. The electrochemical dissolution was seen to initiate from isolated points on grains rather than uniformly across the Li surface, due to the stabilizing solid electrolyte interphase surface film. We discuss the implications for operando STEM liquid-cell imaging and Li-battery applications.

Purpose: Delta relaxation enhanced magnetic resonance (dreMR) imaging requires an auxiliary B0 electromagnet capable of shifting the main magnetic field within a clinical 1.5 Tesla (T) MR system. In this work, the main causes of interaction between an actively shielded, insertable resistive B0 electromagnet and a 1.5T superconducting system are systematically identified and mitigated., Methods: The effects of nonideal fabrication of the field-shifting magnet are taken into consideration through careful measurement during winding and improved accuracy in the design of the associated active shield. The shielding performance of the resultant electromagnet is compared against a previously built system in which the shield design was based on an ideal primary coil model. Hardware and software approaches implemented to eliminate residual image artifacts are presented in detail., Results: The eddy currents produced by the newly constructed dreMR system are shown to have a significantly smaller "long-time-constant" component, consistent with the hypothesis that less energy is deposited into the cryostat of the MR system., Conclusion: With active compensation, the dreMR imaging system is capable of 0.22T field shifts within a clinical 1.5T MRI with no significant residual eddy-current fields., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: To design and build a head insert gradient coil to use in conjunction with body gradients for superior imaging., Materials and Methods: The use of the boundary element method to solve for a gradient coil wire pattern on an arbitrary surface allowed us to incorporate engineering changes into the electromagnetic design of a gradient coil directly. Improved wire pattern design was combined with robust manufacturing techniques and novel cooling methods., Results: The finished coil had an efficiency of 0.15 mT/m/A in all three axes and allowed the imaging region to extend across the entire head and upper part of the neck., Conclusion: The ability to adapt an electromagnetic design to necessary changes from an engineering perspective leads to superior coil performance., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: Magnetic field homogeneity is important in all aspects of magnetic resonance imaging. A new approach to increase field homogeneity is presented that allows dynamic and adaptive control over the flow of current over a single surface using a network of actively controlled solid-state switches., Methods: Computer simulations were completed demonstrating the potential of this approach. Wire patterns were produced using the boundary element method to remove magnetic field inhomogeneities over multiple regions of interest. Field maps and regions of interest histograms were compared with and without the shim present. A prototype was constructed confirming the feasibility of this approach within the magnetic resonance environment. Metal-oxide-semiconductor field-effect transistors were used. Two field maps were acquired with the prototype producing gradient and offset field profiles, respectively. The experimental field profiles were compared with simulation., Results: The wire patterns significantly increased field homogeneity over all regions of interest investigated. The field profiles produced by the prototype matched simulation. No imaging artifacts were produced., Conclusions: An approach to control the shape of a current distribution over a single surface has been described. This method has the potential to improve field homogeneity over any desired region of interest and is particularly well suited for dynamic applications. The method is feasible with current technology and construction techniques., (Copyright © 2013 Wiley Periodicals, Inc.)

Eddy currents are generated in MR by the use of rapidly switched electromagnets, resulting in time varying and spatially varying magnetic fields that must be either minimized or corrected. This problem is further complicated when non-cylindrical insert magnets are used for specialized applications. Interruption of the coupling between an insert coil and the MR system is typically accomplished using active magnetic shielding. A new method of actively shielding insert gradient and shim coils of any surface geometry by use of the boundary element method for coil design with a minimum energy constraint is presented. This method was applied to shield x- and z-gradient coils for two separate cases: a traditional cylindrical primary gradient with cylindrical shield and, to demonstrate its versatility in surface geometry, the same cylindrical primary gradients with a rectangular box-shaped shield. For the cylindrical case this method produced shields that agreed with analytic solutions. For the second case, the rectangular box-shaped shields demonstrated very good shielding characteristics despite having a different geometry than the primary coils., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The time-varying magnetic fields created by the gradient coils in magnetic resonance imaging can produce negative effects on image quality and the system itself. Additionally, they can be a limiting factor to the introduction of non-MR devices such as cardiac pacemakers, orthopedic implants, and surgical robotics. The ability to model the induced currents produced by the switching gradient fields is key to developing methods for reducing these unwanted interactions. In this work, a framework for the calculation of induced currents on conducting surface geometries is summarized. This procedure is then compared to two separate experiments: (1) the analysis of the decay of currents induced upon a conducting cylinder by an insert gradient set within a head only 7 T MR scanner; and (2) analysis of the heat deposited into a small conductor by a uniform switching magnetic field at multiple frequencies and two distinct conductor thicknesses. The method was shown to allow the accurate modeling of the induced time-varying field decay in the first case, and was able to provide accurate estimation of the rise in temperature in the second experiment to within 30% when the skin depth was greater than or equal to the thickness of the conductor.

Lithium-ion batteries have revolutionized portable electronics and will be a key to electrifying transport vehicles and delivering renewable electricity. Amorphous silicon (a-Si) is being intensively studied as a high-capacity anode material for next-generation lithium-ion batteries. Its lithiation has been widely thought to occur through a single-phase mechanism with gentle Li profiles, thus offering a significant potential for mitigating pulverization and capacity fade. Here, we discover a surprising two-phase process of electrochemical lithiation in a-Si by using in situ transmission electron microscopy. The lithiation occurs by the movement of a sharp phase boundary between the a-Si reactant and an amorphous Li(x)Si (a-Li(x)Si, x ~ 2.5) product. Such a striking amorphous-amorphous interface exists until the remaining a-Si is consumed. Then a second step of lithiation sets in without a visible interface, resulting in the final product of a-Li(x)Si (x ~ 3.75). We show that the two-phase lithiation can be the fundamental mechanism underpinning the anomalous morphological change of microfabricated a-Si electrodes, i.e., from a disk shape to a dome shape. Our results represent a significant step toward the understanding of the electrochemically driven reaction and degradation in amorphous materials, which is critical to the development of microstructurally stable electrodes for high-performance lithium-ion batteries.

Despite a resurgent interest in the macro-level relationship between Latino immigration and violent crime, research has overlooked an important shift in immigrant settlement whereby Latino migrants are increasingly bypassing traditional receiving communities in favor of non-traditional ones. Additionally, how the impact of this new settlement pattern on violence is conditioned by race and ethnicity has yet to be explored. Using year 2000 race/ethnic-specific arrest data for 326 California, New York, and Texas census places, the current study explores the relationship between recent Latino immigration and White, Black, and Latino violent crime across both traditional and non-traditional immigrant destinations. Results suggest that (1) recent Latino immigration is generally unassociated with violence across all communities, (2) recent Latino immigration is associated with decreased violence in traditional destinations but slightly increased violence in non-traditional destinations, and (3) there are important race/ethnic differences in these relationships. Implications and directions for future research are discussed., (Copyright © 2012 Elsevier Inc. All rights reserved.)