Objectives/Goals: pT217-tau is a novel fluid biomarker that predicts onset of Alzheimer’s disease (AD) symptoms, but little is known about how pT217-tau arises in brain, as soluble pT217-tau is dephosphorylated postmortem in the humans. Aging macaques naturally develop tau pathology with the same qualitative pattern and sequence as humans, including cortical pathology. Methods/Study Population: The etiology of pT217-tau in aging brains can be probed in rhesus macaques, where perfusion fixation allows capture of phosphorylated proteins in their native state. We utilized multi-label immunofluorescence and immunoperoxidase and immunogold immunoelectron microscopy to examine the subcellular localization of early-stage pT217-tau in entorhinal cortex (ERC) and dorsolateral prefrontal cortex (dlPFC) of aged rhesus macaques with naturally occurring tau pathology and assayed pT217-tau levels in blood plasma using an ultrasensitive nanoneedle approach. Results/Anticipated Results: pT217-tau labeling is primarily observed in postsynaptic compartments, accumulating in: 1) dendritic spines on the calcium-storing smooth endoplasmic reticulum spine apparatus near asymmetric glutamatergic-like synapses and 2) in dendritic shafts, where it aggregated on microtubules, often “trapping” endosomes associated with Aβ42. The dendrites expressing pT217-tau were associated with autophagic vacuoles and dysmorphic mitochondria, indicative of early neurite degeneration. We observed trans-synaptic pT217-tau trafficking between neurons within omega-shaped bodies and endosomes, specifically near excitatory, but not inhibitory synapses. We also examined pT217-tau in blood plasma in macaques across age-span and observed a statistically significant age-related increase in pT217-tau. Discussion/Significance of Impact: We provide direct evidence of pT217-tau trafficking between neurons near synapses to “seed” tau pathology in higher brain circuits, interfacing with the extracellular space to become accessible to CSF and blood. The expression of pT217-tau in dendrites with early signs of degeneration may help to explain why this tau species can herald future diseases.

We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.

We report on experimental observation of non-laminar proton acceleration modulated by a strong magnetic field in laser irradiating micrometer aluminum targets. The results illustrate the coexistence of ring-like and filamentation structures. We implement the knife edge method into the radiochromic film detector to map the accelerated beams, measuring a source size of 30–110 μm for protons of more than 5 MeV. The diagnosis reveals that the ring-like profile originates from low-energy protons far off the axis whereas the filamentation is from the near-axis high-energy protons, exhibiting non-laminar features. Particle-in-cell simulations reproduced the experimental results, showing that the short-term magnetic turbulence via Weibel instability and the long-term quasi-static annular magnetic field by the streaming electric current account for the measured beam profile. Our work provides direct mapping of laser-driven proton sources in the space-energy domain and reveals the non-laminar beam evolution at featured time scales.

Success of any needle-based medical procedures depends on accurate placement of the needle at the target location. However, accurate targeting and control of flexible self-actuating (active) needle are challenging. We have developed a shape memory alloy-actuated flexible needle steered by a 3D Cartesian robot and performed a comparative study of four, non-model-based, coordinated control methodologies for the combined robot steering and flexible-needle insertion process for surgical interventions. Investigated four controllers are: proportional–integral–derivative (PID), PID with the cubic of positional error term (PID-P3), static PID sliding mode controller, and robust adaptive PID sliding mode controller (RAPID-SMC). Relative efficacies of these controllers are demonstrated by performing experiements using a tissue-mimicking soft material phantom. Results from experiments have reavealed that RAPID-SMC is superior to other three controllers.

We investigate kinetic entropy-based measures of the non-Maxwellianity of distribution functions in plasmas, i.e. entropy-based measures of the departure of a local distribution function from an associated Maxwellian distribution function with the same density, bulk flow and temperature as the local distribution. First, we consider a form previously employed by Kaufmann & Paterson (J. Geophys. Res., vol. 114, 2009, A00D04), assessing its properties and deriving equivalent forms. To provide a quantitative understanding of it, we derive analytical expressions for three common non-Maxwellian plasma distribution functions. We show that there are undesirable features of this non-Maxwellianity measure including that it can diverge in various physical limits and elucidate the reason for the divergence. We then introduce a new kinetic entropy-based non-Maxwellianity measure based on the velocity-space kinetic entropy density, which has a meaningful physical interpretation and does not diverge. We use collisionless particle-in-cell simulations of two-dimensional anti-parallel magnetic reconnection to assess the kinetic entropy-based non-Maxwellianity measures. We show that regions of non-zero non-Maxwellianity are linked to kinetic processes occurring during magnetic reconnection. We also show the simulated non-Maxwellianity agrees reasonably well with predictions for distributions resembling those calculated analytically. These results can be important for applications, as non-Maxwellianity can be used to identify regions of kinetic-scale physics or increased dissipation in plasmas.

The aim of this study was to develop and externally validate a simple-to-use nomogram for predicting the survival of hospitalised human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients (hospitalised person living with HIV/AIDS (PLWHAs)). Hospitalised PLWHAs (n = 3724) between January 2012 and December 2014 were enrolled in the training cohort. HIV-infected inpatients (n = 1987) admitted in 2015 were included as the external-validation cohort. The least absolute shrinkage and selection operator method was used to perform data dimension reduction and select the optimal predictors. The nomogram incorporated 11 independent predictors, including occupation, antiretroviral therapy, pneumonia, tuberculosis, Talaromyces marneffei, hypertension, septicemia, anaemia, respiratory failure, hypoproteinemia and electrolyte disturbances. The Likelihood χ2 statistic of the model was 516.30 (P = 0.000). Integrated Brier Score was 0.076 and Brier scores of the nomogram at the 10-day and 20-day time points were 0.046 and 0.071, respectively. The area under the curves for receiver operating characteristic were 0.819 and 0.828, and precision-recall curves were 0.242 and 0.378 at two time points. Calibration plots and decision curve analysis in the two sets showed good performance and a high net benefit of nomogram. In conclusion, the nomogram developed in the current study has relatively high calibration and is clinically useful. It provides a convenient and useful tool for timely clinical decision-making and the risk management of hospitalised PLWHAs.

Cadmium (Cd) is a toxic heavy metal that poses a threat to the health of humans and animals. It can cause serious damage to the small intestine, which is the main absorption site of Cd and the primary target organ after oral administration. Our previous study found that zinc chelate of hydroxy analogue of methionine (Zn-HMTB), a new type of feed additive, decreased Cd accumulation in the liver and kidneys. The aim of this study was to investigate the effect of Zn-HMTB on Cd absorption and Cd-induced toxicity in the small intestine of piglets. Twenty-four piglets (Landrace × Large White, 13.22 ± 0.58 kg BW) were randomly divided into four dietary treatment groups: basal diet, and diets containing 30 mg/kg Cd from CdCl2 and 0, 100 or 200 mg/kg Zn from Zn-HMTB. The experiment lasted 27 days. The feed intake and final BW of each piglet were recorded at the end of the experiment. Gastrointestinal (GI) tract tissue and samples of liver, kidney, spleen, heart, lung and longissimus muscle tissue and faeces were collected. The concentrations of Cd and metal trace elements in the GI tract and organs were analysed, as was the relative messenger RNA (mRNA) expression of inflammatory cytokines and metal element transporters in the small intestine, and epithelial apoptosis in the small intestine. The results showed that, compared with Cd-treated piglets, piglets in the Zn-HMTB and Cd cotreatment groups had less Cd deposition in the stomach, ileum, caecum, colon, liver, kidneys, spleen, lungs, heart and muscles (P < 0.05), and lower Cd concentrations in faeces (P < 0.05), suggesting that Zn-HMTB increased Cd absorption and the excretion of Cd in other forms (possibly urine). Zinc chelate of hydroxy analogue of methionine increased Zn deposition in the jejunum and the relative mRNA expression of divalent metal transporters 1 and zinc transporter 5 in the duodenum (P < 0.05), indicating that Zn-HMTB may promote the absorption and transportation of Cd and Zn together by upregulating metal element transporters. Competition between Zn and Cd may be responsible for accelerating Cd excretion. Furthermore, Zn-HMTB reduced Cd-induced apoptosis of enterocytes and inflammatory stimuli in the small intestine, suggesting that Zn-HMTB reduced Cd-induced toxicity to the small intestine. These results suggest that Zn-HMTB can be helpful in decreasing Cd accumulation in the GI tract and organs of piglets and relieving Cd-induced toxicity to the small intestine but cannot reduce the absorption of Cd.

Thermosonic wire bonding is a common fabrication process for connecting devices in electronic packaging. However, when the free air ball (FAB) is compressed onto the I/O pad of the chip during bonding procedure, chip cracking may occur if the contact pressure is too large. This study proposes an effective simulation technique that can predict the wire ball geometry after bonding in an accurate range. The contact force obtained in the simulation can be used for possible die cracking behavior evaluation. The simulation in this study used the explicit time integration scheme to deal with the time marching problem, and the second-order precision arbitrary Lagrangian-Eulerian (ALE) algorithm was used to deal with the large deformation of the wire ball during the bonding process. In addition, the equilibrium smoothing algorithm in LS-DYNA can make the contact behavior and geometry of the bonding wire almost the same as the experiment, which can also significantly reduce the distortion of the mesh geometry after remeshing.

Using time-resolved laser-scanning confocal microscopy and ultrafast optical pump/THz probe spectroscopy, we measure photoluminescence (PL) and THz-conductivity in perovskite micro-crystals and films. PL quenching and lifetime variations occur from local heterogeneity. Ultrafast THz-spectra measure sharp quantum transitions from excitonic Rydberg states, providing weakly bound excitons with a binding energy of ~13.5 meV at low temperatures. Ab-initio electronic structure calculations give a direct band gap of 1.64 eV, a dielectric constant of ~18, heavy electrons, and light holes, resulting in weakly bound excitons, consistent with the binding energies from the experiment. The complementary spectroscopy and simulations reveal fundamental insights into perovskite light-matter interactions.

In liquid-filled batteries, the liquid electrolytes may escape or present a fire hazard and an inert spacer is needed to separate the electrodes. Alternative polymer-based electrolytes are of current technological interest. Solid polymer electrolytes are non-volatile, non-corrosive materials, which can readily be processed into any shape or size. However, despite possessing the required mechanical properties, they have inherently lower conductivity. Gel-based systems are an attempt to strike a balance between the high conductivity of organic liquid electrolytes and the dimensional stability of a solid polymer.

Rectorite was modified with dodecyl benzyl dimethyl ammonium chloride to form organic-modified rectorite (OREC). OREC was used as a filler additive to modify gel polymer electrolytes (GPEs) and prepare composite gel polymer electrolytes (CPEs) which consisted of polymethyl methacrylate (PMMA) used as a polymer matrix, propylene carbonate (PC), used as a plasticizer, and LiClO4, used as a lithium ion producer. A variety of physical and chemical techniques was used to characterize the CPEs. The interlayer d spacing of OREC was much larger than that of the initial rectorite (2.22 nm). OREC also possesses a fine microscopic structure, and has a hydrophobic surface. Molau and XRD analysis of CPEs indicate that OREC has good compatibility with the components of CPEs and can be dispersed well. The effects of temperature and OREC dose on properties were studied. The temperature dependence of ionic conductivity of CPEs is well fitted by the VTF (Vogel-Tamman-Fulcher) relation. OREC doses of 5 phr gave the greatest ionic conductivity. This amount also greatly increased the plasticizer maintenance levels. Due to the occupancy of free volume space in the polymer matrix of CPEs by OREC, the bulk resistance of the CPEs was lowered and the glass transition temperature (T g) increased. The sheet structure of OREC is thought to improve the decomposition temperature of CPEs.

Physical and chemical properties of graphene-metal interfaces have been largely examined with the objective of producing nanostructured carbon-based electronic devices. Although electronic properties are key to such devices, appropriate structural, thermal and mechanical properties are important for device performance as well. One of the most studied is the graphene-titanium (G-Ti) interface. Titanium is a low density, high strength versatile metal that can form alloys with desirable properties for applications ranging from aerospace to medicine. Small clusters and thin films of titanium deposited on graphene have also been examined. However, while some experiments show that thin films of titanium on graphene can be removed without damaging graphene hexagonal structure, others reported the formation of titanium-carbide (TiC) at G-Ti interfaces. In a previous work [ACS Appl. Mater. Interfaces, 2017, 9 (38), pp 33288-33297], we have shown that pristine G-Ti interfaces are resilient to large thermal fluctuations even when G-Ti structures lie on curved or kinked substrates. Here, using classical molecular dynamics with the third-generation Charge Optimized Many Body (COMB3) potential, we show that di-interstitial defective G-Ti structures on a copper substrate with a relatively large curvature kink, present signs of TiC formation. This result might help explain the different experimental results mentioned above.

The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.

The objectives of this study were to determine the effect and mode of action of Saccharomyces cerevisiae (YST2) on enteric methane (CH4) mitigation in pigs. A total of 12 Duroc×Landrace×Yorkshire male finisher pigs (60±1 kg), housed individually in open-circuit respiration chambers, were randomly assigned to two dietary groups: a basal diet (control); and a basal diet supplemented with 3 g/YST2 (1.8×1010 live cells/g) per kg diet. At the end of 32-day experiment, pigs were sacrificed and redox potential (Eh), pH, volatile fatty acid concentration, densities of methanogens and acetogens, and expression of methyl coenzyme-M reductase subunit A gene were determined in digesta contents from the cecum, colon and rectum. Results showed that S. cerevisiae YST2 decreased (P<0.05) the average daily enteric CH4 production by 25.3%, lowered the pH value from 6.99 to 6.69 in the rectum, and increased the Eh value in cecum and colon by up to −55 mV (P<0.05). Fermentation patterns were also altered by supplementation of YST2 as reflected by the lower acetate, and higher propionate molar proportion in the cecum and colon (P<0.05), resulting in lower acetate : propionate ratio (P<0.05). Moreover, there was a 61% decrease in Methanobrevibacter species in the upper colon (P<0.05) and a 19% increase in the acetogen community in the cecum (P<0.05) of treated pigs. Results of our study concluded that supplementation of S. cerevisiae YST2 at 3 g/kg substantially decreased enteric CH4 production in pigs.

The Jurassic Linglong granites, intrusive into the North China Craton (NCC) in eastern China, provide a critical record of the first major episode of lithospheric-scale extension and magmatism in NE China during Mesozoic time. Our U–Pb zircon dating reveals that the Linglong granites were emplaced during 161–158 Ma, shortly after the inception of a shallow subduction of the Palaeo-Pacific plate beneath East Asia during Middle Jurassic time. These granites have high alkali contents (K2O + Na2O = 8–9 wt%), low MgO and Mg no. values and variable Cr–Ni abundances. Their relatively high Ba and Sr concentrations, relatively low heavy rare Earth element (HREE) and strongly fractionated REE patterns characterize them as high Ba–Sr granites. The negative whole-rock εNd(t) values ranging from −22.4 to −10.9 and wide-ranging zircon εHf(t) values of −39.1 to −1.5 suggest that magmas of the Linglong granites were produced by partial melting of a garnet-amphibolite-bearing lower crust of the Jiaobei Terrane and by re-melting of the Triassic ultrahigh-pressure (UHP) metamorphic rocks and alkaline suites of the Sulu Terrane. The occurrence in the granitic rocks of inherited zircons of the Neoarchaean, Palaeoproterozoic, Neoproterozoic, Palaeozoic and Triassic ages suggests that magmas of the Linglong granites interacted with the ancient crust in these terranes during their ascent. Asthenospheric upwelling, induced by the steepening and rapid rollback of the Palaeo-Pacific slab during Late Jurassic time, provided the heat source for the inferred lower crustal melting. Trench migration and thermal weakening of the crust caused extensional deformation and thinning in the eastern part of the NCC.

To alleviate adverse effects of heavy metal toxicity, diverse range of removing methods have been suggested, that is usage of algae, agricultural by-products and microorganisms. Here, we investigated lead (Pb) biosorption efficacy by two lactic acid bacteria species (LABs) in broiler chickens. In an in vitro study, Pb was added to culture medium of LABs (Lactobacillus pentosus ITA23 and Lactobacillus acidipiscis ITA44) in the form of lead acetate. Results showed that these LABs were able to absorb more than 90% of Pb from the culture medium. In follow-up in vivo study, LABs mixture was added to diet of broiler chickens contained lead acetate (200 mg/kg). Pb exposure significantly increased lipid peroxidation and decreased antioxidant activity in liver. The changes were recovered back to normal level upon LABs supplementation. Moreover, addition of LABs eliminated the liver tissue lesion and the suppressed performance in Pb-exposed chicks. Analysis of liver and serum samples indicated 48% and 28% reduction in Pb accumulation, respectively. In conclusion, results of this study showed that L. pentosus ITA23 and L. acidipiscis ITA44 effectively biosorb and expel dietary Pb from gastrointestinal tract of chickens.

Presently, physical limitations are restricting the development of the microelectronic industry driven by Moore's law. To achieve high-performance, small form factor, and lightweight applications, new electronic packaging methods have exceeded Moore's law. This research proposes a double-chip stacking structure in an embedded fan-out wafer-level packaging with double-sided interconnections. The overall reliability of the solder joints and redistributed lines is assessed through finite element analysis. The application of soft lamination material and selection of a carrier material whose coefficient of thermal expansion (CTE) is close to that of the printed circuit board can effectively enhance the reliability of solder joints over more than 1,000 cycles. A trace/pad junction whose direction is parallel to the major direction of the CTE mismatch is recommended, and the curved portion of trace lines can absorb the expansion of metal lines and filler material. Design-on-simulation methodology is necessary to develop novel packaging structures in the electronic packaging industry.