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OBJECTIVES/GOALS: Utilize polymer-based fiber scaffolds and machine learning methods applied to patient biomarker data to enhance and personalize T cell expansion and production for T cell therapy in chronic lymphocytic leukemia. METHODS/STUDY POPULATION: Scaffolds are 1) generated from a co-polymer blend of PDMS and PCL with controlled fiber diameters and pore size, 2) coated with activating antibodies to CD3 and CD28, and 3) used to stimulate T cells from both healthy donors and CLL patients. CLL patients have pre-annotated mutation burdens and clinical biomarkers. T cell populations will be analyzed for exhaustion markers and phenotypes before, during, and after expansion. Cell functionality will be measured by cytokine secretion, cell cycle analysis, and fold expansion, with respect to platform parameters, and analyzed with inputs of disease markers and exhaustion profile of isolated T cells using regression and random forest classifiers. RESULTS/ANTICIPATED RESULTS: We previously showed that engineering the mechanical rigidity of activating substrates can enhance and rescue T cell expansion from exhausted populations. Now we aim to study a broader range of compositions and geometry of scaffolds with respect to capacity to expand CLL T cells. Preliminary data with fiber diameters ranging from 300 nm to 6 um confirm the effect of geometry in modulating expansion. A biorepository of T cells from 80 CLL patients have been isolated concurrently. Anticipated results include correlating exhaustion profile of T cells with clinical biomarkers and identifying markers associated with expansion on panel of platform parameters. DISCUSSION/SIGNIFICANCE OF IMPACT: T cell therapy has shown particular promise in treating blood cancers, yet significant percentage of T cells isolated from patients undergoing treatments are unresponsive to activation. A powerful tool is to predict if and how patient T cells can be robustly expanded on a personalized approach.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
Multifunctional nanoparticles are an emerging area of research, impacting numerous fields ranging from biomedical applications to energy. While initial core–shell structures consisted of similar materials, such as Au–Ag or CdTe–CdSe nanoparticles, recent work has expanded this line of investigation to include particles of dissimilar materials. However, there are several challenges when synthesizing dissimilar material systems. In this work, a method for doping the shell of an Au–ZnO nanosphere is demonstrated. Several metal dopants are investigated, including Cu, Ce, Er, Nd, Tm, and Yb. The ZnO shell is nucleated on the gold nanosphere core via an ascorbic acid–assisted growth, and the dopant is intercalated uniformly into the shell during the self-assembly phase of the shell formation. The doping and polycrystalline shell are confirmed using a series of qualitative and quantitative methods. This multi-material nanoparticle synthesis strategy opens the door for future applications in sensing, photocatalysis, and bioimaging.
Perceived loneliness, an increasingly prevalent social issue, is closely associated with major depressive disorder (MDD). However, the neural mechanisms previously implicated in key cognitive and affective processes in loneliness and MDD still remain unclear. Such understanding is critical for delineating the psychobiological basis of the relationship between loneliness and MDD.
We isolated the unique and interactive cognitive and neural substrates of loneliness and MDD among 27 MDD patients (mean age = 51.85 years, 20 females), and 25 matched healthy controls (HCs; mean age = 48.72 years, 19 females). We assessed participants' behavioral performance and neural regional and network functions on a Stroop color-word task, and their resting-state neural connectivity.
Behaviorally, we found greater incongruence-related accuracy cost in MDD patients, but reduced incongruence effect on reaction time in lonelier individuals. When performing the Stroop task, loneliness positively predicted prefrontal-anterior cingulate-parietal connectivity across all participants, whereas MDD patients showed a decrease in connectivity compared to controls. Furthermore, loneliness negatively predicted parietal and cerebellar activities in MDD patients, but positively predicted the same activities in HCs. During resting state, MDD patients showed reduced parietal-anterior cingulate connectivity, which again positively correlated with loneliness in this group.
We speculate the distinct neurocognitive profile of loneliness might indicate increase in both bottom-up attention and top-down executive control functions. However, the upregulated cognitive control processes in lonely individuals may eventually become exhausted, which may in turn predispose to MDD onset.
The co-occurrence of hepatic cystic echinococcosis (CE) and alveolar echinococcosis (AE) is extremely rare. Here, we present the clinical manifestations and treatment outcomes of three cases with co-occurring CE and AE in the liver. Computed tomography (CT), magnetic resonance imaging and 18FFluorodeoxyglucose Positron Emission Tomography-CT were used for preoperative diagnosis. Specimens were taken intraoperatively and sent for pathological studies to confirm the coexistence of CE and AE by laminated membrane, daughter cysts or germinal layer and infiltration structure. Albendazole was prescribed after operation for 12 months. All patients were completely recovered and showed no recurrence at last follow-up. Therefore, surgical intervention and postoperative application of albendazole are recommended for patients with concurrence of hepatic AE and CE.
Investigate short- and long-term effects of Superstorm Sandy on multiple morbidities among the elderly.
We examined emergency department visits; outpatient visits; and hospital admissions for cardiovascular disease (CVD), respiratory disease, and injury among residents residing in 8 affected counties immediately, 4 months, and 12 months following Superstorm Sandy. Control groups were defined as visits/admissions during the identical time window in the 5 years before (2007-2011) and 1 year after (2013-2014) the storm in affected and nonaffected counties in New York. We performed Poisson regression to test whether there was an association of increased visits/admissions for periods following Superstorm Sandy while controlling for covariates.
We found that the risk for CVD, respiratory disease, and injury visits/admissions was more than twice as high immediately, 4 months, and 12 months after the storm than it was in the control periods. Women were at greater risk at all time periods for CVD (risk ratio [RR], 2.04) and respiratory disease (RRs: 1.89 to 1.92). Whites had higher risk for CVD, respiratory disease, and injury than other racial groups during each period.
We observed increases in CVD, respiratory disease, and injury up to a year following Superstorm Sandy. Findings demonstrate the need to incorporate short- and long-term health effects into public health recovery. (Disaster Med Public Health Preparedness. 2019;13:28-32)
The bulk van der Waals crystal Mn3Si2Te6 (MST) has been irradiated with a proton beam of 2 MeV at a fluence of 1×1018 H+ cm-2. The temperature dependent magnetization measurements show a drastic decrease in the magnetization of 49.2% in the H//c direction observed in ferrimagnetic state. This decrease in magnetization is also reflected in the isothermal magnetization curves. No significant change in the ferrimagnetic transition temperature (75 K) was reflected after irradiation. Electron paramagnetic resonance (EPR) spectroscopy shows no magnetically active defects present after irradiation. Here, experimental findings gathered from MST bulk crystals via magnetic measurements, magnetocaloric effect, and heat capacity are discussed.
van der Waals (vdW) magnetic materials show promise in being the foundation for future spintronic technology. The magnetic behavior of Fe2.7GeTe2 (FGT), a vdW itinerant ferromagnet, was investigated before and after proton irradiation. Proton irradiation of the sample was carried out at a fluence of 1×1018 cm-2. The magnetization measurements revealed a small increase of saturation magnetization (Ms) of about 4% upon proton irradiation of the sample, in which, the magnetic field was applied parallel to the c-axis. X-ray photoelectron spectroscopy for pristine and irradiated FGT revealed a general decrease in intensity after irradiation for Ge and Te and an increase in peak intensity of unavoidable surface iron oxide. Furthermore, no noticeable change in the Curie temperature (TC =152 K) is observed in temperature dependent magnetization variation. This work signifies the importance of employing protons in tuning the magnetic properties of vdW materials.
To validate a system to detect ventilator associated events (VAEs) autonomously and in real time.
Retrospective review of ventilated patients using a secure informatics platform to identify VAEs (ie, automated surveillance) compared to surveillance by infection control (IC) staff (ie, manual surveillance), including development and validation cohorts.
The Massachusetts General Hospital, a tertiary-care academic health center, during January–March 2015 (development cohort) and January–March 2016 (validation cohort).
Ventilated patients in 4 intensive care units.
The automated process included (1) analysis of physiologic data to detect increases in positive end-expiratory pressure (PEEP) and fraction of inspired oxygen (FiO2); (2) querying the electronic health record (EHR) for leukopenia or leukocytosis and antibiotic initiation data; and (3) retrieval and interpretation of microbiology reports. The cohorts were evaluated as follows: (1) manual surveillance by IC staff with independent chart review; (2) automated surveillance detection of ventilator-associated condition (VAC), infection-related ventilator-associated complication (IVAC), and possible VAP (PVAP); (3) senior IC staff adjudicated manual surveillance–automated surveillance discordance. Outcomes included sensitivity, specificity, positive predictive value (PPV), and manual surveillance detection errors. Errors detected during the development cohort resulted in algorithm updates applied to the validation cohort.
In the development cohort, there were 1,325 admissions, 479 ventilated patients, 2,539 ventilator days, and 47 VAEs. In the validation cohort, there were 1,234 admissions, 431 ventilated patients, 2,604 ventilator days, and 56 VAEs. With manual surveillance, in the development cohort, sensitivity was 40%, specificity was 98%, and PPV was 70%. In the validation cohort, sensitivity was 71%, specificity was 98%, and PPV was 87%. With automated surveillance, in the development cohort, sensitivity was 100%, specificity was 100%, and PPV was 100%. In the validation cohort, sensitivity was 85%, specificity was 99%, and PPV was 100%. Manual surveillance detection errors included missed detections, misclassifications, and false detections.
Manual surveillance is vulnerable to human error. Automated surveillance is more accurate and more efficient for VAE surveillance.
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 present study investigated the effects of different levels of urea nitrogen (N) fertilizer on nutrient accumulation, in vitro rumen gas production and fermentation characteristics of forage oat straw (FOS) from oats (Avena sativa L. ‘Qinghai 444’) grown in the Tibet region of China. Fertilizer, applied at seeding (day 1), stem elongation (days 52–54) and heading (days 63–67), increased plant height and prolonged the maturity stage of the plant by 4–11 days compared with the non-fertilized control. Oat plants were harvested at maturity at the node 3–4 cm above ground, and then separated into grains and FOS. Both FOS and grain yields increased quadratically with increasing N fertilization, and their theoretical maximums occurred at the N fertilizing rates of 439 and 385 kg/ha, respectively. Increases in N fertilization did not affect the hemicellulose content of FOS, but substantially promoted the accumulation of crude protein, cellulose and lignin, resulting in a decrease in the energy content available for metabolism. A 72-h incubation of FOS with rumen fluids from lactating cows showed that increasing N resulted in FOS that showed a slower fermentation rate, decreased in vitro dry matter disappearance and lower cumulative gas production, but unchanged fermentation gas composition. Nitrogen fertilization increased the final pH in culture fluids and decreased the microbial volatile fatty acid (VFA) production. The molar proportions of acetate and propionate were not affected, but molar propionate proportion decreased linearly with increasing urea fertilization, and consequently, the ratio of lipogenic (e.g., acetate and butyrate)-to-glucogenic acids (propionate) tended to increase. In brief, increasing urea N fertilization promoted the growth of forage oats and increased the biomass yield as well as the crude protein and cellulose content of FOS. Considering the negative effect of increased lignin content on nutrient digestibility and total VFA production, the suggested range of urea N fertilization is 156–363 kg N/ha for forage oats planted in Tibet to retain the nutritive value of FOS in the rumen.
Legionnaires’ disease (LD) is a globally distributed systemic infectious disease. The burden of LD in many regions is still unclear, especially in Asian countries including China. A survey of Legionella infection using real-time PCR and nested sequence-based typing (SBT) was performed in two hospitals in Shanghai, China. A total of 265 bronchoalveolar lavage fluid (BALF) specimens were collected from hospital A between January 2012 and December 2013, and 359 sputum specimens were collected from hospital B throughout 2012. A total of 71 specimens were positive for Legionella according to real-time PCR focusing on the 5S rRNA gene. Seventy of these specimens were identified as Legionella pneumophila as a result of real-time PCR amplification of the dotA gene. Results of nested SBT revealed high genetic polymorphism in these L. pneumophila and ST1 was the predominant sequence type. These data revealed that the burden of LD in China is much greater than that recognized previously, and real-time PCR may be a suitable monitoring technology for LD in large sample surveys in regions lacking the economic and technical resources to perform other methods, such as urinary antigen tests and culture methods.
A completely randomized experiment for planting highland barley in 36 field plots of the Lhasa Agricultural Experiment Station was applied to investigate the effect of urea nitrogen (N) fertilization levels of 0 (control), 156, 258, 363, 465 and 570 kg/ha on nutrient accumulation, in vitro rumen gas production and fermentation characteristics of highland barley straw (HBS). Each urea application was divided into three portions of 0.4, 0.3 and 0.3 and sequentially fertilized at seeding (growth stage (GS) 0), stem elongation (GS 32) and heading (GS 49), respectively. The maturity stage lasted 5–13 days longer in response to the urea N fertilization compared with the control. After removing grains, HBS biomass was harvested at maturity. The biomass yields of leaf, stem, straw and grain were increased quadratically with increasing urea N fertilization, and HBS and grain yields peaked at the estimated urea N fertilization levels of 385 and 428 kg/ha, respectively. The increase of urea N fertilization increased the accumulation of crude protein, cellulose and lignin, and decreased the content of ash and hemicellulose in HBS, resulting in a decrease of the energy content available to be metabolized. After incubating HBS for 72 h with rumen fluids from lactating cows, the urea N fertilization decreased in vitro dry matter disappearance and cumulative gas production, and slightly altered fermentation end-gas composition. Urea N fertilization decreased microbial volatile fatty acid production, but did not alter the ratio of lipogenic acetate and butyrate to glucogenic propionate. In a brief, the current urea N fertilization strategy promoted the growth of the highland barley and increased biomass yield, protein and cellulose accumulation of HBS. A urea N fertilization level ⩽385 kg/ha could be sufficient for growth of highland barley in Tibet without a consequent nutritive reduction in ruminal digestion.
We compare the host galaxies of 902 supernovae, including Type Ia, II and Ibc, which are selected by cross-matching the Asiago Supernova Catalog with the SDSS DR7. We further selected 213 galaxies by requiring the light fraction of spectral observations > 15%, which could represent well the global properties of the galaxies. The diagrams related to Dn(4000), HδA, stellar masses, SFRs and specific SFRs for the SNe hosts show that almost all SNe II and most of SNe Ibc occur in SF galaxies. A significant fraction of SNe Ia occurs in AGNs and Absorp galaxies. These results are compared with those of the 689 comparison galaxies where the SDSS fiber captures < 15% of the total light. These comparison galaxies appear biased towards higher 12+log(O/H) (~0.1dex) at a given stellar mass, suggesting the aperture effect should be kept in mind when the properties of the hosts for different types of SNe are discussed.
Hemispherical electron plasma waves generated from ultraintense laser interacting with a solid target having a subcritical preplasma is studied using particle-in-cell simulation. As the laser pulse propagates inside the preplasma, it becomes self-focused due to the response of the plasma electrons to the ponderomotive force. The electrons are mainly heated via betatron resonance absorption and their thermal energy can become higher than the ponderomotive energy. The hot electrons easily penetrate through the thin solid target and appear behind it as periodic hemispherical shell-like layers separated by the laser wavelength.
The biochemical basis of resistance to the acetyl-coenzyme A carboxylase
(ACCase)-inhibiting herbicide diclofop-methyl was investigated in a
resistant wild oat population (R1), which does not exhibit a resistant
ACCase. Rates of foliar uptake and translocation of
[14C]-diclofop were the same in the R1 vs. susceptible (S)
populations. However, the level of phytotoxic diclofop acid was always found
to be lower in the R1 vs. S plants, with a concomitant higher level (up to
1.7-fold) of nontoxic polar diclofop metabolites in R1 relative to the S
plants. These results indicate that a non–target-site-based mechanism of
enhanced rate of diclofop acid metabolism confers resistance in population
R1. Moreover, the high-performance liquid chromotography elution profile of
the major diclofop metabolites in R1 is similar to that of wheat, suggesting
resistance in individuals of population R1 involves a wheat-like
detoxification system mediated by cytochrome P450 monooxygenases. In
addition, lower level of tissue diclofop acid was also observed using
nonradioactive ultra-performance liquid chromatography–mass spectrometry
analysis in resistant individuals of three other resistant wild oat
populations (R2, R3, and R4) known to posses ACCase gene resistance
mutations. These results establish that either one or at least two
independent resistance mechanisms (target-site ACCase resistance mutations
and non–target-site enhanced rates of herbicide metabolism) can be present
in individual wild oat plants.
We performed a thorough investigation of mid-infrared heavy-to-light hole intersubband absorption in the valence band of p-doped GaAs quantum wells with AlAs barriers. For the p-type doping a high-purity solid carbon source was used. The experimental results are compared with theoretical simulations. The inclusion of layer inter-diffusion well reproduces the transition energies. We estimate a 6-10 Å inter-diffusion length that is consistent with electron microscopy measurements. A careful analysis of our results provides valuable information for further design of emitters and detectors based on hole intersubband transitions in the valence band.