This study explores the capabilities of the Coherent X-ray Imaging Instrument at the Linac Coherent Light Source to image small biological samples. The weak signal from small samples puts a significant demand on the experiment. Aerosolized Omono River virus particles of ∼40 nm in diameter were injected into the submicrometre X-ray focus at a reduced pressure. Diffraction patterns were recorded on two area detectors. The statistical nature of the measurements from many individual particles provided information about the intensity profile of the X-ray beam, phase variations in the wavefront and the size distribution of the injected particles. The results point to a wider than expected size distribution (from ∼35 to ∼300 nm in diameter). This is likely to be owing to nonvolatile contaminants from larger droplets during aerosolization and droplet evaporation. The results suggest that the concentration of nonvolatile contaminants and the ratio between the volumes of the initial droplet and the sample particles is critical in such studies. The maximum beam intensity in the focus was found to be 1.9 × 10¹² photons per µm² per pulse. The full-width of the focus at half-maximum was estimated to be 500 nm (assuming 20% beamline transmission), and this width is larger than expected. Under these conditions, the diffraction signal from a sample-sized particle remained above the average background to a resolution of 4.25 nm. The results suggest that reducing the size of the initial droplets during aerosolization is necessary to bring small particles into the scope of detailed structural studies with X-ray lasers.

Infection after renal transplantation remains a major cause of morbidity and death, especially infection from the extensively drug-resistant bacteria, A. baumannii. A total of fourteen A. baumannii isolates were isolated from the donors’ preserved fluid from DCD (donation after cardiac death) renal transplantation and four isolates in the recipients’ draining liquid at the Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, from March 2013 to November 2014. An outbreak of A. baumannii emerging after DCD renal transplantation was tracked to understand the transmission of the pathogen. PFGE displayed similar DNA patterns between isolates from the same hospital. Antimicrobial susceptibility tests against thirteen antimicrobial agents were determined using the K-B diffusion method and eTest. Whole-genome sequencing was applied to investigate the genetic relationship of the isolates. With the clinical data and research results, we concluded that the A. baumannii isolates 3R1 and 3R2 was probably transmitted from the donor who acquired the bacteria during his stay in the ICU, while isolate 4R1 was transmitted from 3R1 and 3R2 via medical manipulation. This study demonstrated the value of integration of clinical profiles with molecular methods in outbreak investigation and their importance in controlling infection and preventing serious complications after DCD transplantation.

Climate change could significantly affect consumer demand for energy in buildings, as changing temperatures may alter heating and cooling loads. Warming climates could also lead to the increased adoption and use of cooling technologies in buildings. We assess residential electricity and natural gas demand in Los Angeles, California under multiple climate change projections and investigate the potential for energy efficiency to offset increased demand. We calibrate residential energy use against metered data, accounting for differences in building materials and appliances. Under temperature increases, we find that without policy intervention, residential electricity demand could increase by as much as 41–87% between 2020 and 2060. However, aggressive policies aimed at upgrading heating/cooling systems and appliances could result in electricity use increases as low as 28%, potentially avoiding the installation of new generation capacity. We therefore recommend aggressive energy efficiency, in combination with low-carbon generation sources, to offset projected increases in residential energy demand.

Exosomes are nanoscale extracellular vesicles that are shed from different cells in the body. Exosomes encapsulate several biomolecules including lipids, proteins, and nucleic acids, and can therefore play a key role in cellular communication. These vesicles can be isolated from different body fluids and their small sizes make them attractive in various biomedical applications. Here, we review state-of-the art approaches in exosome isolation and purification, and describe their potential use in cancer vaccines, drug delivery, and diagnostics.

A mixed design was created using text and game-like multimedia to instruct in the content of physics. The study assessed which variables predicted learning gains after a 1-h lesson on the electric field. The three manipulated variables were: (1) level of embodiment; (2) level of active generativity; and (3) presence of story narrative. Two types of tests were administered: (1) a traditional text-based physics test answered with a keyboard; and (2) a more embodied, transfer test using the Wacom large tablet where learners could use gestures (long swipes) to create vectors and answers. The 166 participants were randomly assigned to four conditions: (1) symbols and text; (2) low embodied; (3) high embodied/active; or (4) high embodied/active with narrative. The last two conditions were active because the on-screen content could be manipulated with gross body gestures gathered via the Kinect sensor. Results demonstrated that the three groups that included embodiment learned significantly more than the symbols and text group on the traditional keyboard post-test. When knowledge was assessed with the Wacom tablet format that facilitated gestures, the two active gesture-based groups scored significantly higher. In addition, engagement scores were significantly higher for the two active embodied groups. The Wacom results suggest test sensitivity issues; the more embodied test revealed greater gains in learning for the more embodied conditions. We recommend that as more embodied learning comes to the fore, more sensitive tests that incorporate gesture be used to accurately assess learning. The predicted differences in engagement and learning for the condition with the graphically rich story narrative were not supported. We hypothesize that a narrative effect for motivation and learning may be difficult to uncover in a lab experiment where participants are primarily motivated by course credit. Several design principles for mediated and embodied science education are proposed.

Course-based undergraduate research experiences (CUREs) meet national recommendations for integrating research experiences into life science curricula. As such, CUREs have grown in popularity and many research studies have focused on student outcomes from CUREs. Institutional change literature highlights that understanding faculty is also key to new pedagogies succeeding. To begin to understand faculty perspectives on CUREs, we conducted semi-structured interviews with 61 faculty who teach CUREs regarding why they teach CUREs, what the outcomes are, and how they would discuss a CURE with a colleague. Using grounded theory, participant responses were coded and categorized as tangible or intangible, related to both student and faculty-centered themes. We found that intangible themes were prevalent, and that there were significant differences in the emphasis on tangible themes for faculty who have developed their own independent CUREs when compared with faculty who implement pre-developed, national CUREs. We focus our results on the similarities and differences among the perspectives of faculty who teach these two different CURE types and explore trends among all participants. The results of this work highlight the need for considering a multi-dimensional framework to understand, promote, and successfully implement CUREs.

We recommend using backward design to develop course-based undergraduate research experiences (CUREs). The defining hallmark of CUREs is that students in a formal lab course explore research questions with unknown answers that are broadly relevant outside the course. Because CUREs lead to novel research findings, they represent a unique course design challenge, as the dual nature of these courses requires course designers to consider two distinct, but complementary, sets of goals for the CURE: 1) scientific discovery milestones (i.e., research goals) and 2) student learning in cognitive, psychomotor, and affective domains (i.e., pedagogical goals). As more undergraduate laboratory courses are re-imagined as CUREs, how do we thoughtfully design these courses to effectively meet both sets of goals? In this Perspectives article, we explore this question and outline recommendations for using backward design in CURE development.

Nursing behavior is notoriously difficult to study in arboreal primates, particularly when offspring suckle inconspicuously in nests. Orangutans have the most prolonged nursing period of any mammal, with the cessation of suckling (weaning) estimated to occur at 6 to 8 years of age in the wild. Milk consumption is hypothesized to be relatively constant over this period, but direct evidence is limited. We previously demonstrated that trace element analysis of bioavailable elements from milk, such as barium, provides accurate estimates of early-life diet transitions and developmental stress when coupled with growth lines in the teeth of humans and nonhuman primates. We provide the first detailed nursing histories of wild, unprovisioned orangutans (Pongo abelii and Pongo pygmaeus) using chemical and histological analyses. Laser ablation inductively coupled plasma mass spectrometry was used to determine barium distributions across the teeth of four wild-shot individuals aged from postnatal biological rhythms. Barium levels rose during the first year of life in all individuals and began to decline shortly after, consistent with behavioral observations of intensive nursing followed by solid food supplementation. Subsequent barium levels show large sustained fluctuations on an approximately annual basis. These patterns appear to be due to cycles of varying milk consumption, continuing until death in an 8.8-year-old Sumatran individual. A female Bornean orangutan ceased suckling at 8.1 years of age. These individuals exceed the maximum weaning age reported for any nonhuman primate. Orangutan nursing may reflect cycles of infant demand that relate to fluctuating resource availability.

The Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 Å. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD). This architecture enables allosteric interactions between the domains that are important for ligand recognition and receptor activation. By combining the structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and the HD play a central role in transmitting the signal employing a unique GPCR activation mechanism, distinct from other multi-domain GPCRs.

This study investigates the presence of dynamical patterns of interpersonal coordination in extended deceptive conversations across multimodal channels of behavior. Using a novel "devil’s advocate" paradigm, we experimentally elicited deception and truth across topics in which conversational partners either agreed or disagreed, and where one partner was surreptitiously asked to argue an opinion opposite of what he or she really believed. We focus on interpersonal coordination as an emergent behavioral signal that captures interdependencies between conversational partners, both as the coupling of head movements over the span of milliseconds, measured via a windowed lagged cross correlation (WLCC) technique, and more global temporal dependencies across speech rate, using cross recurrence quantification analysis (CRQA). Moreover, we considered how interpersonal coordination might be shaped by strategic, adaptive conversational goals associated with deception. We found that deceptive conversations displayed more structured speech rate and higher head movement coordination, the latter with a peak in deceptive disagreement conversations. Together the results allow us to posit an adaptive account, whereby interpersonal coordination is not beholden to any single functional explanation, but can strategically adapt to diverse conversational demands.