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Background: Sickle cell disease is the most common human monogenetic disease, and its risks are amplified during pregnancy. Methods: This report describes a 35-year-old woman with HgbSS sickle cell disease who developed hyperhemolysis syndrome after undergoing an exchange transfusion during pregnancy. Results: In addition to conventional medical treatment, the patient received prepartum hyperbaric oxygen therapy (HBOT), totaling 17 treatments for the indication of severe anemia. She experienced significant clinical improvement while undergoing HBOT and ultimately delivered a healthy preterm infant by cesarean section. Conclusions: The risks, benefits, and challenges of using HBOT in this unique context are discussed.

Abstract Background Despite the low-risk nature of participation in most clinical anesthesia trials, subject recruitment on the same day as surgery is often restricted due to the concerns of researchers and local research ethics boards that same-day consent may not afford adequate time and opportunity for patients to weigh and make decisions, as well as perceptions of patient vulnerability immediately prior to surgery that could impact the voluntary nature and the rigor of the informed consent process. However, specialties such as anesthesiology, critical care, interventional radiology, and emergency medicine have a varied pattern of practice and patient acquaintance that does not typically afford the luxury of time or, in many cases, advance consent for participation in research. Indeed, the initial encounter between anesthesiologists and patients undergoing elective procedures routinely occurs on the day of surgery. Concerns of coercion related to same-day consent for clinical anesthesia research trials have not been borne out in the literature, and represent a significant obstacle to clinical researchers, as well as to the patients who are denied opportunities for potential benefit through participation in research studies. Methods We describe the protocol for a prospective randomized controlled trial examining the voluntariness of patient consent, solicited either in advance of surgery or on the same day, to participate in an anesthesia research study at Women’s College Hospital. One hundred fourteen patients scheduled to undergo ambulatory anterior cruciate ligament repair facilitated by general anesthesia with an adductor canal block will be randomized for recruitment either (a) in the pre-operative assessment clinic before the day of surgery or (b) on the day of surgery, to be approached for consent to participate in a fabricated research study of adjunct medications in adductor canal blocks. Regardless of allocation, patients in both groups will receive the same routine standard of care and will complete a post-operative questionnaire to signal perceptions of undue influence in the process of providing informed consent for the fabricated trial. Discussion This study will inform trial design and practice guidelines surrounding the amount of time patients ought to be afforded in order to make durable decisions to participate (or not) in clinical research studies. This is expected to impact trial recruitment in a variety of clinical settings where researchers have only brief opportunities to interface with patients. Trial registration The trial was registered prospectively on the Open Science Framework (OSF), registration #46twc, on 2023-Mar-17.

Abstract Shape transformations of active composites (ACs) depend on the spatial distribution of constituent materials. Voxel-level complex material distributions can be encoded by 3D printing, offering enormous freedom for possible shape-change 4D-printed ACs. However, efficiently designing the material distribution to achieve desired 3D shape changes is significantly challenging yet greatly needed. Here, we present an approach that combines machine learning (ML) with both gradient-descent (GD) and evolutionary algorithm (EA) to design AC plates with 3D shape changes. A residual network ML model is developed for the forward shape prediction. A global-subdomain design strategy with ML-GD and ML-EA is then used for the inverse material-distribution design. For a variety of numerically generated target shapes, both ML-GD and ML-EA demonstrate high efficiency. By further combining ML-EA with a normal distance-based loss function, optimized designs are achieved for multiple irregular target shapes. Our approach thus provides a highly efficient tool for the design of 4D-printed active composites.

Abstract Understanding how human activities affect wildlife is fundamental for global biodiversity conservation. Ongoing land use change and human‐induced climate change, compel species to adapt their behaviour in response to shifts in their natural environments. Such responses include changes to a species' diet or trophic ecology, with implications for the wider ecosystem. This is particularly the case for predatory species or those that occupy high positions within trophic webs, such as raptors. Between 2002 and 2019, we observed 1578 feeding events of the globally near threatened and understudied, Red‐necked Falcon (Falco chicquera) in Bangladesh. We explored the effects of mean monthly temperature, precipitation, temperature differences, and urban land cover on (a) mean prey weights and (b) dietary composition of 15 falcon pairs. Falcons hunted smaller prey items during months with increased temperatures and precipitation, and in more urban areas. However, during months with increased temperature differences, falcons tended to prey on larger prey items. Being specialist aerial hunters, these dietary patterns were largely driven by the probabilities of bats and birds in the diet. Falcons were more likely to prey on bats during warmer and wetter months. Furthermore, urban pairs tended to prey on bats, whereas more rural pairs tended to prey on birds. Mean monthly temperature difference, i.e., a proxy for climate change, was better at explaining the probability of bats in the falcon diet than mean monthly temperature alone. Anthropogenic dietary shifts can have deleterious effects on species with declining populations or those of conservation concern. The effects of urbanisation and human‐induced climate change are expected to continue into the foreseeable future. Therefore, our findings represent a cornerstone in our understanding of how falcons respond to an increasingly human‐dominated world.

We take a bottom-up first-principles approach to designing a two-qubit gate between fluxonium qubits for minimal error, speed, and control simplicity. Our proposed architecture consists of two fluxoniums coupled via a resonator. The use of a simple linear coupler has many practical benefits, including the possibility of material optimization for suppressing loss, reducing fabrication complexity, and increasing yield by circumventing the need for Josephson junctions. Crucially, a resonator-as-coupler approach also suggests a clear path to increased connectivity between fluxonium qubits, by reducing capacitive loading when the coupler has a high impedance. After performing analytic and numerical analyses of the circuit Hamiltonian and gate dynamics, we tune circuit parameters to destructively interfere sources of coherent error, revealing an efficient fourth-order scaling of coherent error with gate duration. For component properties from the literature, we predict an open-system average controlled-Z (cz) gate infidelity of 1.86×10^{−4} in 70 ns.

Abstract To date, studies have not yet established the mechanisms underpinning differences in autistic and non-autistic emotion recognition. The current study first investigated whether autistic and non-autistic adults differed in terms of the precision and/or differentiation of their visual emotion representations and their general matching abilities, and second, explored whether differences therein were related to challenges in accurately recognizing emotional expressions. To fulfil these aims, 45 autistic and 45 non-autistic individuals completed three tasks employing dynamic point light displays of emotional facial expressions. We identified that autistic individuals had more precise visual emotion representations than their non-autistic counterparts, however, this did not confer any benefit for their emotion recognition. Whilst for non-autistic people, non-verbal reasoning and the interaction between precision of emotion representations and matching ability predicted emotion recognition, no variables contributed to autistic emotion recognition. These findings raise the possibility that autistic individuals are less guided by their emotion representations, thus lending support to Bayesian accounts of autism.

Summary: We investigated whether birds build nests in repeatable styles and, if so, whether styles were associated with past nest-building experience. Laboratory, captive bred zebra finches in an Experimental group were given nest-building experience, whereas, birds in a Control group were not. Each pair (n = 20) then built four nests that underwent image analyses for nest size, geometric shape and entrance orientation. Birds built nests in repeatable styles, with lower morphometric variation among nests built by the same pair and higher morphometric variation among nests built by different pairs. Morphology was not associated with construction time, body weight, nor age of birds. We found lower morphometric variation among nests built by the Experimental group, which also used less material to build nests compared to the Control group. Prior experience may therefore have been advantageous, as learning to reduce material usage while achieving a similar product (nest) may have lowered building costs.

Abstract Background The expectation of pandemic-induced severe resource shortages has prompted authorities to draft and update frameworks to guide clinical decision-making and patient triage. While these documents differ in scope, they share a utilitarian focus on the maximization of benefit. This utilitarian view necessarily marginalizes certain groups, in particular individuals with increased medical needs. Main body Here, we posit that engagement with the disability critique demands that we broaden our understandings of justice and fairness in clinical decision-making and patient triage. We propose the capabilities theory, which recognizes that justice requires a range of positive capabilities/freedoms conducive to the achievement of meaningful life goals, as a means to do so. Informed by a disability rights critique of the clinical response to the pandemic, we offer direction for the construction of future clinical triage protocols which will avoid ableist biases by incorporating a broader apprehension of what it means to be human. Conclusion The clinical pandemic response, codified across triage protocols, should embrace a form of justice which incorporates a vision of pluralistic human capabilities and a valuing of positive freedoms.

Traditional methods of capturing people’s dietary intake are complex and labour-intensive, requiring a high level of literacy and time. Speech recording has potential to reduce these barriers, and recent technological advances have greatly increased the viability of this approach. The aim of this paper is to establish the current state of research on the usage of speech records in dietary assessment. To this end, we performed a systematic literature review and summarised the current state of research along a conceptual framework that captures the components involved in using speech records for dietary assessment. Six databases from the nutrition and computing domains were interrogated, resulting in 21 relevant papers. Speech recording in an unstructured format was preferred when compared against other methods by all three studies reporting comparisons. High technological satisfaction and ease of use were noted by all eight studies reporting user acceptance. When recording data, 78% of studies focused on collecting prospective food records. The choice of device reflected this, with 15 of 18 studies reporting a form of handheld, portable collection device intended to be always available. To process data, nine studies performed automated speech transcription achieving an average accuracy of 83%, seven of which utilized a readily available commercial service. Of the five studies that used natural language processing to further automate analysis, an average accuracy of 82% was reported. Further research is required to adapt these prototypes to address practical challenges in dietary assessment and monitoring (e.g. self-monitoring for low-literacy users).

Abstract Background An increasing body of evidence implicates the resident gut microbiota as playing a critical role in type 2 diabetes (T2D) pathogenesis. We previously reported significant improvement in postprandial glucose control in human participants with T2D following 12-week administration of a 5-strain novel probiotic formulation (‘WBF-011’) in a double-blind, randomized, placebo controlled setting (NCT03893422). While the clinical endpoints were encouraging, additional exploratory measurements were needed in order to link the motivating mechanistic hypothesis - increased short-chain fatty acids - with markers of disease. Results Here we report targeted and untargeted metabolomic measurements on fasting plasma (n = 104) collected at baseline and end of intervention. Butyrate and ursodeoxycholate increased among participants randomized to WBF-011, along with compelling trends between butyrate and glycated haemoglobin (HbA1c). In vitro monoculture experiments demonstrated that the formulation’s C. butyricum strain efficiently synthesizes ursodeoxycholate from the primary bile acid chenodeoxycholate during butyrogenic growth. Untargeted metabolomics also revealed coordinated decreases in intermediates of fatty acid oxidation and bilirubin, potential secondary signatures for metabolic improvement. Finally, improvement in HbA1c was limited almost entirely to participants not using sulfonylurea drugs. We show that these drugs can inhibit growth of formulation strains in vitro. Conclusion To our knowledge, this is the first description of an increase in circulating butyrate or ursodeoxycholate following a probiotic intervention in humans with T2D, adding support for the possibility of a targeted microbiome-based approach to assist in the management of T2D. The efficient synthesis of UDCA by C. butyricum is also likely of interest to investigators of its use as a probiotic in other disease settings. The potential for inhibitory interaction between sulfonylurea drugs and gut microbiota should be considered carefully in the design of future studies.

Hyperbaric oxygen therapy (HBOT) is known to be associated with pulmonary oxygen toxicity. However, the effect of modern HBOT protocols on pulmonary function is not completely understood. The present study evaluates pulmonary function test changes in patients undergoing serial HBOT. We prospectively collected data on patients undergoing HBOT from 2016–2021 at a tertiary referral center (protocol registration NCT05088772). Patients underwent pulmonary function testing with a bedside spirometer/pneumotachometer prior to HBOT and after every 20 treatments. HBOT was performed using 100% oxygen at a pressure of 2.0–2.4 atmospheres absolute (203–243 kPa) for 90 minutes, five times per week. Patients’ charts were retrospectively reviewed for demographics, comorbidities, medications, HBOT specifications, treatment complications, and spirometry performance. Primary outcomes were defined as change in percent predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced mid-expiratory flow (FEF25-75), after 20, 40, and 60 HBOT sessions. Data was analyzed with descriptive statistics and mixed-model linear regression. A total of 86 patients were enrolled with baseline testing, and the analysis included data for 81 patients after 20 treatments, 52 after 40 treatments, and 12 after 60 treatments. There were no significant differences in pulmonary function tests after 20, 40, or 60 HBOT sessions. Similarly, a subgroup analysis stratifying the cohort based on pre-existing respiratory disease, smoking history, and the applied treatment pressure did not identify any significant changes in pulmonary function tests during HBOT. There were no significant longitudinal changes in FEV1, FVC, or FEF25-75 after serial HBOT sessions in patients regardless of pre-existing respiratory disease. Our results suggest that the theoretical risk of pulmonary oxygen toxicity following HBOT is unsubstantiated with modern treatment protocols, and that pulmonary function is preserved even in patients with pre-existing asthma, chronic obstructive lung disease, and interstitial lung disease.

Traditional methods to study raptor diet are usually limited temporally, e.g. prey remains at nesting sites, and are unsuitable to examine dietary changes throughout the year. Using web-sourced photography, we explore temporal patterns in prey size and key prey species between sexes of the sexually dimorphic Eurasian sparrowhawk (Accipiter nisus) throughout the United Kingdom. We examined 666 photographs of sparrowhawk on prey and identified the prey species involved, together with sparrowhawk sex. Changes in prey size and proportions of key prey species over time (seasonally and monthly) were explored for each sex. Prey weight was substantially higher for females than males. However, on average, prey size for both sexes declined during the summer period (May–June) being the lowest in June, which is the main nestling-rearing month for both sparrowhawks and their prey. Compared with summer, rock doves (Columba livia) were more important prey for female sparrowhawk in winter. Whereas, for males, Eurasian blackbirds (Turdus merula) were more important in spring compared with autumn. Web-sourced photography can overcome several limitations of previous methods used to study raptor diet including the ability to quantify diet between the sexes throughout the entire year, however, may also introduce a prey-size bias toward larger prey items.

Liver kinase B1 (LKB1) is a potent tumor suppressor that regulates cellular energy balance and metabolism as an upstream kinase of the AMP-activated protein kinase (AMPK) pathway. LKB1 regulates cancer cell invasion and metastasis in multiple cancer types, including breast cancer. In this study, we evaluated LKB1’s role as a regulator of the tumor microenvironment (TME). This was achieved by seeding the MDA-MB-231-LKB1 overexpressing cell line onto adipose and tumor scaffolds, followed by the evaluation of tumor matrix-induced tumorigenesis and metastasis. Results demonstrated that the presence of tumor matrix enhanced tumorigenesis in both MDA-MB-231 and MDA-MB-231-LKB1 cell lines. Metastasis was increased in both MDA-MB-231 and -LKB1 cells seeded on the tumor scaffold. Endpoint analysis of tumor and adipose scaffolds revealed LKB1-mediated tumor microenvironment remodeling as evident through altered matrix protein production. The proteomic analysis determined that LKB1 overexpression preferentially decreased all major and minor fibril collagens (collagens I, III, V, and XI). In addition, proteins observed to be absent in tumor scaffolds in the LKB1 overexpressing cell line included those associated with the adipose matrix (COL6A2) and regulators of adipogenesis (IL17RB and IGFBP4), suggesting a role for LKB1 in tumor-mediated adipogenesis. Histological analysis of MDA-MB-231-LKB1-seeded tumors demonstrated decreased total fibril collagen and indicated decreased stromal cell presence. In accordance with this, in vitro condition medium studies demonstrated that the MDA-MB-231-LKB1 secretome inhibited adipogenesis of adipose-derived stem cells. Taken together, these data demonstrate a role for LKB1 in regulating the tumor microenvironment through fibril matrix remodeling and suppression of adipogenesis.

Abstract Data from wildlife rehabilitation centers (WRCs) can provide on‐the‐ground records of causes of raptor morbidity and mortality, allowing threat patterns to be explored throughout time and space. We provide an overview of native raptor admissions to four WRCs in England and Wales, quantifying the main causes of morbidity and mortality, trends over time, and associations between threats and urbanization between 2001 and 2019. Throughout the study period, 14 raptor species were admitted totalling 3305 admission records. The Common Buzzard (Buteo buteo; 31%) and Tawny Owl (Strix aluco; 29%) were most numerous. Relative to the proportion of breeding individuals in Britain and Ireland, Peregrine Falcons (Falco peregrinus), Little Owls (Athene noctua), and Western Barn Owls (Tyto alba) were over‐represented in the admissions data by 103%, 73%, and 69%, respectively. Contrastingly Northern Long‐eared Owls (Asio otus), Western Marsh Harriers (Circus aeruginosus), and Merlin (Falco columbarius) were under‐represented by 187%, 163%, and 126%, respectively. Across all species, vehicle collisions were the most frequent anthropogenic admission cause (22%), and orphaned young birds (10%) were most frequent natural cause. Mortality rate was highest for infection/parasite admissions (90%), whereas orphaned birds experienced lowest mortality rates (16%). For one WRC, there was a decline in admissions over the study period. Red Kite (Milvus milvus) admissions increased over time, whereas Common Buzzard and Common Kestrel admissions declined. There were significant declines in the relative proportion of persecution and metabolic admissions and an increase in orphaned birds. Urban areas were positively associated with persecution, building collisions, and unknown trauma admissions, whereas vehicle collisions were associated with more rural areas. Many threats persist for raptors in England and Wales, however, have not changed substantially over the past two decades. Threats associated with urban areas, such as building collisions, may increase over time in line with human population growth and subsequent urban expansion.

Objective:. The purpose of this review is to examine the effect of dexmedetomidine on delayed neurocognitive recovery (dNCR; cognitive dysfunction ≥1 week postoperative) after major noncardiac surgery. Background:. Dexmedetomidine (DEX) effectively reduces delirium in the intensive care unit and reportedly attenuates cognitive decline following major noncardiac surgery. Ascertaining the true effect on postoperative cognition is difficult because studies are limited by suboptimal selection of cognitive assessment tools, timing of testing, and criteria for defining significant cognitive decline Methods:. Prospective randomized trials comparing perioperative DEX to placebo for major noncardiac surgery assessing cognitive function ≥1 week postoperative were included. Pediatric, nonhuman, and non-English trials, and those where executive function was not assessed were excluded. Data were abstracted by 3 reviewers independently and in parallel according to PRISMA guidelines. The a priori binary primary outcome is dNCR defined as cognitive function declining by the minimal clinically important difference or accepted alternate measure (eg, Reliable Change Index ≥1.96). Bias was assessed with the Cochrane Collaboration tool. Data were pooled using a random effects model. Results:. Among 287 citations identified, 26 (9%) met criteria for full-text retrieval. Eleven randomized trials (1233 participants) were included for qualitative analysis, and 7 trials (616 participants) were included for meta-analysis of dNCR. Dexmedetomidine did not reduce the incidence of dNCR significantly (OR 0.57, 95% CI 0.30–1.10, P = 0.09) compared with placebo. There was no difference in the incidence of delirium (OR 0.94, 95% CI 0.55–1.63, P = 0.83) and a higher incidence of hemodynamic instability (OR 2.11, 95% CI 1.22–3.65, P = 0.008). Conclusions:. Dexmedetomidine does not reduce dNCR 1 week after major noncardiac surgery. This meta-analysis does not yet support the use of perioperative DEX to improve short term cognitive outcomes at this time; trials underway may yet change this conclusion while larger trials are needed to refine the point estimate of effect and examine long-term cognitive outcomes.

Abstract The Legume Information System (LIS; https://legumeinfo.org) houses genetic and genomic data, integrated in various online tools to allow comparative genomic analyses. The website and database maintain data for more than two dozen species, particularly focusing on crop and model species and holding data for other diverse species of taxonomic interest. Major analysis features include genome browsers, sequence‐search tools, legume‐focused gene families and a phylogenetic tree viewer, a gene annotation service (which places a submitted gene into a gene family and phylogenetic tree), an interactive microsynteny and pan‐genome viewer, a novel viewer of genetic variant data, genetic maps and viewers, a Data Store for data sets such as assemblies and annotations, InterMine instances for querying genetic and genomic data, and a tool for viewing geographic distributions of germplasm accessions. LIS also integrates with several other legume data resources and tools, including PeanutBase (https://peanutbase.org), SoyBase (https://soybase.org), Medicago Hapmap (https://medicagohapmap2.org), Alfalfa Breeder's Toolbox (https://alfalfatoolbox.org), and the Legume Federation (https://legumefederation.org).

Anatomical dissection is almost ubiquitous in modern medical education, masking a complex history of its practice. Dissection with the express purpose of understanding human anatomy began more than two millennia ago with Herophilus, but was soon after disavowed in the third century BCE. Historical evidence suggests that this position was based on common beliefs that the body must remain whole after death in order to access the afterlife. Anatomical dissection did not resume for almost 1500 years, and in the interim anatomical knowledge was dominated by (often flawed) reports generated through the comparative dissection of animals. When a growing recognition of the utility of anatomical knowledge in clinical medicine ushered human dissection back into vogue, it recommenced in a limited setting almost exclusively allowing for dissection of the bodies of convicted criminals. Ultimately, the ethical problems that this fostered, as well as the increasing demand from medical education for greater volumes of human dissection, shaped new considerations of the body after death. Presently, body bequeathal programs are a popular way in which individuals offer their bodies to medical education after death, suggesting that the once widespread views of dissection as punishment have largely dissipated.

Conventional mitogen-activated protein kinase (MAPK) family members regulate diverse cellular processes involved in tumor initiation and progression, yet the role of ERK5 in cancer biology is not fully understood. Triple-negative breast cancer (TNBC) presents a clinical challenge due to the aggressive nature of the disease and a lack of targeted therapies. ERK5 signaling contributes to drug resistance and metastatic progression through distinct mechanisms, including activation of epithelial-to-mesenchymal transition (EMT). More recently a role for ERK5 in regulation of the extracellular matrix (ECM) has been proposed, and here we investigated the necessity of ERK5 in TNBC tumor formation. Depletion of ERK5 expression using the CRISPR/Cas9 system in MDA-MB-231 and Hs-578T cells resulted in loss of mesenchymal features, as observed through gene expression profile and cell morphology, and suppressed TNBC cell migration. In vivo xenograft experiments revealed ERK5 knockout disrupted tumor growth kinetics, which was restored using high concentration Matrigel™ and ERK5-ko reduced expression of the angiogenesis marker CD31. These findings implicated a role for ERK5 in the extracellular matrix (ECM) and matrix integrity. RNA-sequencing analyses demonstrated downregulation of matrix-associated genes, integrins, and pro-angiogenic factors in ERK5-ko cells. Tissue decellularization combined with cryo-SEM and interrogation of biomechanical properties revealed that ERK5-ko resulted in loss of key ECM fiber alignment and mechanosensing capabilities in breast cancer xenografts compared to parental wild-type cells. In this study, we identified a novel role for ERK5 in tumor growth kinetics through modulation of the ECM and angiogenesis axis in breast cancer.

We present a comprehensive architectural analysis for a proposed fault-tolerant quantum computer based on cat codes concatenated with outer quantum error-correcting codes. For the physical hardware, we propose a system of acoustic resonators coupled to superconducting circuits with a two-dimensional layout. Using estimated physical parameters for the hardware, we perform a detailed error analysis of measurements and gates, including cnot and Toffoli gates. Having built a realistic noise model, we numerically simulate quantum error correction when the outer code is either a repetition code or a thin rectangular surface code. Our next step toward universal fault-tolerant quantum computation is a protocol for fault-tolerant Toffoli magic state preparation that significantly improves upon the fidelity of physical Toffoli gates at very low qubit cost. To achieve even lower overheads, we devise a new magic state distillation protocol for Toffoli states. Combining these results together, we obtain realistic full-resource estimates of the physical error rates and overheads needed to run useful fault-tolerant quantum algorithms. We find that with around 1000 superconducting circuit components, one could construct a fault-tolerant quantum computer that can run circuits, which are currently intractable for classical computers. Hardware with 18 000 superconducting circuit components, in turn, could simulate the Hubbard model in a regime beyond the reach of classical computing.

Sulfate is the predominant electron acceptor for anaerobic oxidation of methane (AOM) in marine sediments. This process is carried out by a syntrophic consortium of anaerobic methanotrophic archaea (ANME) and sulfate reducing bacteria (SRB) through an energy conservation mechanism that is still poorly understood. It was previously hypothesized that ANME alone could couple methane oxidation to dissimilatory sulfate reduction, but a genetic and biochemical basis for this proposal has not been identified. Using comparative genomic and phylogenetic analyses, we found the genetic capacity in ANME and related methanogenic archaea for sulfate reduction, including sulfate adenylyltransferase, APS kinase, APS/PAPS reductase and two different sulfite reductases. Based on characterized homologs and the lack of associated energy conserving complexes, the sulfate reduction pathways in ANME are likely used for assimilation but not dissimilation of sulfate. Environmental metaproteomic analysis confirmed the expression of 6 proteins in the sulfate assimilation pathway of ANME. The highest expressed proteins related to sulfate assimilation were two sulfite reductases, namely assimilatory-type low-molecular-weight sulfite reductase (alSir) and a divergent group of coenzyme F420-dependent sulfite reductase (Group II Fsr). In methane seep sediment microcosm experiments, however, sulfite and zero-valent sulfur amendments were inhibitory to ANME-2a/2c while growth in their syntrophic SRB partner was not observed. Combined with our genomic and metaproteomic results, the passage of sulfur species by ANME as metabolic intermediates for their SRB partners is unlikely. Instead, our findings point to a possible niche for ANME to assimilate inorganic sulfur compounds more oxidized than sulfide in anoxic marine environments.

Quantum random access memory (QRAM)—memory which stores classical data but allows queries to be performed in superposition—is required for the implementation of numerous quantum algorithms. While naive implementations of QRAM are highly susceptible to decoherence and hence not scalable, it has been argued that the bucket-brigade QRAM architecture [Giovannetti et al., Phys. Rev. Lett. 100, 160501 (2008)] is highly resilient to noise, with the infidelity of a query scaling only logarithmically with the memory size. In prior analyses, however, this favorable scaling followed directly from the use of contrived noise models, thus leaving open the question of whether experimental implementations would actually enjoy the purported scaling advantage. In this work, we study the effects of decoherence on QRAM in full generality. Our main result is a proof that this favorable infidelity scaling holds for arbitrary error channels (including, e.g., depolarizing noise and coherent errors). Our proof identifies the origin of this noise resilience as the limited entanglement among the memory’s components, and it also reveals that significant architectural simplifications can be made while preserving the noise resilience. We verify these results numerically using a novel classical algorithm for the efficient simulation of noisy QRAM circuits. Our findings indicate that QRAM can be implemented with existing hardware in realistically noisy devices, and that high-fidelity queries are possible without quantum error correction. Furthermore, we also prove that the benefits of the bucket-brigade architecture persist when quantum error correction is used, in which case the scheme offers improved hardware efficiency and resilience to logical errors.

Qubit measurements are central to quantum information processing. In the field of superconducting qubits, standard readout techniques are limited not only by the signal-to-noise ratio, but also by state relaxation during the measurement. In this work, we demonstrate that the limitation due to relaxation can be suppressed by using the many-level Hilbert space of superconducting circuits: In a multilevel encoding, the measurement is corrupted only when multiple errors occur. Employing this technique, we show that we can directly resolve transmon gate errors at the level of one part in 10^{3}. Extending this idea, we apply the same principles to the measurement of a logical qubit encoded in a bosonic mode and detected with a transmon ancilla, implementing a proposal by Hann et al. [Phys. Rev. A 98, 022305 (2018)PLRAAN2469-992610.1103/PhysRevA.98.022305]. Qubit state assignments are made based on a sequence of repeated readouts, further reducing the overall infidelity. This approach is quite general, and several encodings are studied; the codewords are more distinguishable when the distance between them is increased with respect to photon loss. The trade-off between multiple readouts and state relaxation is explored and shown to be consistent with the photon-loss model. We report a logical assignment infidelity of 5.8×10^{-5} for a Fock-based encoding and 4.2×10^{-3} for a quantum error correction code (the S=2, N=1 binomial code). Our results not only improve the fidelity of quantum information applications, but also enable more precise characterization of process or gate errors.

Background: We still do not understand the key drivers or prevalence of genetic monogamy in mammals despite the amount of attention that the evolution of mammalian monogamy has received. There have been numerous reviews of the hypotheses proposed to explain monogamy, some of which focused on animals in general, while others focused on particular classes like birds or mammals, or on specific orders within a class. Because monogamy is rare in mammals overall but relatively common in some of the orders in which it has been observed (e.g., Primates, Macroscelidea, and Carnivora), mammals provide a unique taxon in which to study the evolution and maintenance of monogamy However, the term “monogamy” encompasses related but separate phenomena; i.e., social monogamy (pair-living by opposite-sex conspecifics) and genetic monogamy or reproductive monogamy (mating exclusivity). A recent review of mammalian monogamy reported that 226 species (9%) in 9 orders (35%) were socially monogamous, although socially monogamous mammals are not necessarily genetically monogamous.Methods: Since factors that predispose socially monogamous mammals to be genetically monogamous are still subject to debate, we conducted meta-analyses using model selection to determine the relative importance of several life history, demographic, and environmental factors in predicting genetic monogamy.Results: We found sufficient data to include 41 species in our analysis, about 2x more than have been included in previous analyses of mammalian genetic monogamy. We found that living as part of a socially monogamous pair vs. in a group was the best predictor of genetic monogamy, either by itself or in combination with high levels of paternal care. A male-biased sex ratio and low population density were inversely related to the number of pairs that were genetically monogamous, but not to the production of intra-pair young or litters.Conclusion: Our results agree with the results of some previous analyses but suggest that more than one factor may be important in driving genetic monogamy in mammals.

The extracellular matrix (ECM) is a critical cue to direct tumorigenesis and metastasis. Although two-dimensional (2D) culture models have been widely employed to understand breast cancer microenvironments over the past several decades, the 2D models still exhibit limited success. Overwhelming evidence supports that three dimensional (3D), physiologically relevant culture models are required to better understand cancer progression and develop more effective treatment. Such platforms should include cancer-specific architectures, relevant physicochemical signals, stromal–cancer cell interactions, immune components, vascular components, and cell-ECM interactions found in patient tumors. This review briefly summarizes how cancer microenvironments (stromal component, cell-ECM interactions, and molecular modulators) are defined and what emerging technologies (perfusable scaffold, tumor stiffness, supporting cells within tumors and complex patterning) can be utilized to better mimic native-like breast cancer microenvironments. Furthermore, this review emphasizes biophysical properties that differ between primary tumor ECM and tissue sites of metastatic lesions with a focus on matrix modulation of cancer stem cells, providing a rationale for investigation of underexplored ECM proteins that could alter patient prognosis. To engineer breast cancer microenvironments, we categorized technologies into two groups: (1) biochemical factors modulating breast cancer cell-ECM interactions and (2) 3D bioprinting methods and its applications to model breast cancer microenvironments. Biochemical factors include matrix-associated proteins, soluble factors, ECMs, and synthetic biomaterials. For the application of 3D bioprinting, we discuss the transition of 2D patterning to 3D scaffolding with various bioprinting technologies to implement biophysical cues to model breast cancer microenvironments.

ABSTRACT The anaerobic oxidation of methane by anaerobic methanotrophic (ANME) archaea in syntrophic partnership with deltaproteobacterial sulfate-reducing bacteria (SRB) is the primary mechanism for methane removal in ocean sediments. The mechanism of their syntrophy has been the subject of much research as traditional intermediate compounds, such as hydrogen and formate, failed to decouple the partners. Recent findings have indicated the potential for extracellular electron transfer from ANME archaea to SRB, though it is unclear how extracellular electrons are integrated into the metabolism of the SRB partner. We used metagenomics to reconstruct eight genomes from the globally distributed SEEP-SRB1 clade of ANME partner bacteria to determine what genomic features are required for syntrophy. The SEEP-SRB1 genomes contain large multiheme cytochromes that were not found in previously described free-living SRB and also lack periplasmic hydrogenases that may prevent an independent lifestyle without an extracellular source of electrons from ANME archaea. Metaproteomics revealed the expression of these cytochromes at in situ methane seep sediments from three sites along the Pacific coast of the United States. Phylogenetic analysis showed that these cytochromes appear to have been horizontally transferred from metal-respiring members of the Deltaproteobacteria such as Geobacter and may allow these syntrophic SRB to accept extracellular electrons in place of other chemical/organic electron donors. IMPORTANCE Some archaea, known as anaerobic methanotrophs, are capable of converting methane into carbon dioxide when they are growing syntopically with sulfate-reducing bacteria. This partnership is the primary mechanism for methane removal in ocean sediments; however, there is still much to learn about how this syntrophy works. Previous studies have failed to identify the metabolic intermediate, such as hydrogen or formate, that is passed between partners. However, recent analysis of methanotrophic archaea has suggested that the syntrophy is formed through direct electron transfer. In this research, we analyzed the genomes of multiple partner bacteria and showed that they also contain the genes necessary to perform extracellular electron transfer, which are absent in related bacteria that do not form syntrophic partnerships with anaerobic methanotrophs. This genomic evidence shows a possible mechanism for direct electron transfer from methanotrophic archaea into the metabolism of the partner bacteria.

Measurement of telomere length by fluorescent in situ hybridization is widely used for biomedical and epidemiological research, but there has been relatively little development of the technology in the 20 years since it was first reported. This report describes the use of dual gammaPNA (γPNA) probes that hybridize at alternating sites along a telomere and give rise to Förster resonance energy transfer (FRET) signals. Bright staining of telomeres is observed in nuclei, chromosome spreads and tissue samples. The use of FRET detection also allows for elimination of wash steps, normally required to remove unhybridized probes that would contribute to background signals. We found that these wash steps can diminish the signal intensity through the removal of bound, as well as unbound probes, so eliminating these steps not only accelerates the process but also enhances the quality of staining. Thus, γPNA FRET pairs allow for brighter and faster staining of telomeres in a wide range of research and clinical formats.