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Reconfigurable transistors are an emerging device technology adding new functionalities while lowering the circuit architecture complexity. However, most investigations focus on digital applications. Here, we demonstrate a single vertical nanowire ferroelectric tunnel field-effect transistor (ferro-TFET) that can modulate an input signal with diverse modes including signal transmission, phase shift, frequency doubling, and mixing with significant suppression of undesired harmonics for reconfigurable analogue applications. We realize this by a heterostructure design in which a gate/source overlapped channel enables nearly perfect parabolic transfer characteristics with robust negative transconductance. By using a ferroelectric gate oxide, our ferro-TFET is non-volatilely reconfigurable, enabling various modes of signal modulation. The ferro-TFET shows merits of reconfigurability, reduced footprint, and low supply voltage for signal modulation. This work provides the possibility for monolithic integration of both steep-slope TFETs and reconfigurable ferro-TFETs towards high-density, energy-efficient, and multifunctional digital/analogue hybrid circuits. Increasing functional density is desirable for future scaling of electronics. Here, the authors use a nanowire ferroelectric tunnel field-effect transistor to achieve reconfigurable signal modulations for low-power and high-density analogue circuits.

Antibodies against P . falciparum merozoites fix complement to inhibit blood-stage replication in naturally-acquired and vaccine-induced immunity; however, specific targets of these functional antibodies and their importance in protective immunity are unknown. Among malaria-exposed individuals, we show that complement-fixing antibodies to merozoites are more strongly correlated with protective immunity than antibodies that inhibit growth quantified using the current reference assay for merozoite vaccine evaluation. We identify merozoite targets of complement-fixing antibodies and identify antigen-specific complement-fixing antibodies that are strongly associated with protection from malaria in a longitudinal study of children. Using statistical modelling, combining three different antigens targeted by complement-fixing antibodies could increase the potential protective effect to over 95%, and we identify antigens that were common in the most protective combinations. Our findings support antibody-complement interactions against merozoite antigens as important anti-malaria immune mechanisms, and identify specific merozoite antigens for further evaluation as vaccine candidates. Antibodies against Plasmodium falciparum merozoites that fix complement can inhibit blood-stage replication. Here, Reiling et al. show that complement-fixing antibodies strongly correlate with protective immunity in children, identify the merozoite targets, and predict antigen combinations that should result in strong protection.

X-Rated Supernova A link between long γ-ray bursts (GRBs) and supernovae has been established, but whether there is a similar relationship between the weaker and softer X-ray flashes and supernovae is unclear. GRB/XRF 060218, spotted by the Swift satellite on 18 February this year, may supply that missing link. In the first of four papers on this novel burster, Campana et al . report the sighting of the X-ray signature of a shock break-out, possible evidence of a supernova in progress. Pian et al . report the optical discovery of a type Ic supernova 2006aj associated with GRB/XRF 060218. Soderberg et al . report radio and X-ray observations that show that XRF 060218 is 100 times less energetic than, but of a type that is ten times more common than cosmological GRBs. Mazzali et al . modelled the spectra and light curve of SN 2006aj to show that it had a much smaller explosion energy and ejected much less mass than other GRB-supernovae, suggesting that it was produced by a star with a mass was only about 20 times that of the Sun, leaving behind a neutron star, rather than a black hole. Radio and X-ray observations of X-ray flash XRF 060218, which is associated with supernova SN 2006aj, show that this event is 100 times less energetic but ten times more common than cosmological gamma-ray bursts (GRBs). The production of relativistic ejecta seems to be the key physical distinction between GRBs/XRFs and ordinary supernovae. Over the past decade, long-duration γ-ray bursts (GRBs)—including the subclass of X-ray flashes (XRFs)—have been revealed 1 , 2 , 3 to be a rare variety of type Ibc supernova. Although all these events result from the death of massive stars, the electromagnetic luminosities of GRBs and XRFs exceed those of ordinary type Ibc supernovae by many orders of magnitude. The essential physical process that causes a dying star to produce a GRB or XRF, and not just a supernova, is still unknown. Here we report radio and X-ray observations of XRF 060218 (associated 4 with supernova SN 2006aj), the second-nearest 5 , 6 GRB identified until now. We show that this event is a hundred times less energetic but ten times more common than cosmological GRBs. Moreover, it is distinguished from ordinary type Ibc supernovae by the presence of 10 48  erg coupled to mildly relativistic ejecta, along with a central engine (an accretion-fed, rapidly rotating compact source) that produces X-rays for weeks after the explosion. This suggests that the production of relativistic ejecta is the key physical distinction between GRBs or XRFs and ordinary supernovae, while the nature of the central engine (black hole or magnetar) may distinguish typical bursts from low-luminosity, spherical events like XRF 060218.

Malaria is a potentially life-threatening disease with approximately half of the world’s population at risk. Young children and pregnant women are hit hardest by the disease. B cells and antibodies are part of an adaptive immune response protecting individuals continuously exposed to the parasite. An infection with Plasmodium falciparum can cause dysregulation of B cell homeostasis, while antibodies are known to be key in controlling symptoms and parasitemia. BAFF is an instrumental cytokine for the development and maintenance of B cells. Pregnancy alters the immune status and renders previously clinically immune women at risk of severe malaria, potentially due to altered B cell responses associated with changes in BAFF levels. In this prospective study, we investigated the levels of BAFF in a malaria-endemic area in mothers and their infants from birth up to 9 months. We found that BAFF-levels are significantly higher in infants than in mothers. BAFF is highest in cord blood and then drops rapidly, but remains significantly higher in infants compared to mothers even at 9 months of age. We further correlated BAFF levels to P . falciparum- specific antibody levels and B cell frequencies and found a negative correlation between BAFF and both P . falciparum -specific and total proportions of IgG + memory B cells, as well as CD27 − memory B cells, indicating that exposure to both malaria and other diseases affect the development of B-cell memory and that BAFF plays a part in this. In conclusion, we have provided new information on how natural immunity against malaria is formed.

Background Malaria remains a significant public health concern, especially for the deadliest parasite, Plasmodium falciparum . During acute malaria, various cytokines, including osteopontin (OPN), regulate the immune response. OPN has been shown to be protective against malaria in mice. Nonetheless, its precise function and potential ability to control parasites during acute malaria in humans remain poorly understood. Results Blood samples were collected from Swedish adults with imported malaria, Ugandan children and adults with symptomatic malaria (including follow-up after 42 days), Ugandans with non-malarial fever and healthy individuals from both Uganda and Sweden. Parasitemia was determined by microscopy. Malaria-negative samples were verified by LAMP. OPN and interferon-γ (IFN- γ) levels were measured using ELISA. In children, OPN levels were significantly higher during acute infection compared to levels after 42 days, whereas Ugandan adults showed no difference. Swedish adults with imported malaria had elevated OPN levels compared to both Swedish controls and Ugandan adults with malaria. Parasitemia was significantly correlated with both OPN and IFN-γ levels across the entire cohort. While a significant correlation between OPN and IFN-γ was evident overall, it remained statistically significant only in Ugandan adults when analyzed by subgroups. This suggests that OPN is not just a general marker of inflammation but may be regulated differently during the development of malaria immunity. Conclusions In acute malaria, elevated OPN levels showed a stronger correlation with lack of immunity than age. These findings underscore the potential importance of OPN in malaria, particularly in non-immune individuals.

Background Light microscopy and rapid diagnostic tests (RDT) have long been the recommended diagnostic methods for malaria. However, in recent years, loop-mediated isothermal amplification (LAMP) techniques have been shown to offer superior performance, in particular concerning low-grade parasitaemia, by delivering higher sensitivity and specificity with low laboratory capacity requirements in little more than an hour. In this study, the diagnostic performance of two LAMP kits were assessed head-to-head, compared to highly sensitive quantitative real time PCR (qPCR), in a non-endemic setting. Methods In this retrospective validation study two LAMP kits; Alethia ® Illumigene Malaria kit and HumaTurb Loopamp™ Malaria Pan Detection (PDT) kit, were evaluated head-to-head for detection of Plasmodium -DNA in 133 biobanked blood samples from suspected malaria cases at the Clinical Microbiology Laboratory of Region Skåne, Sweden to determine their diagnostic performance compared to qPCR. Results Of the 133 samples tested, qPCR detected Plasmodium DNA in 41 samples (defined as true positives), and the two LAMP methods detected 41 and 37 of those, respectively. The results from the HumaTurb Loopamp™ Malaria PDT kit were in complete congruence with the qPCR, with a sensitivity of 100% (95% CI 91.40–100%) and specificity of 100% (95% CI 96.07–100%). The Alethia ® Illumigene Malaria kit had a sensitivity of 90.24% (95% CI 76.87–97.28) and a specificity of 95.65% (95% CI 89.24–98.80) as compared to qPCR. Conclusions This head-to-head comparison showed higher performance indicators of the HumaTurb Loopamp™ Malaria PDT kit compared to the Alethia ® illumigene Malaria kit for detection of malaria.

The onset of resistance to artemisinin for malaria treatment has stimulated the quest for novel antimalarial drugs. Herein, the gold(III) coordination complexes Aubipy [Au(bipy)Cl 2 ] + (bipy = 2,2′-bipyridine), Auphen [Au(phen)Cl 2 ] + (phen = phenanthroline), Auterpy [Au(terpy)Cl] 2+ (terpy = 2,2′;6′,2″-terpyridine), and corresponding hydrolyzed species, have been investigated as inhibitors of the Plasmodium falciparum aquaglyceroporin ( Pf AQP) protein by computational methods. Through an in-silico approach using an Umbrella Sampling protocol to sample how Aubipy, Auphen, and Auterpy permeate through the Pf AQP, their permeability coefficients were estimated using the Inhomogeneous Solubility Diffusion (ISD) model with promising results. The efficacy of the gold complexes was then probed by an in vitro assay testing the growth inhibition in chloroquine sensitive and resistant P. falciparum strains. In accordance with the computational data, Auterpy achieved the highest efficiency with an IC 50 in the nanomolar range (590 nM) on resistant strain cultures, additionally revealing a good selectivity as compared to its activity against the human aquaglyceroporin 3. Graphical abstract

Severe babesiosis with 9.8% parasitemia was diagnosed in a patient in the Netherlands who had previously undergone splenectomy. We confirmed Babesia venatorum using PCR and sequencing. B. venatorum was also the most prevalent species in Ixodes ricinus ticks collected around the patient's home. Our findings warrant awareness for severe babesiosis in similar patients.

For centuries humans have been fascinated by the natural beauty of horses in motion and their different gaits. Gait classification (GC) is commonly performed through visual assessment and reliable, automated methods for real-time objective GC in horses are warranted. In this study, we used a full body network of wireless, high sampling-rate sensors combined with machine learning to fully automatically classify gait. Using data from 120 horses of four different domestic breeds, equipped with seven motion sensors, we included 7576 strides from eight different gaits. GC was trained using several machine-learning approaches, both from feature-extracted data and from raw sensor data. Our best GC model achieved 97% accuracy. Our technique facilitated accurate, GC that enables in-depth biomechanical studies and allows for highly accurate phenotyping of gait for genetic research and breeding. Our approach lends itself for potential use in other quadrupedal species without the need for developing gait/animal specific algorithms.

Background The purpose of this study was to describe clinical presentation, epilepsy, EEG, extent and site of the underlying cerebral lesion with special reference towards aetiologic background factors in a population-based group of children with hemiplegic cerebral palsy. Methods Forty-seven children of school- age, fulfilling the SPCE (Surveillance of Cerebral palsy in Europe)-criteria of hemiplegic cerebral palsy, identified via the Swedish cerebral palsy register, were invited and asked to participate in the study. Results Fifteen boys and six girls participated. Of the sixteen children born at term, five had no risk factors for cerebral palsy. Two out of five preterm children presented additional risk factors. Debut of motor impairment was observed in the first year of life in sixteen children. Age at diagnosis varied from 2 months to 6 years. Epilepsy was common and associated with grey- and white matter injury. Conclusions Recognizing the importance of risk factors for cerebral palsy, any child with these risk factors should be offered a check-up by a paediatrician or a paediatric neurologist. Thereby reducing diagnostic delay. Epilepsy is common in hemiplegic cerebral palsy and associated with grey- and white matter injury in this cohort.