A Novel Class of Defensive Compounds in Harvestmen: Hydroxy-γ-Lactones from the Phalangiid Egaenus convexus

When threatened, the harvestman Egaenus convexus (Opiliones: Phalangiidae) ejects a secretion against offenders. The secretion originates from large prosomal scent glands and is mainly composed of two isomers of 4-hydroxy-5-octyl-4,5-dihydro-3H-furan-2-one (1), a β-hydroxy-γ-lactone. The compounds were characterized by GC-MS of their microreaction derivatives, HRMS, and NMR. After the synthesis of all four possible stereoisomers of 1, followed by their separation by chiral-phase GC, the absolute configurations of the lactones in the Egaenus secretion was found to be (4S,5R)-1 (90%) and (4S,5S)-1 (10%). Hydroxy-γ-lactones represent a new class of exocrine defense compounds in harvestmen

Lifting the spin-momentum locking in ultra-thin topological insulator films

Three-dimensional (3D) topological insulators (TIs) are known to carry 2D Dirac-like topological surface states in which spin-momentum locking prohibits backscattering. When thinned down to a few nanometers, the hybridization between the topological surface states at the top and bottom surfaces results in a topological quantum phase transition, which can lead to the emergence of a quantum spin Hall phase. Here, we study the thickness-dependent transport properties across the quantum phase transition on the example of (Bi$_{0.16}$Sb$_{0.84}$)$_2$Te$_3$ films, with a four-tip scanning tunnelling microscope. Our findings reveal an exponential drop of the conductivity below the critical thickness. The steepness of this drop indicates the presence of spin-conserving backscattering between the top and bottom surface states, effectively lifting the spin-momentum locking and resulting in the opening of a gap at the Dirac point. Our experiments provide crucial steps towards the detection of quantum spin Hall states in transport measurements

Probing edge state conductance in ultra-thin topological insulator films

Quantum spin Hall (QSH) insulators have unique electronic properties, comprising a band gap in their two-dimensional interior and one-dimensional spin-polarized edge states in which current flows ballistically. In scanning tunneling microscopy (STM), the edge states manifest themselves as a localized density of states. However, there is a significant research gap between the observation of edge states in nanoscale spectroscopy, and the detection of ballistic transport in edge channels which typically relies on transport experiments with microscale lithographic contacts. Here, we study few-layer films of the three-dimensional topological insulator (Bi$_{x}$Sb$_{1-x})_2$Te$_3$, for which a topological transition to a two-dimensional topological QSH insulator phase has been proposed. Indeed, an edge state in the local density of states is observed within the band gap. Yet, in nanoscale transport experiments with a four-tip STM, 2 and 3 quintuple layer films do not exhibit a ballistic conductance in the edge channels. This demonstrates that the detection of edge states in spectroscopy can be misleading with regard to the identification of a QSH phase. In contrast, nanoscale multi-tip transport experiments are a robust method for effectively pinpointing ballistic edge channels, as opposed to trivial edge states, in quantum materials

HD-EEG Based Classification of Motor-Imagery Related Activity in Patients With Spinal Cord Injury

Brain computer interfaces (BCIs) are thought to revolutionize rehabilitation after SCI, e.g., by controlling neuroprostheses, exoskeletons, functional electrical stimulation, or a combination of these components. However, most BCI research was performed in healthy volunteers and it is unknown whether these results can be translated to patients with spinal cord injury because of neuroplasticity. We sought to examine whether high-density EEG (HD-EEG) could improve the performance of motor-imagery classification in patients with SCI. We recorded HD-EEG with 256 channels in 22 healthy controls and 7 patients with 14 recordings (4 patients had more than one recording) in an event related design. Participants were instructed acoustically to either imagine, execute, or observe foot and hand movements, or to rest. We calculated Fast Fourier Transform (FFT) and full frequency directed transfer function (ffDTF) for each condition and classified conditions pairwise with support vector machines when using only 2 channels over the sensorimotor area, full 10-20 montage, high-density montage of the sensorimotor cortex, and full HD-montage. Classification accuracies were comparable between patients and controls, with an advantage for controls for classifications that involved the foot movement condition. Full montages led to better results for both groups (p < 0.001), and classification accuracies were higher for FFT than for ffDTF (p < 0.001), for which the feature vector might be too long. However, full-montage 10–20 montage was comparable to high-density configurations. Motor-imagery driven control of neuroprostheses or BCI systems may perform as well in patients as in healthy volunteers with adequate technical configuration. We suggest the use of a whole-head montage and analysis of a broad frequency range

Marrow transplants from unrelated donors for patients with aplastic anemia: Minimum effective dose of total body irradiation

AbstractPatients with aplastic anemia who do not have suitably HLA-matched, related donors generally receive immunosuppressive treatment as first-line therapy and are considered for transplantation from an unrelated donor only if they fail to respond to immunosuppressive treatment. In this setting, rates of transplantation-related morbidity and mortality have been high. We conducted a prospective study to determine the minimal dose of total body irradiation (TBI) sufficient to achieve sustained engraftment when it is used in combination with 3 cycles of 30 mg/kg of antithymocyte globulin (ATG) and 4 cycles of 50 mg/kg of cyclophosphamide (CY). We also wanted to determine the tolerability and toxicity of the regimen. The starting dosage of TBI was 3 x 200 cGy given over 2 days following CY/ATG. The TBI dose was to be escalated in increments of 200 cGy if graft failure occurred in the absence of prohibitive toxicity, and de-escalated for toxicity in the absence of graft failure. Twenty-one female and 29 male patients aged 1.3 to 46.5 years (median age, 14.4 years) underwent transplantation at 14 medical centers. The time interval from diagnosis to transplantation was 2.8 to 264 months (median, 14.5 months). All patients had been transfused multiple times and all had received 1 to 11 courses (median, 4 courses) of immunosuppressive treatment and other modalities of treatment. In 38 cases, the donors were HLA-A, -B and -DR phenotypically matched with the patients, and, in 12 cases, the donor phenotype differed from that of the recipient by 1 HLA antigen. Recipients of mismatched transplants were considered separately for TBI dose modification, and this study is still ongoing. Seven patients did not tolerate ATG and were prepared with 6 x 200 cGy of TBI plus 120 mg/kg of CY. Of the HLA-matched recipients prepared with CY/ATG/TBI, all 20 who received 3 x 200 or 2 x 200 cGy of TBI achieved engraftment, and 10 are alive. Of the 13 patients who received 1 x 200 cGy of TBI, 1 failed to engraft, and 8 are alive. Each of 10 patients who received an HLA-nonidentical transplant achieved engraftment, and 3 of 6 who were given 3 x 200 cGy of TBI, and 4 of 4 who were given 2 x 200 cGy are alive. Pulmonary toxicity occurred in 8 of 30 patients who were given 3 x 200 or 2 x 200 cGy of TBI concurrently with ATG and CY at 200 mg/kg, and in 2 of 13 patients who received 1 x 200 cGy of TBI, a pattern that suggests a decrease in toxicity with TBI dose de-escalation. Overall, the highest probability of survival (73%) was observed among patients who underwent transplantation within 1 year of diagnosis, compared with patients who underwent transplantation after a longer period of disease. In addition, younger patients (aged < or = 20 years) were more likely to survive than older patients (aged > 20 years). Thus, for patients with an HLA-matched, unrelated donor, a TBI dose of 200 cGy (in combination with CY/ATG) was sufficient to allow for engraftment without inducing prohibitive toxicity. As in previous studies, patient age and pretransplantation disease duration remain important prognostic factors.Biol Blood Marrow Transplant 2001;7(4):208-15

SPA: Economical and workload-driven indexing for data analytics in the cloud

Selective queries are not uncommon in large-scale data analytics, for example, when drilling down into a specific customer in a dashboard. Traditionally, selective queries are accelerated by creating secondary indexes. However, because of their large size, expensive maintenance, and difficulty to tune and automate, indexes are typically not used in modern cloud data warehouses or data lakes. Instead, such systems rely mostly on full table scans and lightweight optimizations like min/max filtering, whose effectiveness depends heavily on the data layout and value distributions.We propose SPA as the vision for automatically optimizing selective queries for immutable copy-on-write data formats. SPA adaptively indexes subsets of the data in an incremental and workload-driven manner. It makes fine-grained decisions and continuously monitors their benefit, dynamically allocating an optimization budget in a way that bounds the additional cost of indexing. Furthermore, it guarantees a performance improvement in the cases where indexes - potentially partial ones - prove to be beneficial. When indexes lose their benefit due to a shifting workload, they are gradually deconstructed in favor of optimizations that accommodate recent trends. As SPA does not require information about updates performed on the data, it can also be employed as an accelerator for systems that do not control the data, e.g., in cloud data lakes

Status of the BELLE II Pixel Detector

The Belle II experiment at the super KEK B-factory (SuperKEKB) in Tsukuba, Japan, has been collecting $e^+e^−$ collision data since March 2019. Operating at a record-breaking luminosity of up to $4.7×10^{34} cm^{−2}s^{−1}$, data corresponding to $424 fb^{−1}$ has since been recorded. The Belle II VerteX Detector (VXD) is central to the Belle II detector and its physics program and plays a crucial role in reconstructing precise primary and decay vertices. It consists of the outer 4-layer Silicon Vertex Detector (SVD) using double sided silicon strips and the inner two-layer PiXel Detector (PXD) based on the Depleted P-channel Field Effect Transistor (DePFET) technology. The PXD DePFET structure combines signal generation and amplification within pixels with a minimum pitch of $(50×55) μm^2$. A high gain and a high signal-to-noise ratio allow thinning the pixels to $75 μm$ while retaining a high pixel hit efficiency of about $99$. As a consequence, also the material budget of the full detector is kept low at $≈0.21$$\frac{X}{X_0}$ per layer in the acceptance region. This also includes contributions from the control, Analog-to-Digital Converter (ADC), and data processing Application Specific Integrated Circuits (ASICs) as well as from cooling and support structures. This article will present the experience gained from four years of operating PXD; the first full scale detector employing the DePFET technology in High Energy Physics. Overall, the PXD has met the expectations. Operating in the intense SuperKEKB environment poses many challenges that will also be discussed. The current PXD system remains incomplete with only 20 out of 40 modules having been installed. A full replacement has been constructed and is currently in its final testing stage before it will be installed into Belle II during the ongoing long shutdown that will last throughout 2023

Strategies for protein synthetic biology

Proteins are the most versatile among the various biological building blocks and a mature field of protein engineering has lead to many industrial and biomedical applications. But the strength of proteins—their versatility, dynamics and interactions—also complicates and hinders systems engineering. Therefore, the design of more sophisticated, multi-component protein systems appears to lag behind, in particular, when compared to the engineering of gene regulatory networks. Yet, synthetic biologists have started to tinker with the information flow through natural signaling networks or integrated protein switches. A successful strategy common to most of these experiments is their focus on modular interactions between protein domains or domains and peptide motifs. Such modular interaction swapping has rewired signaling in yeast, put mammalian cell morphology under the control of light, or increased the flux through a synthetic metabolic pathway. Based on this experience, we outline an engineering framework for the connection of reusable protein interaction devices into self-sufficient circuits. Such a framework should help to ‘refacture’ protein complexity into well-defined exchangeable devices for predictive engineering. We review the foundations and initial success stories of protein synthetic biology and discuss the challenges and promises on the way from protein- to protein systems design