Decomposition of symmetric tensor fields in the presence of a flat contact projective structure

Let $M$ be an odd-dimensional Euclidean space endowed with a contact 1-form $\alpha$. We investigate the space of symmetric contravariant tensor fields on $M$ as a module over the Lie algebra of contact vector fields, i.e. over the Lie subalgebra made up by those vector fields that preserve the contact structure. If we consider symmetric tensor fields with coefficients in tensor densities, the vertical cotangent lift of contact form $\alpha$ is a contact invariant operator. We also extend the classical contact Hamiltonian to the space of symmetric density valued tensor fields. This generalized Hamiltonian operator on the symbol space is invariant with respect to the action of the projective contact algebra $sp(2n+2)$. The preceding invariant operators lead to a decomposition of the symbol space (expect for some critical density weights), which generalizes a splitting proposed by V. Ovsienko

FPGA-Based Portable Ultrasound Scanning System with Automatic Kidney Detection

Bedsides diagnosis using portable ultrasound scanning (PUS) offering comfortable diagnosis with various clinical advantages, in general, ultrasound scanners suffer from a poor signal-to-noise ratio, and physicians who operate the device at point-of-care may not be adequately trained to perform high level diagnosis. Such scenarios can be eradicated by incorporating ambient intelligence in PUS. In this paper, we propose an architecture for a PUS system, whose abilities include automated kidney detection in real time. Automated kidney detection is performed by training the Viola–Jones algorithm with a good set of kidney data consisting of diversified shapes and sizes. It is observed that the kidney detection algorithm delivers very good performance in terms of detection accuracy. The proposed PUS with kidney detection algorithm is implemented on a single Xilinx Kintex-7 FPGA, integrated with a Raspberry Pi ARM processor running at 900 MHz

JAK2 V617F Constitutive Activation Requires JH2 Residue F595: A Pseudokinase Domain Target for Specific Inhibitors

The JAK2 V617F mutation present in over 95% of Polycythemia Vera patients and in 50% of Essential Thrombocythemia and Primary Myelofibrosis patients renders the kinase constitutively active. In the absence of a three-dimensional structure for the full-length protein, the mechanism of activation of JAK2 V617F has remained elusive. In this study, we used functional mutagenesis to investigate the involvement of the JH2 αC helix in the constitutive activation of JAK2 V617F. We show that residue F595, located in the middle of the αC helix of JH2, is indispensable for the constitutive activity of JAK2 V617F. Mutation of F595 to Ala, Lys, Val or Ile significantly decreases the constitutive activity of JAK2 V617F, but F595W and F595Y are able to restore it, implying an aromaticity requirement at position 595. Substitution of F595 to Ala was also able to decrease the constitutive activity of two other JAK2 mutants, T875N and R683G, as well as JAK2 K539L, albeit to a lower extent. In contrast, the F595 mutants are activated by erythropoietin-bound EpoR. We also explored the relationship between the dimeric conformation of EpoR and several JAK2 mutants. Since residue F595 is crucial to the constitutive activation of JAK2 V617F but not to initiation of JAK2 activation by cytokines, we suggest that small molecules that target the region around this residue might specifically block oncogenic JAK2 and spare JAK2 wild-type

JAK2 Exon 14 Deletion in Patients with Chronic Myeloproliferative Neoplasms

BACKGROUND: The JAK2 V617F mutation in exon 14 is the most common mutation in chronic myeloproliferative neoplasms (MPNs); deletion of the entire exon 14 is rarely detected. In our previous study of >10,000 samples from patients with suspected MPNs tested for JAK2 mutations by reverse transcription-PCR (RT-PCR) with direct sequencing, complete deletion of exon 14 (Deltaexon14) constituted <1% of JAK2 mutations. This appears to be an alternative splicing mutation, not detectable with DNA-based testing. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the possibility that MPN patients may express the JAK2 Deltaexon14 at low levels (<15% of total transcript) not routinely detectable by RT-PCR with direct sequencing. Using a sensitive RT-PCR-based fluorescent fragment analysis method to quantify JAK2 Deltaexon14 mRNA expression relative to wild-type, we tested 61 patients with confirmed MPNs, 183 with suspected MPNs (93 V617F-positive, 90 V617F-negative), and 46 healthy control subjects. The Deltaexon14 variant was detected in 9 of the 61 (15%) confirmed MPN patients, accounting for 3.96% to 33.85% (mean = 12.04%) of total JAK2 transcript. This variant was also detected in 51 of the 183 patients with suspected MPNs (27%), including 20 of the 93 (22%) with V617F (mean [range] expression = 5.41% [2.13%-26.22%]) and 31 of the 90 (34%) without V617F (mean [range] expression = 3.88% [2.08%-12.22%]). Immunoprecipitation studies demonstrated that patients expressing Deltaexon14 mRNA expressed a corresponding truncated JAK2 protein. The Deltaexon14 variant was not detected in the 46 control subjects. CONCLUSIONS/SIGNIFICANCE: These data suggest that expression of the JAK2 Deltaexon14 splice variant, leading to a truncated JAK2 protein, is common in patients with MPNs. This alternatively spliced transcript appears to be more frequent in MPN patients without V617F mutation, in whom it might contribute to leukemogenesis. This mutation is missed if DNA rather than RNA is used for testing

Comparisons with amyloid-β reveal an aspartate residue that stabilizes fibrils of the aortic amyloid peptide medin

Aortic medial amyloid (AMA) is the most common localized human amyloid, occurring in virtually all of the Caucasian population over the age of 50. The main protein component of AMA, medin, readily assembles into amyloid-like fibrils in vitro. Despite the prevalence of AMA, little is known about the self-assembly mechanism of medin or the molecular architecture of the fibrils. The amino acid sequence of medin is strikingly similar to the sequence of the Alzheimer's disease (AD) amyloid-beta (Aβ) polypeptides around the structural turn region of Aβ where mutations associated with familial, early onset AD, have been identified. D25 and K30 of medin align with residues D23 and K28 of Aβ that are known to form a stabilizing salt bridge in some fibril morphologies. Here we show that substituting D25 of medin with asparagine (D25N) impedes assembly into fibrils and stabilizes non-cytotoxic oligomers. Wild-type medin, by contrast, aggregates into β-sheet rich amyloid-like fibrils within 50 h. A structural analysis of wild-type fibrils by solid-state NMR suggests a molecular repeat unit comprising at least two extended β-strands, separated by a turn stabilized by a D25-K30 salt-bridge. We propose that D25 drives the assembly of medin by stabilizing the fibrillar conformation of the peptide, and is thus reminiscent of the influence of D23 on the aggregation of Aβ. Pharmacological comparisons of wild-type medin and D25N will help to ascertain the pathological significance of this poorly under-stood protein

Measurement of the Generalized Polarizabilities of the Proton in Virtual Compton Scattering

We propose to conduct a measurement of the Virtual Compton Scattering reaction in Hall C that will allow the precise extraction of the two scalar Generalized Polarizabilities (GPs) of the proton in the region of $Q^2=0.05~(GeV/c)^2$ to $Q^2=0.50~(GeV/c)^2$. The Generalized Polarizabilities are fundamental properties of the proton, that characterize the system's response to an external electromagnetic (EM) field. They describe how easily the charge and magnetization distributions inside the system are distorted by the EM field, mapping out the resulting deformation of the densities in the proton. As such, they reveal unique information regarding the underlying system dynamics and provide a key for decoding the proton structure in terms of the theory of the strong interaction that binds its elementary quark and gluon constituents together. Recent measurements of the proton GPs have challenged the theoretical predictions, particularly in regard to the electric polarizability. The magnetic GP, on the other hand, can provide valuable insight to the competing paramagnetic and diamagnetic contributions in the proton, but it is poorly known within the region where the interplay of these processes is very dynamic and rapidly changing.The unique capabilities of Hall C, namely the high resolution of the spectrometers combined with the ability to place the spectrometers in small angles, will allow to pin down the dynamic signature of the GPs through high precision measurements combined with a fine mapping as a function of $Q^2$. The experimental setup utilizes standard Hall C equipment, as was previously employed in the VCS-I (E12-15-001) experiment, namely the HMS and SHMS spectrometers and a 10 cm liquid hydrogen target. A total of 59 days of unpolarized 75 $\mu A$ electron beam with energy of 1100 MeV (6 days) and 2200 MeV (53 days) is requested for this experiment

The Solenoidal Large Intensity Device (SoLID) for JLab 12 GeV

The Solenoidal Large Intensity Device (SoLID) is a new experimental apparatus planned for Hall A at the Thomas Jefferson National Accelerator Facility (JLab). SoLID will combine large angular and momentum acceptance with the capability to handle very high data rates at high luminosity. With a slate of approved high-impact physics experiments, SoLID will push JLab to a new limit at the QCD intensity frontier that will exploit the full potential of its 12 GeV electron beam. In this paper, we present an overview of the rich physics program that can be realized with SoLID, which encompasses the tomography of the nucleon in 3-D momentum space from Semi-Inclusive Deep Inelastic Scattering (SIDIS), expanding the phase space in the search for new physics and novel hadronic effects in parity-violating DIS (PVDIS), a precision measurement of $J/\psi$ production at threshold that probes the gluon field and its contribution to the proton mass, tomography of the nucleon in combined coordinate and momentum space with deep exclusive reactions, and more. To meet the challenging requirements, the design of SoLID described here takes full advantage of recent progress in detector, data acquisition and computing technologies. In addition, we outline potential experiments beyond the currently approved program and discuss the physics that could be explored should upgrades of CEBAF become a reality in the future.Comment: This white paper for the SoLID program at Jefferson Lab was prepared in part as an input to the 2023 NSAC Long Range Planning exercise. To be submitted to J. Phys.

Establishment of Wolbachia strain wAlbB in Malaysian populations of Aedes aegypti for dengue control

Dengue has enormous health impacts globally. A novel approach to decrease dengue incidence involves the introduction of Wolbachia endosymbionts that block dengue virus transmission into populations of the primary vector mosquito, Aedes aegypti. The wMel Wolbachia strain has previously been trialed in open releases of Ae. aegypti; however, the wAlbB strain has been shown to maintain higher density than wMel at high larval rearing temperatures. Releases of Ae. aegypti mosquitoes carrying wAlbB were carried out in 6 diverse sites in greater Kuala Lumpur, Malaysia, with high endemic dengue transmission. The strain was successfully established and maintained at very high population frequency at some sites or persisted with additional releases following fluctuations at other sites. Based on passive case monitoring, reduced human dengue incidence was observed in the release sites when compared to control sites. The wAlbB strain of Wolbachia provides a promising option as a tool for dengue control, particularly in very hot climates