Operating Cooperatively (OC) Sensor for Highly Specific Recognition of Nucleic Acids

Molecular Beacon (MB) probes have been extensively used for nucleic acid analysis because of their ability to produce fluorescent signal in solution instantly after hybridization. The indirect binding of MB probe to a target analyte offers several advantages, including: improved genotyping accuracy and the possibility to analyse folded nucleic acids. Here we report on a new design for MB-based sensor, called \u27Operating Cooperatively\u27 (OC), which takes advantage of indirect binding of MB probe to a target analyte. The sensor consists of two unmodified DNA strands, which hybridize to a universal MB probe and a nucleic acid analyte to form a fluorescent complex. OC sensors were designed to analyze two human SNPs and E.coli 16S rRNA. High specificity of the approach was demonstrated by the detection of true analyte in over 100 times excess amount of single base substituted analytes. Taking into account the flexibility in the design and the simplicity in optimization, we conclude that OC sensors may become versatile and efficient tools for instant DNA and RNA analysis in homogeneous solution

Isolated X-ray -- infrared sources in the region of interaction of the supernova remnant IC 443 with a molecular cloud

The nature of the extended hard X-ray source XMMU J061804.3+222732 and its surroundings is investigated using XMM-Newton, Chandra, and Spitzer observations. This source is located in an interaction region of the IC 443 supernova remnant with a neighboring molecular cloud. The X-ray emission consists of a number of bright clumps embedded in an extended structured non-thermal X-ray nebula larger than 30" in size. Some clumps show evidence for line emission at ~1.9 keV and ~3.7 keV at the 99% confidence level. Large-scale diffuse radio emission of IC 443 passes over the source region, with an enhancement near the source. An IR source of about 14" x 7" size is prominent in the 24 um, 70 um, and 2.2 um bands, adjacent to a putative Si K-shell X-ray line emission region. The observed IR/X-ray morphology and spectra are consistent with those expected for J/C-type shocks of different velocities driven by fragmented supernova ejecta colliding with the dense medium of a molecular cloud. The IR emission of the source detected by Spitzer can be attributed to both continuum emission from an HII region created by the ejecta fragment and line emission excited by shocks. This source region in IC 443 may be an example of a rather numerous population of hard X-ray/IR sources created by supernova explosions in the dense environment of star-forming regions. Alternative Galactic and extragalactic interpretations of the observed source are also discussed.Comment: The Astrophysical Journal, v. 677 (April 2008), in pres

An update on treatment modalities for ulnar nerve entrapment: A literature review

Context: Ulnar nerve entrapment is a relatively common entrapment syndrome second only in prevalence to carpal tunnel syndrome. The potential anatomic locations for entrapment include the brachial plexus, cubital tunnel, and Guyon�s canal. Ulnar nerve entrapment is more so prevalent in pregnancy, diabetes, rheumatoid arthritis, and patients with occupations involving periods of prolonged elbow flexion and/or wrist dorsiflexion. Cyclists are particularly at risk of Guyon�s canal neuropathy. Patients typically present with sensory deficits of the palmar aspect of the fourth and fifth digits, followed by motor symptoms, including decreased pinch strength and difficulty fastening shirt buttons or opening bottles. Evidence Acquisition: Literature searches were performed using the belowMeSHTerms using Mendeley version 1.19.4. Search fields were varied until further searches revealed no new articles. All articles were screened by title and abstract. Decision was made to include an article based on its relevance and the list of final articles was approved three of the authors. This included reading the entirety of the artice. Anyquestion regarding the inclusion of anarticlewasdiscussed by all authors untilanagreementwasreached. Results: X-rayandCTplay a role in diagnosiswhenabonyinjury is thought to be related to the pathogenesis (i.e., fracture of thehook of the hamate.) MRI plays a role where soft tissue is thought to be related to the pathogenesis (i.e., tumor or swelling.) Electromyography and nerve conduction also play a role in diagnosis. Medicalmanagement, in conjunction with physical therapy, shows limited promise. However, minimally invasive techniques, including peripheral percutaneous electrode placement and ultrasound-guided electrode placement, have all been recently studied and show great promise. When these techniques fail, clinicians should resort to decompression, which can be done endoscopically or through an open incision. Endoscopic ulnar decompression shows great promise as a surgical option with minimal incisions. Conclusions: Clinical diagnosis of ulnar nerve entrapment can often be delayed and requires the suspicion as well as a thorough neurological exam. Early recognition and diagnois are important for early institution of treatment. A wide array of diagnostic imaging can be useful in ruling out bony, soft tissue, or vascular etiologies, respectively. However, clinicians should resort to electrodiagnostic testing when a definitive diagnois is needed. Many new minimally invasive techniques are in the literature and show great promise; however, further large scale trials are needed to validate these techniques. Surgical options remains as a gold standard when adequate symptom relief is not achieved through minimally invasive means. © 2020, Author(s)

MAGIC J0616+225 as delayed TeV emission of cosmic-rays diffusing from SNR IC 443

We present a theoretical model that explains the high energy phenomenology of the neighborhood of SNR IC 443, as observed with the Major Atmospheric Gamma Imaging Cherenkov (MAGIC) telescope and the Energetic Gamma-Ray Experiment Telescope (EGRET). We interpret MAGIC J0616+225 as delayed TeV emission of cosmic-rays diffusing from IC 443 and interacting with a known cloud located at a distance of about 20 pc in the foreground of the remnant. This scenario naturally explains the displacement between EGRET and MAGIC sources, their fluxes, and their spectra. We compare this model with others recently presented, and discuss how it can be tested with observations by the Gamma-ray Large Area Telescope (GLAST).Comment: Accepted for publication in MNRAS Letter

Peripheral neuromodulation for the management of headache

Context: Neuromodulation is an expanding field of study for headache treatment to reduce pain by targeting structures within the nervous system that are commonly involved in headache pathophysiology, such as the vagus nerve (VNS), occipital nerves, or sphenopalatine ganglion (SPG) for stimulation. Pharmaceutical medical therapies for abortive and prophylactic treatment, such as triptans, NSAIDs, beta-blockers, TCAs, and antiepileptics, are effective for some individuals, but the role that technology plays in investigating other therapeutic modalities is essential. Peripheral neuromodulation has gained popularity and FDA approval for use in treating certain headaches and migraine headache conditions, particularly in those who are refractory to treatment. Early trials found FDA approved neurostimulatory implant devices, including Cephaly and SpringTMS, improved patient-oriented outcomes with reductions in headaches per month (frequency) and severity. Evidence Acquisition: This was a narrative review. The sources for this review are as follows: Searching on PubMed, Google Scholar, Medline, and ScienceDirect from 1990 - 2019 using keywords: Peripheral Neuromodulation, Headache, vagus nerve, occipital nerves, sphenopalatine ganglion. Results: The first noninvasive neurostimulator device approved for migraine treatment was the Cefaly device, an external trigeminal nerve stimulation device (e-TNS) that transcutaneously excites the supratrochlear and supraorbital branches of the ophthalmic nerve. The second noninvasive neurostimulation device receiving FDA approval was the single-pulse transcranial magnetic stimulator, SpringTMS, positioned at the occiput to treat migraine with aura. GammaCore is a handheld transcutaneous vagal nerve stimulator applied directly to the neck at home by the patient for treatment of cluster headache (CH) and migraine. Several other devices are in development for the treatment of headaches and target headache evolution at different levels and inputs. The Scion device is a caloric vestibular stimulator (CVS) which interfaces with the user through a set of small cones resting in the ear canal on either side and held in place by modified over-ear headphones. The pulsante SPG Microstimulator is a patient-controlled device implanted in the patient�s upper jaw via an hour-long oral procedure to target the sphenopalatine ganglion. The occipital nerve stimulator (ONS) is an invasive neuromodulation device for headache treatment that consists of an implanted pulse generator on the chest wall connected to a subcutaneous lead with 4 - 8 electrodes that is tunneled the occiput. Conclusions: The aim of this review is to provide a comprehensive overview of the efficacy, preliminary outcomes, and limitations of neurostimulatory implants available for use in the US and those pending further development. © 2020, Author(s)

IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome

Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species

Pion and proton showers in the CALICE scintillator-steel analogue hadron calorimeter

Showers produced by positive hadrons in the highly granular CALICE scintillator-steel analogue hadron calorimeter were studied. The experimental data were collected at CERN and FNAL for single particles with initial momenta from 10 to 80 GeV/c. The calorimeter response and resolution and spatial characteristics of shower development for proton- and pion-induced showers for test beam data and simulations using Geant4 version 9.6 are compared.Comment: 26 pages, 16 figures, JINST style, changes in the author list, typos corrected, new section added, figures regrouped. Accepted for publication in JINS

Performance of the first prototype of the CALICE scintillator strip electromagnetic calorimeter

A first prototype of a scintillator strip-based electromagnetic calorimeter was built, consisting of 26 layers of tungsten absorber plates interleaved with planes of 45x10x3 mm3 plastic scintillator strips. Data were collected using a positron test beam at DESY with momenta between 1 and 6 GeV/c. The prototype's performance is presented in terms of the linearity and resolution of the energy measurement. These results represent an important milestone in the development of highly granular calorimeters using scintillator strip technology. This technology is being developed for a future linear collider experiment, aiming at the precise measurement of jet energies using particle flow techniques

The Time Structure of Hadronic Showers in highly granular Calorimeters with Tungsten and Steel Absorbers

The intrinsic time structure of hadronic showers influences the timing capability and the required integration time of hadronic calorimeters in particle physics experiments, and depends on the active medium and on the absorber of the calorimeter. With the CALICE T3B experiment, a setup of 15 small plastic scintillator tiles read out with Silicon Photomultipliers, the time structure of showers is measured on a statistical basis with high spatial and temporal resolution in sampling calorimeters with tungsten and steel absorbers. The results are compared to GEANT4 (version 9.4 patch 03) simulations with different hadronic physics models. These comparisons demonstrate the importance of using high precision treatment of low-energy neutrons for tungsten absorbers, while an overall good agreement between data and simulations for all considered models is observed for steel.Comment: 24 pages including author list, 9 figures, published in JINS

Shower development of particles with momenta from 15 GeV to 150 GeV in the CALICE scintillator-tungsten hadronic calorimeter

We present a study of showers initiated by electrons, pions, kaons, and protons with momenta from 15 GeV to 150 GeV in the highly granular CALICE scintillator-tungsten analogue hadronic calorimeter. The data were recorded at the CERN Super Proton Synchrotron in 2011. The analysis includes measurements of the calorimeter response to each particle type as well as measurements of the energy resolution and studies of the longitudinal and radial shower development for selected particles. The results are compared to Geant4 simulations (version 9.6.p02). In the study of the energy resolution we include previously published data with beam momenta from 1 GeV to 10 GeV recorded at the CERN Proton Synchrotron in 2010.Comment: 35 pages, 21 figures, 8 table