Metastases suppressor NME2 associates with telomere ends and telomerase and reduces telomerase activity within cells

Analysis of chromatin-immunoprecipitation followed by sequencing (ChIP-seq) usually disregards sequence reads that do not map within binding positions (peaks). Using an unbiased approach, we analysed all reads, both that mapped and ones that were not included as part of peaks. ChIP-seq experiments were performed in human lung adenocarcinoma and fibrosarcoma cells for the metastasis suppressor non-metastatic 2 (NME2). Surprisingly, we identified sequence reads that uniquely represented human telomere ends in both cases. In vivo presence of NME2 at telomere ends was validated using independent methods and as further evidence we found intranuclear association of NME2 and the telomere repeat binding factor 2. Most remarkably, results demonstrate that NME2 associates with telomerase and reduces telomerase activity in vitro and in vivo, and sustained NME2 expression resulted in reduced telomere length in aggressive human cancer cells. Anti-metastatic function of NME2 has been demonstrated in human cancers, however, mechanisms are poorly understood. Together, findings reported here suggest a novel role for NME2 as a telomere binding protein that can alter telomerase function and telomere length. This presents an opportunity to investigate telomere-related interactions in metastasis suppression

Demonstrating a superconducting dual-rail cavity qubit with erasure-detected logical measurements

A critical challenge in developing scalable error-corrected quantum systems is the accumulation of errors while performing operations and measurements. One promising approach is to design a system where errors can be detected and converted into erasures. A recent proposal aims to do this using a dual-rail encoding with superconducting cavities. In this work, we implement such a dual-rail cavity qubit and use it to demonstrate a projective logical measurement with erasure detection. We measure logical state preparation and measurement errors at the $0.01\%$-level and detect over $99\%$ of cavity decay events as erasures. We use the precision of this new measurement protocol to distinguish different types of errors in this system, finding that while decay errors occur with probability $\sim 0.2\%$ per microsecond, phase errors occur 6 times less frequently and bit flips occur at least 170 times less frequently. These findings represent the first confirmation of the expected error hierarchy necessary to concatenate dual-rail erasure qubits into a highly efficient erasure code

Psychometric Curve and Behavioral Strategies for Whisker-Based Texture Discrimination in Rats

The rodent whisker system is a major model for understanding neural mechanisms for tactile sensation of surface texture (roughness). Rats discriminate surface texture using the whiskers, and several theories exist for how texture information is physically sensed by the long, moveable macrovibrissae and encoded in spiking of neurons in somatosensory cortex. However, evaluating these theories requires a psychometric curve for texture discrimination, which is lacking. Here we trained rats to discriminate rough vs. fine sandpapers and grooved vs. smooth surfaces. Rats intermixed trials at macrovibrissa contact distance (nose >2 mm from surface) with trials at shorter distance (nose <2 mm from surface). Macrovibrissae were required for distant contact trials, while microvibrissae and non-whisker tactile cues were used for short distance trials. A psychometric curve was measured for macrovibrissa-based sandpaper texture discrimination. Rats discriminated rough P150 from smoother P180, P280, and P400 sandpaper (100, 82, 52, and 35 µm mean grit size, respectively). Use of olfactory, visual, and auditory cues was ruled out. This is the highest reported resolution for rodent texture discrimination, and constrains models of neural coding of texture information

Phase I (first-in-man) prophylactic vaccine′s clinical trials: Selecting a clinical trial site

An appropriately equipped and staffed Phase I unit is critical for smooth conduct of a first-in-man clinical trial. The first-in-man prophylactic vaccine trial(s) requires basic infrastructure of clinical trial site, experienced and dedicated site staff and healthy adults as volunteers. The facility should have access to equipment, emergency services, laboratory, pharmacy and archiving.In terms of design, infrastructure, workflow and manpower, a Phase I unit for testing a novel vaccine or drug are quite similar. However, there are some important attributes, which should be taken into consideration, while performing pre-trial site selection for conducting phase I trial with a new or novel vaccine

Short term analysis of healed post-tubercular kyphosis in younger children based on principles of congenital kyphosis

Background: The patients with healed severe progressive tubercular kyphosis may develop late-onset paraplegia. A particular subgroup of these children (Type IB progression) may benefit from the management principles of congenital kyphosis. Self-correction may be observed by selective continued growth of anterior vertebral epiphyseal end-plates over the posterior fused mass. We report a series of cases with posterior fusion of progressive post-tubercular kyphosis with an aim to prevent further progression of kyphosis and to assess if any gradual self correction is seen in followup. Materials and Methods: Twelve children fulfilling inclusion criteria of clinicoradiological, hematological diagnosis of healed spine TB having no or <2 spine at risk signs having documented progression of kyphosis and neural deficit underwent posterior fusion in situ without instrumentation, using autogenous iliac crest grafts as well as allograft donor bone graft. They were followed up to maximum of 5 years. Results: All 12 children had a progressive increase in angle preoperatively. Mean followup was 3.6 years. Post surgery, 66% showed a clinical improvement and correction, 25% had static angle, and worsening in one patient. Thus, overall 91% have a favorable result. Conclusion: The mechanism of correction of deformity in presence of posterior fusion is continued growth of the anterior epiphyseal end plates and hence this leads to selective differential anterior column growth giving gradual correction of kyphosis. This avoids anterior, technically demanding and complex, internal gibbus surgeries. This procedure is simple, safe, and less morbid with good results, avoiding long term disability to the patients in selected group of patients

A quantum‐based diagnostics approach for additive manufacturing machine

Abstract Current Additive Manufacturing machines have limited techniques to observe process conditions and to decrease process errors. In order to overcome these limitations and increase the level and accuracy of machine intelligence, machine conditions need to be monitored more meticulously. A novel method for the condition monitoring of a 3D‐printer is proposed in this paper. Quantum support vector machine (QSVM) is compiled for recognizing the health condition of the 3D‐printer. The proposed quantum machine learning approach helps in monitoring the health state of the machine and classifies the same as healthy or aberrant. Classical machine learning approaches are inefficient to process the large amount of experimental data in real time. For better decision‐making on such big data, quantum machine learning approaches are deployed which are much more efficient due to their exponential speed and parallel operation on complex sensor data, they show speedups in both the dimensionality and number of experimental data deployed to train the algorithm. The simulation results show that the proposed method has higher accuracy in fault diagnosis than the traditional Support Vector Machine. All the numerical simulations and experiments have been carried out on a real quantum hardware provided by the IBM Quantum computing over the cloud