Optimization of 5-axis milling processes using process models

Productivity and part quality are extremely important for all machining operations, but particularly for 5-axis milling where the machine tool cost is relatively higher, and most parts have complex geometries and high quality requirements with tight tolerances. 5- axis milling, presents additional challenges in modeling due to more complex tool and workpiece interface geometry, and process mechanics. In this paper, modeling and optimization of 5-axis processes with cutting strategy selection are presented. The developed process models are used for cutting force predictions using a part-tool interface identification method which is also presented. Based on the model predictions and simulations, best cutting conditions are identified. Also, for finish process of a complex surface, machining time is estimated using three machining strategy alternatives. Results are demonstrated by example applications, and verified by experiments

Infection with a Brazilian isolate of Zika virus generates RIG‐I stimulatory RNA and the viral NS5 protein blocks type I IFN induction and signalling

Zika virus (ZIKV) is a major public health concern in the Americas. We report that ZIKV infection and RNA extracted from ZIKV infected cells potently activated the induction of type I interferons (IFNs). This effect was fully dependent on the mitochondrial antiviral signalling protein (MAVS), implicating RIG‐I‐like receptors (RLRs) as upstream sensors of viral RNA. Indeed, RIG‐I and the related RNA sensor MDA5 contributed to type I IFN induction in response to RNA from infected cells. We found that ZIKV NS5 from a recent Brazilian isolate blocked type I IFN induction downstream of RLRs and also inhibited type I IFN receptor (IFNAR) signalling. We defined the ZIKV NS5 nuclear localization signal and report that NS5 nuclear localization was not required for inhibition of signalling downstream of IFNAR. Mechanistically, NS5 blocked IFNAR signalling by both leading to reduced levels of STAT2 and by blocking phosphorylation of STAT1, two transcription factors activated by type I IFNs. Taken together, our observations suggest that ZIKV infection induces a type I IFN response via RLRs and that ZIKV interferes with this response by blocking signalling downstream of RLRs and IFNAR

Congenital partial arhinia: a case report

Congenital arhinia is an extremely rare anomaly consisting of an absence of external nasal structures and nasal passages. Fewer than 30 cases have been reported. Patients with a familial absence of the nose have been reported, but the effects of genetic and maternal factors are unknown. Midface hypoplasia may accompany arhinia. Accompanying malformations are thought to be caused by an absent or rudimentary nose. A patient with partial congenital arhinia is presented and the embryology and literature review are discussed

Benign paroxysmal positional vertigo after radiologic scanning: a case series

<p>Abstract</p> <p>Introduction</p> <p>Benign paroxysmal positional vertigo (BPPV) is the most common type of vertigo. It is frequently seen in elderly patients, and the course of the attack may easily mimic cerebrovascular disease. A BPPV attack after a radiologic examination has not been reported previously. We report the cases of two patients who had BPPV attacks after radiologic imaging.</p> <p>Case presentation</p> <p>The first patient with headache and tremor was admitted to the radiology department for cranial computed tomography (CT) imaging. During scanning, she was asked to lie in the supine position with no other head movements for approximately 10 minutes. After the cranial CT imaging, she stood up rapidly, and suddenly experienced a vertigo attack and nausea. The second patient was admitted to the radiology department for evaluation of his renal arteries. During the renal magnetic resonance angiography, he was in the supine position for 20 minutes and asked not to move. After the examination, he stood up rapidly with the help of the technician and suddenly experienced a vertigo attack with nausea and vomiting. The results of standard laboratory analyses and their neurologic examinations were within normal limits and Dix-Hallpike tests showed rotatory nystagmus in both cases. An Epley maneuver was performed to the patients. The results of a control Dix-Hallpike tests after 1 Epley maneuver were negative in both patients.</p> <p>Conclusion</p> <p>Radiologists and clinicians must keep in mind that after radiologic imaging in which the patient is still for some time in the supine position and then helped to stand up rapidly, a BPPV attack may occur.</p

Tracking Target Signal Strengths on a Grid using Sparsity

Multi-target tracking is mainly challenged by the nonlinearity present in the measurement equation, and the difficulty in fast and accurate data association. To overcome these challenges, the present paper introduces a grid-based model in which the state captures target signal strengths on a known spatial grid (TSSG). This model leads to \emph{linear} state and measurement equations, which bypass data association and can afford state estimation via sparsity-aware Kalman filtering (KF). Leveraging the grid-induced sparsity of the novel model, two types of sparsity-cognizant TSSG-KF trackers are developed: one effects sparsity through $\ell_1$-norm regularization, and the other invokes sparsity as an extra measurement. Iterative extended KF and Gauss-Newton algorithms are developed for reduced-complexity tracking, along with accurate error covariance updates for assessing performance of the resultant sparsity-aware state estimators. Based on TSSG state estimates, more informative target position and track estimates can be obtained in a follow-up step, ensuring that track association and position estimation errors do not propagate back into TSSG state estimates. The novel TSSG trackers do not require knowing the number of targets or their signal strengths, and exhibit considerably lower complexity than the benchmark hidden Markov model filter, especially for a large number of targets. Numerical simulations demonstrate that sparsity-cognizant trackers enjoy improved root mean-square error performance at reduced complexity when compared to their sparsity-agnostic counterparts.Comment: Submitted to IEEE Trans. on Signal Processin

A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo

Experiments with replication-competent SARS-CoV-2 were performed in the Biomedicum BSL3 core facility, Karolinska Institutet. We thank Jonas Klingström for providing Calu-3 cells and sharing the Swedish SARS-CoV-2 isolate, and Alex Sigal from the Africa Health Research Institute for providing the beta variant (B.1.351/501Y.V2) isolate. We thank Penny Moore and the NICD (South Africa) for providing the B.1.351/beta variant spike plasmid, which was generated using funding from the South African Medical Research Council. We gratefully acknowledge the G2P-UK National Virology consortium funded by MRC/UKRI (grant ref: MR/W005611/1.) and the Barclay Lab at Imperial College for providing the B.1.617.2 spike plasmid. All cryo-EM data were collected in the Karolinska Institutet’s 3D-EM facility. We thank Agustin Ure for assistance with figure generation and Tomas Nyman (Protein Science Facility at KI) for providing access to SPR instruments. L.H. was supported by the David och Astrid Hageléns stiftelse, the Clas Groschinskys Minnesfond and a Jonas Söderquist’s scholarship. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 101003653 (CoroNAb), to B.M. and G.M.M. B.M.H. is supported by the Knut and Alice Wallenberg Foundation (KAW 2017.0080 and KAW 2018.0080). The work was supported by project grants from the Swedish Research Council to E.S. (2020-02682), B.M.H. (2017-6702 and 2018-3808), B.M. (2018-02381) and to G.M.M. (2018-03914 and 2018-03843). E.S. is supported by Karolinska Institutet Foundation Grants, National Molecular Medicine Program Grants, and the grants from the SciLifeLab National COVID-19 Research Program, financed by the Knut and Alice Wallenberg Foundation. We thank National Microscopy Infrastructure, NMI (VR-RFI 2016-00968).N

Coastal shoreline change assessments at global scales

During the present era of rapid climate change and sea-level rise, coastal change science is needed at global, regional, and local scales. Essential elements of this science, regardless of scale, include that the methods are defendable and that the results are independently verifiable. The recent contribution by Almar et al.1 does not achieve either of these measures as shown by: (i) the use of an error-prone proxy for coastal shoreline and (ii) analyses that are circular and explain little of the data variance