Subnanosecond Fluctuations in Low-Barrier Nanomagnets

Fast magnetic fluctuations due to thermal torques have useful technological functionality ranging from cryptography to probabilistic computing. The characteristic time of fluctuations in typical uniaxial anisotropy magnets studied so far is bounded from below by the well-known energy relaxation mechanism. This time scales as $\alpha^{-1}$, where $\alpha$ parameterizes the strength of dissipative processes. Here, we theoretically analyze the fluctuating dynamics in easy-plane and antiferromagnetically coupled nanomagnets. We find in such magnets, the dynamics are strongly influenced by fluctuating intrinsic fields, which give rise to an additional dephasing-type mechanism for washing out correlations. In particular, we establish two time scales for characterizing fluctuations (i) the average time for a nanomagnet to reverse|which for the experimentally relevant regime of low damping is governed primarily by dephasing and becomes independent of $\alpha$, (ii) the time scale for memory loss of a single nanomagnet|which scales as $\alpha^{-1/3}$ and is governed by a combination of energy dissipation and dephasing mechanism. For typical experimentally accessible values of intrinsic fields, the resultant thermal-fluctuation rate is increased by multiple orders of magnitude when compared with the bound set solely by the energy relaxation mechanism in uniaxial magnets. This could lead to higher operating speeds of emerging devices exploiting magnetic fluctuations

Does Segmental Kyphosis Affect Surgical Outcome after a Posterior Decompressive Laminectomy in Multisegmental Cervical Spondylotic Myelopathy?

Study DesignRetrospective analysis.PurposeTo compare results of laminectomy in multisegmental compressive cervical myelopathy (CSM) with lordosis versus segmental kyphosis.Overview of LiteratureLaminectomy is an established procedure for decompression in CSM with cervical lordosis. However in patients with segmental kyphosis, it is associated with risk of progression of kyphosis and poor outcome. Whether this loss of sagittal alignment affects functional outcome is not clear.MethodsWe retrospectively reviewed 68 patients who underwent laminectomy for CSM from 1998 to 2009. As per preoperative magnetic resonance images, 36 patients had preoperative lordosis (Group 1) and 32 had segmental kyphosis (Group 2). We studied age at the time of surgery, duration of preoperative symptoms, recovery rate, magnitude of postoperative backward shifting of spinal cord and loss of sagittal alignment.ResultsMean follow up was 5.05 years (range, 2–13 years) and mean age at the time of surgery 61.88 years. Group 1 had 20 men and 16 women and Group 2 had 19 men and 13 women. Mean recovery rate in Group 1 was 60.32%, in Group 2 was 63.7% without any statistical difference (p-value 0.21, one tailed analysis of variance). Two patients of Group 1 had loss of cervical lordosis by five degrees. In Group 2 seven patients had progression of segmental kyphosis by 5–10 degrees and two patients by more than 10 degrees. Mean cord shift was more in Group 1 (mean, 2.41 mm) as compared to Group 2 (mean, –1.97 mm) but it had no correlation to recovery rate. Patients with younger age (mean, 57 years) and less duration of preoperative symptoms (mean, 4.86 years) had better recovery rate (75%).ConclusionsClinical outcome in CSM is not related to preoperative cervical spine alignment. Thus, lordosis is not mandatory for planning laminectomy in CSM. Good outcome is expected in younger patients operated earliest after onset of symptoms

Sessile Serrated Adenomas in the Proximal Colon are Likely to be Flat, Large and Occur in Smokers

Aim: To examine the epidemiology and the morphology of the proximal sessile serrated adenomas (SSAs). Methods: We conducted a retrospective study to identify patients with SSAs using a university-based hospital pathology database query from January 2007 to April 2011. Data collected included: age, gender, ethnicity, body mass index, diabetes, smoking, family history of colorectal cancer, aspirin, and statin use. We collected data on morphology of SSAs including site (proximal or distal), size, and endoscopic appearance (flat or protuberant). We also compared proximal SSAs to proximal tubular adenomas detected during same time period

An intranasal ASO therapeutic targeting SARS-CoV-2

The COVID-19 pandemic is exacting an increasing toll worldwide, with new SARS-CoV-2 variants emerging that exhibit higher infectivity rates and that may partially evade vaccine and antibody immunity. Rapid deployment of non-invasive therapeutic avenues capable of preventing infection by all SARS-CoV-2 variants could complement current vaccination efforts and help turn the tide on the COVID-19 pandemic. Here, we describe a novel therapeutic strategy targeting the SARS-CoV-2 RNA using locked nucleic acid antisense oligonucleotides (LNA ASOs). We identify an LNA ASO binding to the 5′ leader sequence of SARS-CoV-2 that disrupts a highly conserved stem-loop structure with nanomolar efficacy in preventing viral replication in human cells. Daily intranasal administration of this LNA ASO in the COVID-19 mouse model potently suppresses viral replication (>80-fold) in the lungs of infected mice. We find that the LNA ASO is efficacious in countering all SARS-CoV-2 “variants of concern” tested both in vitro and in vivo. Hence, inhaled LNA ASOs targeting SARS-CoV-2 represents a promising therapeutic approach to reduce or prevent transmission and decrease severity of COVID-19 in infected individuals. LNA ASOs are chemically stable and can be flexibly modified to target different viral RNA sequences and could be stockpiled for future coronavirus pandemics

Progenitor identification and SARS-CoV-2 infection in human distal lung organoids

The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange. Three-dimensional in vitro human distal lung culture systems would strongly facilitate investigation of pathologies including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. We generated long-term feeder-free, chemically defined culture of distal lung progenitors as organoids derived from single adult human alveolar epithelial type II (AT2) or KRT5+ basal cells. AT2 organoids exhibited AT1 transdifferentiation potential while basal cell organoids developed lumens lined by differentiated club and ciliated cells. Single cell analysis of basal organoid KRT5+ cells revealed a distinct ITGA6+ITGB4+ mitotic population whose proliferation further segregated to a TNFRSF12Ahi subfraction comprising ~10% of KRT5+ basal cells, residing in clusters within terminal bronchioles and exhibiting enriched clonogenic organoid growth activity. Distal lung organoids were created with apical-out polarity to display ACE2 on the exposed external surface, facilitating SARS-CoV-2 infection of AT2 and basal cultures and identifying club cells as a novel target population. This long-term, feeder-free organoid culture of human distal lung, coupled with single cell analysis, identifies unsuspected basal cell functional heterogeneity and establishes a facile in vitro organoid model for human distal lung infections including COVID-19-associated pneumonia