Synthesis of a norcantharidin-tethered guanosine: Protein phosphatase-1 inhibitors that change alternative splicing.

Phosphorylation and dephosphorylation of splicing factors play a key role in pre-mRNA splicing events, and cantharidin and norcantharidin analogs inhibit protein phosphatase-1 (PP1) and change alternative pre-mRNA splicing. Targeted inhibitors capable of selectively inhibiting PP-1 could promote exon 7 inclusion in the survival-of-motorneuron-2 gene (SMN2) and shift the proportion of SMN2 protein from a dysfunctional to a functional form. As a prelude to the development of norcantharidin-tethered oligonucleotide inhibitors, the synthesis a norcantharidin-tethered guanosine was developed in which a suitable tether prevented the undesired cyclization of norcantharidin monoamides to imides and possessed a secondary amine terminus suited to the synthesis of oligonucleotides analogs. Application of this methodology led to the synthesis of a diastereomeric mixture of norcantharidin-tethered guanosines, namely bisammonium (1R,2S,3R,4S)- and (1S,2R,3S,4R)-3-((4-(2-(((((2R,3R,4R,5R)-5-(2-amino-6-oxo-1,6- dihydro-9H-purin-9-yl)-2-(hydroxymethyl)-4-methoxytetrahydrofuran-3-yl) oxy) oxidophosphoryl) oxy) ethyl)-phenethyl)(methyl)carbamoyl)-7-oxabicyclo[2.2.1] heptane-2-carboxylate, which showed activity in an assay for SMN2 pre-mRNA splicin

The Effect of Manual Therapy on Muscle Stiffness in Healthy Individuals

The purpose of this study was to evaluate the immediate and delayed changes in muscle stiffness (in a resting and contracted state) related to DN of the gastrocnemius compared to a sham DN condition. To further investigate this relationship, we investigated these changes at the site of the TP, as well as at a standard site (medial head of the gastrocnemius). We hypothesize that gastrocnemius DN reduces muscle stiffness in individuals with TP

Formulation and performance of variational integrators for rotating bodies

Variational integrators are obtained for two mechanical systems whose configuration spaces are, respectively, the rotation group and the unit sphere. In the first case, an integration algorithm is presented for Euler’s equations of the free rigid body, following the ideas of Marsden et al. (Nonlinearity 12:1647–1662, 1999). In the second example, a variational time integrator is formulated for the rigid dumbbell. Both methods are formulated directly on their nonlinear configuration spaces, without using Lagrange multipliers. They are one-step, second order methods which show exact conservation of a discrete angular momentum which is identified in each case. Numerical examples illustrate their properties and compare them with existing integrators of the literature

Integrable discretizations of some cases of the rigid body dynamics

A heavy top with a fixed point and a rigid body in an ideal fluid are important examples of Hamiltonian systems on a dual to the semidirect product Lie algebra $e(n)=so(n)\ltimes\mathbb R^n$. We give a Lagrangian derivation of the corresponding equations of motion, and introduce discrete time analogs of two integrable cases of these systems: the Lagrange top and the Clebsch case, respectively. The construction of discretizations is based on the discrete time Lagrangian mechanics on Lie groups, accompanied by the discrete time Lagrangian reduction. The resulting explicit maps on $e^*(n)$ are Poisson with respect to the Lie--Poisson bracket, and are also completely integrable. Lax representations of these maps are also found.Comment: arXiv version is already officia

Solar Cell Cracks and Finger Failure Detection Using Statistical Parameters of Electroluminescence Images and Machine Learning

A wide range of defects, failures, and degradation can develop at different stages in the lifetime of photovoltaic modules. To accurately assess their effect on the module performance, these failures need to be quantified. Electroluminescence (EL) imaging is a powerful diagnostic method, providing high spatial resolution images of solar cells and modules. EL images allow the identification and quantification of different types of failures, including those in high recombination regions, as well as series resistance-related problems. In this study, almost 46,000 EL cell images are extracted from photovoltaic modules with different defects. We present a method that extracts statistical parameters from the histogram of these images and utilizes them as a feature descriptor. Machine learning algorithms are then trained using this descriptor to classify the detected defects into three categories: (i) cracks (Mode B and C), (ii) micro-cracks (Mode A) and finger failures, and (iii) no failures. By comparing the developed methods with the commonly used one, this study demonstrates that the pre-processing of images into a feature vector of statistical parameters provides a higher classification accuracy than would be obtained by raw images alone. The proposed method can autonomously detect cracks and finger failures, enabling outdoor EL inspection using a drone-mounted system for quick assessments of photovoltaic fields.</p

Host investment into symbiosis varies among genotypes of the legume Acmispon strigosus, but host sanctions are uniform.

Efficient host control predicts the extirpation of ineffective symbionts, but they are nonetheless widespread in nature. We tested three hypotheses for the maintenance of symbiotic variation in rhizobia that associate with a native legume: partner mismatch between host and symbiont, such that symbiont effectiveness varies with host genotype; resource satiation, whereby extrinsic sources of nutrients relax host control; and variation in host control among host genotypes. We inoculated Acmispon strigosus from six populations with three Bradyrhizobium strains that vary in symbiotic effectiveness on sympatric hosts. We measured proxies of host and symbiont fitness in single- and co-inoculations under fertilization treatments of zero added nitrogen (N) and near-growth-saturating N. We examined two components of host control: 'host investment' into nodule size during single- and co-inoculations, and 'host sanctions' against less effective strains during co-inoculations. The Bradyrhizobium strains displayed conserved growth effects on hosts, and host control did not decline under experimental fertilization. Host sanctions were robust in all hosts, but host lines from different populations varied significantly in measures of host investment in both single- and co-inoculation experiments. Variation in host investment could promote variation in symbiotic effectiveness and prevent the extinction of ineffective Bradyrhizobium from natural populations

Recurrent mutualism breakdown events in a legume rhizobia metapopulation.

Bacterial mutualists generate major fitness benefits for eukaryotes, reshaping the host phenotype and its interactions with the environment. Yet, microbial mutualist populations are predicted to generate mutants that defect from providing costly services to hosts while maintaining the capacity to exploit host resources. Here, we examined the mutualist service of symbiotic nitrogen fixation in a metapopulation of root-nodulating Bradyrhizobium spp. that associate with the native legume Acmispon strigosus. We quantified mutualism traits of 85 Bradyrhizobium isolates gathered from a 700 km transect in California spanning 10 sampled A. strigosus populations. We clonally inoculated each Bradyrhizobium isolate onto A. strigosus hosts and quantified nodulation capacity and net effects of infection, including host growth and isotopic nitrogen concentration. Six Bradyrhizobium isolates from five populations were categorized as ineffective because they formed nodules but did not enhance host growth via nitrogen fixation. Six additional isolates from three populations failed to form root nodules. Phylogenetic reconstruction inferred two types of mutualism breakdown, including three to four independent losses of effectiveness and five losses of nodulation capacity on A. strigosus. The evolutionary and genomic drivers of these mutualism breakdown events remain poorly understood

Review of Student-Built Spectroscopy Instrumentation Projects

Copyright © 2020 American Chemical Society and Division of Chemical Education, Inc. One challenge of teaching chemical analysis is the proliferation of sophisticated, but often impenetrable, instrumentation in the modern laboratory. Complex instruments, and the software that runs them, distance students from the physical and chemical processes that generate the analytical signal. A solution to this challenge is the introduction of a student-driven instrument-building project. Visible absorbance spectroscopy is well-suited to such a project due to its relative simplicity and the ubiquity of absorbance measurements. This Article reviews simple instructor- A nd student-built instruments for spectroscopy, providing an overview of common designs, components, and applications. This comprehensive summary includes options that are suitable for in-person or remote learning with K-12 students and undergraduates in general chemistry, analytical chemistry, instrumental analysis, and electronics courses

Discrete Routh Reduction

This paper develops the theory of abelian Routh reduction for discrete mechanical systems and applies it to the variational integration of mechanical systems with abelian symmetry. The reduction of variational Runge-Kutta discretizations is considered, as well as the extent to which symmetry reduction and discretization commute. These reduced methods allow the direct simulation of dynamical features such as relative equilibria and relative periodic orbits that can be obscured or difficult to identify in the unreduced dynamics. The methods are demonstrated for the dynamics of an Earth orbiting satellite with a non-spherical $J_2$ correction, as well as the double spherical pendulum. The $J_2$ problem is interesting because in the unreduced picture, geometric phases inherent in the model and those due to numerical discretization can be hard to distinguish, but this issue does not appear in the reduced algorithm, where one can directly observe interesting dynamical structures in the reduced phase space (the cotangent bundle of shape space), in which the geometric phases have been removed. The main feature of the double spherical pendulum example is that it has a nontrivial magnetic term in its reduced symplectic form. Our method is still efficient as it can directly handle the essential non-canonical nature of the symplectic structure. In contrast, a traditional symplectic method for canonical systems could require repeated coordinate changes if one is evoking Darboux' theorem to transform the symplectic structure into canonical form, thereby incurring additional computational cost. Our method allows one to design reduced symplectic integrators in a natural way, despite the noncanonical nature of the symplectic structure.Comment: 24 pages, 7 figures, numerous minor improvements, references added, fixed typo

Secure Opportunistic Multipath Key Exchange

The security of today\u27s widely used communication security protocols is based on trust in Certificate Authorities (CAs). However, the real security of this approach is debatable, since certificate handling is tedious and many recent attacks have undermined the trust in CAs. On the other hand, opportunistic encryption protocols such as Tcpcrypt, which are currently gaining momentum as an alternative to no encryption, have similar security to using untrusted CAs or self-signed certificates: they only protect against passive attackers. In this paper, we present a key exchange protocol, Secure Multipath Key Exchange (SMKEX), that enables all the benefits of opportunistic encryption (no need for trusted third parties or pre-established secrets), as well as proven protection against some classes of active attackers. Furthermore, SMKEX can be easily extended to a trust-on-first-use setting and can be easily integrated with TLS, providing the highest security for opportunistic encryption to date while also increasing the security of standard TLS. We show that SMKEX is made practical by the current availability of path diversity between different AS-es. We also show a method to create path diversity with encrypted tunnels without relying on the network topology. These allow SMKEX to provide protection against most adversaries for a majority of Alexa top 100 web sites. We have implemented SMKEX using a modified Multipath TCP kernel implementation and a user library that overwrites part of the socket API, allowing unmodified applications to take advantage of the security provided by SMKEX