THE SPIRALS ON THE OBLATE AND PROLATE SPHEROIDS OF LORENTZ-MINKOWSKI 3− SPACE R13

Spirials are differentiable curves that meet all meridians of a rotational surface at a constant angle. In this study, we obtain differential equations of all spirals on hyperbolic oblate and Lorentzian prolate spheroids. Then we define the general parametrizations of spirals which are solutions of differential equations

Structure of SNX9 SH3 in complex with a viral ligand reveals the molecular basis of its unique specificity for alanine-containing class I SH3 motifs

Class I SH3 domain-binding motifs generally comply with the consensus sequence [R/K]x0PxxP, the hydrophobic residue 0 being proline or leucine. We have studied the unusual 0 = Ala-specificity of SNX9 SH3 by determining its complex structure with a peptide present in eastern equine encephalitis virus (EEEV) nsP3. The structure revealed the length and composition of the n-Src loop as important factors determining specificity. We also compared the affinities of EEEV nsP3 peptide, its mutants, and cellular ligands to SNX9 SH3. These data suggest that nsP3 has evolved to minimize reduction of conformational entropy upon binding, hence acquiring stronger affinity, enabling takeover of SNX9. The RxAPxxP motif was also found in human T cell leukemia virus-1 (HTLV-1) Gag polyprotein. We found that this motif was required for efficient HTLV-1 infection, and that the specificity of SNX9 SH3 for the RxAPxxP core binding motif was importantly involved in this process.Peer reviewe

Antidepressant and Antipsychotic Drugs Reduce Viral Infection by SARS-CoV-2 and Fluoxetine Shows Antiviral Activity Against the Novel Variants in vitro

Repurposing of currently available drugs is a valuable strategy to tackle the consequences of COVID-19. Recently, several studies have investigated the effect of psychoactive drugs on SARS-CoV-2 in cell culture models as well as in clinical practice. Our aim was to expand these studies and test some of these compounds against newly emerged variants. Several antidepressants and antipsychotic drugs with different primary mechanisms of action were tested in ACE2/TMPRSS2-expressing human embryonic kidney cells against the infection by SARS-CoV-2 spike protein-dependent pseudoviruses. Some of these compounds were also tested in human lung epithelial cell line, Calu-1, against the first wave (B.1) lineage of SARS-CoV-2 and the variants of concern, B.1.1.7, B.1.351, and B.1.617.2. Several clinically used antidepressants, including fluoxetine, citalopram, reboxetine, imipramine, as well as antipsychotic compounds chlorpromazine, flupenthixol, and pimozide inhibited the infection by pseudotyped viruses with minimal effects on cell viability. The antiviral action of several of these drugs was verified in Calu-1 cells against the B.1 lineage of SARS-CoV-2. By contrast, the anticonvulsant carbamazepine, and novel antidepressants ketamine, known as anesthetic at high doses, and its derivatives as well as MAO and phosphodiesterase inhibitors phenelzine and rolipram, respectively, showed no activity in the pseudovirus model. Furthermore, fluoxetine remained effective against pseudoviruses with common receptor binding domain mutations, N501Y, K417N, and E484K, as well as B.1.1.7 (alpha), B.1.351 (beta), and B.1.617.2 (delta) variants of SARS-CoV-2. Our study confirms previous data and extends information on the repurposing of these drugs to counteract SARS-CoV-2 infection including different variants of concern, however, extensive clinical studies must be performed to confirm our in vitro findings.Peer reviewe

A Generic, Scalable, and Rapid Time-Resolved Förster Resonance Energy Transfer-Based Assay for Antigen Detection—SARS-CoV-2 as a Proof of Concept

Peer reviewe

Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants

Here the authors describe a small antibody-like protein that can prevent infection by diverse SARS-CoV-2 variants in cell culture and in mice that were intranasally treated with this inhibitor before or shortly after being exposed to the virus.The emergence of increasingly immunoevasive SARS-CoV-2 variants emphasizes the need for prophylactic strategies to complement vaccination in fighting the COVID-19 pandemic. Intranasal administration of neutralizing antibodies has shown encouraging protective potential but there remains a need for SARS-CoV-2 blocking agents that are less vulnerable to mutational viral variation and more economical to produce in large scale. Here we describe TriSb92, a highly manufacturable and stable trimeric antibody-mimetic sherpabody targeted against a conserved region of the viral spike glycoprotein. TriSb92 potently neutralizes SARS-CoV-2, including the latest Omicron variants like BF.7, XBB, and BQ.1.1. In female Balb/c mice intranasal administration of just 5 or 50 micrograms of TriSb92 as early as 8 h before but also 4 h after SARS-CoV-2 challenge can protect from infection. Cryo-EM and biochemical studies reveal triggering of a conformational shift in the spike trimer as the inhibitory mechanism of TriSb92. The potency and robust biochemical properties of TriSb92 together with its resistance against viral sequence evolution suggest that TriSb92 could be useful as a nasal spray for protecting susceptible individuals from SARS-CoV-2 infection.Peer reviewe

Complications related to surgically assisted rapid palatal expansion

Objective. The goals of this retrospective clinical study were to identify surgically assisted rapid palatal expansion (SARPE) complications and assess their incidence, with the aim of informing surgeons and orthodontists of the risks of this widely used procedure before they recommend it to patients. Study Design. Between June 2008 and July 2010, 60 patients (23 women and 37 men) underwent SARPE according to a defined multidisciplinary protocol at the University of Marmara, Istanbul, Turkey. Results. Twelve patients (20%) suffered from nasal bleeding. Of these 12, 2 patients suffered late-onset bleeding beginning on postoperative day 8, and in the other 10, nasal bleeding was insignificant. Three patients reported excessive lacrimation postoperatively. Minor problems related to pain and numbness were all temporary. Conclusions. SARPE procedures have traditionally been reported to be associated with low morbidity, especially in comparison with other orthognathic surgical procedures. However, many complications have been reported

Characterizing the Growth of One Student\u27s Mathematical Understanding in a Multi-Representational Learning Environment

The purpose of this study was to characterize the growth of one student’s mathematical understanding and use of different representations about a geometric transformation, dilation. We accomplished this purpose by using the Pirie-Kieren model jointly with the Semiotic Representation Theory as a lens. Elif, a 10th- grade student, was purposefully chosen as the case for this study because of the growth of mathematical understanding about dilation she exhibited over time. Elif participated in task-based interviews before, during and after participating in a variety of transformation lessons where she used multiple representations, including physical and virtual manipulatives. The results revealed that Elif was able to progress in her mathematical understanding from informal levels to the formal levels in the Pirie-Kieren model as she performed treatments and conversions, movements involving different registers of representations. The results also showed numerous examples of Elif’s mathematical understanding based on folding back activities, complementary aspects of acting and expressing, and interventions. Using the two theories together provides a powerful and holistic approach to a deeper understanding of mathematical learning by characterizing and articulating the growth of mathematical understanding and the way of mathematical thinking