Synthesis of 7-(Dialkylaminoalkyl)-benzo [c] phenothiazines; The Metalation of 7H-Benzo [c] phenothiazine With \u3cem\u3en\u3c/em\u3e-Butyllithium

Introduction: Phenothiazine is one of the more widely investigated heterocyclic molecules known to modern chemistry. The founding of the synthetic dye industry in the latter part of the nineteenth century stimulated many new fields of organic research, one of which was phenothiazine chemistry. Bernthsen, known as father of phenothiazine chemistry, first synthesized (1) this compound in 1883, after suspecting its presence in the nucleus of the methylene blue dyes. Since that time phenothiazine and its derivatives have found uses as antioxidants (2), antihistamines (3), antiemetics (4), and in the treatment of Parkinson\u27s disease (5). During the past decade, considerable attention has been given to N-(dialkylaminoalkyl)-phenothiazine types because of their excellent effect in suppressing nausea (4) and in the treatment of neruopsychiatric disorders (6). More recently, the tranquilizing activity of certain N-(dialkylaminoalkyl)-phenothiazine types has been reported (7), Thus, the pharmacological usefulness of phenothiazine derivatives is well-established. On the other hand, the known chemistry of the benzophenothiazines is quite limited. Vast opportunity exists for chemotherapeutic investigations in this area, and only recently some penetration into this field of endeavor was begun. In 1942, it was (8) demonstrated that tumor growth inhibition occurred with some simple benzophenothiazine types. Talukdar and Shirley (9) recently prepared a series of 12-(dialkylaminoalkyl)-benzo [a] phenothiazines for pharmacological evaluation, but the results of these tests are not yet available. In view of such a wide spectrum of pharmacological application enjoyed by phenothiazine and its derivatives, and the opportunity for chemotherapeutic investigation in the field of benzophenothiazine chemistry, it is felt that benzophenothizines structurally related to some of the more useful phenothiazine types should be synthesized and pharmacologically evaluated. This research is primarily concerned with the preparation of 7-(dialkylaminoalkyl)-benzo [c] phenothiazines, compounds similar in structure to the therapeutically useful phenothiazine types. In connection with the synthesis of these N-alkylated benzophenothiazines, there was considerable interest in finding new and better methods of introducing substituents into the lesser accessible positions of the benzophenothiazine nucleus. In an effort to do this, a study of the metalation of 7H-benzo [c] phenothiazine with n-butyllithium was undertaken. The compounds prepared in this investigation are currently being tested by the Eli Lilly Company of Indianapolis, Indiana, for central nervous system effects and by the National Cancer Institute for anti-cancer activity. It is hoped that the results of this research will in some way benefit the extensive program now being conducted for the development of new and more useful drugs

Reading-to-learn from subject-matter texts: A digital storytelling circle approach

Digital storytelling circles (DSCs) are multimodal platforms aimed at improving students’ comprehension of subject matter texts. In a small group, students in a DSC engage in reading, writing, speaking, listening, viewing, using digital tools, and manipulating texts and instructional strategies. Roles are assigned to each group member as they use the tools provided by the multimodal platform to create a digital story. Most of the literature supports the notion that the experience of creating digital stories can have a positive impact on students’ acquisition of literacy skills and their motivation to engage with the text. This chapter presents a model for using DSCs in the post-reading phase of a Directed Reading Activity (DRA). Case study findings highlight two DSCs that exhibited qualities of developing the literacy strategies necessary in reading-to-learn with complex content area texts.https://nsuworks.nova.edu/fse_facbooks/1000/thumbnail.jp

The Two Variables in The Triple System HR 6469=V819 Her: One Eclipsing, One Spotted

A complete BV light curve, from 14 nights of good data obtained with the Vanderbilt University-Tennessee State University (VU-TSU) automatic telescope, are presented and solved with the Wilson-Devinney program. Third light is evaluated, with the companion star brighter by 0.58m in V and 0.11m in B. The eclipses are partial. Inferred color indices yield F2 V and F8 V for the eclipsing pair and G8 IV-III for the distant companion star. After removing the variability due to eclipses, we study the residual variability of the G8 IV-III star over the ten years 1982 to 1992. Each yearly light curve is fit with a two-spot model. Three relatively long-lived spots are identified, with rotation periods of 85.9d, 85.9d, and 86.1d. The weak and intermittent variability is understood because the G8 IV-III star has a Rossby number at the threshold for the onset of heavy spottedness

A pseudomolecule assembly of the Rocky Mountain elk genome

Rocky Mountain elk (Cervus canadensis) populations have significant economic implications to the cattle industry, as they are a major reservoir for Brucella abortus in the Greater Yellowstone area. Vaccination attempts against intracellular bacterial diseases in elk populations have not been successful due to a negligible adaptive cellular immune response. A lack of genomic resources has impeded attempts to better understand why vaccination does not induce protective immunity. To overcome this limitation, PacBio, Illumina, and Hi-C sequencing with a total of 686-fold coverage was used to assemble the elk genome into 35 pseudomolecules. A robust gene annotation was generated resulting in 18,013 gene models and 33,422 mRNAs. The accuracy of the assembly was assessed using synteny to the red deer and cattle genomes identifying several chromosomal rearrangements, fusions and fissions. Because this genome assembly and annotation provide a foundation for genome-enabled exploration of Cervus species, we demonstrate its utility by exploring the conservation of immune system-related genes. We conclude by comparing cattle immune system-related genes to the elk genome, revealing eight putative gene losses in elk

Biomedical imaging research opportunities workshop IV: A white paper

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134967/1/mp5838.pd

Modulation of the thalamus by microburst vagus nerve stimulation: a feasibility study protocol

Vagus nerve stimulation (VNS) was the first device-based therapy for epilepsy, having launched in 1994 in Europe and 1997 in the United States. Since then, significant advances in the understanding of the mechanism of action of VNS and the central neurocircuitry that VNS modulates have impacted how the therapy is practically implemented. However, there has been little change to VNS stimulation parameters since the late 1990s. Short bursts of high frequency stimulation have been of increasing interest to other neuromodulation targets e.g., the spine, and these high frequency bursts elicit unique effects in the central nervous system, especially when applied to the vagus nerve. In the current study, we describe a protocol design that is aimed to assess the impact of high frequency bursts of stimulation, called “Microburst VNS”, in subjects with refractory focal and generalized epilepsies treated with this novel stimulation pattern in addition to standard anti-seizure medications. This protocol also employed an investigational, fMRI-guided titration protocol that permits personalized dosing of Microburst VNS among the treated population depending on the thalamic blood-oxygen-level-dependent signal. The study was registered on clinicaltrials.gov (NCT03446664). The first subject was enrolled in 2018 and the final results are expected in 2023

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead