The brachyopoid Hadrokkosaurus bradyi from the early Middle Triassic of Arizona, and a phylogenetic analysis of lower jaw characters in temnospondyl amphibians

The holotype of the brachyopoid temnospondyl Hadrokkosaurus bradyi, represented by a right lower jaw ramus, is re−ex− amined based upon new data and revision of various morphological features. Additional fragmentary jaw material re− ferred to this species is briefly described. Prominent features are a large postsymphyseal foramen that is anteriorly open, and prearticular and surangular buttresses for support of the articular. Brachyopoid characters include a long and robust postglenoid area formed by surangular and prearticular, anterior and posterior keels on at least some marginal dentary teeth, and subtriangular outline of the adductor fossa in dorsal view. Five features of the holotype ramus, long thought to be at odds with its brachyopoid or temnospondyl nature, are critically re−evaluated. A phylogenetic analysis of lower jaw characters in temnospondyls retrieves most of the clades found in more comprehensive data sets, but the statistical node support is low. Brachyopoids are monophyletic, with Hadrokkosaurus emerging as their most basal taxon

Cas3 Protein—A Review of a Multi-Tasking Machine

Cas3 has essential functions in CRISPR immunity but its other activities and roles, in vitro and in cells, are less widely known. We offer a concise review of the latest understanding and questions arising from studies of Cas3 mechanism during CRISPR immunity, and highlight recent attempts at using Cas3 for genetic editing. We then spotlight involvement of Cas3 in other aspects of cell biology, for which understanding is lacking—these focus on CRISPR systems as regulators of cellular processes in addition to defense against mobile genetic element

Controlled, parametric, individualized, 2D and 3D imaging measurements of aerosol deposition in the respiratory tract of healthy human volunteers: in vivo data analysis

Background: To provide a validation dataset for aerosol deposition modeling, a clinical trial was performed in which the inhalation parameters and the inhaled aerosol were controlled or characterized.Methods: Eleven, healthy, never-smokers, male participants completed the study. Each participant performed two inhalations of 99mTc-labeled aerosol from a vibrating mesh nebulizer, which differed by a single controlled parameter (aerosol particle size: “small” or “large”; inhalation: “deep” or “shallow”; carrier gas: air or a helium–oxygen mix). The deposition measurements were made by planar imaging, and single photon emission computed tomography–computed tomography (SPECT-CT).Results: The difference between the mean activity measured by two-dimensional imaging and that delivered from the nebulizer was 2.7%, which was not statistically significant. The total activity deposited was significantly lower in the left lung than in the right lung (p&lt;0.0001) with a mean ratio (left/right) of 0.87±0.1 standard deviation (SD). However, when normalized to lung air volume, the left lung deposition was significantly higher (p=0.0085) with a mean ratio of 1.08±0.12 SD. A comparison of the three-dimensional central-to-peripheral (nC/P3D) ratio showed that it was significantly higher for the left lung (p&lt;0.0001) with a mean ratio (left/right) of 1.36±0.20 SD. The effect of particle size was statistically significant on the nC/P3D ratio (p=0.0014), extrathoracic deposition (p=0.0037), and 24-hr clearance (p&lt;0.0001), contrary to the inhalation parameters, which showed no effect.Conclusions: This article presents the results of an analysis of the in vivo deposition data, obtained in a clinical study designed to provide data for model validation. This study has demonstrated the value of SPECT imaging over planar, the influence of particle size on regional distribution within the lung, and differences in deposition between the left and right lungs.<br/

Molecular insights into DNA interference by CRISPR-associated nuclease-helicase Cas3

Mobile genetic elements in bacteria are neutralized by a system based on clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins. Type I CRISPR-Cas systems use a “Cascade” ribonucleoprotein complex to guide RNA specifically to complementary sequence in invader double-stranded DNA (dsDNA), a process called “interference.” After target recogni- tion by Cascade, formation of an R-loop triggers recruitment of a Cas3 nuclease-helicase, completing the interference process by destroying the invader dsDNA. To elucidate the molecular mecha- nism of CRISPR interference, we analyzed crystal structures of Cas3 from the bacterium Thermobaculum terrenum, with and without a bound ATP analog. The structures reveal a histidine-aspartate (HD)-type nuclease domain fused to superfamily-2 (SF2) helicase domains and a distinct C-terminal domain. Binding of ATP analog at the interface of the SF2 helicase RecA-like domains rearranges a motif V with implications for the enzyme mechanism. The HD- nucleolytic site contains two metal ions that are positioned at the end of a proposed nucleic acid-binding tunnel running through the SF2 helicase structure. This structural alignment suggests a mecha- nism for 3′ to 5′ nucleolytic processing of the displaced strand of invader DNA that is coordinated with ATP-dependent 3′ to 5′ trans- location of Cas3 along DNA. In agreement with biochemical studies, the presented Cas3 structures reveal important mechanistic details on the neutralization of genetic invaders by type I CRISPR-Cas systems

Costs of the police service and mental healthcare pathways experienced by individuals with enduring mental health needs

Background Substantial policy, communication and operational gaps exist between mental health services and the police for individuals with enduring mental health needs. Aims To map and cost pathways through mental health and police services, and to model the cost impact of implementing key policy recommendations. Method Within a case-linkage study, we estimated 1-year individual-level healthcare and policing costs. Using decision modelling, we then estimated the potential impact on costs of three recommended service enhancements: street triage, Mental Health Act assessments for all Section 136 detainees and outreach custody link workers. Results Under current care, average 1-year mental health and police costs were £10 812 and £4552 per individual respectively (n = 55). The cost per police incident was £522. Models suggested that each service enhancement would alter per incident costs by between −8% and +6%. Conclusions Recommended enhancements to care pathways only marginally increase individual-level costs

Application of Asymmetric IRT Modeling to Discrete-Option Multiple-Choice Test Items

Asymmetric IRT models have been shown useful for capturing heterogeneity in the number of latent subprocesses underlying educational test items (Lee and Bolt, 2018a). One potentially useful practical application of such models is toward the scoring of discrete-option multiple-choice (DOMC) items. Under the DOMC format, response options are independently and randomly administered up to the (last) keyed response, and thus the scheduled number of distractor response options to which an examinee may be exposed (and consequently the overall difficulty of the item) can vary. In this paper we demonstrate the applicability of Samejima's logistic positive exponent (LPE) model to response data from an information technology certification test administered using the DOMC format, and discuss its advantages relative to a two-parameter logistic (2PL) model in addressing such effects. Application of the LPE in the context of DOMC items is shown to (1) provide reduced complexity and a superior comparative fit relative to the 2PL, and (2) yield a latent metric with reduced shrinkage at high proficiency levels. The results support the potential use of the LPE as a basis for scoring DOMC items so as to account for effects related to key location

Regulation of androgen receptor mRNA and protein in the rat testis by testosterone

__Abstract__ Adult rats were treated with ethane dimethane sulphonate (EDS), an agent that destroys Leydig cells. Within 5 days after EDS treatment, the levels of testosterone (T) in the circulation and in the testis were decreased to very low values, which makes it possible to manipulate the testicular T concentration through administration of exogenous T. Spermatogenesis was not markedly affected within 5 days after EDS treatment, also not in the absence of T administration. In testes of EDS-treated rats, the androgen receptor mRNA (ARmRNA) level remained unaltered for 5 days. In ventral prostate, however, this treatment caused a pronounced upregulation of the level of ARmRNA, which could be counteracted by implantation of silastic T implants immediately after EDS treatment. In EDS-treated rats carrying a T implant and in untreated rats, the same number of specific [3H]R1881 binding sites was observed using a total testis nuclear fraction (Scatchard analysis). In testes from EDS-treated rats without T implants, androgen receptors (AR) did not fractionate into the nuclear fraction; however, the total testicular AR content in these animals (measured by nuclear [3H]R1881 binding after receptor transformation through injection of a high dose of T, 2 h before killing the rats) remained unaltered. Immunoprecipitation and Western blotting using anti N-terminal antibodies seemed to indicate that the total testicular amount of AR protein in the EDS-treated rats was very low as compared to that in EDS-treated rats carrying T implants and in untreated rats. Even after receptor retransformation (by injection of a high dose of T) the receptors were not quantitatively detected by immunoprecipitation and Western blotting. This may point to a structural modification of the AR that occurs in the prolonged absence of androgens

Superhumps in Cataclysmic Binaries. XXIII. V442 Ophiuchi and RX J1643.7+3402

We report the results of long observing campaigns on two novalike variables: V442 Ophiuchi and RX J1643.7+3402. These stars have high-excitation spectra, complex line profiles signifying mass loss at particular orbital phases, and similar orbital periods (respectively 0.12433 and 0.12056 d). They are well-credentialed members of the SW Sex class of cataclysmic variables. Their light curves are also quite complex. V442 Oph shows periodic signals with periods of 0.12090(8) and 4.37(15) days, and RX J1643.7+3402 shows similar signals at 0.11696(8) d and 4.05(12) d. We interpret these short and long periods respectively as a "negative superhump" and the wobble period of the accretion disk. The superhump could then possibly arise from the heating of the secondary (and structures fixed in the orbital frame) by inner-disk radiation, which reaches the secondary relatively unimpeded since the disk is not coplanar. At higher frequencies, both stars show another type of variability: quasi-periodic oscillations (QPOs) with a period near 1000 seconds. Underlying these strong signals of low stability may be weak signals of higher stability. Similar QPOs, and negative superhumps, are quite common features in SW Sex stars. Both can in principle be explained by ascribing strong magnetism to the white dwarf member of the binary; and we suggest that SW Sex stars are borderline AM Herculis binaries, usually drowned by a high accretion rate. This would provide an ancestor channel for AM Hers, whose origin is still mysterious.Comment: PDF, 41 pages, 4 tables, 16 figures; accepted, in press, to appear December 2002, PASP; more info at http://cba.phys.columbia.edu

Perceptions of COVID-19 Vaccines: Lessons from Selected Populations Who Experience Discrimination in the Australian Healthcare System

COVID-19 vaccination is particularly challenging among populations who have experienced discrimination in healthcare settings. This paper presents qualitative findings from in-depth interviews about COVID-19 vaccination conducted in Australia between October 2020 and November 2021. Data from four different studies are presented; each population has unique experiences of discrimination within the healthcare system: Aboriginal people; people who inject drugs (PWID); people living with HIV (PLHIV); and gay and bisexual men (GBM). Analyses were guided by the behavioural and social determinants model that forms the basis of the World Health Organization’s “data for action: achieving high uptake of COVID-19 vaccines” interim guidance. All populations viewed vaccination as necessary for community protection, although narratives of community care were most common among Aboriginal people. Concerns about vaccine safety were expressed by all participant groups, although participants living with HIV and GBM were more trusting of vaccines possibly because of their ongoing and usually positive past experiences with biomedical technologies for HIV management and sexual health. Aboriginal participants reported distrust of mainstream government and participants who inject drugs expressed a more generalised suspicion about COVID-19 and its origins. Practical problems related to transport, booking appointments for vaccination and so forth, were more common among participants living with HIV and GBM, possibly because these specific interviews were conducted throughout 2021 when vaccines were more available, whereas data for the other populations were collected before the vaccine rollout. Findings show that vaccine willingness is shaped by past experiences of discrimination in healthcare setting, but different histories of discrimination can differently impact vaccine willingness. Promotional messaging and delivery must take account of these important differences so to not treat these populations homogenously