Religious Freedom, Church–State Separation, and the Ministerial Exception

The Hosanna-Tabor case concerns the separation of church and state, an arrangement that is often misunderstood but is nevertheless a critical dimension of the freedom of religion protected by the First Amendment to our Constitution. For nearly a thousand years, the tradition of Western constitutionalism - the project of protecting political freedom by marking boundaries to the power of government - has been assisted by the principled commitment to religious liberty and to church-state separation, correctly understood. A community that respects - as ours does - both the importance of, and the distinction between, the spheres of political and religious authority is one in which the fundamental rights of all are more secure. A government that acknowledges this distinction, and the limits to its own reach, is one that will more consistently protect and vindicate the liberties of both individuals and institutions.The “ministerial exception,” at issue in Hosanna-Tabor, is a clear and crucial implication of religious liberty, church autonomy, and the separation of church and state. Because any worthwhile account of religious freedom would respect the authority of religious communities to select freely their own clergy, ministers, teachers, and doctrines, any such account must include something like the ministerial-exception rule. Reasonably constructed and applied, this rule helps civil decision-makers to avoid deciding essentially religious questions. In addition, and more importantly, it protects the fundamental freedom of religious communities to educate and form their members. Although the exception may, in some cases, block lawsuits against religious institutions and communities for discrimination, it rests on the overriding and foundational premise that there are some questions the civil courts do not have the power to answer, some wrongs that a constitutional commitment to church-state separation puts beyond the law’s corrective reach. The civil authority - that is, the authority of a constitutional government - lacks “competence” to intervene in such questions, not so much because they lie beyond its technical or intellectual capacity, but because they lie beyond its jurisdiction

Whole genome sequencing of Plasmodium vivax isolates reveals frequent sequence and structural polymorphisms in erythrocyte binding genes.

Plasmodium vivax malaria is much less common in Africa than the rest of the world because the parasite relies primarily on the Duffy antigen/chemokine receptor (DARC) to invade human erythrocytes, and the majority of Africans are Duffy negative. Recently, there has been a dramatic increase in the reporting of P. vivax cases in Africa, with a high number of them being in Duffy negative individuals, potentially indicating P. vivax has evolved an alternative invasion mechanism that can overcome Duffy negativity. Here, we analyzed single nucleotide polymorphism (SNP) and copy number variation (CNV) in Whole Genome Sequence (WGS) data from 44 P. vivax samples isolated from symptomatic malaria patients in southwestern Ethiopia, where both Duffy positive and Duffy negative individuals are found. A total of 123,711 SNPs were detected, of which 22.7% were nonsynonymous and 77.3% were synonymous mutations. The largest number of SNPs were detected on chromosomes 9 (24,007 SNPs; 19.4% of total) and 10 (16,852 SNPs, 13.6% of total). There were particularly high levels of polymorphism in erythrocyte binding gene candidates including merozoite surface protein 1 (MSP1) and merozoite surface protein 3 (MSP3.5, MSP3.85 and MSP3.9). Two genes, MAEBL and MSP3.8 related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. Variation in gene copy number was also concentrated in genes involved in host-parasite interactions, including the expansion of the Duffy binding protein gene (PvDBP) on chromosome 6 and MSP3.11 on chromosome 10. Based on the phylogeny constructed from the whole genome sequences, the expansion of these genes was an independent process among the P. vivax lineages in Ethiopia. We further inferred transmission patterns of P. vivax infections among study sites and showed various levels of gene flow at a small geographical scale. The genomic features of P. vivax provided baseline data for future comparison with those in Duffy-negative individuals and allowed us to develop a panel of informative Single Nucleotide Polymorphic markers diagnostic at a micro-geographical scale

An Experimental Investigation of Applying Mica2 Motes in Pavement Condition Monitoring

Pavement maintenance is vital for travel safety, thus detecting dangerous road conditions in a real-time fashion is desirable. Using an off-the-shelf wireless sensor network to detect such conditions at a low cost poses many challenges. In order to meet these challenges, a Mica2 Mote sensor network is adopted in this study to process and transmit data collected from three external analog sensors. Consequentially, several hardware and software interfaces are developed to complete a pavement monitoring system that uses temperature and moisture presence to detect hazardous road conditions. Surge Time Synchronization is explored in this specific application to enable the wireless sensor network to operate in a low power consumption mode. A fairly simplistic pattern classification algorithm is embedded into the motes to create the smart wireless sensing application. A series of outdoor tests are conducted in this study paying special attention to the survivability of fragile analog sensors in harsh roadway conditions. In this regard, a novel solution called the ``Sensor-Road Button''(SRB) is developed and validated experimentally. This is one of several exercises made in this study to enable the application of sensor technologies in intelligent transportation systems (ITS). The size of the wireless sensor network in this study is relatively small, utilizing a total of five motes in order to fully exploit the transmitting range of each mote. Long testing periods (i.e., uninterrupted 12-hour time frames for each period of data collection) add an additional advantage, allowing for the evaluation of the selected wireless sensor network for long-term monitoring using the low power consumption mode under Surge Time Synchronization. Many performance metrics of the adopted small-size, large-interval Mica2 Motes wireless sensor network are revealed in this study through a series of data processing efforts. Results are presented to examine (i) inter-node connectivity and transmitting range, (ii) battery life, (iii) the length of the initial network connection time as affected by methods of setting up tests under practical conditions, (iv) error rate and analysis of different error types (showing the importance of the subsequent data cleansing step), and (v) other network routing properties including the parent time histories for each mote. The results and analysis form a database for future efforts to better understand, appreciate, and improve the performance of Mica2 Motes. This study will thus benefit robust real-world implementation of off-the-shelf sensor network products such as Mica2 Motes in terms of hardware development and data processing.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Rapid End-Point Quantitation of Prion Seeding Activity with Sensitivity Comparable to Bioassays

A major problem for the effective diagnosis and management of prion diseases is the lack of rapid high-throughput assays to measure low levels of prions. Such measurements have typically required prolonged bioassays in animals. Highly sensitive, but generally non-quantitative, prion detection methods have been developed based on prions' ability to seed the conversion of normally soluble protease-sensitive forms of prion protein to protease-resistant and/or amyloid fibrillar forms. Here we describe an approach for estimating the relative amount of prions using a new prion seeding assay called real-time quaking induced conversion assay (RT-QuIC). The underlying reaction blends aspects of the previously described quaking-induced conversion (QuIC) and amyloid seeding assay (ASA) methods and involves prion-seeded conversion of the alpha helix-rich form of bacterially expressed recombinant PrPC to a beta sheet-rich amyloid fibrillar form. The RT-QuIC is as sensitive as the animal bioassay, but can be accomplished in 2 days or less. Analogous to end-point dilution animal bioassays, this approach involves testing of serial dilutions of samples and statistically estimating the seeding dose (SD) giving positive responses in 50% of replicate reactions (SD50). Brain tissue from 263K scrapie-affected hamsters gave SD50 values of 1011-1012/g, making the RT-QuIC similar in sensitivity to end-point dilution bioassays. Analysis of bioassay-positive nasal lavages from hamsters affected with transmissible mink encephalopathy gave SD50 values of 103.5–105.7/ml, showing that nasal cavities release substantial prion infectivity that can be rapidly detected. Cerebral spinal fluid from 263K scrapie-affected hamsters contained prion SD50 values of 102.0–102.9/ml. RT-QuIC assay also discriminated deer chronic wasting disease and sheep scrapie brain samples from normal control samples. In principle, end-point dilution quantitation can be applied to many types of prion and amyloid seeding assays. End point dilution RT-QuIC provides a sensitive, rapid, quantitative, and high throughput assay of prion seeding activity

Diagnostic Yield of Transbronchial Lung Cryobiopsy Compared to Transbronchial Forceps Biopsy in Patients with Sarcoidosis in a Prospective, Randomized, Multicentre Cross-Over Trial

Background: Transbronchial lung forceps biopsy (TBLF) is of limited value for the diagnosis of interstitial lung disease (ILD). However, in cases with predominantly peribronchial pathology, such as sarcoidosis, TBLF is considered to be diagnostic in most cases. The present study examines whether transbronchial lung cryobiopsy (TBLC) is superior to TBLF in terms of diagnostic yield in cases of sarcoidosis. Methods: In this post hoc analysis of a prospective, randomized, controlled, multicentre study, 359 patients with ILD requiring diagnostic bronchoscopic tissue sampling were included. TBLF and TBLC were both used for each patient in a randomized order. Histological assessment was undertaken on each biopsy and determined whether sarcoid was a consideration. Results: A histological diagnosis of sarcoidosis was established in 17 of 272 cases for which histopathology was available. In 6 out of 17 patients, compatible findings were seen with both TBLC and TBLF. In 10 patients, where the diagnosis of sarcoidosis was confirmed by TBLC, TBLF did not provide a diagnosis. In one patient, TBLF but not TBLC confirmed the diagnosis of sarcoidosis. Conclusions: In this post hoc analysis, the histological diagnosis of sarcoidosis was made significantly more often by TBLC than by TBLF. As in other idiopathic interstitial pneumonias (IIPs), the use of TBLC should be considered when sarcoidosis is suspected

Complex Reorganization and Predominant Non-Homologous Repair Following Chromosomal Breakage in Karyotypically Balanced Germline Rearrangements and Transgenic Integration

We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically-interpreted translocations and inversions. We confirm that the recently described phenomenon of “chromothripsis” (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline where it can resolve to a karyotypically balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign CNVs. We compared these results to experimentally-generated DNA breakage-repair by sequencing seven transgenic animals, and revealed extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion is the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations