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Calcineurin B homologous protein 3 (CHP3) is an EF-hand Ca2+-binding protein involved in regulation of cancerogenesis, cardiac hypertrophy, and neuronal development through interactions with sodium/proton exchangers (NHEs) and signalling proteins. While the importance of Ca2+ binding and myristoylation for CHP3 function has been recognized, the underlying molecular mechanism remained elusive. In this study, we demonstrate that Ca2+ binding and myristoylation independently affect the conformation and functions of human CHP3. Ca2+ binding increased local flexibility and hydrophobicity of CHP3 indicative of an open conformation. The Ca2+-bound CHP3 exhibited a higher affinity for NHE1 and associated stronger with lipid membranes compared to the Mg2+-bound CHP3, which adopted a closed conformation. Myristoylation enhanced the local flexibility of CHP3 and decreased its affinity to NHE1 independently of the bound ion, but did not affect its binding to lipid membranes. The data exclude the proposed Ca2+-myristoyl switch for CHP3. Instead, a Ca2+-independent exposure of the myristoyl moiety is induced by binding of the target peptide to CHP3 enhancing its association to lipid membranes. We name this novel regulatory mechanism 'target-myristoyl switch'. Collectively, the interplay of Ca2+ binding, myristoylation, and target binding allows for a context-specific regulation of CHP3 functions. [ABSTRACT FROM AUTHOR]

Redding argues against these "rule of law ideologues" who privilege state courts with "proper" lawyers. Instead, Redding argues, the court left I talaq i where and with whom it has historically tended to be-namely, in the largely private, non-state sphere of individual Muslim men's decision-making processes. [Extracted from the article]

This study aimed to determine the 1-year prevalence of delirium and the impact of hospitalization characteristics on delirium across 34 services. In this prospective cohort study of elderly in-patients (>65 years, N = 10,261), delirium was determined with the Delirium Observation Screening Scale (DOS) and the Intensive Care Delirium Screening Checklist (ICDSC) in a single sample over one year. We calculated univariate and multiple logistic regression analyses to understand the power of association between delirium, 34 services, sociodemographic, and admission/discharge factors. The prevalence of delirium across all included services was 32%. The odds of developing delirium was highest for intensive care units (ICU, 83.3%, OR 12.34), high for intermediate care units (IMC, 39.8%, OR 1.42) and medical services (34.2%, OR 1.19), and lower for surgical services (28.7%, OR 0.72). Compared with patients without delirium, patients with delirium were older (76.6 vs. 75 years), hospitalized twice as long (14.3 vs. 7.7 days), more commonly had pre-existent dementia (OR 11.98), and were more likely to die in-hospital (OR 24.20) and be admitted from (OR 2.75–2.97) and discharged to institutions (OR 1.66–3.97). This study elaborated on the 1-year prevalence of delirium across 34 services and confirmed previous pooled findings in addition to providing new insights regarding the course of hospitalization in elderly patients. • Delirium in elderly inpatients across 34 services in single sample • Prevalence of delirium, impact of hospitalization characteristics • Delirium highest in intensive care units, lowest in surgical services • Delirium in elderly admitted from institutions and emergencies more frequently • Delirious elderly hospitalized longer, institutionalized, deceased more commonly [ABSTRACT FROM AUTHOR]

Why did the famous North Indian modernist and founder of the Muhammadan Anglo-Oriental College in Aligarh, Sayyid Aḥmad Khān (d. 1315/1898), lash out against emulation (taqlīd) in Islamic law (fiqh)? The usual explanation is that he wanted to shift religious authority away from the religious scholars (ʿulamāʾ) toward ordinary Muslims. Countering this claim, I argue that his goal and that of his followers and associates at Aligarh was not primarily to 'democratize' Islamic knowledge by doing away with the traditional edifice of Islamic law in general and the four established Sunni legal schools in particular. Rather, Sayyid Aḥmad Khān and his associates attacked taqlīd because, in their view, it failed to yield reliable, certain knowledge (yaqīn). Drawing on Urdu writings, I demonstrate that these modernist thinkers did not engage with the inner logic of Islamic law but rather measured it according to higher, theological, and philosophical standards. In their quest for certainty, they were inspired both by a scientific worldview as well as colonial conceptions of law. [ABSTRACT FROM AUTHOR]

This introduction to the special section of South Asia: Journal of South Asian Studies, titled 'Religious Minorities in Pakistan', reviews the existing scholarship on this topic, points out gaps in the research, and discusses problematic notions and assumptions in both popular and academic discourses on minorities. Furthermore, it attempts a definition of the term 'religious minority', demonstrates its extensive entanglement with the question of caste—a characteristic specific to the South Asian case—and situates this discourse within broader debates about post-colonial state-building, the history of sectarianism in the region, contestations over religious authority, and the striving for a coherent political and cultural identity in Pakistan, the second-largest Muslim nation in the world. [ABSTRACT FROM AUTHOR]

At first glance, Christians and Shi'is occupy starkly differing socio-economic and religious positions in Pakistani society. Yet, this article argues that both communities share some remarkable similarities in their engagement with the seemingly hostile Pakistani state. Both Christians and Shi'is have not given up on claiming their stakes as full citizens of the nation despite repeated attempts by parts of the majority population to ostracise and exclude them. I show how they continue to re-read the early history of Pakistan, attempt to prove their unwavering loyalty to the state, try to build bridges with the majority community and, finally, portray themselves as being a spiritual elite that still guarantees the initial promise of Pakistan. [ABSTRACT FROM AUTHOR]

Calcineurin B homologous proteins (CHPs) belong to the EF‐hand Ca2+‐binding protein (EFCaBP) family. They have multiple important functions including the regulation of the Na+/H+ exchanger 1 (NHE1). The human isoforms CHP1 and CHP2 share high sequence similarity, but have distinct expression profiles with CHP2 levels for instance increased in malignant cells. These CHPs bind Ca2+ with high affinity. Biochemical data indicated that Ca2+ can regulate their functions. Experimental evidence for Ca2+‐modulated structural changes was lacking. With a newly established fluorescent probe hydrophobicity (FPH) assay, we detected Ca2+‐induced conformational changes in both CHPs. These changes are in line with an opening of their hydrophobic pocket that binds the CHP‐binding region (CBD) of NHE1. Whereas the pocket is closed in the absence of Ca2+ in CHP2, it is still accessible for the dye in CHP1. Both CHPs interacted with CBD in the presence and absence of Ca2+. Isothermal titration calorimetry (ITC) analysis revealed high binding affinity for both CHPs to CBD with equilibrium dissociation constants (KDs) in the nanomolar range. The KD for CHP1:CBD was not affected by Ca2+, whereas Ca2+‐depletion increased the KD 7‐fold for CHP2:CBD showing a decreased affinity. The data indicate an isoform specific regulatory interaction of CHP1 and CHP2 with NHE1. [ABSTRACT FROM AUTHOR]

Standard pulsewidth modulation (PWM) schemes for modular multilevel converters (MMC) have neglected deviations of the module voltages from the mean module voltage of an MMC arm as well as the dynamic change in the module voltages since their last measurement and during the switching period. This induces an output voltage error. Large output voltage errors disturb the higher level closed-loop control of the MMC, such that control targets cannot be met anymore. The output voltage error can be reduced using advanced PWM methods that predict and include the dynamic change of the individual module voltages during a switching period in the calculations for the duty cycle. This paper shows measurement results obtained from an experimental medium-voltage prototype, proving that advanced methods lead to much lower output voltage errors than the standard methods, but cannot fulfill the expectations raised by the simulations documented in the literature. In order to overcome the limitations of the old method, a new method that includes the semiconductor voltage drop and parasitic resistances is introduced and evaluated with measurements in this paper. Furthermore, simulation results showing the influence of the considered modulation methods on the closed-loop current control performance are presented. [ABSTRACT FROM AUTHOR]

This paper introduces a picture system that can be used in functional imaging experiments exploring interpersonal relations. This is important for psychotherapy research to understand the neural basis of psychological treatment effects. Pictures have many advantages for the design of functional imaging experiments, but no picture system illustrating interpersonal behavior patterns is, to date, available. We therefore developed, on the basis of a validated card-sorting test, the Interpersonal Relations Picture System. In summary, 43 pictures with 2 or more stick figures in different social situations and 9 control pictures were composed. To test the relation between each picture and the appropriate description, two successive online surveys, including 1058 and 675 individuals respectively, were conducted. Using two question types, the grade expressiveness of each picture was assessed. In total, 24 pictures and 6 control pictures met our criteria for sufficient strength and consistency with the appropriate description. Both measures are correlated with each other in all pictures illustrating interpersonal behavior, but not in the control pictures. Relations to other stimulus types and the applicability of the new picture system in functional neuroimaging methods are discussed. It is concluded that the new system will be helpful in studying the profound effect of relational change in psychotherapy. [ABSTRACT FROM AUTHOR]

Laser ablation - spark discharge - optical emission spectroscopy (LA-SD-OES) and Laser-induced breakdown spectroscopy (LIBS) are applied for the analysis of minor elements Manganese (Mn) and Chromium (Cr) in steel and for the chemical imaging of micro-patterned photoresist layers. In LA-SD-OES a weak laser pulse (typical energy 50 μJ to 5 mJ) triggers an electric discharge between a high voltage electrode and the laser ablated spot on the sample surface. Intense emission lines of neutral and singly-ionized atoms are observed with both spectroscopic techniques. However, lines of doubly-ionized atoms are detected with LA-SD-OES only. The line intensities of C III and Al III increase with decreasing laser pulse energy, surprisingly. The appearance of intense doubly-ionized lines indicates that the mechanisms of plasma excitation are different in LA-SD-OES compared to LIBS and that the combined plasma is not in local thermodynamic equilibrium at low laser energy. The calibration curves of Mn and Cr in industrial steel reveal steeper slope (higher sensitivity) for the Mn II and Cr II lines measured with LA-SD-OES and for the Mn I and Cr I lines measured with LIBS. Chemical imaging of the photoresist layer with LA-SD-OES at the atomic lines of C I and C III and the molecular band of CN reveals all details of the sample. Similar images are obtained for C I and CN using LIBS, however, no image contrast is obtained at the C III line. The very low pulse energy in LA-SD-OES enables soft sampling and may be beneficial also for the analysis and imaging of sensitive material. Unlabelled Image • Laser-triggered localized spark excitation and optical spectroscopy (LA-SD-OES) • Enhanced emission lines of singly and doubly ionized atoms with LA-SD-OES • Higher sensitivity for minor elements Mn and Cr in steel obtained with ionic lines • Chemical imaging of micro-patterned polymer using a C III emission line [ABSTRACT FROM AUTHOR]

Background: Predisposing and precipitating factors for delirium for the elderly, over the age of 65 years, are known, but not for the very old, over 80 years. As the society is getting older and evermore patients will reach >80 years, more evidence of the factors and their contribution to delirium is required in this patient group. Methods: In the course of 1 year, 3,076 patients above 80 years were screened prospectively for delirium based on a Delirium Observation Screening (DOS) scale, Intensive Care Delirium Screening Checklist (ICDSC), and a DSM (Diagnostic and Statistical Manual)-5 nursing instrument (ePA-AC) construct. Relevant predisposing and precipitating factors for delirium were assessed with a multiple regression analysis. Results: Of 3,076 patients above 80 years, 1,285 (41.8%) developed a delirium, which led to twice prolonged hospitalization (p < 0.001), requirement for subsequent assisted living (OR 2.2, CI: 1.73–2.8, p < 0.001), and increased mortality (OR 24.88, CI: 13.75–45.03, p < 0.001). Relevant predisposing factors were dementia (OR 15.6, CI: 10.17–23.91, p < 0.001), pressure sores (OR 4.61, CI: 2.74–7.76, p < 0.001), and epilepsy (OR 3.65, CI: 2.12–6.28, p < 0.0001). Relevant precipitating factors were acute renal failure (4.96, CI: 2.38–10.3, p < 0.001), intracranial hemorrhage (OR 8.7, CI: 4.27–17.7, p < 0.001), and pleural effusions (OR 3.25, CI: 1.77–17.8, p < 0.001). Conclusion: Compared to the general delirium rate of approximately 20%, the prevalence of delirium doubled above the age of 80 years (41.8%) due to predisposing factors uncommon in younger patients. [ABSTRACT FROM AUTHOR]

The Na+/H+ exchanger NHE1 is critical for cell vitality as it controls intracellular pH and cell volume. Its functionality is influenced by calcineurin B homologous proteins (CHPs). The human isoform CHP3 is important for transport of NHE1 to the plasma membrane and for its activity. Here, we characterized the binding interaction of human CHP3 with the regulatory domain of NHE1. The exact binding site of CHP3 was previously debated. CHP3 as well as both regions of NHE1 in question were produced and purified. CHP3 specifically formed stable complexes with the CHP-binding region (CBD) of NHE1 (residues 503-545) in size-exclusion chromatography (SEC), but not with the C-terminal region (CTD, residues 633-815). CTD was functional as shown by Ca2+-dependent binding of calmodulin in SEC analysis. CHP3 bound with high affinity to CBD with an equilibrium dissociation constant (KD) of 56 nM determined by microscale thermophoresis. The high affinity was substantiated by isothermal calorimetry analysis (KD = 3 nM), which also revealed that the interaction with CBD is strongly exothermic (ΔG° = −48.6 kJ/mol, ΔH = −75.3 kJ/mol, −TΔS° = 26.7 kJ/mol). The data provide insights in the molecular mechanisms that underlie the regulatory interaction of CHP3 and NHE1 and more general of calcineurin homologous proteins with their target proteins. [ABSTRACT FROM AUTHOR]

The optical emission of plasma on industrial steel samples induced by Laser Ablation-Spark Discharge-Optical Emission Spectroscopy (LA-SD-OES) and by Laser-Induced Breakdown Spectroscopy (LIBS) is investigated and correlated to the volume of ablated steel material. The 36 steel samples investigated have an iron content C(Fe) above 94 wt%. The excitation energy in LIBS (laser pulse of 55 mJ) and in LA-SD-OES (laser pulse of 5 mJ and spark discharge of 50 mJ) is the same. In LA-SD-OES, the optical emission of plasma and the size of ablation craters are very similar for all samples and a linear calibration curve for Mn is measured (R2 = 0.99). In LIBS, however, a pronounced dependence of the plasma emission and of the crater volume on the steel matrix is observed and calibration curves show a strong cross-sensitivity to other elements such as Si (matrix effect). The hardness, grain size, and phase of steel samples are analyzed to correlate the matrix effect in LIBS measurements to a physical property of the specimen. The different behavior for LA-SD-OES and LIBS is probably due to different processes of sampling and plasma excitation. From our results we conclude that LA-SD-OES enables for the element analysis of industrial steel largely independent of composition and structure of samples while in LIBS the matrix effect has to be taken into account. [Display omitted] • Novel technique LA-SD-OES for the element analysis of steel. • Analyte emission intensities are independent of other elements in steel matrix. • Sampling in LA-SD-OES is independent of steel composition. • Linear calibration curves with high R2 for minor elements in steel. • LA-SD-OES overcomes strong matrix effect observed in LIBS of same samples. [ABSTRACT FROM AUTHOR]

Delirium screening in acute care settings is a resource intensive process with frequent deviations from screening protocols. A predictive model relying only on daily collected nursing data for delirium screening could expand the populations covered by such screening programs. Here, we present the results of the development and validation of a series of machine-learning based delirium prediction models. For this purpose, we used data of all patients 18 years or older which were hospitalized for more than a day between January 1, 2014, and December 31, 2018, at a single tertiary teaching hospital in Zurich, Switzerland. A total of 48,840 patients met inclusion criteria. 18,873 (38.6%) were excluded due to missing data. Mean age (SD) of the included 29,967 patients was 71.1 (12.2) years and 12,231 (40.8%) were women. Delirium was assessed with the Delirium Observation Scale (DOS) with a total score of 3 or greater indicating that a patient is at risk for delirium. Additional measures included structured data collected for nursing process planning and demographic characteristics. The performance of the machine learning models was assessed using the area under the receiver operating characteristic curve (AUC). The training set consisted of 21,147 patients (mean age 71.1 (12.1) years; 8,630 (40.8%) women|) including 233,024 observations with 16,167 (6.9%) positive DOS screens. The test set comprised 8,820 patients (median age 71.1 (12.4) years; 3,601 (40.8%) women) with 91,026 observations with 5,445 (6.0%) positive DOS screens. Overall, the gradient boosting machine model performed best with an AUC of 0.933 (95% CI, 0.929 - 0.936). In conclusion, machine learning models based only on structured nursing data can reliably predict patients at risk for delirium in an acute care setting. Prediction models, using existing data collection processes, could reduce the resources required for delirium screening procedures in clinical practice. • Delirium can be reliably predicted with machine-learning models using nursing data. • Delirium prediction models with few predictors can perform as well as more complex ones. • Despite the implementation of screening programs, delirium is often not diagnosed. [ABSTRACT FROM AUTHOR]

The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2nd, although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T ('Basel cluster'), including 157 identical sequences at the root of the 'Basel cluster', some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503. Author summary: COVID-19 was first reported in December 2019 in Wuhan, China, and has spread around the globe since. The most common tool for tracking and containing the spread of the disease-causing virus–SARS-CoV-2 –are classical epidemiology and contact tracing, which collapse under too high case burdens as seen in this pandemic. However, whole-genome sequencing and phylogenetic analyses of the viral genomes will be crucial to understand the virus evolution and outbreak dynamics to ultimately stop the spread of the disease. Here we combined epidemiological data and whole-genome sequences originating from the time of the arrival of the virus in early 2020 in a typical medium-sized European city, namely Basel-City, Switzerland. On one hand, we identified limited community spread of very distinct viral variants originating from travel returners, which is possibly due to the heightened attention and restrictions imposed on international travellers. On the other hand, we find evidence for large cryptic community spread of a single virus variant in the city, which we infer to have originated around mid-February 2020 in the larger tri-national area around Basel, and which has epidemiological links to a mass gathering event in the region of Alsace, France. [ABSTRACT FROM AUTHOR]

Transcranial color-coded duplex sonography (TCCS) and computed tomography angiography (CTA) are widely used to identify intracranial stenoses (ISs). We assessed concordance of IS grading between TCCS and CTA and proposed new TCCS criteria for severe IS ≥70%. One hundred two stroke patients (70 ± 13 y) with TCCS-identified IS were included. TCCS and CTA were performed within 24 h after admission. TCCS peak systolic velocity cutoffs for <50%/50%-69% stenoses were ≥155/≥220 cm/s (middle cerebral artery [MCA]-M1), ≥100/≥140 cm/s (MCA-M2), ≥120/≥155 cm/s (anterior cerebral artery [ACA]-A1), ≥100/≥145 cm/s (posterior cerebral artery [PCA]-P1 and PCA-P2), ≥90/≥120 cm/s (vertebral artery [VA]-V4) and ≥100/≥140 cm/s (basilar artery [BA]). Criteria for ≥70% stenoses were, despite variable flow velocities, post-stenotic flow alterations and/or leptomeningeal collateral flow. One hundred seventy-seven ISs were detected by TCCS. The number and grade (<50%/50%-69%/≥70%) of ISs were MCA 70 (39/19/12), BA 24 (9/11/4), ACA 21 (14/7/0), PCA 49 (29/15/5) and VA 13 (2/6/5). IS localization was confirmed by CTA in 84 of 177 cases (48%): MCA, 41/70 (59%); BA, 16/24 (67%); ACA 2/21, (10%); PCA, 17/49 (35%); VA, 8/13 (62%). Concordance between TCCS and CTA grading was (<50%/50%-69%/≥70%) 17%/19%/77%. TCCS and CTA exhibited substantial differences in the detection and grading of IS. Higher concordance rates for severe stenosis support our proposed TCCS criteria. [ABSTRACT FROM AUTHOR]

• Laser-triggered localized spark excitation and optical spectroscopy (LA-SD-OES). • Chemical imaging by LA-SD-OES and laser-induced breakdown spectroscopy (LIBS). • Differences in optical emission spectra measured by LA-SD-OES and LIBS. • Hyperspectral image contrast in LA-SD-OES and LIBS discussed. • Physical processes involved in laser-triggered spark formation analyzed. Chemical imaging by Laser ablation – spark discharge – optical emission spectroscopy (LA-SD-OES) is presented. A low-energy laser pulse triggers an electric spark between a metal electrode tip and a sample and the excited plasma is analyzed by OES. Without a laser pulse the spark is suppressed as the applied electric field strength is below the self-breakdown threshold in air. The laser-triggered discharge is spatially confined to a plasma channel between tip and ablated spot on the sample. This localization of the electric spark enables for element imaging with high spatial resolution not feasible with spark-OES. Human fingerprints, mesoscopic layered samples, and micro-patterned polymer layers are spectrochemically imaged. The image contrast defined as signal to background ratio of the analyte emission line intensity is higher for LA-SD-OES than for Laser-induced breakdown spectroscopy (LIBS) at low laser energy. We also measure the lag time between laser pulse and spark depending on the applied electrode voltage and the distance between tip and sample and discuss the results in terms of avalanche ionization in air. The optical spectra measured by LA-SD-OES and LIBS in the same experimental setup are similar. Higher ionized emission lines are detected with LA-SD-OES only. [ABSTRACT FROM AUTHOR]