Miracle-dz/UniFAR-FTUs huggingface dataset:
NMR-based site-resolved profiling of (cid:2) -amyloid misfolding reveals structural transitions from pathologically relevant spherical oligomer to fibril

Increasing evidence highlights the central role of neurotoxic oligomers of the 42-residue-long (cid:2) -amyloid (A (cid:2) 42) in Alzheimer’s disease (AD). However, very limited information is available on the structural transition from oligomer to fibril, partic-ularly for pathologically relevant amyloids. To the best of our knowledge, we present here the first site-specific structural characterization of A (cid:2) 42 misfolding, from toxic oligomeric assembly yielding a similar conformation to an AD-associated A (cid:2) 42 oligomer, into a fibril. Transmission EM (TEM) analysis revealed that a spherical amyloid assembly (SPA) of A (cid:2) 42 with a 15.6 (cid:3) 2.1-nm diameter forms in a (cid:2) 30- (cid:4) M A (cid:2) 42 solution after a (cid:2) 10-h incubation at 4 °C, followed by a slow conversion into fibril at (cid:2) 180 h. Immunological analysis suggested that the SPA has a surface structure similar to that of amylospheroid (ASPD), a patient-derived toxic A (cid:2) oligomer, which had a diameter of 10–15 nm in negative-stain TEM. Solid-state NMR analyses indicated that the SPA structure involves a (cid:2) -loop- (cid:2) motif, which significantly differed from the triple- (cid:2) motif observed for the A (cid:2) 42 fibril. The comparison of the 13 C chemical shifts of SPAwiththoseofthefibrilpreparedintheaboveconditionsand interstrand distance measurements suggested a large conformational change involving rearrangements of intermolecular (cid:2) -sheet into in-register parallel (cid:2) -sheet during the misfolding. A comparison of the SPA and ASPD 13 C chemical shifts indicated that SPA is structurally similar to the ASPD relevant to AD. These observations provide insights into the architecture and key structural transitions of amyloid oligomers relevant for AD pathology.
Best Practices for Alchemical Free Energy Calculations

Alchemical free energy calculations are a useful tool for predicting free energy differences associated with the transfer of molecules from one environment to another. The hallmark of these methods is the use of "bridging" potential energy functions representing \emph{alchemical} intermediate states that cannot exist as real chemical species. The data collected from these bridging alchemical thermodynamic states allows the efficient computation of transfer free energies (or differences in transfer free energies) with orders of magnitude less simulation time than simulating the transfer process directly. While these methods are highly flexible, care must be taken in avoiding common pitfalls to ensure that computed free energy differences can be robust and reproducible for the chosen force field, and that appropriate corrections are included to permit direct comparison with experimental data. In this paper, we review current best practices for several popular application domains of alchemical free energy calculations, including relative and absolute small molecule binding free energy calculations to biomolecular targets.
T2 Relaxometry of Normal Pediatric Brain Development

Objective: The NIH MRI Study of Normal brain Development [1] is a large ongoing multi-center study of brain and behavior development in healthy children. As part of that study we have established normal age-related changes in quantitative MR relaxometry parameters. We report here on the T2 relaxation time constant evolution in several brain regions for children within the range of birth to 4-years, 5-months. The goal of this study is to provide a publicly available normative pediatric MRI and behavior database, which can subsequently be used in studies assessing normal brain development and deviation due to various neurological disorders. Methods: The sampling plan consisted of acquiring both cross-sectional and longitudinal T2 relaxometry data for 75 subjects between the age of 0 and 4-years, 5months, with a total of 201 scans. Data acquisition consisted of two sets of dual contrast fast/turbo spin echo (FSE/TSE) images on GE and Siemens 1.5T scanners, resulting in four effective echo times (TEeff ̃15, 80, 120, 160 ms). T2 relaxation time constants were estimated on a voxel-by-voxel basis using a single exponential model. Regions of interest (ROIs) were selected on the resulting parametric T2 maps to investigate the dependence of this tissue-specific parameter on age. A monoexponential was also used to model the measured T2 as a function of age in specific ROIs, using the equation proposed by Engelbrecht et al. [2]:
Pleistocene variability of the Subtropical Convergence at East Tasman Plateau: Evidence from planktonic foraminiferal Mg/Ca (ODP Site 1172A)

Combined measurements of Mg/Ca and stable oxygen isotopes in tests of the planktonic foraminifer G. bulloides from Ocean Drilling Program (ODP) Site 1172A (East Tasman Plateau) allowed us to reconstruct sea surface temperature (SSTMg/Ca), sea surface salinity (SSS), and hence variations in the Subtropical Convergence (STC) in the southwestern Tasman Sea over the last four major glacial‐interglacial changes. During interglacials the commonly enhanced SSTMg/Ca and SSS correspond to a lowered marine productivity and a lowered terrigenous flux, implying that the STC separating cool, high‐nutrient Subantarctic Surface Water from warm, saline, oligotrophic Subtropical Surface Water and hence the band of zonal westerlies responsible for the eolian dust flux were located south of East Tasman Plateau. The warm East Australian Current was well established during warm periods and propagated far south. During glacial times, SSTMg/Ca and SSS were lower, while both marine productivity and eolian flux increased. Such conditions prevailed during glacial Marine Isotope Stages MIS 12, MIS 10, and to a lesser degree MIS 6 and implied the extended northward influence of Subantarctic Surface Water and a shift of the STC to <44°S. The overall climatic signal at Site 1172A appears to be largely attenuated when compared to published climate records from comparable latitudes to the west and to the east. SSTMg/Ca amplitudes were more pronounced in the subantarctic Indian Ocean and at Chatham Rise. They exhibit a consistent pattern suggesting that latitudinal shifts of the STC occurred synchronously in the subantarctic Indian Ocean and at Chatham Rise but were largely damped at East Tasman Plateau due to the influence of the East Australian Current.
Black shale deposition on the northwest African Shelf during the Cenomanian/Turonian oceanic anoxic event: Climate coupling and global organic carbon burial

High-resolution geochemical records from a depth transect through the Cenomanian/Turonian (C/T) Tarfaya Basin (northwest African Shelf) reveal high-amplitude fluctuations in accumulation rates of organic carbon (OC), redox-sensitive and sulphide-forming trace metals, and biomarkers indicative of photic zone euxinia. These fluctuations are in general coeval and thus imply a strong relationship of OC burial and water column redox conditions. The pacing and regularity of the records and the absence of a prominent continental signature suggest a dynamic depositional setting linked to orbital and higher-frequency forcing. Determining the dominant frequency depends on the definition of the most pronounced oceanic anoxic event (OAE2) and its duration. We propose that eccentricity is the main forcing factor at Tarfaya and controlled fluctuations in wind-driven upwelling of nutrient-rich, oxygen-depleted intermediate waters from the adjacent Atlantic and the periodic development of photic zone and bottom water euxinia on the mid-Cretaceous northwest African shelf. Accumulation records clearly identify the basin center as the primary site of sediment deposition with highest temporal variability and an up to six-fold increase in OC burial from similar to2 g/m(2) . yr prior to the OAE2 to similar to12 g/m(2) . yr during the OAE2. Photic zone and bottom water euxinia alternated with periods of greater oxygenation of the water column in response to climate forcing. Mass balance calculations imply that similar to2% of the overall global excess OC burial associated with the OAE2 was deposited in the Tarfaya Basin, an area that represented only similar to0.05% of the total global C/T ocean floor. In fact, the lateral extent of similar black shales along the African continental margin indicates that this part of the ocean contributed significantly to the global increase in organic carbon burial during the OAE2.
Financial Institutions Center Acceptable Risk : A Study of Global Currency Trading Rooms in the US and Japan

In this study, I explore the idea of "acceptable risk" at the organizational level of analysis in a sample of currency-trading rooms embedded in different national cultures, and develop and test a multi-level model of how national culture and the organizational context, in particular the control strategies and the norms of acceptable risk within risktaking units, shape their risk-taking behavior and performance. The results show that "acceptable risk" as defined within the micro-environment of the trading room does influence actual organizational risk-taking, though national culture does not. In addition, market control strategies were related to better risk-transformation in these trading rooms. This paper was presented at the Wharton Financial Institutions Center’s conference on The Performance of Financial Institutions, May 8-10, 1997.
STUDY OF PLATELET INDICES IN PREGNANCY INDUCED HYPERTENSION (PIH)

Background: Hypertension is one of the common medical complications of pregnancy and contributes significantly to maternal and perinatal morbidity and mortality. Hypertension is a sign of an underlying pathology which may be pre-existing or appear for the first time during pregnancy. Various haematological changes like numerical and functional platelet abnormalities, alteration in haemoglobin and erythrocyte parameters and increase in the procoagulant state of normal pregnancy are seen. Aims and Objectives: Evaluation of Platelet indices in PIH. To identify the early platelet parameters predictive of preeclampsia and HELLP syndrome. Materials and methods: A 2 year study was carried out in the Dept. of pathology ESIMC, Bangalore on 100 PIH cases. Platelet indices is done in all the cases. P values for all parameters were statistically derived and evaluated. Results: Total of 100 cases were included in the study. 37 were mild GH, 9 cases were severe GH, 29 cases were mild preeclampsia and 25 cases were in severe preeclampsia group. Thrombocytopenia was observed in 23 cases and elevated MPV in 49 cases. Conclusion: Thrombocytopenia is identified as the most common complications of PIH and at times may be life threatening. Therefore estimation of platelet indices can be considered as an early, simple and rapid procedure in the assessment of severity of pre-eclampsia and to prevent progression to HELLP syndrome and DIC. Key Words: Hypertension, preeclampsia, eclampsia, Platelet indices.
University of Birmingham Mobile Health Technology for Atrial Fibrillation Management Integrating Decision Support, Education, and Patient Involvement

BACKGROUND: Mobile Health technology for the management of patients with atrial ﬁbrillation is unknown. METHODS: The simple mobile AF (mAF) App was designed to incorporate clinical decision-support tools (CHA 2 DS 2 -VASc [Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes Mellitus, Prior Stroke or TIA, Vascular disease, Age 65–74 years, Sex category], HAS-BLED [Hypertension, Abnormal renal/ liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly], SAMe-TT 2 R 2 [Sex, Age < 60 years, Medical history, Treatment, Tobacco use, Race] scores), educational materials, and patient involvement strategies with self-care protocols and structured follow-up. Patients with atrial ﬁbrillation were randomized into 2 groups (mAF App vs usual care) in a cluster randomized design pilot study. Patients’ knowledge, quality of life, drug adherence, and anticoagulation satisfaction were evaluated at baseline, 1 month, and 3 months. Usability, feasibility, and acceptability of the mAFApp were assessed at 1 month. RESULTS: A total of 113 patients were randomized to mAF App intervention (mean age, 67.4 years; 57.5% were male; mean follow-up, 69 days), and 96 patients were randomized to usual care (mean age, 70.9 years; 55.2% were male; mean follow-up, 95 days). More than 90% of patients reported that the mAF education, and patient-involvement strategies, signiﬁcantly improved knowledge, drug adherence, quality of life, and anticoagulation satisfaction.
Real - time Neuroimaging and Cognitive Monitoring Using Wearable Dry EEG

— Goal: We present and evaluate a wearable high-density dry electrode EEG system and an open-source software framework for online neuroimaging and state classification. Methods: The system integrates a 64-channel dry EEG form-factor with wireless data streaming for online analysis. A real-time software framework is applied, including adaptive artifact rejection, cortical source localization, multivariate effective connectivity inference, data visualization, and cognitive state classification from connectivity features using a constrained logistic regression approach (ProxConn). We evaluate the system identification methods on simulated 64-channel EEG data. Then we evaluate system performance, using ProxConn and a benchmark ERP method, in classifying response errors in 9 subjects using the dry EEG system. Results: Simulations yielded high accuracy (AUC=0.97±0.021) for real-time cortical connectivity estimation. Response error classification using cortical effective connectivity (sdDTF) was significantly above chance with similar performance (AUC) for cLORETA (0.74±0.09) and LCMV (0.72±0.08) source localization. Cortical ERP-based classification was equivalent to ProxConn for cLORETA (0.74±0.16) but significantly better for LCMV (0.82±0.12). Conclusion: We demonstrated the feasibility for real-time cortical connectivity analysis and cognitive state classification from high-density wearable dry EEG. Significance: This paper is the first validated application of these methods to 64-channel dry EEG. The work addresses a need for robust real-time measurement and interpretation of complex brain activity in the dynamic environment of the wearable setting. Such advances can have broad impact in research, medicine, and brain-computer interfaces. The pipelines are made freely available in the open-source SIFT and BCILAB toolboxes.
Estimating Rainfall Recharge and Soil Water Residence Times in Pukekohe, New Zealand, by Combining Geophysical, Chemical, and Isotopic Methods

The combined use of geophysical (time domain reflectometry [TDR]), isotopic (δ18 O and δ2H) and chemical (NO 3 ‐N, Cl) techniques indicates that residence times in the unsaturated zone of a fractured basalt aquifer in the Pukekohe region of the North Island, New Zealand, are at least six months. Each technique provides useful information on specific aspects of recharge and residence times, but combined they provide a basis for determining the mechanisms of water movement in the unsaturated zone. TDR soil moisture measurements provide similar rainfall recharge estimates as model calculations over longer time periods (monthly or seasonal) but may be more accurate for shorter time scales (weekly or daily).
Reverse Genetics with a Full-length Infectious cDNA Clone of Bovine 1 Torovirus 2

Torovirus (ToV) has recently been classified in the new family Tobaniviridae, although it belonged to the 23 Coronavirus (CoV) family historically. Reverse genetics systems for many CoVs have been established, but 24 none exist for ToVs. Here, we describe a reverse genetics system using a full-length infectious cDNA clone of 25 bovine ToV (BToV) in a bacterial artificial chromosome (BAC). Recombinant BToV containing genetic markers 26 had the same phenotype as wild-type (wt) BToV. To generate two types of recombinant virus, the 27 Hemagglutinin-esterase (HE) gene was manipulated, since cell-adapted wtBToV generally loses the full- 28 length HE (HEf), resulting in soluble HE (HEs). First, recombinant viruses with HEf and HA-tagged HEf or 29 HEs genes were rescued; these showed no significant differences in cell growth, suggesting that HE is not 30 essential for viral growth in cells. Then, recombinant virus in which HE was replaced by the Enhanced Green 31 Fluorescent Protein (EGFP) gene expressed EGFP in infected cells, but showed significantly reduced viral 32 growth compared to wtBToV. Moreover, the recombinant virus readily deleted the EGFP gene after one 33 passage. Interestingly, one variant with mutations in non-structural proteins (NSPs) showed improved EGFP 34 expression and viral growth during serial passages, although it eventually deleted the EGFP gene, suggesting 35 that these mutations contributed to EGFP gene acceptance. These recombinant viruses provide new insights 36 regarding BToV and its reverse genetics will help advance understanding of this neglected pathogen. 37 the full-length genomic sequences three plaque-purified BToV analyzed. We tried to determine the 5’ terminal end of these viruses using the 5’ RACE method, but several different sequences were observed in the terminal three bases; 5’ -TGACGT- 3’, 5’ - GTACGT- 3’, 5’ -GGACGT- 3’, 5’ -GACGT- 3’, 5’ -ACGT- 3’, 5’ -(-)CGT- 3’. The sequence at the 5’ terminal end of three BToVs (25, 33) two PToVs (Accession and all shared the 5’ -TGACGT- 3’ sequence, whereas equine ToV showed 5’ -ACGT- 3’ (74). Whether the differences observed in the BToVs were intrinsic of BToV or to suboptimal experimental condition of the RACE method remained unclear. However, 5’ -TGACGT-3, previously reported in published BToVs and PToVs, was found in only one out of seven in our analysis, whereas 5’ -ACGT- 3’ reported in equine BToV is a consensus sequence. Thus, in this study, the sequence at 5’ terminal end of BToV was set as 5’ -ACGT- 3’. Two BToV clones showed the same sequence; from these, one was selected as the parent virus (wtBToV).
Posttraumatic stress disorder among older adults: A differential item functioning analysis of PTSD in ICD-11 and DSM-5.

OBJECTIVE Distinct models of posttraumatic stress disorder (PTSD) are outlined in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the 11th version of the International Classification of Diseases (ICD-11). Limited data exists about the validity of these models among older adults. This study examines the probable prevalence rates of PTSD in older adults; the factorial validity of both models; and symptom-endorsement bias across sex. METHOD Using a nationally representative (United States) sample (n = 5,366) of older adults aged 60 years and older, alternative PTSD factor models were tested using confirmatory factor analysis (CFA), and item bias was assessed using differential item functioning (DIF) analysis. PTSD was measured without the functional impairment criterion, likely resulting in inflated prevalence rates. RESULTS DSM-5 (9.5%) PTSD prevalence was significantly higher than ICD-11 (8.7%). Women were more likely to meet criteria for DSM-5 (OR = 1.79) and ICD-11 (OR = 1.38) PTSD. CFA results showed that both models of PTSD had excellent fit. Four DSM-5 symptoms demonstrated DIF, with females more likely to endorse three symptoms (B1: "unwanted memories"; B4: "feeling upset"; and E6: "sleep problems") and males more likely to endorse one symptom (E2: "reckless or self-destructive behavior"). No DIF was present for the 6 ICD-11 symptoms. CONCLUSION Both PTSD models perform well among older adults, although there is evidence of DIF in the DSM-5 model. A considerable proportion of older adults met diagnostic requirements for PTSD, thus highlighting the importance of trauma-related research among older adult populations. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Eccentric Loading Compared with Shock Wave Treatment for Chronic Insertional Achilles Tendinopathy

Background: Nonoperative management of chronic tendinopathy of the Achilles tendon insertion has been poorly studied. With the recently demonstrated effectiveness of eccentric loading and of repetitive low-energy shock wave therapy in patients with midsubstance Achilles tendinopathy, the aim of the present randomized, controlled trial was to verify the effectiveness of both procedures exclusively in patients with insertional Achilles tendinopathy.
Mantle viscosity from Monte Carlo inversion of very long baseline interferometry data

Using a Monte Carlo approach, we determine the mantle viscosity profiles which best fit the currently observed very long baseline interferometry (VLBI) baseline lengths in North America. Our inversion, which is based on the deglaciation model ICE-1 and on the most recent VLBI global solution (we employ the Goddard Space Flight Center VLBI solution 1102, which contains data through July 1998 (Ma and Ryan, 1998)), demonstrates that the observations are best fit for a shallow upper mantle with viscosity below the traditional reference value of 1021 Pa s. The lower mantle viscosity cannot be unequivocally determined by means of VLBI data alone. In fact, our inversion indicates that two distinct solutions are possible. The first is characterized by a lower mantle with viscosity of a few times 1021 Pa s, a value in agreement with that derived by the global set of relative sea level curves. The second admissible solution corresponds to a lower mantle with viscosity close to 1023 Pa s. We have found that the viscosity of the transition zone may vary between 5×1021 and 5×1022 Pa s, i.e., larger than the lowest admissible values found for the lower mantle viscosity. The results of the Monte Carlo inversion are essentially stable with respect to time, since similar viscosity profiles are suggested if the VLBI global solution 1014 is employed, which contained data through July 1995. However, the increased precision of VLBI data since that time has somewhat narrowed the set of admissible viscosity profiles above the 670-km depth discontinuity. Choosing various subsets of solution 1102, we have also tested the robustness of the results presented, with reference to possible data contaminations due to tectonic deformations.