Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein Kinase A (PKA) Type I Interacts with P-Rex1, a Rac Guanine Nucleotide Exchange Factor

Morphology of migrating cells is regulated by Rho GTPases and fine-tuned by protein interactions and phosphorylation. PKA affects cell migration potentially through spatiotemporal interactions with regulators of Rho GTPases. Here we show that the endogenous regulatory (R) subunit of type I PKA interacts with P-Rex1, a Rac guanine nucleotide exchange factor that integrates chemotactic signals. Type I PKA holoenzyme interacts with P-Rex1 PDZ domains via the CNB B domain of RIα, which when expressed by itself facilitates endothelial cell migration. P-Rex1 activation localizes PKA to the cell periphery, whereas stimulation of PKA phosphorylates P-Rex1 and prevents its activation in cells responding to SDF-1 (stromal cell-derived factor 1). The P-Rex1 DEP1 domain is phosphorylated at Ser-436, which inhibits the DH-PH catalytic cassette by direct interaction. In addition, the P-Rex1 C terminus is indirectly targeted by PKA, promoting inhibitory interactions independently of the DEP1-PDZ2 region. A P-Rex1 S436A mutant construct shows increased RacGEF activity and prevents the inhibitory effect of forskolin on sphingosine 1-phosphate-dependent endothelial cell migration. Altogether, these results support the idea that P-Rex1 contributes to the spatiotemporal localization of type I PKA, which tightly regulates this guanine exchange factor by a multistep mechanism, initiated by interaction with the PDZ domains of P-Rex1 followed by direct phosphorylation at the first DEP domain and putatively indirect regulation of the C terminus, thus promoting inhibitory intramolecular interactions. This reciprocal regulation between PKA and P-Rex1 might represent a key node of integration by which chemotactic signaling is fine-tuned by PKA.
Threshold cointegration and adaptive shrinkage

This paper considers Bayesian estimation of the threshold vector error correction (TVECM) model in moderate to large dimensions. Using the lagged cointegrating error as a threshold variable gives rise to additional difficulties that are typically solved by relying on large sample approximations. Relying on Markov chain Monte Carlo methods we circumvent these issues by avoiding computationally prohibitive estimation strategies like the grid search. Due to the proliferation of parameters we use novel global-local shrinkage priors in the spirit of Griffin and Brown (2010). We illustrate the merits of our approach in an application to five exchange rates vis-a-vis the US dollar and assess whether a given currency is over or undervalued. Moreover, we perform a forecasting comparison to investigate whether it pays off to adopt a non-linear modeling approach relative to a set of simpler benchmark models.
Gene Expression of Islet Cell Antigen p69 in Human, Mouse, and Rat

Based on the detection of specific antibodies and T-cell sensitization in patients with IDDM, islet cell antigen p69 (ICAp69) has been suggested to be a target antigen of diabetic autoimmunity. The biological function, tissue expression, and developmental kinetics of ICAp69 are largely unknown. We analyzed ICAp69 expression at the gene transcription and protein level in human and rodent tissues. By using template-calibrated quantitative reverse transcriptase polymerase chain reaction (RT-PCR), high levels of ICAp69 mRNA were found in human pancreatic islets and brain. In mouse and rat, ICAp69 gene expression peaked in islet cell lines followed by testis, islets, and brain. ICAp69 mRNA was found at low levels in other organs by RT-PCR but not by Northern blot analysis. In mice, ICAp69 transcription becomes detectable in fetal life, and fetal and adult gene expression patterns are similar. Western blot analysis of human and mouse tissues showed high expression of ICAp69 in brain, testis, pancreatic tissue, and islet cell lines. In these organs, ICAp69 immunoreactivity is predominately localized at the blood brain barrier (capillary endothelium), at the blood testis barrier (Sertoli cells and spermatids), and in pancreatic islets (β-cells). The subcellular localization of ICAp69 to endoplasmic reticulum, Golgi complex, and vesicles by immune electron microscopy suggests a role of this neuroendocrine molecule in cellular protein traffic and processing.
Identifying Drivers of China's Provincial Wastewater Reuse Outcomes Using Qualitative Comparative Analysis

In water‐scarce regions of China, wastewater reuse is increasingly considered as a potential component of China's future water resource management strategy. Currently, the percentage of wastewater reuse varies substantially across Chinese provinces, but conditions leading to a high rate of wastewater reuse have not been elucidated clearly. In this work, we use fuzzy‐set qualitative comparative analysis (fsQCA) to identify the drivers of high and low percentages of wastewater reuse in water‐stressed Chinese provinces in 2013. We find that among the five conditions studied (per capita water availability, urban population, access to sea, access to urban space, and access to agricultural land), a high percentage of wastewater reuse is primarily driven by water stress and access to urban green space. Consequently, policies should consider targeting provinces with these attributes where wastewater reuse is more likely to be successful. Further, our results show that there is asymmetry in the conditions that lead to high and low percentages of wastewater reuse, and that the drivers for and against reuse identified in this study are not completely analogous to those identified in previous studies. As such, the drivers for and against wastewater reuse should not be generalized without due consideration of the local context.
Olfactory Epithelium as a Novel Toxic Target Following an Intravenous Administration of Vincristine to Mice

To delineate morphological characteristics of olfactory lesions induced by vincristine (VCR), a vinca alkaloid derivative with antitumor activity, male BALB/c mice were given a single intravenous injection of 1.95 mg/kg, an estimated 10% lethal dose (designated as day 1). The animals were serially sacrificed on days 2, 3, 5, 10, 15 and 60, and the nasal mucosa was examined histopathologically. Cell death was noted in the olfactory epithelia adjacent to the respiratory epithelia from days 2 to 5. Inflammatory responses were not detected throughout the observation periods. Cell death was identified as apoptotic by the terminal deoxyribonucleotidy l transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay and electron microscopy. Mitotic figures and proliferating cell nuclear antigen (PCNA)-positive reactions were diffusely scattered in both the basal and sensory cells. On days 10 or after, no prominent histological abnormalities were noted in the olfactory epithelia, which suggests the aforementioned lesions were completely recovered. These results demonstrate that it is essential to perform histopathologica l evaluation of the nasal mucosa during an early preclinical stage for novel antitumor drugs, since olfactory lesions due to the certain compound s like VCR may not be detected by any other procedure.
Government Bond Yields at the Effective Lower Bound: International Evidence

Empirical evidence on the potential impact of central bank policies on government bond yields at the effective lower bound (ELB) is presented for nine economies. We quantify the content of central bank communications and consider international policy spillovers. At the ELB, yields at the medium-to-longer end of the yield curve remain responsive to news for a few years after the ELB is reached. Yields become more sensitive to the content central bank communication at the ELB. Our results provides further evidence that central bank communication is an important element of monetary policy making when the interest rate tool loses efficacy.
Redistribution, inequality and political participation: evidence from Mexico during the 2008 financial crisis.

This paper explores the relationship between a large government cash transfer programme, changes in inequality, and political participation in Mexico. The results show that increases in the coverage of the programme during the 2008 financial crisis resulted in greater individual participation in the last presidential elections and in higher individual propensity to vote, particularly for the incumbent party. The programme was particularly effective in increasing political participation among rural and indigenous groups, and had a mitigating effect on participation in presidential elections and the propensity to vote among the urban unskilled. The programme resulted also in reductions in individual participation in protests. Further analysis suggests that these changes were driven by redistributive gains following the changes to the cash transfer programme.
PCKGen: A Phase Change Memory based cryptographic key generator

Physical Unclonable Function (PUF) is widely known as an effective countermeasure to withstand non-invasive computational attacks as well as invasive tempering attacks on trusted computing systems. However, vast majority of the PUFs reported to-date are defined by static Challenge-Response Pairs (CRPs) with inferior security. In this paper, we propose a novel design of dynamically reconfigurable PUF based on Phase Change Memory (PCM) technology to yield refreshed cryptographic keys whenever the need arises to achieve enhanced security. A dedicated circuit framework is also introduced to reinforce the diversity of the CRP sets and improve the stability of the proposed PUF. Extensive simulation results show that our proposed work promises a clean delineation from the security bottlenecks faced by the state-of-the-art PUF designs.
Time Trends in the Published Risks of Stroke and Death due to Endarterectomy for Symptomatic Carotid Stenosis

Background: Large randomised trials performed in the 1980s and early 1990s showed that carotid endarterectomy (CEA) is beneficial for patients with recently symptomatic severe stenosis. Some surgeons have argued that the operative risk of stroke and death has fallen over the last decade due to refinements in operative technique, and that the indications for surgery should therefore now be broadened. Yet, studies of routinely collected data report higher operative mortality than in the trials, and surgical case series without independent post-operative assessment by a neurologist may not provide reliable data on stroke risk. Methods: We performed a systematic review of all studies published between 1994 and 2001 inclusive that which reported the risks of stroke and death for symptomatic carotid stenosis, and compared the reported risks and patient characteristics with those in the ECST and NASCET and with our previous review of studies published prior to 1995. Pooled estimates of the operative risk of stroke and death were obtained by Mantel-Haenszel meta-analysis. Results: Of 383 studies published between 1994 and 2001, only 45 reported operative risks for patients with symptomatic stenosis separately. The pooled operative risk of stroke and death reported in studies published by surgeons only (4.2%, 95% CI = 2.9–5.5, 34 studies) was significantly lower (p < 0.0001) than that in the ECST and NASCET combined (7.0%, 95% CI = 6.2–8.0), whereas the pooled risk reported in studies that involved neurologists was similar (6.5%, 95% CI = 4.3–8.7, 11 studies, p = 0.6). In contrast, operative mortality in ECST and NASCET was significantly lower than in other studies published between 1994 and 2001. By comparison with our previous review, when stratified according to involvement of neurologists, we found no evidence of a reduction in published risks of death or stroke and death due to CEA between 1985 and 2001. Conclusions: There is no evidence of a systematic reduction over the last decade in the published risks of stroke and death due to CEA for symptomatic stenosis. Operative risks in studies with comparable outcome assessment are similar to ECST and NASCET. The surgical data from the large trials are still likely therefore to be applicable to routine clinical practice.
Mapping the Invisible: The Informal Food Economy of Cape Town, South Africa

This report argues that it is essential to understand the dynamics of the informal food retail sector because of its vital role in ensuring greater access to food by the urban poor. Existing policy frameworks to address food security and to govern the informal sector tend to neglect informal retail in the food system. As a result, the sector is poorly understood. The report therefore attempts to identify the characteristics of the sector that impact on its ability to address the food needs of the neighbourhoods in which the businesses are located. Although the research is focused on Cape Town, the findings are of broader relevance.
SNP signatures of selection on standing genetic variation and their association with adaptive phenotypes along gradients of ecological speciation in lake whitefish species pairs (Coregonus spp.)

As populations adapt to novel environments, divergent selection will promote heterogeneous genomic differentiation via reductions in gene flow for loci underlying adaptive traits. Using a data set of over 100 SNP markers, genome scans were performed to investigate the effect of natural selection maintaining differentiation in five lakes harbouring sympatric pairs of normal and dwarf lake whitefish (Coregonus clupeaformis). A variable proportion of SNPs (between 0% and 12%) was identified as outliers, which corroborated the predicted intensity of competitive interactions unique to each lake. Moreover, strong reduction in heterozygosity was typically observed for outlier loci in dwarf but not in normal whitefish, indicating that directional selection has been acting on standing genetic variation more intensively in dwarf whitefish. SNP associations in backcross hybrid progeny identified 16 genes exhibiting genotype–phenotype associations for four adaptive traits (growth, swimming activity, gill rakers and condition factor). However, neither simple relationship between elevated levels of genetic differentiation with adaptive phenotype nor conspicuous genetic signatures for parallelism at outlier loci were detected, which underscores the importance of independent evolution among lakes. The integration of phenotypic, transcriptomic and functional genomic information identified two candidate genes (sodium potassium ATPase and triosephosphate isomerase) involved in the recent ecological divergence of lake whitefish. Finally, the identification of several markers under divergent selection suggests that many genes, in an environment‐specific manner, are recruited by selection and ultimately contributed to the repeated ecological speciation of a dwarf phenotype.
Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. The Cardiovascular Health Study.

BACKGROUND AND PURPOSE Our aim was to identify potential risk factors for and clinical manifestations of white matter findings on cranial MRI in elderly people. METHODS Medicare eligibility lists were used to obtain a representative sample of 5888 community-dwelling people aged 65 years or older. Correlates of white matter findings were sought among 3301 participants who underwent MRI scanning and denied a history of stroke or transient ischemic attack. Participants underwent extensive standardized evaluations at baseline and on follow-up, including standard questionnaires, physical examination, multiple blood tests, electrocardiogram, pulmonary function tests, carotid sonography, and M-mode echocardiography. Neuroradiologists graded white matter findings from 0 (none) to 9 (maximal) without clinical information. RESULTS Many potential risk factors were related to the white matter grade, but in the multivariate model the factors significantly (all P < .01) and independently associated with increased grade were greater age, clinically silent stroke on MRI, higher systolic blood pressure, lower forced expiratory volume in 1 second (FEV1), and income less than $50,000 per year. If excluded, FEV1 was replaced in the model by female sex, history of smoking, and history of physician-diagnosed hypertension at the baseline examination. Many clinical features were correlated with the white matter grade, especially those indicating impaired cognitive and lower extremity function. CONCLUSIONS White matter findings were significantly associated with age, silent stroke, hypertension, FEV1, and income. The white matter findings may not be considered benign because they are associated with impaired cognitive and lower extremity function.
Advances in multicellular spheroids formation

Three-dimensional multicellular spheroids (MCSs) have a complex architectural structure, dynamic cell–cell/cell–matrix interactions and bio-mimicking in vivo microenvironment. As a fundamental building block for tissue reconstruction, MCSs have emerged as a powerful tool to narrow down the gap between the in vitro and in vivo model. In this review paper, we discussed the structure and biology of MCSs and detailed fabricating methods. Among these methods, the approach in microfluidics with hydrogel support for MCS formation is promising because it allows essential cell–cell/cell–matrix interactions in a confined space.
On the cellularity of the cyclotomic Birman–Murakami–Wenzl algebras

The cyclotomic Birman–Murakami–Wenzl (or BMW) algebras ℬnk were introduced by Häring‐Oldenburg as a generalization of the BMW algebras associated with the cyclotomic Hecke algebras of type G(k, 1, n) (also known as Ariki–Koike algebras) and type B knot theory. In the PhD thesis of the second author and previous work of the authors, these algebras are shown to be free of rank kn (2n−1)! over ground rings with parameters satisfying the so‐called ‘admissibility conditions’, the most general conditions under which these results can hold. These conditions are build from the representation theory of ℬ2k and are necessary and sufficient in order for these results to hold. (A review of these admissibility conditions and their differences with others used in the literature is provided in this paper.) Furthermore, ℬnk may be topologically realized, in terms of affine/cylindrical tangles, as a cyclotomic version of the Kauffman tangle algebra, and bases that can be explicitly described both algebraically and diagrammatically were obtained. In this paper, it is shown that these bases combined with a carefully constructed lifting of an arbitrary cellular basis of the Ariki–Koike algebras yield a cellular basis of the cyclotomic BMW algebras, in the sense of Graham and Lehrer, thereby establishing cellularity of the algebra under the most general conditions available in the literature.
Correlation of retinal nerve fiber layer measured by scanning laser polarimeter to visual field in ischemic optic neuropathy.

OBJECTIVE To evaluate the relationship between retinal nerve fiber layer (RNFL) measurement with scanning laser polarimetry (SLP) and standard automated perimetry (SAP) in nonarteritic anterior ischemic optic neuropathy (NAION). METHODS In this prospective observational case series, all subjects (28 eyes with NAION) underwent SAP and SLP. The RNFL retardation measurements and visual field test points were grouped into 6 corresponding sectors. The contralateral uninvolved eye was used as control. The relationship between RNFL retardation and SAP was evaluated with the Spearman nonparametric technique and linear regression analysis. The main outcome measure was correlation of SLP RNFL parameters and SAP. RESULTS Global and sectoral SLP parameters showed a significant difference in affected eyes compared with controls. The strongest correlations were seen between mean deviation and number (r = -0.524; P = .004), ellipse modulation (r = 0.5026; P = .006), and maximum modulation (r = 0.526; P = .004). Superior sectoral visual field indexes showed a strong correlation with inferior RNFL changes (r = 0.522; P<.008). Linear regression confirmed a strong relationship between the superior sectoral visual field indexes and the inferior RNFL. CONCLUSION Scanning laser polarimetry was able to identify structural changes of the RNFL globally and in the inferior SLP sector with functional loss in NAION.
Epidemiology of sudden infant death syndrome (SIDS) in the Tyrol before and after an intervention campaign.

OBJECTIVE We investigated the epidemiology of sudden infant death syndrome (SIDS) in the Tyrol before and after an intervention campaign. PATIENTS AND METHODS Descriptive characteristics and risk factors of SIDS before the campaign were assessed in a retrospective case-control study (1984 to 1994). In April 1994 a country-wide information campaign on modifiable risk behaviours was initiated. Thereafter we prospectively collected data on child care practices four to six weeks after birth for all infants born in the Tyrol (participation rate 72%; n = 28,361) and evaluated new SIDS cases (1994 to 1998). For this purpose two questionnaires were used, one with 96 items for the evaluation of all SIDS cases and assessment of child care practices before 1994, and the other with 24 items for prospective data collection. RESULTS The incidence of SIDS decreased from 1.83 (mean incidence, 1984-1994) to 0.4/1000 live births immediately after the campaign and remained low until 1998. The frequency of maternal smoking during pregnancy declined (22.9% vs. 14.5%, p < 0.01), as did the prevalence of the prone sleeping position (53.7% vs. 5.4%, p < 0.001) and of non-breastfeeding (21.3% vs. 6.7%, p < 0.001). All these variables were prominent risk factors for SIDS before the campaign and remained significant thereafter. On account of the markedly reduced prevalence of the prone sleeping position, smoking became the most common SIDS risk factor. The prevalence of sleeping on the side significantly increased (5.1% vs. 36.4%, p < 0.001) and the social status of mothers of SIDS infants tended to be lower than that before the campaign. The clear winter preponderance of SIDS which was evident before the campaign disappeared, or was even reversed. CONCLUSIONS Our study documents the long-term efficacy of a low-cost intervention campaign by way of health education. Further efforts must be directed toward lower social classes, thereby focusing on maternal smoking and avoidance of the side sleeping position.
Silver, bighead, and common carp orient to acoustic particle motion when avoiding a complex sound

Behavioral responses of silver carp (Hypopthalmichthys molitrix), bighead carp (H. nobilis), and common carp (Cyprinus carpio) to a complex, broadband sound were tested in the absence of visual cues to determine whether these species are negatively phonotaxic and the roles that sound pressure and particle motion might play mediating this response. In a dark featureless square enclosure, groups of 3 fish were tracked and the distance of each fish from speakers and their swimming trajectories relative to sound pressure and particle acceleration were analyzed before, and then while an outboard motor sound was played. All three species exhibited negative phonotaxis during the first two exposures after which they ceased responding. The median percent time fish spent near the active speaker for the first two trials decreased from 7.0% to 1.3% for silver carp, 7.9% to 1.1% for bighead carp, and 9.5% to 3% for common carp. Notably, when close to the active speaker fish swam away from the source and maintained a nearly perfect 0° orientation to the axes of particle acceleration. Fish did not enter sound fields greater than 140 dB (ref. 1 μPa). These results demonstrate that carp avoid complex sounds in darkness and while initial responses may be informed by sound pressure, sustained oriented avoidance behavior is likely mediated by particle motion. This understanding of how invasive carp use particle motion to guide avoidance could be used to design new acoustic deterrents to divert them in dark, turbid river waters.