Miracle-dz/UniFAR-FTUs huggingface dataset:
Environmental Variability and Oceanographic Dynamics of the Central and Southern Coastal Zone of Sonora in the Gulf of California

This study analyzed monthly and inter-annual variability of mesoscale phenomena, including the El Nino Southern Oscillation (ENSO), the Pacific Decadal Oscillation (PDO) climate indexes and wind intensity considering their influence on sea surface temperature (SST) and chlorophyll a (Chl-a). These analyses were performed to determine the effects, if any, of climate indexes and oceanographic and environmental variability on the central and southern coastal ecosystem of Sonora in the Gulf of California (GC). Monthly satellite images of SST (°C) and Chl-a concentration were used with a 1-km resolution for oceanographic and environmental description, as well as monthly data of the climate indexes and wind intensity from 2002–2015. Significant differences (p > 0.05) were observed while analyzing the monthly variability results of mesoscale phenomena, SST and Chl-a, where the greatest percentage of anti-cyclonic gyres and filaments was correlated with a greater Chl-a concentration in the area of study, low temperatures and, thus, greater productivity. Moreover, the greatest percentage of intrusion was correlated with the increase in temperature and cyclonic gyres and a strong decrease of Chl-a concentration values, causing oligotrophic conditions in the ecosystem and a decrease in upwelling and filament occurrence. As for the analysis of the interannual variability of mesoscales phenomena, SST, Chl-a and winds, the variability between years was not significant (p > 0.05), so no correlation was observed between variabilities or phenomena. The results of the monthly analyses of climate indexes, environmental variables and wind intensity did not show significant differences for the ENSO and PDO indexes (p > 0.05). Nonetheless, an important correlation could be observed between the months of negative anomalies of the ENSO with high Chl-a concentration values and intense winds, as well as with low SST values. The months with positive ENSO anomalies were correlated with high SST values, low Chl-a concentration and moderate winds. Significant inter-annual differences were observed for climate indexes where the years with high SST values were related to the greatest positive anomaly of ENSO, of which 2002 and 2009 stood out, characterized as moderate Nino years, and 2015 as a strong El Nino year. The years with the negative ENSO anomaly were related to the years of lower SST values, of which 2007–2008 and 2010–2011 stood out, characterized as moderate Ninas. Thus, variability associated with mesoscale oceanographic phenomena and seasonal and inter-annual variations of climate indexes had a great influence on the environmental conditions of the coastal ecosystem of Sonora in the Gulf of California.
Towards European harmonisation of contagious equine metritis diagnosis through interlaboratory trials

The performance of culture and PCR methods routinely used to diagnose contagious equine metritis (CEM) was evaluated and compared by two interlaboratory trials involving a total of 24 European laboratories, including 22 National Reference Laboratories for CEM. Samples were swab specimens artificially contaminated with bacteria present in the genital tract of Equidae, some with and some without Taylorella equigenitalis, the causative agent of CEM, and T asinigenitalis, responsible for possible misidentification as T equigenitalis. Throughout both interlaboratory trials, PCR performed better in terms of specificity and sensitivity than the culture method, supporting the assertion that PCR should be accepted for CEM diagnosis. However, the culture performance during the second interlaboratory trial was better than during the first one, suggesting that the expertise of participants improved. This reveals the advantage of regular interlaboratory trials to constantly improve the expertise of laboratories. It also shows the need to develop new culture media that are more selective and/or better geared to the metabolism of T equigenitalis in order to improve the bacteriological diagnosis of CEM.
Prospects for the Detection of the Deep Solar Meridional Circulation

We perform helioseismic holography to assess the noise in p-mode travel-time shifts which would form the basis of inferences of large-scale flows throughout the solar convection zone. We also derive the expected travel times from a parameterized return (equatorward) flow component of the meridional circulation at the base of the convection zone from forward models under the assumptions of the ray and Born approximations. From estimates of the signal-to-noise ratio for measurements focused near the base of the convection zone, we conclude that the helioseismic detection of the deep meridional flow including the return component may not be possible using travel-time measurements spanning an interval less than a solar cycle. We speculate that this conclusion may be generally true for other helioseismic methods under the assumption that the underlying measurements are equivalently limited by solar realization noise.
Cytokines in Sjögren's syndrome: potential therapeutic targets

The dysregulated cytokine network in Sjögren's Syndrome (SS) is reflected by local and systemic overexpression of pro-inflammatory cytokines and absent or low levels of anti-inflammatory cytokines. To date, the use of cytokine based therapies in SS has been disappointing. Oral administration of low dose interferon (IFN) α showed inconsistent efficacy in various studies and failed to achieve the primary endpoint in a pivotal randomised controlled trial. Similarly, neither of the two tumour necrosis factor (TNF)-α blockers tested (etanercept and infliximab) showed efficacy in placebo controlled trials. Although the rationale for low dose oral IFN treatment has not been firmly established, TNF blockade was based on solid preclinical data. Therefore, the reason for the lack of efficacy is unclear, but recent data suggest that unexpected biological effects of TNF antagonists may have contributed to this. Cytokines, given their central role in the pathogenesis of SS, remain attractive targets for future treatments, despite the disappointing early results. Inflammatory cytokines are obvious candidates, and agents against several of them are available or under development for other autoimmune diseases similar to SS. New candidate cytokines such as IL-17 and IL-12 and/or IL-23 may provide promising targets for SS. Additionally, as an alternative to systemic treatment, which has the risk of potentially severe side effects, the use of local cytokine directed therapy should be explored.
Genotype-Specific Abnormalities in Mitochondrial Function Associate with Distinct Profiles of Energy Metabolism and Catecholamine Content in Pheochromocytoma and Paraganglioma

Purpose: Pheochromocytomas and paragangliomas (PGL) are neuroendocrine tumors of sympathetic and parasympathetic paraganglia. This study investigated the relationships between genotype-specific differences in mitochondrial function and catecholamine content in PGL tumors. Experimental Design: Respiratory chain enzyme assays and 1H-nuclear magnetic resonance (NMR) spectroscopy at 500 MHz were conducted on homogenates of 35 sporadic PGLs and 59 PGLs from patients with hereditary mutations in succinate dehydrogenase subunits B and D (SDHB, SDHD), succinate dehydrogenase assembly factor 2, von Hippel-Lindau (VHL), rearranged during transfection (RET), neurofibromatosis type 1 (NF1), and myc-associated factor X. Results: In SDHx-related PGLs, a significant decrease in complex II activity (P < 0.0001) and a significant increase in complex I, III, and IV enzyme activities were observed when compared to sporadic, RET, and NF1 tumors. Also, a significant increase in citrate synthase (P < 0.0001) enzyme activity was observed in SDHx-related PGLs when compared to sporadic-, VHL-, RET-, and NF1-related tumors. An increase in succinate accumulation (P < 0.001) and decrease in ATP/ADP/AMP accumulation (P < 0.001) was observed when compared to sporadic PGLs and PGLs of other genotypes. Positive correlations (P < 0.01) were observed between respiratory chain complex II activity and total catecholamine content and ATP/ADP/AMP and total catecholamine contents in tumor tissues. Conclusions: This study for the first time establishes a relationship between determinants of energy metabolism, like activity of respiratory chain enzyme complex II, ATP/ADP/AMP content, and catecholamine content in PGL tumors. Also, this study for the first time successfully uses NMR spectroscopy to detect catecholamines in PGL tumors and provides ex vivo evidence for the accumulation of succinate in PGL tumors with an SDHx mutation. Clin Cancer Res; 19(14); 3787–95. ©2013 AACR.
Past and current asbestos exposure and future mesothelioma risks in Britain: The Inhaled Particles Study (TIPS)

Abstract Background Occupational and environmental airborne asbestos concentrations are too low and variable for lifetime exposures to be estimated reliably, and building workers and occupants may suffer higher exposure when asbestos in older buildings is disturbed or removed. Mesothelioma risks from current asbestos exposures are therefore not known. Methods We interviewed and measured asbestos levels in lung samples from 257 patients treated for pneumothorax and 262 with resected lung cancer, recruited in England and Wales. Average lung burdens in British birth cohorts from 1940 to 1992 were estimated for asbestos-exposed workers and the general population. Results Regression analysis of British mesothelioma death rates and average lung burdens in birth cohorts born before 1965 suggests a lifetime mesothelioma risk of approximately 0.01% per fibre/mg of amphiboles in the lung. In those born since 1965, the average lung burden is ∼1 fibre/mg among those with no occupational exposure. Conclusions The average lifetime mesothelioma risk caused by recent environmental asbestos exposure in Britain will be about 1 in 10 000. The risk is an order of magnitude higher in a subgroup of exposed workers and probably in occupants in the most contaminated buildings. Further data are needed to discover whether asbestos still present in buildings, particularly schools, is a persistent or decreasing hazard to workers who disturb it and to the general population, and whether environmental exposure occurs predominantly in childhood or after beginning work. Similar studies are needed in other countries to estimate continuing environmental and occupational mesothelioma hazards worldwide, including the contribution from chrysotile.
Adaptive Coding of Reward Value by Dopamine Neurons

It is important for animals to estimate the value of rewards as accurately as possible. Because the number of potential reward values is very large, it is necessary that the brain's limited resources be allocated so as to discriminate better among more likely reward outcomes at the expense of less likely outcomes. We found that midbrain dopamine neurons rapidly adapted to the information provided by reward-predicting stimuli. Responses shifted relative to the expected reward value, and the gain adjusted to the variance of reward value. In this way, dopamine neurons maintained their reward sensitivity over a large range of reward values.
MicroRNA Signature Characterizes Primary Tumors That Metastasize in an Esophageal Adenocarcinoma Rat Model

Objective To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC). Background The incidence of esophageal adenocarcinoma (EAC) has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies. Methods The modified Levrat’s surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA) along with upstream and downstream targets. miRNA-linked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5) and metastasis negative (n=28) primary tumors. Results The epithelial origin of distant metastasis was established by IF using villin (VIL1) and mucin 5AC (MUC5AC) antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-92a-3p (p=0.0001), miR-141-3p (p=0.0022), miR-451-1a (p=0.0181) and miR133a-3p (p=0.0304). Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2. Conclusion In vivo metastasis was confirmed in the modified Levrat’s model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized.
Real-World Experiences of the Coaching Pathos: Orchestration of NCAA Division I Sport

Sport coaching is marked by a pathos created by limited control and limited awareness, contradictory beliefs, and novelty. Still, coaches can enhance the likelihood of optimal outcomes through orchestration, a process marked by unobtrusive, flexible actions that enhance athletes’ ability to work toward competitive goals (Jones & Wallace, 2005). This research sought to create a detailed understanding of pathos and orchestration in collegiate coaching. Participants were 10 head coaches from National Collegiate Athletic Association universities. Analysis of semistructured interviews produced four themes: (a) true control is limited but attempted control is extensive, (b) orchestration strategies are varied in context and method, (c) relationships enhance the effectiveness of the orchestration process, and (d) planning the next step allows for relative stability in the pathos. These results expand our understanding of pathos and orchestration, suggesting the concepts have promise in educating coaches about so.
Paradox Research in Management Science: Looking Back to Move Forward

Paradox studies offer vital and timely insights into an array of organizational tensions. Yet this field stands at a critical juncture. Over the past 25 years, management scholars have drawn foundational insights from philosophy and psychology to apply a paradox lens to organizational phenomena. Yet extant studies selectively leverage ancient wisdom, adopting some key insights while abandoning others. Using a structured content analysis to review the burgeoning management literature, we surface six key themes, which represent the building blocks of a meta-theory of paradox. These six themes received varying attention in extant studies: paradox scholars emphasize types of paradoxes, collective approaches, and outcomes, but pay less attention to relationships within paradoxes, individual approaches, and dynamics. As this analysis suggests, management scholars have increasingly simplified the intricate, often messy phenomena of paradox. Greater simplicity renders phenomena understandable and testable, however, oversimplifying complex realities can foster reductionist and incomplete theories. We therefore propose a future research agenda targeted at enriching a meta-theory of paradox by reengaging these less developed themes. Doing so can sharpen the focus of this field, while revisiting its rich conceptual roots to capture the intricacies of paradox. This future research agenda leverages the potential of paradox across diverse streams of management science.
Dome-headed, small-brained island mammal from the Late Cretaceous of Romania

Significance Island-living animals often differ from close relatives and mainland contemporaries in unusual ways, as best demonstrated by modern and Cenozoic mammals that are dwarfed or evolved aberrant anatomical features. However, it is unclear whether mammals from the Age of Dinosaurs followed this same pattern. We describe the fossil skeleton of a previously undiscovered peculiar Cretaceous island-dwelling mammal from Romania, which has a domed skull and one of the smallest brains (proportional to body size) of any mammal, living or extinct, but retains enlarged regions of the brain related to sensory processing. These unusual features were probably related to the species’ island habitat and demonstrate that the ability to adapt to island environments developed early in mammalian history. The island effect is a well-known evolutionary phenomenon, in which island-dwelling species isolated in a resource-limited environment often modify their size, anatomy, and behaviors compared with mainland relatives. This has been well documented in modern and Cenozoic mammals, but it remains unclear whether older, more primitive Mesozoic mammals responded in similar ways to island habitats. We describe a reasonably complete and well-preserved skeleton of a kogaionid, an enigmatic radiation of Cretaceous island-dwelling multituberculate mammals previously represented by fragmentary fossils. This skeleton, from the latest Cretaceous of Romania, belongs to a previously unreported genus and species that possesses several aberrant features, including an autapomorphically domed skull and one of the smallest brains relative to body size of any advanced mammaliaform, which nonetheless retains enlarged olfactory bulbs and paraflocculi for sensory processing. Drawing on parallels with more recent island mammals, we interpret these unusual neurosensory features as related to the island effect. This indicates that the ability to adapt to insular environments developed early in mammalian history, before the advent of therian mammals, and mammals with insular-related modifications were key components of well-known dwarfed dinosaur faunas. Furthermore, the specimen suggests that brain size reduction, in association with heightened sensory acuity but without marked body size change, is a novel expression of the island effect in mammals.
Developing the Capacity of Ethics Consultants to Promote Just Resource Allocation

One of the most striking findings of the study by Foglia and colleagues (2009) was that clinicians and managers were most concerned with limited resources while ethics committee chairpersons focused largely on other concerns. Similarly, in our experience in surveying clinicians, we find that they often face limited resources and the need to ration ‘at the bedside’ yet rarely seek advice from ethics consultants to address the attendant ethical concerns. We agree with the authors that addressing these issues “will require added skills” (28); it may also require a broader theoretical framework that draws more explicitly from political philosophy than clinical ethics usually does, yet is nevertheless applicable in a clinical setting. Here we will complement the authors’ discussion with such a normative perspective based on integrative social contract theory, and offer some practical suggestions for addressing the organizational challenge of resource allocation efficiently and fairly.
Hedgehog Signaling Regulates Sensory Cell Formation and Auditory Function in Mice and Humans

Auditory perception is mediated through a finite number of mechanosensory hair cells located in a specialized sensory epithelium within the inner ear. The formation of the appropriate number of hair cells and the location of those cells is crucial for normal auditory function. However, the factors that regulate the formation of this epithelium remain poorly understood. Truncating mutations in the transcription factor GLI3, a downstream effector of the Hedgehog (HH) pathway, lead to a partial loss of HH signaling and cause Pallister-Hall syndrome (PHS). Here, we report that cochleae from a mouse model of PHS (Gli3Δ699), which produces only the truncated, repressor form of GLI3, have a variably penetrant phenotype that includes an increase in the size of the sensory epithelium and the development of large ectopic sensory patches in Kölliker's organ (KO). Consistent with the mouse model, some PHS individuals exhibit hearing loss across a broad range of frequencies. Moreover, inhibition of HH signaling in vitro results in an increase in the size of the prosensory domain, a precursor population that gives rise to the sensory epithelium, whereas treatment with Sonic hedgehog (SHH) inhibits prosensory formation. Finally, we demonstrate that HH signaling within the cochlea regulates expression of prosensory markers and that the effects of HH in KO are dependent on activation of Notch, an inducer of prosensory fate. These results suggest that HH signaling plays a key role in the specification, size, and location of the prosensory domain, and therefore of hair cells, within the cochlea.
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone

Cilia have a unique diffusion barrier (“gate”) within their proximal region, termed transition zone (TZ), that compartmentalises signalling proteins within the organelle. The TZ is known to harbour two functional modules/complexes (Meckel syndrome [MKS] and Nephronophthisis [NPHP]) defined by genetic interaction, interdependent protein localisation (hierarchy), and proteomic studies. However, the composition and molecular organisation of these modules and their links to human ciliary disease are not completely understood. Here, we reveal Caenorhabditis elegans CEP-290 (mammalian Cep290/Mks4/Nphp6 orthologue) as a central assembly factor that is specific for established MKS module components and depends on the coiled coil region of MKS-5 (Rpgrip1L/Rpgrip1) for TZ localisation. Consistent with a critical role in ciliary gate function, CEP-290 prevents inappropriate entry of membrane-associated proteins into cilia and keeps ARL-13 (Arl13b) from leaking out of cilia via the TZ. We identify a novel MKS module component, TMEM-218 (Tmem218), that requires CEP-290 and other MKS module components for TZ localisation and functions together with the NPHP module to facilitate ciliogenesis. We show that TZ localisation of TMEM-138 (Tmem138) and CDKL-1 (Cdkl1/Cdkl2/Cdkl3/Cdlk4 related), not previously linked to a specific TZ module, similarly depends on CEP-290; surprisingly, neither TMEM-138 or CDKL-1 exhibit interdependent localisation or genetic interactions with core MKS or NPHP module components, suggesting they are part of a distinct, CEP-290-associated module. Lastly, we show that families presenting with Oral-Facial-Digital syndrome type 6 (OFD6) have likely pathogenic mutations in CEP-290-dependent TZ proteins, namely Tmem17, Tmem138, and Tmem231. Notably, patient fibroblasts harbouring mutated Tmem17, a protein not yet ciliopathy-associated, display ciliogenesis defects. Together, our findings expand the repertoire of MKS module-associated proteins—including the previously uncharacterised mammalian Tmem80—and suggest an MKS-5 and CEP-290-dependent assembly pathway for building a functional TZ.
Prescription Drug Misuse Among College Students

Prescription drug misuse (PDM) is a well-documented trend among college students, with a rising prevalence in recent years. Motivations for PDM are an important aspect of the dynamics surrounding this behavior. Using a sample of undergraduate students taken from a large southern university (N = 841), this study separates users based on their motives into typologies of instrumental, recreational, or mixed motive users and examines the differences between them using a number of social learning, social control, and strain-based risk factors while also comparing them with non-users. The results show that social learning risk factors, specifically those related to the concepts of differential association and differential reinforcement, as well as the use of other drugs, exert the greatest impact on likelihood of PDM between the motivational typologies.