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A network perspective on multi-scale water governance in the Lake Champlain Basin, Vermont
No full textThe prevalence and persistence of harmful cyanobacterial blooms demonstrate the importance of governance systems that effectively engage with many actors to address nonpoint pollution from a variety of sources across multiple spatial domains. Although the importance of social-ecological alignment on effective governance is increasingly clear, governance systems often evolve incrementally and in a manner that fails to adequately align resources and governance networks with biophysical structures, processes, and legacies. Through a survey of water governance actors in the Lake Champlain Basin, we map the structure of the water governance network and identify the key information brokers, flows of resources, and ongoing collaborative partnerships. We measure cross-scale and within-scale linkages to characterize the degree of coordination across space and scale using exponential random graph models, finding distinct differences in governance activities by mode of coordination. We also show that coordination in the system is largely a function of geographic proximity and shared issues of concern, demonstrating the importance of multidimensional, social-ecological perspectives in the collaborative governance of freshwater systems. Specific to the Lake Champlain Basin, our findings suggest that as the transformation of the governance system proceeds, cross-scale and inter-watershed coordination must be regularized to maintain learning and innovation across the system as it pursues its clean water goals
A MISO Frequency Diverse Array Implementation
No full textThe separation of RF signals from different angles of arrival is a key objective for a radarreceiver. A common approach to spatial separation relies on the measurement of a linear phaseprogression across multiple receive antenna elements, where the rate of progression relates directlyto a spatial angle of arrival.With a single antenna receiver, spatial separation can still be achieved using spatially diverseemission structures. One such emission structure is the Frequency Diverse Array (FDA), whichtransmits a frequency shifted version of a common waveform out of each element. Due to thefrequency shifts, the peak of the mainbeam sweeps across time and space.With a careful choice of waveform and frequency shift, the waveforms transmitted from eachelement can be identified and separated in delay, and only a single receiver antenna element isneeded to measure a phase progression across the waveform responses or "virtual array" in delay.In this thesis, a Multiple Input Single Output (MISO) radar system capable of performingrange, Doppler, and spatial estimation will be presented and experimentally validated. The systemleverages key features of the LFMCW-FDA emission structure to achieve a single channel receiverarchitecture which can realize the aforementioned performance and simultaneously remain computationally inexpensive. When compared to other spatially diverse emissions, the system is shownto retain the unambiguous range and Doppler spaces. The potential for this type of emission structure to be used in a search radar context is also explored. Additionally, an adaptive processingalgorithm will be introduced along with simulated results showing an improved ability to separateclosely spaced scatterers in range and space
Deep Learning Dynamic Allostery of G-Protein-Coupled Receptors
No full textG-protein-coupled receptors (GPCRs) make up the largest superfamily of human membrane proteins and represent primary targets of ∼1/3 of currently marketed drugs. Allosteric modulators have emerged as more selective drug candidates compared with orthosteric agonists and antagonists. However, many X-ray and cryo-EM structures of GPCRs resolved so far exhibit negligible differences upon the binding of positive and negative allosteric modulators (PAMs and NAMs). The mechanism of dynamic allosteric modulation in GPCRs remains unclear. In this work, we have systematically mapped dynamic changes in free energy landscapes of GPCRs upon binding of allosteric modulators using the Gaussian accelerated molecular dynamics (GaMD), deep learning (DL), and free energy prOfiling Workflow (GLOW). GaMD simulations were performed for a total of 66 μs on 44 GPCR systems in the presence and absence of the modulator. DL and free energy calculations revealed significantly reduced dynamic fluctuations and conformational space of GPCRs upon modulator binding. While the modulator-free GPCRs often sampled multiple low-energy conformational states, the NAMs and PAMs confined the inactive and active agonist-G-protein-bound GPCRs, respectively, to mostly only one specific conformation for signaling. Such cooperative effects were significantly reduced for binding of the selective modulators to “non-cognate” receptor subtypes. Therefore, GPCR allostery exhibits a dynamic “conformational selection” mechanism. In the absence of available modulator-bound structures as for most current GPCRs, it is critical to use a structural ensemble of representative GPCR conformations rather than a single structure for compound docking (“ensemble docking”), which will potentially improve structure-based design of novel allosteric drugs of GPCRs
Three-dimensional topology dataset of folded radar stratigraphy in northern Greenland
No full textWe present a dataset of reconstructed three-dimensional (3D) englacial stratigraphic horizons in northern Greenland. The data cover four different regions representing key ice-dynamic settings in Greenland: (i) the onset of Petermann Glacier, (ii) a region upstream of the 79° North Glacier (Nioghalvfjerdsbræ), near the northern Greenland ice divide, (iii) the onset of the Northeast Greenland Ice Stream (NEGIS) and (iv) a 700 km wide region extending across the central ice divide over the entire northern part of central Greenland. In this paper, we promote the advantages of a 3D perspective of deformed englacial stratigraphy and explain how 3D horizons provide an improved basis for interpreting and reconstructing the ice-dynamic history. The 3D horizons are provided in various formats to allow a wide range of applications and reproducibility of results
Cold agglutinin disease: A case report with atypical clinical findings
No full textA grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.A female in her 60s presented to the allergy and immunology clinic for further investigation of ongoing dermatitis. She presented with chronic acrocyanosis, mainly in her left lower extremity, extending distally from her mid thigh with concurrent ulcerations in her foot resulting in immobility secondary to pain. She experienced these symptoms for years without a definitive diagnosis. The lack of diagnosis was due, in part, to her atypical symptoms and laboratory findings that required a high level of clinical suspicion to diagnose. Extensive autoimmune workup was largely unrevealing with the exception of a cold agglutinin titer of 1:250 and a positive anticomplement C3b direct antiglobulin test. A diagnosis of cold agglutinin disease was made and treatment with rituximab monotherapy was initiated
Longitudinal Impact of the COVID-19 Pandemic on Stress and Occupational Well-Being of Mental Health Professionals: An International Study
No full textBackground
Increased levels of occupational stress among health professionals during the COVID-19 pandemic have been documented. Few studies have examined the effects of the pandemic on mental health professionals despite the heightened demand for their services.
Method
A multilingual, longitudinal, global survey was conducted at 3 time points during the pandemic among members of the World Health Organization’s Global Clinical Practice Network. A total of 786 Global Clinical Practice Network members from 86 countries responded to surveys assessing occupational distress, well-being, and posttraumatic stress symptoms.
Results
On average, respondents’ well-being deteriorated across time while their posttraumatic stress symptoms showed a modest improvement. Linear growth models indicated that being female, being younger, providing face-to-face health services to patients with COVID-19, having been a target of COVID-related violence, and living in a low- or middle-income country or a country with a higher COVID-19 death rate conveyed greater risk for poor well-being and higher level of stress symptoms over time. Growth mixed modeling identified trajectories of occupational well-being and stress symptoms. Most mental health professions demonstrated no impact to well-being; maintained moderate, nonclinical levels of stress symptoms; or showed improvements after an initial period of difficulty. However, some participant groups exhibited deteriorating well-being approaching the clinical threshold (25.8%) and persistently high and clinically significant levels of posttraumatic stress symptoms (19.6%) over time.
Conclusions
This study indicates that although most mental health professionals exhibited stable, positive well-being and low stress symptoms during the pandemic, a substantial minority of an already burdened global mental health workforce experienced persistently poor or deteriorating psychological status over the course of the pandemic
A heterologous expression platform in Aspergillus nidulans for the elucidation of cryptic secondary metabolism biosynthetic gene clusters: discovery of the Aspergillus fumigatus sartorypyrone biosynthetic pathway
No full textAspergillus fumigatus is a serious human pathogen causing life-threatening Aspergillosis in immunocompromised patients. Secondary metabolites (SMs) play an important role in pathogenesis, but the products of many SM biosynthetic gene clusters (BGCs) remain unknown. In this study, we have developed a heterologous expression platform in Aspergillus nidulans, using a newly created genetic dereplication strain, to express a previously unknown BGC from A. fumigatus and determine its products. The BGC produces sartorypyrones, and we have named it the spy BGC. Analysis of targeted gene deletions by HRESIMS, NMR, and microcrystal electron diffraction (MicroED) enabled us to identify 12 products from the spy BGC. Seven of the compounds have not been isolated previously. We also individually expressed the polyketide synthase (PKS) gene spyA and demonstrated that it produces the polyketide triacetic acid lactone (TAL), a potentially important biorenewable platform chemical. Our data have allowed us to propose a biosynthetic pathway for sartorypyrones and related natural products. This work highlights the potential of using the A. nidulans heterologous expression platform to uncover cryptic BGCs from A. fumigatus and other species, despite the complexity of their secondary metabolomes
Using pre-surgical suspicion to guide insula implantation strategy
No full textRationale
Insular epilepsy can be a challenging diagnosis due to overlapping semiology and scalp EEG findings with frontal, temporal, and parietal lobe epilepsies. Stereotactic electroencephalography (sEEG) provides an opportunity to better localize seizure onset. The possibility of improved localization is balanced by implantation risk in this vascularly rich anatomic region. We review both safety and pre-implantation factors involved in insular electrode placement across four years at an academic medical center.
Methods
Presurgical data, operative reports, and invasive EEG summaries were retrospectively reviewed for patients undergoing invasive epilepsy monitoring on the insula from 2016 through 2019. EEG reports were reviewed to record the presence of insula ictal and interictal involvement. We recorded which presurgical findings suggested insular involvement (insula lesion on MRI, insula changes on PET/SPECT/scalp EEG, characteristic semiology, or history of failed anterior temporal lobectomy). The likelihood of pre-sEEG insular onset was categorized as low suspicion if no presurgical findings were present (“rule out”), moderate suspicion if one finding was present, and high suspicion if two or more findings were present.
Results
76 patients received 189 insular electrodes as part of their implantation strategy for 79 surgical cases. Seven patients (8.9%) had insular ictal onset. One clinically significant complication (left hemiparesis) occurred in a patient with moderate suspicion for insular onset. There were 38 low suspicion cases, 36 moderate suspicion cases, and 5 high suspicion cases for pre-sEEG insula ictal onset. Two low suspicion (5.3%), three moderate suspicion (8.6%), and two high suspicion (40%) cases had insular ictal onset.
Conclusions
The insula can safely receive sEEG. Having two or more presurgical factors indicating insular onset is a strong, albeit incomplete, predictor of insular seizure onset. Using pre-implantation clinical findings can offer clinicians predictive value for targeting the insula during invasive EEG monitoring
Predicting climate-driven distribution shifts in Hyalomma marginatum (Ixodidae)
No full textHyalomma marginatum is an important tick species which is the main vector of Crimean–Congo haemorrhagic fever and spotted fever. The species is predominantly distributed in parts of southern Europe, North Africa and West Asia. However, due to ongoing climate change and increasing reports of H. marginatum in central and northern Europe, the expansion of this range poses a potential future risk. In this study, an ecological niche modelling approach to model the current and future climatic suitability of H. marginatum was followed. Using high-resolution climatic variables from the Chelsa dataset and an updated list of locations for H. marginatum, ecological niche models were constructed under current environmental conditions using MaxEnt for both current conditions and future projections under the ssp370 and ssp585 scenarios. Models show that the climatically suitable region for H. marginatum matches the current distributional area in the Mediterranean basin and West Asia. When applied to future projections, the models suggest a considerable expansion of H. marginatum's range in the north in Europe as a result of rising temperatures. However, a decline in central Anatolia is also predicted, potentially due to the exacerbation of drought conditions in that region
Oligosaccharide production and signaling correlate with delayed flowering in an Arabidopsis genotype grown and selected in high [CO2]
No full textSince industrialization began, atmospheric CO2 ([CO2]) has increased from 270 to 415 ppm and is projected to reach 800-1000 ppm this century. Some Arabidopsis thaliana (Arabidopsis) genotypes delayed flowering in elevated [CO2] relative to current [CO2], while others showed no change or accelerations. To predict genotype-specific flowering behaviors, we must understand the mechanisms driving flowering response to rising [CO2]. [CO2] changes alter photosynthesis and carbohydrates in plants. Plants sense carbohydrate levels, and exogenous carbohydrate application influences flowering time and flowering transcript levels. We asked how organismal changes in carbohydrates and transcription correlate with changes in flowering time under elevated [CO2]. We used a genotype (SG) of Arabidopsis that was selected for high fitness at elevated [CO2] (700 ppm). SG delays flowering under elevated [CO2] (700 ppm) relative to current [CO2] (400 ppm). We compared SG to a closely related control genotype (CG) that shows no [CO2]-induced flowering change. We compared metabolomic and transcriptomic profiles in these genotypes at current and elevated [CO2] to assess correlations with flowering in these conditions. While both genotypes altered carbohydrates in response to elevated [CO2], SG had higher levels of sucrose than CG and showed a stronger increase in glucose and fructose in elevated [CO2]. Both genotypes demonstrated transcriptional changes, with CG increasing genes related to fructose 1,6-bisphosphate breakdown, amino acid synthesis, and secondary metabolites; and SG decreasing genes related to starch and sugar metabolism, but increasing genes involved in oligosaccharide production and sugar modifications. Genes associated with flowering regulation within the photoperiod, vernalization, and meristem identity pathways were altered in these genotypes. Elevated [CO2] may alter carbohydrates to influence transcription in both genotypes and delayed flowering in SG. Changes in the oligosaccharide pool may contribute to delayed flowering in SG. This work extends the literature exploring genotypic-specific flowering responses to elevated [CO2]