Miracle-dz/UniFAR-FTUs huggingface dataset:
Vesicular glutamate transporter 2 is required for the respiratory and parasympathetic activation produced by optogenetic stimulation of catecholaminergic neurons in the rostral ventrolateral medulla of mice in vivo

Catecholaminergic neurons of the rostral ventrolateral medulla (RVLM‐CA neurons; C1 neurons) contribute to the sympathetic, parasympathetic and neuroendocrine responses elicited by physical stressors such as hypotension, hypoxia, hypoglycemia, and infection. Most RVLM‐CA neurons express vesicular glutamate transporter (VGLUT)2, and may use glutamate as a ionotropic transmitter, but the importance of this mode of transmission in vivo is uncertain. To address this question, we genetically deleted VGLUT2 from dopamine‐β‐hydroxylase‐expressing neurons in mice [DβHCre/0;VGLUT2flox/flox mice (cKO mice)]. We compared the in vivo effects of selectively stimulating RVLM‐CA neurons in cKO vs. control mice (DβHCre/0), using channelrhodopsin‐2 (ChR2–mCherry) optogenetics. ChR2–mCherry was expressed by similar numbers of rostral ventrolateral medulla (RVLM) neurons in each strain (~400 neurons), with identical selectivity for catecholaminergic neurons (90–99% colocalisation with tyrosine hydroxylase). RVLM‐CA neurons had similar morphology and axonal projections in DβHCre/0 and cKO mice. Under urethane anesthesia, photostimulation produced a similar pattern of activation of presumptive ChR2‐positive RVLM‐CA neurons in DβHCre/0 and cKO mice. Photostimulation in conscious mice produced frequency‐dependent respiratory activation in DβHCre/0 mice but no effect in cKO mice. Similarly, photostimulation under urethane anesthesia strongly activated efferent vagal nerve activity in DβHCre/0 mice only. Vagal responses were unaffected by α1‐adrenoreceptor blockade. In conclusion, two responses evoked by RVLM‐CA neuron stimulation in vivo require the expression of VGLUT2 by these neurons, suggesting that the acute autonomic responses driven by RVLM‐CA neurons are mediated by glutamate.
Green fluorescent protein as a novel tool to measure apoptosis and necrosis.

BACKGROUND Several apoptosis-detecting methods are currently available. Many of them are work intensive and require the additional use of antibodies, dyes, specific substrates, or enzymatic reactions. A simple, fast, and reliable method was developed to test for apoptosis or necrosis using mouse and human cell lines (e.g., Jurkat, A20.2J, and PB3c cells) stably transfected with a vector coding for green fluorescent protein (GFP) as indicator cells. METHODS Apoptosis in GFP-transfected cell lines was induced either by soluble Fas-Ligand (sFasL), recombinant human TRAIL (rhTRAIL), or interleukin-3 (IL-3) deprivation. Necrosis was induced by polyclonal anti-A20 and complement treatment of GFP-transfected A20. Cells were analyzed by flow cytometry for GFP fluorescence. Propidium iodide and Annexin V staining were used to confirm the results obtained with the GFP-method. RESULTS Live GFP-transfected cells show a strong fluorescence intensity, which is significantly diminished upon induction of apoptosis, whereas necrotic GFP-transfected cells almost completely lose their GFP-associated fluorescence. Apoptosis but not necrosis of GFP-transfected cells was blocked by the use of a caspase inhibitor. The results are highly comparable to conventional apoptosis-detecting methods. CONCLUSIONS The advantage of our GFP-based assay compared with other methods is the analysis of apoptosis or necrosis without the necessity for additional staining or washing steps, making it an ideal tool for screening apoptotic or necrotic stimuli.
A multimedia approach to fluid power system design

The design of fluid power systems is a multidisciplinary activity requiring not only considerable background knowledge and experience but also the use of numerous design resources. Current design resources are fragmented and offer no structured guidance. The paper describes the first year of a three-year project to create an integrated multimedia environment for fluid power system design and instruction using Java and other Internet based technologies. Prototype software is under development and has been tested on a number of different platforms.
Cdc16p, Cdc23p and Cdc27p form a complex essential for mitosis.

Cdc16p, Cdc23p and Cdc27p are all essential proteins required for cell cycle progression through mitosis in Saccharomyces cerevisiae. All three proteins contain multiple tandemly repeated 34 amino acid tetratricopeptide repeats (TPRs). Using two independent assays, two‐hybrid analysis in vivo and co‐immunoprecipitation in vitro, we demonstrate that Cdc16p, Cdc23p and Cdc27p self associate and interact with one another to form a macromolecular complex. A temperature sensitive mutation in the most highly conserved TPR domain of Cdc27p results in a greatly reduced ability to interact with Cdc23p, but has no effect on interactions with wild‐type Cdc27p or Cdc16p. The specificity of this effect indicates that TPRs can mediate protein‐protein interactions and that this mutation may define an essential interaction for cell cycle progression in yeast. The conservation of at least two of the three proteins from yeast to man suggests that this protein complex is essential for mitosis in a wide range of eukaryotes.
A proteomic view of mycobacteria

Tuberculosis, the disease caused by Mycobacterium tuberculosis, remains a relevant public health issue. This is due mostly to the coepidemiology with HIV/AIDS, the appearance of multidrug‐resistant strains globally, and failure of BCG (bacillus Calmette–Guerin) vaccination to confer complete protection. This bacterium was one of the first to have its genome sequenced, yet over a decade after the release of the genomic information, the characterization of its phylogenetic tree and of different strain variants inside this species revealed that much is still needed to be done for a full understanding of the M. tuberculosis genome and proteome. Current methods using LC‐MS/MS and hybrid high‐resolution mass spectrometers can identify 2400–2800 proteins of the 4000 predicted genes in M. tuberculosis. In this article, we review relevant details of this bacterium's pathology and immunology, describing articles where proteomics helped the community to tackle some of the organism biology, from understanding strain diversity, cellular structure composition, immunogenicity, and host–pathogen interactions. Finally, we will discuss the challenges yet to be fulfilled in order to better characterize M. tuberculosis by proteomics.
Characterization of a 65 kDa NIF in the nuclear matrix of the monocot Allium cepa that interacts with nuclear spectrin‐like proteins

Plant cells have a well organized nucleus and nuclear matrix, but lack orthologues of the main structural components of the metazoan nuclear matrix. Although data is limited, most plant nuclear structural proteins are coiled‐coil proteins, such as the NIFs (nuclear intermediate filaments) in Pisum sativum that cross‐react with anti‐intermediate filament and anti‐lamin antibodies, form filaments 6–12 nm in diameter in vitro, and may play the role of lamins. We have investigated the conservation and features of NIFs in a monocot species, Allium cepa, and compared them with onion lamin‐like proteins. Polyclonal antisera against the pea 65 kDa NIF were used in 1D and 2D Western blots, ICM (imunofluorescence confocal microscopy) and IEM (immunoelectron microscopy). Their presence in the nuclear matrix was analysed by differential extraction of nuclei, and their association with structural spectrin‐like proteins by co‐immunoprecipitation and co‐localization in ICM. NIF is a conserved structural component of the nucleus and its matrix in monocots with Mr and pI values similar to those of pea 65 kDa NIF, which localized to the nuclear envelope, perichromatin domains and foci, and to the nuclear matrix, interacting directly with structural nuclear spectrin‐like proteins. Its similarities with some of the proteins described as onion lamin‐like proteins suggest that they are highly related or perhaps the same proteins.
Response to novelty predicts the locomotor and nucleus accumbens dopamine response to cocaine

The relationship between a rat's locomotor response to a novel environment and its behavioral and dopaminergic responses to cocaine was examined. Subjects were divided into two groups based on their locomotor response to a novel environment. Subjects who had a novelty response above the median were classified as high responders (HR), while those with a novelty response below the median were classified as low responders (LR). Following administration of cocaine‐HC1 (0, 2.5, 5.0, 10.0, or 15.0 mg/kg), HR rats showed a greater locomotor response than LR rats. Moreover, there was a significant correlation between a subject's locomotor response to the novel environment and the locomotor response to either 10.0 (r = 0.65) or 15.0 (r = 0.92) mg/kg cocaine. In a separate experiment, the extracellular concentration of dopamine in the nucleus accumbens (NACC) was monitored using microdialysis procedures. Following cocaine administration (15.0 mg/kg) HR rats showed a larger NACC dopamine response and greater locomotor activity than LR rats. In addition, there was a threefold greater locomotor activity to dopamine ratio in HR rats than in LR rats. A correlation between a subject's locomotor response to a novel environment and the dopaminergic response to cocaine was also evident. These results suggest that differences in the locomotor response to cocaine can, to some degree, be predicted by a rat's locomotor response to a novel environment, and that variations in dopamine‐dependent mechanisms of the NACC may underlie these individual differences.
Natural history of asymptomatic pancreatic cystic neoplasms.

BACKGROUND The management of asymptomatic pancreatic cysts is controversial and indications for excision are based on pathology and natural history. OBJECTIVES This study aimed to examine outcomes of asymptomatic lesions using a protocol based on size and cyst fluid analysis. METHODS Asymptomatic cysts were identified from a prospectively maintained database. Sequential cross-sectional imaging studies were assessed, and results of endoscopic ultrasound-guided aspiration were co-analysed. RESULTS A total of 338 asymptomatic patients underwent evaluation. Overall, 84 cysts were <1.5 cm and 254 were ≥1.5 cm in diameter. Median patient follow-up was 5.1 years [interquartile range (IQR): 4.1-6.9 years]. In the group in which cysts measured <1.5 cm in diameter, median cyst size was 1.0 cm (IQR: 0.6-1.2 cm) at presentation and increased to 1.2 cm (IQR: 0.7-1.6 cm) during follow-up. Five (6.0%) patients underwent resection, all within 2 months of presentation. In the group in which cysts measured ≥1.5 cm in diameter, median cyst size was 2.5 cm (IQR: 2.0-3.4 cm) at presentation and increased to 2.7 cm (IQR: 3.0-4.2 cm). A total of 63 (24.8%) patients underwent resection. Surgery was performed with 2 months in 53 (84.1%) patients, within 12 months in four (6.3%) patients and at >12 months post-presentation in six (9.5%) patients. A total of 70.6% of resected specimens were identified as malignancies or mucinous lesions. CONCLUSIONS Asymptomatic cysts of <1.5 cm in diameter can safely be followed by imaging and are expected to undergo little change. A quarter of all asymptomatic cysts measuring ≥1.5 cm are appropriately resected based on imaging and cyst fluid analysis.
SAR micromotion target detection based on gapped sine curves

This paper presents a detection algorithm for micromotion targets, such as rotating antennas, in the synthetic aperture radar (SAR) geometry. It utilizes target's range cell migration characteristics, i.e. a micromotion target takes on a sine cure in the slowtime-range image, but with incontinuity or gaps when clutter (and part of target energy) is suppressed. Two-stage detection, including MTI and the extended Hough transform, is used to suppress clutter and to extract the sine curve. Quasi-real SAR data of Isleta Lake demonstrate high SNR gains and good detection performance.
Possible Role of Lysophosphatidic Acid in Rat Model of Hypoxic Pulmonary Vascular Remodeling

Pulmonary hypertension is characterized by cellular and structural changes in the vascular wall of pulmonary arteries. We hypothesized that lysophosphatidic acid (LPA), a bioactive lipid, is implicated in this vascular remodeling in a rat model of hypoxic pulmonary hypertension. Exposure of Wistar rats to 10% O2 for 3 weeks induced an increase in the mean serum levels of LPA, to 40.9 (log-detransformed standard deviations: 23.4–71.7) μM versus 21.6 (11.0–42.3) μM in a matched control animal group (P = 0.037). We also observed perivascular LPA immunohistochemical staining in lungs of hypoxic rats colocalized with the secreted lysophospholipase D autotaxin (ATX). Moreover, ATX colocalized with mast cell tryptase, suggesting implication of these cells in perivascular LPA production. Hypoxic rat lungs expressed more ATX transcripts (2.4-fold) and more transcripts of proteins implicated in cell migration: β2 integrin (1.74-fold), intracellular adhesion molecule 1 (ICAM-1; 1.84-fold), and αM integrin (2.70-fold). Serum from the hypoxic group of animals had significantly higher chemoattractant properties toward rat primary lung fibroblasts, and this increase in cell migration could be prevented by the LPA receptor 1 and 3 antagonists. LPA also increased adhesive properties of human pulmonary artery endothelial cells as well as those of human peripheral blood mononuclear cells, via the activation of LPA receptor 1 or 3 followed by the stimulation of gene expression of ICAM-1, β−1, E-selectin, and vascular cell adhesion molecule integrins. In conclusion, chronic hypoxia increases circulating and tissue levels of LPA, which might induce fibroblast migration and recruitment of mononuclear cells in pulmonary vasculature, both of which contribute to pulmonary vascular remodeling.
Sustainable construction and socio-technical transitions in London's mega-projects

Sustainable construction attempts to mitigate the destructive impacts of building on the global environment. Mega-projects in London, such as Blackfriars Station and the Shard, symbolise urban renewal and are promoted as engines for sustainable development, principally through their use of sustainably procured materials. Unique buildings which are monumental and often state backed act as niches or incubators for sustainable construction, because they operate as protected spaces where the general rules of construction do not apply. Decision making in sustainable construction is complicated by the multiple state and public stakeholders involved in projects such as large stations and skyscrapers, and the different perspectives of architects, developers, procurement specialists, end users and others. While there are diverse actors involved, there has been some international convergence in the construction sector around how to deliver sustainability, and sustainable procurement has become the primary social and technological change through which more sustainable approaches to construction are delivered. Using interviews and questionnaires undertaken with six leading contractors involved in some of London's mega property and transport infrastructure projects, we analyse how sustainability procurement is deployed in the construction industry. Socio-technical transition theory provides a way to understand the context-specific developments led through mega-projects, which are at the forefront of promoting the use of sustainably procured materials and technologies. Our research demonstrates that moves to deploy a more sustainable approach are based around modifications to current practices rather than fundamental transformation. Cost and risks are frequently cited as barriers to the sustainable procurement of materials, while some contractors are sceptical of the improvements that can be delivered through sustainable procurement.
Performance characteristics of collaborative beamforming for wireless sensor networks with Gaussian distributed sensor nodes

Collaborative beamforming has been recently introduced in the context of wireless sensor networks (WSNs) to increase the transmission range of individual sensor nodes. In this paper, it is proposed to model the spatial distribution of sensor nodes in a cluster using Gaussian probability density function (pdf). Gaussian pdf is more appropriate for many WSN applications than the previously considered uniform pdf which is more suitable when sensor nodes are deployed one at a time. The average beampattern and its characteristics, the distribution function of the beampattern level in the sidelobe region, and the upper bound on the outage probability of sidelobes are derived using the theory of random arrays.
Angiotensin-converting enzyme polymorphism in schizophrenia, bipolar disorders, and their first-degree relatives

Background Family, twin and adoption studies have provided major evidence for the role of genetics in numerous psychiatric disorders including schizophrenia (SZ) and bipolar disorders (BDs). As SZ and BD have some susceptibility genes in common and since unaffected first-degree relatives of these patients carry a high likelihood of these susceptibility genes, we aimed to elucidate the role of angiotensin-converting enzyme (ACE) genetic variants in patients with SZ, BD and their first-degree relatives. Methods The study sample comprised 239 patients with SZ, 184 patients with BD, 284 unaffected first-degree biological relatives of patients with SZ and 301 unaffected first-degree biological relatives of patients with BD and 210 healthy controls. The ACE genotypes were determined by polymerase chain reaction. Results ACE insertion/deletion polymorphism was associated with SZ and BD. DD genotype and D allele distributions in bipolar patients and their first-degree relatives were significantly higher than those of SZ patients, their relatives, and controls. In contrast, II genotype and I allele were reduced in both the patient groups and their relatives as compared with controls. Conclusion In this study, the D allele might be responsible for clustering of psychotic symptoms and results in the psychotic manifestations of BD, whereas I allele seems to be protective against development of SZ and BD. SZ and BD characterized by similar or different gene variant in ACE could be a useful marker for these psychiatric disorders, if this polymorphism is replicated in the future studies.
Selective loss of dopaminergic neurons and formation of Lewy body‐like aggregations in α‐synuclein transgenic fly neuronal cultures

A key pathological feature of Parkinson's disease (PD) is the selective loss of dopaminergic neurons accompanied by the formation of Lewy bodies (LB). Given the complex nature of the disease, it is imperative to develop a model system suitable for molecular and cellular manipulation in order to study the mechanisms underlying the pathogenesis of PD. Here, we report that a new in vitro model of PD has been developed by using Drosophila melanogaster primary neuronal cultures expressing a human mutant α‐synuclein (α‐Syn; A30P). The selective loss of dopaminergic (DA) neurons was observed when α‐Syn was pan‐neuronally expressed while non‐dopaminergic neurons (e.g. GABAergic) were not influenced. This degeneration was also observed even when α‐Syn was specifically expressed in DA neurons, demonstrating α‐Syn toxicity is DA cell‐autonomous. In all experiments, cultures 5 days or older showed clear degeneration of DA neurons whereas this degeneration was not significant in 3‐day‐old cultures. In addition, there were intracellular aggregations in 5‐day or older α‐Syn neurons that were recognized by anti‐α‐Syn or ubiquitin antibodies, demonstrating the formation of LB‐like inclusions. By contrast, no such aggregations were found in 3‐day‐old neurons. The results demonstrate that mutated human α‐Syn expressed in Drosophila primary neuronal cultures causes the selective loss of DA neurons and the formation of cellular aggregations. Therefore, this is one of the first in vitro models recapitulating two important cellular features of PD and will be useful in examining mechanisms underlying selective neurodegeneration mediated by α‐Syn.
A Population-Based Evaluation of Readmissions After First Hospitalization for Acute Pancreatitis

Objective This study aimed to evaluate the burden and pattern of pancreatitis-related readmissions after index hospitalization for acute pancreatitis (AP). Methods We identified all unique white or black Allegheny County residents with first hospital admission for AP from 1996 to 2005 using the Pennsylvania Health Care Cost Containment Council data set. The final study population consisted of patients (n = 6010) who survived index admission and had follow-up data on readmissions. The etiology was determined using associated diagnosis codes. We analyzed pancreatitis-related readmissions until the third quarter of 2007 (median follow-up time, 39 months). Results The absolute risk and total burden of readmissions were 21.9% and 2947 for primary AP, respectively, 5.8% and 812 for primary chronic pancreatitis (CP), respectively, and 32.3% and 6612 for any pancreatitis diagnosis, respectively. Patients with alcohol etiology (etiology on index admission in 20.3%; responsible for 41.6%–50.4% readmissions) and subsequent diagnosis of CP (any CP diagnosis, 12.8%; responsible for 73% readmissions) accounted for a disproportionately higher fraction of readmissions. Readmission risk decreased with increasing age. A small fraction of patients accounted for most readmissions. Conclusions Readmission after AP is influenced by demographics, etiology, and subsequent CP diagnosis. Future studies should focus on understanding the factors driving readmissions in high-risk individuals to develop strategies for reducing pancreatitis-related readmissions and health care costs.
Development of Solution Buffer Layers for RABiTS Based YBCO Coated Conductors

The main objective of this research is to find a suitable alternate solution based seed layer for the standard RABiTS three-layer architecture of physical vapor deposited CeO<sub>2</sub> cap/YSZ barrier/Y<sub>2</sub>O<sub>3</sub> seed on Ni-5%W metal tape. In the present work, we have identified CeO<sub>2</sub> buffer layer as a potential replacement for Y<sub>2</sub>O<sub>3</sub> seeds. Using a metal-organic deposition (MOD) process, we have grown smooth, crack-free, epitaxial thin films of CeO<sub>2</sub> (pure and Zr, Cu and Gd-doped) directly on biaxially textured Ni-5W substrates in short lengths. Detailed XRD studies indicate that a single epitaxial CeO<sub>2</sub> phase with slightly improved out-of-plane texture compared to the texture of the underlying Ni-W substrates can be achieved in pure, undoped CeO<sub>2</sub> samples. We have also demonstrated the growth of YSZ barrier layers on pure CeO<sub>2</sub> seeds using sputtering. Both sputtered CeO<sub>2</sub> cap layers and MOD-YBCO films were grown epitaxially on these YSZ-buffered MOD-CeO<sub>2</sub>/Ni-5W substrates. High critical currents per unit width, I<sub>c</sub> of 264 A/cm (critical current density, J<sub>c</sub> of 3.3 MA/cm<sup>2</sup>) at 77 K and 0.01 T was achieved for 0.8 μm thick MOD-YBCO films grown on MOD-CeO<sub>2</sub> seeds. These results indicate that CeO<sub>2</sub> films can be grown directly on Ni-5W substrates and still support high performance YBCO coated conductors. This work holds promise for a route for producing low-cost buffer architecture for RABiTS based YBCO coated conductors.