Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Roles of Epoxyeicosanoids in Regulating Cardiac Mitochondria

Maintenance of a healthy pool of mitochondria is important for the function and survival of terminally differentiated cells such as cardiomyocytes. Epoxyeicosatrienoic acids (EETs) are epoxy lipids derived from metabolism of arachidonic acid by cytochrome P450 epoxygenases. We have previously shown that EETs trigger a protective response limiting mitochondrial dysfunction and reducing cellular death. The aim of this study was to investigate whether EET-mediated effects influence mitochondrial quality in HL-1 cardiac cells during starvation. HL-1 cells were subjected to serum- and amino acid free conditions for 24h. We employed a dual-acting synthetic analog UA-8 (13-(3-propylureido)tridec-8-enoic acid), possessing both EET-mimetic and soluble epoxide hydrolase (sEH) inhibitory properties, or 14,15-EET as model EET molecules. We demonstrated that EET-mediated events significantly improved mitochondrial function as assessed by preservation of the ADP/ATP ratio and oxidative respiratory capacity. Starvation induced mitochondrial hyperfusion observed in control cells was attenuated by UA-8. However, EET-mediated events did not affect the expression of mitochondrial dynamic proteins Fis1, DRP-1 or Mfn2. Rather we observed increased levels of OPA-1 oligomers and increased mitochondrial cristae density, which correlated with the preserved mitochondrial function. Increased DNA binding activity of pCREB and Nrf1/2 and increased SIRT1 activity together with elevated mitochondrial proteins suggest EET-mediated events led to preserved mitobiogenesis. Thus, we provide new evidence for EET-mediated events that preserve a healthier pool of mitochondria in cardiac cells following starvation-induced stress.
The impact of phosphorus fertilizer placement on crop production

Improved phosphorus (P) fertilizer management is viewed as a way to improve yields in highly productive cropping system. A study was conducted at numerous sites during the 1990’s to assess plant density and yield of canola (Brassica napus L.), barley (Hordeum vulgare L.), spring wheat (Triticum aestivum L.), and winter wheat respond to greater P fertilizer rates (0, 15, 30, 45, and 60 kg P ha -1 ) when seed placed and side banded. We did find that canola stand was insensitive to rates of P tested when banded, but greater rates of seed-placed P caused stand thinning. It is thought the compensatory growth of canola was the reason why canola yield did not respond to P treatment. Both barley and winter wheat yielded most when the greatest rates of P were applied. Spring wheat showed a similar response when P was side banded, thus indicating improved tolerance with P placed away from seed. Therefore, spring wheat was the only crop that fit with our hypotheses; side banding P will allow crops to respond positively to greater rates of P fertilizer. The fact the cereal crop density was unresponsive to P management indicates that seedlings show early-season better tolerance than canola. Unlike canola, yieldforming factors for cereal crops responded to greater rates of P.
The XP customer role in practice: three studies

The customer is the only nondeveloper role in extreme programming (XP). The customer's explicit responsibilities are to drive the project, providing project requirements (user stories) and quality control (acceptance testing): unfortunately the customer must also shoulder a number of implicit responsibilities including liaison with external project stakeholders, especially project funders, clients, and end users, while maintaining the trust of both the development team and the wider business. In this paper, we report on a series of case studies of the customer role in XP projects. We have found that customers have a pressured and stressful role, leading to issues of sustainability.
Practice Patterns and Attitudes Toward the Role of Endoscopic Ultrasound in Staging of Gastrointestinal Malignancies: A Survey of Physicians and Surgeons

BACKGROUND AND AIMS:It is unknown how physician specialties other than gastroenterologists that manage gastrointestinal (GI) malignancies utilize endoscopic ultrasound (EUS) in their practices. The aim of this study was to (i) assess the proportion of gastroenterologists, oncologists, and surgeons that utilize EUS for staging of GI malignancies; (ii) assess the general availability of EUS; and (iii) determine which factors are associated with the use and availability of EUS.METHODS:A self-administered questionnaire was mailed out to 1,200 randomly selected gastroenterologists, oncologists, and surgeons throughout the United States.RESULTS:The data was analyzed from 521 (43%) responses. There were 60% respondents who had EUS available within their practices. There was greater availability of EUS within the practices of surgeons (81%; p < 0.001), within academic practices (87%; p = < 0.001), and in practices that serve a population >500,000 (p < 0.001). The majority of respondents (71%) utilized EUS in their practices. There was a similar utilization of EUS across specialties (p = NS). There was greater utilization of EUS in academic centers (82%; p < 0.001), in practices that served a community of >500,000 (p = 0.003), and among respondents who had been in practice for less than 5 yr (p = 0.005). Employing logistic regression models for utilization of EUS, lesser number of years in practice, and availability of EUS were found to be the only significant predictors of utilization.CONCLUSIONS:The majority of practitioners utilized EUS in management of GI malignancies. There was similar utilization of EUS across specialties. EUS is available to the majority of practitioners who manage GI malignancies.
BMP signaling restricts hemato-vascular development from lateral mesoderm during somitogenesis

The bone morphogenetic protein (BMP) signaling pathway is essential during gastrulation for the generation of ventral mesoderm, which makes it a challenge to define functions for this pathway at later stages of development. We have established an approach to disrupt BMP signaling specifically in lateral mesoderm during somitogenesis, by targeting a dominant-negative BMP receptor to Lmo2+ cells in developing zebrafish embryos. This results in expansion of hematopoietic and endothelial cells, while restricting the expression domain of the pronephric marker pax2.1. Expression of a constitutively active receptor and transplantation experiments were used to confirm that BMP signaling in lateral mesoderm restricts subsequent hemato-vascular development. The results show that the BMP signaling pathway continues to function after cells are committed to a lateral mesoderm fate, and influences subsequent lineage decisions by restricting hemato-vascular fate in favor of pronephric development.
Cleavage of 3',5'-pyrophosphate-linked dinucleotides by ribonuclease A and angiogenin.

Recently, 3',5'-pyrophosphate-linked 2'-deoxyribodinucleotides were shown to be >100-fold more effective inhibitors of RNase A superfamily enzymes than were the corresponding monophosphate-linked (i.e., standard) dinucleotides. Here, we have investigated two ribo analogues of these compounds, cytidine 3'-pyrophosphate (P'-->5') adenosine (CppA) and uridine 3'-pyrophosphate (P'-->5') adenosine (UppA), as potential substrates for RNase A and angiogenin. CppA and UppA are cleaved efficiently by RNase A, yielding as products 5'-AMP and cytidine or uridine cyclic 2',3'-phosphate. The k(cat)/K(m) values are only 4-fold smaller than for the standard dinucleotides CpA and UpA, and the K(m) values (10-16 microM) are lower than those reported for any earlier small substrates (e.g., 500-700 microM for CpA and UpA). The k(cat)/K(m) value for CppA with angiogenin is also only severalfold smaller than for CpA, but the effect of lengthening the internucleotide linkage on K(m) is more modest. Ribonucleotide 3',5'-pyrophosphate linkages were proposed previously to exist in nature as chemically labile intermediates in the pathway for the generation of cyclic 2',3'-phosphate termini in various RNAs. We demonstrate that in fact they are relatively stable (t(1/2) > 15 days for uncatalyzed degradation of UppA at pH 6 and 25 degrees C) and that cleavage in vivo is most likely enzymatic. Replacements of the RNase A catalytic residues His12 and His119 by alanine reduce activity toward UppA by approximately 10(5)-and 10(3.3)-fold, respectively. Thus, both residues play important roles. His12 probably acts as a base catalyst in cleavage of UppA (as with RNA). However, the major function of His119 in RNA cleavage, protonation of the 5'-O leaving group, is not required for UppA cleavage because the pK(a) of the leaving group is much lower than that for RNA substrates. A crystal structure of the complex of RNase A with 2'-deoxyuridine 3'-pyrophosphate (P'-->5') adenosine (dUppA), determined at 1.7 A resolution, together with models of the UppA complex based on this structure suggest that His119 contributes to UppA cleavage through a hydrogen bond with a nonbridging oxygen atom in the pyrophosphate and through pi-pi stacking with the six-membered ring of adenine.
Supraglacial Streams and Rivers

Supraglacial meltwater channels that flow on the surfaces of glaciers, ice sheets, and ice shelves connect ice surface climatology with subglacial processes, ice dynamics, and eustatic sea level changes. Their important role in transferring water and heat across and into ice is currently absent from models of surface mass balance and runoff contributions to global sea level rise. Furthermore, relatively little is known about the genesis, evolution, hydrology, hydraulics, and morphology of supraglacial rivers, and a first synthesis and review of published research on these unusual features is lacking. To that end, we review their ( a) known geographical distribution; ( b) formation, morphology, and sediment transport processes; ( c) hydrology and hydraulics; and ( d) impact on ice sheet surface energy balance, heat exchange, basal conditions, and ice shelf stability. We conclude with a synthesis of key knowledge gaps and provide recommendations for future research. ▪ Supraglacial streams and rivers transfer water and heat on glaciers, connecting climate with subglacial hydrology, ice sliding, and global sea level. ▪ Ice surface melting may expand under a warming climate, darkening the ice surface and further increasing melt.
Intelligent Vision Systems: Exploring the State-of-the-Art and Opportunities for the Future

Vision and video applications are becoming pervasive in mobile and embedded systems. Consumer wearable devices require capabilities for real-time video analytics and prolonged battery lifetimes, which is further driving the need for innovative system designs with low-power, reliability and high performance. Further, the increasing resolution of image sensors in these mobile systems places an increasing demand on both the memory storage as well as the computational power. Such stringent requirements have given rise to accelerator-rich architectures in system on-chips, where the primary computational burden is handled by dedicated hardware accelerators. In this paper we provide an overview of the current state-of-the-art in vision accelerators. We further discuss the opportunities to improve energy efficiency by minimizing Dynamic Random Access Memory (DRAM) refreshes and explore techniques to exploit algorithmic resilience for reduction in compute units while maintaining reliable system accuracy and performance.
A case for dynamic frequency tuning in on-chip networks

Performance and power are the first order design metrics for network-on-chips (NoCs) that have become the de-facto standard in providing scalable communication backbones for multicores/CMPs. However, NoCs can be plagued by higher power consumption and degraded throughput if the network and router are not designed properly. Towards this end, this paper proposes a novel router architecture, where we tune the frequency of a router in response to network load to manage both performance and power. We propose three dynamic frequency tuning techniques, FreqBoost, FreqThrtl and FreqTune, targeted at congestion and power management in NoCs. As enablers for these techniques, we exploit Dynamic Voltage and Frequency Scaling (DVFS) and the imbalance in a generic router pipeline through time stealing. Experiments using synthetic workloads on a 8x8 wormhole-switched mesh interconnect show that FreqBoost is a better choice for reducing average latency (maximum 40%) while, FreqThrtl provides the maximum benefits in terms of power saving and energy delay product (EDP). The FreqTune scheme is a better candidate for optimizing both performance and power, achieving on an average 36% reduction in latency, 13% savings in power (up to 24% at high load), and 40% savings (up to 70% at high load) in EDP. With application benchmarks, we observe IPC improvement up to 23% using our design. The performance and power benefits also scale for larger NoCs.
Two channels WiFi MIMO transmission over typical GI multimode fibers

Demonstrated is a successful MIMO transmission over a single standard GI MM fiber with the use of commercially available IEEE 802.11n access points. 50% increase of the total bit rate (versus single channel operation) was achieved, both with the use of 5.4 km long 50 μm core MM fiber and 4.4 km long 62.5 μm core fiber. The results clearly show the possibility of MIMO transmission over MM fiber pass band and corresponding increase of the transmission capacity of the fiber.
TP53 protein accumulation and gene mutation in relation to overexpression of MDM2 protein in ovarian borderline tumours and stage I carcinomas

Three hundred and seventy‐four early‐stage ovarian tumours, including 27 borderline tumours and 347 stage I carcinomas, were investigated immunohistochemically for overexpression of the TP53 and MDM2 proteins. TP53 (p53) and MDM2 alterations were detected in 15 and 4 per cent of borderline tumours, and in 50 and 13 per cent of stage I carcinomas, respectively. Mutations in the TP53 gene (exons 5–8) were demonstrated in 29 of the 50 stage I carcinomas studied, using denaturing gel electrophoresis followed by direct sequencing. TP53 overexpression was seen less often in tumours of mucinous and endometrioid type than in tumours of other histological types and more often in moderately and poorly differentiated than in well differentiated tumours. MDM2 protein overexpression was seen more often in clear cell carcinoma than in tumours of other histological types. These results indicate that TP53 abnormalities play a crucial role, and MDM2 abnormalities a minor role, in the development of early‐stage ovarian carcinoma. There was no significant association between TP53 or MDM2 alterations and survival in multivariate analysis. © 1997 John Wiley & Sons, Ltd.
Macrophage Migration Inhibitory Factor in Acute Adipose Tissue Inflammation

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and has been implicated in inflammatory diseases. However, little is known about the regulation of MIF in adipose tissue and its impact on wound healing. The aim of this study was to investigate MIF expression in inflamed adipose and determine its role in inflammatory cell recruitment and wound healing. Adipose tissue was harvested from subcutaneous adipose tissue layers of 24 healthy subjects and from adipose tissue adjacent to acutely inflamed wounds of 21 patients undergoing wound debridement. MIF protein and mRNA expression were measured by ELISA and RT-PCR. Cell-specific MIF expression was visualized by immunohistochemistry. The functional role of MIF in cell recruitment was investigated by a chemotaxis assay and by flow cytometry of labeled macrophages that were injected into Mif –/–and wildtype mice. Wound healing was evaluated by an in vitro scratch assay on human fibroblast monolayers. MIF protein levels of native adipose tissue and supernatants from acutely inflamed wounds were significantly elevated when compared to healthy controls. MIF mRNA expression was increased in acutely inflamed adipose tissue indicating the activation of MIF gene transcription in response to adipose tissue inflammation. MIF is expressed in mature adipocytes and in infiltrated macrophages. Peripheral blood mononuclear cell migration was significantly increased towards supernatants derived from inflamed adipose tissue. This effect was partially abrogated by MIF-neutralizing antibodies. Moreover, when compared to wildtype mice, Mif –/–mice showed reduced infiltration of labeled macrophages into LPS-stimulated epididymal fat pads in vivo. Finally, MIF antibodies partially neutralized the detrimental effect of MIF on fibroblast wound healing. Our results indicate that increased MIF expression and rapid activation of the MIF gene in fat tissue adjacent to acute wound healing disorders may play a role in cell recruitment to the site of inflammation and wound healing.
An Essential Poison: Synthesis and Degradation of Cyclic Di-AMP in Bacillus subtilis

ABSTRACT Gram-positive bacteria synthesize the second messenger cyclic di-AMP (c-di-AMP) to control cell wall and potassium homeostasis and to secure the integrity of their DNA. In the firmicutes, c-di-AMP is essential for growth. The model organism Bacillus subtilis encodes three diadenylate cyclases and two potential phosphodiesterases to produce and degrade c-di-AMP, respectively. Among the three cyclases, CdaA is conserved in nearly all firmicutes, and this enzyme seems to be responsible for the c-di-AMP that is required for cell wall homeostasis. Here, we demonstrate that CdaA localizes to the membrane and forms a complex with the regulatory protein CdaR and the glucosamine-6-phosphate mutase GlmM. Interestingly, cdaA, cdaR, and glmM form a gene cluster that is conserved throughout the firmicutes. This conserved arrangement and the observed interaction between the three proteins suggest a functional relationship. Our data suggest that GlmM and GlmS are involved in the control of c-di-AMP synthesis. These enzymes convert glutamine and fructose-6-phosphate to glutamate and glucosamine-1-phosphate. c-di-AMP synthesis is enhanced if the cells are grown in the presence of glutamate compared to that in glutamine-grown cells. Thus, the quality of the nitrogen source is an important signal for c-di-AMP production. In the analysis of c-di-AMP-degrading phosphodiesterases, we observed that both phosphodiesterases, GdpP and PgpH (previously known as YqfF), contribute to the degradation of the second messenger. Accumulation of c-di-AMP in a gdpP pgpH double mutant is toxic for the cells, and the cells respond to this accumulation by inactivation of the diadenylate cyclase CdaA. IMPORTANCE Bacteria use second messengers for signal transduction. Cyclic di-AMP (c-di-AMP) is the only second messenger known so far that is essential for a large group of bacteria. We have studied the regulation of c-di-AMP synthesis and the role of the phosphodiesterases that degrade this second messenger. c-di-AMP synthesis strongly depends on the nitrogen source: glutamate-grown cells produce more c-di-AMP than glutamine-grown cells. The accumulation of c-di-AMP in a strain lacking both phosphodiesterases is toxic and results in inactivation of the diadenylate cyclase CdaA. Our results suggest that CdaA is the critical diadenylate cyclase that produces the c-di-AMP that is both essential and toxic upon accumulation.
Analysis of lateral redistribution of a plasma membrane glycoprotein- monoclonal antibody complex [corrected] [published erratum appears in J Cell Biol 1988 Apr;106(4):following 1403]

The lateral redistribution of a major murine glycoprotein, GP80, was studied on locomoting fibroblasts, using rhodamine-conjugated mAbs and ultralow light level digitized fluorescence microscopy. Confirming an earlier study (Jacobson, K., D. O'Dell, B. Holifield, T.L. Murphy, and J. T. August. 1984. J. Cell Biol. 99:1613-1623), the distribution of GP80 was coupled with cell locomotion; motile cells exhibited a gradated distribution of the GP80-mAb complex over the cell surface, increasing from the front to the rear, whereas stationary cells exhibited a nearly uniform GP80 distribution. By monitoring locomoting single cells, we found the gradated fluorescence distribution to be maintained as an approximate steady state. Newly extended leading edges were almost devoid of the fluorescence labeling. This was strikingly demonstrated in prechilled cells in which the extension of fluorescence- free leading edges caused a pronounced boundary between fluorescent and nonfluorescent zones. Subsequently this boundary eroded gradually in a manner consistent with diffusional relaxation. Evidence indicated that the GP80 redistribution was primarily caused by the lateral motion of GP80 in the plasma membrane and not via intracellular membrane traffic. Two cell locomotion models which, in principle, could account for the GP80 redistribution were tested: the retrograde lipid flow (RLF) model (Bretscher, M. S., 1984. Science (Wash. DC). 224:681-686) and an alternative hypothesis, the retraction-induced spreading (RIS) model. The predictions of these models were stimulated by computer and compared with experiment to assess which model was more appropriate. Whereas both models predicted steady-state gradients similar to the experimental result, only the RIS model predicted the lack of retrograde movement of the fluorescent boundary.
Independent populations of primed F1 guinea pig T lymphocytes respond to antigen-pulsed parental peritoneal exudate cells

Thymus-dependent (T) lymphocytes from (2 x 13)F1 hybrid guinea pigs immunized to ovalbumin (OVA) in complete Freund's adjuvant can be stimulated to proliferate in vitro by antigen-pulsed peritoneal exudate cells (PECs) derived from either strain 2 or strain 13 donors. In this communication, we show that the population of primed F1 T lymphocytes which can be activated by antigen-pulsed strain 2 PECs is largely independent of the population of cells that can be activated by antigen- pulsed strain 13 PECs. This was demonstrated by both positive and negative selection procedures. In the former, T lymphocytes from OVA- primed (2 x 13)F1 donors were enriched by initial culture with OVA- pulsed strain 2 or strain 13 PECs for 1 wk. Cells selected by culture with OVA-pulsed strain 2 PECs responded well to OVA-pulsed strain 2 PECs and poorly to OVA-pulsed strain 13 PECs. If positive selection had been carried out with OVA-pulsed strain 13 PECs, the selected F1 T cells responded well to OVA-pulsed 13 PECs and poorly to OVA-pulsed 2 PECs. Negative selection was achieved by short term culture with antigen-pulsed PECs and by eliminating proliferating cells by treatment with bromodeoxyuridine and light. This procedure demonstrated that the population of primed F1 T lymphocytes which are responsive to OVA or to purified protein derivative of tuberculin can be divided into subpopulations uniquely responsive to antigen on either strain 2 or strain 13 PECs. Evidence was presented to indicate that this selective responsiveness was not the result of the action of alloantigen-specific suppressor cells. The results are considered in terms of current concepts of the genetic and molecular regulation of the interaction of PECs and T lymphocytes.