Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Basis of Substrate Selectivity of E. coli Prolidase

Prolidases, metalloproteases that catalyze the cleavage of Xaa-Pro dipeptides, are conserved enzymes found in prokaryotes and eukaryotes. In humans, prolidase is crucial for the recycling of collagen. To further characterize the essential elements of this enzyme, we utilized the Escherichia coli prolidase, PepQ, which shares striking similarity with eukaryotic prolidases. Through structural and bioinformatic insights, we have extended previous characterizations of the prolidase active site, uncovering a key component for substrate specificity. Here we report the structure of E. coli PepQ, solved at 2.0 Å resolution. The structure shows an antiparallel, dimeric protein, with each subunit containing N-terminal and C-terminal domains. The C-terminal domain is formed by the pita-bread fold typical for this family of metalloproteases, with two Mg(II) ions coordinated by five amino-acid ligands. Comparison of the E. coli PepQ structure and sequence with homologous structures and sequences from a diversity of organisms reveals distinctions between prolidases from Gram-positive eubacteria and archaea, and those from Gram-negative eubacteria, including the presence of loop regions in the E. coli protein that are conserved in eukaryotes. One such loop contains a completely conserved arginine near the catalytic site. This conserved arginine is predicted by docking simulations to interact with the C-terminus of the substrate dipeptide. Kinetic analysis using both a charge-neutralized substrate and a charge-reversed variant of PepQ support this conclusion, and allow for the designation of a new role for this key region of the enzyme active site.
Metal‐mediated climate susceptibility in a warming world: Larval and latent effects on a model amphibian

Although sophisticated models predict the effects of future temperatures on ectotherms, few also address how ubiquitous sublethal contaminants alter an organism's response to thermal stress. In ectotherms, higher metabolic rates from warming temperatures can beneficially speed metabolism and development. If compounded by chronic, sublethal pollution, additional resource demands for elimination or detoxification may limit their ability to cope with rising temperatures—the toxicant‐induced climate susceptibility hypothesis. In outdoor bioassays, using natural lake water as the background, the authors investigated the development of a model ectotherm in 6 levels of Cd, Cu, and Pb mixtures and 3 thermal regimes of diel temperature fluctuations: ambient, +1.5 °C, and +2.5 °C. Warming had no effect on wild‐caught Cope's gray tree frog (Hyla chrysoscelis) until metals concentrations were approximately 10‐fold of their bioavailable chronic criterion unit (sums of bioavailable fractions of chronic criteria concentrations). In treatments with ≥10 bioavailable chronic criterion units and +1.5 °C, growth increased. Conversely, in treatments with 28 bioavailable chronic criterion units and maximal +2.5 °C warming, growth declined and the body condition of postmetamorphic juveniles at 20 d was 34% lower than that of juveniles from background conditions (lake water at ambient temperatures). These findings suggest toxicant‐induced climate susceptibility with long‐term latent effects on the juvenile life stage. Sublethal contaminants can intensify the impact on aquatic ectotherms at the most conservative levels of predicted global warming over the next century. Environ Toxicol Chem 2016;35:1872–1882. © 2015 SETAC
Scene Graph Parsing as Dependency Parsing

In this paper, we study the problem of parsing structured knowledge graphs from textual descriptions. In particular, we consider the scene graph representation that considers objects together with their attributes and relations: this representation has been proved useful across a variety of vision and language applications. We begin by introducing an alternative but equivalent edge-centric view of scene graphs that connect to dependency parses. Together with a careful redesign of label and action space, we combine the two-stage pipeline used in prior work (generic dependency parsing followed by simple post-processing) into one, enabling end-to-end training. The scene graphs generated by our learned neural dependency parser achieve an F-score similarity of 49.67% to ground truth graphs on our evaluation set, surpassing best previous approaches by 5%. We further demonstrate the effectiveness of our learned parser on image retrieval applications.
Waiting can be an optimal conservation strategy, even in a crisis discipline

Significance Every year, more species are driven to extinction by the combined pressures of habitat destruction, invasive species, and climate change. These ongoing losses have created a “crisis culture” in conservation, where project funds are spent as soon as they are received. We challenge this orthodoxy and demonstrate how strategic delays can improve efficiency. Waiting can allow agencies to leverage additional benefits from their funds, through investment, capacity building, or monitoring and research. With the right amount of delay, limited conservation resources can protect more species. Surprisingly, they can even do so in less time. Our results suggest that, in addition to their current focus on where to target resources, conservation managers should carefully choose when to spend these funds. Biodiversity conservation projects confront immediate and escalating threats with limited funding. Conservation theory suggests that the best response to the species extinction crisis is to spend money as soon as it becomes available, and this is often an explicit constraint placed on funding. We use a general dynamic model of a conservation landscape to show that this decision to “front-load” project spending can be suboptimal if a delay allows managers to use resources more strategically. Our model demonstrates the existence of temporal efficiencies in conservation management, which parallel the spatial efficiencies identified by systematic conservation planning. The optimal timing of decisions balances the rate of biodiversity decline (e.g., the relaxation of extinction debts, or the progress of climate change) against the rate at which spending appreciates in value (e.g., through interest, learning, or capacity building). We contrast the benefits of acting and waiting in two ecosystems where restoration can mitigate forest bird extinction debts: South Australia’s Mount Lofty Ranges and Paraguay’s Atlantic Forest. In both cases, conservation outcomes cannot be maximized by front-loading spending, and the optimal solution recommends substantial delays before managers undertake conservation actions. Surprisingly, these delays allow superior conservation benefits to be achieved, in less time than front-loading. Our analyses provide an intuitive and mechanistic rationale for strategic delay, which contrasts with the orthodoxy of front-loaded spending for conservation actions. Our results illustrate the conservation efficiencies that could be achieved if decision makers choose when to spend their limited resources, as opposed to just where to spend them.
Complete DNA Sequence, Comparative Genomics, and Prevalence of an IncHI2 Plasmid Occurring among Extraintestinal Pathogenic Escherichia coli Isolates

ABSTRACT We have sequenced a large plasmid that occurs among avian pathogenic Escherichia coli isolates. This plasmid, pAPEC-O1-R, is a 241,387-bp IncHI2 plasmid which is cotransmissible via bacterial conjugation with a ColBM virulence plasmid, encodes resistance to eight antimicrobial agents, and appears to occur at low rates among extraintestinal E. coli isolates.
Peri‐operative outcomes and complications after laparoscopic vs robot‐assisted dismembered pyeloplasty: a systematic review and meta‐analysis

To analyse the current difference between dismembered robot‐assisted pyeloplasty (RAP) and laparoscopic pyeloplasty (LP) in the treatment of pelvi‐ureteric junction (PUJ) obstruction as of 26 June 2017, focusing on operating time, length of hospital stay, complication rate, and success rate.
Differential equations and asymptotic solutions for arithmetic Asian options: ‘Black–Scholes formulae’ for Asian rate calls

In this article, we present a simplified means of pricing Asian options using partial differential equations (PDEs). We first provide a concise derivation of the well-known similarity reduction and exact Laplace transform solution. We then analyse the problem afresh as a power series in the volatility-scaled contract duration, with a view to obtaining an asymptotic solution for the low-volatility limit, a limit which presents difficulties in the context of the general Laplace transform solution. The problem is approached anew from the point of view of asymptotic expansions and the results are compared with direct, high precision, inversion of the Laplace transform and with numerical results obtained by V. Linetsky and J. Vecer. Our asymptotic formulae are little more complicated than the standard Black–Scholes formulae and, working to third order in the volatility-scaled expiry, are accurate to at least four significant figures for standard test problems. In the case of zero risk-neutral drift, we have the solution to fifth order and, for practical purposes, the results are effectively exact. We also provide comparisons with the hybrid analytic and finite-difference method of Zhang.
Trajectories of change in cognitive function in people with chronic obstructive pulmonary disease

AIMS AND OBJECTIVES To describe changes in cognitive function, as measured by the trail making test; to identify distinct patterns of change in cognitive function; and to examine predictors of change in cognitive function in people with severe chronic obstructive pulmonary disease. BACKGROUND How cognitive function changes in people with chronic obstructive pulmonary disease and what factors influence those changes over time is not well known, despite the fact that it declines rapidly in this population and significantly impacts functional decline in healthy older adults. DESIGN A secondary analysis and longitudinal study with a follow-up period of 3 years. METHODS A data set from the National Emphysema Treatment Trial provided participant data. Patients with severe chronic obstructive pulmonary disease (n = 307) were recruited at a clinical site. Several demographic and clinical measures were assessed at baseline. Trail making test scores were measured at baseline, 1, 2 and 3 years. RESULTS Cognitive function was stable for 3 years in people with chronic obstructive pulmonary disease. However, four distinct patterns of change in cognitive function were identified. Age, education, 6-min walk distance and cognitive impairment scores at baseline on the trail making test Part B were significant predictors of worsening cognitive function and below-average cognitive function over 3 years. CONCLUSIONS These findings suggest that increasing exercise capacity improves cognitive function and delays deterioration of cognitive function in people with COPD. RELEVANCE TO CLINICAL PRACTICE Understanding the trajectories of change in cognitive function and predictors of change in cognitive function over 3 years may enable health care providers to identify patients at greatest risk of developing mental deterioration and those who might benefit from interventions to improve cognitive function. Health care providers should periodically assess and frequently screen people with COPD for cognitive function.
Proteoglycans: Road Signs for Neurite Outgrowth

Proteoglycans in the central nervous system play integral roles as “traffic signals” for the direction of neurite outgrowth. This attribute of proteoglycans is a major factor in regeneration of the injured central nervous system. In this review, the structures of proteoglycans and the evidence suggesting their involvement in the response following spinal cord injury are presented. The review further describes the methods routinely used to determine the effect proteoglycans have on neurite outgrowth. The effects of proteoglycans on neurite outgrowth are not completely understood as there is disagreement on what component of the molecule is interacting with growing neurites and this ambiguity is chronicled in an historical context. Finally, the most recent findings suggesting possible receptors, interactions, and sulfation patterns that may be important in eliciting the effect of proteoglycans on neurite outgrowth are discussed. A greater understanding of the proteoglycan-neurite interaction is necessary for successfully promoting regeneration in the injured central nervous system.
Cortical depth profiles of luminance contrast responses in human V1 and V2 using 7 T fMRI

Neural activity in early visual cortex is modulated by luminance contrast. Cortical depth (i.e., laminar) contrast responses have been studied in monkey early visual cortex, but not in humans. In addition to the high spatial resolution needed and the ensuing low signal‐to‐noise ratio, laminar studies in humans using fMRI are hampered by the strong venous vascular weighting of the fMRI signal. In this study, we measured luminance contrast responses in human V1 and V2 with high‐resolution fMRI at 7 T. To account for the effect of intracortical ascending veins, we applied a novel spatial deconvolution model to the fMRI depth profiles. Before spatial deconvolution, the contrast response in V1 showed a slight local maximum at mid cortical depth, whereas V2 exhibited a monotonic signal increase toward the cortical surface. After applying the deconvolution, both V1 and V2 showed a pronounced local maximum at mid cortical depth, with an additional peak in deep grey matter, especially in V1. Moreover, we found a difference in contrast sensitivity between V1 and V2, but no evidence for variations in contrast sensitivity as a function of cortical depth. These findings are in agreement with results obtained in nonhuman primates, but further research will be needed to validate the spatial deconvolution approach.
Environmental Life Cycle Inventory of Crystalline Silicon Photovoltaic Module Production

Together with 11 European and US photovoltaic companies an extensive effort has been made to collect Life Cycle Inventory (LCI) data that represents the status of production technology for crystalline silicon modules for the year 2004. These data can be used to evaluate the environmental impacts of photovoltaic solar energy systems. The new data covers all processes from silicon feedstock production via wafer- and cell- to module manufacturing. All commercial wafer technologies are covered, i.e multi- and mono-crystalline wafers as well as ribbon technologies. For monocrystalline silicon wafer production further improvement of the data quality is recommended.
The impact of lignin downregulation on alfalfa yield, chemical composition, and in vitro gas production.

BACKGROUND Lignin is a complex, phenolic polymer found in plant cell walls that is essential for mechanical support, water and mineral transport, and defense in vascular plants. Over ten different enzymes play a role in the synthesis of lignin in plants. Suppression of any one enzyme or combinations of these enzymes may change the concentration and composition of lignin in the genetically transformed plants. Two lines of alfalfa that were downregulated for caffeoyl coenzyme A O-methyltransferase were used to assess the impact of lignin downregulation on chemical composition and fermentation rate and extent using an in vitro gas production technique. A total of 64 samples consisting of two reduced lignin (RL) and two controls (CL), four field replicates, two cutting intervals (CIs; 28 and 35 days), and two cuts (Cut-1 and Cut-3) were used. RESULTS No differences were detected in yield, crude protein, neutral detergent fiber (aNDF), and acid detergent fiber between the lines when harvested at the 28-day CI. The acid detergent lignin (ADL) concentration in RL alfalfa lines was significantly (P < 0.001) lower than in the CL. In alfalfa harvested at the 35-day CI, the RL alfalfa resulted in lower (P < 0.001) yield than CL. RL alfalfa lines had 24% and 22% lower (P < 0.001) ADL in Cut-1 and Cut-3 respectively than CL lines. The in vitro dry matter digestibility and aNDF digestibility (both as determined by the near-infrared reflectance method) were greater (P < 0.001) in RL than in CL lines harvested at the 35-day CI. In alfalfa harvested at the 35-day CI, extent of in vitro gas production and metabolizable energy content were greater in RL than in CL alfalfa. RL lines had 3.8% indigestible aNDF per unit ADL, whereas CL had 3.4% (P < 0.01). The positive effect of lignin downregulation was more pronounced when intervals between harvests were longer (35-day CI compared with the 28-day CI). CONCLUSION Lignin downregulation in alfalfa offers an opportunity to extend harvesting time (CI) for higher yield without compromising the nutritional quality of the alfalfa forage for dairy and livestock feeding. However, the in vitro results reported here warrant further study using in vivo methods. © 2018 Society of Chemical Industry.
Combined Electrical and Optical Analysis of the Efficiency Roll-Off in Phosphorescent Organic Light-Emitting Diodes

Organic light-emitting diodes (OLEDs) could be the thin-film display and lighting technology of the future, but for lighting applications their diminishing efficiency at high brightness is a problem, the underlying cause of which is unclear. In a comprehensive analysis of phosphorescent OLEDs, the authors find, in contrast to previous conclusions, that in these devices triplet-polaron quenching (TPQ) is the dominant process behind the efficiency roll-off. This style of analysis and the understanding it brings could provide a breakthrough in solid-state lighting performance.
Increased HE4 mRNA Expression Correlates with High Level Of eIF3a mRNA And Better Survival in Women with Epithelial Ovarian Cancer

Human epididymis protein 4 (HE4) is one of the most promising biomarkers for epithelial ovarian cancer (EOC). The majority of previous studies utilized the serum level or tissue protein expression of HE4 based upon immunohistochemistry (IHC) to evaluate the role of HE4 in the diagnosis, prognosis, and surveillance of EOC, but very little is known about HE4 mRNA expression. Eukaryotic translation initiation factor 3a (eIF3a) is implicated in oncogenesis and has been investigated extensively as a potential biomarker for malignancy. We previously reported a positive correlation between IHC expressions of eIF3a and HE4 in EOC. In the present study, we performed RT-PCR to determine mRNA expressions of HE4 and eIF3a in 30 normal ovarian tissues, 45 benign, 20 borderline and 94 malignant ovarian tumors. The association of HE4 and eIF3a mRNA expressions with clinicopathological characteristics and patient survivals was investigated. IHC was also performed in the same participants to investigate the correlation between mRNA and protein levels of HE4. HE4 mRNA level was found to be 48.42 ± 74.55 (mean ± SD, range: 0.01-343.99), significantly higher in primary EOC than in the borderline tumor, benign tumor, and normal ovarian tissue (P<0.001). The cutoff value was 13.99 for HE4 to discriminate malignant from benign tumors at 68.1% sensitivity and 93.0% specificity. By Spearman's correlation test, HE4 mRNA expression was indicated to positively correlate with serum CA125 level (r=0.530, P<0.001). Higher HE4 mRNA expression was associated with decreased frequency of lymph node metastasis (P=0.038) and better overall survival (OS) (P=0.007) in primary EOC. Multivariable analysis showed an independent prognostic value of the relative mRNA level of HE4 greater than one for OS (Hazard Ratio, 0.069, 95%CI, 0.009-0.530, P=0.010). eIF3a mRNA expression in women with primary EOC was 0.95 ± 1.19 (mean ± SD, range: 0.06-7.46), which was in a positive linear correlation with HE4 mRNA expression (r=0.310, P=0.002). In the present study, the HE4 mRNA level was unparalleled with IHC expression of HE4 (P>0.05). Collectively, our study revealed that increased HE4 mRNA expression correlates with high level of eIF3a mRNA and better survival in women with EOC, which calls for further investigations.
What happens to the unsuccessful spermatozoa?

To study apoptosis as a functional pathway in mature spermatozoa and apoptosis correlated to the acrosome reaction via the intracellular calcium concentration, semen samples from 27 healthy human donors were treated with inducers of apoptosis (betulinic acid, thapsigargin), inducers of the acrosome reaction (thapsigargin, calcium ionophore) or hydrogen peroxide to produce reactive oxygen species with and without prior incubation with a calcium chelator. Computer‐assisted sperm analysis, flow cytometry, and transmission electron microscopy were performed to analyze changes in the acrosomal status and in apoptotic features. Betulinic acid, thapsigargin, and the calcium ionophore treatment resulted in an increased number of sperm cells with caspase 9 and caspase 3 activation, disrupted mitochondrial membrane potential, and a reacted acrosome. Sperm motility was decreased in all cases. Transmission electron analyses showed ultra‐morphological changes, such as membrane integrity, membrane blebbing, the formation of head vacuoles, defects of the nuclear envelope, nuclear fragmentation, and the acrosome reaction. Acrosome reaction and apoptotic features decreased due to the reduction in intracellular calcium by the calcium chelator NP‐EGTA, AM. Therefore, apoptotic cell death in acrosome‐reacted sperm cells mediated by high intracellular calcium levels is possible.
A facile approach to spinning multifunctional conductive elastomer fibres with nanocarbon fillers

Electrically conductive elastomeric fibres prepared using a wet-spinning process are promising materials for intelligent textiles, in particular as a strain sensing component of the fabric. However, these fibres, when reinforced with conducting fillers, typically result in a compromise between mechanical and electrical properties and, ultimately, in the strain sensing functionality. Here we investigate the wet-spinning of polyurethane (PU) fibres with a range of conducting fillers such as carbon black (CB), single-walled carbon nanotubes (SWCNTs), and chemically converted graphene. We show that the electrical and mechanical properties of the composite fibres were strongly dependent on the aspect ratio of the filler and the interaction between the filler and the elastomer. The high aspect ratio SWCNT filler resulted in fibres with the highest electrical properties and reinforcement, while the fibres produced from the low aspect ratio CB had the highest stretchability. Furthermore, PU/SWCNT fibres presented the largest sensing range (up to 60% applied strain) and the most consistent and stable cyclic sensing behaviour. This work provides an understanding of the important factors that influence the production of conductive elastomer fibres by wet-spinning, which can be woven or knitted into textiles for the development of wearable strain sensors.
Gastrointestinal , Hepatobiliary , and Pancreatic Pathology Serotonin Activates Dendritic Cell Function in the Context of Gut Inflammation

From the Departments of Pathology and Molecular Medicine and Medicine,* Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; the Centre National de la Recherche Scientifique, Biotechnologie and Biotherapie UMR 7225, Hôpital de la Pitié-Salpêtrière, Paris, France; the CNRS/Université UMR 8147, Hôpital Necker-Enfants Malades, Paris, France; and the Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan