Miracle-dz/UniFAR-FTUs huggingface dataset:
Enigmatic Presence of Mitochondrial Complex I in Trypanosoma brucei Bloodstream Forms

ABSTRACT The presence of mitochondrial respiratory complex I in the pathogenic bloodstream stages of Trypanosoma brucei has been vigorously debated: increased expression of mitochondrially encoded functional complex I mRNAs is countered by low levels of enzymatic activity that show marginal inhibition by the specific inhibitor rotenone. We now show that epitope-tagged versions of multiple complex I subunits assemble into α and β subcomplexes in the bloodstream stage and that these subcomplexes require the mitochondrial genome for their assembly. Despite the presence of these large (740- and 855-kDa) multisubunit complexes, the electron transport activity of complex I is not essential under experimental conditions since null mutants of two core genes (NUBM and NUKM) showed no growth defect in vitro or in mouse infection. Furthermore, the null mutants showed no decrease in NADH:ubiquinone oxidoreductase activity, suggesting that the observed activity is not contributed by complex I. This work conclusively shows that despite the synthesis and assembly of subunit proteins, the enzymatic function of the largest respiratory complex is neither significant nor important in the bloodstream stage. This situation appears to be in striking contrast to that for the other respiratory complexes in this parasite, where physical presence in a life-cycle stage always indicates functional significance.
On the Game‐Theoretic Foundations of Competitive Search Equilibrium

We provide a unified directed search framework with general production and matching specifications that encompass most of the existing literature. We prove the existence of subgame perfect Nash equilibria in pure firm strategies in a finite version of the model. We use this result to derive a more complete characterization of the equilibrium set for the finite economy and to extend convergence results as the economy becomes large to general production and matching specifications. The latter extends the microfoundations for the standard market utility assumption used in competitive search models with a continuum of agents to new environments.
In Vitro Priming Recapitulates In Vivo HIV-1 Specific T Cell Responses, Revealing Rapid Loss of Virus Reactive CD4+ T Cells in Acute HIV-1 Infection

Background The requirements for priming of HIV-specific T cell responses initially seen in infected individuals remain to be defined. Activation of T cell responses in lymph nodes requires cell-cell contact between T cells and DCs, which can give concurrent activation of T cells and HIV transmission. Methodology The study aim was to establish whether DCs pulsed with HIV-1 could prime HIV-specific T cell responses and to characterize these responses. Both infectious and aldrithiol-2 inactivated noninfectious HIV-1 were compared to establish efficiencies in priming and the type of responses elicited. Findings Our findings show that both infectious and inactivated HIV-1 pulsed DCs can prime HIV-specific responses from naïve T cells. Responses included several CD4+ and CD8+ T cell epitopes shown to be recognized in vivo by acutely and chronically infected individuals and some CD4+ T cell epitopes not identified previously. Follow up studies of acute and recent HIV infected samples revealed that these latter epitopes are among the earliest recognized in vivo, but the responses are lost rapidly, presumably through activation-induced general CD4+ T cell depletion which renders the newly activated HIV-specific CD4+ T cells prime targets for elimination. Conclusion Our studies highlight the ability of DCs to efficiently prime naïve T cells and induce a broad repertoire of HIV-specific responses and also provide valuable insights to the pathogenesis of HIV-1 infection in vivo.
Large-scale short-term urban taxi demand forecasting using deep learning

The world has seen in recent years great successes in applying deep learning (DL) for many application domains. Though powerful, DL is not easy to be used well. In this invited paper, we study an urban taxi demand forecast problem using DL, and we show a number of key insights in modeling a domain problem as a suitable DL task. We also conduct a systematic comparison of two recent deep neural networks (DNNs) for taxi demand prediction, i.s. , the ST-ResNet and FLC-Net, on New York city taxi record dataset. Our experimental results show DNNs indeed outperform most traditional machine learning techniques, but such superior results can only be achieved with proper design of the right DNN architecture, where domain knowledge plays a key role.
Bird species recognition based on SVM classifier and decision tree

Bird species recognition is a challenging problem due to the variant illumination and different view point of camera. In this paper, a new feature which is the ratio between the distance of the eye to the root of beak and the distance of the width of the beak is used to distinguish the different bird species. Integrated the new feature into the multi-scale decision tree and the SVM framework, a new bird species recognition algorithm is proposed to get the final recognition result. The Experiment results show that the proposed new feature can improve the correct classification rate about nine percent.
Improving human action recognitionby temporal attention

Recently, deep learning methods have been extensively applied for action recognition in videos. Most existing deep networks equally treat every video frame and directly assign a video label to all the frames sampled from it. However, discriminative action may occurs sparsely in a few key frames in a video, and other frames are less relevant or even irrelevant to the action class. Equally treating all the frames will hurt performance. To address this issue, we propose a temporal attention model which learns to recognize human actions in videos while focusing selectively on the informative frames. Our model does not need explicit annotations regarding such informative frames during training and testing. Specifically, we adopt Recurrent Neural Network (RNN) with Long Short-Term Memory (LSTM) unit and attaches higher importance to the frames which are discriminative for the task at hand. Our method consistently improves on no-attention methods, with both RGB and optical flow based deep ConvNets. We achieve state-of-the-art performance on two challenging datasets of UCF101 and HMDB51.
Immunohistochemical expression of CD44 in oral squamous cell carcinoma in relation to histomorphological parameters and clinicopathological factors

Oral squamous cell carcinoma (OSCC) is characterised by its variable clinical course. In addition to the routinely used TNM and Union for International Cancer Control systems, patient‐specific prognostic/predictive biomarkers are needed. Promising biomarkers include the determination of the cancer stem cell compartment, which can be identified by CD44 expression (among other things). The aim of this study was to evaluate the impact of CD44 in OSCC in terms of correlation with histomorphology, especially targeting features of EMT, and its influence on patient prognosis.
Impaired Cargo Clearance in the Retinal Pigment Epithelium (RPE) Underlies Irreversible Blinding Diseases

Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways lead to the accumulation of lipofuscin and pyridinium bis-retinoid A2E aggregates and chemically modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased proteolytic and oxidative stress, resulting in irreversible damage to post-mitotic RPE cells and development of blinding conditions such as age-related macular degeneration, Stargardt disease and choroideremia. Here, we review how impaired cargo handling in the RPE results in their dysfunction, discuss new findings from our laboratory and consider how newly discovered roles for lysosomes and the autophagy pathway could provide insights into retinopathies. Studies of these dynamic, molecular events have also been spurred on by recent advances in optics and imaging technology. Mechanisms underpinning lysosomal impairment in other degenerative conditions including storage disorders, α-synuclein pathologies and Alzheimer’s disease are also discussed. Collectively, these findings help transcend conventional understanding of these intracellular compartments as simple waste disposal bags to bring about a paradigm shift in the way lysosomes are perceived.
Neuroprotective effects of 20(S)‐protopanaxatriol (PPT) on scopolamine‐induced cognitive deficits in mice

20(S)‐protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has been reported to have neuroprotective effects and to improve memory. The present study was designed to investigate the protective effect of PPT on scopolamine‐induced cognitive deficits in mice. Male Institute of Cancer Research mice were pretreated with 2 different doses of PPT (20 and 40 μmol/kg) for 27 days by intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected intraperitoneally for 9 days to induce memory impairment. Thirty minutes after the last pretreatment, the locomotor activity was firstly examined to evaluate the motor function of mice. Then, memory‐related behaviors were evaluated, and the related mechanism was further researched. It was founded that PPT treatment significantly reversed scopolamine‐induced cognitive impairment in the object location recognition experiment, the Morris water maze test, and the passive avoidance task, showing memory‐improving effects. PPT also significantly improved cholinergic system reactivity and suppressed oxidative stress, indicated by inhibition of acetylcholinesterase activity, elevation of acetylcholine levels, increasing superoxide dismutase activity and lowering levels of malondialdehyde in the hippocampus. In addition, the expression levels of Egr‐1, c‐Jun, and cAMP responsive element binding in the hippocampus were significantly elevated by PPT administration. These results suggest that PPT may be a potential drug candidate for the treatment of cognitive deficit in Alzheimer's disease.
Confidence intervals for differences between volumes under receiver operating characteristic surfaces (VUS) and generalized Youden indices (GYIs)

This article explores both existing and new methods for the construction of confidence intervals for differences of indices of diagnostic accuracy of competing pairs of biomarkers in three-class classification problems and fills the methodological gaps for both parametric and non-parametric approaches in the receiver operating characteristic surface framework. The most widely used such indices are the volume under the receiver operating characteristic surface and the generalized Youden index. We describe implementation of all methods and offer insight regarding the appropriateness of their use through a large simulation study with different distributional and sample size scenarios. Methods are illustrated using data from the Alzheimer's Disease Neuroimaging Initiative study, where assessment of cognitive function naturally results in a three-class classification setting.
Alcohol Marketing during the UEFA EURO 2016 Football Tournament: A Frequency Analysis

This study examined the frequency and nature of alcohol marketing references in broadcasts of the 2016 UEFA (Union of European Football Associations) European Championships football tournament in the United Kingdom (UK). Eighteen matches from across the tournament were recorded in full as broadcast in the UK, including all four matches featuring the English national team and all seven featuring the French national team. All visual and verbal references to alcohol marketing were recorded using a tool with high inter-rater reliability. A total of 2213 alcohol marketing references were recorded, an average of 122.94 per broadcast and 0.65 per broadcast minute (0.52 per minute in-play and 0.80 per minute out-of-play). Almost all references were visual (97.5%), with 77.9% occurring around the pitch border. Almost all (90.6%) were indirect references to alcohol brands (e.g., references to well-known slogans), compared to only 9.4% direct references to brands (e.g., brand names). The frequency of references to alcohol marketing was high. Although the overall proportion of direct brand references was low, the high proportion of indirect references demonstrates that alcohol producers were able to circumvent the French national law governing alcohol marketing (the Loi Évin) using indirect “alibi marketing”. To ensure the spirit of the Loi Évin regulations are achieved, stricter enforcement may be required to limit exposure to alcohol marketing, particularly for young people.
Translocator protein (18 kDa): an update on its function in steroidogenesis

Translocator protein (18 kDa) (TSPO) is a ubiquitous mitochondrial protein. Studies of its responses to drug and endogenous ligands have shown TSPO to be involved either directly or indirectly in numerous biological functions, including mitochondrial cholesterol transport and steroid hormone biosynthesis, porphyrin transport and heme synthesis, apoptosis, cell proliferation, and anion transport. Localised to the outer mitochondrial membrane of steroidogenic cells, TSPO has been shown to associate with cytosolic and mitochondrial proteins as part of a large multiprotein complex involved in mitochondrial cholesterol transport, the rate‐limiting step in steroidogenesis. There is general agreement as to the structure and pharmacology of TSPO. Stimulation of TSPO has been shown to have therapeutic use as anxiolytics by inducing allopregnanolone production in the brain, and also potentially for re‐establishing androgen levels in hypogonadal ageing animals. Until recently, there has been general agreement regarding the role of TSPO in steroidogenesis. However, recent studies involving genetic depletion of TSPO in mice have created controversy about the role of this protein in steroid and heme synthesis. We review the data on the structure and function of TSPO, as well as the recent results obtained using various genetic animal models. Taken together, these studies suggest that TSPO is a unique mitochondrial pharmacological target for diseases that involve increased mitochondrial activity, including steroidogenesis. Although there is no known mammalian species that lacks TSPO, it is likely that, because of the importance of this ancient protein in evolution and mitochondrial function, redundant mechanisms may exist to replace it under circumstances when it is removed.
Evaluation of a Live Attenuated Human Metapneumovirus Vaccine in Adults and Children

Abstract We conducted a phase I clinical trial of an experimental live attenuated recombinant human metapneumovirus (HMPV) vaccine (rHMPV-Pa) sequentially in adults, HMPV-seropositive children, and HMPV-seronegative children, the target population for vaccination. rHMPV-Pa was appropriately restricted in replication in adults and HMPV-seropositive children but was overattenuated for HMPV-seronegative children.
Grain boundary segregation in Ni-base (718 plus) superalloy

Abstract Segregation of phosphorus and molybdenum to grain boundaries in a commercial grade Ni-base (718 plus) superalloy subjected to different heat treatments has been examined using a field emission gun scanning transmission electron microscope with energy dispersive X-ray microanalysis. The results indicate that P and Mo concentrations at grain boundaries increase in linear manner with the square root of aging time.
Measurement of Rayleigh Wave Beams Using Angle Beam Wedge Transducers as the Transmitter and Receiver with Consideration of Beam Spreading

A theoretical model, along with experimental verification, is developed to describe the generation, propagation and reception of a Rayleigh wave using angle beam wedge transducers. The Rayleigh wave generation process using an angle beam wedge transducer is analyzed, and the actual Rayleigh wave sound source distributions are evaluated numerically. Based on the reciprocity theorem and considering the actual sound source, the Rayleigh wave beams are modeled using an area integral method. The leaky Rayleigh wave theory is introduced to investigate the reception of the Rayleigh wave using the angle beam wedge transducers, and the effects of the wave spreading in the wedge and transducer size are considered in the reception process. The effects of attenuations of the Rayleigh wave and leaky Rayleigh wave are discussed, and the received wave results with different sizes of receivers are compared. The experiments are conducted using two angle beam wedge transducers to measure the Rayleigh wave, and the measurement results are compared with the predictions using different theoretical models. It is shown that the proposed model which considers the wave spreading in both the sample and wedges can be used to interpret the measurements reasonably.
Proton pump inhibitors alter the composition of the gut microbiota

Objective Proton pump inhibitors (PPIs) are drugs used to suppress gastric acid production and treat GI disorders such as peptic ulcers and gastro-oesophageal reflux. They have been considered low risk, have been widely adopted, and are often over-prescribed. Recent studies have identified an increased risk of enteric and other infections with their use. Small studies have identified possible associations between PPI use and GI microbiota, but this has yet to be carried out on a large population-based cohort. Design We investigated the association between PPI usage and the gut microbiome using 16S ribosomal RNA amplification from faecal samples of 1827 healthy twins, replicating results within unpublished data from an interventional study. Results We identified a significantly lower abundance in gut commensals and lower microbial diversity in PPI users, with an associated significant increase in the abundance of oral and upper GI tract commensals. In particular, significant increases were observed in Streptococcaceae. These associations were replicated in an independent interventional study and in a paired analysis between 70 monozygotic twin pairs who were discordant for PPI use. We propose that the observed changes result from the removal of the low pH barrier between upper GI tract bacteria and the lower gut. Conclusions Our findings describe a significant impact of PPIs on the gut microbiome and should caution over-use of PPIs, and warrant further investigation into the mechanisms and their clinical consequences.
RICTOR amplification identifies a subgroup in small cell lung cancer and predicts response to drugs targeting mTOR

Small cell lung cancer (SCLC) is an aggressive cancer that represents ~15% of all lung cancers. Currently there are no targeted therapies to treat SCLC. Our genomic analysis of a metastatic SCLC cohort identified recurrent RICTOR amplification. Here, we examine the translational potential of this observation. RICTOR was the most frequently amplified gene observed (~14% patients), and co-amplified with FGF10 and IL7R on chromosome 5p13. RICTOR copy number variation correlated with RICTOR protein expression in SCLC cells. In parallel, cells with RICTOR copy number (CN) gain showed increased sensitivity to three mTOR inhibitors, AZD8055, AZD2014 and INK128 in cell growth assays, with AZD2014 demonstrating the best inhibition of downstream signaling. SCLC cells with RICTOR CN gain also migrated more rapidly in chemotaxis and scratch wound assays and were again more sensitive to mTOR inhibitors. The overall survival in SCLC patients with RICTOR amplification was significantly decreased (p = 0.021). Taken together, our results suggest that SCLC patients with RICTOR amplification may constitute a clinically important subgroup because of their potential response to mTORC1/2 inhibitors.
Structure of subcomplex Iβ of mammalian respiratory complex I leads to new supernumerary subunit assignments

Significance Mitochondrial complex I (proton-pumping NADH:ubiquinone oxidoreductase) is the largest respiratory chain enzyme. Mammalian complex I contains 45 subunits: the structures of the 14 “core” subunits (which are sufficient for catalysis and conserved from bacteria to humans) were described in the 5-Å resolution structure of Bos taurus complex I, but only 14 supernumerary subunits could be located. Here, we exploit new structural information from the membrane domain of mammalian complex I to assign eight further supernumerary subunits. We locate two oxidatively-folded CHCH-domain subunits in the intermembrane space, and reveal a second LYR protein–acyl carrier protein module. Thus, we extend knowledge of how the supernumerary subunits are arranged around the core, and provide insights into their roles in biogenesis and regulation. Mitochondrial complex I (proton-pumping NADH:ubiquinone oxidoreductase) is an essential respiratory enzyme. Mammalian complex I contains 45 subunits: 14 conserved “core” subunits and 31 “supernumerary” subunits. The structure of Bos taurus complex I, determined to 5-Å resolution by electron cryomicroscopy, described the structure of the mammalian core enzyme and allowed the assignment of 14 supernumerary subunits. Here, we describe the 6.8-Å resolution X-ray crystallography structure of subcomplex Iβ, a large portion of the membrane domain of B. taurus complex I that contains two core subunits and a cohort of supernumerary subunits. By comparing the structures and composition of subcomplex Iβ and complex I, supported by comparisons with Yarrowia lipolytica complex I, we propose assignments for eight further supernumerary subunits in the structure. Our new assignments include two CHCH-domain containing subunits that contain disulfide bridges between CX9C motifs; they are processed by the Mia40 oxidative-folding pathway in the intermembrane space and probably stabilize the membrane domain. We also assign subunit B22, an LYR protein, to the matrix face of the membrane domain. We reveal that subunit B22 anchors an acyl carrier protein (ACP) to the complex, replicating the LYR protein–ACP structural module that was identified previously in the hydrophilic domain. Thus, we significantly extend knowledge of how the mammalian supernumerary subunits are arranged around the core enzyme, and provide insights into their roles in biogenesis and regulation.
New Results Involving a Class of Generalized Hurwitz- Lerch Zeta Functions and Their Applications

In this paper, we study a certain class of generalized Hurwitz-Lerch zeta functions. We derive several new and useful properties of these generalized Hurwitz-Lerch zeta functions such as (for example) their partial differential equations, new series and Mellin-Barnes type contour integral representations involving Fox’s H-function and a pair of summation formulas. More importantly, by considering their application in Number Theory, we construct a new continuous analogue of Lippert’s Hurwitz measure. Some statistical applications are also given.
257-Tbit/s Weakly Coupled 10-Mode C + L-Band WDM Transmission

Partial multiple-input multiple-output (MIMO)-based weakly coupled mode-division multiplexing (MDM) transmission is proposed to reduce the MIMO matrix size in MDM. This technique can mitigate the burden of MIMO processing for high-order few-mode fiber (FMF) transmission. In this paper, we first show that modal XT can be sufficiently suppressed over the C+L band using a weakly coupled FMF and a highly mode-selective multiplexer/demultiplexer. Next, 10-mode-multiplexed 336-WDM transmission of dual-carrier 12-Gbaud dual-polarization-quadrature phase-shift keying signals over a 48-km weakly coupled FMF using only 2 × 2 or 4 × 4 partial MIMOs is demonstrated. To the best of our knowledge, in this experiment, we achieved a record fiber capacity of 257 Tbps with an aggregate spectral efficiency of 30.5 bit/s/Hz in single-core fiber transmission.