Miracle-dz/UniFAR-FTUs huggingface dataset:
Adenovirus Modulates Toll-Like Receptor 4 Signaling by Reprogramming ORP1L-VAP Protein Contacts for Cholesterol Transport from Endosomes to the Endoplasmic Reticulum

ABSTRACT Human adenoviruses (Ads) generally cause mild self-limiting infections but can lead to serious disease and even be fatal in high-risk individuals, underscoring the importance of understanding how the virus counteracts host defense mechanisms. This study had two goals. First, we wished to determine the molecular basis of cholesterol homeostatic responses induced by the early region 3 membrane protein RIDα via its direct interaction with the sterol-binding protein ORP1L, a member of the evolutionarily conserved family of oxysterol-binding protein (OSBP)-related proteins (ORPs). Second, we wished to determine how this interaction regulates innate immunity to adenovirus. ORP1L is known to form highly dynamic contacts with endoplasmic reticulum-resident VAP proteins that regulate late endosome function under regulation of Rab7-GTP. Our studies have demonstrated that ORP1L-VAP complexes also support transport of LDL-derived cholesterol from endosomes to the endoplasmic reticulum, where it was converted to cholesteryl esters stored in lipid droplets when ORP1L was bound to RIDα. The virally induced mechanism counteracted defects in the predominant cholesterol transport pathway regulated by the late endosomal membrane protein Niemann-Pick disease type C protein 1 (NPC1) arising during early stages of viral infection. However, unlike NPC1, RIDα did not reconstitute transport to endoplasmic reticulum pools that regulate SREBP transcription factors. RIDα-induced lipid trafficking also attenuated proinflammatory signaling by Toll-like receptor 4, which has a central role in Ad pathogenesis and is known to be tightly regulated by cholesterol-rich “lipid rafts. ” Collectively, these data show that RIDα utilizes ORP1L in a way that is distinct from its normal function in uninfected cells to fine-tune lipid raft cholesterol that regulates innate immunity to adenovirus in endosomes. IMPORTANCE Early region 3 proteins encoded by human adenoviruses that attenuate immune-mediated pathology have been a particularly rich source of information regarding intracellular protein trafficking. Our studies with the early region 3-encoded RIDα protein also provided fundamental new information regarding mechanisms of nonvesicular lipid transport and the flow of molecular information at membrane contacts between different organelles. We describe a new pathway that delivers cholesterol from endosomes to the endoplasmic reticulum, where it is esterified and stored in lipid droplets. Although lipid droplets are attracting renewed interest from the standpoint of normal physiology and human diseases, including those resulting from viral infections, experimental model systems for evaluating how and why they accumulate are still limited. Our studies also revealed an intriguing relationship between lipid droplets and innate immunity that may represent a new paradigm for viruses utilizing these organelles.
Area-Time Efficient Scaling-Free CORDIC Using Generalized Micro-Rotation Selection

This paper presents an area-time efficient CORDIC algorithm that completely eliminates the scale-factor. By suitable selection of the order of approximation of Taylor series the proposed CORDIC circuit meets the accuracy requirement, and attains the desired range of convergence. Besides we have proposed an algorithm to redefine the elementary angles for reducing the number of CORDIC iterations. A generalized micro-rotation selection technique based on high speed most-significant-1-detection obviates the complex search algorithms for identifying the micro-rotations. The proposed CORDIC processor provides the flexibility to manipulate the number of iterations depending on the accuracy, area and latency requirements. Compared to the existing recursive architectures the proposed one has 17% lower slice-delay product on Xilinx Spartan XC2S200E device.
Pediatric Asthma Management: Study of the Family Asthma Management System Scale with a Portuguese Sample

This study examines the reliability and validity of the Family Asthma Management System Scale (FAMSS), with a sample of 31 Portuguese children with asthma (aged 7–13 years) and their parents and its associations with asthma morbidity, asthma knowledge (AKQ) and psychopathological symptoms (BSI) in parents. The FAMSS demonstrated good internal consistency (α = 0.86) and convergent validity, with significant associations with AKQ. No associations were found with levels of asthma control or symptoms severity, but correlations with number of parents’ reported exacerbations and with BSI were found. The FAMSS proved to be an adequate instrument to assess families’ asthma management.
A Strain-Specific Epitope of Enterovirus 71 Identified by Cryo-Electron Microscopy of the Complex with Fab from Neutralizing Antibody

ABSTRACT Enterovirus 71 (EV71) is a picornavirus that causes outbreaks of hand, foot, and mouth disease (HFMD), primarily in the Asia-Pacific area. Unlike coxsackievirus A16, which also causes HFMD, EV71 induces severe neuropathology leading to high fatalities, especially among children under the age of 6 years. Currently, no established vaccines or treatments are available against EV71 infection. The monoclonal antibody MA28-7 neutralizes only specific strains of EV71 that have a conserved glycine at amino acid VP1-145, a surface-exposed residue that maps to the 5-fold vertex and that has been implicated in receptor binding. The cryo-electron microscopy structure of a complex between EV71 and the Fab fragment of MA28-7 shows that only one Fab fragment occupies each 5-fold vertex. A positively charged patch, which has also been implicated in receptor binding, lies within the Fab footprint. We identify the strain-specific epitope of EV71 and discuss the possible neutralization mechanisms of the antibody.
Real-Time Architecture for a Robust Multi-Scale Stereo Engine on FPGA

In this work, we present a real-time implementation of a stereo algorithm on field-programmable gate array (FPGA). The approach is a phase-based model that allows computation with sub-pixel accuracy. The algorithm uses a robust multi-scale and multi-orientation method that optimizes the estimation extraction with respect to the local image structure support. With respect to the state of the art, our work increases the on-chip power of computation compared to previous approaches in order to obtain a good accuracy of results with a large disparity range. In addition, our approach is specially suited for unconstrained environments applications thanks to the robustness of the phase information, capable of dealing with severe illumination changes and with small affine deformation between the image pair. This work also includes the rectification images circuitry in order to exploit the epipolar constraints on the chip. The dedicated circuit can rectify and process images of VGA resolution at a frame rate of 57 fps. The implementation uses a fine pipelined method (also with superscalar units) and multiple user defined parameters that lead to a high working frequency and a good adaptability to different scenarios. In the paper, we present different results and we compare them with state of the art approaches.
Application-Driven End-to-End Traffic Predictions for Low Power NoC Design

As chip multiprocessors keep increasing the number of cores on the chip, the network-on-chip (NoC) technology is becoming essential for interconnecting the cores. While NoCs result in noticeable performance boost over conventional bus systems, they consume a non-negligible fraction of the system power. One promising solution is to dynamically adjust the working frequencies/voltages of the switches as well as the links between switches in the NoC to match the traffic flows. The question is when to adjust and by how much. Most previous works take a passive approach by reacting to fluctuations in local traffic flows. Unfortunately, this approach may be too slow and too conservative in adjusting the working frequencies/voltages. Since applications often exhibit periodic behaviors, we propose a hardware mechanism to proactively adjust the frequencies/voltages of switches and/or links in NoC by predicting the application runtime traffic. The evaluations show that our design achieves 86% dynamic power savings of the links in the on-chip network, and the resulting overheads from mispredictions are tolerable.
Dual inverse effects of lipoprotein(a) on the dementia process in Japanese late‐onset Alzheimer's disease

Background: The role of lipoprotein metabolism in the dementia process has attracted increasing attention. It is universally accepted that apolipoprotein E4 (ApoE) is a risk factor for late‐onset Alzheimer's disease, however, the role of lipoprotein(a) (Lp(a)) remains unclear. Therefore, we conducted the present study to clarify the association between Lp(a) and dementia.
Psychosocially Supportive Design: The Case for Greater Attention to Social Space Within the Pediatric Hospital

Objective: Models of patient and family-centered care advocate catering to psychosocial needs when designing healthcare facilities yet there is little evidence available to determine how the built environment can cater to psychosocial needs. This article highlights the obstacles to overcoming this knowledge deficit in the pursuit of evidence-based guidelines to inform social provisions within the pediatric hospital setting. It will propose a working definition for psychosocial space and identify new research directions to enhance understandings of the relationship between social space and well-being. Background: While traditional multibed ward configurations afforded opportunities for peer support relationships to develop, both for patients and caregivers, the contemporary preference for single-occupancy rooms intensifies the need to critically examine social spaces within the pediatric hospital. Methods: Research suggests a correlation between social support and well-being. This article reviews the research underpinning contemporary understandings of this relationship; it positions literature from sociology, environmental psychology, and evidence-based design to highlight the limitations of this knowledge and identify where additional research is required to inform evidence-based design guidelines for psychosocially supportive spaces within pediatric healthcare settings. Conclusions: Evidence regarding the therapeutic value of social support within the pediatric hospital is not sufficiently sophisticated or conclusive to inform guidelines for the provision of social space with pediatric hospitals. There is an urgent need for targeted research to inform evidence-based design guidelines; this will demand a broad disciplinary approach.
Human Papillomavirus Type 16 E6/E7 Upregulation of Nucleophosmin Is Important for Proliferation and Inhibition of Differentiation

ABSTRACT The E6 and E7 oncoproteins of high-risk human papillomaviruses (HPVs) are together sufficient to cause cellular transformation. Nucleophosmin (NPM) was identified as a protein with increased levels in two-dimensional (2-D) gel analysis of human foreskin keratinocytes (HFKs) expressing E7 following methylcellulose-induced differentiation. Analysis of NPM expression in E7-expressing cells and E6- and E7-expressing cells in culture and in organotypic rafts confirmed the increased levels observed in 2-D gel analysis. The elevated expression of NPM was determined to be posttranscriptional and was attributed to increased v-akt murine thymoma viral oncogene (AKT) activity in the E6- and E7-expressing cells. Depletion of NPM caused a reduction in the replicative capacity of E7- and E6/E7-expressing HFKs and an increase in markers of differentiation. Also, the p53 and pRb tumor suppressor levels are increased with the knockdown of NPM in E6/E7-expressing cells, and, interestingly, p14ARF is relocalized from the nucleolus to the nucleoplasm and cytoplasm in these cells. The results show for the first time that NPM is required for the proliferation and inhibition of differentiation observed in HPV E6- and E7-expressing primary cells.
Retrograde Drilling of Osteochondral Lesions of the Talus

This study evaluates the use of retrograde drilling in medial osteochondral lesions of the talus (OLTs) with intact articular surfaces. During a 2-year period, 8 consecutive patients underwent surgical treatment for symptomatic posterior medial OLT. All patients underwent arthroscopy of the ankle followed by retrograde drilling of the talar lesion. A novel cannulated system was used to target the lesion, remove the necrotic segment, and then backfill using Grafton gel. The average age of the patients was 36 years old (range, 12-49 years). Follow-up ranged from 8 to 44 months (mean 24 months). One patient was lost to follow-up. Of the remaining 7, outcomes were assessed with a modified American Orthopaedic Foot and Ankle Society (AOFAS) ankle/ hindfoot scale and the SF-12 general health survey. Four patients had repeat magnetic resonance imaging scans at 1-year follow-up. The preoperative AOFAS scores from the modified hindfoot scale ranged from 0 to 41 (mean 22). Postoperative scores ranged from 52 to 68 (mean 56), with a mean improvement of 34 points. The SF-12 has 2 components: the physical component score (PCS) and the mental component score (MCS). Mean preoperative and latest follow-up SF-12 PCS scores were 35.8 and 44.0, respectively. Mean preoperative and latest follow-up SF-12 MCS scores were 40.7 and 52.8, respectively. In this limited series, this technique appears to give comparable short-term results to previously described techniques. Use of a cannulated system simplifies the surgical procedure. Overall, this procedure offers decreased operative time and maximizes safety and accuracy with retrograde talar drilling.
The efficacy of stereotactic radiosurgery in the management of Vestibular Schwannomas – a retrospective analysis

Vestibular Schwannomas (VS) are benign tumours arising from the neural sheath of the vestibular nerve, located near the auditory canal and cerebello-pontine angle adjacent to the brainstem making tumours “malignant by position”. With high complication rates following surgery for tumour resection it is essential that alternative yet comparable management options such as Stereotactic Radiosurgery (SRS) be more fully evaluated in order to attain its efficacy and provide patients with alternative treatment modalities. The aim of this study was to critically evaluate the treatment outcomes of patients treated with SRS for Vestibular Schwannomas at the Cromwell Hospital's Gamma Knife Centre between 1998 and 2002. To facilitate this, information regarding patient's clinical history and SRS treatment parameters was collated and analysed via departmental on-line systems. In total the study provided a representative sample size of 74 patients with follow up data ranging from 6 months to 4 years post SRS (with a median of 12 months). At the maximum point of follow up attained by each patient 43% had an overall smaller tumour volume than at the time of treatment whilst 18% demonstrated a volume increase and 39% remained unchanged. In total 67% demonstrated evidence of decreased central tumour contrast enhancement (necrosis). 27% of patients suffered some form of immediate complication post SRS, all of which had resolved within 6 months. No correlation was found between the severity of the complication, prescription dose and tumour volume. Results are comparable with those from other published series highlighting a positive response from the tumour (decrease in volume) with few immediate complications, largely unchanged severity of symptoms post SRS and no negative impact on the patients quality of life. Although a number of significant papers have been published regarding the role of SRS in the management of VS there remains no definitive answer as to the best management option. Tumour control rates are comparable in both options and whilst both have their limitations, complication rates are generally much lower in the SRS group. Even so it is yet to be widely accepted as the treatment of choice in suitable cases. Nonetheless broadening the knowledge base with more research and education regarding the benefits of SRS will allow it to be promoted as a primary, contemporary treatment option in the management of VS.
Comparative Analysis of Complete Genome Sequences of Three Avian Coronaviruses Reveals a Novel Group 3c Coronavirus

ABSTRACT In this territory-wide molecular epidemiology study of coronaviruses (CoVs) in Hong Kong involving 1,541 dead wild birds, three novel CoVs were identified in three different bird families (bulbul CoV HKU11 [BuCoV HKU11], thrush CoV HKU12 [ThCoV HKU12], and munia CoV HKU13 [MuCoV HKU13]). Four complete genomes of the three novel CoVs were sequenced. Their genomes (26,396 to 26,552 bases) represent the smallest known CoV genomes. In phylogenetic trees constructed using chymotrypsin-like protease (3CLpro), RNA-dependent RNA polymerase (Pol), helicase, spike, and nucleocapsid proteins, BuCoV HKU11, ThCoV HKU12, and MuCoV HKU13 formed a cluster distantly related to infectious bronchitis virus and turkey CoV (group 3a CoVs). For helicase, spike, and nucleocapsid, they were also clustered with a CoV recently discovered in Asian leopard cats, for which the complete genome sequence was not available. The 3CLpro, Pol, helicase, and nucleocapsid of the three CoVs possessed higher amino acid identities to those of group 3a CoVs than to those of group 1 and group 2 CoVs. Unique genomic features distinguishing them from other group 3 CoVs include a distinct transcription regulatory sequence and coding potential for small open reading frames. Based on these results, we propose a novel CoV subgroup, group 3c, to describe this distinct subgroup of CoVs under the group 3 CoVs. Avian CoVs are genetically more diverse than previously thought and may be closely related to some newly identified mammalian CoVs. Further studies would be important to delineate whether the Asian leopard cat CoV was a result of interspecies jumping from birds, a situation analogous to that of bat and civet severe acute respiratory syndrome CoVs.
Interplay of RNA Elements in the Dengue Virus 5′ and 3′ Ends Required for Viral RNA Replication

ABSTRACT Dengue virus (DENV) is a member of the Flavivirus genus of positive-sense RNA viruses. DENV RNA replication requires cyclization of the viral genome mediated by two pairs of complementary sequences in the 5′ and 3′ ends, designated 5′ and 3′ cyclization sequences (5′-3′ CS) and the 5′ and 3′ upstream of AUG region (5′-3′ UAR). Here, we demonstrate that another stretch of six nucleotides in the 5′ end is involved in DENV replication and possibly genome cyclization. This new sequence is located downstream of the AUG, designated the 5′ downstream AUG region (5′ DAR); the motif predicted to be complementary in the 3′ end is termed the 3′ DAR. In addition to the UAR, CS and DAR motifs, two other RNA elements are located at the 5′ end of the viral RNA: the 5′ stem-loop A (5′ SLA) interacts with the viral RNA-dependent RNA polymerase and promotes RNA synthesis, and a stem-loop in the coding region named cHP is involved in translation start site selection as well as RNA replication. We analyzed the interplay of these 5′ RNA elements in relation to RNA replication, and our data indicate that two separate functional units are formed; one consists of the SLA, and the other includes the UAR, DAR, cHP, and CS elements. The SLA must be located at the 5′ end of the genome, whereas the position of the second unit is more flexible. We also show that the UAR, DAR, cHP, and CS must act in concert and therefore likely function together to form the tertiary RNA structure of the circularized DENV genome.
VLSI Design of a Large-Number Multiplier for Fully Homomorphic Encryption

This paper presents the design of a power- and area-efficient high-speed 768000-bit multiplier, based on fast Fourier transform multiplication for fully homomorphic encryption operations. A memory-based in-place architecture is presented for the FFT processor that performs 64000-point finite-field FFT operations using a radix-16 computing unit and 16 dual-port SRAMs. By adopting a special prime as the base of the finite field, the radix-16 calculations are simplified to requiring only additions and shift operations. A two-stage carry-look-ahead scheme is employed to resolve carries and obtain the multiplication result. The multiplier design is validated by comparing its results with the GNU Multiple Precision (GMP) arithmetic library. The proposed design has been synthesized using 90-nm process technology with an estimated die area of 45.3 mm2. At 200 MHz, the large-number multiplier offers roughly twice the performance of a previous implementation on an NVIDIA C2050 graphics processor unit and is 29 times faster than the Xeon X5650 CPU, while at the same time consuming a modest 0.97 W.
A Haploid Genetic Screen Identifies Heparan Sulfate Proteoglycans Supporting Rift Valley Fever Virus Infection

ABSTRACT Rift Valley fever virus (RVFV) causes recurrent insect-borne epizootics throughout the African continent, and infection of humans can lead to a lethal hemorrhagic fever syndrome. Deep mutagenesis of haploid human cells was used to identify host factors required for RVFV infection. This screen identified a suite of enzymes involved in glycosaminoglycan (GAG) biogenesis and transport, including several components of the cis-oligomeric Golgi (COG) complex, one of the central components of Golgi complex trafficking. In addition, disruption of PTAR1 led to RVFV resistance as well as reduced heparan sulfate surface levels, consistent with recent observations that PTAR1-deficient cells exhibit altered Golgi complex morphology and glycosylation defects. A variety of biochemical and genetic approaches were utilized to show that both pathogenic and attenuated RVFV strains require GAGs for efficient infection on some, but not all, cell types, with the block to infection being at the level of virion attachment. Examination of other members of the Bunyaviridae family for GAG-dependent infection suggested that the interaction with GAGs is not universal among bunyaviruses, indicating that these viruses, as well as RVFV on certain cell types, employ additional unidentified virion attachment factors and/or receptors. IMPORTANCE Rift Valley fever virus (RVFV) is an emerging pathogen that can cause severe disease in humans and animals. Epizootics among livestock populations lead to high mortality rates and can be economically devastating. Human epidemics of Rift Valley fever, often initiated by contact with infected animals, are characterized by a febrile disease that sometimes leads to encephalitis or hemorrhagic fever. The global burden of the pathogen is increasing because it has recently disseminated beyond Africa, which is of particular concern because the virus can be transmitted by widely distributed mosquito species. There are no FDA-licensed vaccines or antiviral agents with activity against RVFV, and details of its life cycle and interaction with host cells are not well characterized. We used the power of genetic screening in human cells and found that RVFV utilizes glycosaminoglycans to attach to host cells. This furthers our understanding of the virus and informs the development of antiviral therapeutics.