Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative comparison of drusen segmented on SD-OCT versus drusen delineated on color fundus photographs.

PURPOSE Spectral domain-optical coherence tomography (SD-OCT) may be useful for efficient measurement of drusen in patients with age-related macular degeneration (AMD). Areas identified as drusen from semiautomated segmentation of drusen on SD-OCT were compared to those identified from review of digital color fundus photographs (CFPs). METHODS Twelve eyes with nonneovascular AMD were prospectively imaged with digital CFP and SD-OCT. For each eye, areas on CFP in which at least two of three retina specialists agreed on drusen presence produced the composite CFP drusen map. Automated image analysis produced another CFP map. Areas identified as drusen by segmentation on SD-OCT B-scans were plotted as the SD-OCT drusen map. The CFP and SD-OCT maps were compared and agreement was quantified. Disagreement was characterized into distinct types, and the frequency of each type was quantified. RESULTS There was general agreement between CFP and SD-OCT in identifying presence and absence of drusen, with mean agreement in 82% ± 9% of total image pixels. Most disagreement (80% ± 15%) occurred at drusen margins. There was a trend toward greater detection of drusen with SD-OCT in eyes with larger drusen and with hyperpigmentation. There was a trend toward greater detection of smaller drusen by CFP. CONCLUSIONS Good agreement was demonstrated in drusen detection between CFP and SD-OCT. Areas of disagreement underscore limitations of CFP-based measurement of drusen, particularly in the sizing of large, soft drusen. SD-OCT shows great promise as an adjunctive tool for assessing drusen burden in AMD. (ClinicalTrials.gov number, NCT00734487.).
Reduced bone mineral density in Chinese children with phenylketonuria

Abstract Background: Phenylketonuria (PKU) is an autosomal recessive metabolic disorder. Dietary control of classic PKU needs restriction of natural proteins. The diet results in unbalanced nutrition, which might affect the physical development of the patients. Our aim was to evaluate bone mineral density (BMD) in children with PKU. Methods: To investigate the BMD of children with PKU, 41 children with PKU and 64 healthy controls were recruited (all 3–4 years of age). Body weight and height, BMD, Phe blood levels, thyroid function, calcium, phosphorus, iron metabolism markers, and vitamin D3 were measured. Results: Body height and BMD of patients were lower than in controls. The BMD of controls was positively associated with age, body weight and height. In patients, BMD was positively associated with body weight. There was no correlation between Phe blood levels and BMD in patients. Blood levels of alkaline phosphatase were higher in patients compared to controls. Blood calcium levels were higher in 4-year-old patients, while the body weight was lower compared to controls. Thyroid function, iron metabolism markers, vitamin D3 levels and IGF-1 levels were normal. Conclusions: Reduced BMD was observed in children with phenylketonuria, but the exact reasons for this remain to be elucidated.
MAximum Multicore POwer (MAMPO) — An automatic multithreaded synthetic power virus generation framework for multicore systems

The practically attainable worst case power consumption for a computer system is a significant design parameter and it is a very tedious process to determine it by manually writing high power consuming code snippets called power viruses. Previous research efforts towards automating the power virus generation process are all limited to the single core processors and are not effective when applied to multicore parallel systems as the components like the interconnection network, shared caches, DRAM and coherence directory also contribute significantly to the power consumption of a multicore parallel system. In this paper we propose MAximum Multicore POwer (MAMPO), which is the pioneer attempt towards a framework to automatically generate a multithreaded power virus for a given multicore parallel system configuration. We show that the the power viruses generated by MAMPO consume 40% to 89% more power than running multiple copies of single-core power viruses like MPrime torture test and the most recent published previous work called SYMPO on 3 different parallel multicore system configurations. The superiority of the MAMPO viruses are also shown by comparing the power consumption of the MAMPO viruses with that of the workloads in the PARSEC benchmark suite and that of the commercial Java benchmark SPECjbb. The MAMPO viruses consume 45% to 98% more power than that of the average power consumption of the workloads in the PARSEC suite and 41% to 56% more power than that of the commercial benchmark SPECjbb.
Named Entity Recognition in Estonian

The task of Named Entity Recognition (NER) is to identify in text predefined units of information such as person names, organizations and locations. In this work, we address the problem of NER in Estonian using supervised learning approach. We explore common issues related to building a NER system such as the usage of language-agnostic and languagespecific features, the representation of named entity tags, the required corpus size and the need for linguistic tools. For system training and evaluation purposes, we create a gold standard NER corpus. On this corpus, our CRF-based system achieves an overallF1-score of 87%.
Transfer of graded potentials at the photoreceptor-interneuron synapse

To characterize the transfer of graded potentials and the properties of the associated noise in the photoreceptor-interneuron synapse of the blowfly (Calliphora vicina) compound eye, we recorded voltage responses of photoreceptors (R1-6) and large monopolar cells (LMC) evoked by: (a) steps of light presented in the dark; (b) contrast steps; and (c) pseudorandomly modulated contrast stimuli at backgrounds covering 6 log intensity units. Additionally, we made recordings from photoreceptor axon terminals. Increased light adaptation gradually changed the synaptic signal transfer from low-pass to band-pass filtering. This was accompanied by decreased synaptic delay and increased contrast gain, but the overall synaptic gain and the intrinsic noise (i.e., transmission noise) were reduced. Based on these results, we describe a descriptive synaptic model, in which the kinetics of the tonic transmitter (histamine) release from the photoreceptor axon terminals change with mean photoreceptor depolarization. During signal transmission, tonic transmitter release is augmented by voltage- dependent contrast-enhancing mechanisms in the photoreceptor axons that produce fast transients from the rising phases of the photoreceptor responses and add these enhanced voltages to the original photoreceptor responses. The model can predict the experimental findings and it agrees with the recently proposed theory of maximizing sensory information.
Fun and fair: influencing turn-taking in a multi-party game with a virtual agent

Language-based interfaces for children hold great promise in education, therapy, and entertainment. An important subset of these interfaces includes those with a virtual agent that mediates the interaction. When participants are groups of children, the agent will need to exert a certain amount of turn-taking control to ensure that all group members participate and benefit from the experience, but must do so without being so overtly directive as to undermine the children's enjoyment of and engagement in the task. We present a hierarchy of nonverbal and verbal behaviors that a virtual agent can employ flexibly when passing the conversational turn. When used effectively, these behaviors can equalize participation, and potentially decrease the amount of overlapping speech among participants, improving automatic speech recognition in turn. We evaluated the behaviors by having children play a language-based game twice, once with a flexible host and once with an inflexible host that did not have access to the behaviors. Post-game opinion cards revealed no difference between the conditions with respect to fun or likability of the host, despite the flexible agent eliciting more evenly distributed play.
IgG and IgA with Potential Microbial-Binding Activity Are Expressed by Normal Human Skin Epidermal Cells

The innate immune system of the skin is thought to depend largely on a multi-layered mechanical barrier supplemented by epidermis-derived antimicrobial peptides. To date, there are no reports of antimicrobial antibody secretion by the epidermis. In this study, we report the expression of functional immunoglobulin G (IgG) and immunoglobulin A (IgA), previously thought to be only produced by B cells, in normal human epidermal cells and the human keratinocyte line HaCaT. While B cells express a fully diverse Ig, epidermal cell-expressed IgG or IgA showed one or two conservative VHDJH rearrangements in each individual. These unique VDJ rearrangements in epidermal cells were found neither in the B cell-derived Ig VDJ databases published by others nor in our positive controls. IgG and IgA from epidermal cells of the same individual had different VDJ rearrangement patterns. IgG was found primarily in prickle cells, and IgA was mainly detected in basal cells. Both epidermal cell-derived IgG and IgA showed potential antibody activity by binding pathogens like Staphylococcus aureus, the most common pathogenic skin bacteria, but the microbial-binding profile was different. Our data indicates that normal human epidermal cells spontaneously express IgG and IgA, and we speculate that these Igs participate in skin innate immunity.
Role of ecological factors and reproductive strategies in structuring freshwater mussel communities

Freshwater mussel community composition within two drainage basins in Alabama, U.S.A. , was better explained by patterns of variability in the fish community and the type of strategy used by mussels for infecting host-fishes than by patterns of variability in microhabitat. Mussel species richness increased in a downstream direction, and large-stream sites were characterized by a distinctive faunal assemblage that was similar between drainages. In contrast, faunal composition of headwater sites varied widely between drainages. Patterns of mussel community variation were correlated with patterns of fish community variation but not with habitat. Densities of host-specialist mussels with elaborate host-attracting mechanisms and host-generalist mussels were independent of host-fish densities, and these mussels were present throughout the drainages. Densities of host-specialist mussels without elaborate host-attracting mechanisms were correlated positively with host-fish densities and were absent or rare in head.
Functional and mutational landscapes of BRCA1 for homology-directed repair and therapy resistance

BRCA1 plays a critical role in homology-directed repair (HDR) of DNA double strand breaks, and the repair defect of BRCA1-mutant cancer cells is being targeted with platinum drugs and poly (ADP-ribose) polymerase (PARP) inhibitors. We have employed relatively simple and sensitive assays to determine the function of BRCA1 variants or mutants in two HDR mechanisms, homologous recombination (HR) and single strand annealing (SSA), and in conferring resistance to cisplatin and olaparib in human cancer cells. Our results define the functionality of the top 22 patient-derived BRCA1 missense variants and the contribution of different domains of BRCA1 and its E3 ubiquitin ligase activity to HDR and drug resistance. Importantly, our results also demonstrate that the BRCA1-PALB2 interaction dictates the choice between HR and SSA. These studies establish functional and mutational landscapes of BRCA1 for HDR and therapy resistance, while revealing novel insights into BRCA1 regulatory mechanisms and HDR pathway choice. DOI: http://dx.doi. org/10.7554/eLife.21350. 001
Calcitonin Inhibits SDCP-Induced Osteoclast Apoptosis and Increases Its Efficacy in a Rat Model of Osteoporosis

Introduction Treatment for osteoporosis commonly includes the use of bisphosphonates. Serious side effects of these drugs are caused by the inhibition of bone resorption as a result of osteoclast apoptosis. Treatment using calcitonin along with bisphosphonates overcomes these side-effects in some patients. Calcitonin is known to inhibit bone resorption without reducing the number of osteoclasts and is thought to prolong osteoclast survival through the inhibition of apoptosis. Further understanding of how calcitonin inhibits apoptosis could prove useful to the development of alternative treatment regimens for osteoporosis. This study aimed to analyze the mechanism by which calcitonin influences osteoclast apoptosis induced by a bisphosphate analog, sintered dicalcium pyrophosphate (SDCP), and to determine the effects of co-treatment with calcitonin and SDCP on apoptotic signaling in osteoclasts. Methods Isolated osteoclasts were treated with CT, SDCP or both for 48 h. Osteoclast apoptosis assays, pit formation assays, and tartrate-resistant acid phosphatase (TRAP) staining were performed. Using an osteoporosis rat model, ovariectomized (OVX) rats received calcitonin, SDCP, or calcitonin + SDCP. The microarchitecture of the fifth lumbar trabecular bone was investigated, and histomorphometric and biochemical analyses were performed. Results Calcitonin inhibited SDCP-induced apoptosis in primary osteoclast cultures, increased Bcl-2 and Erk activity, and decreased Mcl-1 activity. Calcitonin prevented decreased osteoclast survival but not resorption induced by SDCP. Histomorphometric analysis of the tibia revealed increased bone formation, and microcomputed tomography of the fifth lumbar vertebrate showed an additive effect of calcitonin and SDCP on bone volume. Finally, analysis of the serum bone markers CTX-I and P1NP suggests that the increased bone volume induced by co-treatment with calcitonin and SDCP may be due to decreased bone resorption and increased bone formation. Conclusions Calcitonin reduces SDCP-induced osteoclast apoptosis and increases its efficacy in an in vivo model of osteoporosis.
Rates of DNA Sequence Profiles for Practical Values of Read Lengths

A recent study by one of the authors has demonstrated the importance of profile vectors in DNA-based data storage. We provide exact values and lower bounds on the number of profile vectors for finite values of alphabet size <inline-formula> <tex-math notation="LaTeX">$q$ </tex-math></inline-formula>, read length <inline-formula> <tex-math notation="LaTeX">$\ell $ </tex-math></inline-formula>, and word length <inline-formula> <tex-math notation="LaTeX">$n$ </tex-math></inline-formula>. Consequently, we demonstrate that for <inline-formula> <tex-math notation="LaTeX">$q\ge 2$ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$n\le q^{\ell /2-1}$ </tex-math></inline-formula>, the number of profile vectors is at least <inline-formula> <tex-math notation="LaTeX">$q^{\kappa n}$ </tex-math></inline-formula> with <inline-formula> <tex-math notation="LaTeX">$\kappa $ </tex-math></inline-formula> very close to 1. In addition to enumeration results, we provide a set of efficient encoding and decoding algorithms for certain families of profile vectors.
The impact of ulcerative colitis is greater in unmarried and young patients.

GOALS To determine whether the perceived impact of ulcerative colitis (UC) on activities of living (illness intrusiveness) is greater for people who are not living in a married or common-law relationship. BACKGROUND In general, social and occupational achievement is not greatly impaired by UC, yet patients, especially young adults, often have interpersonal concerns. METHODS One hundred fifty-five outpatients with UC were assessed for disease activity, and completed self-reports of marital status, income, social support and illness intrusiveness. RESULTS Fifty-one patients (32.9%) were single, separated or divorced, and 104 patients (67.1%) were married or in common-law relationships. Compared with those who were married or in common-law relationships, single or separated patients were younger, had a lower household income, had lived with UC for fewer years and were less satisfied with social support. Among 135 patients in remission, marital status was significantly associated with illness intrusiveness, controlling for age, income and perceived social support (F=5.73; P=0.02). Low social support (F=4.94; P=0.03) and younger age (F=7.24; P=0.008) were independently associated with illness intrusiveness. Single patients in remission reported illness intrusiveness of similar severity to that reported by patients with active disease. CONCLUSIONS The perceived impact of UC on the lives of patients is greater in those who are not married or living in common-law relationships. Youth, single status and lower social support commonly coexist, and exert additive effects on the functional impact of UC. Resources to improve social support should be directed toward this group of patients.
Characterization of the Human Cytomegalovirus gH/gL/UL128-131 Complex That Mediates Entry into Epithelial and Endothelial Cells

ABSTRACT The entry of human cytomegalovirus (HCMV) into biologically relevant epithelial and endothelial cells involves endocytosis followed by low-pH-dependent fusion. This entry pathway is facilitated by the HCMV UL128, UL130, and UL131 proteins, which form one or more complexes with the virion envelope glycoprotein gH/gL. gH/gL/UL128-131 complexes appear to be distinct from the gH/gL/gO complex, which likely facilitates entry into fibroblasts. In order to better understand the assembly and protein-protein interactions of gH/gL/UL128-131 complexes, we generated HCMV mutants lacking UL128-131 proteins and nonreplicating adenovirus vectors expressing gH, gL, UL128, UL130, and UL131. Our results demonstrate that UL128, UL130, and UL131 can each independently assemble onto gH/gL scaffolds. However, the binding of individual UL128-131 proteins onto gH/gL can significantly affect the binding of other proteins; for example, UL128 increased the binding of both UL130 and UL131 to gH/gL. Direct interactions between gH/UL130, UL130/UL131, gL/UL128, and UL128/UL130 were also observed. The export of gH/gL complexes from the endoplasmic reticulum (ER) to the Golgi apparatus and cell surface was dramatically increased when all of UL128, UL130, and UL131 were coexpressed with gH/gL (with or without gO expression). Incorporation of gH/gL complexes into the virion envelope requires transport beyond the ER. Thus, we concluded that UL128, UL130, and UL131 must all bind simultaneously onto gH/gL for the production of complexes that can function in entry into epithelial and endothelial cells.
Physical response of mid‐ocean ridge hydrothermal systems to local earthquakes

Observations from the East Pacific Rise (EPR) and the Endeavour segment of the Juan de Fuca Ridge show that local earthquake swarms can lead to increased hydrothermal venting temperatures after a delay of several days. I develop two models for this process. In the temperature perturbation model, a new pathway opens to a heat source, and the temperatures of fluids leaving the reaction zone increase. By considering the exchange of heat between the fluid flowing up a conduit and the wall rock, I solve for the resulting perturbation to venting temperatures. For flow in a crack the response is delayed, and the delay increases as the crack narrows or the reaction zone deepens, but for a pipe the venting temperature increases either quickly or barely at all. In the pressure perturbation model, there is a transient increase in pressures at depth due to a decrease in porosity, the release of overpressured fluids, or a readjustment of pressures in response to a change in the relative permeabilities of the upflow and downflow zones. One‐dimensional solutions for pressure diffusion show that this model can lead to a delayed increase in outflow fluxes which may be accompanied by increased venting temperatures. The temperature perturbation model fits the data from the EPR event well. The Endeavour event is less well constrained, and both models can fit the observations adequately. Local seismic networks and time series of fluid flux, chemistry, and temperature will be required to fully exploit hydrothermal perturbation events to infer subseafloor hydrology.
The D++ algorithm: Real-Time and collision-free path-planning for mobile robot

This paper proposed an improved algorithm that we call “D++” which can be applied to real-time and collision-free path -planning to solve some problems of common methods at present. D++ algorithm combines the Dijkstra's algorithm with sensor-based method so that D++ algorithm can deal with problems of unknown, large, complex, or dynamic environment, and need only local environmental information initially to find a shortest path. In the later of this article, we demonstrated some examples to show that D++ algorithm is very efficient for path-planning and also very practicable on real mobile robot system.
How do lncRNAs regulate transcription?

Eukaryotic genomes encode thousands of long noncoding RNAs, and many of these function in transcriptional regulation. It has recently become apparent that RNA, itself the product of transcription, is a major regulator of the transcriptional process. In particular, long noncoding RNAs (lncRNAs), which are so numerous in eukaryotes, function in many cases as transcriptional regulators. These RNAs function through binding to histone-modifying complexes, to DNA binding proteins (including transcription factors), and even to RNA polymerase II. In other cases, it is the act of lncRNA transcription rather than the lncRNA product that appears to be regulatory. We review recent progress in elucidating the molecular mechanisms by which lncRNAs modulate gene expression and future opportunities in this research field.
Higher metal-ligand coordination in the catalytic site of cobalt-substituted Thermoanaerobacter brockii alcohol dehydrogenase lowers the barrier for enzyme catalysis.

Thermoanaerobacter brockii alcohol dehydrogenase (TbADH) is a zinc-dependent NADP(+)/H-linked class enzyme that reversibly catalyzes the oxidation of secondary alcohols to their corresponding ketones. Cobalt substitution studies of other members of the alcohol dehydrogenase (ADH) family showed that the cobalt-containing ADHs have a similar active site structure but slightly decreased activity compared to wild-type zinc ADHs. In contrast, the cobalt-substituted TbADH (Co-TbADH) exhibits an increase in specific activity compared to the native enzyme [Bogin, O. , Peretz, M. , and Burstein, Y. (1997) Protein Sci. 6, 450-458]. However, the structural basis underlying this behavior is not yet clear. To shed more light on this issue, we studied the local structure and electronics at the catalytic metal site in Co-TbADH by combining X-ray absorption (XAS) and quantum chemical calculations. Importantly, we show that the first metal-ligand coordination shell of Co-TbADH is distorted compared to its native tetrahedral coordination shell and forms an octahedral structure. This is mediated presumably by the addition of two water molecules and results in more positively charged catalytic metal ions. Recently, we have shown that the metal-ligand coordination number of the zinc ion in TbADH changes dynamically during substrate turnover. These structural changes are associated with a higher coordination number of the native catalytic zinc ion and the consequent buildup of a positive charge. Here we propose that the accumulation of a higher coordination number and positive charge at the catalytic metal ion in TbADH stabilizes the structure of the catalytic transition state and hence lowers the barrier for enzyme catalysis.