Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of topical aqueous sirolimus on tear production in normal dogs and dogs with refractory dry eye

PURPOSE To evaluate the effect of twice daily aqueous 0.02% sirolimus drops on tear production in normal dogs and dogs with refractory keratoconjunctivitis sicca (KCS). METHODS Two groups of dogs were studied. Ten normal dogs with no signs of ocular disease were administered topical 0.02% sirolimus ophthalmic solution in right eye, and a vehicle control in the left eye twice daily for 4 weeks. Complete ophthalmic examinations, including Schirmer tear test were performed weekly. Eighteen dogs with refractory KCS were randomly assigned to receive 0.02% sirolumus ophthalmic solution or 0.02% tacrolimus ophthalmic solution twice daily. Complete ophthalmic examinations were was performed at 2 and 6 weeks following treatment. RESULTS Tear production in the sirolimus-treated eyes of normal dogs was greater when compared to vehicle controls with a mean difference over all time points of 3.46 mm (95% CI 1.17, 5.75; P = 0.006). After 4 weeks of treatment, the mean difference was 5 mm (95% CI 1.95, 8.05; P = 0.002). In dogs with refractory dry eye, 37.5% of eyes treated with sirolimus exhibited increased tear production >4 mm/min after 6 weeks of treatment, compared to 20% of eyes receiving tacrolimus (P = 0.433). One normal dog experienced topical irritation to both sirolimus and vehicle-treatment. Side effects were not reported in any treated eyes with chronic KCS. CONCLUSION Topical 0.02% sirolimus might be an alternative treatment for canine patients with keratoconjunctivits sicca. The drug appears safe when applied topically in an aqueous suspension for up to 6 weeks. While initial results are promising, further studies are warranted.
Managing multiple myeloma in elderly patients

Abstract Multiple myeloma (MM) is a plasma cell neoplasm that affects elderly individuals with two-thirds of patients over 65 years at diagnosis. However, data available are derived from clinical trials conducted in younger patients. Fewer studies investigated treatment options in the elderly. This review summarizes the clinical outcomes and toxicities associated with therapeutic regimens in older patients including doublet, triplet and high dose therapyin newly diagnosed patients and relapsed patients with MM. We highlight the importance of an approach tailored to individuals, incorporates the geriatric frailty assessment, considers comorbiditiess and commits to early recognition and management of toxicities ranging from myelosuppression to polypharmacy. To date, no trial has prospectively investigated a tailored treatment paradigm in older patients based on frailty and/or comorbidities. As the population ages, the proportion of MM patients with advanced age will grow. Studies are indicated to determine optimal treatment approaches in this increasingly heterogeneous geriatric population.
Variability in Rates of Coastal Change Along the Yukon Coast, 1951 to 2015

To better understand the reaction of Arctic coasts to increasing environmental pressure, coastal changes along a 210‐km length of the Yukon Territory coast in north‐west Canada were investigated. Shoreline positions were acquired from aerial and satellite images between 1951 and 2011. Shoreline change rates were calculated for multiple time periods along the entire coast and at six key sites. Additionally, Differential Global Positioning System (DGPS) measurements of shoreline positions from seven field sites were used to analyze coastal dynamics from 1991 to 2015 at higher spatial resolution. The whole coast has a consistent, spatially averaged mean rate of shoreline change of 0.7 ± 0.2 m/a with a general trend of decreasing erosion from west to east. Additional data from six key sites shows that the mean shoreline change rate decreased from −1.3 ± 0.8 (1950s–1970s) to −0.5 ± 0.6 m/a (1970s–1990s). This was followed by a significant increase in shoreline change to −1.3 ± 0.3 m/a in the 1990s to 2011. This increase is confirmed by DGPS measurements that indicate increased erosion rates at local rates up to −8.9 m/a since 2006. Ground surveys and observations with remote sensing data indicate that the current rate of shoreline retreat along some parts of the Yukon coast is higher than at any time before in the 64‐year‐long observation record. Enhanced availability of material in turn might favor the buildup of gravel features, which have been growing in extent throughout the last six decades.
Attitudes to animal euthanasia do not correlate with acceptance of human euthanasia or suicide

Several reasons have been suggested for the elevated risk of suicide experienced by those in the veterinary profession. The current study aimed to investigate possible links between veterinarians' attitudes to ‘convenience’ or non-justified animal euthanasia and attitudes towards human euthanasia and suicide. Veterinary students and graduates had a negative attitude towards convenience animal euthanasia, but their attitudes changed over time (pre-clinical studies, clinical studies and recently graduated). A greater tolerance to euthanasia was displayed in the later years of study and post qualification – primarily by males. Attitudes towards both human euthanasia and suicide, however, remained stable over time and indicated on average a neutral stance. No correlations were found between attitudes to convenience euthanasia and either human euthanasia or suicide, suggesting a tolerance to convenience euthanasia of animals does not lead to desensitisation in valuing human life and a changed attitude to human euthanasia or suicide, or vice versa. Attitudes to human euthanasia and suicide were predictably correlated, perhaps suggesting an overarching attitude towards control over human death. The results of the current study throw into question the argument that it is the changes in attitudes to animal life that affect veterinarian's attitudes to human life and contribute to the high suicide rate.
QUATERNARY SULFUR CYCLE DYNAMICS

The past 3 million years of Earth history are characterized by dramatic changes, which greatly affected the biogeochemical cycling of elements like carbon, sulfur and phosphorous. Here I investigate the effect of these changes on sulfur fluxes and microbially mediated sulfur cycling in marine sediments. Climate driven sea level fluctuations and dynamic topography have greatly affected the areal extent of the continental shelf during the Quaternary. In turn this affects organic matter burial rates and the relative importance of different organic matter remineralization pathways. Since microbial sulfur cycling is the dominant organic matter re-mineralization pathway in marine sediments, this must have affected marine sulfur cycling. Furthermore, previous studies suggested that Quaternary sea level fluctuations caused a considerable increase in the erosion of shelf sediments, which is
Methotrexate therapy of head and neck cancer: improvement in therapeutic index by the use of leucovorin "rescue".

Twenty-one patients with advanced epidermoid carcinoma of the head and neck were treated with 24-hr infusions of methotrexate followed by leucovorin rescue repeated at 4-day intervals. Thirteen of the 21 patients responded with a greater than 50% reduction of tumor mass and 7 of the 13 sustained a greater than 75% reduction. The median duration of tumor regression was 16 weeks. In general, toxicity was tolerable. The rationale of this regimen and its comparison with other methotrexate schedules is discussed.
Message Passing Algorithms for the Dirichlet Diffusion Tree

We demonstrate efficient approximate inference for the Dirichlet Diffusion Tree (Neal, 2003), a Bayesian nonparametric prior over tree structures. Although DDTs provide a powerful and elegant approach for modeling hierarchies they haven’t seen much use to date. One problem is the computational cost of MCMC inference. We provide the first deterministic approximate inference methods for DDT models and show excellent performance compared to the MCMC alternative. We present message passing algorithms to approximate the Bayesian model evidence for a specific tree. This is used to drive sequential tree building and greedy search to find optimal tree structures, corresponding to hierarchical clusterings of the data. We demonstrate appropriate observation models for continuous and binary data. The empirical performance of our method is very close to the computationally expensive MCMC alternative on a density estimation problem, and significantly outperforms kernel density estimators.
The Unprecedented 2016–2017 Arctic Sea Ice Growth Season: The Crucial Role of Atmospheric Rivers and Longwave Fluxes

The 2016–2017 Arctic sea ice growth season (October–March) exhibited one of the lowest values for end‐of‐season sea ice volume and extent of any year since 1979. An analysis of Modern‐Era Retrospective Analysis for Research and Applications, Version 2 atmospheric reanalysis data and Clouds and the Earth's Radiant Energy System radiative flux data reveals that a record warm and moist Arctic atmosphere supported the reduced sea ice growth. Numerous regional episodes of increased atmospheric temperature and moisture, transported from lower latitudes, increased the cumulative energy input from downwelling longwave surface fluxes. In those same episodes, the efficiency of the atmosphere cooling radiatively to space was reduced, increasing the amount of energy retained in the Arctic atmosphere and reradiated back toward the surface. Overall, the Arctic radiative cooling efficiency shows a decreasing trend since 2000. The results presented highlight the increasing importance of atmospheric forcing on sea ice variability demonstrating that episodic Arctic atmospheric rivers, regions of elevated poleward water vapor transport, and the subsequent surface energy budget response is a critical mechanism actively contributing to the evolution of Arctic sea ice.
Covert Shift of Attention Modulates the Ongoing Neural Activity in a Reaching Area of the Macaque Dorsomedial Visual Stream

Background Attention is used to enhance neural processing of selected parts of a visual scene. It increases neural responses to stimuli near target locations and is usually coupled to eye movements. Covert attention shifts, however, decouple the attentional focus from gaze, allowing to direct the attention to a peripheral location without moving the eyes. We tested whether covert attention shifts modulate ongoing neuronal activity in cortical area V6A, an area that provides a bridge between visual signals and arm-motor control. Methodology/Principal Findings We performed single cell recordings from 3 Macaca Fascicularis trained to fixate straight-head, while shifting attention outward to a peripheral cue and inward again to the fixation point. We found that neurons in V6A are influenced by spatial attention. The attentional modulation occurs without gaze shifts and cannot be explained by visual stimulations. Visual, motor, and attentional responses can occur in combination in single neurons. Conclusions/Significance This modulation in an area primarily involved in visuo-motor transformation for reaching may form a neural basis for coupling attention to the preparation of reaching movements. Our results show that cortical processes of attention are related not only to eye-movements, as many studies have shown, but also to arm movements, a finding that has been suggested by some previous behavioral findings. Therefore, the widely-held view that spatial attention is tightly intertwined with—and perhaps directly derived from—motor preparatory processes should be extended to a broader spectrum of motor processes than just eye movements.
Prospective Memory in Patients with Severe Closed-Head Injury: Role of Concurrent Activity and Encoding Instructions

Objectives: To assess the sensitivity of patients who suffered a severe closed-head injury to the manipulation of attentional resources and encoding instructions during the execution of prospective memory tasks. Material and Methods: A group of patients with chronic sequelae of severe closed-head injury and a group of matched normal controls were given an experimental procedure for the assessment of time-based and event-based prospective memory. Availability of attentional resources at the time of intention recall and encoding conditions at the time of giving instructions were varied across experimental sessions. Results: The simultaneous execution of a concurrent task was more detrimental to accuracy in the spontaneous recall of the prospective intention in the post-traumatic than in the normal control group. Moreover, the instruction to encode more extensively by rehearsing aloud and mentally imaging the actions to be performed at the time of the study improved recall accuracy more in the post-traumatic than in the normal control group. Conclusions: Based on these data, we suggest that a prospective memory deficit in post-traumatic patients is due, among other things, to reduced availability of attentional resources and to poor encoding of actions to be performed.
Structural Basis for Phototoxicity of the Genetically Encoded Photosensitizer KillerRed*

KillerRed is the only known fluorescent protein that demonstrates notable phototoxicity, exceeding that of the other green and red fluorescent proteins by at least 1,000-fold. KillerRed could serve as an instrument to inactivate target proteins or to kill cell populations in photodynamic therapy. However, the nature of KillerRed phototoxicity has remained unclear, impeding the development of more phototoxic variants. Here we present the results of a high resolution crystallographic study of KillerRed in the active fluorescent and in the photobleached non-fluorescent states. A unique and striking feature of the structure is a water-filled channel reaching the chromophore area from the end cap of the β-barrel that is probably one of the key structural features responsible for phototoxicity. A study of the structure-function relationship of KillerRed, supported by structure-based, site-directed mutagenesis, has also revealed the key residues most likely responsible for the phototoxic effect. In particular, Glu68 and Ser119, located adjacent to the chromophore, have been assigned as the primary trigger of the reaction chain.
Dynamical system design from a control perspective: finite frequency positive-realness approach

Nonminimum phase zeros are well known to limit the best achievable control performance when the control gain is allowed to be arbitrarily high. On the other hand, the phase crossover appears to be a limiting factor for performance when high-gain controllers are not allowed. In particular, the positive-realness in a finite frequency range seems crucial for achieving good performance in the presence of control constraints. This paper will first give multiple reasons to support this conjecture, and then develop a systematic method for designing mechanical systems to achieve the finite frequency positive-real (FFPR) property. Specifically, we present a state-space characterization of the FFPR property by generalizing the well known Kalman-Yakubovich-Popov lemma to deal with a class of frequency domain inequalities that are required to hold within a finite frequency interval. The result is further extended for uncertain systems to give a sufficient condition for satisfaction of a robust FFPR property. The (nominal) FFPR result is interpreted in the time-domain in terms of input/output signals. Finally, we show that certain sensor/actuator placement problems to achieve the FFPR property can be reduced to finite dimensional convex problems involving linear matrix inequalities. The method is applied to the shape design of a swing-arm for magnetic storage devices with the objective of maximizing the control bandwidth achievable with a limited actuator power.
Excited-state gain dynamics in InGaAs quantum-dot amplifiers

The ultrafast gain recovery dynamics of the first excited state (ES) is studied in an electrically pumped InGaAs quantum-dot amplifier at room temperature and compared with the ground-state (GS) gain dynamics. Pump-probe differential transmission experiments are performed in heterodyne detection and the gain dynamics are investigated as a function of injection current. An ultrafast (<200 fs) initial gain recovery of both GS and ES transition is found, promising for optical signal processing at high bit rates. The obtained results suggest the occurrence of a fast recovery of the state occupation mediated by carrier-carrier scattering as long as a reservoir of carriers in the ESs and wetting layer is present.
Learning preferences towards computerized competitive modes

An online domain-independent competitive gaming system, called JOYCE, was devised to engage students in drill-and-practice exercises. In this paper, theories underpinning the system design are explained. As in the system students are allowed to compete with others in a face-to-face situation, and in network situations where an opponent's identify is revealed or concealed, a preliminary study was conducted to examine students' preferences towards different competition modes and satisfaction towards the learning experience. Results supported JOYCE's incorporation into the learning process and the design and development of the system. Based on the obtained data it was suggested that to increase its intrinsic value and to lessen the negative emotional states which is more easily exhibited in a face-to-face competition situation anonymity is a promising feature to be included in a competitive learning system. Furthermore, various competition modes should be built into e-learning environments to satisfy peoples' different learning mode preferences.
Efficacy and Safety of Povidone-iodine Pleurodesis in Malignant Pleural Effusions

Introduction: Malignant pleural effusion (MPE) is determined by the detection of malignant cells in pleural fluid or pleural tissue. Neoplasm of lung, breast, ovary and lymphoma are the causes of more than 75% of MPE. Pleurodesis is a usual technique in the management of MPE to achieve a symphysis between two layers of the pleura, and various chemical agents have been used in an attempt to produce pleurodesis. With regard to complications and limitations of these sclerosing agents, efficacy and safety of povidone-iodine have been investigated in this study. Materials and Methods: Between June 2014 and June 2016, 63 consecutive patients were admitted to the Department of Thoracic Surgery because of symptomatic MPE. After insertion of a chest tube, pleurodesis with instillation of povidone-iodine was performed. Thyroid and renal function tests were checked, and success rate as well as recurrence of MPE was monitored in the next follow-up visits. Results: The complete response to this procedure was about 53.57%, and failure of treatment was 10.71% with efficacy of 82.2%. The most common complication was pain during instillation (26.9%). Changes in thyroid and renal function tests were not significant. Conclusion: Povidone-iodine is a safe and effective agent with minor side effects in pleurodesis of patients with MPEs and can be used as an accessible and low-cost alternative than other sclerosing agents.
GrubJoin: An Adaptive, Multi-Way, Windowed Stream Join with Time Correlation-Aware CPU Load Shedding

Tuple dropping, though commonly used for load shedding in most data stream operations, is generally inadequate for multiway windowed stream joins. The join output rate can be unnecessarily reduced because tuple dropping fails to exploit the time correlations that are likely to exist among interrelated streams. In this paper, we introduce GrubJoin-an adaptive multiway windowed stream join that effectively performs time correlation-aware CPU load shedding. GrubJoin maximizes the output rate by achieving near-optimal window harvesting, which picks only the most profitable segments of individual windows for the join. Due mainly to the combinatorial explosion of possible multiway join sequences involving different window segments, GrubJoin faces unique challenges that do not exist for binary joins, such as determining the optimal window harvesting configuration in a time-efficient manner and learning the time correlations among the streams without introducing overhead. To tackle these challenges, we formalize window harvesting as an optimization problem, develop greedy heuristics to determine near-optimal window harvesting configurations, and use approximation techniques to capture the time correlations. Our experimental results show that GrubJoin is vastly superior to tuple dropping when time correlations exist and is equally effective when time correlations are nonexistent.
Idiopathic sclerosing orbital pseudotumor in seven cats

Abstract Objective To review the clinical presentation and histopathologic findings on a series of cats with orbital fibrotic disease and compare the data to that of humans with sclerosing orbital pseudotumor. Animals A retrospective study was undertaken, which identified tissue samples from seven cats between 1997 and 2002 with a history of orbital mass effect and pathology characterized by fibrous tissue proliferation. Procedure Information was obtained from medical records for affected cats, including age, sex, clinical signs, management, and outcome, with histopathology re‐examined. Results Six of seven cats presented with unilateral orbital involvement that progressed to bilateral orbital disease despite treatment. Onset was insidious, evolving over weeks to months and was associated with fixation of orbital structures. Owners of six of the cats opted for euthanasia because of disease progression and pain. Histopathology of affected orbital tissue included extensive fibrosis with encapsulation of normal tissues without characteristics of neoplasia. Conclusions Clinical findings and histopathology of globes and orbital tissues in cats bore many similarities to idiopathic sclerosing orbital pseudotumor in humans. In cats, the prognosis for the globe appears to be poor but an elucidation of the pathogenesis and earlier diagnosis coupled with more aggressive treatment modalities as indicated in humans may be beneficial.
Matrix metalloproteinases and their inhibitors in gingival mast cells in persons with and without human immunodeficiency virus infection.

BACKGROUND Mast cells are a prominent cell type in the gingival infiltrate in periodontitis. In this study we examined the expression by gingival mast cells of matrix metalloproteinases, MMP-1, MMP-2, MMP-8 and the tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2. METHODS Gingival specimens from 12 human immunodeficiency virus-negative (HIV-) and 15 HIV-positive (HIV+) patients with chronic marginal periodontitis (CMP), and from 10 HIV- and four HIV+ controls with clinically healthy gingiva (HG) were examined after double immunofluorescence staining for mast cell tryptase, combined with antibodies for MMP-1, MMP-2, MMP-8 or their inhibitors TIMP-1 and TIMP-2. RESULTS In the HIV+CMP, HIV+HG and HIV-CMP groups, all mast cells expressed MMP-1 and MMP-8, whereas a smaller proportion (40-60%) in the HIV-HG controls displayed such staining. The former groups also displayed a significantly higher proportion (39-64%) of mast cells expressing MMP-2 as compared with the HIV-HG group (21-31%). All groups displayed similar proportions of TIMP-1 expressing mast cells (86-100%), whereas significantly increased proportions of TIMP-2+ mast cells were seen in the HIV+CMP, HIV+HG and HIV-CMP groups (18-25%) as compared with the HIV-HG group (8-13%). Mast cells were the cell type that most prominently expressed MMP-1 and MMP-8. MMP-2 expression was also strong in mast cells, but was also similarly expressed in other cell types. CONCLUSION The chronically inflamed periodontal lesions in the present study appeared with little evidence of mast cell degranulation. The results show, however, that mast cells in inflamed gingiva have the potential to degrade extracellular matrix if appropriately triggered.