Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel mitochondrial protein interactors of immunoglobulin light chains causing heart amyloidosis

In immunoglobulin (Ig) light‐chain (LC) (AL) amyloidosis, AL deposition translates into life‐threatening cardiomyopathy. Clinical and experimental evidence indicates that soluble cardiotoxic LCs are themselves harmful for cells, by which they are internalized. Hypothesizing that interaction of soluble cardiotoxic LCs with cellular proteins contributes to damage, we characterized their interactome in cardiac cells. LCs were purified from patients with AL amyloidosis cardiomyopathy or multiple myeloma without amyloidosis (the nonamyloidogenic/noncardiotoxic LCs served as controls) and employed at concentrations in the range observed in AL patients' sera. A functional proteomic approach, based on direct and inverse coimmunoprecipitation and mass spectrometry, allowed identifying LC‐protein complexes. Findings were validated by colocalization, fluorescence lifetime imaging microscopy (FLIM)‐fluorescence resonance energy transfer (FRET), and ultrastructural studies, using human primary cardiac fibroblasts (hCFs) and stem cell‐derived cardiomyocytes. Amyloidogenic cardiotoxic LCs interact in vitro with specific intracellular proteins involved in viability and metabolism. Imaging confirmed that, especially in hCFs, cardiotoxic LCs (not controls) colocalize with mitochondria and spatially associate with selected interactors: mitochondrial optic atrophy 1‐like protein and peroxisomal acyl‐coenzyme A oxidase 1 (FLIM‐FRET efficiencies 11 and 6%, respectively). Cardiotoxic LC‐treated hCFs display mitochondrial ultrastructural changes, supporting mitochondrial involvement. We show that cardiotoxic LCs establish nonphysiologic protein‐protein contacts in human cardiac cells, offering new clues on the pathogenesis of AL cardiomyopathy. —Lavatelli, F. , Imperlini, E. , Orrù, S. , Rognoni, P., Sarnataro, D. , Palladini, G. , Malpasso, G. , Soriano, M. E. , Di Fonzo, A. , Valentini, V. , Gnecchi, M. , Perlini, S. , Salvatore, F. , Merlini, G. Novel mitochondrial protein interactors of immunoglobulin light chains causing heart amyloidosis. FASEB J. 29, 4614‐4628 (2015). www.fasebj. org
Pre-adaptations and the evolution of pollination by sexual deception: Cope's rule of specialization revisited

Pollination by sexual deception is arguably one of the most unusual liaisons linking plants and insects, and perhaps the most illustrative example of extreme floral specialization in angiosperms. While considerable progress has been made in understanding the floral traits involved in sexual deception, less is known about how this remarkable mimicry system might have arisen, the role of pre-adaptations in promoting its evolution and its extent as a pollination mechanism outside the few groups of plants (primarily orchids) where it has been described to date. In the Euro-Mediterranean region, pollination by sexual deception is traditionally considered to be the hallmark of the orchid genus Ophrys. Here, we introduce two new cases outside of Ophrys, in plant groups dominated by generalized, shelter-mimicking species. On the basis of phylogenetic reconstructions of ancestral pollination strategies, we provide evidence for independent and bidirectional evolutionary transitions between generalized (shelter mimicry) and specialized (sexual deception) pollination strategies in three groups of flowering plants, and suggest that pseudocopulation has evolved from pre-adaptations (floral colours, shapes and odour bouquets) that selectively attract male pollinators through shelter mimicry. These findings, along with comparative analyses of floral traits (colours and scents), shed light on particular phenotypic changes that might have fuelled the parallel evolution of these extraordinary pollination strategies. Collectively, our results provide the first substantive insights into how pollination sexual deception might have evolved in the Euro-Mediterranean region, and demonstrate that even the most extreme cases of pollinator specialization can reverse to more generalized interactions, breaking ‘Cope's rule of specialization’.
On the nature of ULF wave power during nightside auroral activations and substorms: 2. temporal evolution

[1] We present a statistical analysis of the time evolution of ground magnetic fluctuations in three (12–48 s, 24–96 s and 48–192 s) period bands during nightside auroral activations. We use an independently derived auroral activation list composed of both substorms and pseudo-breakups to provide an estimate of the activation times of nightside aurora during periods with comprehensive ground magnetometer coverage. One hundred eighty-one events in total are studied to demonstrate the statistical nature of the time evolution of magnetic wave power during the ∼30 min surrounding auroral activations. We find that the magnetic wave power is approximately constant before an auroral activation, starts to grow up to 90 s prior to the optical onset time, maximizes a few minutes after the auroral activation, then decays slightly to a new, and higher, constant level. Importantly, magnetic ULF wave power always remains elevated after an auroral activation, whether it is a substorm or a pseudo-breakup. We subsequently divide the auroral activation list into events that formed part of ongoing auroral activity and events that had little preceding geomagnetic activity. We find that the evolution of wave power in the ∼10–200 s period band essentially behaves in the same manner through auroral onset, regardless of event type. The absolute power across ULF wave bands, however, displays a power law-like dependency throughout a 30 min period centered on auroral onset time. We also find evidence of a secondary maximum in wave power at high latitudes ∼10 min following isolated substorm activations. Most significantly, we demonstrate that magnetic wave power levels persist after auroral activations for ∼10 min, which is consistent with recent findings of wave-driven auroral precipitation during substorms. This suggests that magnetic wave power and auroral particle precipitation are intimately linked and key components of the substorm onset process.
Job stress in the health professions: a study of physicians, nurses, and pharmacists.

Abstract While considerable research has been devoted to job stress within individual health professions, little information has been available for comparing the sources or levels of stress among different groups of health professionals. To bridge that knowledge gap, the Health Professions Stress Inventory (HPSI) was administered via a mail questionnaire to 291 primary care physicians, 379 registered nurses, and 387 pharmacists randomly selected from across the United States. Mean stress scores on the HPSI were significantly different for all three professions, with nurses reporting the greatest levels of stress. Frequency of exposure to individual stressful job situations also differed significantly among the professional groups. While exploratory in nature, the results of this research emphasize the interprofessional differences that must be considered when considering the management of job stress in the health care system.
Blockade of Deubiquitylating Enzyme USP1 Inhibits DNA Repair and Triggers Apoptosis in Multiple Myeloma Cells

Purpose: The ubiquitin proteasome pathway is a validated therapeutic target in multiple myeloma. Deubiquitylating enzyme USP1 participates in DNA damage response and cellular differentiation pathways. To date, the role of USP1 in multiple myeloma biology is not defined. In the present study, we investigated the functional significance of USP1 in multiple myeloma using genetic and biochemical approaches. Experimental Design: To investigate the role of USP1 in myeloma, we utilized USP1 inhibitor SJB3-019A (SJB) for studies in myeloma cell lines and patient multiple myeloma cells. Results: USP1-siRNA knockdown decreases multiple myeloma cell viability. USP1 inhibitor SJB selectively blocks USP1 enzymatic activity without blocking other DUBs. SJB also decreases the viability of multiple myeloma cell lines and patient tumor cells, inhibits bone marrow plasmacytoid dendritic cell–induced multiple myeloma cell growth, and overcomes bortezomib resistance. SJB triggers apoptosis in multiple myeloma cells via activation of caspase-3, caspase-8, and caspase-9. Moreover, SJB degrades USP1 and downstream inhibitor of DNA-binding proteins as well as inhibits DNA repair via blockade of Fanconi anemia pathway and homologous recombination. SJB also downregulates multiple myeloma stem cell renewal/survival-associated proteins Notch-1, Notch-2, SOX-4, and SOX-2. Moreover, SJB induced generation of more mature and differentiated plasma cells. Combination of SJB and HDACi ACY-1215, bortezomib, lenalidomide, or pomalidomide triggers synergistic cytotoxicity. Conclusions: Our preclinical studies provide the framework for clinical evaluation of USP1 inhibitors, alone or in combination, as a potential novel multiple myeloma therapy. Clin Cancer Res; 23(15); 4280–9. ©2017 AACR.
Deep Relationships: The Case of the Vanishing Salesperson

The role and responsibilities of the salesperson continually evolve as firms react to competitive pressures. This paper suggests that in some instances the salesperson will vanish as the contact person for firms engaged in deep relationships. Deep relationships involve the selling firm placing staff on the buying firm's floor space to coordinate acquisition of the product that the buyer needs. The tasks of selling, communication and coordination will remain but be carried out by operational-level people in the selling organization. The forces behind these changes and examples of how these deep relationships operate are described. Implications for the sales organization involve refocusing salespeople on transactional accounts while creating deep relationships with other accounts.
Esaim: Control, Optimisation and Calculus of Variations a Set Oriented Approach to Global Optimal Control *

We describe an algorithm for computing the value function for " all source, single destination " discrete-time nonlinear optimal control problems together with approximations of associated globally optimal control strategies. The method is based on a set oriented approach for the dis-cretization of the problem in combination with graph-theoretic techniques. The central idea is that a discretization of phase space of the given problem leads to an (all source, single destination) shortest path problem on a finite graph. The method is illustrated by two numerical examples, namely a single pendulum on a cart and a parametrically driven inverted double pendulum.
Emergent Target Language Identities Among Latino English Language Learners

ABSTRACT During 2nd language acquisition, a learner’s identity is consigned, juxtaposed, coconstructed, and reified through various affective positions and mitigating linguistic behaviors. Our study of adult Latino ESL students in Dallas, Texas, shows how language socialization experiences are shaped by the learners’ affective stances toward the project of learning and using the English language. Students reflected on how their specific social barriers created conditions that impeded interaction with interlocutors who could potentially aid their socialization process in English.
THE EFFECTS OF CHRONIC NICOTINE TREATEMENT ON PERFORMANCE IN RADIAL – ARM MAZE TASK IN RATS

Chronic (21 consecutive day s) nicotine administration (0.3 m g/ kg b.w., i.p.) im prove working and reference m em ory tested by means of radial arm – m aze. The effect of nicotine is m ore pronounced on short – term m em o (working m em ory ) than on long – term mem ory (ref ry erence memory ). The benefic role of nicotinic acethy lcholine receptors on mem ory performance is attributed to the interaction with dopaminergic and NMDA receptors.
Implications of urbanism for the use of local news media: effects of population concentration on types of news acquisition in Japan

ABSTRACT The Internet, a global computer network enabling people to send and receive information anywhere in the world, also functions as a local medium of communication. This study focuses on the role of the Internet in transmitting local news and examines the effects of community population concentrations as socio-ecological environments on the use of local news media consumed online and offline. Data from 1367 respondents across 156 Japanese communities were used to analyze the relationships between type of community and type of news source. The findings suggest that people who live in highly populated communities tend more often to use the Internet to access local news, whereas those in less populated communities tend to use more traditional mass media. However, the results of this study did not show a relationship between population concentrations within communities and the acquisition of international news, nor did the social features of residents adequately explain the effects of population concentration on the acquisition of local news. These results are consistent with theoretical predictions based on network externalities, urbanism, and collective action. The findings indicate that local news consumption is embedded in local social contexts in a way that international news is not, reinforcing the importance of urbanism in the information age.
MINOS: Multimodal Indoor Simulator for Navigation in Complex Environments

We present MINOS, a simulator designed to support the development of multisensory models for goal-directed navigation in complex indoor environments. The simulator leverages large datasets of complex 3D environments and supports flexible configuration of multimodal sensor suites. We use MINOS to benchmark deep-learning-based navigation methods, to analyze the influence of environmental complexity on navigation performance, and to carry out a controlled study of multimodality in sensorimotor learning. The experiments show that current deep reinforcement learning approaches fail in large realistic environments. The experiments also indicate that multimodality is beneficial in learning to navigate cluttered scenes. MINOS is released open-source to the research community at this http URL . A video that shows MINOS can be found at this https URL
Peripheral blood metabolic and inflammatory factors as biomarkers to ocular findings in diabetic macular edema

Aims To study the association between peripheral blood metabolic and inflammatory factors and presence of diabetic macular edema (DME) and its related anatomic features in type 2 diabetic mellitus (T2DM) patients. Material and methods Observational cross-sectional study on a proof of concept basis. Seventy-six T2DM included patients were divided based on the presence (n = 58) or absence of DME (n = 18) according to optical coherence tomography (OCT). Ultra-widefield fluorescein angiography (UWFA) was performed in DME patients. Fasting peripheral blood sample testing included glycemia, glycated hemoglobin, creatinin and lipid levels among others. Serum levels of a broad panel of cytokines and inflammatory mediators were also analysed. OCT findings included central subfoveal thickness, diffuse retinal thickness (DRT), cystoid macular edema (CME), serous retinal detachment and epirretinal membrane. UWFA items included pattern of DME, presence of peripheral retinal ischemia and enlarged foveal avascular zone (FAZ). Results Metabolic and inflammatory factors did not statistically differ between groups. However, several inflammatory mediators did associate to certain ocular items of DME cases: IL-6 was significantly higher in patients with DRT (p = 0.044), IL-10 was decreased in patients with CME (p = 0.012), and higher IL-8 (p = 0.031) and VEGF levels (p = 0.031) were observed in patients with enlarged FAZ. Conclusion Inflammatory and metabolic peripheral blood factors in T2DM may not be differentially associated to DME when compared to non-DME cases. However, some OCT and UWFA features of DME such as DRT, CME and enlarged FAZ may be associated to certain systemic inflammatory mediators.
THE RELATIONSHIPS BETWEEN CHARACTERISTICS OF CAREGIVERS AND QUALITY OF LIFE AMONG FAMILY CAREGIVERS OF PATIENTS WITH SCHIZOPHRENIA IN INDONESIA

Limited research has been undertaken regarding quality of life among family caregivers of patients with schizophrenia in Indonesia despite the burden they perceived as the impact of caregiving. This study explored the caregiver burden and identified the relationships between characteristics of caregivers and the quality of life. A cross-sectional design was used with 137 family caregivers were recruited from the outpatient department of mental hospital. The characteristics of caregiver form, Burden Assessment Schedule (BAS) and Schizophrenia Caregiver Quality of Life (S-CGQoL) were provided based upon the validity and reliability test. Statistical analyses were conducted by employing descriptive and bivariate analyses. The significant factors related to quality of life consisted of gender, level of education, and employment status.This study suggests that female family caregivers who had low education, and being employed suppose to be the priority regarding the attempts to improve the QoL.
Virtual Full Duplex Wireless Broadcasting via Compressed Sensing

A novel solution is proposed to undertake a frequent task in wireless networks, which is to let all nodes broadcast information to and receive information from their respective one-hop neighboring nodes. The contribution in this paper is twofold. First, as each neighbor selects one message-bearing codeword from its unique codebook for transmission, it is shown that decoding their messages based on a superposition of those codewords through the multiaccess channel is fundamentally a problem of compressed sensing. In the case where each message is designed to consist of a small number of bits, an iterative algorithm based on belief propagation is developed for efficient decoding. Second, to satisfy the half-duplex constraint, each codeword consists of randomly distributed on-slots and off-slots. A node transmits during its on-slots and listens to its neighbors only through its own off-slots. Over one frame interval, each node broadcasts a message to its neighbors and simultaneously receives the superposition of neighbors' signals through its own off-slots and then decodes all messages. The proposed solution fully exploits the multiaccess nature of the wireless medium and addresses the half-duplex constraint at the fundamental level. In a network consisting of Poisson distributed nodes, numerical results demonstrate that the proposed scheme often achieves several times the rate of slotted ALOHA and CSMA with the same packet error rate.
Hypertension and cochlear hearing loss

Abstract This paper presents a review of experimental and clinical research on the contribution of hypertension to cochlear hearing loss. Hypertension is one of the crucial risk factors underlying pathophysiological processes taking place in the cochlea. Several mechanisms explaining these processes have been described, mainly in animal models, such as the disturbance of the inner ear potassium recycling process due to the detrimental action of natriuretic hormone, and the decrease in the cochlear oxygen partial pressure. Current evidence linking hypertension to sensorineural high-frequency cochlear hearing loss in humans may be confounded by other concomitant diseases or risk factors such as age, coronary artery disease, diabetes, obesity, hyperlipidemia, smoking and noise exposure. Therefore, further research in this field is clearly needed.
Handwriting-based model for identification of developmental disorders among North Indian children

Handwriting execution is based on the cognitive, kinesthetic, motor skills, and manual co-ordination skills of an individual. The deterioration in handwriting quality is a common implication of neurological disorders. Difficulty and degradation in handwriting has been attributed to the sensory motor deficits prevalent in developmental disorders. In spite of the association between developmental disorders and handwriting ability, the diagnostic potential of handwriting characteristics remains untapped. The present case control study was conducted among 300 subjects aged 6- to 11-years-old of North Indian origin to measure the potentials of handwriting characteristics to identify the selected developmental disorders namely ADHD, AD/HD, CD and DCD. A significant difference was obtained in the kinematics, relative size, number of handwriting defects, spatial orientation, line quality, and the mirror image presence between children with developmental disorders and typically developing (TD) children. A logistic model based on selected handwriting characteristics showed a cross validated 94.9% accuracy rate for diagnosis of developmental disorders. Receiver operator characteristic curve (ROC) analysis was conducted to assess the diagnostic potential of the model as presented by the area under curve was found to be 98.5%. The method is non-invasive, operationally easy and useful for an early identification of developmental disorders by parents and educators.
Developing Turbulent Flow in a U-Bend of Circular Cross-Section: Measurement and Computation

Laser-Doppler measurements of the longitudinal and circumferential velocity components are reported for developing turbulent flow in a strongly curved 180 deg pipe and its downstream tangent. In the bend, the mean longitudinal velocity component changes little after θ = 90 deg, but the circumferential component never achieves a fully-developed state. Similar behavior is observed in the normal stresses, with large levels of flow anisotropy arising everywhere in the bend and downstream tangent. Between θ = 90 deg and X/D = 5, the circumferential velocity profiles display reversals of the secondary flow which are essentially independent of the Reynolds number. Predictions of the flow development are presented based on a “semi-elliptic” truncation of the Reynolds equations in the main part of the flow with the standard k-e effective viscosity model used to approximate the turbulent stress field. In the immediate vicinity of the wall a simpler treatment, PSL, is adopted that allows the inclusion of the very fine mesh needed to resolve the viscous sublayer without excessive computer storage. The calculated behavior displays reasonably good agreement with the measurements in the bend, including the secondary flow reversals. Downstream of the bend, however, the rate of recovery of the flow is too slow, which points to the same weakness in the turbulence model as found in the recovery region of the flow over a backward-facing step.