Miracle-dz/UniFAR-FTUs huggingface dataset:
Systematic imaging reveals features and changing localization of mRNAs in Drosophila development

mRNA localization is critical for eukaryotic cells and affects numerous transcripts, yet how cells regulate distribution of many mRNAs to their subcellular destinations is still unknown. We combined transcriptomics and systematic imaging to determine tissue-specific expression and subcellular distribution of 5862 mRNAs during Drosophila oogenesis. mRNA localization is widespread in the ovary, depends on the microtubule cytoskeleton and the mRNAs enriched at the posterior cortex share common localization machinery. Localized mRNAs, in particular the posterior class, have distinct gene features and differ in expression level, 3’UTR length and sequence conservation from unlocalized mRNAs. Using cross-tissue comparison we revealed that the localization status of mRNAs differs between epithelial, germline and embryonic cell types and also changes within one cell, the oocyte, over time. This dataset enables the transition from deep mechanistic dissection of singular mRNA localization events towards global understanding of how mRNAs transcribed in the nucleus distribute in cells.
Cross-Linking of Gelatin and Chitosan Complex Nanofibers for Tissue-Engineering Scaffolds

The aim of this study is to investigate cross-linked gelatin–chitosan nanofibers produced by means of electrospinning. Gelatin and chitosan nanofibers were electrospun and then cross-linked by glutaraldehyde (GTA) vapor at room temperature. Scanning electron microscopy (SEM) images showed that the cross-linked mats could keep their nanofibrous structure after being soaked in deionized water at 37° C. The cross-linking mechanism was discussed based on FT-IR results. The two main mechanisms of cross-linking for chitosan and gelatin–chitosan complex are Schiff base reaction and acetalization reaction. For gelatin, the mechanism of cross-linking was Schiff base reaction. The mechanical properties of nanofibrous mats were improved after cross-linking. The biocompatibility of electrospun nanofibrous mats after cross-linking was investigated by the viability of porcine iliac endothelial cells (PIECs). The morphologies of PIECs on the cross-linked nanofibrous mats were observed by SEM. In addition, proliferation of PIECs was tested with the method of methylthiazol tetrazolium (MTT) assay. The results indicate that gelatin–chitosan nanofibrous mats could be a promising candidate for tissue-engineering scaffolds.
Differential behavioral and physiological effects of anodal transcranial direct current stimulation in healthy adults of younger and older age

Changes in γ-aminobutyric acid (GABA) mediated synaptic transmission have been associated with age-related motor and cognitive functional decline. Since anodal transcranial direct current stimulation (atDCS) has been suggested to target cortical GABAergic inhibitory interneurons, its potential for the treatment of deficient inhibitory activity and functional decline is being increasingly discussed. Therefore, after-effects of a single session of atDCS on resting-state and event-related short-interval intracortical inhibition (SICI) as evaluated with double-pulse TMS and dexterous manual performance were examined using a sham-controlled cross-over design in a sample of older and younger participants. The atDCS effect on resting-state inhibition differed in direction, magnitude, and timing, i.e., late relative release of inhibition in the younger and early relative increase in inhibition in the older. More pronounced release of event-related inhibition after atDCS was exclusively seen in the older. Event-related modulation of inhibition prior to stimulation predicted the magnitude of atDCS-induced effects on resting-state inhibition. Specifically, older participants with high modulatory capacity showed a disinhibitory effect comparable to the younger. Beneficial effects on behavior were mainly seen in the older and in tasks requiring higher dexterity, no clear association with physiological changes was found. Differential effects of atDCS on SICI, discussed to reflect GABAergic inhibition at the level of the primary motor cortex, might be distinct in older and younger participants depending on the functional integrity of the underlying neural network. Older participants with preserved modulatory capacity, i.e., a physiologically “young” motor network, were more likely to show a disinhibitory effect of atDCS. These results favor individually tailored application of tDCS with respect to specific target groups.
ournal of Statistical Mechanics : J Theory and Experiment Efficient rare event simulation by optimal nonequilibrium forcing

Rare event simulation and estimation for systems in equilibrium are among the most challenging topics in molecular dynamics. As was shown by Jarzynski and others, nonequilibrium forcing can theoretically be used to obtain equilibrium rare event statistics. The advantage seems to be that the external force can speed up the sampling of the rare events by biasing the equilibrium distribution towards a distribution under which the rare events are no longer rare. Yet algorithmic methods based on Jarzynski’s and related results often fail to be efficient because they are based on sampling in path space. We present a new method that replaces the path sampling problem by minimization of a crossentropy-like functional which boils down to finding the optimal nonequilibrium forcing. We show how to solve the related optimization problem in an efficient way by using an iterative strategy based on milestoning.
Restricted BV gene usage by factor VIII-reactive CD4+ T cells in inhibitor-positive patients with severe hemophilia A

Summary In the present study, we have analyzed the T cell receptor (TCR) repertoires of CD4+ T cells isolated from peripheral blood of 10 inhibitor-positive patients with severe hemophilia A. The distribution of complementarity determining region (CDR3) lengths of the beta chain of the TCRs was analyzed by spectratyping prior to and following in vitrostimulation of the cells with human factor VIII (FVIII). The repertoires of CD4+ T cells of patients were perturbed when compared to those of healthy blood donors. The perturbations of T cell repertoires were heterogeneous among patients with respect to the number and the nature of V-beta (BV) families that exhibited expansion following incubation with FVIII. Some patients showed alterations in one or two BV families, others exhibited more perturbed repertoires affecting 5 to 8 of the 14 BV families tested. Alterations of BV2, BV5 and/or BV9 were consistently found after incubation of CD4+ T cells in the presence of FVIII in 80% of the patients. These findings indicate that the presence of FVIII inhibitors in patients with severe hemophilia A is associated with measurable perturbations of the CD4+ T cell repertoire that results from oligoclonal expansion of FVIII-specific cells and may be relevant for the design of strategies aimed at modulating the anti-FVIII immune responses by T cell-targeted therapy
Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma.

BACKGROUND Preclinical and preliminary clinical data indicate that ch14.18, a monoclonal antibody against the tumor-associated disialoganglioside GD2, has activity against neuroblastoma and that such activity is enhanced when ch14.18 is combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2. We conducted a study to determine whether adding ch14.18, GM-CSF, and interleukin-2 to standard isotretinoin therapy after intensive multimodal therapy would improve outcomes in high-risk neuroblastoma. METHODS Patients with high-risk neuroblastoma who had a response to induction therapy and stem-cell transplantation were randomly assigned, in a 1:1 ratio, to receive standard therapy (six cycles of isotretinoin) or immunotherapy (six cycles of isotretinoin and five concomitant cycles of ch14.18 in combination with alternating GM-CSF and interleukin-2). Event-free survival and overall survival were compared between the immunotherapy group and the standard-therapy group, on an intention-to-treat basis. RESULTS A total of 226 eligible patients were randomly assigned to a treatment group. In the immunotherapy group, a total of 52% of patients had pain of grade 3, 4, or 5, and 23% and 25% of patients had capillary leak syndrome and hypersensitivity reactions, respectively. With 61% of the number of expected events observed, the study met the criteria for early stopping owing to efficacy. The median duration of follow-up was 2.1 years. Immunotherapy was superior to standard therapy with regard to rates of event-free survival (66±5% vs. 46±5% at 2 years, P=0.01) and overall survival (86±4% vs. 75±5% at 2 years, P=0.02 without adjustment for interim analyses). CONCLUSIONS Immunotherapy with ch14.18, GM-CSF, and interleukin-2 was associated with a significantly improved outcome as compared with standard therapy in patients with high-risk neuroblastoma. (Funded by the National Institutes of Health and the Food and Drug Administration; ClinicalTrials.gov number, NCT00026312.)
The Impact of Aerosol Particle Mixing State on the Hygroscopicity of Sea Spray Aerosol

Aerosol particles influence global climate by determining cloud droplet number concentrations, brightness, and lifetime. Primary aerosol particles, such as those produced from breaking waves in the ocean, display large particle–particle variability in chemical composition, morphology, and physical phase state, all of which affect the ability of individual particles to accommodate water and grow into cloud droplets. Despite such diversity in molecular composition, there is a paucity of methods available to assess how particle–particle variability in chemistry translates to corresponding differences in aerosol hygroscopicity. Here, an approach has been developed that allows for characterization of the distribution of aerosol hygroscopicity within a chemically complex population of atmospheric particles. This methodology, when applied to the interpretation of nascent sea spray aerosol, provides a quantitative framework for connecting results obtained using molecular mimics generated in the laboratory with chemically complex ambient aerosol. We show that nascent sea spray aerosol, generated in situ in the Atlantic Ocean, displays a broad distribution of particle hygroscopicities, indicative of a correspondingly broad distribution of particle chemical compositions. Molecular mimics of sea spray aerosol organic material were used in the laboratory to assess the volume fractions and molecular functionality required to suppress sea spray aerosol hygroscopicity to the extent indicated by field observations. We show that proper accounting for the distribution and diversity in particle hygroscopicity and composition are important to the assessment of particle impacts on clouds and global climate.
Management of muscle-invasive bladder cancer in the elderly

Purpose of review The number of cases of muscle-invasive bladder cancer is increasing along with the age of the population. Management of muscle-invasive bladder cancer in the elderly is complex, requiring a multidisciplinary team approach and a comprehensive assessment of each individual patient. Recent findings A geriatric assessment should be used to inform treatment decisions in elderly patients with bladder cancer. There is increasing evidence to support aggressive therapy in appropriate elderly patients, including radical cystectomy and neoadjuvant chemotherapy. Adjuvant chemotherapy also has a role in patients with high-risk disease after cystectomy. A bladder preservation approach with trimodality therapy is a well tolerated and effective alternative to cystectomy in appropriately selected patients. Summary Treatment decisions should not be based on chronologic age alone and advanced age should not preclude aggressive or curative therapy. The recent molecular characterization of bladder cancer and several recent immunotherapy trials provide hope of a more targeted approach to treatment of bladder, potentially improving both effectiveness and tolerability of treatment regimens in the elderly.
Partisanship and the Effectiveness of Oversight

We examine the welfare effects of partisanship in a model of checks and balances. An executive makes a policy proposal and an overseer then decides whether or not to veto the executive's proposal. Both the executive and the overseer have private information as to the correct policy to pursue, and both are motivated by the desire to appear competent. A partisan overseer is one who, in addition to seeking to promote her own reputation, cares how her decision will impact the executive's reputation. Our main result is that partisanship can improve the efficacy of an oversight regime, as the distortions caused by a partisan overseer's desire to affect the executive's reputation can offset the distortions caused by her desire to enhance her own. Our results provide a new rationale for divided government, as partisan considerations are often necessary to prevent the overseer from rubber stamping all executive proposals.
A TaLISMAN: Automatic Text and LIne Segmentation of historical MANuscripts

Historical and artistic handwritten books are valuable cultural heritage (CH) items, as they provide information about tangible and intangible cultural aspects from the past. Massive digitization projects have made these kind of data available to a world-wide population, and pose real challenges for automatic processing. In this scenario, document layout analysis plays a significant role, being a fundamental step of any document image understanding system. In this paper, we present a completely automatic algorithm to perform a robust text segmentation of old handwritten manuscripts on a per-book basis, and we show how to exploit this outcome to find two layout elements, i.e., text blocks and text lines. Our proposed technique have been evaluated on a large and heterogeneous corpus content, and our experimental results demonstrate that this approach is efficient and reliable, even when applied to very noisy and damaged books.
Neuronal Expression of β-Amyloid Precursor Protein Alzheimer Mutations Causes Intracellular Accumulation of a C-terminal Fragment Containing Both the Amyloid β and Cytoplasmic Domains*

Five different Alzheimer mutations of the β-amyloid precursor protein (APP) were expressed in neurons via recombinant herpes simplex virus (HSV) vectors, and the levels of APP metabolites were quantified. The predominant intracellular accumulation product was a C-terminal fragment of APP that co-migrated with the protein product of an HSV recombinant expressing the C-terminal 100 amino acids (C100) of APP, which is known to cause neurodegeneration. Fractionation studies revealed that the C-terminal fragment generated by expression of the Alzheimer mutations, like C100, partitioned into membrane fractions and was particularly enriched in synaptosomes. The processing abnormality caused by expression of the Alzheimer mutations occurs predominantly in neurons. Expression of these mutations or of C100 alone in neurons caused increased secretion of Aβ relative to that of neurons infected with wild type APP recombinant vectors. These data show that expression of APP mutations that cause familial Alzheimer’s disease increases the intracellular accumulation of potentially amyloidogenic and neurotoxic C-terminal fragments of APP in neurons.
Effect of Sexually Transmitted Disease (STD) Coinfections on Performance of Three Commercially Available Immunosorbent Assays Used for Detection of Herpes Simplex Virus Type 2-Specific Antibody in Men Attending Baltimore, Maryland, STD Clinics

ABSTRACT Two hundred seventy-nine serum samples from men attending sexually transmitted disease (STD) clinics in Baltimore, Maryland, were tested for herpes simplex virus type 2 (HSV-2)-specific antibody by three immunosorbent glycoprotein G-2-based assays (the Kalon, Focus, and Biokit assays). The results for all samples with positive results were confirmed by Western blotting (91/279; 32.6% HSV-2 seroprevalence). All patients were also tested for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, human immunodeficiency virus type 1, and hepatitis C virus. The Kalon assay performed very well with samples from this population (90.8% sensitive, 99.4% specific), whereas the Focus assay had a sensitivity (82.6%) much lower than that shown previously. For 19.7% of the samples, the Biokit assay gave an indeterminate result. It was found that the odds of a sample having a Biokit assay indeterminate result compared to that of having a definitive positive or negative results were 3.88 times greater for subjects concurrently infected with N. gonorrhoeae, after the effects of other STDs were controlled for (P = 0.001; 95% confidence interval, 1.78, 8.45). Unfortunately, we were unable to control for HSV-1 infection status in the regression model, which, on the basis of χ2 analysis, might also affect the clarity of the Biokit test. The recommended index cutoff value of 1.1 for the Focus and Kalon assays was found to be optimal for this population.
Phase estimation in speech enhancement — Unimportant, important, or impossible?

In recent years, research in the field of single channel speech enhancement has focused on the enhancement of spectral amplitudes while the noisy spectral phase was left unchanged. In this paper we review the motivation for neglecting phase estimation in the past, and why recent publications imply that the estimation of the clean speech phase may be beneficial after all. Further, we present an algorithm for blindly estimating the clean speech spectral phase from the noisy observation and show that the application of this phase estimate improves the predicted speech quality.
Systematic review toolbox: a catalogue of tools to support systematic reviews

Systematic review is a widely used research method in software engineering, and in other disciplines, for identifying and analysing empirical evidence. The method is data intensive and time consuming, and hence is usually supported by a wide range of software-based tools. However, systematic reviewers have found that finding and selecting tools can be quite challenging. In this paper, we present the Systematic Review Toolbox; a web-based catalogue of tools, to help reviewers find appropriate tools based on their particular needs.
Recognizing depth-rotated objects: evidence and conditions for three-dimensional viewpoint invariance.

Five experiments on the effects of changes of depth orientation on (a) priming the naming of briefly flashed familiar objects, (b) matching individual sample volumes (geons), and (c) classifying unfamiliar objects (that could readily be decomposed into an arrangement of distinctive geons) all revealed immediate (i.e., not requiring practice) depth invariance. The results can be understood in terms of 3 conditions derived from a model of object recognition (I. Biederman, 1987; J. E. Hummel & I. Biederman, 1992) that have to be satisfied for immediate depth invariance: (a) that the stimuli be capable of activating viewpoint-invariant (e.g., geon) structural descriptions (GSDs), (b) that the GSDs be distinctive (different) for each stimulus, and (c) that the same GSD be activated in original and tested views. The stimuli used in several recent experiments documenting extraordinary viewpoint dependence violated these conditions.
Thermal effect of endoscopic thermal vapour ablation on the lung surface in human ex vivo tissue

Purpose: An investigation of the thermal effect and the potential for injury at the lung surface following thermal vapour ablation (InterVapor), an energy-based method of achieving endoscopic lung volume reduction. Methods: Heated water vapour was delivered to fifteen ex vivo human lungs using standard clinical procedure, and the thermal effect at the visceral pleura was monitored with an infrared camera. The time–temperature response was analysed mathematically to determine a cumulative injury quotient, which was compared to published thresholds. Results: The cumulative injury quotients for all 71 treatments of ex vivo tissue were found to be below the threshold for first degree burn and no other markers of tissue injury at the lung surface were observed. Conclusion: The safety profile for thermal vapour ablation is further supported by the demonstration that the thermal effect in a worst-case model is not expected to cause injury at the lung surface.
Listening to the nurse pays off: an integrated Nurse HealthLine programme was associated with significant cost savings.

AIM To estimate the relationship between adherence to nurse recommendations about where to seek care and expenditures for health-care services received by callers to a Nurse HealthLine telephone-based triage programme. METHODS Health-care utilization and claims data from callers to the Nurse HealthLine were included. Adherent callers were those who followed the nurse recommendations, while those who did not were classified as non-adherent. Programme-related savings were estimated using differences in downstream health-care expenditures between adherent and non-adherent callers after using multivariate modelling to adjust for between-group differences. RESULTS Fifty-five per cent of callers were adherent. Nurses were over three times as likely (41% vs. 13%) to recommend seeking a higher level of care (e.g. emergency room vs. urgent care). Regression analyses showed that the impact of getting members to the appropriate place of care was associated with significant annual savings of $13.8 million (P < 0.05), attributable mostly to Medicare, generating a positive return on investment of $1.59. CONCLUSIONS This is the first known Nurse HealthLine triage programme exclusively for Medicare beneficiaries with supplemental coverage. IMPLICATIONS FOR NURSING MANAGEMENT Nurse managers should consider promoting telephone-based triage programmes as complementary to clinical nursing, which has a direct impact on health-care utilization and costs.
Intergalactic H_2 Photodissociation and the Soft UV Background Produced by Population III Objects

We study the effects of the ionizing and dissociating photons produced by PopIII objects on the surrounding intergalactic medium. We find that the typical size of a H_2 photodissociated region, R_d ~ 1-5 kpc, is smaller than the mean distance between sources at z ~ 20-30, but larger than the ionized region by a factor depending on the detailed properties of the emission spectrum. This implies that clearing of intergalactic H_2 occurs before reionization of the universe is complete. In the same redshift range, the soft-UV background in the Lyman-Werner bands, when the intergalactic H and H_2 opacity is included, is found to be J_LW ~ 1d-30 - 1d-27 erg cm^{-2} s^{-1} Hz^{-1}. This value is well below the threshold required for the negative feedback of PopIII objects on the subsequent galaxy formation to be effective in that redshift range.
Mycobacterium marinum causes both long-term subclinical infection and acute disease in the leopard frog (Rana pipiens)

Mycobacterium marinum grows at an optimal temperature of 33 degrees C, far lower than that for M. tuberculosis. Consequently, M. marinum infection of mammals is restricted largely to the cooler surfaces of the body, such as the extremities, but it causes a systemic infection in a large number of poikilothermic animals. Here, we describe a laboratory animal model for M. marinum disease in the leopard frog (Rana pipiens), a natural host species. M. marinum causes a chronic granulomatous, nonlethal disease in immunocompetent frogs. Immunosuppression of the frogs with hydrocortisone results in an acute, fulminant, lethal disease. This animal model, in which a spectrum of tuberculosis-like disease can be produced, will be useful for the dissection of the genetic basis of mycobacterial pathogenesis.