Miracle-dz/UniFAR-FTUs huggingface dataset:
Local Attitudes towards Bear Management after Illegal Feeding and Problem Bear Activity

Simple Summary The “pot bears” received international media attention in 2010 after police discovered the intentional feeding of black bears during the investigation of an alleged marijuana-growing operation in Christina Lake, British Columbia. Residents of this small community were surveyed by phone twice over the following year, before and after government actions. This study aimed to understand local attitudes on how these bears should be managed and whether they differed from existing bear management policy. Results indicate a significant problem with the public view of wildlife feeding and a gap between public and expert opinion on relocation and killing of food-conditioned wildlife. Abstract The “pot bears” received international media attention in 2010 after police discovered the intentional feeding of over 20 black bears during the investigation of an alleged marijuana-growing operation in Christina Lake, British Columbia, Canada. A two-phase random digit dialing survey of the community was conducted in 2011 to understand local perspectives on bear policy and management, before and after a summer of problem bear activity and government interventions. Of the 159 households surveyed in February 2011, most had neutral or positive attitudes towards bears in general, and supported the initial decision to feed the food-conditioned bears until the autumn hibernation. In contrast to wildlife experts however, most participants supported relocating the problem bears, or allowing them to remain in the area, ahead of killing; in part this arose from notions of fairness despite the acknowledged problems of relocation. Most locals were aware of the years of feeding but did not report it, evidently failing to see it as a serious form of harm, even after many bears had been killed. This underscores the importance of preventive action on wildlife feeding and the need to narrow the gap between public and expert opinion on the likely effects of relocation versus killing.
Interstitial Lung Disease Associated with mTOR Inhibitors in Solid Organ Transplant Recipients: Results from a Large Phase III Clinical Trial Program of Everolimus and Review of the Literature

Interstitial lung disease (ILD) has been reported with the use of mammalian target of rapamycin inhibitors (mTORi). The clinical and safety databases of three Phase III trials of everolimus in de novo kidney (A2309), heart (A2310), and liver (H2304) transplant recipients (TxR) were searched using a standardized MedDRA query (SMQ) search for ILD followed by a case-by-case medical evaluation. A literature search was conducted in MEDLINE and EMBASE. Out of the 1,473 de novo TxR receiving everolimus in Phase III trials, everolimus-related ILD was confirmed in six cases (one kidney, four heart, and one liver TxR) representing an incidence of 0.4%. Everolimus was discontinued in three of the four heart TxR, resulting in ILD improvement or resolution. Outcome was fatal in the kidney TxR (in whom everolimus therapy was continued) and in the liver TxR despite everolimus discontinuation. The literature review identified 57 publications on ILD in solid organ TxR receiving everolimus or sirolimus. ILD presented months or years after mTORi initiation and symptoms were nonspecific and insidious. The event was more frequent in patients with a late switch to mTORi. In most cases, ILD was reversed after prompt mTORi discontinuation. ILD induced by mTORi is an uncommon and potentially fatal event warranting early recognition and drug discontinuation.
Serum‐derived exosomes from mice with highly metastatic breast cancer transfer increased metastatic capacity to a poorly metastatic tumor

Altered interaction between CD200 and CD200R represents an example of “checkpoint blockade” disrupting an effective, tumor‐directed, host response in murine breast cancer cells. In CD200R1KO mice, long‐term cure of EMT6 breast cancer, including metastatic spread to lung and liver, was achieved in BALB/c mice. The reverse was observed with 4THM tumors, an aggressive, inflammatory breast cancer, with increased tumor metastasis in CD200R1KO. We explored possible explanations for this difference. We measured the frequency of circulating tumor cells (CTCs) in peripheral blood of tumor bearers, as well as lung/liver and draining lymph nodes. In some cases mice received infusions of exosomes from nontumor controls, or tumor bearers, with/without additional infusions of anticytokine antibodies. The measured frequency of circulating tumor cells (CTCs) in peripheral blood was equivalent in the two models in WT and CD200R1KO mice. Increased metastasis in EMT6 tumor bearers was seen in vivo following adoptive transfer of serum, or serum‐derived exosomes, from 4THM tumor bearers, an effect which was attenuated by anti‐IL‐6, and anti‐IL‐17, but not anti‐TNFα, antibody. Anti‐IL‐6 also attenuated enhanced migration of EMT6 cells in vitro induced by 4THM serum or exosomes, or recombinant IL‐6. Exosome cytokine proteomic profiles responses in 4THM and EMT6 tumor‐bearing mice were regulated by CD200:CD200R interactions, with attenuation of both IL‐6 and IL‐17 in 4THM CD200tg mice, and enhanced levels in 4THM CD200R1KO mice. We suggest these cytokines act on the microenvironment at sites within the host, and/or directly on tumor cells themselves, to increase metastatic potential.
Aerobic Fitness Is Associated With Cardiomyocyte Contractile Capacity and Endothelial Function in Exercise Training and Detraining

Background—Physical fitness and level of regular exercise are closely related to cardiovascular health. A regimen of regular intensity-controlled treadmill exercise was implemented and withdrawn to identify cellular mechanisms associated with exercise capacity and maximal oxygen uptake (&OV0312;2max). Methods and Results—Time-dependent associations between cardiomyocyte dimensions, contractile capacity, and &OV0312;2max were assessed in adult rats after high-level intensity-controlled treadmill running for 2, 4, 8, and 13 weeks and detraining for 2 and 4 weeks. With training, cardiomyocyte length, relaxation, shortening, Ca2+ decay, and estimated cell volume correlated with increased &OV0312;2max (r =0.92, −0.92, 0.88, −0.84, 0.73; P <0.01). Multiple regression analysis identified cell length, relaxation, and Ca2+ decay as the main explanatory variables for V O2max (R2 =0.87, P <0.02). When training stopped, exercise-gained &OV0312;2max decreased 50% within 2 weeks and stabilized at 5% above sedentary controls after 4 weeks. Cardiomyocyte size regressed in parallel with &OV0312;2max and remained (9%) above sedentary after 4 weeks, whereas cardiomyocyte shortening, contraction/relaxation- and Ca2+ ransient time courses, and endothelium-dependent vasorelaxation regressed completely within 2 to 4 weeks of detraining. Cardiomyocyte length, estimated cell volume, width, shortening, and Ca2+decay and endothelium-dependent arterial relaxation all correlated with &OV0312;2max (r =.85, 0.84, 0.75, 0.63, −0.54, −0.37; P <0.01). Multiple regression identified cardiomyocyte length and vasorelaxation as the main determinants for regressed &OV0312;2max during detraining (R2 =0.76, P =0.02). Conclusions—Cardiovascular adaptation to regular exercise is highly dynamic. On detraining, most of the exercise-gained aerobic fitness acquired over 2 to 3 months is lost within 2 to 4 weeks. The close association between cardiomyocyte dimensions, contractile capacity, arterial relaxation, and aerobic fitness suggests cellular mechanisms underlying these changes.
Complementary Therapies in Allergic Rhinitis

Objective. To determine the prevalence of herbal treatment of allergic rhinitis. Methods. In this prospective study, patients who were diagnosed with perennial allergic rhinitis were questioned about their use of natural products/herbal therapies for their symptoms. Results. In total, 230 patients were enrolled. Overall, 37.3% of the patients stated that they had used natural products/herbal therapies at least once. Women were more likely than men to use herbal supplements (38.3% versus 32.4%). Ten different types of herbal supplements were identified, with stinging nettle (Urtica dioicath), black elderberry (Sambucus nigra), and Spirulina being the most common (12.6%, 6.1%, and 5.7%, resp.). Conclusion. This study found a high prevalence of herbal treatment usage for the relief of allergic rhinitis symptoms in Turkey. The herbal products identified in this study and in the literature are discussed.
Cross-tier, label-based security enforcement for web applications

This paper presents SELinks, a programming language focused on building secure multi-tier web applications. SELinks provides a uniform programming model, in the style of LINQ and Ruby on Rails, with language syntax for accessing objects residing either in the database or at the server. Object-level security policies are expressed as fully-customizable, first-class labels which may themselves be subject to security policies. Access to labeled data is mediated via trusted, user-provided policy enforcement functions. SELinks has two novel features that ensure security policies are enforced correctly and efficiently. First, SELinks implements a type system called Fable that allows a protected object's type to refer to its protecting label. The type system can check that labeled data is never accessed directly by the program without first consulting the appropriate policy enforcement function. Second, SELinks compiles policy enforcement code to database-resident user-defined functions that can be called directly during query processing. Database-side checking avoids transferring data to the server needlessly, while still allowing policies to be expressed in a customizable and portable manner. Our experience with two sizable web applications, a modelhealth-care database and a secure wiki with fine-grained security policies, indicates that cross-tier policy enforcement in SELinks is flexible, relatively easy to use, and, when compared to a single-tier approach, improves throughput by nearly an order of magnitude. SELinks is freely available.
miR-345 in Metastatic Colorectal Cancer: A Non-Invasive Biomarker for Clinical Outcome in Non-KRAS Mutant Patients Treated with 3rd Line Cetuximab and Irinotecan

Introduction MicroRNAs (miRNAs) have important regulatory functions in cellular processes and have shown promising potential as prognostic markers for disease outcome in patients with cancer. The aim of the present study was to find miRNA expression profiles in whole blood that were prognostic for overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan. Methods From 138 patients with mCRC in 3rd line therapy with cetuximab and irinotecan in a prospective phase II study, 738 pretreatment miRNAs were isolated and profiled from whole blood using the TaqMan MicroRNA Array v2.0. Mutation status of KRAS, BRAF, and PI3KCA was known. Results After Bonferroni adjustment, 6 miRNAs: (miR-345, miR-143, miR-34a*, miR-628-5p, miR-886-3p and miR-324-3p), were found associated with short OS. miR-345 was the strongest prognostic miRNA, significant in the full cohort and in the non-KRAS mutant population. miR-345, as a continuous variable in the full cohort, resulted in a hazard ratio (HR) of 2.38 per IQR (CI 95%: 1.8–3.1, P-value = 2.86e−07, Bonferroni adjusted, univariable analysis) and a HR = 1.75 per IQR (CI 95%: 1.24–2.48, P-Wald = 1.45e-03) in the multivariable analysis adjusted for gender, age, KRAS, PI3KCA and performance status. miR-345 was prognostic in progression-free survival (PFS) with a HR = 1.63 per IQR (CI 95%: 1.25–2.114, P-Wald = 2.92e-4) in the multivariable analysis. In addition, high miR-345 expression was associated with lack of response to treatment with cetuximab and irinotecan. Conclusion We identified miR-345 in whole blood as a potential biomarker for clinical outcome. MiR-345 was a single prognostic biomarker for both OS and PFS in all patients and also in the non-KRAS mutant population.
Conformational Effects on the Circular Dichroism of Human Carbonic Anhydrase II: A Multilevel Computational Study

Circular Dichroism (CD) spectroscopy is a powerful method for investigating conformational changes in proteins and therefore has numerous applications in structural and molecular biology. Here a computational investigation of the CD spectrum of the Human Carbonic Anhydrase II (HCAII), with main focus on the near-UV CD spectra of the wild-type enzyme and it seven tryptophan mutant forms, is presented and compared to experimental studies. Multilevel computational methods (Molecular Dynamics, Semiempirical Quantum Mechanics, Time-Dependent Density Functional Theory) were applied in order to gain insight into the mechanisms of interaction between the aromatic chromophores within the protein environment and understand how the conformational flexibility of the protein influences these mechanisms. The analysis suggests that combining CD semi empirical calculations, crystal structures and molecular dynamics (MD) could help in achieving a better agreement between the computed and experimental protein spectra and provide some unique insight into the dynamic nature of the mechanisms of chromophore interactions.
Assessing Unrealized Yield Potential of Maize Producing Districts in India

The projected demand of maize production in India in 2050 is 4–5 times of current production. With the scope for area expansion being limited, there is need for enhancement of yield. This calls for identifying areas where huge unrealized yield potential exists. With a view to address the issue, the present study delineates homogeneous agro-climatic zones for maize production system in India taking district as a unit and using the factors production, viz. climate, soil, season and irrigated area under the crop. There are 146 districts in India that grow maize as a major crop. They were divided into 26 zones using multivariate cluster analysis. Study of variation in yield between districts within a zone vis-a-vis crop management practices adopted in those districts was found useful in targeting the yield gaps. These findings can have direct relevance to the maize farmers and district level administrators.
How to tell if your cloud files are vulnerable to drive crashes

This paper presents a new challenge--verifying that a remote server is storing a file in a fault-tolerant manner, i.e., such that it can survive hard-drive failures. We describe an approach called the Remote Assessment of Fault Tolerance (RAFT). The key technique in a RAFT is to measure the time taken for a server to respond to a read request for a collection of file blocks. The larger the number of hard drives across which a file is distributed, the faster the read-request response. Erasure codes also play an important role in our solution. We describe a theoretical framework for RAFTs and offer experimental evidence that RAFTs can work in practice in several settings of interest.
Octopine and nopaline metabolism in Agrobacterium tumefaciens and crown gall tumor cells: role of plasmid genes

Crown gall tumors produced octopine or nopaline or neither compound, depending on the bacterial strain that incited the tumor. The genes specifying production of octopine or nopaline by the tumor were transferred to recipient bacterial strains when the large plasmid associated with virulence was transferred by either conjugation or deoxyribonucleic acid-mediated transformation. Our results, which confirm the work of others (Bomhoff et al., 1976; Goldman et al., 1968; Petit et al., 1970), indicate that, in general, the strains that utilize octopine induce tumors that synthesize octopine, and those that utilize nopaline induce tumors that synthesize nopaline. However, there were several notable exceptions. One class utilized both octopine and nopaline, but the tumors induced by these strains produced only nopaline. Another class utilized nopaline, but their tumors synthesized neither nopaline nor octopine. Mutants were isolated from a number of either octopine- or nopaline-utilizing strains that no longer could utilize the relevant guanido amino acid. These strains, which were mutant in the gene specifying octopine or nopaline oxidase, still retained the permease for these amino acids as well as virulence. Tumors induced by these mutants still synthesized approximately the same levels of octopine and nopaline as tumors induced by their parents. These results suggest that the plasmid gene that determines production of octopine or nopaline by the tumor is distinct from the plasmid gene that determines their catabolism by the bacteria.
Associations Between Retinal Pigment Epithelium and Drusen Volume Changes During the Lifecycle of Large Drusenoid Pigment Epithelial Detachments

Purpose Drusenoid pigment epithelial detachments (PEDs) are a defined path to atrophy in age-related macular degeneration (AMD). We analyzed the relationships between retinal pigment epithelium (RPE) and drusen volume changes during the PED lifecycle, using spectral-domain optical coherence tomography (SD-OCT). Methods Twenty-one cases of drusenoid PED tracked using SD-OCT through periods of growth and collapse were evaluated. Volumetric calculations and piece-wise linear regression analysis were used to determine the breakpoint between growth and collapse. Spectral-domain OCT scans were independently evaluated for the appearance of intraretinal hyperreflective foci, acquired vitelliform lesions (AVLs), and disruptions to the RPE+basal lamina band. Timing of these events with respect to the breakpoint was statistically evaluated. Morphometric characteristics of drusenoid PEDs were correlated with rate of PED collapse and final visual acuity. Results Mean age of subjects was 75.3 years and mean period of follow up was 4.1 years (median 4.5 years; range, 0.6–6.6 years). The lifecycle of drusenoid PEDs was asymmetric, in that the rate of collapse (0.199 mm3/month) is significantly faster (P < 0.001) than the rate of growth (0.022 mm3/month). Appearance of intraretinal hyperreflective foci and AVLs preceded the breakpoint (both P < 0.001). The timing of disruptions to the RPE+basal lamina band did not differ from the breakpoint (P = 0.510). Maximal height, volume, and diameter of drusenoid PEDs were inversely correlated with final visual acuity (all P < 0.001) and positively correlated with the rate of PED collapse (all P < 0.001). Conclusions Spectral-domain OCT signatures, plausibly attributable to anteriorly migrated RPE and disintegration of the RPE layer, precede or occur simultaneously with changes in volume of drusenoid PED during the lifecycle of this lesion.
Role of dual PI3/Akt and mTOR inhibition in Waldenstrom's Macroglobulinemia

Tumorigenesis occurs due to synergistic interactions from a complex of signal transduction processes, including multiple onco-proteins and tumor suppressors such as Ras, Myc, PI3K/Akt/mTOR, Her-2/Neu, p53 and PTEN. Specifically, the PI3K/Akt and mTOR pathways have been shown to play a pivotal role on the initiation and progression of malignancies, enhancing cell survival by stimulating cell proliferation, and inhibiting apoptosis. Therefore, it is critical to examine therapeutic agents that explicitly target both the PI3K/Akt and mTOR signaling cascades in diseases, such as Waldenstrom Macroglobulinemia (WM), that harbor activation of the PI3K/Akt pathway. We demonstrated that dual targeting of the PI3K and mTOR pathways by the novel inhibitor NVP-BEZ235, exhibited toxicity on WM cells by directly targeting the tumor clone and indirectly through an effect on the bone marrow milieu. These findings suggest that dual targeting of the PI3K and mTOR pathways is a better modality of targeted therapy for tumors that harbor activation of the PI3K/mTOR pathways, such as in WM.
Time course of structural changes at identified sensory neuron synapses during long-term sensitization in Aplysia

We have used the gill- and siphon-withdrawal reflex of Aplysia californica to explore the morphological basis of the synaptic plasticity that underlies long-term sensitization. In earlier studies (Bailey and Chen, 1983, 1988a), we described 2 classes of structural changes at identified sensory neuron synapses that occur following long- term sensitization: (1) increases in the number, size, and vesicle complement of active zones and (2) an overall increase in the total number of synaptic varicosities per sensory neuron. In the present study, we have begun to examine which of these anatomical changes might be necessary for the maintenance of long-term sensitization by exploring the time course over which they occur and, in particular, their duration relative to the persistence of the memory assessed behaviorally. Toward this end we have quantitated changes in both the total number of varicosities and their active zone morphology in single HRP-labeled sensory neurons taken from long-term sensitized and control animals at different intervals (1–2 d, 1 week, and 3 weeks) following training. We have found that long-term sensitized animals examined within 48 hr after the completion of training demonstrate an increase in the total number of varicosities per sensory neuron as well as an increase in the incidence, size, and vesicle complement of their synaptic active zones compared with control animals. The increase in the number of varicosities and active zones persists unchanged for at least 1 week, and the increase in active zone number is only partially reversed at the end of 3 weeks. (ABSTRACT TRUNCATED AT 250 WORDS)
Equivalent forgetting rates in long-term memory for diencephalic and medial temporal lobe amnesia

Amnesia can result from damage to either the midline diencephalon or the medial temporal lobe. An important related question has been whether these two forms of amnesia result in similar or different kinds of memory impairment. Earlier studies raised the possibility that differences might exist in the rate of forgetting within long-term memory, specifically, that the forgetting rate is normal in diencephalic amnesia but abnormally rapid in medial temporal lobe amnesia. In the present study, forgetting was studied in five amnesic patients with damage to the medial temporal lobe, six amnesic patients with damage to the diencephalon, and 10 normal subjects. One hundred twenty pictures were presented to the control subjects for 1 sec each and to the amnesic patients for 8 sec each. Retention was then tested after 10 min, 2 hr, and 30–32 hr using four different procedures for testing recognition memory. The different exposure times for the pictures succeeded in matching the performance scores of both groups of amnesic patients and the control subjects at the 10 min retention interval. Both groups of amnesic patients also performed similarly to control subjects at retention delays of 2 hr and 30–32 hr. In addition, performance was nearly identical, regardless whether recognition memory was assessed by asking subjects to select the new items or the old items. The findings emphasize the similarities between medial temporal lobe and diencephalic amnesia.