Miracle-dz/UniFAR-FTUs huggingface dataset:
Aberrant DR5 transport through disruption of lysosomal function suggests a novel mechanism for receptor activation

To examine reciprocal or unilateral implications between two cell destruction processes, autophagy and apoptosis, in 5-Fluorouracil (5-FU)-treated tumor cells, a combination of chemical inhibitors, RNAi and genetic approaches were used. In contrast to cancer cells harboring obstructed apoptosis, either at the DISC or the mitochondrial level, p53-deficiency generated signs of autophagy deregulation upon chemotherapy. On the other, hand disruption of lysosomal function by chloroquine, caused a profound decrease in apoptotic markers appearing in response to 5-FU. DR5, which is essential for 5-FU-induced apoptosis, accumulated in lysosomes and autophagosomes upon chloroquine treatment. Since neither 3-MA, RNAi of critical autophagy regulators or inhibition of cathepsins reversed apoptosis in a similar manner, it is likely that not autophagy per se but rather correct receptor transport is an important factor for 5-FU cytotoxicity. We found that apoptosis generated by TRAIL, the cognate ligand for DR5, remained unchanged upon chloroquine lysosomal interference, indicating that 5-FU activates the receptor by a discrete mechanism. In support, depletion of membrane cholesterol or hampering cholesterol transport drastically reduced 5-FU cytotoxicity. We conclude that targeting of lysosomes by chloroquine deregulates DR5 trafficking and abrogates 5-FU- but not TRAIL-stimulated cell elimination, hence suggesting a novel mechanism for receptor activation.
Longitudinal retention of anatomical knowledge in second‐year medical students

The Radboud University Medical Center has a problem‐based, learner‐oriented, horizontally, and vertically integrated medical curriculum. Anatomists and clinicians have noticed students’ decreasing anatomical knowledge and the disability to apply knowledge in diagnostic reasoning and problem solving. In a longitudinal cohort, the retention of anatomical knowledge gained during the first year of medical school among second‐year medical students was assessed. In May 2011, 346 medical students applied for the second‐year gastro‐intestinal (GI) tract course. The students were asked to participate in a reexamination of a selection of anatomical questions of an examination from October 2009. The examination consisted of a clinical anatomy case scenario and two computed tomography (CT) images of thorax and abdomen in an extended matching format. A total of 165 students were included for analysis. In 2011, students scored significantly lower for the anatomy examination compared to 2009 with a decline in overall examination score of 14.7% (±11.7%). Decrease in knowledge was higher in the radiological questions, compared to the clinical anatomy cases 17.5% (±13.6%) vs. 7.9% (±10.0%), respectively, d = 5.17. In both years, male students scored slightly better compared to female students, and decline of knowledge seems somewhat lower in male students (13.1% (±11.1%) vs. 15.5% (±12.0%), respectively), d = −0.21. Anatomical knowledge in the problem‐oriented horizontal and vertical integrated medical curriculum, declined by approximately 15% 1.5 year after the initial anatomy course. The loss of knowledge in the present study is relative small compared to previous studies. Anat Sci Educ 10: 242–248. © 2016 American Association of Anatomists.
Desmopressin for treatment of platelet dysfunction and reversal of antiplatelet agents: a systematic review and meta‐analysis of randomized controlled trials

Essentials The optimal management of patients with platelet dysfunction undergoing surgery is unclear. This meta‐analysis compared perioperative administration of desmopressin to placebo. Desmopressin reduced red cell transfusions, blood loss and risk of re‐operation due to bleeding. There were too few events to determine if there was a change in the risk of thrombotic events.
How should we compare different genomic estimates of the strength of inbreeding depression?

Yengo et al. (1) evaluate the ability of genomic measures of inbreeding to quantify inbreeding depression. The authors conclude that a measure of inbreeding based on “runs of homozygosity” ( F ROH) had low power and upwardly biased estimates of the amount of inbreeding depression compared with F HOM (a measure of homozygosity relative to Hardy–Weinberg proportions) and F UNI (correlation between uniting gametes; similar to F HOM but with strong weight given to homozygous rare alleles). However, differences among these measures of inbreeding, and how their simulations were parameterized, invalidate these conclusions. Yengo et al. (1) assume that regressions of phenotype ( y ) against F ROH are comparable to regressions of y against F UNI or F HOM … [↵][1]1To whom correspondence should be addressed. Email: martykardos{at}gmail.com. [1]: #xref-corresp-1-1
Purification of zebrafish erythrocytes as a means of identifying a novel regulator of haematopoiesis

Zebrafish embryos are useful to study haematopoietic gene function in vertebrates, although lack of antibodies to zebrafish proteins has limited the purification of specific cell populations. Here, we purified primitive zebrafish erythrocytes using 1, 5‐bis{[2‐(di‐methylamino)ethyl]amino}‐4, 8‐dihydroxyanthracene‐9, 10‐dione (DRAQ5TM), a DNA‐staining fluorescent dye. At 48‐h post‐fertilization, we sorted small‐sized cells from embryos using forward scatter and found that they consisted of DRAQ5high and DRAQ5low populations. DRAQ5high cells contained haemoglobin, lacked myeloperoxidase activity and expressed high levels of embryonic globin (hbae3 and hbbe1.1) mRNA, all characteristics of primitive erythrocytes. Following DRAQ5TM analysis of gata1:dsRed transgenic embryos, we purified primitive DRAQ5high dsRed+ erythrocytes from haematopoietic progenitor cells. Using this method, we identified docking protein 2 (Dok2) as functioning in differentiation of primitive erythrocytes. We conclude that DRAQ5TM‐based flow cytometry enables purification of primitive zebrafish erythrocytes.
Blood values of young Brazilian catfish Pseudoplatystoma corruscans (Agassiz, 1829)

The ranges and mean values of haematocrit, leucocrit, red cell, white cell and differential cell counts and serum protein concentration of young growing Pseudoplatystoma corruscans (n=6) were measured, and serum electrophoretic patterns on cellulose acetate described. Blood was obtained by puncture of the caudal vessels. Using routine staining methods, five different cell types could be distinguished by light microscopy. Mean total cell count was 1.29 x 10 6 cells.ml -1 , while mean plasma protein content was 11.82g. l -1 consisting of five major protein fractions. These haematological characteristics were established as a “working document” upon which to base more extensive studies.
Tristetraprolin disables prostate cancer maintenance by impairing proliferation and metabolic function

Tristetraprolin (TTP) is an RNA-binding protein that post-transcriptionally suppresses gene expression by delivering mRNA cargo to processing bodies (P-bodies) where the mRNA is degraded. TTP functions as a tumor suppressor in a mouse model of B cell lymphoma, and in some human malignancies low TTP expression correlates with reduced survival. Here we report important prognostic and functional roles for TTP in human prostate cancer. First, gene expression analysis of prostate tumors revealed low TTP expression correlates with patients having high-risk Gleason scores and increased biochemical recurrence. Second, in prostate cancer cells with low levels of endogenous TTP, inducible TTP expression inhibits their growth and proliferation, as well as their clonogenic growth. Third, TTP functions as a tumor suppressor in prostate cancer, as forced TTP expression markedly impairs the tumorigenic potential of prostate cancer cells in a mouse xenograft model. Finally, pathway analysis of gene expression data suggested metabolism is altered by TTP expression in prostate tumor cells, and metabolic analyses revealed that such processes are impaired by TTP, including mitochondrial respiration. Collectively, these findings suggest that TTP is an important prognostic indicator for prostate cancer, and augmenting TTP function would effectively disable the metabolism and proliferation of aggressive prostate tumors.
Beneficial Effect of Etidronate Therapy in Immobilized Hip Fracture Patients[Retracted]

OBJECTIVES Hip fracture is among the most common causes of acute immobilization in elderly patients leading to increased bone resorption, and elderly patients with hip fracture are at high risk for a subsequent hip fracture. DESIGN In this double-blind, randomized, prospective study, 80 female patients who were immobilized because of a hip fracture were divided into two groups. The etidronate group received oral administration of 200 mg/day etidronate for 2 wks starting 1 day after the surgery. Then, after a 9-wk intermission, etidronate administration was resumed for 2 wks. The placebo group received placebo in a similar manner. RESULTS At baseline, both groups had high serum concentrations of ionized calcium, high urinary deoxypyridinoline (D-Pyr) concentrations, and decreased calcitriol concentrations, suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of calcitriol. After treatment, serum calcitriol concentrations increased in the etidronate and placebo groups. The etidronate group had significant decreases in serum ionized calcium and urinary D-Pyr, and the placebo group had higher serum calcium and urinary D-Pyr concentrations. CONCLUSIONS Etidronate therapy inhibits bone resorption and improves calcium balance, and such therapy may prevent bone loss and reduce the risk of subsequent hip fracture.
Reliable pedestrian detection using a deep neural network trained on pedestrian counts

Pedestrian detection is an important task for applications like surveillance, driver assistance systems and autonomous driving. We present a novel approach for detecting pedestrians using a deep convolutional neural network (CNN) trained for counting pedestrians. Our method avoids the need for annotation of the position of the pedestrians in the training data via bounding boxes. The deconvolved outputs of the filters of the trained counting model are used to detect the pedestrians. The average miss rate values on the tested datasets were found to be in the same range as other methods in spite of a simpler training using only pedestrian counts. This method is found to be suitable for detecting pedestrians in crowded scenes with occlusion as well as less crowded scenes.
Monitoring Toxicity Associated with Parenteral Sodium Stibogluconate in the Day-Case Management of Returned Travellers with New World Cutaneous Leishmaniasi

Background Patients with New World cutaneous leishmaniasis (NWCL) caused by Leishmania Viannia are treated with parenteral sodium stibogluconate (SbV) to reduce the risk of development of mucocutanous leishmaniasis. Our centre manages patients with NWCL on an outpatient-basis. This study was conducted to assess the safety and efficacy of this approach. Methodology We reviewed records of 67 consecutive NWCL patients, aged 17–61 years, treated as day-cases with 20 mg/kg/day SbV for up to 28 days at our UK centre. Data had been collected in a standardised format at the time of treatment using a care-record tool. Patients reported adverse-effects daily using a structured questionnaire. Blood tests and electrocardiograms were performed twice weekly to monitor for toxicity. Principal Findings Parenteral SbV treatment was associated with an early, significant suppression of mean lymphocyte and platelet counts. By day four of treatment, lymphocytes reduced by 0.53×109/L (CI 0.29×109/L to 0.76×109/L, p<0.001), and platelets by 31,000/µL (CI 16,000/µL to 46,000/µL, p<0.001). SbV was further associated with significant elevation of serum alanine transaminase concentrations, with a mean peak rise of 107 iu/L by day 13 (CI 52 iu/L to 161 iu/L, p<0.001). These disturbances were temporary and did not result in adverse clinical events. Patient-described symptoms were cumulative and at three weeks of treatment, 59.6% of patients experienced myalgia and 29.8% malaise. Treatment adherence and clinical outcomes were comparable to inpatient treatment studies. A total of 1407 individual doses of SbV resulted in only 26 nights' hospital admission, a saving of 1381 bed-days compared to inpatient treatment. Conclusions/Significance In specialist centres, NWCL patients aged below 65 years and without co-morbidities can be safely and effectively treated without hospital admission. This reduces the cost of treatment, and is much preferred by patients. Twice weekly blood and electrocardiographic monitoring may be surplus to requirement in clinically well, low-risk patients.
Comparative Analysis of Major Mosquito Vectors Response to Seed-Derived Essential Oil and Seed Pod-Derived Extract from Acacia nilotica

Botanical metabolites are increasingly realized as potential replacements to chemical insecticides. In the present study, Acacia nilotica seed essential oil and seed pod solvent extracts were tested for bioefficacy against three important types of mosquitoes. Mortality was recorded 24 h post-treatment, while smoke toxicity of adult mosquitoes was recorded at 10 min intervals for 40 min. Seed pod powder was extracted with different solvents and hydrodistilled seed oil chemical constituents were determined by using Gas chromatography mass spectroscopy (GC-MS) -. Larvicidal and adulticidal efficacy of seed hydrodistilled essential oil and solvent extracts were tested against larval and adult mosquitoes. The seed hydrodistilled oil provided strong larvicidal activity against Anopheles stephensi, (LC50 (lethal concentration that kills 50% of the exposed larvae) = 5.239, LC90 (lethal concentration that kills 90% of the exposed larvae) = 9.713 mg/L); Aedes aegypti, (LC50 = 3.174, LC90 = 11.739 mg/L); and Culex quinquefasciatus, (LC50 = 4.112, LC90 = 12.325 mg/L). Smoke toxicities were 82% in Cx. quinquefasciatus, 90% in Ae. aegypti, and 80% mortality in An. stephensi adults, whereas 100% mortality was recorded for commercial mosquito coil. The GC-MS profile of seed essential oil from A. nilotica showed the presence of hexadecane (18.440%) and heptacosane (15.914%), which are the main and active compounds, and which may be involved in insecticidal activity. Overall findings suggest that the seed oil showed strong mosquitocidal activity against mosquito vectors and therefore may provide an ecofriendly replacement to chemical insecticides.
Stability, Strategy-Proofness, and Cumulative Offer Mechanisms

In many-to-one matching with contracts, agents on one side of the market, e.g., workers, can fulfill at most one contract, while agents on the other side of the market, e.g., firms, may desire multiple contracts. Hatfield and Molgrom [6] showed that when firms' preferences are substitutable and size monotonic, the worker-proposing cumulative offer mechanism is stable and strategy-proof (for workers). Recently, stable and strategy-proof matching has been shown to be possible in a number of real-world settings in which preferences are not necessarily substitutable (see, e.g., Sönmez ans Switzer, [13], Sönmez [12] Kamada and Kojima [7], and Aygün and Turhan [1]; this has motivated a search for weakened substitutability conditions that guarantee the existence of stable and strategy-proof mechanisms. Hatfield and Kojima [3] introduced unilateral substitutability and showed that when all firms' preferences are unilaterally substitutable (and size monotonic), the cumulative offer mechanism is stable and strategy-proof. Kominers and Sönmez [9] identified a novel class of preferences, called slot-specific priorities, and showed that if each firm's preferences are in this class, then the cumulative offer mechanism is again stable and strategy-proof. Subsequently, Hatfield and Kominers [4] developed a concept of substitutable completion and showed that when each firm's preferences admit a size monotonic substitutable completion, the cumulative offer mechanism is once more stable and strategy-proof. In this paper, we introduce three novel conditions---observable substitutability, observable size monotonicity, and non-manipulability via contractual terms---and show that when these conditions are satisfied, the cumulative offer mechanism is the unique mechanism that is stable and strategy-proof. Moreover, when the choice function of any firm fails one of our three conditions, we can construct unit-demand choice functions for the other firms such that no stable and strategy-proof mechanism exists. Our results give the first characterization of sufficient and necessary conditions for the guaranteed existence of stable and strategy-proof mechanisms for many-to-one matching with contracts. Our conditions are strictly weaker than the previously known sufficient conditions for the existence of stable and strategy-proof mechanisms; this enables new applications, as well as a new interpretation of prior models of matching with distributional constraints (Hatfield et al. [5]; see also Kamada and Kojima [7,8]). Additionally, our work gives a foundation for the use of cumulative offer mechanisms in many-to-one matching markets with contracts: Whenever a stable and strategy-proof matching mechanism exists, either it must coincide with a cumulative offer mechanism, or its stability and/or strategy-proofness depends crucially on some specific interdependence of preferences across hospitals that rules out certain unit-demand choice functions.
On the Complexity of the Minimum Cost Homomorphism Problem for Reflexive Multipartite Tournaments

For digraphs $D$ and $H$, a mapping $f: V(D)\dom V(H)$ is a homomorphism of $D$ to $H$ if $uv\in A(D)$ implies $f(u)f(v)\in A(H). $ For a fixed digraph $H$, the homomorphism problem is to decide whether an input digraph $D$ admits a homomorphism to $H$ or not, and is denoted as HOMP($H$). Digraphs are allowed to have loops, but not allowed to have parallel arcs. A natural optimization version of the homomorphism problem is defined as follows. If each vertex $u \in V(D)$ is associated with costs $c_i(u), i \in V(H)$, then the cost of the homomorphism $f$ is $\sum_{u\in V(D)}c_{f(u)}(u)$. For each fixed digraph $H$, we have the {\em minimum cost homomorphism problem for} $H$ and denote it as MinHOMP($H$). The problem is to decide, for an input graph $D$ with costs $c_i(u),$ $u \in V(D), i\in V(H)$, whether there exists a homomorphism of $D$ to $H$ and, if one exists, to find one of minimum cost. In a recent paper, we posed a problem of characterizing polynomial time solvable and NP-hard cases of the minimum cost homomorphism problem for acyclic multipartite tournaments with possible loops (w.p.l.). In this paper, we solve the problem for reflexive multipartite tournaments and demonstrate a considerate difficulty of the problem for the whole class of multipartite tournaments w.p.l. using, as an example, acyclic 3-partite tournaments of order 4 w.p.l. \footnote{This paper was submitted to Discrete Mathematics on April 6, 2007}
Machine Theory of Mind

Theory of mind (ToM; Premack & Woodruff, 1978) broadly refers to humans' ability to represent the mental states of others, including their desires, beliefs, and intentions. We propose to train a machine to build such models too. We design a Theory of Mind neural network -- a ToMnet -- which uses meta-learning to build models of the agents it encounters, from observations of their behaviour alone. Through this process, it acquires a strong prior model for agents' behaviour, as well as the ability to bootstrap to richer predictions about agents' characteristics and mental states using only a small number of behavioural observations. We apply the ToMnet to agents behaving in simple gridworld environments, showing that it learns to model random, algorithmic, and deep reinforcement learning agents from varied populations, and that it passes classic ToM tasks such as the "Sally-Anne" test (Wimmer & Perner, 1983; Baron-Cohen et al., 1985) of recognising that others can hold false beliefs about the world. We argue that this system -- which autonomously learns how to model other agents in its world -- is an important step forward for developing multi-agent AI systems, for building intermediating technology for machine-human interaction, and for advancing the progress on interpretable AI.
Targeting the hexosamine biosynthetic pathway and O-linked N-acetylglucosamine cycling for therapeutic and imaging capabilities in diffuse large B-cell lymphoma

The hexosamine biosynthetic pathway (HBP) requires two key nutrients glucose and glutamine for O-linked N-acetylglucosamine (O-GlcNAc) cycling, a post-translational protein modification that adds GlcNAc to nuclear and cytoplasmic proteins. Increased GlcNAc has been linked to regulatory factors involved in cancer cell growth and survival. However, the biological significance of GlcNAc in diffuse large B-cell lymphoma (DLBCL) is not well defined. This study is the first to show that both the substrate and the endpoint O-GlcNAc transferase (OGT) enzyme of the HBP were highly expressed in DLBCL cell lines and in patient tumors compared with normal B-lymphocytes. Notably, high OGT mRNA levels were associated with poor survival of DLBCL patients. Targeting OGT via small interference RNA in DLBCL cells inhibited activation of GlcNAc, nuclear factor kappa B (NF-κB), and nuclear factor of activated T-cells 1 (NFATc1), as well as cell growth. Depleting both glucose and glutamine in DLBCL cells or treating them with an HBP inhibitor (azaserine) diminished O-GlcNAc protein substrate, inhibited constitutive NF-κB and NFATc1 activation, and induced G0/G1 cell-cycle arrest and apoptosis. Replenishing glucose-and glutamine-deprived DLBCL cells with a synthetic glucose analog (ethylenedicysteine-N-acetylglucosamine [ECG]) reversed these phenotypes. Finally, we showed in both in vitro and in vivo murine models that DLBCL cells easily take up radiolabeled technetium-99m-ECG conjugate. These findings suggest that targeting the HBP has therapeutic relevance for DLBCL and underscores the imaging potential of the glucosamine analog ECG in DLBCL.
Seasonal Phenology of the Cerambycid Beetles of East Central Illinois

ABSTRACT We summarize field data on the species composition and seasonal phenology of the community of cerambycid beetles of east central Illinois. Data were drawn from field bioassays conducted during 2009–2012 that tested attraction of adult beetles of diverse species to a variety of synthetic pheromones and host plant volatiles. In total, 34,086 beetles of 114 species were captured, including 48 species from the subfamily Cerambycinae, 41 species from Lamiinae, 19 species from Lepturinae, 2 species from Spondylidinae, and 1 species each from Necydalinae, Parandrinae, Prioninae, and Disteniidae. Most of the best-represented species were attracted to pheromones that were included in field experiments, particularly species that use (R)-3-hydroxyhexan-2-one as a pheromone component. The species captured and their patterns of abundance and seasonal phenology were similar to those in an earlier study conducted in Pennsylvania. The most abundant species identified in both studies included the cerambycines Elaphidion mucronatum (Say), Neoclytus acuminatus acuminatus (F.), Neoclytus mucronatus mucronatus (F.), and Xylotrechus colonus (F.). Cerambycine species became active in an orderly progression from early spring to late fall, whereas most lamiine species were active in the summer and fall, and lepturine species were limited to the summer. Potential cross attraction between some cerambycine species that shared pheromone components may have been averted by differences in seasonal activity period and by minor pheromone components that acted as synergists for conspecifics, antagonists for heterospecifics, or both. These results provide quantitative data on the abundance and seasonal phenology of a large number of species.