Miracle-dz/UniFAR-FTUs huggingface dataset:
Heterogeneity of resistance mutations detectable by next-generation sequencing in TKI-treated lung adenocarcinoma

EGFR-mutated lung adenocarcinomas routinely develop resistance to tyrosine kinase inhibitors (TKI). To better characterize the relative frequencies of the resistance mechanisms, we analyzed 48 EGFR-mutated TKI-resistant specimens from 41 patients. Next-generation sequencing of post-treatment specimens detected EGFR p.T790M in 31 (79%) of 39 patients, PIK3CA mutations in 10 (26%), EGFR p.S768_V769delinsIL in one, and KRAS p.G12C in one. Five PIK3CA mutations were outside of codons 542, 545, and 1047. Three of four pre-treatment specimens did not carry the PIK3CA mutation found in the post-treatment sample. Small cell carcinoma transformation was identified in four patients; none had p.T790M, including two where p.T790M was identified in the co-existing adenocarcinoma. In p.T790M-mutated specimens, the allele frequency was less than 5% in 24% of cases. p.T790M allele frequency was usually lower than that of the sensitizing mutation indicating that the resistance mutation was present either in a subset of cells or, if the sensitizing mutation was amplified, in a subset of the sensitizing alleles of a dominant clone. Eight patients had multiple resistance mutations, suggesting either multiple separate resistant clones or a single clone harboring multiple resistance mechanisms. PIK3CA mutations appear to be a more significant resistance mechanism than previously recognized.
Serologic survey of Toxoplasma gondii antibodies in cats (Felis catus) sold at live animal markets in Southwestern Nigeria

Toxoplasma gondii is a zoonotic parasite causing infection in humans and a wide range of mammals, with cats being the final and only host that excrete T. gondii-resistant oocysts to the environment. This study was designed to investigate the seroprevalence of antibodies to T. gondii in cats sold at Live Animal Markets (LAMs) in Ibadan, Osogbo and Offa, Southwestern Nigeria. Blood samples were randomly collected from 226 cats at these markets and separated sera were tested for the presence of antibodies (IgG) to T. gondii, using two-fold dilutions from 1:20 to 1:320 by the Modified Agglutination Test (MAT). Attributes were analysed using Chi-square and Fisher’s exact tests at P<0.05. Median age of cats was 4.0 months (range: 1–36 months). Of the 226 samples tested, only 10 (4.4%) were positive for anti-T. gondii IgG antibodies at the cut-off titre of 1:20. Nine (4.0%) gave a titre of 1:20; one (0.4%) gave 1:80 while none was positive at 1:40, 1:160 and 1:320 dilutions. Age and gender of cats was not significantly associated with T. gondii infection. Our results showed low prevalence of T. gondii infection in cats sold at LAMs in studied area and suggests confinement as an efficient way of limiting exposure of cats to infection sources.
An improved enzyme-linked immunosorbent assay (ELISA) for detection of Flavobacterium psychrophilum isolated from salmon and rainbow trout

A double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was developed in order to improve the diagnostic of the diseases caused by Flavobacterium psychrophilum in salmon and trout. With incubation steps of 1 hour at 37oC for coating antibodies and 30 minutes at 37oC for antigens and conjugates, the detection limit was in the range of 1 x 10 4 cells ml -1 . Strains isolated from salmon and rainbow trout were successfully identified in an individual ELISA, which confirms the validity of the method for detection of F. psychrophilum serotypes. This biotin-avidin short protocol ELISA could be the technique of choice for seroepidemiological studies because it is a specific, sensitive, rapid and inexpensive procedure.
Ratio of oleic to palmitic acid is a dietary determinant of thrombogenic and fibrinolytic factors during the postprandial state in men.

BACKGROUND The nature of dietary fats affects the postprandial activation of the hemostatic system. OBJECTIVE We investigated whether the ratio of oleic to palmitic acid [and that of monounsaturated to saturated fatty acids (MUFA:SFA)] in the diet affects postprandial concentrations of triacylglycerols, tissue factor (TF), fibrinogen, tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1). DESIGN We studied the effects of diets enriched in olive oil (ROO), high-palmitic sunflower oil (HPSO), butter, or a mixture of vegetable and fish oils (VEFO) on circulating concentrations of the aforementioned factors in 14 healthy men. The fats had ratios of oleic to palmitic acid (MUFA:SFA) of 6.83 (5.43), 2.36 (2.42), 0.82 (0.48), and 13.81 (7.08). RESULTS The largest and longest-lasting postprandial changes in plasma triacylglycerol concentrations were found with the butter-based diet (all P < 0.05). No correlation was observed between the net incremental area under the curve (netAUC) for triacylglycerol and the ratio of oleic to palmitic acid (or MUFA:SFA) in the dietary fats. The netAUCs for TF and PAI-1, however, were inversely related to the ratio of oleic to palmitic acid (and MUFA:SFA) in ROO, HPSO, butter, and VEFO. Similar results were found for the fibrinogen netAUC when VEFO was omitted from the analysis. The netAUC for t-PA was inversely correlated with postprandial concentrations of triacylglycerol. CONCLUSIONS Postprandial concentrations of TF, fibrinogen, and PAI-1 are associated with the ratio of oleic to palmitic acid (MUFA:SFA) in dietary fats. The postprandial t-PA response is related to postprandial concentrations of triacylglycerol.
Modeling the Toxicokinetics of Inhaled Toluene in Rats: Influence of Physical Activity and Feeding Status

Toluene is found in petroleum-based fuels and used as a solvent in consumer products and industrial applications. The critical effects following inhalation exposure involve the brain and nervous system in both humans and experimental animals, whether exposure duration is acute or chronic. The goals of this physiologically based pharmacokinetic (PBPK) model development effort were twofold: (1) to evaluate and explain the influence of feeding status and activity level on toluene pharmacokinetics utilizing our own data from toluene-exposed Long Evans (LE) rats, and (2) to evaluate the ability of the model to simulate data from the published literature and explain differing toluene kinetics. Compartments in the model were lung, slowly and rapidly perfused tissue groups, fat, liver, gut, and brain; tissue transport was blood-flow limited and metabolism occurred in the liver. Chemical-specific parameters and initial organ volumes and blood flow rates were obtained from the literature. Sensitivity analysis revealed that the single most influential parameter for our experimental conditions was alveolar ventilation; other moderately influential parameters (depending upon concentration) included cardiac output, rate of metabolism, and blood flow to fat. Based on both literature review and sensitivity analysis, other parameters (e.g., partition coefficients and metabolic rate parameters) were either well defined (multiple consistent experimental results with low variability) or relatively noninfluential (e.g. organ volumes). Rats that were weight-maintained compared to free-fed rats in our studies could be modeled with a single set of parameters because feeding status did not have a significant impact on toluene pharmacokinetics. Heart rate (HR) measurements in rats performing a lever-pressing task indicated that the HR increased in proportion to task intensity. For rats acclimated to eating in the lab during the day, both sedentary rats and rats performing the lever-pressing task required different alveolar ventilation rates to successfully predict the data. Model evaluation using data from diverse sources together with statistical evaluation of the resulting fits revealed that the model appropriately predicted blood and brain toluene concentrations with some minor exceptions. These results (1) emphasize the importance of experimental conditions and physiological status in explaining differing kinetic data, and (2) demonstrate the need to consider simulation conditions when estimating internal dose metrics for toxicity studies in which kinetic data were not collected.
A double dissociation revealing bidirectional competition between striatum and hippocampus during learning

The multiple memory systems framework proposes that distinct circuits process and store different sorts of information; for example, spatial information is processed by a circuit that includes the hippocampus, whereas certain forms of instrumental conditioning depend on the striatum. Disruption of hippocampal function can enhance striatum-dependent learning in some paradigms, which has been interpreted as evidence that these systems can compete with one another in an intact animal. However, it remains unclear whether such competition can occur in the opposite direction, as suggested by the multiple memory systems framework, or is unidirectional. We addressed this question using lesions and genetic manipulations in mice. Impairment of dorsal striatal function with either excitotoxic lesions or transgenic inhibition of the transcription factor cAMP response element-binding protein, which disrupts striatal synaptic plasticity, impaired striatum-dependent cued learning but enhanced hippocampus-dependent spatial learning. Conversely, excitotoxic lesions of the dorsal hippocampus disrupted spatial learning and enhanced cued learning. This double dissociation demonstrates bidirectional competition that constitutes strong evidence for the parallel operation of distinct memory systems.
Structural transformations of alumina by high energy ball milling

Room temperature, high energy ball milling was applied to various transition aluminas ( γ, K, χ) , producing thermodynamically stable α-alumina–a phenomenon that could otherwise be achieved only by high temperature (1100–1200 °C) heat treatment. The transformation proceeds in two steps. The first one consists of rapid microstructural rearrangements with continuously increasing α-transformation rate. In the second step (1–2 h from the start), only relatively small changes in morphology are observed with a constant α-transformation rate. The rate is influenced only by the milling intensity. The presence or the absence of oxygen in the milling atmosphere has a large influence on the final surface area of α-alumina.
Mean angular diameters, distances and pulsation modes of the classical Cepheids FF Aql and T Vul - CHARA/FLUOR near-infrared interferometric observations

We report the first angular diameter measurements of two classical Cepheids, FF Aql and T Vul, that we have obtained with the FLUOR instrument installed at the CHARA interferometric array. We obtain average limb-darkened angular diameters of \theta_LD = 0.878 +/- 0.013 mas and \theta_LD = 0.629 +/- 0.013 mas, respectively for FF Aql and T Vul. Combining these angular diameters with the HST-FGS trigonometric parallaxes leads to linear radii R = 33.6 +/- 2.2 Rsol and R = 35.6 +/- 4.4 Rsol, respectively. The comparison with empirical and theoretical Period-Radius relations leads to the conclusion that these Cepheids are pulsating in their fundamental mode. The knowledge of the pulsation mode is of prime importance to calibrate the Period-Luminosity relation with a uniform sample of fundamental mode Cepheids.
Dead Block Prediction Considered Not Useful

Dead block predictors (DBPs) improve cache efficiency by identifying blocks that have exhausted their useful lifetime in the cache and prioritizing them for eviction regardless of how much reuse these blocks have experienced. In doing so, DBPs go beyond insertion policies that target only those blocks that have no cache reuse. But how much value do DBPs add over insertion policies? This work examines the opportunity for DBP at the LLC and concludes that its value-add is low over a state-of-the-art insertion policy. Our key result is that LLC evictions are dominated by blocks having no reuse. Even with the optimal replacement policy that maximizes cache reuse through perfect knowledge of the future, an average of 78% of LLC evictions have not experienced any hits. For the remaining evictions that experience LLC reuse, only a fraction is predicted by a state-of-the-art DBP scheme, and the accuracy of these predictions is low. Our first-order limit study shows that a likely coverage ceiling for DBP over the best performing insertion policy is just 6.9% of all LLC evictions. Based on these findings, we argue that the higher complexity of DBP is not justified.
A global analysis of the impacts of urbanization on bird and plant diversity reveals key anthropogenic drivers

Urbanization contributes to the loss of the world's biodiversity and the homogenization of its biota. However, comparative studies of urban biodiversity leading to robust generalities of the status and drivers of biodiversity in cities at the global scale are lacking. Here, we compiled the largest global dataset to date of two diverse taxa in cities: birds (54 cities) and plants (110 cities). We found that the majority of urban bird and plant species are native in the world's cities. Few plants and birds are cosmopolitan, the most common being Columba livia and Poa annua. The density of bird and plant species (the number of species per km2) has declined substantially: only 8% of native bird and 25% of native plant species are currently present compared with estimates of non-urban density of species. The current density of species in cities and the loss in density of species was best explained by anthropogenic features (landcover, city age) rather than by non-anthropogenic factors (geography, climate, topography). As urbanization continues to expand, efforts directed towards the conservation of intact vegetation within urban landscapes could support higher concentrations of both bird and plant species. Despite declines in the density of species, cities still retain endemic native species, thus providing opportunities for regional and global biodiversity conservation, restoration and education.
Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy.

PURPOSE Adjuvant chemotherapy has been associated with mild cognitive decline among a subset of breast cancer survivors. Late cognitive effects after chemotherapy can have a deleterious impact on survivor quality of life and functional health; however, the etiology of chemotherapy-related cognitive dysfunction remains unknown. PATIENTS AND METHODS We present a case of monozygotic twins who are discordant for breast cancer and chemotherapy exposure (ie, one twin contracted breast cancer and underwent chemotherapy, and the other had no breast cancer). As part of a larger study, each was evaluated with standardized, self-report measures of cognitive function, standard neuropsychological tests, and structural and functional magnetic resonance imaging (MRI). RESULTS Results indicated small differences in neuropsychological test performance but striking contrasts in self-reported cognitive complaints and structural and functional MRI images. Specifically, the twin who underwent chemotherapy had substantially more subjective cognitive complaints, more white matter hyperintensities on MRI, and an expanded spatial extent of brain activation during working memory processing than her nonaffected twin. CONCLUSION This case illustrates possible physiologic mechanisms that could produce long-term cognitive complaints among chemotherapy recipients and help formulate hypotheses for further empirical study in the area of chemotherapy-associated cognitive dysfunction.
Load Aware Self-Organising User-Centric Dynamic CoMP Clustering for 5G Networks

Coordinated multi-point (CoMP) is a key feature for mitigating inter-cell interference, improve system throughput, and cell edge performance. However, CoMP implementation requires complex beamforming/scheduling design, increased backhaul bandwidth, additional pilot overhead, and precise synchronization. Cooperation needs to be limited to a few cells only due to this imposed overhead and complexity. Hence, small CoMP clusters will need to be formed in the network. In this paper, we first present a self-organizing, user-centric CoMP clustering algorithm in a control/data plane separation architecture, proposed for 5G to maximize spectral efficiency (SE) for a given maximum cluster size. We further utilize this clustering algorithm and introduce a novel two-stage re-clustering algorithm to reduce high load on cells in hotspot areas and improve user satisfaction. Stage-1 of the algorithm utilizes maximum cluster size metric to introduce additional capacity in the system. A novel re-clustering algorithm is introduced in stage-2 to distribute load from highly loaded cells to neighboring cells with less load for multi-user joint transmission CoMP case. We show that unsatisfied users due to high load can be significantly reduced with minimal impact on SE.
Effects of Dietary Supplementation with the Combination of Zeolite and Attapulgite on Growth Performance, Nutrient Digestibility, Secretion of Digestive Enzymes and Intestinal Health in Broiler Chickens

This study was designed to investigate the effects of basal diets supplemented with a clay product consisting of zeolite and attapulgite (ZA) at 1:1 ratio on growth performance, digestibility of feed nutrients, activities of digestive enzymes in small intestine and intestinal health in broiler chickens. In experiment 1, 112 one-day-old male chickens were randomly divided into 2 groups with 8 replicates of 7 chickens each. In experiment 2, 84 one-day-old male chickens were randomly allocated into 2 groups consisting 6 replicates of 7 chickens each. The experimental diets both consisted of a maize-soybean basal control diet supplemented with 0% or 2% ZA. The diets were fed from 1 to 42 days of age. The results showed that ZA supplementation could increase body weight gain (BWG) and feed intake (FI), but had no significant effect on feed conversion ratio. The apparent digestibility values of crude protein and gross energy were significantly increased (p<0.05) by ZA from 14 to 16 d and 35 to 37 d. Dietary ZA treatment significantly increased (p<0.05) the activities of amylase, lipase and trypsin in jejunal digesta and the activities of maltase and sucrase in jejunal mucosa on days 21 and 42. The ZA supplementation also significantly increased (p<0.05) the catalase activity, reduced (p<0.05) the malondialdehyde concentration in the jejunal mucosa. In addition, a decrease of serum diamine oxidase activity and an increase (p<0.05) in concentration of secretory immunoglobulin A in jejunal mucosa were observed in birds treated with ZA on 21 and 42 days. It is concluded that ZA supplementation (2%) could partially improve the growth performance by increasing BWG and FI. This improvement was achieved through increasing the secretion of digestive enzymes, enhancing the digestibilites of nutrients, promoting intestinal health of broiler chickens.
Potential involvement of IL‐8 in the pathogenesis of human cytomegalovirus infection

The observations that several types of viruses induced interleukin (IL)‐8 production prompted us to investigate the interrelationship between IL‐8 and cytomegalovirus (CMV) infection. CMV infection caused IL‐8 production in a human monocytic cell line, THP‐1, in dose‐ and time‐dependent manners. Moreover, CMV induced IL‐8 gene expression by concurrently activating transcription factors, NF‐κB and AP‐1. Furthermore, CMV infection of human fibroblast cell lines increased gene expression of a specific receptor for IL‐8, CXCR1. IL‐8 in turn enhanced CMV replication in a human embryonic fibroblast, MRC‐5, in dose‐ and time‐dependent manners. Augmented replication eventually culminated in the increased production of infectious CMV virions. Moreover, IL‐8 can attenuate the antiviral activity of interferon (IFN), particularly that of α‐type against picornaviruses such as encephalomyocarditis virus and poliovirus. The inhibitory effects were associated with reduced 2′,5′‐A oligoadenylate synthetase activity. These results would imply that CMV can induce IL‐8, which can augment CMV replication directly and indirectly by counteracting antiviral activity of IFN. J. Leukoc. Biol. 64: 62–67; 1998.
All in the family ? CEO choice and firm organization

Family firms are the most prevalent firm type in the world, particularly in emerging economies. Dynastic family firms tend to have lower productivity relative to other firms, and the reasons behind this underperformance are still an open question. We collect new data on CEO successions for over 800 firms in Latin America and Europe to document their corporate governance choices and, crucially, provide the first causal evidence of the impact of having a family CEO on firm outcomes. Specifically, we establish two key results. First, there is a preference for male heirs in dynastic family CEO successions: when the founding CEO of a firm steps down they are 30% more likely to keep control within the family when they have a son. Second, instrumenting with the gender of the founder’s children we estimate dynastic CEO succession leads to -0.81 standard deviations worse management. Combined with a production function estimate of the relationship between management and productivity, this effect has an implied productivity decrease of 5 to 10%. We find lower skill levels of family CEOs only account for a small share of the gap in management performance. Thus, we propose a new mechanism based on family firms’ implicit employment commitments to their workforce. We build a model with two types of CEOs (family and professional) who decide whether to invest in good management practices. Family CEOs cannot credibly commit to firing employees without incurring a negative reputation cost. This induces lower worker effort and reduces the potential returns to investing in good management practices. We find empirical evidence that supports the idea that family firms are worse managed because of lower skill levels, but crucially also because of reputational constraints on their management practices. 1 ∗Corresponding author. We would like to thank CAF, Santander Travel Awards, Nuffield College, PEDL, The IGC, the World Bank and the IADB for funding various parts of this project. We also thank Carlos Lessa and the IBGE staff for access to the Brazilian Industrial Census (PIA). We are indebted to Abi Adams, Morten Bennedsen, Steve Bond, Serguey Braguinsky, Rachel Cassidy, Ian Crawford, Pascaline Dupas, Dave Donaldson, James Fenske, Katarzyna Habu, Michael Keane, Michael Koelle, Julien Labonne, Simon Quinn, Kalina Manova, Meg Meyer, Anna Sanktjohanser, Margaret Stevens and seminar audiences in Oxford, Stanford, IZA @ DC, UNSW, Stanford Empirical Management Conference, CSAE Conference, OxDev, RES Conference, RES Junior Symposium, Barcelona GSE Summer Forum, CCC at Bocconi, PacDev-Riverside, Toronto, York and Lindau Nobel Laureate Meetings for very helpful comments and discussions. We particularly thank Nick Bloom, Raffaella Sadun and John Van Reenen for their support over the years.
Impact of simple cheating in application-level multicast

We study the impact of cheating nodes in application-level multicast overlay trees. We focus on selfish nodes acting independently, cheating about their distance measurements during the control phase building or maintaining the tree. More precisely, we study, through simulations, the impact of simple cheating strategies in four protocols, representatives of different application-level multicast protocol "families": HBM (a protocol based on a centralized approach), TBCP (a distributed, tree first protocol), NICE (a distributed, tree first protocol based on clustering) and NARADA (a mesh first protocol). We evaluate the impact of cheats on the performance of the overlay trees as perceived by their nodes and the underlying network.