Miracle-dz/UniFAR-FTUs huggingface dataset:
18F-FDG and 18F-FLT-PET Imaging for Monitoring Everolimus Effect on Tumor-Growth in Neuroendocrine Tumors: Studies in Human Tumor Xenografts in Mice

Introduction The mTOR inhibitor everolimus has shown promising results in some but not all neuroendocrine tumors. Therefore, early assessment of treatment response would be beneficial. In this study, we investigated the in vivo and in vitro treatment effect of everolimus in neuroendocrine tumors and evaluated the performance of 18F-FDG and the proliferation tracer 18F-FLT for treatment response assessment by PET imaging. Methods The effect of everolimus on the human carcinoid cell line H727 was examined in vitro with the MTT assay and in vivo on H727 xenograft tumors. The mice were scanned at baseline with 18F-FDG or 18F-FLT and then treated with either placebo or everolimus (5 mg/kg daily) for 10 days. PET/CT scans were repeated at day 1,3 and 10. Results Everolimus showed significant inhibition of H727 cell proliferation in vitro at concentrations above 1 nM. In vivo tumor volumes measured relative to baseline were significantly lower in the everolimus group compared to the control group at day 3 (126±6% vs. 152±6%; p = 0.016), day 7 (164±7% vs. 226±13%; p<0.001) and at day 10 (194±10% vs. 281±18%; p<0.001). Uptake of 18F-FDG and 18F-FLT showed little differences between control and treatment groups, but individual mean uptake of 18F-FDG at day 3 correlated with tumor growth day 10 (r2 = 0.45; P = 0.034), 18F-FLT mean uptake at day 1 correlated with tumor growth day 7 (r2 = 0.63; P = 0.019) and at day 3 18F-FLT correlated with tumor growth day 7 (r2 = 0.87; P<0.001) and day 10 (r2 = 0.58; P = 0.027). Conclusion Everolimus was effective in vitro and in vivo in human xenografts lung carcinoid NETs and especially early 18F-FLT uptake predicted subsequent tumor growth. We suggest that 18F-FLT PET can be used for tailoring therapy for neuroendocrine tumor patients through early identification of responders and non-responders.
Effects of Egg Storage Material and Storage Period on Hatchability in Japanese Quail

The present study aimed to determine the effects of different storage materials and storage period on some hatchability traits of Japanese quail (Cotumix cotumix japonica) eggs. A total of 32 male and 102 female quail (twelve weeks of ages) were housed in multiple-bird cages. Eggs laid were divided into three groups with respect to the period of storage (I = 1 st , 2 nd and 3 rd days, II = 6 th , 7 th and 8 th days, III = 12 th , 13 th and 14 th days) prior to incubation. A total of 816 eggs was stored in 3 different storage environments during each storage period (B = no use of any storage material, P = use of perlite, H = use of hay) and kept in environmental conditions, where the temperature was 21°C and relative humidity was 75%, prior to incubation. Statistical analyses were performed after the exclusion of values pertaining to non-fertile eggs (190 eggs) from the data set. The fertility rate of the eggs in the experiment was 76.7%. In the present study, the influence of storage material and different storage periods on egg weight loss were found to be statistically significant (p<0.01). Upon the comparison of hatchability of fertile eggs values, the influence of storage material was determined to be significant (p<0.05), and the influence of storage period was demonstrated to be significant (p<0.01). The storage materials used were determined not to have any influence on early and late embryonic death rates. Perlite was concluded to be safe for use in the storage of hatching eggs. The extension of the storage period (more than 8 days) resulted in decreased hatchability values of fertile eggs in each group.
Intravascular emboli is an independent risk factor for the prognosis of stage III colorectal cancer patients after radical surgery

Lymphovascular emboli is a prognostic factor in stage II CRC, but the significance of intravascular emboli (IVE) in stage III is unclear. Data from consecutive stage III CRC patients receiving radical surgery between January 2009 and November 2014 were retrospectively collected. The expression of CD133 was tested by immumohistochemical (IHC) staining. The potential prognosis risk factors were tested using univariate and multivariate survival analyses. IVE was significantly associated with CD133 expression (P < 0.001), gross tumor morphology (P = 0.001), histologic type (p < 0.001), lymph node status (pN) (p < 0.001), sub-class of stage III (p = 0.001), and serum CA199 level (p = 0.022). IVE, CD133 expression and lymph node status (pN) were independent risk factors for overall survival (OS) (p < 0.001, p = 0.003, and p = 0.008, respectively) and disease-free survival (DFS) (p < 0.001, p = 0.004, and p = 0.007, respectively) in stage III CRC. IVE might be an independent risk factor for the prognosis of stage III CRC patients after radical surgery. IVE might express a cancer stem cell (CSC) phenotype.
From the Bargaining Table to the Ballot Box: Political Effects of Right to Work Laws

Labor unions directly affect wages, employment, industrial structure, and inequality. But unions also influence the economy and labor market indirectly through their effects on politics, providing candidates with voters, volunteers, and contributions, and lobbying on public policy. We use the enactment of right-to-work laws---which weaken unions by removing agency shop protections---to estimate the effect of unions on politics and policy from 1980-2016. Comparing counties on either side of a state and right-to-work border to causally identify the effects of the state laws, we find that right-to-work laws reduce Democratic Presidential vote shares by 3.5 percentage points. We find similar effects in Senate, House, and Gubernatorial races, as well as on state legislative control. Turnout is also 2 percentage points lower in right-to-work counties after passage. Exploring the mechanisms, we find that right-to-work laws dampen organized labor contributions to Democrats and that potential Democratic voters are less likely to be contacted to vote. The weakening of unions also has large downstream effects: fewer working-class candidates serve in state legislatures and Congress, while state policy moves in a more conservative direction.
Kneser-Ney Smoothing on Expected Counts

Widely used in speech and language processing, Kneser-Ney (KN) smoothing has consistently been shown to be one of the best-performing smoothing methods. However, KN smoothing assumes integer counts, limiting its potential uses—for example, inside Expectation-Maximization. In this paper, we propose a generalization of KN smoothing that operates on fractional counts, or, more precisely, on distributions over counts. We rederive all the steps of KN smoothing to operate on count distributions instead of integral counts, and apply it to two tasks where KN smoothing was not applicable before: one in language model adaptation, and the other in word alignment. In both cases, our method improves performance significantly.
Unicorn: Continual Learning with a Universal, Off-policy Agent

Some real-world domains are best characterized as a single task, but for others this perspective is limiting. Instead, some tasks continually grow in complexity, in tandem with the agent's competence. In continual learning, also referred to as lifelong learning, there are no explicit task boundaries or curricula. As learning agents have become more powerful, continual learning remains one of the frontiers that has resisted quick progress. To test continual learning capabilities we consider a challenging 3D domain with an implicit sequence of tasks and sparse rewards. We propose a novel agent architecture called Unicorn, which demonstrates strong continual learning and outperforms several baseline agents on the proposed domain. The agent achieves this by jointly representing and learning multiple policies efficiently, using a parallel off-policy learning setup.
Local Cattle and Badger Populations Affect the Risk of Confirmed Tuberculosis in British Cattle Herds

Background The control of bovine tuberculosis (bTB) remains a priority on the public health agenda in Great Britain, after launching in 1998 the Randomised Badger Culling Trial (RBCT) to evaluate the effectiveness of badger (Meles meles) culling as a control strategy. Our study complements previous analyses of the RBCT data (focusing on treatment effects) by presenting analyses of herd-level risks factors associated with the probability of a confirmed bTB breakdown in herds within each treatment: repeated widespread proactive culling, localized reactive culling and no culling (survey-only). Methodology/Principal Findings New cases of bTB breakdowns were monitored inside the RBCT areas from the end of the first proactive badger cull to one year after the last proactive cull. The risk of a herd bTB breakdown was modeled using logistic regression and proportional hazard models adjusting for local farm-level risk factors. Inside survey-only and reactive areas, increased numbers of active badger setts and cattle herds within 1500 m of a farm were associated with an increased bTB risk. Inside proactive areas, the number of M. bovis positive badgers initially culled within 1500 m of a farm was the strongest predictor of the risk of a confirmed bTB breakdown. Conclusions/Significance The use of herd-based models provide insights into how local cattle and badger populations affect the bTB breakdown risks of individual cattle herds in the absence of and in the presence of badger culling. These measures of local bTB risks could be integrated into a risk-based herd testing programme to improve the targeting of interventions aimed at reducing the risks of bTB transmission.
A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes

The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya – either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells of diverse multicellular animals. Studies of Gcna-mutant C. elegans and mice indicate that GCNA has functioned in reproduction for at least 600 million years. Homology to IDR-containing proteins implicated in DNA damage repair suggests that GCNA proteins may protect the genomic integrity of cells carrying a heritable genome. DOI: http://dx.doi. org/10.7554/eLife.19993. 001
Understanding nomadic collaborative learning groups

The paper builds on the work of Rossito et al. (2014) on collaborative nomadic work to develop three categories of practice of nomadic collaborative learning groups. Our study is based on interviews, workshops and observations of two undergraduate student’s group practices engaged in self-organised, long-term collaborations within the frame of Problem and Project Based Learning. By analysing the patterns of nomadic collaborative learning we identify and discuss how the two groups of students incorporate mobile and digital technologies as well as physical and/or non-digital technologies into their group work. Specifically, we identify the following categories of nomadic collaborative learning practices: ‘orchestration of work phases, spaces and activities’, ‘the orchestration of multiple technologies’ and ‘orchestration of togetherness’. We found that for both groups of students there was a fluidity, situatedness and improvisational aspect to how they negotiate the orchestration of their work. Their ways of utilising space, places, technologies and activities over time was a complex interweaving of the digital and physical. We conclude by suggesting that the three categories of practice identified are important for deepening our understanding of nomadic collaborative learning groups.
Germ Cell Nuclear Factor Regulates Gametogenesis in Developing Gonads

Expression of germ cell nuclear factor (GCNF; Nr6a1), an orphan member of the nuclear receptor gene family of transcription factors, during gastrulation and neurulation is critical for normal embryogenesis in mice. Gcnf represses the expression of the POU-domain transcription factor Oct4 (Pou5f1) during mouse post-implantation development. Although Gcnf expression is not critical for the embryonic segregation of the germ cell lineage, we found that sexually dimorphic expression of Gcnf in germ cells correlates with the expression of pluripotency-associated genes, such as Oct4, Sox2, and Nanog, as well as the early meiotic marker gene Stra8. To elucidate the role of Gcnf during mouse germ cell differentiation, we generated an ex vivo Gcnf-knockdown model in combination with a regulated CreLox mutation of Gcnf. Lack of Gcnf impairs normal spermatogenesis and oogenesis in vivo, as well as the derivation of germ cells from embryonic stem cells (ESCs) in vitro. Inactivation of the Gcnf gene in vivo leads to loss of repression of Oct4 expression in both male and female gonads.
Col-OSSOS: z-Band Photometry Reveals Three Distinct TNO Surface Types

Several different classes of trans-Neptunian objects (TNOs) have been identified based on their optical and near-infrared colors. As part of the Colours of the Outer Solar System Origins Survey (Col-OSSOS), we have obtained g-, r-, and z-band photometry of 26 TNOs using Subaru and Gemini Observatories. Previous color surveys have not utilized z-band reflectance, and the inclusion of this band reveals significant surface reflectance variations between sub-populations. The colors of TNOs in g − r and r − z show obvious structure, and appear consistent with the previously measured bi-modality in g − r. The distribution of colors of the two dynamically excited surface types can be modeled using the two-component mixing models from Fraser & Brown. With the combination of g − r and r − z, the dynamically excited classes can be separated cleanly into red and neutral surface classes. In g − r and r − z, the two dynamically excited surface groups are also clearly distinct from the cold classical TNO surfaces, which are red, with and r − z ≲ 0.6, while all dynamically excited objects with similar g − r colors exhibit redder r − z colors. The z-band photometry makes it possible for the first time to differentiate the red excited TNO surfaces from the red cold classical TNO surfaces. The discovery of different r − z colors for these cold classical TNOs makes it possible to search for cold classical surfaces in other regions of the Kuiper Belt and to completely separate cold classical TNOs from the dynamically excited population, which overlaps in orbital parameter space.
Benefit–Cost Analysis of Foot-and-Mouth Disease Vaccination at the Farm-Level in South Vietnam

This study aimed to analyze the financial impact of foot-and-mouth disease (FMD) outbreaks in cattle at the farm-level and the benefit–cost ratio (BCR) of biannual vaccination strategy to prevent and eradicate FMD for cattle in South Vietnam. Production data were collected from 49 small-scale dairy farms, 15 large-scale dairy farms, and 249 beef farms of Long An and Tay Ninh province using a questionaire. Financial data of FMD impacts were collected using participatory tools in 37 villages of Long An province. The net present value, i.e., the difference between the benefits (additional revenue and saved costs) and costs (additional costs and revenue foregone), of FMD vaccination in large-scale dairy farms was 2.8 times higher than in small-scale dairy farms and 20 times higher than in beef farms. The BCR of FMD vaccination over 1 year in large-scale dairy farms, small-scale dairy farms, and beef farms were 11.6 [95% confidence interval (95% CI) 6.42–16.45], 9.93 (95% CI 3.45–16.47), and 3.02 (95% CI 0.76–7.19), respectively. The sensitivity analysis showed that varying the vaccination cost had more effect on the BCR of cattle vaccination than varying the market price. This benefit-cost analysis of biannual vaccination strategy showed that investment in FMD prevention can be financially profitable, and therefore sustainable, for dairy farmers. For beef cattle, it is less certain that vaccination is profitable. Additional benefit-cost analysis study of vaccination strategies at the national-level would be required to evaluate and adapt the national strategy to achieve eradication of this disease in Vietnam.
Glial M6B stabilizes the axonal membrane at peripheral nodes of Ranvier

Glycoprotein M6B and the closely related proteolipid protein regulate oligodendrocyte myelination in the central nervous system, but their role in the peripheral nervous system is less clear. Here we report that M6B is located at nodes of Ranvier in peripheral nerves where it stabilizes the nodal axolemma. We show that M6B is co‐localized and associates with gliomedin at Schwann cell microvilli that are attached to the nodes. Developmental analysis of sciatic nerves, as well as of myelinating Schwann cells/dorsal root ganglion neurons cultures, revealed that M6B is already present at heminodes, which are considered the precursors of mature nodes of Ranvier. However, in contrast to gliomedin, which accumulates at heminodes with or prior to Na+ channels, we often detected Na+ channel clusters at heminodes without any associated M6B, indicating that it is not required for initial channel clustering. Consistently, nodal cell adhesion molecules (NF186, NrCAM), ion channels (Nav1.2 and Kv7.2), cytoskeletal proteins (AnkG and βIV spectrin), and microvilli components (pERM, syndecan3, gliomedin), are all present at both heminodes and mature nodes of Ranvier in Gpm6b null mice. Using transmission electron microscopy, we show that the absence of M6B results in progressive appearance of nodal protrusions of the nodal axolemma, that are often accompanied by the presence of enlarged mitochondria. Our results reveal that M6B is a Schwann cell microvilli component that preserves the structural integrity of peripheral nodes of Ranvier.
Canonical and Noncanonical Actions of Arabidopsis Histone Deacetylases in Ribosomal RNA Processing

Histone deacetylases promote pre-rRNA processing by repressing the expression of key regulators and regulating rRNA methylation through direct binding to rRNA and snoRNAs. Ribosome biogenesis is a fundamental process required for all cellular activities. Histone deacetylases play critical roles in many biological processes including transcriptional repression and rDNA silencing. However, their function in pre-rRNA processing remains poorly understood. Here, we discovered a previously uncharacterized role of Arabidopsis thaliana histone deacetylase HD2C in pre-rRNA processing via both canonical and noncanonical manners. HD2C interacts with another histone deacetylase HD2B and forms homo- and/or hetero-oligomers in the nucleolus. Depletion of HD2C and HD2B induces a ribosome-biogenesis deficient phenotype and aberrant accumulation of 18S pre-rRNA intermediates. Our genome-wide analysis revealed that HD2C binds and represses the expression of key genes involved in ribosome biogenesis. Using RNA immunoprecipitation and sequencing, we further uncovered a noncanonical mechanism of HD2C directly associating with pre-rRNA and small nucleolar RNAs to regulate rRNA methylation. Together, this study reveals a multifaceted role of HD2C in ribosome biogenesis and provides mechanistic insights into how histone deacetylases modulate rRNA maturation at the transcriptional and posttranscriptional levels.
Characterization of the Ruler Protein Interaction Interface on the Substrate Specificity Switch Protein in the Yersinia Type III Secretion System*

Many pathogenic Gram-negative bacteria use the type III secretion system (T3SS) to deliver effector proteins into eukaryotic host cells. In Yersinia, the switch to secretion of effector proteins is induced first after intimate contact between the bacterium and its eukaryotic target cell has been established, and the T3SS proteins YscP and YscU play a central role in this process. Here we identify the molecular details of the YscP binding site on YscU by means of nuclear magnetic resonance (NMR) spectroscopy. The binding interface is centered on the C-terminal domain of YscU. Disrupting the YscU-YscP interaction by introducing point mutations at the interaction interface significantly reduced the secretion of effector proteins and HeLa cell cytotoxicity. Interestingly, the binding of YscP to the slowly self-cleaving YscU variant P264A conferred significant protection against autoproteolysis. The YscP-mediated inhibition of YscU autoproteolysis suggests that the cleavage event may act as a timing switch in the regulation of early versus late T3SS substrates. We also show that YscUC binds to the inner rod protein YscI with a dissociation constant (Kd) of 3.8 μm and with 1:1 stoichiometry. The significant similarity among different members of the YscU, YscP, and YscI families suggests that the protein-protein interactions discussed in this study are also relevant for other T3SS-containing Gram-negative bacteria.
Analysis of Optimal Sensor Positions for Activity Classification and Application on a Different Data Collection Scenario

This paper focuses on optimal sensor positioning for monitoring activities of daily living and investigates different combinations of features and models on different sensor positions, i.e., the side of the waist, front of the waist, chest, thigh, head, upper arm, wrist, and ankle. Nineteen features are extracted, and the feature importance is measured by using the Relief-F feature selection algorithm. Eight classification algorithms are evaluated on a dataset collected from young subjects and a dataset collected from elderly subjects, with two different experimental settings. To deal with different sampling rates, signals with a high data rate are down-sampled and a transformation matrix is used for aligning signals to the same coordinate system. The thigh, chest, side of the waist, and front of the waist are the best four sensor positions for the first dataset (young subjects), with average accuracy values greater than 96%. The best model obtained from the first dataset for the side of the waist is validated on the second dataset (elderly subjects). The most appropriate number of features for each sensor position is reported. The results provide a reference for building activity recognition models for different sensor positions, as well as for data acquired from different hardware platforms and subject groups.