Miracle-dz/UniFAR-FTUs huggingface dataset:
The upper bound of cumulative return of a trading series

We present an upper bound of cumulative return in financial trading time series to formulate the most possible profit of many trades. The bound can be used to formally analyze the cumulative return varied by the number of trades, the mean return, and transaction cost rate. We also prove and show the validation of the upper bound, and verify the trend of cumulative return is consistent with that of the proposed bound via simulation experiments. Introducing a set of stochastic assessment methodology based on bootstrap into the organization of experimental data, we illustrate the influence on cumulative return from the relationship between the mean of return and transaction cost rate, technical trading rules, and stock indexes. To the best of our knowledge, this is the first to present and prove a bound of cumulative return of a stock trading series in theory. Both theoretical analyses and simulation experiments show the presented bound is a good mathematical tool to evaluate the trading risks and chances using given trading rules in stock trading markets.
A Direct Comparison of Theta Power and Frequency to Speed and Acceleration

Decades of hippocampal neurophysiology research have linked the hippocampal theta rhythm to voluntary movement. A consistent observation has been a robust correlation between the amplitude (or power) and frequency of hippocampal theta and running speed. Recently, however, it has been suggested that acceleration, not running speed, is the dominating influence on theta frequency. There is an inherent interdependence among these two variables, as acceleration is the rate of change in velocity. Therefore, we investigated theta frequency and amplitude of the local-field potential recorded from the stratum pyramidale, stratum radiatum, and stratum lacunosum moleculare of the CA1 subregion, considering both speed and acceleration in tandem as animals traversed a circular task or performed continuous alternation. In male and female rats volitionally controlling their own running characteristics, we found that running speed carries nearly all of the variability in theta frequency and power, with a minute contribution from acceleration. These results contradicted a recent publication using a speed-clamping task, where acceleration and movement are compelled through the use of a bottomless car (Kropff et al., 2021a). Therefore, we reanalyzed the speed-clamping data replicating a transient increase in theta frequency during acceleration. Compared with track running rats, the speed-clamped animals exhibited lower velocities and acceleration values but still showed a stronger influence of speed on theta frequency relative to acceleration. As navigation is the integration of many sensory inputs that are not necessarily linearly related, we offer caution in making absolute claims regarding hippocampal physiology from correlates garnered from a single behavioral repertoire. SIGNIFICANCE STATEMENT A long-standing, replicable observation has been the increase of hippocampal theta power and frequency with increasing running speed. Recently, however, an experimental approach that clamps the running speed of an animal has suggested that acceleration is the dominant influence. Therefore, we analyzed data from freely behaving rats as well as data from the speed-clamping experiment. In unrestrained behavior, speed remains the dominant behavioral correlate to theta amplitude and frequency. Positive acceleration in the speed-clamp experiment induced a transient increase in theta frequency and power. However, speed retained the dominant influence over theta frequency, changing with velocity in both acceleration and deceleration conditions.
Exploratory analysis of tumor imaging in a Phase 2 trial with cabozantinib in gastrointestinal stromal tumor: lessons learned from study EORTC STBSG 1317 ‘CaboGIST’

Abstract Background Gastrointestinal stromal tumors (GISTs) are malignant mesenchymal tumors arising in the gastrointestinal tract. Their systemic treatment is based on the use of tyrosine kinase inhibitors (TKIs) with imatinib, sunitinib, and regorafenib being the preferred agents. Assessment of tumor response to TKI treatment in GISTs is traditionally done according the Response Evaluation Criteria in Solid Tumors (RECIST), while Choi criteria have also been proposed as alternative tool assessing both volumetric and density changes on computer tomography (CT) scans. EORTC STBSG 1317 ‘CaboGIST’ was a single-arm prospective Phase 2 trial which met its primary endpoint, as 60% of patients previously treated with imatinib and sunitinib were progression-free at 12 weeks (95% CI 45–74%) based on local RECIST assessment. Materials and methods We report here an exploratory analysis of local versus central RECIST version 1.1 assessment and a comparison of RECIST version 1.1 versus Choi criteria. Results Comparisons between local and central RECIST version 1.1 at week 12 revealed discrepancies in 17/43 evaluable cases (39.5%). When comparing Choi with local and central RECIST version 1.1, discrepancies were observed in 27/43 (62.8%) and 21/43 (48.8%) cases, respectively. A total of 68% of evaluable patients were progression-free and alive at week 12 based on local RECIST, 84% according to central RECIST analysis and 81% when applying Choi criteria. Central assessment upgraded the treatment response both with RECIST version 1.1 and Choi. Conclusions The results of this exploratory analysis support the conclusion that cabozantinib is active in patients with metastatic or recurrent GIST after treatment with imatinib and sunitinib and confirm once again the limitations of RECIST to capture response to TKI in GIST, and the importance to include density changes in the response evaluation in this setting. Clinical trial number: EORTC 1317, NCT02216578
Trajectories of Insomnia Symptoms Among Aging Employees and Their Associations With Memory, Learning Ability, and Concentration After Retirement - A Prospective Cohort Study (2000–2017)

Objectives We applied a person-oriented approach and used latent class linear mixed models to identify sleep trajectories that explain memory, concentration, and learning ability problems after retirement. Methods Data consist of prospective surveys from four phases of the Helsinki Health Study between 2000–2017 (n = 3748, aged 55–77 years, 80% women). Multinomial regression was used to examine the associations between sleep trajectories and cognitive function, adjusting for sociodemographic, health-related behavior, and health factor covariates. Results Among statutory retirees, three latent group trajectories of insomnia-related symptoms were identified: stable low, decreasing, and increasing. Among those who had retired for disability reasons, we identified one additional latent group trajectory: stable high. Insomnia symptoms were associated with worse cognitive function. Discussion Early detection of insomnia symptoms would be a potential intervention point to improve both sleep quality and prevent cognitive decline in later life. However, intervention studies are needed.
DNA metabarcoding uncovers the diet of subterranean rodents in China

Objective A type of rodent called a zokor causes great harm to agriculture and forestry production due to its large and sophisticated diet. As this rodent lives subterrane for most of its life, researchers know little about its dietary habits. Further understanding of its diet is important for developing green and sustainable control strategies for the zokor. Methods Chloroplast trnL gene and internal transcription spacer 1 primers were selected for high-throughput sequencing of stomach contents of captured zokor by DNA metabarcoding. Results A total of 25 zokors were selected, the food list of 32 families, 80 genera, and 154 species was obtained. At the family level, it was found that zokors mainly fed on Asteraceae, Poaceae, Rosaceae, Pinaceae, Brassicaceae, and Apiaceae. At the genus level, zokors mainly fed on Echinops, Littledalea, Artemisia, Picea, Cirsium, and Elymus. The diet alpha diversity of Eospalax cansus was slightly higher than that of Eospalax cansus (P>0.05). The zokor’s diet is highly phconsistent with the resources of its habitat. Most food choices tend to be the same between the two zokors. They fed primarily on Calamagrostis, Cirsium, Echinops, Medicago, Sanguisorba, and Taraxacum. Zokors mainly fed on the roots of perennial herbs, which are important source of energy. Conclusion High-throughput sequencing-based DNA metabarcoding technology has effectively revealed the diet of zokors and indicated that zokors are food generalists.
StrategiesCell Life with Intracellular Targeting Combining a Strategy to Prolong Dendritic Enhancing DNA Vaccine Potency by

We have recently shown that intradermal coadministration of DNA encoding Ag with DNA encoding inhibitors of apoptosis, including Bcl-x L , prolongs dendritic cell (DC) life and thereby enhances the potency of DNA vaccines in vivo. We have also demonstrated that DNA vaccines targeting Ag to subcellular compartments, using proteins such as Mycobacterium tuberculosis heat shock protein 70, calreticulin, or the sorting signal of the lysosome-associated membrane protein type 1 (LAMP-1), enhanced DNA vaccine potency. In this study, we reasoned that the combination of a strategy to prolong DC life with intracellular targeting strategies might produce a more effective DNA vaccine against human papillomavirus E7. We showed that coadministration of DNA encoding Bcl-x L with DNA encoding E7/heat shock protein 70, calreticulin/E7, or Sig/E7/LAMP-1 resulted in further enhancement of the E7-speciﬁc CD8 (cid:1) T cell response for all three constructs. Of these strategies, mice vaccinated with Sig/E7/ LAMP-1 DNA mixed with Bcl-x L DNA showed the greatest increase in E7-speciﬁc CD8 (cid:1) T cells ( (cid:1) 13-fold increase). This combination of strategies resulted in increased CD8 (cid:1) T cell functional avidity, an increased E7-speciﬁc CD4 (cid:1) Th1 cell response, enhanced tumor treatment ability, and stronger long-term tumor protection when compared with mice vaccinated without Bcl-x L DNA. Therefore, DNA vaccines that combine strategies to enhance intracellular Ag processing and prolong DC life have potential clinical implications for control of viral infection and neoplasia. The Journal of Immunology, 2003, 171: 2970–2976. with ﬂow cytometry analysis and tumor treatment experiments were evaluated by ANOVA. Comparisons between individual data points were made using Student’s t test. In the tumor protection experiment, the principal outcome of interest was time to development of tumor. The event time distributions for different mice were compared by Kaplan and Meier and by log-rank analyses.
Puerarin protects against sepsis-induced myocardial injury through AMPK-mediated ferroptosis signaling

Objective: Research suggests that Puerarin may protect against sepsis-induced myocardial damage. However, the mechanisms responsible for Puerarin’s cardioprotective effect remain largely unclear. In this study, our objective is to investigate the role of Puerarin-induced AMPK-mediated ferroptosis signaling in protecting myocardial injury. Methods: 48 male Sprague-Dawley rats were randomly divided into four groups: control group, LPS group, LPS + Pue group, LPS + Pue + Era (Erastin, ferroptosis activator) group, or LPS + Pue + CC (compound C, AMPK inhibitor) group. During the experiment, cardiac systolic function indexes and myocardial histopathological changes were monitored. The serum levels of myocardial injury marker enzyme, inflammatory response related marker enzyme, and oxidative stress related-marker enzyme were measured with ELISA. Apoptotic cardiomyocytes, the iron content in myocardial tissue, apoptosis-related proteins, AMPK, and ferroptosis-related proteins were determined. Results: Puerarin inhibited the myocardial injury induced by LPS. The cardioprotective effects of Puerarin decreased after adding ferroptosis-activating compound Erastin. The protein expression levels of GPX4 and ferritin were down-regulated, whereas ACSL4, TFR, and heart iron content were up-regulated in LPS + Pue + Era group compared with LPS+Pue group. A significant difference was identified between LPS + Pue + Era group and LPS + Pue group in P-AMPK and T-AMPK levels. Meanwhile, after providing CC, P-AMPK/T-AMPK was significantly reduced, the protein expression levels of GPX4 and ferritin were down-regulated. ACSL4, TFR, and the heart iron content were up-regulated in LPS + Pue + CC group compared to LPS + Pue group. Conclusions: Puerarin protected against sepsis-induced myocardial injury, and AMPK-mediated ferroptosis signaling played a crucial role in its cardioprotective effect.
Impact of agile intuition on innovation behavior: Chinese evidence and a new proposal

With the tendency toward economic and strategy decoupling between China and the United States and amidst the anti-globalization trend, enterprises are facing unprecedented challenges and opportunities. In this study, we reveal how the agile intuition (AI) of top managers with respect to the external environment affects enterprise innovation behavior (IB) based on the cognition–behavior framework. Strategic learning (SL) is considered a moderator, and knowledge sharing (KS) is considered a mediator. The survey sample consists of 305 managers from 47 enterprises in China during the COVID-19 period. The empirical results show that top management agile intuition significantly promotes enterprise IB; knowledge sharing (KS) partially mediates the relationship between top manager AI and enterprise IB; and SL suppresses the promotion effect of top manager AI on enterprise IB to a certain extent, hindering blind innovation. In a surprising result, we find that strategic guidance by an external consultant does not significantly affect the enterprise IB in China.
Cell surface–tethered IL-12 repolarizes the tumor immune microenvironment to enhance the efficacy of adoptive T cell therapy

Immune-activating cytokines such as interleukin-12 (IL-12) hold strong potential for cancer immunotherapy but have been limited by high systemic toxicities. We describe here an approach to safely harness cytokine biology for adoptive cell therapy through uniform and dose-controlled tethering onto the surface of the adoptively transferred cells. Tumor-specific T cells tethered with IL-12 showed superior antitumor efficacy across multiple cell therapy models compared to conventional systemic IL-12 coadministration. Mechanistically, the IL-12–tethered T cells supported a strong safety profile by driving interferon-γ production and adoptively transferred T cell activity preferentially in the tumor. Immune profiling revealed that the tethered IL-12 reshaped the suppressive tumor immune microenvironment, including triggering a pronounced repolarization of monocytic myeloid-derived suppressor cells into activated, inflammatory effector cells that further supported antitumor activity. This tethering approach thus holds strong promise for harnessing and directing potent immunomodulatory cytokines for cell therapies while limiting systemic toxicities.
Circadian activities of the brain MNK‐eIF4E signalling axis contribute to diurnal rhythms of some cognitive functions

Although it is well recognized that the circadian timing system profoundly influences cognitive performance, the underlying molecular mechanisms remain poorly defined. Our previous work has found that the mitogen‐activated protein kinase‐interacting kinase (MNK)‐eukaryotic translation initiation factor 4E (eIF4E) axis, a conserved cellular signalling pathway regulating mRNA translation, modulates the function of the suprachiasmatic nucleus (SCN), the master circadian clock. Here, with the use of a combination of genetic, biochemical and behavioural approaches, we investigated the distribution and temporal regulation of eIF4E phosphorylation in the brain and its role in regulating the diurnal oscillations of some aspects of cognition in mice. We found that activities of the MNK‐eIF4E axis, as indicated by the level of eIF4E phosphorylation at Ser209, exhibited significant circadian oscillations in a variety of brain regions, including but not limited to the prefrontal cortex, the hippocampus, the amygdala and the cerebellum. Phosphorylated eIF4E was enriched in neurons but not in astrocytes or microglia. Mice lacking eIF4E phosphorylation (eIF4ES209A/S209A) or the MNKs (Mnk1−/−,2−/−), the kinases that phosphorylate eIF4E, exhibited impaired diurnal variations of novel object recognition, object location memory, Barnes maze learning and ambulatory activities. Together, these results suggest that circadian activities of the MNK‐eIF4E axis contribute to the diurnal rhythms of some cognitive functions, highlighting a role for rhythmic translational control in circadian regulation of cognitive performance.
Engineering cryoelectrospun elastin-alginate scaffolds to serve as stromal extracellular matrices

Scaffold-based regenerative strategies that emulate physical, biochemical, and mechanical properties of the native extracellular matrix (ECM) of the region of interest can influence cell growth and function. Existing ECM-mimicking scaffolds, including nanofiber (NF) mats, sponges, hydrogels, and NF-hydrogel composites are unable to simultaneously mimic typical composition, topography, pore size, porosity, and viscoelastic properties of healthy soft-tissue ECM. In this work, we used cryoelectrospinning to fabricate 3D porous scaffolds with minimal fibrous backbone, pore size and mechanical properties similar to soft-tissue connective tissue ECM. We used salivary glands as our soft tissue model and found the decellularized adult salivary gland (DSG) matrix to have a fibrous backbone, 10–30 μm pores, 120 Pa indentation modulus, and ∼200 s relaxation half time. We used elastin and alginate as natural, compliant biomaterials and water as the solvent for cryoelectrospinning scaffolds to mimic the structure and viscoelasticity of the connective tissue ECM of the DSG. Process parameters were optimized to produce scaffolds with desirable topography and compliance similar to DSG, with a high yield of >100 scaffolds/run. Using water as solvent, rather than organic solvents, was critical to generate biocompatible scaffolds with desirable topography; further, it permitted a green chemistry fabrication process. Here, we demonstrate that cryoelectrospun scaffolds (CESs) support penetration of NIH 3T3 fibroblasts 250–450 µm into the scaffold, cell survival, and maintenance of a stromal cell phenotype. Thus, we demonstrate that elastin-alginate CESs mimic many structural and functional properties of ECM and have potential for future use in regenerative medicine applications.
Computed tomography myelography technique and spinal morphometry in healthy Yucatan pigs

Porcine models of spinal cord injury (SCI) have an irreplaceable role in the development of experimental therapies. There is little literature regarding CT myelogram (CTM) techniques in swine and morphometry in miniature swine has not been established. A CT-guided method for performing myelography as well as reference values for spinal morphometry in healthy Yucatan miniature swine is lacking. The goal of this study is to describe a CT-guided method of performing CTM in a porcine model of SCI and to establish spinal morphometric reference values in mature Yucatan pigs. Six healthy, Yucatan sows, 9 months of age, weighing between 39–57.7kg, with no history of spinal disease, spinal injury, or neurologic deficits on physical exam were used in this study. CT myelography was performed in each sow under general anesthesia. CT scout images were used to guide needle placement at the L3-L4 intervertebral site. Once correct needle placement was confirmed using a 1ml test injection, a full dose of iodinated contrast (0.3ml/kg) was injected slowly over a 2-minute time period. Morphometry was performed using area measurements of the spinal cord (SC), vertebral body (VB), dural sac (DS), and vertebral canal (VC) at the mid-body and the intervertebral disc space of each spinal segment. Of the quantitative measurements, the spinal cord surface area had the widest range of values and the greatest coefficient of variance (CV) while those parameters for the vertebral canal had a low CV. Of the morphometric ratios, the DS:VC, had the lowest CV while the spinal cord ratios to DS and VC had the highest (>30). The vertebral canal surface area and the dural space: vertebral canal ratio may serve as reference values in future studies using this animal model.
Loss of METTL3 attenuates blastic plasmacytoid dendritic cell neoplasm response to PRMT5 inhibition via IFN signaling

Key Points PRMT5 is highly expressed in BPDCN, and pharmacological inhibition of PRMT5 activity disrupts splicing of key RNA methylation genes. Depletion of METTL3 diminishes BPDCN cell response to PRMT5 inhibition due to elevated IFN signaling mediated via the IRF7-IFIT1 axis.
Standardization of regulatory nodes for engineering heterologous gene expression: a feasibility study

The potential of LacI/Ptrc, XylS/Pm, AlkS/PalkB, CprK/PDB3 and ChnR/PchnB regulatory nodes, recruited from both Gram‐negative and Gram‐positive bacteria, as the source of parts for formatting expression cargoes following the Standard European Vector Architecture (SEVA) has been examined. The five expression devices, which cover most known regulatory configurations in bacteria were assembled within exactly the same plasmid backbone and bearing the different functional segments arrayed in an invariable DNA scaffold. Their performance was then analysed in an Escherichia coli strain of reference through the readout of a fluorescence reporter gene that contained strictly identical translation signal elements. This approach allowed us to describe and compare the cognate expression systems with quantitative detail. The constructs under scrutiny diverged considerably in their capacity, expression noise, inducibility and ON/OFF ratios. Inspection of such a variance exposed the different constraints that rule the optimal arrangement of functional DNA segments in each case. The data highlighted also the ease of standardizing inducer‐responsive devices subject to transcriptional activation as compared to counterparts based on repressors. The study resulted in a defined collection of formatted expression cargoes lacking any cross talk while offering a panoply of choices to potential users and help interoperability of the specific constructs.