Miracle-dz/UniFAR-FTUs huggingface dataset:
The linkages between photosynthesis, productivity, growth and biomass in lowland Amazonian forests

Understanding the relationship between photosynthesis, net primary productivity and growth in forest ecosystems is key to understanding how these ecosystems will respond to global anthropogenic change, yet the linkages among these components are rarely explored in detail. We provide the first comprehensive description of the productivity, respiration and carbon allocation of contrasting lowland Amazonian forests spanning gradients in seasonal water deficit and soil fertility. Using the largest data set assembled to date, ten sites in three countries all studied with a standardized methodology, we find that (i) gross primary productivity (GPP) has a simple relationship with seasonal water deficit, but that (ii) site‐to‐site variations in GPP have little power in explaining site‐to‐site spatial variations in net primary productivity (NPP) or growth because of concomitant changes in carbon use efficiency (CUE), and conversely, the woody growth rate of a tropical forest is a very poor proxy for its productivity. Moreover, (iii) spatial patterns of biomass are much more driven by patterns of residence times (i.e. tree mortality rates) than by spatial variation in productivity or tree growth. Current theory and models of tropical forest carbon cycling under projected scenarios of global atmospheric change can benefit from advancing beyond a focus on GPP. By improving our understanding of poorly understood processes such as CUE, NPP allocation and biomass turnover times, we can provide more complete and mechanistic approaches to linking climate and tropical forest carbon cycling.
Does aspirin use reduce the risk for cancer?

Recently, studies have reported that aspirin has chemopreventive properties. In this study, we used the Taiwan NHI database, which covers a population of 23 million (99.99%) Taiwanese from 2001 to 2011. This was a case–control study which identified 601,733 patients using ICD-9-CM codes who were diagnosed with cancer. Each case with 4 eligible controls was matched for age, sex, and index date and adjusted for confounding factors. The observed overall cancer risk (adjusted OR (AOR), 0.95; 95% CI 0.94 to 0.96) reduced with aspirin use, specifically, colorectal (AOR, 0.97; 95% CI 0.94 to 0.99) and digestive system (AOR, 0.96; 95% CI 0.94 to 0.98) cancers. Findings from the Asian population would contribute to the discussion on aspirin's safety profile.
Adenovirus-mediated knockdown of activin A receptor type 2A attenuates immune-induced hepatic fibrosis in mice and inhibits interleukin-17-induced activation of primary hepatic stellate cells

Fibrosis induces a progressive loss of liver function, thus leading to organ failure. Activins are secreted proteins that belong to the transforming growth factor (TGF)-β superfamily, which initiate signaling by binding to their two type II receptors: Activin A receptor type 2A (ACVR2A) and activin A receptor type 2B. Previous studies that have explored the mechanisms underlying immune-induced hepatic fibrosis have mainly focused on TGF-β signaling, not activin signaling. To investigate the role of the activin pathway in this disease, adenovirus particles containing short hairpin (sh)RNA targeting ACVR2A mRNA (Ad-ACVR2A shRNA) were administered to mice, which were chronically treated with concanavalin A (Con A). The pathological changes in the liver were evaluated with hematoxylin/eosin staining, Masson trichrome staining and immunohistochemical assay. The results detected an increase in serum activin A and liver ACVR2A in Con A-treated animals. Conversely, liver function was partially restored and fibrotic injury was attenuated when activin signaling was blocked. In addition, the activation of hepatic stellate cells (HSCs) in response to Con A was suppressed by Ad-ACVR2A shRNA, as evidenced by decreased α-smooth muscle actin, and type I and IV collagen expression. Furthermore, primary mouse HSCs (mHSCs) were activated when exposed to interleukin (IL)-17A or IL-17F, which are two major cytokines produced by cluster of differentiation 4+ T helper 17 cells. The levels of activin A, type I and IV collagen were determined with ELISA kits and the expression of fibrotic molecules was determined with western blot analysis. Conversely, blocking activin/ACVR2A impaired the potency of HSCs to produce collagens in response to IL-17s. In addition, C terminus phosphorylation of Smad2 on Ser465 and Ser467, induced by either Con A in the liver or by IL-17s in mHSCs, was partly inhibited when activin A/ACVR2A signaling was suppressed. Collectively, the present study demonstrated an involvement of activated activin A/ACVR2A/Smad2 signaling in immune-induced hepatic fibrosis.
Human mammaglobin: A specific marker for breast cancer prognosis.

PURPOSE In this study, we examined the expression of human mammaglobin (hMAM) mRNA and the protein levels in patients with breast cancer and their relationship with prognostic clinicopathological parameters. METHODS hMAM mRNA expression in leucocytes from peripheral blood samples from patients diagnosed with primary invasive breast cancer (IC), carcinoma in situ (CIS), or benign breast diseases was analyzed using RT-PCR. The hMAM protein levels and expression patterns in tissue from 3 patient groups were evaluated by immunohistochemical staining, and several non-breast neoplasms were selected as negative controls, undergoing the same examination. RESULTS The expression of hMAM mRNA was significantly higher in patients with IC or CIS compared to those with benign tumors (both<0.01). Immunohistochemical staining revealed similar results, where patients with IC or CIS had higher levels of hMAM protein (p<0.01 and p<0.01, respectively), while none of the negative controls expressed hMAM. Further analyses showed a strong correlation between hMAM protein/mRNA expression and clinicopathological factors, such as histological grade, clinical stage, and lymph node status, in patients with IC. CONCLUSION The hMAM mRNA and protein expression profiles validate the potential of hMAM as a specific marker for breast cancer diagnosis and target treatment delivery.
Renewal Monte Carlo: Renewal Theory Based Reinforcement Learning

In this paper, we present an online reinforcement learning algorithm, called Renewal Monte Carlo (RMC), for infinite horizon Markov decision processes with a designated start state. RMC is a Monte Carlo algorithm and retains the advantages of Monte Carlo methods including low bias, simplicity and ease of implementation while, at the same time, circumvents their key drawbacks of high variance and delayed (end of episode) updates. The key ideas behind RMC are as follows. First, under any reasonable policy, the reward process is ergodic. So, by renewal theory, the performance of a policy is equal to the ratio of expected discounted reward to the expected discounted time over a regenerative cycle. Second, by carefully examining the expression for performance gradient, we propose a stochastic approximation algorithm that only requires estimates of the expected discounted reward and discounted time over a regenerative cycle and their gradients. We propose two unbiased estimators for evaluating performance gradients—a likelihood ratio based estimator and a simultaneous perturbation based estimator—and show that for both estimators, RMC converges to a locally optimal policy. We also generalize the RMC algorithm to post-decision state models. We conclude by presenting numerical experiments on a randomly generated MDP and event driven communication.
Eucalyptus leaf extract inhibits intestinal fructose absorption, and suppresses adiposity due to dietary sucrose in rats

Sucrose is more lipogenic than starch, and the extreme ingestion of sucrose induces adiposity and obesity. The aim of this study was to examine the effect of the eucalyptus (Eucalyptus globulus) leaf extract (ELE) on adiposity due to dietary sucrose in rats. In addition, in this study, the effect of ELE on intestinal fructose absorption was also examined. Rats were fed a high-sucrose diet (75 % in calorie base) with or without ELE (10 g/kg diet) for 5 weeks. Body weight was lower in the rats receiving ELE than in the controls (342 (sd 37·9) v. 392 (sd 26·0) g (n 7); P<0·05). Furthermore, ELE resulted in decreases in the triacylglycerol concentrations in the plasma (1·44 (sd 0·448) v. 2·79 (sd 0·677) mmol/l (n 7); P<0·05) and liver (19·1 (sd 5·07) v. 44·1 (sd 16·28) μmol/g (n 7); P<0·05). In contrast, ELE did not show any significant effects in the rats fed a starch diet. When rats were orally given ELE 10 min before fructose administration, the intestinal fructose absorption, which was examined by measuring the elevated concentration of fructose in the portal vein at 30 min after the fructose administration, was significantly inhibited in a dose-dependent manner. Furthermore, in rats fed a high-fructose diet, the plasma and hepatic triacylglycerol concentrations were significantly decreased by ELE. These results indicate that ELE, which inhibits the intestinal fructose absorption, can suppress adiposity in rats that ingest large amounts of sucrose or fructose.
Automated plant species identification—Trends and future directions

Current rates of species loss triggered numerous attempts to protect and conserve biodiversity. Species conservation, however, requires species identification skills, a competence obtained through intensive training and experience. Field researchers, land managers, educators, civil servants, and the interested public would greatly benefit from accessible, up-to-date tools automating the process of species identification. Currently, relevant technologies, such as digital cameras, mobile devices, and remote access to databases, are ubiquitously available, accompanied by significant advances in image processing and pattern recognition. The idea of automated species identification is approaching reality. We review the technical status quo on computer vision approaches for plant species identification, highlight the main research challenges to overcome in providing applicable tools, and conclude with a discussion of open and future research thrusts.
Automated classification of text sentiment

The ability to identify sentiment in text, referred to as sentiment analysis, is one which is natural to adult humans. This task is, however, not one which a computer can perform by default. Identifying sentiments in an automated, algorithmic manner will be a useful capability for business and research in their search to understand what consumers think about their products or services and to understand human sociology. Here we propose two new Genetic Algorithms (GAs) for the task of automated text sentiment analysis. The GAs learn whether words occurring in a text corpus are either sentiment or amplifier words, and their corresponding magnitude. Sentiment words, such as 'horrible', add linearly to the final sentiment. Amplifier words in contrast, which are typically adjectives/adverbs like 'very', multiply the sentiment of the following word. This increases, decreases or negates the sentiment of the following word. The sentiment of the full text is then the sum of these terms. This approach grows both a sentiment and amplifier dictionary which can be reused for other purposes and fed into other machine learning algorithms. We report the results of multiple experiments conducted on large Amazon data sets. The results reveal that our proposed approach was able to outperform several public and/or commercial sentiment analysis algorithms.
Enhancing Placebo Effects in Somatic Symptoms Through Oxytocin

Objective Placebo effects relieve various somatic symptoms, but it is unclear how they can be enhanced to maximize positive treatment outcomes. Oxytocin administration may potentially enhance placebo effects, but few studies have been performed, and they have had conflicting findings. The study aim was to investigate the influence of positive verbal suggestions and oxytocin on treatment expectations and placebo effects for pain and itch. Methods One hundred eight female participants were allocated to one of the following four groups: (1) oxytocin with positive verbal suggestions, (2) placebo with positive verbal suggestions, (3) oxytocin without suggestions, and (4) placebo without suggestions. The administration of 24 IU oxytocin or a placebo spray was preceded by positive verbal suggestions regarding the pain- and itch-relieving properties of the spray or no suggestions, depending on group allocation. Pain was assessed with a cold pressor test, and itch was assessed with histamine iontophoresis. Results Positive verbal suggestions induced expectations of lower pain (F = 4.77, p = .031) and itch (F = 5.38, p = .022). Moreover, positive verbal suggestions elicited placebo analgesia (F = 5.48, p = .021) but did not decrease itch. No effect of oxytocin on the placebo effect or on expectations was found. Conclusions Positive suggestions induced placebo analgesia but oxytocin did not enhance the placebo effect. Study limitations are that we only included a female sample and a failure to induce placebo effect for itch. Future studies should focus on how oxytocin might influence placebo effects, taken into account the role of sex, dose-dependent effects, and various expectation manipulations. Trial registration: The study was registered as a clinical trial on www.trialregister. nl (number 6376).
A Neutrophil Proteomic Signature in Surgical Trauma Wounds

Non-healing wounds continue to be a clinical challenge for patients and medical staff. These wounds have a heterogeneous etiology, including diabetes and surgical trauma wounds. It is therefore important to decipher molecular signatures that reflect the macroscopic process of wound healing. To this end, we collected wound sponge dressings routinely used in vacuum assisted therapy after surgical trauma to generate wound-derived protein profiles via global mass spectrometry. We confidently identified 311 proteins in exudates. Among them were expected targets belonging to the immunoglobulin superfamily, complement, and skin-derived proteins, such as keratins. Next to several S100 proteins, chaperones, heat shock proteins, and immune modulators, the exudates presented a number of redox proteins as well as a discrete neutrophil proteomic signature, including for example cathepsin G, elastase, myeloperoxidase, CD66c, and lipocalin 2. We mapped over 200 post-translational modifications (PTMs; cysteine/methionine oxidation, tyrosine nitration, cysteine trioxidation) to the proteomic profile, for example, in peroxiredoxin 1. Investigating manually collected exudates, we confirmed presence of neutrophils and their products, such as microparticles and fragments containing myeloperoxidase and DNA. These data confirmed known and identified less known wound proteins and their PTMs, which may serve as resource for future studies on human wound healing.
Functional disruption of the Golgi apparatus protein ARF1 sensitizes MDA-MB-231 breast cancer cells to the antitumor drugs Actinomycin D and Vinblastine through ERK and AKT signaling

Increasing evidence indicates that the Golgi apparatus plays active roles in cancer, but a comprehensive understanding of its functions in the oncogenic transformation has not yet emerged. At the same time, the Golgi is becoming well recognized as a hub that integrates its functions of protein and lipid biosynthesis to signal transduction for cell proliferation and migration in cancer cells. Nevertheless, the active function of the Golgi apparatus in cancer cells has not been fully evaluated as a target for combined treatment. Here, we analyzed the effect of perturbing the Golgi apparatus on the sensitivity of the MDA-MB-231 breast cancer cell line to the drugs Actinomycin D and Vinblastine. We disrupted the function of ARF1, a protein necessary for the homeostasis of the Golgi apparatus. We found that the expression of the ARF1-Q71L mutant increased the sensitivity of MDA-MB-231 cells to both Actinomycin D and Vinblastine, resulting in decreased cell proliferation and cell migration, as well as in increased apoptosis. Likewise, the combined treatment of cells with Actinomycin D or Vinblastine and Brefeldin A or Golgicide A, two disrupting agents of the ARF1 function, resulted in similar effects on cell proliferation, cell migration and apoptosis. Interestingly, each combined treatment had distinct effects on ERK1/2 and AKT signaling, as indicated by the decreased levels of either phospho-ERK1/2 or phospho-AKT. Our results suggest that disruption of Golgi function could be used as a strategy for the sensitization of cancer cells to chemotherapy.
Broadening CD4+ and CD8+ T Cell Responses against Hepatitis C Virus by Vaccination with NS3 Overlapping Peptide Panels in Cross-Priming Liposomes

ABSTRACT Despite the introduction of effective drugs to treat patients with chronic hepatitis C virus (HCV) infection, a vaccine would be the only means to substantially reduce the worldwide disease burden. An incomplete understanding of how HCV interacts with its human host and evades immune surveillance has hampered vaccine development. It is generally accepted that in infected individuals, a narrow repertoire of exhausted T cells is a hallmark of persistent infection, whereas broad, vigorous CD4+ and CD8+ T cell responses are associated with control of acute hepatitis C. We employed a vaccine approach based on a mixture of peptides (pepmix) spanning the entire sequence of HCV nonstructural protein 3 (NS3) in cross-priming cationic liposomes (CAF09) to facilitate a versatile presentation of all possible T cell epitopes, regardless of the HLA background of the vaccine recipient. Here, we demonstrate that vaccination of mice with NS3 pepmix broadens the repertoire of epitope-specific T cells compared to the corresponding recombinant protein (rNS3). Moreover, vaccination with rNS3 induced only CD4+ T cells, whereas the NS3 pepmix induced a far more vigorous CD4+ T cell response and was as potent a CD8+ T cell inducer as an adenovirus-vectored vaccine expressing NS3. Importantly, the cellular responses are dominated by multifunctional T cells, such as gamma interferon-positive (IFN-γ+) tumor necrosis factor alpha-positive (TNF-α+) coproducers, and displayed cytotoxic capacity in mice. In conclusion, we present a novel vaccine approach against HCV, inducing a broadened T cell response targeting both immunodominant and potential subdominant epitopes, which may be key elements to counter T cell exhaustion and prevent chronicity. IMPORTANCE With at least 700,000 annual deaths, development of a vaccine against hepatitis C virus (HCV) has high priority, but the tremendous ability of the virus to dodge the human immune system poses great challenges. Furthermore, many chronic infections, including HCV infection, have a remarkable ability to drive initially strong CD4+ and CD8+ T cell responses against dominant epitopes toward an exhausted, dysfunctional state. Thus, new and innovative vaccine approaches to control HCV should be evaluated. Here, we report on a novel peptide-based nanoparticle vaccine strategy (NS3 pepmix) aimed at generating T cell immunity against potential subdominant T cell epitopes that are not efficiently targeted by vaccination with full-length recombinant protein (rNS3) or infection with HCV. As proof of concept, we found that NS3 pepmix excels in broadening the repertoire of epitope-specific, multifunctional, and cytotoxic CD4+ and CD8+ T cells compared to vaccination with rNS3, which generated only CD4+ T cell responses.
Statistically Weighted Voting Analysis of Microarrays for Molecular Pattern Selection and Discovery Cancer Genotypes

Summary We developed a methodological approach to genetic class discovery using gene expression microarray data, which is based a on statistically-oriented class-prediction method called Statistically Weighted Voting (SWV) analysis integrating with clinical risk factor and survival analyses, and statistics of Gene Ontology annotation terms which we use to validate candidate biomarker selection. Our approach provides a "voting" class prediction function constructed using the most informative and robust discrete segments (sub-regions) of all covariate ranges and their gradated pairs, which thus allows to model the interactions of variables (genes). We show here that the SWV-based methodology can be adapted for microarray data and profitably used to biomarker selection and discovered two genetic classes associated with essentially improvement of classical histological grade II of human breast cancer. Our findings show that small and reliable genetic grade signatures could improve an individual prognosis for patients with histologic grated II and, thus after further biomedical validation, be used in therapeutic planning for breast cancer patients.
ACPA IgG galactosylation associates with disease activity in pregnant patients with rheumatoid arthritis

Objectives Patients with autoantibody-positive rheumatoid arthritis (RA) are less likely to experience pregnancy-induced improvement of RA disease activity (DAS28-C reactive protein (CRP)) compared with patients with autoantibody-negative RA. Anti-citrullinated protein antibodies (ACPAs) are the most specific autoantibodies for RA. We previously demonstrated that disease improvement is associated with changes in total IgG glycosylation, which regulate antibody effector function. Therefore, we sought to analyse the ACPA-IgG glycosylation profile during pregnancy with the aim to understand the lower change of pregnancy-induced improvement of the disease in patients with autoantibody-positive RA. Methods ACPA-IgGs were purified from ACPA-positive patient sera (n=112) of the Pregnancy-induced Amelioration of Rheumatoid Arthritis cohort, a prospective study designed to investigate pregnancy-associated improvement of RA. The fragment crystallisable (Fc)glycosylation profile of ACPA-IgGs was characterised by mass spectrometry and compared with that of total IgG derived from the same patients or from ACPA-negative patients. Results All ACPA-IgG subclasses display significant changes in the level of galactosylation and sialylation during pregnancy, although less pronounced than in total IgG. The pregnancy-induced increase in ACPA-IgG galactosylation, but not sialylation, associates with lower DAS28-CRP. In ACPA-positive patients, no such association was found with changes in the galactosylation of total IgG, whereas in ACPA-negative patients changes in disease activity correlated well with changes in the galactosylation of total IgG. Conclusions In ACPA-positive RA, the pregnancy-induced change in galactosylation of ACPA-IgG, and not that of total IgG, associates with changes in disease activity. These data may indicate that in ACPA-positive patients the galactosylation of ACPA-IgG is of more pathogenic relevance than that of total IgG.
Identification and characterization of wheat stem rust resistance gene Sr21 effective against the Ug99 race group at high temperature

Wheat stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), is a devastating foliar disease. The Ug99 race group has combined virulence to most stem rust (Sr) resistance genes deployed in wheat and is a threat to global wheat production. Here we identified a coiled-coil, nucleotide-binding leucine-rich repeat protein (NLR) completely linked to the Ug99 resistance gene Sr21 from Triticum monococcum. Loss-of-function mutations and transgenic complementation confirmed that this gene is Sr21. Sr21 transcripts were significantly higher at high temperatures, and this was associated with significant upregulation of pathogenesis related (PR) genes and increased levels of resistance at those temperatures. Introgression of Sr21 into hexaploid wheat resulted in lower levels of resistance than in diploid wheat, but transgenic hexaploid wheat lines with high levels of Sr21 expression showed high levels of resistance. Sr21 can be a valuable component of transgenic cassettes or gene pyramids combining multiple resistance genes against Ug99.