Miracle-dz/UniFAR-FTUs huggingface dataset:
New Insights into Non-Avian Dinosaur Reproduction and Their Evolutionary and Ecological Implications: Linking Fossil Evidence to Allometries of Extant Close Relatives

It has been hypothesized that a high reproductive output contributes to the unique gigantism in large dinosaur taxa. In order to infer more information on dinosaur reproduction, we established allometries between body mass and different reproductive traits (egg mass, clutch mass, annual clutch mass) for extant phylogenetic brackets (birds, crocodiles and tortoises) of extinct non-avian dinosaurs. Allometries were applied to nine non-avian dinosaur taxa (theropods, hadrosaurs, and sauropodomorphs) for which fossil estimates on relevant traits are currently available. We found that the reproductive traits of most dinosaurs conformed to similar-sized or scaled-up extant reptiles or birds. The reproductive traits of theropods, which are considered more bird-like, were indeed consistent with birds, while the traits of sauropodomorphs conformed better to reptiles. Reproductive traits of hadrosaurs corresponded to both reptiles and birds. Excluding Massospondylus carinatus , all dinosaurs studied had an intermediary egg to body mass relationship to reptiles and birds. In contrast, dinosaur clutch masses fitted with either the masses predicted from allometries of birds (theropods) or to the masses of reptiles (all other taxa). Theropods studied had probably one clutch per year. For sauropodomorphs and hadrosaurs, more than one clutch per year was predicted. Contrary to current hypotheses, large dinosaurs did not have exceptionally high annual egg numbers (AEN). Independent of the extant model, the estimated dinosaur AEN did not exceed 850 eggs (75,000 kg sauropod) for any of the taxa studied. This estimated maximum is probably an overestimation due to unrealistic assumptions. According to most AEN estimations, the dinosaurs studied laid less than 200 eggs per year. Only some AEN estimates obtained for medium to large sized sauropods were higher (200-400 eggs). Our results provide new (testable) hypotheses, especially for reproductive traits that are insufficiently documented or lacking from the fossil record. This contributes to the understanding of their evolution.
Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis

Background Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. Methods We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. Results We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. Conclusion The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group.
Molecular Pathways: Oncologic Pathways and Their Role in T-cell Exclusion and Immune Evasion—A New Role for the AXL Receptor Tyrosine Kinase

With the clinical impact of CTLA-4 and PD-1/PD-L1 immune checkpoint therapies, widespread interest in cancer immunotherapy has been ignited. However, the rate and extent of clinical responses to approved therapies are limited and often nonexistent in many solid tumors. This is partially because immune checkpoint therapies are most effective against T-cell–inflamed tumors, and non–T-cell–inflamed or T-cell–excluded tumors remain a significant barrier. New strategies are needed to overcome immune resistance mechanisms that arise during tumor development, which result in T-cell exclusion. Approaches may need to be combined with conventional therapies such as chemotherapy, radiotherapy, and molecularly targeted therapy, and many clinical trials are ongoing. This review discusses the challenge of T-cell exclusion and innate oncologic pathways that contribute to this problem, including β-catenin, STAT3, NF-κB, PTEN, and AXL tyrosine kinase. The GAS6/AXL pathway is of interest immunologically, as its targeting can lead to greater antitumor immune responses after radiotherapy. In addition, several targeted therapies that are selective and nonselective for AXL are in preclinical and clinical development in acute myelogenous leukemia and renal cell cancer. There remains much to learn, but the future is bright for anti-AXL therapies, though effective combinations and their impact may not be realized for years to come. Clin Cancer Res; 23(12); 2928–33. ©2017 AACR.
Age-Associated Differences in Infection of Human Skin in the SCID Mouse Model of Varicella-Zoster Virus Pathogenesis

ABSTRACT Varicella-zoster virus (VZV) is the skin-tropic human alphaherpesvirus responsible for both varicella-zoster and herpes zoster. Varicella-zoster and herpes zoster skin lesions have similar morphologies, but herpes zoster occurs disproportionally in older individuals and is often associated with a more extensive local rash and severe zoster-related neuralgia. We hypothesized that skin aging could also influence the outcome of the anterograde axonal transport of VZV to skin. We utilized human skin xenografts maintained in immunodeficient (SCID) mice to study VZV-induced skin pathology in vivo in fetal and adult skin xenografts. Here we found that VZV replication is enhanced in skin from older compared to younger adults, correlating with clinical observations. In addition to measures of VZV infection, we examined the expression of type I interferon (IFN) pathway components in adult skin and investigated elements of the cutaneous proliferative and inflammatory response to VZV infection in vivo. Our results demonstrated that VZV infection of adult skin triggers intrinsic IFN-mediated responses such as we have described in VZV-infected fetal skin xenografts, including MxA as well as promyelocytic leukemia protein (PML), in skin cells surrounding lesions. Further, we observed that VZV elicited altered cell signaling and proliferative and inflammatory responses that are involved in wound healing, driven by follicular stem cells. These cellular changes are consistent with VZV-induced activation of STAT3 and suggest that VZV exploits the wound healing process to ensure efficient delivery of the virus to keratinocytes. Adult skin xenografts offer an approach to further investigate VZV-induced skin pathologies in vivo. IMPORTANCE Varicella-zoster virus (VZV) is the agent responsible for both varicella-zoster and herpes zoster. Herpes zoster occurs disproportionally in older individuals and is often associated with a more extensive local rash and severe zoster-related neuralgia. To examine the effect of skin aging on VZV skin lesions, we utilized fetal and adult human skin xenografts maintained in immunodeficient (SCID) mice. We measured VZV-induced skin pathology, examined the expression of type I interferon (IFN) pathway components in adult skin, and investigated elements of the cutaneous proliferative and inflammatory response to VZV infection in vivo. Our results demonstrate that characteristics of aging skin are preserved in xenografts; that VZV replication is enhanced in skin from older compared to younger adults, correlating with clinical observations; and that VZV infection elicits altered cell signaling and inflammatory responses. Adult skin xenografts offer an approach to further investigate VZV-induced skin pathologies in vivo.
Comparison of the pharmacokinetics of two formulations of hydroxyethyl starch in healthy horses

A lower molecular weight and molar substitution formulation (130/0.4) of hydroxyethyl starch solution has been shown to have a more sustained effect on COP and similar hemodynamic effects as a higher molecular weight and molar substitution formulation (600/0.75) in healthy horses. In humans, these pharmacodynamic characteristics are coupled with more rapid clearance and decreased adverse coagulation effects and accumulation. The objective of this study was to determine and compare the pharmacokinetics of these two formulations in horses. Eight healthy horses were given a 10 mL/kg bolus of each formulation (600/0.75 and 130/0.4) of hydroxyethyl starch solution in a randomized crossover design. Blood was collected, and plasma was harvested for plasma levels over 24 h. Pharmacokinetic parameters for each horse were estimated from a noncompartmental analysis. Treatment with 600/0.75 resulted in a higher initial plasma concentration (C0 ), systemic half-life (t1/2 ), and overall drug exposure (AUC0-inf ) in addition to decreased elimination rate (β), volume of distribution (Vd), and clearance (CL), compared to treatment with 130/0.4 (P < 0.001). The pharmacokinetic findings combined with previous pharmacodynamics findings suggest that 130/0.4 can provide similar benefits to 600/0.75 with a lower risk of accumulation in the circulation.
Substance use and the treatment of resistant depression in adolescents.

OBJECTIVE Despite the known association between substance use disorders and major depressive disorder (MDD) among adolescents, little is known regarding substance use among adolescents with MDD. METHOD Youths with MDD who had not improved after an adequate selective serotonin reuptake inhibitor trial (N = 334) were enrolled in the Treatment of SSRI-Resistant Depression in Adolescents trial. Analyses examined substance use (via the Drug Use Severity Index) and changes therein in relation to treatment and depressive symptoms. Adolescents meeting substance use disorder criteria via the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version at baseline were excluded. RESULTS Substance use was common: 28.1% reported repeated experimentation at baseline. Substance-related impairment was associated with baseline depression severity, older age, physical/sexual abuse, family conflict, hopelessness, and comorbid oppositional defiant disorder/conduct disorder. There was significant improvement in substance-related impairment among adolescents who responded to MDD treatment. Baseline suicidal ideation was higher among the subjects who progressed to high substance-related impairment (≥ 75th percentile) versus those whose substance-related impairment remained low (< 75th percentile), and parental depressive symptoms predicted persistence of high substance-related impairment during the study. The MDD response was best among the adolescents with low 12 week substance-related impairment scores regardless of whether they had high or low baseline substance-related impairment. There were no significant differential effects of specific treatments, pharmacological or cognitive-behavioral therapy, on substance use. CONCLUSIONS Substance use is common among adolescents with treatment-resistant MDD. The subjects who had persistently low substance-related impairment or who demonstrated reduced substance-related impairment had better MDD treatment response, although the direction of this association is uncertain.
Decomposition of the finest root branching orders: linking belowground dynamics to fine-root function and structure

Root turnover is fastest in the finest roots of the root system (first root order). Additionally, tissue chemistry varies among even the finest root orders and between white roots and older, pigmented roots. Yet the effects of pigmentation and order on root decomposition have rarely been examined. We separated the first four root orders (all <1 mm) of four temperate tree species into three classes: white first- and second-order roots; pigmented first- and second-order roots; and pigmented third- and fourth-order roots. Roots were enclosed in litterbags and buried under their own and under a common species canopy in a 34-year-old common garden in Poland. When comparing decomposition of different root orders over 36 months, pigmented third- and fourth-order roots with a higher C:N ratio decomposed more rapidly, losing 20–40% of their mass, than pigmented first- and second-order roots, which lost no more than 20%. When comparing decomposition of roots of different levels of pigmentation within the same root .
ACE Phenotyping as a Guide Toward Personalized Therapy With ACE Inhibitors

Background: Angiotensin-converting enzyme (ACE) inhibitors (ACEI) are widely used in the management of cardiovascular diseases but with significant interindividual variability in the patient’s response. Objectives: To investigate whether interindividual variability in the response to ACE inhibitors is explained by the “ACE phenotype”—for example, variability in plasma ACE concentration, activity, and conformation and/or the degree of ACE inhibition in each individual. Methods: The ACE phenotype was determined in plasma of 14 patients with hypertension treated chronically for 4 weeks with 40 mg enalapril (E) or 20 mg E + 16 mg candesartan (EC) and in 20 patients with hypertension treated acutely with a single dose (20 mg) of E with or without pretreatment with hydrochlorothiazide. The ACE phenotyping included (1) plasma ACE concentration; (2) ACE activity (with 2 substrates: Hip-His-Leu and Z-Phe-His-Leu and calculation of their ratio); (3) detection of ACE inhibitors in patient’s blood (indicator of patient compliance) and the degree of ACE inhibition (ie, adherence); and (4) ACE conformation. Results: Enalapril reduced systolic and diastolic blood pressure in most patients; however, 20% of patients were considered nonresponders. Chronic treatment results in 40% increase in serum ACE concentrations, with the exception of 1 patient. There was a trend toward better response to ACEI among patients who had a higher plasma ACE concentration. Conclusion: Due to the fact that “20% of patients do not respond to ACEI by blood pressure drop,” the initial blood ACE level could not be a predictor of blood pressure reduction in an individual patient. However, ACE phenotyping provides important information about conformational and kinetic changes in ACE of individual patients, and this could be a reason for resistance to ACE inhibitors in some nonresponders.
Candidatus Syngnamydia Venezia, a Novel Member of the Phylum Chlamydiae from the Broad Nosed Pipefish, Syngnathus typhle

Chlamydia are obligate intracellular bacteria and important pathogens of humans and animals. Chlamydia-related bacteria are also major fish pathogens, infecting epithelial cells of the gills and skin to cause the disease epitheliocystis. Given the wide distribution, ancient origins and spectacular diversity of bony fishes, this group offers a rich resource for the identification and isolation of novel Chlamydia. The broad-nosed pipefish (Syngnathus typhle) is a widely distributed and genetically diverse temperate fish species, susceptible to epitheliocystis across much of its range. We describe here a new bacterial species, Candidatus Syngnamydia venezia; epitheliocystis agent of S. typhle and close relative to other chlamydial pathogens which are known to infect diverse hosts ranging from invertebrates to humans.
Robust Predictive Current Control With Variable-Gain Adaptive Disturbance Observer for PMLSM

For high-velocity/high-precision linear motion systems, one of the most important factors that influence their dynamic performance is the characteristic of the inner current loop. The proportional–integral controller is the most practical strategy used for current control. However, its linear structure and imperfect decoupling capability make it difficult to obtain satisfying transient response under multiple operation conditions. The predictive current control (PCC) is designed as the current controller contributes to its superior performance. The main drawback of the PCC lies in its sensitivity against the unavoidable disturbances due to the parameters mismatch and the unmodeled dynamics. In this paper, an online adaptation-gain update method that can extend the inductance robust limit is proposed. First, by analyzing the closed-loop transfer function of the PCC system in the discrete domain, the effect of disturbances is discussed. Then, to eliminate the static current errors and improve the transient response, an adaptive disturbance observer is introduced. However, the direct dependence of the equivalent integral gain of the observer on the inductance in the controller leads to the deteriorative current response as the larger inductance mismatch exists. Therefore, an improved variable-gain method utilizing the current estimation errors is developed to reduce the current overshoot and the oscillation. Meanwhile, the design consideration for the two additional parameters of the proposed method is made by full-digital simulation. Finally, the effectiveness of the proposed method is uniformly verified with both simulation and experimental results.
The Heart Trumps the Head: Desirability Bias in Political Belief Revision

Understanding how individuals revise their political beliefs has important implications for society. In a preregistered study (N = 900), we experimentally separated the predictions of 2 leading theories of human belief revision—desirability bias and confirmation bias—in the context of the 2016 U.S. presidential election. Participants indicated who they desired to win, and who they believed would win, the election. Following confrontation with evidence that was either consistent or inconsistent with their desires or beliefs, they again indicated who they believed would win. We observed a robust desirability bias—individuals updated their beliefs more if the evidence was consistent (vs. inconsistent) with their desired outcome. This bias was independent of whether the evidence was consistent or inconsistent with their prior beliefs. In contrast, we found limited evidence of an independent confirmation bias in belief updating. These results have implications for the relevant psychological theories and for political belief revision in practice.
Automatic Control for Aircraft

ANOTHER step towards the elimination of the physical and nervous strain upon the pilot in a long flight, caused by his having to maintain continuous manual control over the machine, has just been accomplished by the linking up of several separate devices into one synchronized piece of apparatus for use in such cases. A De Havilland “Dragon” passenger aircraft has been acquired by Messrs. Air Travel and Survey, of Sydney, for photographic survey work. The technique of this demands that the machine must fly on a dead straight line and a level keel for periods, and an automatic pilot that can control this while the crew attend to other photographic duties has been in existence for some time. This apparatus in its latest form, known as a ‘deviator’, keeps the machine on a given course, but the direction of this must be controlled by the pilot. The new apparatus adds to this a Marconi Wireless 'homing' device which sets the aircraft's course in the direction of the transmitting station, when tuned in to that wave-length. The station would normally be an aerodrome with a special call sign, but ordinary broadcasting stations may be used, provided that the pilot can identify them. He thus has nothing to do except to watch and adjust the wireless receiving apparatus as necessary. This machine was successfully demonstrated on February 17 at Croydon. It brings within sight the day when the pilot of a big aircraft will merely have to exercise a general watch over the instruments in his cabin, more comparable with the manner in which the captain of a ship controls his craft.
High performance ES40-derived silica membranes for desalination

I Declaration by author . III Publications during candidature . IV Publications included in this thesis . IV Contributions by others to the thesis . VI Statement of parts of the thesis submitted to qualify for the award of another degree . VI Acknowledgements . VII
Gender, age, and concomitant diseases of melanosis coli in China: a multicenter study of 6,090 cases

Backgrounds and Aims Melanosis coli (MC) is a noninflammatory, benign, and reversible colonic disorder, but its detection rates in China are unclear. We therefore aimed to analyze the epidemiological characteristics of MC in China. Methods We assessed the detection rates, associated factors and concomitant diseases of MC in the patients who underwent colonoscopy at eight medical centers across five regions of China between January 2006 and October 2016. All data were procured from the electronic database established at each participating institutions. Results Among the 342,922 included cases, MC was detected in 6,090 cases (detection rate = 1.78%, 95% confidence interval, 1.73%–1.82%) at a mean age of 60 years. The detection rate gradually increased yearly, and along with the increasing age regardless of gender, while a rapid increase presented in the patients ≥60 years of age (0.58% for ≤25 years, 1.22% for 25–59 years, and 3.19% for ≥60 years). The detection rate was higher in females than in males; however, the rate of per-year increase was higher in males than in females at age of ≥60 years, which was 1.85-fold of that in females. Among cancer, polyp, inflammation, and diverticula, polyp was the most common concomitant disease of MC and identified in 41.72% of MC patients. Conclusions MC detection rates were increased annually and elevated in older patients, particularly in male patients. Males in the elderly population of ≥60 years were most likely to have MC. Colonic polyp is the most common concomitant disease of MC.
In Vitro Assessment of Total Phenolic and Flavonoid Contents, Antioxidant and Photoprotective Activities of Crude Methanolic Extract of Aerial Parts of Capnophyllum peregrinum (L.) Lange (Apiaceae) Growing in Algeria

Background: Capnophyllum peregrinum (L.) Lange (Apiaceae) is the unique taxon of capnophyllum genus in Algerian flora. It has never been investigated in regards to its total phenolic and flavonoid contents and antioxidant and photoprotective activities. Methods: C. peregrinum aerial parts extracted with absolute methanol. The total flavonoid and phenolic contents of the extract were evaluated to determine their correlation with the antioxidant and photoprotective activities of the extract. Results: The methanolic extract demonstrated a significant amount of phenolics and flavonoids (74.06 ± 1.23 mg GAE/g, 44.09 ± 2.13 mg QE/g, respectively) and exhibited good antioxidant activity in different systems, especially in 1,1-Diphenyl-2-picrylhydrazyl (DPPH), reducing power and total antioxidant capacity assays. Furthermore the extract showed high photoprotective activity with the sun protection factor (SPF) value = 35.21 ± 0.18. Conclusions: The results of the present study show, that the methanolic extract could be used as a natural sunscreen in pharmaceutics or cosmetic formulations and as a valuable source of natural antioxidants.