Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel JAZ co‐operativity and unexpected JA dynamics underpin Arabidopsis defence responses to Pseudomonas syringae infection

Summary Pathogens target phytohormone signalling pathways to promote disease. Plants deploy salicylic acid (SA)‐mediated defences against biotrophs. Pathogens antagonize SA immunity by activating jasmonate signalling, for example Pseudomonas syringae pv. tomato DC3000 produces coronatine (COR), a jasmonic acid (JA) mimic. This study found unexpected dynamics between SA, JA and COR and co‐operation between JAZ jasmonate repressor proteins during DC3000 infection. We used a systems‐based approach involving targeted hormone profiling, high‐temporal‐resolution micro‐array analysis, reverse genetics and mRNA‐seq. Unexpectedly, foliar JA did not accumulate until late in the infection process and was higher in leaves challenged with COR‐deficient P. syringae or in the more resistant JA receptor mutant coi1. JAZ regulation was complex and COR alone was insufficient to sustainably induce JAZs. JAZs contribute to early basal and subsequent secondary plant defence responses. We showed that JAZ5 and JAZ10 specifically co‐operate to restrict COR cytotoxicity and pathogen growth through a complex transcriptional reprogramming that does not involve the basic helix‐loop‐helix transcription factors MYC2 and related MYC3 and MYC4 previously shown to restrict pathogen growth. mRNA‐seq predicts compromised SA signalling in a jaz5/10 mutant and rapid suppression of JA‐related components on bacterial infection.
Microstructure and Mechanical Properties of 14Cr-ODS Steels with Zr Addition

Abstract In this study, oxide dispersion strengthened (ODS) ferritic steels with nominal composition of Fe–14Cr–2W–0.35Y2O3 (14Cr non Zr-ODS) and Fe–14Cr–2W–0.3Zr–0.35Y2O3 (14Cr–Zr-ODS) were fabricated by mechanical alloying (MA) and hot isostatic pressing (HIP) technique to explore the impact of Zr addition on the microstructure and mechanical properties of 14Cr-ODS steels. Microstructure characterization revealed that Zr addition led to the formation of finer oxides, which was identified as Y4Zr3O12, with denser dispersion in the matrix. The ultimate tensile strength (UTS) of the non Zr-ODS steel is about 1201 MPa, but UTS of the Zr-ODS steel increases to1372 MPa, indicating the enhancement of mechanical properties by Zr addition.
Predictors of ongoing implantation in IVF in a good prognosis group of patients.

BACKGROUND The aim of this study was to investigate whether, in a large randomized trial, it is possible to identify specific maternal and/or embryo variables that could independently correlate with ongoing implantation in IVF/ICSI. METHODS In a Scandinavian study, 661 women were randomized to elective single embryo transfer or double embryo transfer. Women aged <36 years undergoing their first or second IVF cycle and with at least two good quality embryos were eligible. Only one cycle per subject was included. In the present study, cycles with 0 or 100% ongoing implantation (n = 520) were analysed regarding maternal and embryo variables. RESULTS In this selected study group, the ongoing implantation rate was 195/734 (26.6%). In the univariate analysis, first IVF cycle, conventional IVF as fertilization method and 4-cell embryos showed a statistically higher ongoing implantation rate than did second IVF cycle, ICSI and non-4-cell embryos. In the multivariate analysis the same variables correlated independently to ongoing implantation. In addition, ovarian sensitivity correlated independently to ongoing implantation. CONCLUSION This information should be used when selecting the number of embryos for transfer with the overall aim to reduce the rate of multiple births while maintaining a satisfactory birth rate.
Retention of HIV-Infected Children in the First 12 Months of Anti-Retroviral Therapy and Predictors of Attrition in Resource Limited Settings: A Systematic Review

Current UNAIDS goals aimed to end the AIDS epidemic set out to ensure that 90% of all people living with HIV know their status, 90% initiate and continue life-long anti-retroviral therapy (ART), and 90% achieve viral load suppression. In 2014 there were an estimated 2.6 million children under 15 years of age living with HIV, of which only one-third were receiving ART. Little literature exists describing retention of HIV-infected children in the first year on ART. We conducted a systematic search for English language publications reporting on retention of children with median age at ART initiation less than ten years in resource limited settings. The proportion of children retained in care on ART and predictors of attrition were identified. Twelve studies documented retention at one year ranging from 71–95% amongst 31877 African children. Among the 5558 children not retained, 4082 (73%) were reported as lost to follow up (LFU) and 1476 (27%) were confirmed to have died. No studies confirmed the outcomes of children LFU. Predictors of attrition included younger age, shorter duration of time on ART, and severe immunosuppression. In conclusion, significant attrition occurs in children in the first 12 months after ART initiation, the majority attributed to LFU, although true outcomes of children labeled as LFU are unknown. Focused efforts to ensure retention and minimize early mortality are needed as universal ART for children is scaled up.
Immunogenicity of Recombinant Protective Antigen and Efficacy against Aerosol Challenge with Anthrax

ABSTRACT Immunization with a recombinant form of the protective antigen (rPA) from Bacillus anthracis has been carried out with rhesus macaques. Rhesus macaques immunized with 25 μg or more of B. subtilis-expressed rPA bound to alhydrogel had a significantly increased immunoglobulin G (IgG) response to rPA compared with macaques receiving the existing licensed vaccine from the United Kingdom (anthrax vaccine precipitated [AVP]), although the isotype profile was unchanged, with bias towards the IgG1 and IgG2 subclasses. Immune macaque sera from all immunized groups contained toxin-neutralizing antibody and recognized all the domains of PA. While the recognition of the N terminus of PA (domains 1 to 3) was predominant in macaques immunized with the existing vaccines (AVP and the U.S. vaccine anthrax vaccine adsorbed), macaques immunized with rPA recognized the N- and C-terminal domains of PA. Antiserum derived from immunized macaques protected macrophages in vitro against the cytotoxic effects of lethal toxin. Passive transfer of IgG purified from immune macaque serum into naive A/J mice conferred protection against challenge with B. anthracis in a dose-related manner. The protection conferred by passive transfer of 500 μg macaque IgG correlated significantly (P = 0.003; r = 0.4) with the titers of neutralizing antibody in donor macaques. Subsequently, a separate group of rhesus macaques immunized with 50 μg of Escherichia coli-derived rPA adsorbed to alhydrogel was fully protected against a target dose of 200 50% lethal doses of aerosolized B. anthracis. These data provide some preliminary evidence for the existence of immune correlates of protection against anthrax infection in rhesus macaques immunized with rPA.
Uterine artery blood flow, fetal hypoxia and fetal growth

Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success.
Corelease of nitric oxide and prostaglandins mediates flow-dependent dilation of rat gracilis muscle arterioles.

We have studied the mechanisms responsible for the mediation of flow (shear stress)-induced dilation of isolated arterioles of rat gracilis muscle. Active diameter of arterioles at a constant perfusion pressure (PP, 80 mmHg) was approximately 92 microns, while their passive diameter (Ca(2+)-free solution) was approximately 165 microns. At a constant PP the stepwise increase in flow of the perfusion solution (PS, 0-60 microliters/min in 10-microliters/min steps) elicited a gradual increase in diameter up to approximately 140 microns. Flow-induced dilations were eliminated by the removal of the endothelium of arterioles (by air). Dilations were significantly reduced by the cyclooxygenase blocker, indomethacin (Indo, 10(-5) M), by the nitric oxide synthase blocker, N omega-nitro-L-arginine (L-NNA, 10(-4) M), or by the endothelium-derived relaxing factor inhibitor, oxyhemoglobin (Hb, 10(-5) M), as indicated by the significant changes in the slope of the regression lines of the flow-diameter curves. For example, during administration of the inhibitors, dilation to 60 microliters/min perfusate flow was reduced by 41.1, 54.3, and 39.3%, respectively. Combined application of Indo and L-NNA almost completely eliminated flow-induced dilation. Arteriolar dilation maintained calculated wall shear stress close to control values (approximately 30 dyn/cm2 at 60 microliters/min) despite increases in flow, but when the dilation was inhibited by removal of the endothelium or by the combined administration of Indo and L-NNA, wall shear stress was greatly increased as a function of increases in flow of the PS (approximately 125 dyn/cm2). (ABSTRACT TRUNCATED AT 250 WORDS)
Local Delivery of Cannabinoid-Loaded Microparticles Inhibits Tumor Growth in a Murine Xenograft Model of Glioblastoma Multiforme

Cannabinoids, the active components of marijuana and their derivatives, are currently investigated due to their potential therapeutic application for the management of many different diseases, including cancer. Specifically, Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) – the two major ingredients of marijuana – have been shown to inhibit tumor growth in a number of animal models of cancer, including glioma. Although there are several pharmaceutical preparations that permit the oral administration of THC or its analogue nabilone or the oromucosal delivery of a THC- and CBD-enriched cannabis extract, the systemic administration of cannabinoids has several limitations in part derived from the high lipophilicity exhibited by these compounds. In this work we analyzed CBD- and THC-loaded poly-ε-caprolactone microparticles as an alternative delivery system for long-term cannabinoid administration in a murine xenograft model of glioma. In vitro characterization of THC- and CBD-loaded microparticles showed that this method of microencapsulation facilitates a sustained release of the two cannabinoids for several days. Local administration of THC-, CBD- or a mixture (1∶1 w:w) of THC- and CBD-loaded microparticles every 5 days to mice bearing glioma xenografts reduced tumour growth with the same efficacy than a daily local administration of the equivalent amount of those cannabinoids in solution. Moreover, treatment with cannabinoid-loaded microparticles enhanced apoptosis and decreased cell proliferation and angiogenesis in these tumours. Our findings support that THC- and CBD-loaded microparticles could be used as an alternative method of cannabinoid delivery in anticancer therapies.
Caenorhabditis elegans dnj-14, the orthologue of the DNAJC5 gene mutated in adult onset neuronal ceroid lipofuscinosis, provides a new platform for neuroprotective drug screening and identifies a SIR-2.1-independent action of resveratrol

Adult onset neuronal lipofuscinosis (ANCL) is a human neurodegenerative disorder characterized by progressive neuronal dysfunction and premature death. Recently, the mutations that cause ANCL were mapped to the DNAJC5 gene, which encodes cysteine string protein alpha. We show here that mutating dnj-14, the Caenorhabditis elegans orthologue of DNAJC5, results in shortened lifespan and a small impairment of locomotion and neurotransmission. Mutant dnj-14 worms also exhibited age-dependent neurodegeneration of sensory neurons, which was preceded by severe progressive chemosensory defects. A focussed chemical screen revealed that resveratrol could ameliorate dnj-14 mutant phenotypes, an effect mimicked by the cAMP phosphodiesterase inhibitor, rolipram. In contrast to other worm neurodegeneration models, activation of the Sirtuin, SIR-2.1, was not required, as sir-2.1; dnj-14 double mutants showed full lifespan rescue by resveratrol. The Sirtuin-independent neuroprotective action of resveratrol revealed here suggests potential therapeutic applications for ANCL and possibly other human neurodegenerative diseases.
A taxonomy framework for unsupervised outlier detection techniques for multi-type data sets

The term "outlier" can generally be defined as an observation that is significantly different from the other values in a data set. The outliers may be instances of error or indicate events. The task of outlier detection aims at identifying such outliers in order to improve the analysis of data and further discover interesting and useful knowledge about unusual events within numerous applications domains. In this paper, we report on contemporary unsupervised outlier detection techniques for multiple types of data sets and provide a comprehensive taxonomy framework and two decision trees to select the most suitable technique based on data set. Furthermore, we highlight the advantages, disadvantages and performance issues of each class of outlier detection techniques under this taxonomy framework.
Architectural Explorations for Modeling Procedural Skill Decay

There is great interest in mission-critical domains to minimize the decay of expert skill: the decrement in performance observed after a period of disuse. To better understand skill decay and to test theories and systems aimed at minimizing its effects, it is useful to create computational models capable of exhibiting its main effects. No models of expert knowledge (represented as production rules) skill decay have been developed within cognitive architectures. This work explores how skill decay might be realized within an architecture. It also discusses implementation issues with a focus on psychologicallyplausible approaches and explanations of skill decay effects. Although implemented in the EASE architecture, the issues discussed in this paper are relevant to all rule-learning, production-system based cognitive architectures.
Finite-Time Input-to-State Stability and Applications to Finite-Time Control Design

This paper extends the well-known concept, Sontag's input-to-state stability (ISS), to finite-time control problems. In other words, a new concept, finite-time input-to-state stability (FTISS), is proposed and then is applied to both the analysis of finite-time stability and the design of finite-time stabilizing feedback laws of control systems. With finite-time stability, nonsmoothness has to be considered, and serious technical challenges arise in the design of finite-time controllers and the stability analysis of the closed-loop system. It is found that FTISS plays an important role as the conventional ISS in the context of asymptotic stability analysis and smooth feedback stabilization. Moreover, a robust adaptive controller is proposed to handle nonlinear systems with parametric and dynamic uncertainties by virtue of FTISS and related arguments.
Design of Peptoid-Based Coating to Reduce Biofouling in Gas Exchange Devices

In recent decades, membrane technology has been used commonly in biomedical area. However, membrane fouling is a widespread problem in different applications. One method to minimize fouling is through surface modification of membranes. My research explores a novel polymer to minimize nonspecific protein adsorption in biomedical applications. It firstly focuses on grafting the electrically neutral NMEG peptoid, containing 2-methoxyethyl side chains, to polysulfone (PSU) membrane via polydopamine. Contact angle measurements indicated that the hydrophilicity of the peptoid-grafted membranes was significantly improved while the pore size and strength of the membranes remained unchanged. The modified membranes showed an improved fouling resistance when tested with bovine serum albumin, lysozyme and fibrinogen proteins. To further investigate the low fouling surfaces, peptoid length was varied length of peptoids (NMEG5, NMEG10, NMEG15 and NMEG20). The effect of peptoid length and grafting density on fouling resistance of the membranes was studied. Static adsorption experiments with bovine serum albumin revealed that there is an optimal grafting density to improve fouling resistance of peptoid modified membranes, which was dependent on the length and amount of the grafted peptoids. To evaluate the application of modified membrane in the biomedical field, the dynamic fouling resistance of peptoid grafted surfaces, cross-flow filtration tests using bovine serum solution as the feed, was designed and built. According to the cross-flow filtration results, NMEG modified membranes showed a significant improvement in antifouling ability. Furthermore, flux recovery ratios obtained from NMEG modified membranes were much higher than unmodified membranes. The outcome of this study suggests that peptoids are a promising material for fouling-resistant membrane surface modification.
Productivity in Pharmaceutical Biotechnology R&D: The Role of Experience and Alliances

Using data on over 900 firms for the period 1988-2000, we estimate the effect on phase-specific biotech and pharmaceutical R&D success rates of a firm's overall experience, its experience in the relevant therapeutic category, the diversification of its experience across categories, the industry's experience in the category, and alliances with large and small firms. We find that success probabilities vary substantially across therapeutic categories and are negatively correlated with mean sales by category, which is consistent with a model of dynamic, competitive entry. Returns to experience are statistically significant but economically small for the relatively straightforward phase 1 trials. We find evidence of large, positive and diminishing returns to a firm's overall experience (across all therapeutic categories) for the larger and more complex late-stage trials that focus on a drug's efficacy. There is some evidence that a drug is more likely to complete phase 3 if developed by firms whose experience is focused rather than broad (diseconomies of scope). There is evidence of positive knowledge spillovers across firms for phase 1. However, for phase 2 and phase 3 the estimated effects of industry-wide experience are negative, which may reflect either higher Food and Drug Administration (FDA) approval standards in crowded therapeutic categories or that firms in such categories must pursue more difficult targets. Products developed in an alliance tend to have a higher probability of success, at least for the more complex phase 2 and phase 3 trials, and particularly if the licensee is a large firm.
Pressor Responses to Noxious Stimuli in Hypertensive Patients: Effects of Reserpine and Chlorothiazide

The pressor and pulse rate responses to three standardized noxious stimuli were determined in groups of hypertensive patients receiving reserpine and chlorothiazide, alone and in combination. Although the drugs caused a significant decline in resting blood pressure, they failed to diminish the actual magnitude of the elevations in pressure and heart rate resulting from either physical or psychological stimuli. The possible physiological interpretations and the therapeutic implications of these data have been pointed out.
Optimal Policies Against Profit Shifting: The Role of Controlled-Foreign-Company Rules

By introducing controlled-foreign-company (CFC) rules, the parent country of a multinational firm reserves the right to tax the income of the firm's foreign affiliates if the tax rate in the affiliate's host country is below a specified threshold. We identify the conditions under which binding CFC rules are part of the optimal tax mix when governments can set the statutory tax rate, a thin capitalization rule and the CFC rule. We also analyze the effects of economic and financial integration on the optimal policy mix. Our results correspond to the actual development of anti-avoidance rules in OECD countries.
A Novel Distributed Max-Weight Link Scheduler for Multi-Transmit/Receive Wireless Mesh Networks

Multi-transmit-receive capability is fast becoming a significant feature of next-generation wireless mesh networks. It enables routers to transmit or receive distinct packets from multiple neighbors simultaneously. A key problem, however, is designing a distributed link-scheduling algorithm that ensures high network capacity. In this paper, we propose dMaxQ, which is a novel queue-length-aware distributed link scheduler that requires only one-hop neighbors' queue information and uses the celebrated max-weight policy in a distributed manner. We have evaluated the performance of dMaxQ in different network topologies for both single-hop and multihop traffic models and compared it against other approaches, including two queue-length-aware centralized algorithms and state-of-the-art distributed approaches: JazzyMAC and receive-oriented multiple access. The results show that for single-hop and multihop traffic scenarios, dMaxQ obtains, respectively, 100% and 90% of the throughput achieved by the theoretical centralized policy. Other distributed algorithms, such as JazzyMAC, only managed 25% of the theoretical throughput.