Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro reconstruction and analysis of evolutionary variation of the tomato acylsucrose metabolic network

Significance Throughout the course of human history, plant-derived natural products have been used in medicines, in cooking, as pest control agents, and in rituals of cultural importance. Plants produce rapidly diversifying specialized metabolites as protective agents and to mediate interactions with beneficial organisms. In vitro reconstruction of the cultivated tomato insect protective acylsucrose biosynthetic network showed that four acyltransferase enzymes are sufficient to produce the full set of naturally occurring compounds. This system enabled identification of simple changes in enzyme structure leading to much of the acylsucrose diversity produced in epidermal trichomes of wild tomato. These findings will enable analysis of trichome specialized metabolites throughout the Solanaceae and demonstrate the feasibility of engineering these metabolites in plants and microorganisms. Plant glandular secreting trichomes are epidermal protuberances that produce structurally diverse specialized metabolites, including medically important compounds. Trichomes of many plants in the nightshade family (Solanaceae) produce O-acylsugars, and in cultivated and wild tomatoes these are mixtures of aliphatic esters of sucrose and glucose of varying structures and quantities documented to contribute to insect defense. We characterized the first two enzymes of acylsucrose biosynthesis in the cultivated tomato Solanum lycopersicum. These are type I/IV trichome-expressed BAHD acyltransferases encoded by Solyc12g006330─or S. lycopersicum acylsucrose acyltransferase 1 (Sl-ASAT1)─and Solyc04g012020 (Sl-ASAT2). These enzymes were used—in concert with two previously identified BAHD acyltransferases—to reconstruct the entire cultivated tomato acylsucrose biosynthetic pathway in vitro using sucrose and acyl-CoA substrates. Comparative genomics and biochemical analysis of ASAT enzymes were combined with in vitro mutagenesis to identify amino acids that influence CoA ester substrate specificity and contribute to differences in types of acylsucroses that accumulate in cultivated and wild tomato species. This work demonstrates the feasibility of the metabolic engineering of these insecticidal metabolites in plants and microbes.
Better vaccination strategies for better people

In this paper, we study the vaccination of graphs against the outbreak of infectious diseases, in the following natural model generalizing a model by Aspnes et al.: An infectious disease breaks out at a random node of the graph and propagates along the edges of the graph. Vaccinated nodes cannot be infected, nor pass on the infection, whereas all other nodes do. The decisions on which nodes get vaccinated must be made before the random outbreak location is known. There is a cost associated with vaccination and a different cost with getting infected. In this model, we provide two results. First, we improve the approximation guarantee for finding the best vaccination strategy from O(log1.5 n) to O(log z) (where z is the support size of the outbreak distribution), by rounding a natural linear program with region-growing techniques. Second, we analyze the impact of autonomy on the part of the nodes: while a benevolent authority may suggest which nodes should be vaccinated, nodes may opt out after being chosen. We analyze the "Price of Opting Out" in this sense under partially altruistic behavior. Individuals base their decisions on their own cost and the societal cost, the latter scaled by some factor ß. If the altruism parameter is ß=0, it is known that the Price of Anarchy and Price of Stability can be Θ(n). We show that with positive altruism, Nash Equilibria may not exist, but the Price of Opting Out is at most 1/ß (whereas the Price of Anarchy can remain at Θ(n)).
Mycoplasma genitalium: an efficient strategy to generate genetic variation from a minimal genome

Mycoplasma genitalium, a human pathogen associated with sexually transmitted diseases, is unique in that it has smallest genome of any known free‐living organism. The goal of this study was to investigate if and how M. genitalium uses a minimal genome to generate genetic variations. We analysed the sequence variability of the third gene (MG192 or mgpC) of the M. genitalium MgPa adhesion operon, demonstrated that the MG192 gene is highly variable among and within M. genitalium strains in vitro and in vivo, and identified MG192 sequence shifts in the course of in vitro passage of the G37 type strain and in sequential specimens from an M. genitalium‐infected patient. In order to establish the origin of the MG192 variants, we examined nine genomic loci containing partial copies of the MgPa operon, known as MgPar sequences. Our analysis suggests that the MG192 sequence variation is achieved by recombination between the MG192 expression site and MgPar sequences via gene cross‐over and, possibly, also by gene conversion. It appears plausible that M. genitalium has the ability to generate unlimited variants from its minimized genome, which presumably allows the organism to adapt to diverse environments and/or to evade host defences by antigenic variation.
Accuracy of three depression screening scales to diagnose major depressive episodes in older adults without neurocognitive disorders

Objective: To determine the sensitivity and specificity of three depression screening scales to diagnose major depressive episodes in the elderly. Methods: Participants (n=129, 88% female) answered a semi-structured psychiatric interview (Mini International Neuropsychiatric Interview) to determine the diagnosis of major depressive disorder. After this, depressive symptoms in depressed and non-depressed subjects were assessed by independent administration of the 15-item Geriatric Depression Scale (GDS-15), Patient Health Questionnaire-9 (PHQ-9), and 17-item Hamilton Rating Scale for Depression (HDRS-17). Results: Patients with major depression and controls did not differ in age and gender distribution. The sensitivity and specificity of all scales to identify a major depressive episode in older adults were ≥ 90%. There were no significant differences between the areas under the curve for PHQ-9 vs. HDRS-17 (z = 1.2, p = 0.2), PHQ-9 vs. GDS-15 (z = 0.26, p = 0.8), or HDRS-17 vs. GDS-15 (z = 1.2, p = 0.2). Conclusion: This study provides evidence supporting the use of PHQ-9 and GDS-15, both of which are simple to administer and easy to interpret, to diagnose major depressive episodes in older adults without neurocognitive disorders.
Presence of brood affects caste differentiation in the social wasp, Polistes exclamans Viereck (Hymenoptera: Vespidae).

In social insect colonies the sterile individuals that assume the worker role realize their reproductive potential through working and rearing the queen's brood. We have examined the role of the presence of brood in the nest as a determinant of caste in the social wasp Polistes exclamans Viereck. We predicted that wasps in colonies where there was no brood would behave like future queens, while wasps in colonies in which brood care was an option would behave like workers. Brood presence was manipulated by removing eggs and larvae or the whole nest from experimental colonies and leaving brood in control colonies. Ability to tolerate cold temperatures was used as an indicator of caste when comparing females emerging in experimental colonies to females emerging in control colonies. Females emerging in experimental colonies survived longer at cold temperatures than those emerging in control colonies. This indicates that females developed characteristics more typical of future queens in response to deprivation of brood. P. exclamans is characterized by small colonies whose nests are destroyed frequently. Therefore caste plasticity in adult females of P. exclamans is advantageous. Key-words: Caste determination, nesting cycle, Polistes exclamans, production schedules
Longitudinal versus Cross-sectional Evaluations of Leukocyte Telomere Length Dynamics: Age-Dependent Telomere Shortening is the Rule

Background. Leukocyte telomere length (LTL) is considered a biomarker of human aging and based on cross-sectional studies it shortens with age. However, longitudinal studies reported that many adults display LTL lengthening. Methods. Using Southern blots, we compared cross-sectional rates of age-related LTL change across a ∼20 year age range with those based on longitudinal evaluations in three surveys (S1, S2, and S3) with three time intervals: S1–S2 (5.8 years), S2–S3 (6.6 years), and S1–S3 (12.4 years). Hierarchical linear modeling was used to explore LTL dynamics using LTL data from S1, S2, and S3. Results. Cross-sectionally, mean LTL shortenings were 24.6, 25.4, and 23.6 bp/y at S1, S2, and S3, respectively. Longitudinally, more variation was observed in the rate of LTL change during the shorter than longer follow-up periods. Furthermore, using simple differences in LTL, 14.4% and 10.7% of individuals displayed LTL lengthening during S1–S2 and S2–S3, respectively, but only 1.5% during S1–S3 (p < 0.001). The estimated mean rate of LTL shortening based on averaging empirical Bayes’ estimates of LTL from a parsimonious hierarchical linear modeling model was 31 bp/y with a range from 23 to 47 bp/y with none of the participants showing LTL lengthening over the average 12.4 years of follow-up. Conclusions. As aging displays a unidirectional progression, it is unlikely that LTL elongates with age. LTL elongation in longitudinal studies primarily reflects measurement errors of LTL in relation to the duration of follow-up periods.
Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer

Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes.
Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia in the elderly, and affects millions of people worldwide. As the number of AD cases continues to increase in both developed and developing countries, finding therapies that effectively halt or reverse disease progression constitutes a major research and public health challenge. Since the identification of the amyloid-β peptide (Aβ) as the major component of the amyloid plaques that are characteristically found in AD brains, a major effort has aimed to determine whether and how Aβ leads to memory loss and cognitive impairment. A large body of evidence accumulated in the past 15 years supports a pivotal role of soluble Aβ oligomers (AβOs) in synapse failure and neuronal dysfunction in AD. Nonetheless, a number of basic questions, including the exact molecular composition of the synaptotoxic oligomers, the identity of the receptor(s) to which they bind, and the signaling pathways that ultimately lead to synapse failure, remain to be definitively answered. Here, we discuss recent advances that have illuminated our understanding of the chemical nature of the toxic species and the deleterious impact they have on synapses, and have culminated in the proposal of an Aβ oligomer hypothesis for Alzheimer’s pathogenesis. We also highlight outstanding questions and challenges in AD research that should be addressed to allow translation of research findings into effective AD therapies.
Memory for emotional and neutral information: Gender and individual differences in emotional sensitivity

In studies of autobiographical memory, women typically remember more emotional information than do men. The present study evaluated whether women recall more emotional information than men when the content of an event is controlled. Participants read a script containing emotional and neutral information, under instructions to prepare advice for the characters addressing either interpersonal issues (emotional focus), concrete plans (neutral focus), or with no particular topic suggested (undirected focus). After writing out advice, on a surprise memory test women recalled more emotional information than men in all focus conditions with no deficit in neutral recall. Women recalled more neutral information than men in the neutral focus condition. A measure of emotional sensitivity mediated the gender difference in emotional recall suggesting that memory for emotional information is not solely a function of gender.
Sensitivity study of Radarsat-2 polarimetric SAR to crop height and fractional vegetation cover of corn and wheat

ABSTRACT Increasing studies have been conducted to investigate the potential of polarimetric synthetic aperture radar (SAR) in crop growth monitoring due to the capability of penetrating the clouds, haze, light rain, and vegetation canopy. This study investigated the sensitivity of 16 parameters derived from C-band Radarsat-2 polarimetric SAR data to crop height and fractional vegetation cover (FVC) of corn and wheat. The in-situ measured crop height and FVC were collected from 29 April to 30 September 2013, at the study site in southwest Ontario, Canada. A total of 10 Radarsat-2 polarimetric SAR images were acquired throughout the same growing season. It was observed that at the early growing stage, the corn height was strongly correlated with the SAR parameters including HV (R2 = 0.88), HH-VV (R2 = 0.84), and HV/VV (R2 = 0.80), and the corn FVC was significantly correlated with HV (R2 = 0.79) and HV/VV (R2 = 0.92), but the correlation became weaker at the later growing stage. The sensitivity of the SAR parameters to wheat variables was very low and only HV and Yamaguchi helix scattering showed relatively good but negative correlations with wheat height (R2 = 0.57 and R2 = 0.39) at the middle growing stage. These findings indicated that Radarsat-2 polarimetric SAR (C-band) has a great potential in crop height and FVC estimation for broad-leaf crops, as well as identifying the changes in crop canopy structures and phenology.
AUGMENTED LAGRANGIAN METHOD FOR TOTAL VARIATION RESTORATION WITH NON-QUADRATIC FIDELITY

Recently augmented Lagrangian method has been successfully applied to image restoration. We extend the method to total variation (TV) restoration models with non-quadratic fidelities. We will first introduce the method and present an iterative algorithm for TV restoration with a quite general fidelity. In each iteration, three sub-problems need to be solved, two of which can be very efficiently solved via Fast Fourier Transform (FFT) implementation or closed form solution. In general the third sub-problem need iterative solvers. We then apply our method to TV restoration with $L^1$ and Kullback-Leibler (KL) fidelities, two common and important data terms for deblurring images corrupted by impulsive noise and Poisson noise, respectively. For these typical fidelities, we show that the third sub-problem also has closed form solution and thus can be efficiently solved. In addition, convergence analysis of these algorithms are given. Numerical experiments demonstrate the efficiency of our method.
School-based HPV immunization of young adolescents: Effects of two brief health interventions

Adolescent immunization rates for human papillomavirus (HPV) are low and interventions within school-based health centers (SBHCs) may increase HPV uptake and series completion. We examined the effect of a parent health message intervention on HPV vaccination intent, first dose uptake and series completion among adolescents who received care at SBHCs. Via computer-assisted telephone interviews (CATI), 445 parents of young adolescents were randomly assigned to 2 two-level interventions using a 2 × 2 design (rhetorical question (RQ) or no-RQ and one-sided or two-sided message). The RQ intervention involved asking the parent a question they were likely to endorse (e.g., “Do you want to protect your daughter from cervical cancer? ”) with the expectation that they would then behave in a manner consistent with their endorsement (i.e., agree to vaccinate). For the one-sided message, parents were given information that emphasized the safety and effectiveness of HPV vaccine, whereas the two-sided message acknowledged that some parents might have concerns about the vaccine, followed by reassurance regarding the safety and effectiveness. At CATI conclusion, parents indicated intentions to have their adolescents vaccinated. Parents who endorsed any intent were sent a consent form to return and all adolescents with signed returned consents were vaccinated at SBHCs. Medical records were reviewed for uptake/completion. Parents were 87% female; adolescents were 66% male and racially/ethnically diverse. 42.5% of parents indicated some intention to immunize, 51.4% were unsure, and 6.1% were not interested. 34% (n = 151) of adolescents received their first dose with series completion rates of 67% (n = 101). The RQ component of the intervention increased intention to vaccinate (RR = 1.45; 95%CI 1.16,1.81), but not first dose uptake or series completion. The 1-sided and 2-sided messages had no effect. This brief, RQ health intervention enhanced intent, but did not impact vaccination rates, likely due to the time delay between the intervention and consent form receipt.
On Feelings as a Heuristic for Making Offers in Ultimatum Negotiations

This research examined how reliance on emotional feelings as a heuristic influences how offers are made. Results from three experiments using the ultimatum game show that, compared with proposers who do not rely on their feelings, proposers who rely on their feelings make less generous offers in the standard ultimatum game, more generous offers in a variant of the game allowing responders to make counteroffers, and less generous offers in a dictator game in which no responses are allowed. Reliance on feelings triggers a more literal form of play, whereby proposers focus more on how they feel toward the content of the offers than on how they feel toward the possible outcomes of those offers, as if the offers were the final outcomes. Proposers who rely on their feelings also tend to focus on gist-based construals of the negotiation that capture only the essential aspects of the situation.
Training residents in problem-solving treatment of depression: a pilot feasibility and impact study.

BACKGROUND AND OBJECTIVES Primary care patients with depression may prefer or require a non-pharmacological treatment such as counseling. We investigated the feasibility of teaching family medicine residents an evidence-based brief counseling intervention for depression (Problem-solving Treatment of Depression for Primary Care [PST-PC]). METHODS Eleven residents over 3 consecutive years were provided a brief training program in PST-PC. Residents were evaluated for skill acquisition, changes in self efficacy, intentions to improve their care for depression, and post-residency integration of PST-PC into their daily practice. RESULTS Trainees met established criteria for competency to administer PST-PC. They improved to moderate-to-high levels of self efficacy for treating depression, including for their counseling skills, and in their intentions to improve their depression management. At up to 3 years post residency, 90% indicated they were using PST-PC, often in a modified form, and also for illnesses other than depression. They indicated they would recommend the training to new residents. CONCLUSIONS The PST-PC training program evaluated in this study is feasible in residency training and appears to influence practice post residency. These findings warrant continued investigation of this training program with a larger sample of residents and evaluation of outcomes with depressed patients treated with PST-PC in real-world practice settings.
Roles of Islet Toll-Like Receptors in Pig to Mouse Islet Xenotransplantation

Although innate immunity plays important roles in xenograft rejection, there have been few studies on the role of toll-like receptors (TLRs) in xenotransplantation. Furthermore, most studies focused on the recipient's TLRs. Therefore, we investigated whether TLRs in porcine islets can contribute to islet xenograft rejection. Adult porcine islets were isolated and stimulated by polyinosinic/polycytidylic acid (poly I:C) or lipopolysaccharide (LPS). Both poly I:C and LPS stimulation in porcine islets induced expression of chemokines (RANTES, MCP-1, IP-10, and IL-8), cytokines (IL-6 and type I interferons), and adhesion molecules (VCAM-1 and ICAM-1). Porcine islet supernatants stimulated by TLR agonists induced chemotaxis of human leukocytes. They also induced procoagulant activation (tissue factor and fgl-2). However, TLR stimulation did not influence insulin secretion. When porcine MyD88 was knocked down using shRNA lentivirus, TLR-mediated induction of proinflammatory mediators and procoagulants was attenuated. When LPS was injected to MyD88 or TLR4 knockout mice after porcine islet transplantation, LPS stimulation on donor islets interfered with islet xenograft tolerance induction by anti-CD154 antibodies. Inflammatory cell infiltration and expression of proinflammatory chemokines and cytokines in islet xenografts also increased. In conclusion, TLR activation in porcine islets induced both a proinflammatory and procoagulant response and thereby contributed to xenograft rejection.
Side-Channel Leakage Models for RISC Instruction Set Architectures from Empirical Data

Side-channel attacks are currently among the most serious threats for embedded systems. Popular countermeasures to mitigate the impact of such attacks are masking schemes, where secret intermediate values are split in two or more values by virtue of secret sharing. Processing the secret happens on separate execution paths, which are executed on the same central processing unit (CPU). In case of unwanted correlations between different registers inside the CPU the shared secret may leak out through a side-channel. This problem is particularly evident on low cost embedded systems, such as nodes for the Internet of Things (IoT), where cryptographic algorithms are often implemented in pure software on a reduced instruction set computer (RISC). On such an architecture, all data manipulation operations are carried out on the contents of the CPU's register file. This means that all intermediate values of the cryptographic algorithm at some stage pass through the register file. Towards avoiding unwanted correlations and leakages thereof, special care has to be taken in the mapping of the registers to intermediate values of the algorithm. In this work, we describe an empirical study that reveals effects of unintended unmasking of masked intermediate values and thus leaking secret values. The observed phenomena are related to the leakage of masked hardware implementations caused by glitches in the combinatorial path of the circuit but the effects are abstracted to the level of the instruction set architecture on a RISC CPU. Furthermore, we discuss countermeasures to have the compiler thwart such leakages.