Miracle-dz/UniFAR-FTUs huggingface dataset:
Moonlighting proteins: putting the spotlight on enzymes

ABSTRACT AROGENATE DEHAYDRATASE2 (ADT2) is a member of the Arabidopsis thaliana ADT family. All members of this family act as arogenate dehydratases in phenylalanine biosynthesis, decarboxylating/dehydrating arogenate to phenylalanine. ADT2 is detected in stromules, and as a ring around the equatorial plane of dividing chloroplasts, indicating it has a second, non-enzymatic function in chloroplast division. Here, we provide further evidence for this alternative role of ADT2. First, we demonstrate that ADT2 and FtsZ co-localize around the equatorial plane at the same time. Second, FtsZ expression in an adt2 mutant was analyzed, as well as ADT2 expression in three Arabidopsis chloroplast division mutants, ACCUMULATION AND REPLICATION OF CHLOROPLASTS3 (ARC3), ARC5 and ARC6. In arc3 and arc6 mutants, ADT2 is misexpressed and resembles the expression of FtsZ in the same mutants. However, in the arc5 mutant, ADT2 ring positioning is observed at constriction points indicating proper relative timing. ADT2 expression in the arc mutants shows that the role of ADT2 in chloroplast division occurs prior to ARC5, but is dependent on ARC3 and ARC6. Abbreviations used: ADT: arogenate dehydratase, ARC: accumulation and replication of chloroplasts, CFP: cyan fluorescent protein, dpi: days post infiltration, FtsZ: filamentous temperature sensitive Z, PD: plastid division, Phe: phenylalanine, YFP: yellow fluorescent protein.
Understanding the Coastal Ecocline: Assessing Sea–Land Interactions at Non-tidal, Low-Lying Coasts Through Interdisciplinary Research

Coastal zones connect terrestrial and marine ecosystems forming a unique environment that is under increasing anthropogenic pressure. Rising sea levels, sinking coasts, and changing precipitation patterns modify hydrodynamic gradients and may enhance sea-land exchange processes in both tidal and non-tidal systems. Furthermore, the removal of flood protection structures as restoration measure contributes locally to the changing coastlines. A detailed understanding of the ecosystem functioning of coastal zones and the interactions between connected terrestrial and marine ecosystems is still lacking. Here, we propose an interdisciplinary approach to the investigation of interactions between land and sea at shallow coasts, and discuss the advantages and the first results provided by this approach as applied by the research training group Baltic TRANSCOAST. A low-lying fen peat site including the offshore shallow sea area on the southern Baltic Sea coast has been chosen as a model system to quantify hydrophysical, biogeochemical, sedimentological, and biological processes across the land-sea interface. Recently introduced rewetting measures might have enhanced submarine groundwater discharge as indicated by distinct patterns of salinity gradients in the near shore sediments, making the coastal waters in front of the study site a mixing zone of fresh- and brackish water. High nutrient loadings, dissolved inorganic carbon, and dissolved organic matter originating from the degraded peat may affect micro- and macro-phytobenthos, with the impact propagating to higher trophic levels. The terrestrial part of the study site is subject to periodic brackish water intrusion caused by occasional flooding, which has altered the hydraulic and biogeochemical properties of the prevailing peat soils. The stable salinity distribution in the main part of the peatland reveals the legacy of flooding events. Generally, elevated sulfate concentrations are assumed to influence greenhouse gas emissions, mainly by inhibiting methane production, yet our investigations indicate complex interactions between the different biogeochemical element cycles (e.g. carbon and sulfur) caused by connected hydrological pathways. In conclusion, sea-land interactions are far reaching, occurring on either side of the interface, and can only be understood when both long-term and event-based patterns and different spatial scales are taken into account in interdisciplinary research that involves marine and terrestrial expertise.
Learning without Interaction Requires Separation

One of the key resources in large-scale learning systems is the number of rounds of communication between the server and the clients holding the data points. We study this resource for systems with two types of constraints on the communication from each of the clients: local differential privacy and limited number of bits communicated. For both models the number of rounds of communications is captured by the number of rounds of interaction when solving the learning problem in the statistical query (SQ) model. For many learning problems known efficient algorithms require many rounds of interaction. Yet little is known on whether this is actually necessary. In the context of classification in the PAC learning model, Kasiviswanathan et al. (2008) constructed an artificial class of functions that is PAC learnable with respect to a fixed distribution but cannot be learned by an efficient non-interactive (or one-round) SQ algorithm. Here we show that a similar separation holds for any class with large margin complexity that is closed under negation, without assumptions on the distribution. That is, classes of functions that cannot be represented as large-margin linear separators. In particular this is true for linear separators and decision lists. To prove this separation we show that non-interactive SQ algorithms can only learn function classes of low margin complexity. Our lower bound also holds against a stronger class of algorithms that for which only queries that depend on labels are non-interactive (we refer to them as label-non-adaptive). We complement this lower bound with a new efficient and label-non-adaptive SQ learning algorithm whose complexity is polynomial in the margin complexity. We thus obtain a new characterization of margin complexity that might be of independent interest.
Imperative Instruction for Pressurized Metered-Dose Inhalers: Provider Perspectives

BACKGROUND: Reports show that many patients do not use their pressurized metered-dose inhalers (pMDIs) effectively. The National Heart, Lung, and Blood Institute recommends that health-care providers educate and assess patients' pMDI technique at each opportunity. However, limited data exist regarding how often pediatric primary care providers perform assessments and which methods they use. We sought to (1) identify instructional methods used to teach pMDI use, (2) describe how pMDI use is reassessed at follow-up visits, and (3) describe primary care provider attitudes and barriers to in-office pMDI instruction. METHODS: A 34-item electronic survey was distributed from August to December 2016 via E-mail to local pediatric primary care providers. Descriptive statistics were used for analysis. RESULTS: Sixty two of 223 potential primary care providers (28%) responded. Physicians and nurse practitioners were identified most often as the providers of pMDI education (53%). When first prescribing a pMDI, only 10% reported having the patient practice inhaler use in the office and receive feedback. Only 19% “always” reassessed the technique, even for patients with poorly controlled asthma. Among those who reassessed the technique, most (76%) did so verbally, and only 42% asked the patients to demonstrate pMDI use. Only 32% reported that typical patient education in their setting was adequate to ensure proper pMDI use. Commonly cited barriers included time (84%) and access to demo pMDIs (67%). Provider solutions included video tutorials and access to demo inhalers. CONCLUSIONS: Many pediatric primary care providers did not demonstrate or have patients practice pMDI use when teaching or assessing pMDI technique, and the reassessment rate was low even for patients with poorly controlled asthma. Identifying and training a consistent pMDI educator and obtaining demo pMDIs may abate some barriers. Respiratory therapists could appropriately fulfill this educator role. Brief, repeated pMDI practice for motor learning could promote more stable pMDI mastery.
HO Endonuclease-Initiated Recombination in Yeast Meiosis Fails To Promote Homologous Centromere Pairing and Is Not Constrained To Utilize the Dmc1 Recombinase

Crossover recombination during meiosis is accompanied by a dramatic chromosome reorganization. In Saccharomyces cerevisiae, the onset of meiotic recombination by the Spo11 transesterase leads to stable pairwise associations between previously unassociated homologous centromeres followed by the intimate alignment of homologous axes via synaptonemal complex (SC) assembly. However, the molecular relationship between recombination and global meiotic chromosome reorganization remains poorly understood. In budding yeast, one question is why SC assembly initiates earliest at centromere regions while the DNA double strand breaks (DSBs) that initiate recombination occur genome-wide. We targeted the site-specific HO endonuclease to various positions on S. cerevisiae’s longest chromosome in order to ask whether a meiotic DSB’s proximity to the centromere influences its capacity to promote homologous centromere pairing and SC assembly. We show that repair of an HO-mediated DSB does not promote homologous centromere pairing nor any extent of SC assembly in spo11 meiotic nuclei, regardless of its proximity to the centromere. DSBs induced en masse by phleomycin exposure likewise do not promote homologous centromere pairing nor robust SC assembly. Interestingly, in contrast to Spo11, HO-initiated interhomolog recombination is not affected by loss of the meiotic kinase, Mek1, and is not constrained to use the meiosis-specific Dmc1 recombinase. These results strengthen the previously proposed idea that (at least some) Spo11 DSBs may be specialized in activating mechanisms that both 1) reinforce homologous chromosome alignment via homologous centromere pairing and SC assembly, and 2) establish Dmc1 as the primary strand exchange enzyme.
A hierarchical clustering approach to identify repeated enrollments in web survey data

Introduction Online surveys are a valuable tool for social science research, but the perceived anonymity provided by online administration may lead to problematic behaviors from study participants. Particularly, if a study offers incentives, some participants may attempt to enroll multiple times. We propose a method to identify clusters of non-independent enrollments in a web-based study, motivated by an analysis of survey data which tests the effectiveness of an online skin-cancer risk reduction program. Methods To identify groups of enrollments, we used a hierarchical clustering algorithm based on the Euclidean distance matrix formed by participant responses to a series of Likert-type eligibility questions. We then systematically identified clusters that are unusual in terms of both size and similarity, by repeatedly simulating datasets from the empirical distribution of responses under the assumption of independent enrollments. By performing the clustering algorithm on the simulated datasets, we determined the distribution of cluster size and similarity under independence, which is then used to identify groups of outliers in the observed data. Next, we assessed 12 other quality indicators, including previously proposed and study-specific measures. We summarized the quality measures by cluster membership, and compared the cluster groupings to those found when using the quality indicators with latent class modeling. Results and conclusions When we excluded the clustered enrollments and/or lower-quality latent classes from the analysis of study outcomes, the estimates of the intervention effect were larger. This demonstrates how including repeat or low quality participants can introduce bias into a web-based study. As much as is possible, web-based surveys should be designed to verify participant quality. Our method can be used to verify survey quality and identify problematic groups of enrollments when necessary.
Pharmacologic Ascorbate Reduces Radiation-Induced Normal Tissue Toxicity and Enhances Tumor Radiosensitization in Pancreatic Cancer.

: Chemoradiation therapy is the mainstay for treatment of locally advanced, borderline resectable pancreatic cancer. Pharmacologic ascorbate (P-AscH-, i.e., intravenous infusions of ascorbic acid, vitamin C), but not oral ascorbate, produces high plasma concentrations capable of selective cytotoxicity to tumor cells. In doses achievable in humans, P-AscH- decreases the viability and proliferative capacity of pancreatic cancer via a hydrogen peroxide (H2O2)-mediated mechanism. In this study, we demonstrate that P-AscH- radiosensitizes pancreatic cancer cells but inhibits radiation-induced damage to normal cells. Specifically, radiation-induced decreases in clonogenic survival and double-stranded DNA breaks in tumor cells, but not in normal cells, were enhanced by P-AscH-, while radiation-induced intestinal damage, collagen deposition, and oxidative stress were also reduced with P-AscH- in normal tissue. We also report on our first-in-human phase I trial that infused P-AscH- during the radiotherapy "beam on. " Specifically, treatment with P-AscH- increased median overall survival compared with our institutional average (21.7 vs. 12.7 months, P = 0.08) and the E4201 trial (21.7 vs. 11.1 months). Progression-free survival in P-AscH--treated subjects was also greater than our institutional average (13.7 vs. 4.6 months, P < 0.05) and the E4201 trial (6.0 months). Results indicated that P-AscH- in combination with gemcitabine and radiotherapy for locally advanced pancreatic adenocarcinoma is safe and well tolerated with suggestions of efficacy. Because of the potential effect size and minimal toxicity, our findings suggest that investigation of P-AscH- efficacy is warranted in a phase II clinical trial. SIGNIFICANCE: These findings demonstrate that pharmacologic ascorbate enhances pancreatic tumor cell radiation cytotoxicity in addition to offering potential protection from radiation damage in normal surrounding tissue, making it an optimal agent for improving treatment of locally advanced pancreatic adenocarcinoma.
Associations of adiposity and parental diabetes with prediabetes among adolescents in Kuwait: A cross‐sectional study

Prediabetes, a high‐risk state for developing diabetes, has become more prevalent among children and adolescents in recent decades. This study sought to estimate the prevalence of prediabetes and assess its association with adiposity among adolescents in Kuwait. Also, to determine whether maternal and paternal history of diabetes associate with offspring prediabetes in a sex‐specific manner.
Fruit and vegetable intake and pancreatic cancer risk in a population‐based cohort study in Japan

Oxidative stress and chronic inflammation are potential pathogenic factors of pancreatic cancer. Although fruits and vegetables are abundant in antioxidants and anti‐inflammatory constituents, the reported associations between fruit and vegetable intake and pancreatic cancer risk have been inconsistent. Here, we investigated the association between fruit and vegetable intake and pancreatic cancer risk as part of the Japan Public Health Center‐based Prospective Study. The analysis included 90,185 participants who responded to a medical and lifestyle questionnaire during 1995–1998. Associations between fruit and vegetable intake and pancreatic cancer risk were evaluated with Cox proportional hazards models. Additional analyses were stratified by smoking status and body mass index. During follow‐up (median duration, 16.9 years), 577 participants were diagnosed with pancreatic cancer. In multivariate‐adjusted models, pancreatic cancer risk was inversely associated with total fruit intake (highest vs. lowest intake quartile; hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.57–0.95, p‐trend: 0.116) and positively associated with total vegetable intake (HR: 1.30, 95% CI: 1.01–1.66, p‐trend: 0.151). For total fruit intake, the inverse association with pancreatic cancer risk was more apparent in never smokers (HR: 0.67, 95% CI: 0.47–0.97, p‐trend: 0.034). For total vegetable intake, the positive association was statistically significant in ever smokers (HR: 1.49, 95% CI: 1.01–2.19, p‐trend: 0.043) and statistically nonsignificant in never smokers. In summary, total fruit intake and total vegetable intake had inverse and positive associations, respectively, with pancreatic cancer risk. Vegetable intake may correlate with increased risk partly because of the influence of smoking on vegetable intake.
Near-maximum principle for general recursive utility optimal control problem

ABSTRACT In this study, we introduce a general recursive utility optimal control problem driven by a fully nonlinear stochastic differential system. In order to investigate Pontryagin's stochastic maximum principle for this new optimal control problem, we establish the near-optimal control system for the original problem and obtain the related near-maximum principle. Two examples are also provided to illustrate the near-maximum principle.
The effect of tamoxifen therapy on the endometrium and ovarian cyst formation in patients with breast cancer

Objective To evaluate the effect of tamoxifen on female reproductive organs in women with breast cancer. Methods We retrospectively reviewed the medical records of 309 women with breast cancer who were currently receiving tamoxifen and undergoing regular gynecological examination. Results We evaluated 92 pre- and 217 postmenopausal women. The prevalence of endometrial thickening was 12% in the pre- and 10.6% in the postmenopausal group. An endometrial biopsy was performed in 43 women and confirmed endometrial cancer in 1, endometrial polyps in 14, and endometrial hyperplasia in 4 women. Transvaginal ultrasonography showed 25 cases of newly developed ovarian cysts. Most ovarian cysts had disappeared during follow-up. Conclusion Tamoxifen use in women with breast cancer causes few complications and is considered safe for female reproductive organs in case of regular gynecological examination.
Comparison of Laparoscopic Versus Open Gastrectomy for Treatment of Gastric Cancer: Analysis of a Textbook Outcome.

INTRODUCTION Open gastrectomy (OG) has long been the preferred surgical approach worldwide for treatment of gastric cancer (GC). Nowadays, several randomized prospective trials have confirmed improvements in postoperative outcomes for laparoscopic gastrectomy (LG) compared with open procedures, with similar oncologic outcomes. However, many of these studies come from Eastern countries. MATERIALS AND METHODS A prospective nonrandomized study was conducted with all patients operated of GC at Ramón y Cajal University Hospital from January 2015 to December 2017. Of the 96 patients enrolled, 47 patients underwent LG and 49 OG. Textbook outcome was defined as the percentage of patients who underwent a complete tumor resection with at least 15 lymph nodes (LNs) in the resected specimen and an uneventful postoperative course, without hospital readmission. RESULTS A textbook outcome was achieved in 51.04% of patients operated of GC. The outcome parameter "no severe postoperative complication" had the greatest negative impact on the textbook outcome. A statistically higher number of patients with early cancer (40% versus 16.3%) and subtotal gastrectomy (57.5% versus 34.7%) were found in the laparoscopic group. No statistical differences were found between open and laparoscopic approaches regarding operating time, rate of microscopic margin positivity, hospital stay, number of retrieved LNs, complications, reinterventions, mortality, and readmissions. No statistical differences in textbook outcome were found between both groups (57.14% versus 45%; P = .25). CONCLUSIONS LG for treatment of GC seems to be safe and feasible with similar textbook outcomes compared with OG.
A longitudinal, within‐person investigation of the association between the P3 ERP component and externalizing behavior problems in young children

BACKGROUND Externalizing problems, including aggression and conduct problems, are thought to involve impaired attentional capacities. Previous research suggests that the P3 event-related potential (ERP) component is an index of attentional processing, and diminished P3 amplitudes to infrequent stimuli have been shown to be associated with externalizing problems and attention-deficit/hyperactivity disorder (ADHD). However, the vast majority of this prior work has been cross-sectional and has not examined young children. The present study is the first investigation of whether within-individual changes in P3 amplitude predict changes in externalizing problems, providing a stronger test of developmental process. METHOD Participants included a community sample of children (N = 153) followed longitudinally at 30, 36, and 42 months of age. Children completed an oddball task while ERP data were recorded. Parents rated their children's aggression and ADHD symptoms. RESULTS Children's within-individual changes in the P3 amplitude predicted concomitant within-child changes in their aggression such that smaller P3 amplitudes (relative to a child's own mean) were associated with more aggression symptoms. However, changes in P3 amplitudes were not significantly associated with ADHD symptoms. CONCLUSIONS Findings suggest that the P3 may play a role in development of aggression, but do not support the notion that the P3 plays a role in development of early ADHD symptoms.
RapidHARe: A computationally inexpensive method for real-time human activity recognition from wearable sensors

Recent human activity recognition (HAR) methods, based on on-body inertial sensors, have achieved increasing performance; however, this is at the expense of longer CPU calculations and greater energy consumption. Therefore, these complex models might not be suitable for real-time prediction in mobile systems, e.g., in elder-care support and long-term health-monitoring systems. Here, we present a new method called RapidHARe for real-time human activity recognition based on modeling the distribution of a raw data in a half-second context window using dynamic Bayesian networks. Our method does not employ any dynamic-programming-based algorithms, which are notoriously slow for inference, nor does it employ feature extraction or selection methods. In our comparative tests, we show that RapidHARe is an extremely fast predictor, one and a half times faster than artificial neural networks (ANNs) methods, and more than eight times faster than recurrent neural networks (RNNs) and hidden Markov models (HMMs). Moreover, in performance, RapidHare achieves an F1 score of 94.27\% and accuracy of 98.94\%, and when compared to ANN, RNN, HMM, it reduces the F1-score error rate by 45\%, 65\%, and 63\% and the accuracy error rate by 41\%, 55\%, and 62\%, respectively. Therefore, RapidHARe is suitable for real-time recognition in mobile devices.