Miracle-dz/UniFAR-FTUs huggingface dataset:
Accessibility of the Shine–Dalgarno sequence dictates N-terminal codon bias in E. coli

Despite considerable effort, no physical mechanism has been experimentally shown to explain the N-terminal codon bias in prokaryotic genomes. Using a systematic study of synonymous substitutions in two endogenous E. coli genes, we show that interactions between the coding region and the upstream Shine–Dalgarno sequence modulate both the rate of mRNA degradation and the efficiency of translation-initiation via a ‘ribosome-protection’ mechanism, which ultimately affects cellular fitness. We further demonstrate that occlusion of the Shine–Dalgarno sequence depends on the formation of non-equilibrium secondary structures, which may include long-range contacts, highlighting the role of co-transcriptional mRNA folding and the influence of the 5’-untranslated region in determining the optimal coding sequence. Finally, a statistical analysis of the E. coli genome also specifically implicates avoidance of intra-molecular base-pairing with the Shine–Dalgarno sequence. Our results therefore provide general physical insights into the coding-level sequence features that optimize protein expression in prokaryotes.
Daily Oral Chondroitin Sulfate Oligosaccharides for Knee Joint Pain in Healthy Subjects: A Randomized, Blinded, Placebo-Controlled Study

The increased rate of population aging in Japan has led to an increase in the incidence of osteoarthritis (OA). Chondroitin sulfate has been reported to reduce the pain and swelling associated with OA and to improve knee function. We evaluated the safety and effects of oral chondroitin sulfate oligosaccharides on knee function in a randomized, double-blinded, placebo-controlled parallel group comparison study of healthy Japanese subjects with knee joint pain. Subjects were randomly divided into test and placebo groups and given either active-test capsules containing 100 mg of chondroitin sulfate oligosaccharides or placebo capsules daily for 8 weeks. The Japanese Knee Osteoarthritis Measure (JKOM), Visual Analog Scale (VAS), blood and physical examinations, and medical interviews were performed at weeks 0, 4, and 8, and the locomotive syndrome risk test was performed at weeks 0 and 8 during the test intake period. The JKOM scores did not significantly differ between the test groups. However, among subjects with worse VAS scores, those in the active test group had significantly lower JKOM scores at 8 weeks, compared to those in the placebo group. Moreover, chondroitin sulfate oligosaccharide treatment tended to improve the subjects' scores on the stand-up test, which evaluates the risk of locomotive syndrome. Furthermore, no abnormal changes or severe adverse events were observed during physical or blood examinations or medical interviews. Our results suggest that chondroitin sulfate oligosaccharides improve knee pain and are safe for 8-week intake.
An operational earthquake forecasting system (OEFS) to control induced seismicity in the Groningen natural gas field

This ‘white paper’ proposes to develop a data-informed operational system to forecast induced seismicity, and the associated seismic hazard in the Groningen natural gas field. The goals of developing and maintaining such an Operational Earthquake Forecasting System (OEFS) are 1) to provide a unified environment to test and align research efforts from, e.g., the DeepNL and KEM national research programs; 2) to improve the quality of seismic hazard forecasts by combining a broad range of measured data with ‘evergreen’ models based on large-scale numerical simulation and systematic data assimilation; and 3) to provide a testbed for the development of operational procedures to minimize seismic hazard and risk such as (adaptive) traffic light systems, or optimized spatial and temporal production and/or re-injection rates. Like weather forecasting systems, OEFS depends on data assimilation, e.g. the systematic combination of uncertain measured data with uncertain models such that the combined result has a better forecasting capability than the data or models on their own. The aim is to use physics-based models in OEFS whenever possible, in combination with probabilistic models whenever necessary. The wide variety in temporal and spatial scales that govern the physical processes behind induced seismicity imply that OEFS will have to be based on a combination of multiple computational models, if necessary using simplified physics, which will be computationally intensive. Moreover, to systematically capture uncertainties in geology and physical parameters, OEFS will need to make use of ensembles of realizations which further increases the computational requirements. Developing and maintaining OEFS will therefore be a major exercise which is probably best done by one or more large technological institutes (KNMI, TNO, Deltares) with input from academic institutions.
Marginal Structural Models with Counterfactual Effect Modifiers

Abstract In health and social sciences, research questions often involve systematic assessment of the modification of treatment causal effect by patient characteristics. In longitudinal settings, time-varying or post-intervention effect modifiers are also of interest. In this work, we investigate the robust and efficient estimation of the Counterfactual-History-Adjusted Marginal Structural Model (van der Laan MJ, Petersen M. Statistical learning of origin-specific statically optimal individualized treatment rules. Int J Biostat. 2007;3), which models the conditional intervention-specific mean outcome given a counterfactual modifier history in an ideal experiment. We establish the semiparametric efficiency theory for these models, and present a substitution-based, semiparametric efficient and doubly robust estimator using the targeted maximum likelihood estimation methodology (TMLE, e.g. van der Laan MJ, Rubin DB. Targeted maximum likelihood learning. Int J Biostat. 2006;2, van der Laan MJ, Rose S. Targeted learning: causal inference for observational and experimental data, 1st ed. Springer Series in Statistics. Springer, 2011). To facilitate implementation in applications where the effect modifier is high dimensional, our third contribution is a projected influence function (and the corresponding projected TMLE estimator), which retains most of the robustness of its efficient peer and can be easily implemented in applications where the use of the efficient influence function becomes taxing. We compare the projected TMLE estimator with an Inverse Probability of Treatment Weighted estimator (e.g. Robins JM. Marginal structural models. In: Proceedings of the American Statistical Association. Section on Bayesian Statistical Science, 1-10. 1997a, Hernan MA, Brumback B, Robins JM. Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. Epidemiology. 2000;11:561–570), and a non-targeted G-computation estimator (Robins JM. A new approach to causal inference in mortality studies with sustained exposure periods - application to control of the healthy worker survivor effect. Math Modell. 1986;7:1393–1512.). The comparative performance of these estimators is assessed in a simulation study. The use of the projected TMLE estimator is illustrated in a secondary data analysis for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial where effect modifiers are subject to missing at random.
Human papillomavirus in foetal and maternal tissues from miscarriage cases

Abstract Early miscarriage is still a concern, and viral infections are recognised as one of the causes of this adverse outcome. The causal relationship between HPV and miscarriage remains controversial. The aim of the study was to evaluate whether HPV infection indeed may occur in both the maternal and placental tissue in cases of miscarriage. Decidual and chorionic villi fragments (n = 118) were dissected from 81 miscarriage cases, 68 spontaneous and 13 intentional. HPV DNA was detected using the consensus primers MY09/11; in eight cases (9.9%, 8/81), seven of which (10.3%) were from spontaneous miscarriages and one (7.7%), was from an intentional miscarriage. The deciduas (4/8) and chorionic villi (5/8) were both infected with HPV. A reverse line blot was used to genotype HPV positive samples and revealed HPV6, 11, 58, 66 and 82. Although the results obtained cannot infer an association between HPV and pregnancy loss, it cannot be ruled out. Impact Statement What is already known on this subject? Miscarriages are considered to be the most common complication in pregnancy. Several possible causes of miscarriage have been considered, and the role of infections as one of those is confirmed, especially during the second trimester of pregnancy. The prevalence of HPV in conception products is still questionable. However, an HPV infection should not be ignored and its association with miscarriage must be considered. What the results of this study add? The present study reveals the presence of HPV in the foetal and maternal tissues of conception. What the implications are of these findings for clinical practice and/or further research? This issue deserves further investigation aiming to clarify the role of HPV in miscarriage cases; which are mainly related to the specific type and grade of tissues’ abnormalities found co-topographically with a virus presence.
Are there general laws for digit evolution in squamates? The loss and re‐evolution of digits in a clade of fossorial lizards (Brachymeles, Scincinae)

Evolutionary simplification of autopodial structures is a major theme in studies of body‐form evolution. Previous studies on amniotes have supported Morse's law, that is, that the first digit reduced is Digit I, followed by Digit V. Furthermore, the question of reversibility for evolutionary digit loss and its implications for “Dollo's law” remains controversial. Here, we provide an analysis of limb and digit evolution for the skink genus Brachymeles. Employing phylogenetic, morphological, osteological, and myological data, we (a) test the hypothesis that digits have re‐evolved, (b) describe patterns of morphological evolution, and (c) investigate whether patterns of digit loss are generalizable across taxa. We found strong statistical support for digit, but not limb re‐evolution. The feet of pentadactyl species of Brachymeles are very similar to those of outgroup species, while the hands of these lineages are modified (2‐3‐3‐3‐2) and a have a reduced set of intrinsic hand muscles. Digit number variation suggests a more labile Digit V than Digit I, contrary to Morse's law. The observed pattern of digit variation is different from that of other scincid lizards (Lerista, Hemiergis, Carlia). Our results present the first evidence of clade‐specific modes of digit reduction.
Effect of Scoparia dulcis ( Linn . ) and Aerva lanata ( Linn . ) Whole Plant and Fruit Part Extracts on Ethylene Glycol Induced Urolithiasis in Male Albino Rats

The potential of two commonly used phytotherapeutic agents such as Scoparia dulcis (Linn.) and Aerva lanata (Linn.) in the management of Calcium oxalate urolithiasis has been studied in male albino rats. Oral feeding of Ethylene glycol resulted in hyperoxaluria, increased renal excretion of calcium, phosphate and decreased level of magnesium, uric acid, citrate, creatinine as well as increased level of serum uric acid and creatinine. The pH level also decreased in Ethylene glycol administered rat urine. Administration with aqueous extract of whole plant and fruit part of Scoparia dulcis and Aerva lanata gradually reduced the stone constituents and increased the stone inhibiting constituents. Comparatively animal group supplemented with fruit part of Scoparia dulcis in combination with Aerva lanata showed significantly reduced stone forming constituents and increased stone inhibiting constituents. This indicates that the fruit part of Scoparia dulcis in combination with Aerva lanata is endowed with higher antiurolithiatic activity
Rainbow Cycles in Flip Graphs

The flip graph of triangulations has as vertices all triangulations of a convex $n$-gon, and an edge between any two triangulations that differ in exactly one edge. An $r$-rainbow cycle in this graph is a cycle in which every inner edge of the triangulation appears exactly $r$ times. This notion of a rainbow cycle extends in a natural way to other flip graphs. In this paper we investigate the existence of $r$-rainbow cycles for three different flip graphs on geometric classes of objects: the aforementioned flip graph of triangulations of a convex $n$-gon, the flip graph of plane trees on an arbitrary set of $n$ points, and the flip graph of non-crossing perfect matchings on a set of $n$ points in convex position. In addition, we consider two flip graphs on classes of non-geometric objects: the flip graph of permutations of $\{1,2,\dots,n\}$ and the flip graph of $k$-element subsets of $\{1,2,\dots,n\}$. In each of the five settings, we prove the existence and non-existence of rainbow cycles for different values of $r$, $n$ and $k$.
The correlation of copy number variations with longevity in a genome-wide association study of Han Chinese

Copy number variations (CNVs) have been shown to cause numerous diseases, however, their roles in human lifespan remain elusive. In this study, we investigate the association of CNVs with longevity by comparing the Han Chinese genomes of long-lived individuals from 90 to 117 years of age and the middle-aged from 30 to 65. Our data demonstrate that the numbers of CNVs, especially deletions, increase significantly in a direct correlation with longevity. We identify eleven CNVs that strongly associate with longevity; four of them locate in the chromosome bands, 7p11.2, 20q13.33, 19p12 and 8p23.3 and overlap partially with the CNVs identified in long-lived Danish or U.S. populations, while the other seven have not been reported previously. These CNV regions encode nineteen known genes, and some of which have been shown to affect aging-related phenotypes such as the shortening of telomere length (ZNF208), the risk of cancer (FOXA1, LAMA5, ZNF716), and vascular and immune-related diseases (ARHGEF10, TOR2A, SH2D3C). In addition, we found several pathways enriched in long-lived genomes, including FOXA1 and FOXA transcription factor networks involved in regulating aging or age-dependent diseases such as cancer. Thus, our study has identified longevity-associated CNV regions and their affected genes and pathways. Our results suggest that the human genome structures such as CNVs might play an important role in determining a long life in human.
Kinetics of antibody responses to PfRH5-complex antigens in Ghanaian children with Plasmodium falciparum malaria

Plasmodium falciparum PfRH5 protein binds Ripr, CyRPA and Pf113 to form a complex that is essential for merozoite invasion of erythrocytes. The inter-genomic conservation of the PfRH5 complex proteins makes them attractive blood stage vaccine candidates. However, little is known about how antibodies to PfRH5, CyRPA and Pf113 are acquired and maintained in naturally exposed populations, and the role of PfRH5 complex proteins in naturally acquired immunity. To provide such data, we studied 206 Ghanaian children between the ages of 1–12 years, who were symptomatic, asymptomatic or aparasitemic and healthy. Plasma levels of antigen-specific IgG and IgG subclasses were measured by ELISA at several time points during acute disease and convalescence. On the day of admission with acute P. falciparum malaria, the prevalence of antibodies to PfRH5-complex proteins was low compared to other merozoite antigens (EBA175, GLURP-R0 and GLURP-R2). At convalescence, the levels of RH5-complex-specific IgG were reduced, with the decay of PfRH5-specific IgG being slower than the decay of IgG specific for CyRPA and Pf113. No correlation between IgG levels and protection against P. falciparum malaria was observed for any of the PfRH5 complex proteins. From this we conclude that specific IgG was induced against proteins from the PfRH5-complex during acute P. falciparum malaria, but the prevalence was low and the IgG levels decayed rapidly after treatment. These data indicate that the levels of IgG specific for PfRH5-complex proteins in natural infections in Ghanaian children were markers of recent exposure only.
Using CRISPR/Cas9 to Knock out Amylase in Acinar Cells Decreases Pancreatitis-Induced Autophagy

Pancreatic cancer is a malignant neoplasm that originates from acinar cells. Acinar cells get reprogrammed to become duct cells, resulting in pancreatic cancer. Pancreatitis is an acinar cell inflammation, leading to “impaired autophagy flux”. Pancreatitis promotes acinar-to-ductal transdifferentiation. Expression of amylase gets eliminated during the progression of pancreatic cancer. Amylase is considered as an acinar cell marker; however, its function in cells is not known. Thus, we investigated whether amylase affects the acinar cell autophagy and whether it plays any role in development of pancreatitis. Here, we knocked out ATG12 in a pancreatic cancer cells and acinar cells using CRISPR/Cas9. Autophagy inhibition led to an increase in the expression of duct cell markers and a simultaneous decrease in that of acinar cell markers. It also caused an increase in cell viability and changes in mitochondrial morphology. Next, we knocked out amylase in acinar cells. Amylase deficiency decreased autophagy induced by pancreatitis. Our results suggest that amylase controls pancreatitis-induced autophagy. We found that eliminating amylase expression contributes to pancreatic cancer etiology by decreasing autophagy. Furthermore, our results indicate that amylase plays a role in selective pancreatitis-induced autophagy of pancreatic enzyme vesicles.
Syndrome Z and Its Association with Obstructive Sleep Apnea

It is clear that obstructive sleep apnea (OSA) and metabolism syndrome share a similar pathophysilogic milieu that would be expected to increase the risk of cardiovascular disease. In patients with established coronary artery disease, treatment of OSA may confer long term cardiovascular benefits. Prevention of nocturnal hypoxemia, sympathetic activation and pressor surges in addition to reduction of daytime sympathetic activity, blood pressure and insulin resistance by continuous positive airway pressure would improve cardiovascular outcomes in patients with metabolic syndrome.
Predicting Authorship and Author Traits from Keystroke Dynamics

Written text transmits a good deal of nonverbal information related to the author’s identity and social factors, such as age, gender and personality. However, it is less known to what extent behavioral biometric traces transmit such information. We use typist data to study the predictiveness of authorship, and present first experiments on predicting both age and gender from keystroke dynamics. Our results show that the model based on keystroke features, while being two orders of magnitude smaller, leads to significantly higher accuracies for authorship than the text-based system. For user attribute prediction, the best approach is to combine the two, suggesting that extralinguistic factors are disclosed to a larger degree in written text, while author identity is better transmitted in typing behavior.
Impaired DNA demethylation of C/EBP sites causes premature aging

Here, Schäfer et al. investigated whether DNA methylation alterations are involved in aging. Using knockout mice for adapter proteins for site-specific demethylation by TET methylcytosine dioxygenases Gadd45a and Ing1, they show that enhancer methylation can affect aging and imply that C/EBP proteins play an unexpected role in this process.
Treatment Mechanisms

This chapter presents an overview of the mechanisms on which faecal sludge (FS) treatment processes are based, and highlights those on which the treatment technologies discussed in subsequent chapters rely. Many FS treatment technologies are based on those developed for wastewater and wastewater sludge treatment, but it is important to remember that these technologies cannot be directly transferred. FS characteristics differ greatly from wastewater, and have a direct impact on the effi ciency of treatment mechanisms (Spellman, 1997; Kopp and Dichtl, 2001). Important properties of the sludge to consider include stabilisation, organic load, particle size and density, dissolved oxygen, temperature, pH, water content and viscosity. The current understanding of physical, biological and chemical mechanisms in FS management (FSM) is limited and has been acquired via empirical observations over the years. It is important that this lack of knowledge is overcome in order to improve the design and operation of FS treatment technologies. For more detailed background information on wastewater treatment mechanisms, it is recommended that the reader refers to an engineering textbook specifi c to this topic.
Current Challenges in Delivery and Cytosolic Translocation of Therapeutic RNAs

RNA interference (RNAi) is a fundamental cellular process for the posttranscriptional regulation of gene expression. RNAi can exogenously be modulated by small RNA oligonucleotides, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), or by antisense oligonucleotides. These small oligonucleotides provided the scientific community with powerful and versatile tools to turn off the expression of genes of interest, and hold out the promise of new therapeutic solutions against a wide range of gene-associated pathologies. However, unmodified nucleic acids are highly instable in biological systems, and their weak interaction with plasma proteins confers an unfavorable pharmacokinetics. In this review, we first provide an overview of the most efficient chemical strategies that, over the past 30 years, have been used to significantly improve the therapeutic potential of oligonucleotides. Oligonucleotides targeting and delivery technologies are then presented, including covalent conjugates between oligonucleotides and targeting ligand, and noncovalent association with lipid or polymer nanoparticles. Finally, we specifically focus on the endosomal escape step, which represents a major stumbling block for the effective use of oligonucleotides as therapeutic agents. The need for approaches to quantitatively measure endosomal escape and cytosolic arrival of biomolecules is discussed in the context of the development of efficient oligonucleotide targeting and delivery vectors.
A Review of Application of Affordance Theory in Information Systems

This paper analyzes the status quo and tendency of the affordance theory in Information System literature, which can help us understand the relationship between technologies, users and organizations. This would pose a significant value on the related organizational changes and the use of social media. Based on the data from top journals, we reviewed 111 papers from Information Systems, Organization Studies and Management literatures on affordances according to the method of bibliometrics. From the analysis, we know that although the Information System discipline was a relatively late adopter, there is a large space to explore affordances in IS context. Based on the theoretical framework of affordances existence, perception, actualization and effects, we review the primary researches on affordances in IS discipline. In conclusion, IS scholars should focus on the affordance actualization, consider social affordances alongside technological affordances and improve our understanding of IT/IS-related organizational change and social media use in complicated social process.