Miracle-dz/UniFAR-FTUs huggingface dataset:
Composability of regulatory sequences controlling transcription and translation in Escherichia coli

The inability to predict heterologous gene expression levels precisely hinders our ability to engineer biological systems. Using well-characterized regulatory elements offers a potential solution only if such elements behave predictably when combined. We synthesized 12,563 combinations of common promoters and ribosome binding sites and simultaneously measured DNA, RNA, and protein levels from the entire library. Using a simple model, we found that RNA and protein expression were within twofold of expected levels 80% and 64% of the time, respectively. The large dataset allowed quantitation of global effects, such as translation rate on mRNA stability and mRNA secondary structure on translation rate. However, the worst 5% of constructs deviated from prediction by 13-fold on average, which could hinder large-scale genetic engineering projects. The ease and scale this of approach indicates that rather than relying on prediction or standardization, we can screen synthetic libraries for desired behavior.
Peripheral blood RNA gene expression profiling in patients with bacterial meningitis

Objectives: The aim of present study was to find genetic pathways activated during infection with bacterial meningitis (BM) and potentially influencing the course of the infection using genome-wide RNA expression profiling combined with pathway analysis and functional annotation of the differential transcription. Methods: We analyzed 21 patients with BM hospitalized in 2008. The control group consisted of 18 healthy subjects. The RNA was extracted from whole blood, globin mRNA was depleted and gene expression profiling was performed using GeneChip Human Gene 1.0 ST Arrays which can assess the transcription of 28,869 genes. Gene expression profile data were analyzed using Bioconductor packages and Bayesian modeling. Functional annotation of the enriched gene sets was used to define the altered genetic networks. We also analyzed whether gene expression profiles depend on the clinical course and outcome. In order to verify the microarray results, the expression levels of ten functionally relevant genes with high statistical significance (CD177, IL1R2, IL18R1, IL18RAP, OLFM4, TLR5, CPA3, FCER1A, IL5RA, and IL7R) were confirmed by quantitative real-time (qRT) PCR. Results: There were 8569 genes displaying differential expression at a significance level of p < 0.05. Following False Discovery Rate (FDR) correction, a total of 5500 genes remained significant at a p-value of < 0.01. Quantitative RT-PCR confirmed the differential expression in 10 selected genes. Functional annotation and network analysis indicated that most of the genes were related to activation of humoral and cellular immune responses (enrichment score 43). Those changes were found in both adults and in children with BM compared to the healthy controls. The gene expression profiles did not significantly depend on the clinical outcome, but there was a strong influence of the specific type of pathogen underlying BM. Conclusion: This study demonstrates that there is a very strong activation of immune response at the transcriptional level during BM and that the type of pathogen influences this transcriptional activation.
Task Avoidance, Number Skills and Parental Learning Difficulties as Predictors of Poor Response to Instruction

Altogether 1,285 Finnish children were followed up from the end of kindergarten through Grade 1. All were nonreaders at school entrance. The aim was to delineate predictors of resistance to treatment that are evidenced as little or no reading progress during Grade 1. On the basis of reading achievement in Grade 1 spring, four subgroups were formed. These were fast, average, and slow reading acquisition and slow progress in both reading and math. Kindergarten spring scores in phonological awareness, letter knowledge, rapid naming, and number skills differentiated well among the groups, the latter two being more robust predictors. Task avoidance added to the prediction over and above cognitive skills. Its effect disappeared when parental history of reading and math difficulties was included in the equation. The present results depict poor response to instruction as a general learning problem rather than a specific reading difficulty. Poor response to instruction differs from dyslexia also in that treatment resisters start school with cognitive prerequisites that do not indicate severe reading and math problems.
Planning promotes goal striving.

d etermining the factors that promote successful goal striving is one of the fundamental questions studied by selfregulation and motivation researchers (Bargh, Gollwitzer, & Oettingen, 2010; Gollwitzer & Moskowitz, 1996; Oettingen & Gollwitzer, 2001). A number of theories, and supporting empirical data, suggest that the type of goal chosen and the commitment to that goal are important determinants in whether an individual carries out the behaviors necessary for goal attainment (e.g., Ajzen, 1985; Bandura, 1997; Carver & Scheier, 1998; Elliot, 2008; Locke & Latham, 2006; Molden & Dweck, 2006; Oettingen, Pak, & Schnetter, 2001). Within these models, choosing or accepting a goal or standard is the central act of will in the pursuit of goals. We agree with this contention but argue in this chapter that further acts of will should facilitate goal attainment, in particular, when goal striving is confronted with implemental problems (e.g., difficulties getting started because of failure to use opportunities to do so; sticking to ongoing goal striving in the face of distractions, temptations, and competing goals). Such acts of will can take the form of making plans that specify when, where, and how an instrumental goaldirected response is to be enacted. More specifically, the person may take control over (i.e., selfregulate) goal striving by making if–then plans (i.e., form implementation intentions) that specify an anticipated critical situation and link it to an instrumental goaldirected response.
Effects of elevated carbon dioxide and temperature on locomotion and the repeatability of lateralization in a keystone marine mollusc

ABSTRACT Recent work has shown that the behaviour of marine organisms can be affected by elevated PCO2, although little is known about the effect of multiple stressors. We therefore investigated the effect of elevated PCO2 and temperature on locomotion and behaviour during prey searching in the marine gastropod Concholepas concholepas, a predator characteristic of the southeastern Pacific coast. Movement duration, decision time, route finding and lateralization were measured using a T-maze tank with a prey positioned behind a barrier. Four treatments, representing present day and near-future scenarios of ocean acidification and warming were used in rearing the individuals for 6 months. Regardless of the treatment, no significant differences were found in relative and absolute lateralization before and after exposure for 6 months. However, relative lateralization was not repeatable for animals tested after 6 months at elevated PCO2 at both experimental temperatures, whereas it was repeatable in individuals kept at the present day level of PCO2. We suggest that these effects may be related to a behavioural malfunction caused by elevated PCO2. Movement duration, decision time and route finding were not repeatable. However, movement duration and decision time increased and route finding decreased in elevated PCO2 (at 15°C), suggesting that elevated PCO2 has negative effects on the locomotor and sensory performance of C. concholepas in the presence of a prey odour, thereby decreasing their ability to forage efficiently. Highlighted Article: Elevated levels of CO2 affect route finding, locomotion and repeatability of lateralization of a keystone marine mollusc in a T-maze.
Hypocalcemia Increase the Severity of the Clinical Degree of Covid-19 Patients

Introduction: Coronavirus Disease 2019 (Covid-19) can cause electrolyte imbalances, one of which is hypocalcemia. Hypocalcemia has been identified as a predictor of the severity of Covid-19. This research aimed to determine the correlation between hypocalcemia and the clinical degrees of Covid-19 patients at UNS Hospital. Method: This study used a cross-sectional design with a population of Covid-19 patients treated at the Covid-19 ward at UNS Hospital in 2020-2022. Samples were collected from medical records by purposive sampling technique that met the inclusion and exclusion criterias. Results: There were 90 cases of hypocalcemia in Covid-19 patients. Mild hypocalcemia (88.9%) was found more than severe hypocalcemia (11.1%). Hypocalcemia was more common in male sex (54.4%), aged 46-65 years (70%), and in moderate clinical degree (31.1%). The Kolmogorov-Smirnov statistical test results showed a significant correlation between hypocalcemia and the clinical degree of Covid-19 with p=0.009 (p<0.05). The Spearman statistical test results showed that there was a fairly strong and statistically significant correlation between hypocalcemia and the clinical degree of Covid-19 where r=0.310 and p=0.003 (p<0.05). Conclusion: There is a fairly strong and statistically significant unidirectional correlation between hypocalcemia and the clinical degree of Covid-19 patients.
The sensitivity and specificity of the neurological examination in polyneuropathy patients with clinical and electrophysiological correlations

Introduction Polyneuropathy is one of the most prevalent neurologic disorders. Although several studies explored the role of the neurological examination in polyneuropathy, they were mostly restricted to specific subgroups of patients and have not correlated examination findings with symptoms and electrophysiological results. Objectives To explore the sensitivity and specificity of different neurological examination components in patients with diverse etiologies for polyneuropathy, find the most sensitive combination of examination components for polyneuropathy detection, and correlate examination findings with symptoms and electrophysiological results. Methods Patients with polyneuropathy attending the neuromuscular clinic from 01/2013 to 09/2015 were evaluated. Inclusion criteria included symptomatic polyneuropathy, which was confirmed by electrophysiological studies. 47 subjects with no symptoms or electrophysiological findings suggestive for polyneuropathy, served as controls. Results The total cohort included 312 polyneuropathy patients, with a mean age of 60±14 years. Abnormal examination was found in 95%, most commonly sensory findings (86%). The most common abnormal examination components were impaired ankle reflexes (74%), vibration (73%), and pinprick (72%) sensation. Combining ankle reflex examination with vibration or pinprick perception had the highest sensitivity, of 88%. The specificities of individual examination component were generally high, excluding ankle reflexes (62%), and vibration perception (77%). Abnormal examination findings were correlated with symptomatic weakness and worse electrophysiological parameters. Conclusion The neurological examination is a valid, sensitive and specific tool for diagnosing polyneuropathy, and findings correlate with polyneuropathy severity. Ankle reflex examination combined with either vibration or pinprick sensory testing is the most sensitive combination for diagnosing polyneuropathy, and should be considered minimal essential components of the physical examination in patients with suspected polyneuropathy.
Learning and Evolution in Neural Networks

This article describes simulations on populations of neural networks that both evolve at the population level and learn at the individual level. Unlike other simulations, the evolutionary task (finding food in the environment) and the learning task (predicting the next position of food on the basis of present position and planned network's movement) are different tasks. In these conditions, learning influences evolution (without Lamarckian inheritance of learned weight changes) and evolution influences learning. Average but not peak fitness has a better evolutionary growth with learning than without learning. After the initial generations, individuals that learn to predict during life also improve their food-finding ability during life. Furthermore, individuals that inherit an innate capacity to find food also inherit an innate predisposition to learn to predict the sensory consequences of their movements. They do not predict better at birth, but they do learn to predict better than individuals of the initial generation given the same learning experience. The results are interpreted in terms of a notion of dynamic correlation between the fitness surface and the learning surface. Evolution succeeds in finding both individuals that have high fitness and individuals that, although they do not have high fitness at birth, end up with high fitness because they learn to predict.
Strongly Unforgeable and Efficient Proxy Signature Scheme with Fast Revocation Secure in the Standard Model

The existing proxy signature schemes with the proxy revocation function are proven to be malleable and do not possess strong unforgeability. Motivated by these concerns, a new proxy signature scheme with fast revocation is proposed, and it can be proved that the proposed scheme can achieve strong unforgeability in the standard model. By using this scheme, the original signer can generate the delegation warrant for the proxy signer, and at the same time, he/she can perform the immediate revocation to completely terminate the delegation when needed. Analyses show that the proposed scheme satisfies all of the security requirements of proxy signature and has shorter public parameters than the existing ones.
UvA-DARE ( Digital Academic Repository ) Dominance of objects over context in a mediotemporal lobe model of schizophrenia

Background: A large body of evidence suggests impaired context processing in schizophrenia. Here we propose that this impairment arises from defective integration of mediotemporal ‘what’ and ‘where’ routes, carrying object and spatial information to the hippocampus. Methodology and Findings: We have previously shown, in a mediotemporal lobe (MTL) model, that the abnormal connectivity between MTL regions observed in schizophrenia can explain the episodic memory deficits associated with the disorder. Here we show that the same neuropathology leads to several context processing deficits observed in patients with schizophrenia: 1) failure to choose subordinate stimuli over dominant ones when the former fit the context, 2) decreased contextual constraints in memory retrieval, as reflected in increased false alarm rates and 3) impaired retrieval of contextual information in source monitoring. Model analyses show that these deficits occur because the ‘schizophrenic MTL’ forms fragmented episodic representations, in which objects are overrepresented at the expense of spatial contextual information. Conclusions and Significance: These findings highlight the importance of MTL neuropathology in schizophrenia, demonstrating that it may underlie a broad spectrum of deficits, including context processing and memory impairments. It is argued that these processing deficits may contribute to central schizophrenia symptoms such as contextually inappropriate behavior, associative abnormalities, conversational drift, concreteness and delusions. Citation: Talamini LM, Meeter M (2009) Dominance of Objects over Context in a Mediotemporal Lobe Model of Schizophrenia. PLoS ONE 4(8): e6505. doi:10.1371/journal.pone. 0006505 Editor: André Aleman, University of Groningen, Netherlands Received March 10, 2009; Accepted June 4, 2009; Published August 4, 2009 Copyright: 2009 Talamini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Grant sponsor: Dutch National Science Foundation (NWO), www.nwo. nl. Grant numbers: 051-04-102 and 402-01-635. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: L.M. Talamini@uva.nl
Altered cell cycle kinetics, gene expression, and G1 restriction point regulation in Rb-deficient fibroblasts

Fibroblasts prepared from retinoblastoma (Rb) gene-negative mouse embryos exhibit a shorter G1 phase of the growth cycle and smaller size than wild-type cells. In addition, the mutant cells are no longer inhibited by low levels of cycloheximide at any point in G1 but do remain sensitive to serum withdrawal until late in G1. Certain cell cycle-regulated genes showed no temporal or quantitative differences in expression. In contrast, cyclin E expression in Rb-deficient cells is deregulated in two ways. Cyclin E mRNA is generally derepressed in mutant cells and reaches peak levels about 6 h earlier in G1 than in wild-type cells. Moreover, cyclin E protein levels are higher in the Rb-/- cells than would be predicted from the levels of its mRNA. Thus, the selective growth advantage conferred by Rb gene deletion during tumorigenesis may be explained in part by changes in the regulation of cyclin E. In addition, the mechanisms defining the restriction point of late G1 may consist of at least two molecular events, one cycloheximide sensitive and pRb dependent and the other serum sensitive and pRb independent.
Technical difficulties during the training phase for Tightrope® and percutaneous lateral fabellar suture techniques for cranial cruciate ligament repair.

OBJECTIVE To compare level of difficulty, deviations from technical description and postoperative assessment during the training of veterinary students, small animal surgical residents, and a board certified surgeon for Tightrope® (TR) and percutaneous lateral fabella suture (pLFS) techniques for cranial cruciate ligament (CCL) repair. STUDY DESIGN Prospective study. SAMPLE POPULATION Cadaveric canine pelvic limbs (n = 32). METHODS Sixteen 3rd year veterinary students, 6 small animal surgical residents and a Diplomate of the American College of Veterinary Surgeons performed the TR and pLFS techniques on paired limbs. Perceived level of difficulty, duration of surgery, and technical deviations were assessed by questionnaire, radiographs, and dissection. Results were compared between techniques with McNemar's test. RESULTS The TR procedure was perceived as more technically demanding than the pLFS by veterinary students and residents. Technical deviations were overall more common after TR than pLFS, and in limbs repaired by students, regardless of procedure. The most difficult aspect of the TR consists of the bone tunnels whereas for pLFS it was passing the suture around the femorofabellar ligament. The sensitivity of radiographs for detection of technical deviations was 39% after TR and 50% after pLFS. CONCLUSION Technical deviations are more common during the training phase of TR than pLFS, and the sensitivity of radiographs to detect those is low. Repeated practice on cadavers followed by dissection is recommended before use in patients.
Nonparametric estimation in a multiplicative censoring model with symmetric noise

ABSTRACT We consider the model , , where the , the and thus the are all independent and identically distributed. The 's have density f and are the variables of interest, the 's are multiplicative noise with uniform density on , for some 0<a<1, and the two sequences are independent. However, only the 's are observed. We study nonparametric estimation of both the density f and the corresponding survival function. In each context, a projection estimator of an auxiliary function is built, from which estimator of the function of interest is deduced. Risk bounds in term of integrated squared error are provided, showing that the dimension parameter associated with the projection step has to perform a compromise. Thus, a model selection strategy is proposed in both cases of density and survival function estimation. The resulting estimators are proven to reach the best possible risk bounds. Simulation experiments illustrate the good performances of the estimators and a real data example is described.
Presentation by a major histocompatibility complex class I molecule of nucleoprotein peptide expressed in two different genes of an influenza virus transfectant

Major histocompatibility (MHC) class I glycoproteins are specialized to present to CD8+ T cells, peptides that originate from proteins synthesized within the cytoplasm. Conventional killed vaccines are unable to get into the cell cytoplasm and therefore fail to expand the CD8+ T cell population. We have created a novel influenza transfectant virus, R10, which carries an immunogenic peptide from the nucleoprotein (NP) of PR8 influenza virus in its hemagglutinin (HA) and another similar peptide in its HK influenza virus NP. The two peptides are both presented by H-2Db and bind with approximately equal affinity. They can compete with one another for binding to H-2Db. Yet in cells infected with R10, both peptides are presented efficiently enough to expand the respective cytotoxic T lymphocyte (CTL) precursors in vivo and to serve as targets for CTL lysis in vitro. It has been proposed that proteins bearing signal sequences may be processed by a transporter-independent pathway. To investigate this, we infected the transporter-deficient cell line RMA-S with the R10 virus to see if the NP peptide expressed by the HA would be presented. The result shows that even the presence of a signal peptide in the HA does not overcome the lack of a transporter function, suggesting that the presentation of both peptides is dependent on functional transporter proteins. Our data also suggest the feasibility of creating by genetic engineering, recombinant vaccines expressing multiple epitopes that can effectively stimulate a cellular immune response.
Continuous tracer infusion to measure in vivo metabolite turnover rates in trout

This paper describes a double dorsal aorta catheterization technique allowing the measurement of substrate turnover rates by continuous infusion of metabolic tracers in rainbow trout. The placement of both catheters can be performed in about 30 min with minimal surgical training. As a practical example of a routine substrate flux measurement, glucose turnover rate of resting trout was measured by primed continuous infusion of 6-[3H]glucose through one of the catheters and blood sampling from the other. The animals maintained resting metabolic rate, normal blood glucose and low blood lactate concentrations throughout the experiments. Glucose isotopic steady state was achieved in less than 40 min, and mean turnover rate was 9.0±0.7 µmol kg-1 min-1 (N=8). Comparison with published glucose turnover rates measured in trout and other teleost species suggest that values previously obtained using the 'bolus injection technique' are underestimates of true flux rates. We conclude that the simple surgical technique presented here opens the door to the dynamic study of substrate kinetics under a variety of experimental conditions and that it can be adapted to the investigation of most metabolic substrates, including fatty acids, glycerol, amino acids and lactate, in addition to glucose. Future application of the continuous infusion technique under steady-state as well as non-steady-state conditions will add a new dimension to the general understanding of fish metabolism.