Miracle-dz/UniFAR-FTUs huggingface dataset:
Germline replications and somatic mutation accumulation are independent of vegetative life span in Arabidopsis

Significance In contrast to animals, plants lack a segregated germline. Instead, all plant tissue is derived from small clusters of meristematic cells that throughout development give rise to vegetative tissues and only late in development to reproductive organs. Hence, mutations acquired during vegetative growth can be passed on to offspring; it is generally believed that older plants will acquire more such mutations over their lifetimes due to replication during cell division. Here we measure the number of DNA replications occurring in the cell lineage leading to gametes and demonstrate that the number of replications is independent of life span, suggesting that older plants may not be passing on more mutations to their offspring relative to younger plants. In plants, gametogenesis occurs late in development, and somatic mutations can therefore be transmitted to the next generation. Longer periods of growth are believed to result in an increase in the number of cell divisions before gametogenesis, with a concomitant increase in mutations arising due to replication errors. However, there is little experimental evidence addressing how many cell divisions occur before gametogenesis. Here, we measured loss of telomeric DNA and accumulation of replication errors in Arabidopsis with short and long life spans to determine the number of replications in lineages leading to gametes. Surprisingly, the number of cell divisions within the gamete lineage is nearly independent of both life span and vegetative growth. One consequence of the relatively stable number of replications per generation is that older plants may not pass along more somatically acquired mutations to their offspring. We confirmed this hypothesis by genomic sequencing of progeny from young and old plants. This independence can be achieved by hierarchical arrangement of cell divisions in plant meristems where vegetative growth is primarily accomplished by expansion of cells in rapidly dividing meristematic zones, which are only rarely refreshed by occasional divisions of more quiescent cells. We support this model by 5-ethynyl-2′-deoxyuridine retention experiments in shoot and root apical meristems. These results suggest that stem-cell organization has independently evolved in plants and animals to minimize mutations by limiting DNA replication.
Darriwilian (Middle Ordovician) chemostratigraphy linked to graptolite, conodont and trilobite biostratigraphy in the Fågelsång-3 drill core, Scania, Sweden

Abstract A recent core drilling in the geologically classical Fågelsång area resulted in a 58.70-m-long drill core through the lowermost Sandbian Sularp Shale, the Darriwilian Almelund Shale and Komstad Limestone, and part of the late Tremadocian to earliest Darriwilian Tøyen Shale. The shales contain zone index graptolites that are used for an update of the standard Darriwilian graptolite zone succession in Baltoscandia in which six zones are now recognized. The Komstad Limestone interval and lowermost part of the Almelund Shale have been subdivided into four conodont zones. The δ13Corg chemostratigraphy, which has been established through the entire drill core based on 120 closely spaced samples, shows a somewhat subdued development of the middle Darriwilian Isotope Carbon Excursion (MDICE), which is dated in terms of graptolite biostratigraphy. The Fågelsång isotope curve is correlated with a closely similar δ13Ccarb curve from a coeval, apparently stratigraphically essentially continuous, succession at Kårgärde in south-central Sweden, which previously has been subdivided into 13 conodont zones and subzones. For the first time, these conodont zonal units can be calibrated with Fågelsång graptolite zones using δ13Corg chemostratigraphy. The several new results of this study are expected to be useful for assessing biostratigraphic relations between units in shale and carbonate facies in Baltoscandia and elsewhere in the world.
A critical appraisal of overdiagnosis: estimates of its magnitude and implications for lung cancer screening

Background: The magnitude of overdiagnosis is a critical and unresolved issue in lung cancer (LC) screening:(1) its contribution to the increase in survival constitutes specious evidence of benefit;(2) overdiagnosed individuals who undergo resection will experience a reduction in life expectancy, partially or completely offsetting the benefit received by others in whom earlier intervention proves curative. Method: Critical analysis of studies in opposition and support of the view that LC screening imposes a substantial burden of overdiagnosis. Results: Approximately 25%, possibly more, of radiographically (chest x ray) diagnosed LC appears to be overdiagnosed. Based on the observed tumour volume doubling time of low dose CT identified small malignant pulmonary nodules, CT will markedly augment lead time, increasing exposure to competing lethal morbidities, thereby increasing overdiagnosis. Conclusion: To reduce all-cause mortality, CT screening will need to reduce LC mortality by an amount that exceeds the increase in mortality attributable to surgery and loss of pulmonary reserve in persons who are overdiagnosed or pathologically understaged (ie, with occult micrometastases). Presently, there is no evidence that CT screening will achieve any reduction in LC mortality.
Lung Adenocarcinoma Originates from Retrovirus Infection of Proliferating Type 2 Pneumocytes during Pulmonary Post-Natal Development or Tissue Repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer.
SiaA/D Interconnects c-di-GMP and RsmA Signaling to Coordinate Cellular Aggregation of Pseudomonas aeruginosa in Response to Environmental Conditions

Pseudomonas aeruginosa has emerged as an important opportunistic human pathogen that is often highly resistant to eradication strategies, mediated in part by the formation of multicellular aggregates. Cellular aggregates may occur attached to a surface (biofilm), at the air-liquid interface (pellicle), or as suspended aggregates. Compared to surface attached communities, knowledge about the regulatory processes involved in the formation of suspended cell aggregates is still limited. We have recently described the SiaA/D signal transduction module that regulates macroscopic cell aggregation during growth with, or in the presence of the surfactant SDS. Targets for SiaA/D mediated regulation include the Psl polysaccharide, the CdrAB two-partner secretion system and the CupA fimbriae. While the global regulators c-di-GMP and RsmA are known to inversely coordinate cell aggregation and regulate the expression of several adhesins, their potential impact on the expression of the cupA operon remains unknown. Here, we investigated the function of SiaA (a putative ser/thr phosphatase) and SiaD (a di-guanylate cyclase) in cupA1 expression using transcriptional reporter fusions and qRT-PCR. These studies revealed a novel interaction between the RsmA posttranscriptional regulatory system and SiaA/D mediated macroscopic aggregation. The RsmA/rsmY/Z system was found to affect macroscopic aggregate formation in the presence of surfactant by impacting the stability of the cupA1 mRNA transcript and we reveal that RsmA directly binds to the cupA1 leader sequence in vitro. We further identified that transcription of the RsmA antagonist rsmZ is controlled in a SiaA/D dependent manner during growth with SDS. Finally, we found that the siaD transcript is also under regulatory control of RsmA and that overproduction of RsmA or the deletion of siaD results in decreased cellular cyclic di-guanosine monophosphate (c-di-GMP) levels quantified by a transcriptional reporter, demonstrating that SiaA/D connects c-di-GMP and RsmA/rsmY/Z signaling to reciprocally regulate cell aggregation in response to environmental conditions.
Fall-risk assessment by combined movement related potentials and co-contraction index monitoring

In this paper we propose a novel approach for online fall-risk assessment based on concurrent EEG and EMG monitoring. The fall-risk evaluation is based on: i) clinical condition of the individual, ii) environment, iii) EMG agonist-antagonist co-contraction analysis and iv) Movement Related Potentials and event related desynchronizations occurrence/absence. The fall-risk assessment evaluation algorithm has been implemented on a FPGA (Altera Cyclone V SE 5CSEMA5F31C6N) in order to realize an autonomous and stand-alone fall prevention tool. The experimental results (based on a dataset of 10 individuals) are described and demonstrate the validity of the algorithm and its FPGA implementation, which responds in 41ms, well within the 300ms time limit according to a study on 45 fallers and 80 non-fallers (with 74 years average age).
Dissociating the neural mechanisms of memory-based guidance of visual selection

Visual selection is influenced by items in working memory (WM) and priming from implicit memory when a stimulus is repeated across time. WM effects are typically held to be top-down in nature [Soto D, Heinke D, Humphreys GW, Blanco MJ (2005) J Exp Psychol Hum Percept Perform 31:248–261], whereas implicit priming may operate in a bottom-up manner [Theeuwes J, Reimann B, Mortier K (2006) Vis Cogn 14: 466–489]. How WM and implicit priming affects influence visual selection remains poorly understood, however. Here, we report functional MRI evidence that dissociates the neural mechanisms involved in these memory-based effects on selection. The reappearance of a stimulus held in WM enhanced activity in superior frontal gyrus, midtemporal, and occipital areas that are known to encode the prior occurrence of stimuli. In contrast, mere stimulus repetition elicited a suppressive response in the same regions. An additional finding was that a frontothalamic network was sensitive to the behavioral relevance of a match between the contents of WM and the visual search array, enhancing activity when the contents of WM matched the critical target of selection. Items held in WM influence selection by using neural coding distinct to effects of mere repetition.
Maintaining Maintainability = Recognizing Reachability

1 INTRODUCTION How do we assess the maintainablilty of our systems? Given the infinity of parameters we could extract from our programs , what is the least we must collect to tell us the most about maintainablilty? To answer this question, we offer a theoretical model of maintenance effort. We will assume that:
Systematic Review and Meta-Analysis of the Use of Phosphodiesterase Type 5 Inhibitors for Treatment of Erectile Dysfunction following Bilateral Nerve-Sparing Radical Prostatectomy

Prostate cancer is relatively common cancer occurring in males. Radical prostatectomy (RP) is the most effective treatment for a localized tumor but erectile dysfunction (ED) is common complication, even when bilateral nerve-sparing RP (BNSRP) is performed. Clinical trials have shown varied effectiveness of phosphodiesterase type-5 inhibitors (PDE5-Is) for treatment of post-BNSRP ED, but there remains controversy over the application of this treatment and no formal systematic review and meta-analysis for the use of PDE5-Is for this condition has been conducted. This review was to systematically assess the efficacy and safety of oral PDE5-Is for post-BNSRP ED. A database search was conducted to identify randomized controlled trials (RCTs). The comparative efficacy of treatments was analyzed by fixed or random effect modeling. Erectile function was measured using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) question-2, 3 and the Global Assessment Question (GAQ). The rate and incidence of adverse events (AEs) were determined. The quality of included studies was appraised using the Cochrane Collaboration bias appraisal tool. Eight RCTs were included in the analyses. PDE5-Is were effective for treating post-BNSRP ED compared to placebo when erectile function was determined using the IIEF score [mean difference (MD) 5.63, 95% confidence interval (CI) (4.26–6.99)], SEP-2 [relative risk (RR) 1.63, 95% CI (1.18–2.25) ], SEP-3 [RR 2.00, 95% CI (1.27–3.15) ] and GAQ [RR 3.35, 95% CI (2.68–4.67) ]. The subgroup analysis could find a trend that longer treatment duration, higher dosage, on-demand dosing, sildenafil and mild ED are associated with more responsiveness to PDE5-Is. PDE5-Is were overall well tolerated with headache being the most commonly reported AE. Our data provides compelling evidence for the use of PDE5-Is as a primary treatment for post-BNSRP ED. However, further studies are required to optomize usage parameters (such as dosage and duration of treatment).
Quantitative intramuscular myoelectric activity of lumbar portions of psoas and the abdominal wall during a wide variety of tasks.

PURPOSE Since most previous reports of EMG activation profiles from psoas and the abdominal wall have been qualitative, the objective of this work was to document myoelectric activity from these deep muscles. This knowledge is required to assist in choosing specific training exercises and for making rehabilitation decisions that require knowledge of normalized and calibrated muscle activation levels in different tasks. METHODS Intramuscular EMG was collected from five men and three women, in whom amplitudes were normalized to maximum contraction efforts and reported over a wide variety of clinical and rehabilitation tasks. Electrodes were inserted into vertebral portions of psoas and the three layers of the abdominal wall. Normalized signal amplitudes were reported as peak levels and time histories. RESULTS All forms of sit-ups activated psoas (15-35% MVC) more than the curl-up (<10%); psoas was not highly activated during barbell lifting of loads up to 100 kg (< 16% MVC); psoas was most active during maximal hip flexion efforts; push-ups activated psoas up to 25% MVC. Several isometric abdominal exercises were evaluated using the criteria of maximizing abdominal activation while minimizing psoas activity: the side (bridge) support exercise proved the best training method for the abdominal wall. CONCLUSIONS Consideration of deep muscle activity, provided in this report, is important for choosing the most appropriate rehabilitation and training program for an individual. Specific guidance is provided for choosing the best abdominal exercise, together with activation profiles during lifting, during twisting, and during hip rotation.
Comparing static bug finders and statistical prediction

The all-important goal of delivering better software at lower cost has led to a vital, enduring quest for ways to find and remove defects efficiently and accurately. To this end, two parallel lines of research have emerged over the last years. Static analysis seeks to find defects using algorithms that process well-defined semantic abstractions of code. Statistical defect prediction uses historical data to estimate parameters of statistical formulae modeling the phenomena thought to govern defect occurrence and predict where defects are likely to occur. These two approaches have emerged from distinct intellectual traditions and have largely evolved independently, in “splendid isolation”. In this paper, we evaluate these two (largely) disparate approaches on a similar footing. We use historical defect data to apprise the two approaches, compare them, and seek synergies. We find that under some accounting principles, they provide comparable benefits; we also find that in some settings, the performance of certain static bug-finders can be enhanced using information provided by statistical defect prediction.
Molecular epidemiology of malaria in Cameroon. XVI. Longitudinal surveillance of in vitro pyrimethamine resistance in Plasmodium falciparum.

Clinical observations have shown that pyrimethamine resistance develops rapidly in endemic countries where antifolate drugs are used massively for the treatment of Plasmodium falciparum infections. To analyze this phenomenon, the in vitro response of clinical isolates to pyrimethamine and the dihydrofolate reductase (dhfr) gene sequence were analyzed in 2000-2001 and compared with the results obtained since 1994 in Yaounde, Cameroon. Of 139 samples obtained in 2000-2001, 10 (7.2%) isolates were of the wild-type, 116 had pure mutant alleles (2 [1.4%] with a single mutation, 11 [7.9%] with double mutations, and 103 [74.1%] with triple mutations), and 13 (9.4%) had mixed alleles. With the exception of a single isolate with triple mutations (50% inhibitory concentration [IC50] = 84.3 nM), all isolates with pure wild-type dhfr alleles (IC50 < 100 nM) and those with pure mutant dhfr alleles (between 1 and 3 point mutations; IC50 > or = 100 nM) were clearly distinguished by in vitro drug sensitivity assays. The results of the two methods are highly correlated, and both methodologic approaches indicate an increasing proportion of pyrimethamine-resistant isolates in Yaounde over the past eight years (42-45% in 1994-1995, 63-67% in 1997-1998, and 88-92% in 2000-2001). At present, clinical isolates carrying triple dhfr mutations predominate in Yaounde. This situation calls for a regular surveillance of the efficacy of antifolate drugs by all available means, including clinical evaluation, in vitro drug sensitivity assays, molecular markers, and pharmacologic studies.
Disparities in access to physicians and medications for the treatment of substance use disorders between publicly and privately funded treatment programs in the United States.

OBJECTIVE Prior research suggests that publicly funded substance use disorder (SUD) treatment programs lag behind privately funded programs in adoption of evidence-based practices, resulting in disparities in access to high-quality SUD treatment. These disparities highlight a critical public health concern because the majority of SUD patients in the United States are treated in the publicly funded treatment sector. This study uses recent data to examine disparities in access to physicians and availability of medications for the treatment of SUDs between publicly and privately funded SUD treatment programs. METHOD Data were collected from 595 specialty SUD treatment programs from 2007 to 2010 via face-to-face interviews, mailed surveys, and telephone interviews with treatment program administrators. RESULTS Publicly funded programs were less likely than privately funded programs to have a physician on staff, even after controlling for several organizational characteristics that were associated with access to physicians. The results of negative binomial regression indicated that, even after taking into account physician access and other organizational variables, publicly funded programs prescribed fewer SUD medications than privately funded SUD treatment programs. CONCLUSIONS Patients seeking treatment in publicly funded treatment programs continue to face disparities in access to high-quality SUD treatment that supports patients' choices among a range of medication options. However, implementation of the Affordable Care Act may facilitate greater access to physicians and use of medications in publicly funded SUD treatment programs.
Unsupervised Methods to Improve Aspect-Based Sentiment Analysis in Czech

We examine the effectiveness of several unsupervised methods for latent semantics discovery as features for aspect-based sentiment analysis (ABSA). We use the shared task definition from SemEval 2014. In our experiments we use labeled and unlabeled corpora within the restaurants domain for two languages: Czech and English. We show that our models improve the ABSA performance and prove that our approach is worth exploring. Moreover, we achieve new state-of-the-art results for Czech. Another important contribution of our work is that we created two new Czech corpora within the restaurant domain for the ABSA task: one labeled for supervised training, and the other (considerably larger) unlabeled for unsupervised training. The corpora are available to the research community.
Rethinking Soot for summary-based whole-program analysis

Whole-program static analysis has been extensively studied and widely used in the past few decades. For modern object-oriented programs, scalability has become an important issue for using whole-program analysis in real-world tools. In addition, the ever-increasing size of libraries (e.g., the JDK library) and frameworks exacerbates the scalability problems. To achieve the desired level of analysis performance, an effective approach could be to generate and apply analysis summary information for library methods. In this paper, such an approach is referred to as a summary-based whole-program analysis. The challenges for this technique are twofold: (1) carefully designed abstractions and algorithms are needed to create and use client-independent and analysis-specific library summary information; and (2) support for summary generation and application should be effectively incorporated into existing analysis infrastructures. This paper focuses on the second challenge. It uses Soot, a widely-used program analysis framework for Java, as a vehicle to explore some of the important issues in providing analysis infrastructures with capabilities for summary-based analysis. Experimental studies are presented to show that significant savings can potentially be achieved by making a whole-program alias analysis summary-based. To actually achieve these savings, the paper proposes to extend Soot to add support for summary-based analysis. Finally, a brief discussion of the required framework extensions is presented.