Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Systems Biology Peer Review Process File Absolute Quantification of Microbial Proteomes at Different States by Directed Mass Spectrometry Transaction Report

(Note: With the exception of the correction of typographical or spelling errors that could be a source of ambiguity, letters and reports are not edited. The original formatting of letters and referee reports may not be reflected in this compilation.) Thank you again for submitting your work to Molecular Systems Biology. We have now heard back from two of the three referees who accepted to evaluate the study. Since the recommendations provided byy these two referees are very similar, I prefer to make a decision now rather than to delay the process further. As you will see, the referees find the topic of your study of potential interest and are supportive. They raise however a series of points and make several suggestions for modifications, which we would ask you to carefully address in a revision of the present work. The recommendations are very clear in this regard. We would also kindly ask you to deposit the primary MS/MS data from the time course experiments in one of the major public databases and include the relevant identifiers in the Materials and Method section. We also greatly appreciate that you included key datasets in supplementary information. We would however kindly ask you to avoid using the PDF format for large tables and upload these files either as Excel tables or plain text (eg in tab delimited or CSV format). Systems Biology will publish online a Review Process File to accompany accepted manuscripts. When preparing your letter of response, please be aware that in the event of acceptance, your cover letter/point-by-point document will be included as part of this File, which will be available to the scientific community. More information about this initiative is available in our Instructions to Authors. If you have any questions about this initiative, please contact the editorial office msb@embo.org .
Mediterranean diet, kidney function, and mortality in men with CKD.

BACKGROUND AND OBJECTIVES Adherence to a Mediterranean diet may link to a better preserved kidney function in the community as well as a favorable cardiometabolic profile and reduced mortality risk in individuals with manifest CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Dietary habits were determined by 7-day dietary records in a population-based cohort of 1110 Swedish men (age 70 years) from 1991 to 1995, 506 of whom were considered to have CKD because of a GFR<60 ml/min per 1.73 m(2). A Mediterranean Diet Score was calculated, and participants were categorized as having low, medium, or high adherence. Adequate dietary reporters were identified with Goldberg cutoffs (n=597). Deaths were registered during a median follow-up of 9.9 years. RESULTS Compared with low adherents, medium and high adherents were 23% and 42% less likely to have CKD, respectively (adjusted odds ratio [95% confidence interval]=0.77 [0.57 to 1.05] and 0.58 [0.38 to 0.87], respectively, P for trend=0.04). Among those individuals with CKD, phosphate intake and net endogenous acid production were progressively lower across increasing adherence groups. No differences were observed regarding other cardiometabolic risk factors across adherence groups. As many as 168 (33%) CKD individuals died during follow-up. Compared with low adherents, proportional hazards regression associated medium and high adherents to a 25% and 23% lower mortality risk, respectively (adjusted hazard ratio [95% confidence interval]=0.75 [0.52 to 1.06] and 0.77 [0.44 to 1.36], respectively, P for trend=0.10). Sensitivity analyses showed significant and stronger associations when only adequate dietary reporters were considered. CONCLUSIONS Adherence to a Mediterranean dietary pattern is associated with lower likelihood of CKD in elderly men. A greater adherence to this diet independently predicted survival in those patients with manifest CKD. Clinical trials are warranted to test the hypothesis that following such a diet could improve outcomes (independent of other healthy lifestyles) in CKD patients.
Suppression of leukemia development caused by PTEN loss

Multiple genetic or molecular alterations are known to be associated with cancer stem cell formation and cancer development. Targeting such alterations, therefore, may lead to cancer prevention. By crossing our previously established phosphatase and tensin homolog (Pten)-null acute T-lymphoblastic leukemia (T-ALL) model onto the recombination-activating gene 1−/− background, we show that the lack of variable, diversity and joining [V(D)J] recombination completely abolishes the Tcrα/δ-c-myc translocation and T-ALL development, regardless of β-catenin activation. We identify mammalian target of rapamycin (mTOR) as a regulator of β-selection. Rapamycin, an mTOR-specific inhibitor, alters nutrient sensing and blocks T-cell differentiation from CD4−CD8− to CD4+CD8+, the stage where the Tcrα/δ-c-myc translocation occurs. Long-term rapamycin treatment of preleukemic Pten-null mice prevents Tcrα/δ-c-myc translocation and leukemia stem cell (LSC) formation, and it halts T-ALL development. However, rapamycin alone fails to inhibit mTOR signaling in the c-KitmidCD3+Lin− population enriched for LSCs and eliminate these cells. Our results support the idea that preventing LSC formation and selectively targeting LSCs are promising approaches for antileukemia therapies.
Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231.

BACKGROUND Phosphorylation of tau protein at threonine 231 (using full-length tau, 441 amino acids, for the numbering scheme) (p-tau(231)) occurs specifically in postmortem brain tissue of patients with Alzheimer disease (AD) and can be sensitively detected in cerebrospinal fluid (CSF). OBJECTIVES To determine to what extent CSF levels of p-tau(231) distinguish patients with AD from control subjects and from patients with other dementias, and to investigate whether p-tau(231) levels are a better diagnostic marker than levels of total tau protein (t-tau) in CSF. DESIGN AND SETTING Cross-sectional, multicenter, memory clinic-based studies. PARTICIPANTS One hundred ninety-two patients with a clinical diagnosis of AD, frontotemporal dementia (FTD), vascular dementia, Lewy body dementia, or other neurological disorder and healthy controls. MAIN OUTCOME MEASURES Levels of CSF tau proteins as measured with enzyme-linked immunosorbent assays. RESULTS Mean CSF levels of p-tau(231) were significantly elevated in the AD group compared with all other groups. Levels of p-tau(231) did not correlate with dementia severity in AD, and discriminated with a sensitivity of 90.2% and a specificity of 80.0% between AD and all non-AD disorders. Moreover, p-tau(231) levels improved diagnostic accuracy compared with t-tau levels when patients with AD were compared with healthy controls (P =.03) and demented subjects (P<.001), particularly those with FTD (P<.001), but not those with vascular and Lewy body dementias. Sensitivity levels between AD and FTD were raised by p-tau(231) compared with t-tau levels from 57.7% to 90.2% at a specificity level of 92.3% for both markers. CONCLUSION Increased levels of CSF p-tau(231) may be a useful, clinically applicable biological marker for the differential diagnosis of AD, particularly for distinguishing AD from FTD.
Reinforcement Learning with Perceptual Aliasing: The Perceptual Distinctions Approach

It is known that Perceptual Aliasing may significantly diminish the effectiveness of reinforcement learning algorithms [Whitehead and Ballard, 1991]. Perceptual aliasing occurs when multiple situations that are indistinguishable from immediate perceptual input require different responses from the system. For example, if a robot can only see forward, yet the presence of a battery charger behind it determines whether or not it should backup, immediate perception alone is insufficient for determining the most appropriate action. It is problematic since reinforcement algorithms typically learn a control policy from immediate perceptual input to the optimal choice of action. This paper introduces the predictive distinctions approach to compensate for perceptual aliasing caused from incomplete perception of the world. An additional component, a predictive model, is utilized to track aspects of the world that may not be visible at all times. In addition to the control policy, the model must also be learned, and to allow for stochastic actions and noisy perception, a probabilistic model is learned from experience. In the process, the system must discover, on its own, the important distinctions in the world. Experimental results are given for a simple simulated domain, and additional issues are discussed.
What can the 2008/10 broadband flare of PKS 1502+106 tell us? Nuclear opacity, magnetic fields, and the location of gamma rays

Context. The origin of blazar variability, seen from radio up to gamma rays, is still a heavily debated matter and broadband flares offer a unique testbed towards a better understanding of these extreme objects. Such an energetic outburst was detected by Fermi/LAT in 2008 from the blazar PKS 1502+106. The outburst was observed from gamma rays down to radio frequencies. Aims. Through the delay between flare maxima at different radio frequencies, we study the frequency-dependent position of the unit-opacity surface and infer its absolute position with respect to the jet base. This nuclear opacity profile enables the magnetic field tomography of the jet. We also localize the gamma-ray emission region and explore the mechanism producing the flare. Methods. The radio flare of PKS 1502+106 is studied through single-dish flux density measurements at 12 frequencies in the range 2.64 to 226.5 GHz. To quantify it, we employ both a Gaussian process regression and a discrete cross-correlation function analysis. Results. We find that the light curve parameters (flare amplitude and cross-band delays) show a power-law dependence on frequency. Delays decrease with frequency, and the flare amplitudes increase up to about 43 GHz and then decay. This behavior is consistent with a shock propagating downstream the jet. The self-absorbed radio cores are located between about 10 and 4 pc from the jet base and their magnetic field strengths range between 14 and 176 mG, at the frequencies 2.64 to 86.24 GHz. Finally, the gamma-ray active region is located at (1.9 +/- 1.1) pc away from the jet base.
Lakoff's Theory of Moral Reasoning in Presidential Campaign Advertisements, 1952–2012

This study examines the presence and distribution of George Lakoff's Strict Father and Nurturant Parent paradigms of moral reasoning in presidential campaign advertisements between 1952 and 2012. Results show that Republicans outpace Democrats in the general use of moral reasoning and that Republicans are far more likely to use Strict Father language than Democrats. The study found no difference in the use of Strict Father/Nurturant Parent morality throughout history, during times of war and recession, or if the candidate was an incumbent. The Strict Father and Nurturant Parent models of moral reasoning were also evaluated based on their relationship to political issues. Findings reveal that Democrats actively avoid Nurturant Parent reasoning when discussing specific social programs.
Dark Pockets and Decision Support: The Information Technology Value Cycle in Efficient Markets

Introduction During the last thirty years, the financial markets have demonstrated the remarkably dynamic nature of competitive advantage and reward derived from innovative investments in information technology (IT). Pioneers like Batterymarch Financial Management, whose early use of mainframe-based decision support for equity portfolio construction resulted in large profits for the firm, showed the direction that future investments in information technology would take in support of investment management.
Snail1a and Snail1b cooperate in the anterior migration of the axial mesendoderm in the zebrafish embryo

The Snail genes are implicated in processes that involve cell movement, both during embryonic development and tumour progression. In teleosts, the vertebrate Snail1 gene is represented by two distinct genes, snail1a and snail1b (previously snail1 and snail2). These genes are expressed in complementary mesodermal domains and their combined expression matches that of their mammalian counterpart. By analysing their loss and gain of function, we found that the most-anterior axial mesendodermal cells, the precursors of the polster, move in a cohesive manner directed by the activity of snail1a- and snail1b-expressing cells surrounding these precursors. The cell-autonomous function of Snail1 proteins regulates cell motility and influences the behaviour of Snail-negative neighbouring cells. Snail1a is required by the prechordal plate for it to reach its normal position, whereas Snail1b controls the acquisition of its normal shape. These non-redundant functions of Snail1a and Snail1b in controlling axial mesendoderm migration comply with the duplication-degeneration-complementation model, and indicate that Snail genes not only act as inducers of epithelial-to-mesenchymal transition, but also as more general regulators of cell adhesion and movement.
Anova for Unbalanced Data: An Overview

Ecological studies typically involve comparison of biological responses among a variety of environmental conditions. When the response variables have continuous distributions and the conditions are discrete, whether inherently or by design, then it is appropriate to analyze the data using analysis of variance (ANOVA). When data conform to a complete, balanced design (equal numbers of observations in each experimental treatment), it is straightforward to conduct an ANOVA, particularly with the aid of the numerous statistical computing packages that are available. Interpretation of an ANOVA of balanced data is also unambiguous. Unfortunately, for a variety of reasons, it is rare that a practicing ecologist embarks on an analysis of data that are completely balanced. Regardless of its cause, lack of balance necessitates care in the analysis and interpretation. In this paper, our aims is to provide an overview of the consequences of lack of balance and to give some guidelines to analyzing unbalanced data for models involving fixed effects. Our treatment is necessarily cursory and will not substitute for training available from a sequence of courses in mathematical statistics and linear models. It is intended to introduce the reader to the main issues and to the extensive statistical literature that deals with them.
Automata Theory on Sliding Windows

In a recent paper we analyzed the space complexity of streaming algorithms whose goal is to decide membership of a sliding window to a fixed language. For the class of regular languages we proved a space trichotomy theorem: for every regular language the optimal space bound is either constant, logarithmic or linear. In this paper we continue this line of research: We present natural characterizations for the constant and logarithmic space classes and establish tight relationships to the concept of language growth. We also analyze the space complexity with respect to automata size and prove almost matching lower and upper bounds. Finally, we consider the decision problem whether a language given by a DFA/NFA admits a sliding window algorithm using logarithmic/constant space.
Single access retroperitoneoscopic adrenalectomy: initial experience

Today, endoscopic adrenalectomy has become a gold standard in endocrine surgery. To minimize the morbidity and improve cosmesis, single access retroperitoneoscopic adrenalectomy (SARA) has been developed as an alternative to traditional multiport laparoscopy and single port access (SPA) surgery, potentially exploiting even more the already proven benefits of minimally invasive surgery. We applied the SARA technique to adrenalectomy using the posterior retroperitoneal approach. The aim is to highlight the current situation regarding the feasibility and safety of single access retroperitoneoscopic adrenalectomy and to present our initial experience. Between October 2010 and February 2011, a 74-year-old woman (body mass index (BMI) – 31 kg/m2) with pheochromocytoma (1.2 cm in size) and 3 women, aged 45, 46 and 66 years (BMI – 27, 32, 33 kg/m2), respectively, and all diagnosed with Conn's adenoma (from 1.2 cm to 2.0 cm in size), underwent single access retroperitoneoscopic adrenalectomies. Operations were performed using conventional laparoscopic (STORZ) equipment. No conversions to the open or conventional retroperitoneal approach were necessary. There were no perioperative or postoperative complications. Operating time ranged from 60 min to 80 min. All patients left the hospital 2 days after surgery. The single access retroperitoneoscopic technique has been successfully applied to adrenalectomy as an available alternative to multiport laparoendoscopic adrenalectomy and single port access surgery. Exposure, visualization and dissection are the same as in retroperitoneal endoscopic adrenalectomy. The SARA surgery offers patient benefits such as faster convalescence, decreased postoperative scarring, better cosmetic effect and financial benefit.
Rheological Behaviour Of Ethylene Glycol Based Titania Nanofluids

The purpose of this study is to investigate the rheological behaviour of ethylene glycol (EG) based titania nanofluids. Generally, rheology is the study of the deformation and flow of the matter. Nanofluids are dilute liquid suspensions of nanoparticles which at least one critical dimension smaller than ~100nm in which is used to enhance the thermal heat coefficient. Nanofluids have better heat characteristics and have larger thermal conductivities compared to the base fluids, however, the thermal behaviour of nanofluids correlates well with the rheological behaviour of the nanofluids. This indicates the significance of studying the rheology of nanofluids. In order to study the rheology of nanofluids, a set of stable nanofluids have to be prepared with several different concentration and pH value. Then the characterization of nanofluids will be done in terms of stability and viscosity; at different temperature (27 °C, 40 °C, 50 °C and 60 °C); and concentration of titania nanoparticles. Later the viscosity of the nanofluids were analysed to understand the rheology. Titania nanoparticles were dispersed in the EG as the base fluid by twostep method. A surfactant, Sodium Lauryl Sulphate (SLS) was used to stabilize the nanofluids. SLS surfactant helps to reduce agglomeration in the titania nanofluids. From the observation, the samples were stable for not more than a week. For both pH of titania nanofluids (pH 3 and pH 11), the viscosity was increasing with the increment of weight percentages and decrease with the temperature. Furthermore, the shear stress decreases with the temperature and increases with weight percentage.
Increased functional connectivity common to symptomatic amyotrophic lateral sclerosis and those at genetic risk

Objective To discern presymptomatic changes in brain structure or function using advanced MRI in carriers of mutations predisposing to amyotrophic lateral sclerosis (ALS). Methods T1-weighted, diffusion weighted and resting state functional MRI data were acquired at 3 T for 12 asymptomatic mutation carriers (psALS), 12 age-matched controls and affected patients with ALS. Cortical thickness analysis, voxel-based morphometry, volumetric and shape analyses of subcortical structures, tract-based spatial statistics of metrics derived from the diffusion tensor, and resting state functional connectivity (FC) analyses were performed. Results Grey matter cortical thickness and shape analysis revealed significant atrophy in patients with ALS (but not psALS) compared with controls in the right primary motor cortex and right caudate. Comparison of diffusion tensor metrics showed widespread fractional anisotropy and radial diffusivity differences in patients with ALS compared to controls and the psALS group, encompassing parts of the corpus callosum, corticospinal tracts and superior longitudinal fasciculus. While FC in the resting-state sensorimotor network was similar in psALS and controls, FC between the cerebellum and a network comprising the precuneus, cingulate & middle frontal lobe was significantly higher in psALS and affected ALS compared to controls. Conclusions Rather than structural brain changes, increased FC may be among the earliest detectable brain abnormalities in asymptomatic carriers of ALS-causing gene mutations. With replication and significant refinement, this technique has potential in the future assessment of neuroprotective strategies.
MAO-B Elevation in Mouse Brain Astrocytes Results in Parkinson's Pathology

Age-related increases in monoamine oxidase B (MAO-B) may contribute to neurodegeneration associated with Parkinson's disease (PD). The MAO-B inhibitor deprenyl, a long-standing antiparkinsonian therapy, is currently used clinically in concert with the dopamine precursor L-DOPA. Clinical studies suggesting that deprenyl treatment alone is not protective against PD associated mortality were targeted to symptomatic patients. However, dopamine loss is at least 60% by the time PD is symptomatically detectable, therefore lack of effect of MAO-B inhibition in these patients does not negate a role for MAO-B in pre-symptomatic dopaminergic loss. In order to directly evaluate the role of age-related elevations in astroglial MAO-B in the early initiation or progression of PD, we created genetically engineered transgenic mice in which MAO-B levels could be specifically induced within astroglia in adult animals. Elevated astrocytic MAO-B mimicking age related increase resulted in specific, selective and progressive loss of dopaminergic neurons in the substantia nigra (SN), the same subset of neurons primarily impacted in the human condition. This was accompanied by other PD-related alterations including selective decreases in mitochondrial complex I activity and increased mitochondrial oxidative stress. Along with a global astrogliosis, we observed local microglial activation within the SN. These pathologies correlated with decreased locomotor activity. Importantly, these events occurred even in the absence of the PD-inducing neurotoxin MPTP. Our data demonstrates that elevation of murine astrocytic MAO-B by itself can induce several phenotypes of PD, signifying that MAO-B could be directly involved in multiple aspects of disease neuropathology. Mechanistically this may involve increases in membrane permeant H2O2 which can oxidize dopamine within dopaminergic neurons to dopaminochrome which, via interaction with mitochondrial complex I, can result in increased mitochondrial superoxide. Our inducible astrocytic MAO-B transgenic provides a novel model for exploring pathways involved in initiation and progression of several key features associated with PD pathology and for therapeutic drug testing.