Miracle-dz/UniFAR-FTUs huggingface dataset:
Brief Definitive Report

Somatic hypermutation is a specifi c mutagenic process that can diversify the Ig genes at several stages of the B cell diff erentiation pathway: either outside an immune response, leading to repertoire diversifi cation, or during antigen driven responses, leading to affi nity maturation through the selection of B cells displaying better antigen-binding capacities (1). Hypermutation is initiated by activation-induced cytidine deaminase (AID) through an enzymatic process that deaminates cytidines into uracils and is essentially, but not exclusively , targeted at the heavy and light chain V genes of the Ig locus (reference 2; for review see references 3, 4). However, mutations at the Ig locus are equally distributed at G/C and A/T bases, which requires that specifi c error-prone repair pathways process this C-focused lesion to broaden its mutation spectrum (5). In spite of the large number of repair factors able to handle uracils within the eukaryotic cell, only two of them have been shown to contribute to hyper-mutation: uracil N-glycosylase (UNG) and the DNA-binding moiety of the mismatch repair complex (MSH2–MSH6) (6–14). When these two factors are missing, the mutation pattern becomes the imprint of the sole AID action, the replication of uracils generated on both DNA strands resulting in C to T and G to A transitions at the sites of AID deamination (14). Error-prone DNA polymerases, in particular those involved in the replicative bypass of DNA lesions, have been considered as prime candidates to generate mutations at A/T base pairs from the initial deamination event. The Ig gene mutation pattern of patients aff ected with the variant form of the xeroderma pig-mentosum syndrome, a genetic disease corresponding to inactivation of DNA polymerase η (pol η) (15), was shown to be markedly, albeit DNA polymerase η is the sole contributor of A/T modifi cations during immunoglobulin gene hypermutation in the mouse Mutations at A/T bases within immunoglobulin genes have been shown to be generated by a repair pathway involving the DNA-binding moiety of the mismatch repair complex constituted by the MSH2–MSH6 proteins, together with DNA polymerase í µí» (pol í µí»). However, residual A/T mutagenesis is still observed upon inactivation in the mouse of each of these factors, suggesting that the panel of activities involved might be more complex. We reported previously that residual A/T mutagenesis in pol í µí»–defi cient mice was likely contributed by another enzyme not normally involved in hypermutation, DNA polymerase í µí», …
Predictors of the Extent of Carotid Atherosclerosis in Patients Treated with Radiotherapy for Nasopharyngeal Carcinoma

Objective To determine the predictors of the extent of carotid atherosclerosis in patients treated with radiotherapy (RT) for nasopharyngeal carcinoma (NPC). Methods The present study investigated 129 post-RT NPC patients. Carotid atherosclerotic parameters, such as carotid intima-media thickness, carotid arterial stiffness and carotid plaque burden (plaque score, the presence of plaque and ≥50% stenosis) were assessed using ultrasonography. The association between carotid atherosclerotic parameters and nine potential predictors, including age, gender, post-RT duration, radiation dose, chemotherapy, diabetes mellitus, hypertension, hypercholesterolemia, and smoking, were determined using multiple regression. The cutoff values of age, post-RT duration and number of cardiovascular risk factors for the presence of carotid plaque or ≥50% carotid stenosis were analyzed using receiver operating characteristic (ROC) curve analysis. Multiple testing was corrected using Benjamini-Hochberg false discovery rate. Results Age, post-RT duration and number of cardiovascular risk factors were significantly associated with carotid plaque burden (corrected P value, Pcor<0.05). Age of 44.5 years (sensitivity = 99.2% and specificity = 50%, Pcor<0.01) and post-RT duration of 8.5 years (sensitivity = 75.7% and specificity = 64.3%, Pcor<0.001) were the cutoff values for detecting carotid plaque, while post-RT duration of 13.5 years (sensitivity = 66.7% and specificity = 71.6%, Pcor<0.001) and 1.5 cardiovascular risk factors (sensitivity = 40.7% and specificity = 84.3%, Pcor<0.05) were the cutoff values for screening ≥50% carotid stenosis. Conclusions Age, post-RT duration and number of cardiovascular risk factors are significant predictors of carotid atherosclerosis in post-RT NPC patients. Post-RT NPC patients, who are at least 45 years old, with post-RT duration of 9 years or above, and/or have ≥2 cardiovascular risk factors, are more susceptible to carotid atherosclerosis.
Manuscript under review Cognitive and neural foundations of goal-directed decision making: An integrative framework

Recent work has given rise to the view that reward-based decision making is governed by two key controllers: a habit system, which stores stimulus-response associations shaped by past reward, and a goal-oriented system that selects actions based on their anticipated outcomes. The current literature provides a rich body of computational theory addressing habit formation, centering on temporal-difference learning mechanisms. Less progress has been made toward formalizing the processes involved in goal-directed decision making. We draw on recent work in cognitive neuroscience, animal learning, cognitive and developmental psychology and machine learning, to propose a new theory of goal-directed decision making. Our basic proposal is that the brain, within an identifiable network of cortical and subcortical structures, implements a generative model of action: a representation of the interdependencies among states, actions, outcomes, and rewards. Goal-directed decision making is understood as involving a set of procedures for querying this generative model, in order to extract plans for action. We focus on one particularly interesting and powerful form of query, which involves reasoning from the assumption of future reward. The proposed account is formalized in a set of simulations addressing benchmark empirical phenomena, and tested through two human behavioral studies. We discuss the relationship between the proposed framework and other models of decision making, including recent models of perceptual decision making, to which our theory bears an intimate but surprising connection. Botvinick and colleagues Goal-Directed Decision Making 2 Cognitive and neural foundations of goal-directed decision making: An integrative framework Since the earliest days of both psychology and neuroscience, investigators interested in decision making and the control of behavior have recognized a fundamental distinction between habitual action and goal-directed or purposive action. Although the roots of this opposition clearly lie in commonsense notions from folk psychology, some more precise and operational distinctions arose from the classic debates of the first half of the 20th century. There, Hull (1943), Spence (1956) and others characterized action selection as driven primarily by immediate associations from internal and environmental states to responses, while others including Tolman (1932) and McDougall (1923) portrayed it as arising from a process of prospective planning, involving the anticipation, evaluation and comparison of action outcomes. Tolman and other purposivists supported their view by pointing to specific empirical results from research with animals. Two findings that received particular emphasis were latent learning and detour behavior. In Blodgett's (1929) classic demonstration of latent learning, rats ran a …
Memristor Crossbar-Based Hardware Implementation of the IDS Method

Ink drop spread (IDS) is the engine of an active learning method, which is the methodology of soft computing. IDS, as a pattern-based processing unit, extracts useful information from a system that is subjected to modeling. In spite of its excellent potential to solve problems such as classification and modeling compared with other soft-computing tools, finding its simple and fast hardware implementation is still a challenge. This paper describes a new hardware implementation of the IDS method that is based on the memristor crossbar structure. In addition to simplicity, being completely real time, having low latency, and the ability to continue working properly after the occurrence of power failure are some of the advantages of our proposed circuit. Moreover, some of operations in the IDS method have fuzzy nature, and as we will show at the end of this paper, updation of rules in the IDS structure and spiky neural networks are very similar. Therefore, IDS can be considered as a new fuzzy implementation of artificial spiky neural networks as well.
Predictive power dispatch through negotiated locational pricing

A predictive mechanism is proposed in order to reduce price volatility linked to large fluctuations from demand and renewable energy generation in competitive electricity markets. The market participants are modelled as price-elastic units, price-inelastic units, and storage operators. The distributed control algorithm determines prices over a time horizon through a negotiation procedure in order to maximize social welfare while satisfying network constraints. A simple flow allocation method is used to assign responsibility for constraint violations on the network to individual units and a control rule is then used to adjust nodal prices accordingly. Such a framework is appropriate for the inclusion of aggregated household appliances or other ‘virtual’ market participants realized through smart grid infrastructure. Results are examined in detail for a 4-bus network and then success is demonstrated for a densely-populated 39-bus network. Formal convergence requirements are given under a restricted subset of the demonstrated conditions. The scheme is shown to allow storage to reduce price volatility in the presence of fluctuating demand.
Vascular Health and Risk Management Dovepress Utility of High-sensitivity Cardiac Troponin T in Patients Receiving Anthracycline Chemotherapy

Background: Anthracycline chemotherapy remains an integral part of the care for curative intent chemotherapy in breast cancer and non-Hodgkin lymphoma patients. Better tools need to be identified to predict cardiac complications of anthracycline chemotherapy. Materials and methods: We investigated the utility of high-sensitivity cardiac troponin T (hscTnT), N-terminal pro-B-type natriuretic peptide, cardiac troponin T and I, and creatine kinase (CK)-MB in cancer patients receiving anthracycline-based chemotherapy, in order to determine whether baseline levels or changes in these biomarkers may help predict the onset of congestive heart failure. Results: Eighteen consecutive patients with a pathologic diagnosis of breast cancer or non-Hodgkin lymphoma were enrolled. The median dose of doxorubicin exposure was 240 mg/m 2 (range 240–400 mg/m 2). After treatment with doxorubicin, the hscTnT increased to 19.1 pg/mL (P,0.001). CKMB and N-terminal pro-B-type natriuretic peptide levels increased to 1.1 ng/mL and 88.3 pg/mL, respectively (P=0.02). When subjects who had a decline in left ventricular ejection fraction (LVEF) by equilibrium radionuclide ventriculography were compared to those who did not have a change in LVEF, there was a suggestion that those subjects with an elevated baseline hscTnT were more likely to have a decline in LVEF (2.7 pg/mL and 0.1 pg/mL, respectively; P=0.07). Spearman correlation demonstrated that patients with higher baseline hscTnT and CKMB tended to have a greater decline in LVEF (Spearman correlation-0.54, 95% confidence interval-0.80 to-0.08 [P=0.02], and-0.49, 95% confidence interval-0.77 to-0.01 [P=0.04], respectively). Conclusion: Elevations in baseline hscTnT levels are suggestive of an oncology subgroup at high risk of developing cardiac complications from their chemotherapy. Early detection by oncologists with the use of baseline biomarkers may be clinically important in designing interventions to prevent serious anthracycline-based chemotherapy complications.
Impaired response to Listeria in H2-M3–deficient mice reveals a nonredundant role of MHC class Ib–specific T cells in host defense

The major histocompatibility complex (MHC) class Ib molecule H2-M3 primes the rapid expansion of CD8+ T cells by presenting N-formylated bacterial peptides. However, the significance of H2-M3–restricted T cells in host defense against bacteria is unclear. We generated H2-M3–deficient mice to investigate the role of H2-M3 in immunity against Listeria monocytogenes (LM), a model intracellular bacterial pathogen. H2-M3–deficient mice are impaired in early bacterial clearance during primary infection, with diminished LM-specific CD8+ T cell responses and compromised innate immune functions. Although H2-M3–restricted CD8+ T cells constitute a significant proportion of the anti-listerial CD8+ T cell repertoire, the kinetics and magnitude of MHC class Ia–restricted T cell responses are not altered in H2-M3–deficient mice. The fact that MHC class Ia–restricted responses cannot compensate for the H2-M3–mediated immunity suggests a nonredundant role of H2-M3 in the protective immunity against LM. Thus, the early H2-M3–restricted response temporally bridges the gap between innate and adaptive immune responses, subsequently affecting the function of both branches of the immune system.
Estimating image depth using shape collections

Images, while easy to acquire, view, publish, and share, they lack critical depth information. This poses a serious bottleneck for many image manipulation, editing, and retrieval tasks. In this paper we consider the problem of adding depth to an image of an object, effectively 'lifting' it back to 3D, by exploiting a collection of aligned 3D models of related objects. Our key insight is that, even when the imaged object is not contained in the shape collection, the network of shapes implicitly characterizes a shape-specific deformation subspace that regularizes the problem and enables robust diffusion of depth information from the shape collection to the input image. We evaluate our fully automatic approach on diverse and challenging input images, validate the results against Kinect depth readings, and demonstrate several imaging applications including depth-enhanced image editing and image relighting.
First-order-principles-based constructive network topologies: An application to robot inverse dynamics

Modeling physical systems with neural networks (NN) requires expert architects to determine the best number of nodes, layers and activation functions. For complex systems, such as articulated robots, reported results are limited in accuracy and generalization capabilities. In this work, we introduce the concept FOPnet. It is based on first-order principles and system knowledge to determine topologies of parametrized operator networks that accurately model input-output mappings of physical systems. These topologies consist of meaningful building elements and connections as well as a reduced number of parameters that describe the variables' interdependencies. In this way, learning speed is boosted and the model's accuracy, precision and generalization power improved. We apply the methodology to a 7 degrees-of-freedom LWR4 manipulator and discuss the estimation and generalization capabilities of the network. Results are compared to conventional Feed Forward NN as well as a state-of-the-art Deep Recurrent NN. For the considered complex robot dynamics FOPnet was able to achieve a seven orders of magnitude smaller generalization RMSE.
Fraction 1 capsular antigen (F1) purification from Yersinia pestis CO92 and from an Escherichia coli recombinant strain and efficacy against lethal plague challenge

As a first step in formulating an improved plague vaccine, we developed a simple purification strategy that produced high yields of pure cell-associated and culture supernatant-derived fraction 1 capsular antigen (F1) from both avirulent Yersinia pestis C092 (Pgm- Lcr-) and an Escherichia coli F1-producing recombinant strain. Cell-associated F1 was partially purified by sequential ammonium sulfate precipitations of a sodium chloride extract of acetone-dried bacteria harvested from broth cultures. Cell-free F1 was precipitated directly from culture supernatants with a single application of 30% ammonium sulfate. By exploiting the aggregative property of F1, large quantities of purified high-molecular-weight F1 species from both cell extracts and supernatants were isolated in the void volume of a preparative gel filtration column. Highly purified, endotoxin-free F1, combined with two different adjuvants, induced very high F1 titers in mice and protected them against either subcutaneous (70 to 100% survival) or aerosol (65 to 84% survival) challenge with virulent organisms. This protection was independent of the source of the antigen and the adjuvant used. F1-induced protection against both subcutaneous and aerosol challenge was also significantly better than that conferred by immunization with the licensed killed whole-cell vaccine. Our results indicate that F1 antigen represents a major protective component of previously studied crude capsule preparations, and immunity to F1 antigen provides a primary means for the host to overcome plague infection by either the subcutaneous or respiratory route.
Predicting the direction of ornament evolution in Trinidadian guppies (Poecilia reticulata)

Sexual selection is thought to be opposed by natural selection such that ornamental traits express a balance between these two antagonistic influences. Phenotypic variation among populations may indicate local shifts in this balance, or that different stable ‘solutions’ are possible, but testing these alternatives presents a major challenge. In the guppy (Poecilia reticulata), a small freshwater fish with male-limited ornamental coloration, these issues can be addressed by transplanting fish among sites of varying predation pressure, thus effectively manipulating the strength and nature of natural selection. Here, we contrast the evolutionary outcome of two such introductions conducted in the Trinidadian El Cedro and Aripo Rivers. We use sophisticated colour appraisal methods that account for full spectrum colour variation and which incorporate the very latest visual sensitivity data for guppies and their predators. Our data indicate that ornamentation evolved along different trajectories: whereas Aripo males evolved more numerous and/or larger orange, black and iridescent markings, El Cedro males only evolved more extensive and brighter iridescence. Examination of the El Cedro experiment also revealed little or no ornamental evolution at the control site over 29 years, which contrasts markedly with the rapid (approx. 2–3 years) changes reported for introduction populations. Finally, whole colour-pattern analysis suggested that the greatest visual difference between El Cedro introduction and control fish would be perceived by the two most salient viewers: guppies and the putatively dangerous predator Crenicichla alta. We discuss whether and how these evolutionary trajectories may result from founder effects, population-specific mate preferences and/or sensory drive.
A Simple Fixed Parameter Tractable Algorithm for Computing the Hybridization Number of Two (Not Necessarily Binary) Trees

Here, we present a new fixed parameter tractable algorithm to compute the hybridization number r of two rooted, not necessarily binary phylogenetic trees on taxon set X in time (6rr! ) · poly(n), where n = |X|. The novelty of this approach is its use of terminals, which are maximal elements of a natural partial order on X, and several insights from the softwired clusters literature. This yields a surprisingly simple and practical bounded-search algorithm and offers an alternative perspective on the underlying combinatorial structure of the hybridization number problem.
High Prevalence of Hyper-Aerotolerant Campylobacter jejuni in Retail Poultry with Potential Implication in Human Infection

Campylobacter jejuni is a leading cause of foodborne illnesses around the world. Since C. jejuni is microaerophilic and sensitive to oxygen, aerotolerance is important in the transmission of C. jejuni to humans via foods under aerobic conditions. In this study, 70 C. jejuni strains were isolated from retail raw chicken meats and were subject to multilocus sequence typing (MLST) analysis. In the aerotolerance testing by aerobic shaking at 200 rpm, 50 (71.4%) isolates survived after 12 h (i.e., aerotolerant), whereas 20 (28.6%) isolates did not (i.e., aerosensitive). Interestingly, further aerobic cultivation showed that 25 (35.7%) isolates still survived even after 24 h of vigorous aerobic shaking (i.e., hyper-aerotolerant). Compared to aerosensitive strains, the hyper-aerotolerant strains exhibited increased resistance to oxidative stress, both peroxide and superoxide. A mutation of ahpC in hyper-aerotolerant strains significantly impaired aerotolerance, indicating oxidative stress defense plays an important role in hyper-aerotolerance. The aerotolerant and hyper-aerotolerant strains were primarily classified into MLST clonal complexes (CCs)-21 and -45, which are known to be the major CCs implicated in human gastroenteritis. Compared to the aerosensitive strains, CC-21 was more dominant than CC-45 in aerotolerant and hyper-aerotolerant strains. The findings in this study revealed that hyper-aerotolerant C. jejuni is highly prevalent in raw chicken meats. The enhanced aerotolerance in C. jejuni would impact human infection by increasing possibilities of the foodborne transmission of C. jejuni under aerobic conditions.
Scientific rigour in psycho‐oncology trials: why and how to avoid common statistical errors

It is well documented that statistical and methodological flaws are common in much of the health research literature, including psycho‐oncology. These can have far‐reaching effects, including the publishing of misleading results; the wasting of time, effort, and financial resources; exposure of patients to the potential harms of research and decreased confidence in science and researchers by the public.
Shift in the megakaryocyte ploidy in MDS patients: microcytofluorometry with DAPI staining after destaining of Wright‐Giemsa stain

We applied DAPI (4′,6‐diamidino‐2‐phenylindole) staining to the determination of nuclear DNA content in single megakaryocytes in 12 normal subjects and 12 patients with myelodysplastic syndrome (MDS). After the megakaryocytes had been identified on Wright‐Giemsa stained smear and classified according to modified Feinendegen's classification, they were photographed. Then Wright‐Giemsa stain was removed by immersion in 50% ethanol at 37°C for 1 h and 100% methanol at 37°C for 1 h. The specimens were then stained with DAPI solution (DAPI 0.01 mg/ml, pH 7.4 Tris‐EDTA‐2Na buffer solution and 0.01 M 2‐mercaptoethylamine hydrochloride mixed at the ratio of 0.5:98.5:1.0) for more than 30 min. The amount of nuclear DNA in the previously identified megakaryocytes was measured by microcytofluorometry.