Miracle-dz/UniFAR-FTUs huggingface dataset:
Insertional Mutagenesis and Deep Profiling Reveals Gene Hierarchies and a Myc/p53-Dependent Bottleneck in Lymphomagenesis

Retroviral insertional mutagenesis (RIM) is a powerful tool for cancer genomics that was combined in this study with deep sequencing (RIM/DS) to facilitate a comprehensive analysis of lymphoma progression. Transgenic mice expressing two potent collaborating oncogenes in the germ line (CD2-MYC, -Runx2) develop rapid onset tumours that can be accelerated and rendered polyclonal by neonatal Moloney murine leukaemia virus (MoMLV) infection. RIM/DS analysis of 28 polyclonal lymphomas identified 771 common insertion sites (CISs) defining a ‘progression network’ that encompassed a remarkably large fraction of known MoMLV target genes, with further strong indications of oncogenic selection above the background of MoMLV integration preference. Progression driven by RIM was characterised as a Darwinian process of clonal competition engaging proliferation control networks downstream of cytokine and T-cell receptor signalling. Enhancer mode activation accounted for the most efficiently selected CIS target genes, including Ccr7 as the most prominent of a set of chemokine receptors driving paracrine growth stimulation and lymphoma dissemination. Another large target gene subset including candidate tumour suppressors was disrupted by intragenic insertions. A second RIM/DS screen comparing lymphomas of wild-type and parental transgenics showed that CD2-MYC tumours are virtually dependent on activation of Runx family genes in strong preference to other potent Myc collaborating genes (Gfi1, Notch1). Ikzf1 was identified as a novel collaborating gene for Runx2 and illustrated the interface between integration preference and oncogenic selection. Lymphoma target genes for MoMLV can be classified into (a) a small set of master regulators that confer self-renewal; overcoming p53 and other failsafe pathways and (b) a large group of progression genes that control autonomous proliferation in transformed cells. These findings provide insights into retroviral biology, human cancer genetics and the safety of vector-mediated gene therapy.
Relationship between high platelet turnover and platelet function in high-risk patients with coronary artery disease on dual antiplatelet therapy

Summary A high platelet turnover rate produce a population of immature reticulated platelets (RP) that could confer, despite of antiplatelet drugs, a residual platelet reactivity (RPR) in coronary artery disease (CAD) patients. To assess the influence of RP on platelet reactivity in CAD patients on dual antiplatelet therapy we measured RP in 372 patients by using the Sysmex XE-2100 haematology analyzer and platelet function by optical platelet aggregometry (PA) on platelet-rich-plasma induced by 1 mmol arachidonic acid (AA-PA) and 10 μM ADP (ADP-PA). RPR was defined as either AA-PA >20% or ADP-PA >70%. RP were expressed as a percentage of RP of the total optical platelet count (immature platelet fraction; IPF) and as the percentage of RP highly fluorescent (higly fluorescent immature platelet fraction; H-IPF). Moderate but significant positive correlations between PA, IPF, H-IPF, and mean platelet volume (MPV) were found. According to tertiles of IPF, H-IPF and MPV, a significant trend for an increase of platelet aggregation by AA and ADP was evidenced. Furthermore, a significant difference for IPF, H-IPF and MPV between patients with and without RPR was observed. A linear regression analysis showed that IPF, H-IPF and MPV significantly affected PA measured by AA and ADP. At multivariate linear regression analysis these associations were confirmed. Moreover, a logistic regression analysis demonstrated that IPF, H-IPF and MPV significantly influenced the risk of RPR, and in the multivariate model these results remained significant. This study indicates that a high rate of platelet turnover is a new mechanism associated with platelet reactivity in high risk CAD patients on dual antiplatelet therapy.
Effect of Irrigation Regime and Soil Nutrients on the Growth of the Paddy Weed Heteranthera reniformis and Rice Grain Yield

The growth of Heteranthera reniformis, an invasive alien paddy weed, can be affected by cultivation practices. The experiments were conducted using herbicide-free soil to understand the effects of irrigation regimes and nutrient treatments on the growth of H. reniformis, as well as yield parameters while competing with a pre-existing seedbank. The pot experiments were conducted in a randomized complete block design (RBCD) with three replicates and twelve treatments. The four irrigation regimes (IRs): continuous irrigation (CI), soil condition at near saturation (non-puddled) (S), alternate wetting and drying (AWD) irrigation under two conditions [rewatered when the soil water potential reached −25 kPa (25P) and −35 kPa (35P)], and three nutrient treatments (NTs) of 0–0–0 NPK (NT0), 40–25–30 NPK (NT1), 80–50–60 NPK (NT2), kg ha−1 were established. The IRs had a significant effect on the growth of H. reniformis and other paddy field weeds, and the growth of H. reniformis was suppressed in the AWD regimes. NT2 resulted in more rice panicles, higher grain yield, and increased irrigation water use efficiency (IWUE). The highest grain yield and protein content were observed in S–NT2 and 25P–NT2 treatments. The IR and NT can be maintained to prevent yield penalties and reduce the invasiveness of weeds.
28nm CMOS, energy efficient and variability tolerant, 350mV-to-1.0V, 10MHz/700MHz, 252bits frame error-decoder

A minimum design effort methodology to enable energy efficient and variability tolerant ultra-wide voltage-range frame error-decoder design in 28nm CMOS technology is presented. Critical aspects of a digital design development - standard cells, interface, clock tree and implementation - were optimized enabling 1.0V to 350mV functionality, 10x energy reduction, 10MHz to 700MHz frequency, and a reduction of the variability enabling industrial yield at ultra-low voltage. The same design was then ported to 28nm Fully-Depleted SOI (FDSOI), offering up-to 2x higher energy efficiency while validating the design methodology robustness.
Serum Interleukin-6 , Tumor Necrosis Factor and C-reactive Protein in Early Prediction of Severity of Acute Pancreatitis

cute pancreatitis is a protean disease of wide clinical variation ranging from mild abdominal discomfort to a severe hemorrhagic necrotizing attack or even mortality. Early assessment of the severity and prediction the prognosis of acute pancreatitis is an important issue for managing the patients. There are a number of well-known measurements for evaluating the prognosis of acute pancreatitis, such as the Ranson and Glasgow and Acute Physiology and Chronic Health Evaluation (APACHE II) evaluating scoring systems. All of these require measurement of many clinically-based parameters and are very complicated and time-consuming. Optimally, a single, simple and reliable marker would be available to assess the severity of acute pancreatitis. The usefulness of cytokine detection for early assessment of the severity of acute pancreatitis has been reported in the literature, and its sensitivity, specificity and diagnostic accuracy have been discussed also. The aim of this study was to evaluate the capability of serum concentrations of interleukin-6 (IL-6), tumor necrosis factor(TNF), and C-reactive protein (CRP) for early assessment of the severity of acute pancreatitis and compare their sensitivity, specificity and diagnostic accuracy.
The Representation of Illusory and Real Contours in Human Cortical Visual Areas Revealed by Functional Magnetic Resonance Imaging

Illusory contours (perceived edges that exist in the absence of local stimulus borders) demonstrate that perception is an active process, creating features not present in the light patterns striking the retina. Illusory contours are thought to be processed using mechanisms that partially overlap with those of “real” contours, but questions about the neural substrate of these percepts remain. Here, we employed functional magnetic resonance imaging to obtain physiological signals from human visual cortex while subjects viewed different types of contours, both real and illusory. We sampled these signals independently from nine visual areas, each defined by retinotopic or other independent criteria. Using both within- and across-subject analysis, we found evidence for overlapping sites of processing; most areas responded to most types of contours. However, there were distinctive differences in the strength of activity across areas and contour types. Two types of illusory contours differed in the strength of activation of the retinotopic areas, but both types activated crudely retinotopic visual areas, including V3A, V4v, V7, and V8, bilaterally. The extent of activation was largely invariant across a range of stimulus sizes that produce illusory contours perceptually, but it was related to the spatial frequency of displaced-grating stimuli. Finally, there was a striking similarity in the pattern of results for the illusory contour-defined shape and a similar shape defined by stereoscopic depth. These and other results suggest a role in surface perception for this lateral occipital region that includes V3A, V4v, V7, and V8.
Differential contribution of the m7G-cap to the 5′ end-dependent translation initiation of mammalian mRNAs

Many mammalian mRNAs possess long 5′ UTRs with numerous stem-loop structures. For some of them, the presence of Internal Ribosome Entry Sites (IRESes) was suggested to explain their significant activity, especially when cap-dependent translation is compromised. To test this hypothesis, we have compared the translation initiation efficiencies of some cellular 5′ UTRs reported to have IRES-activity with those lacking IRES-elements in RNA-transfected cells and cell-free systems. Unlike viral IRESes, the tested 5′ UTRs with so-called ‘cellular IRESes’ demonstrate only background activities when placed in the intercistronic position of dicistronic RNAs. In contrast, they are very active in the monocistronic context and the cap is indispensable for their activities. Surprisingly, in cultured cells or cytoplasmic extracts both the level of stimulation with the cap and the overall translation activity do not correlate with the cumulative energy of the secondary structure of the tested 5′ UTRs. The cap positive effect is still observed under profound inhibition of translation with eIF4E-BP1 but its magnitude varies for individual 5′ UTRs irrespective of the cumulative energy of their secondary structures. Thus, it is not mandatory to invoke the IRES hypothesis, at least for some mRNAs, to explain their preferential translation when eIF4E is partially inactivated.
Reprints Available Directly from the Publisher Photocopying Permitted by License Only Transient Developmental Expression of Igy and Secretory Component like Protein in the Gut of the Axolotl (ambystoma Mexicanum)

We previously reported that a primitive vertebrate, the Mexican axolotl (Amphibian, Urodela) synthesizes two classes of immunoglobulins. IgM are present in serum early in the development, and represent the bulk of specific antibody synthesis after an antigenic challenge. IgY occur in the serum later during the development, and are relatively insensitive to immunization. We demonstrate in the present work, using immunofluorescence with specific Mabs, that IgY are expressed in the gut epithelium, as secretory molecules. Secretory IgY are well expressed in the stomach and intestinal mucosae of young animals from 1 month after hatching to the seventh month. Thereafter, IgY progressively disappear from the gut and become readily detectable in the serum of 9-month-old preadult immunologically mature animals. Axolotl IgY are closely associated in the gut to secretory component-like (SC) molecules that are well-recognized by antisera to the SC of different mammalian species. This is the first description, in a primitive tetrapode, of an immunoglobulin class that could be the physiological counterpart of mammalian IgA.
Impact and Management of the Mexican Rice Borer (Lepidoptera: Crambidae) in Bioenergy Crop Agroecosystems

vii CHAPTER 1: GENERAL INTRODUCTION . 1 CHAPTER 2: LITERATURE REVIEW . 5 2.1. Taxonomy of E. loftini . 5 2.2. Distribution of E. loftini . 5 2.3. Morphology and Life Cycle of E. loftini . 6 2.4. Host Plants of E. loftini . 8 2.5. Eoreuma loftini Injury to Sugarcane . 9 2.6. Host Plant Resistance to E. loftini.9 2.7. Cultural Control of E. loftini . 10 2.8. Biological Control of E. loftini . 10 2.9. Chemical Control of E. loftini . 12 2.10. Sugarcane and Sorghum as Bioenergy Feedstocks . 12 2.11. Taxonomy of S. invicta . 14 2.12. Distribution of S. invicta . 14 2.13. Solenopsis invicta as an ecological factor in cropping systems . 14 2.14. Solenopsis invicta as an arthropod predator in sugarcane . 15 CHAPTER 3: YIELD RESPONSE TO MEXICAN RICE BORER (LEPIDOPTERA: CRAMBIDAE) INJURY IN BIOENERGY AND CONVENTIONAL SUGARCANE AND SORGHUM . 19 3.
Topology Aware Link Throughput of Slotted Aloha in Rayleigh Block Fading Channels

In this work, we present an accurate analysis of the probability of successful transmission in a slotted Aloha network with an arbitrary topology, provided that the channel can be accurately modeled as Rayleigh block fading channels. The obtained expression also takes into account the effect of different physical layer parameters such as modulation and coding methods. However, its computational complexity grows quickly as the network size increases. To address this, we also present an accurate approximation method in which the probability of success for a link is predicted by considering only a subset of the interfering nodes. A sufficient condition for the accuracy of this prediction is also presented. The validity of the proposed methods are verified by a series of simulations.
Uninsurable Risk and the Determination of Real Interest Rates: An Investigation Using UK Indexed Bonds

This paper investigates the empirical performance of a new class of uninsurable risk models in the context of UK indexed bond market. Using closed form expressions for pricing kernels, we test the ability of three consumption-based models to price indexed bonds in the UK, and …nd that the standard general equilibrium, complete markets model is soundly rejected in favour of two uninsurable-risk models. Of the latter, a model which prohibits all insurance appears to perform better than a model which permits partial insurance. Using the estimated bond price equation, impulse response analysis is undertaken to �
Investigating Biochemical and Developmental Dependencies of Lignification with a Click-Compatible Monolignol Analog in Arabidopsis thaliana Stems

Lignin is a key structural component of plant cell walls that provides rigidity, strength, and resistance against microbial attacks. This hydrophobic polymer also serves a crucial role in water transport. Despite its abundance and essential functions, several aspects of lignin biosynthesis and deposition remain cryptic. Lignin precursors are known to be synthesized in the cytoplasm by complex biosynthetic pathways, after which they are transported to the apoplastic space, where they are polymerized via free radical coupling reactions into polymeric lignin. However, the lignin deposition process and the factors controlling it are unclear. In this study, the biochemical and developmental dependencies of lignification were investigated using a click-compatible monolignol analog, 3-O-propargylcaffeyl alcohol (3-OPC), which can incorporate into both in vitro polymerized lignin and Arabidopsis thaliana tissues. Fluorescence labeling of 3-OPC using click chemistry followed by confocal fluorescence microscopy enabled the detection and imaging of 3-OPC incorporation patterns. These patterns were consistent with endogenous lignification observed in different developmental stages of Arabidopsis stems. However, the concentration of supplied monolignols influenced where lignification occurred at the subcellular level, with low concentrations being deposited in cell corners and middle lamellae and high concentrations also being deposited in secondary walls. Experimental inhibition of multiple lignification factors confirmed that 3-OPC incorporation proceeds via a free radical coupling mechanism involving peroxidases/laccases and reactive oxygen species (ROS). Finally, the presence of peroxide-producing enzymes determined which cell walls lignified: adding exogenous peroxide and peroxidase caused cells that do not naturally lignify in Arabidopsis stems to lignify. In summary, 3-OPC accurately mimics natural lignification patterns in different developmental stages of Arabidopsis stems and allows for the dissection of key biochemical and enzymatic factors controlling lignification.
Nitrogen retention and performance of brown laying hens on diets with different protein content and constant concentration of amino acids and energy

Abstract 1. The aim of this study was to determine the nitrogen balance and the performance of laying hens fed on diets with a protein content lower than the diets currently used in commercial practice but with adequate concentrations of lysine, sulphur amino acids, tryptophan and threonine. 2. Ninety-six Hy-Line Brown hens, 24 weeks old, were divided into 3 groups of 8 replicates and received, for 16 weeks, diets formulated to have 3 different protein concentrations: 170 (control), 150 and 130 g/kg CP and the same energy content. For each protein concentration, the contents of lysine, methionine, methionine+cystine, tryptophan and threonine were maintained at minimum requirement concentrations by supplying synthetic amino acids. 3. In the first half of the trial, egg production and egg weight were similar in all groups. From the 9th week onwards group 150 CP laid heavier eggs and had a slightly lower egg deposition and total mass. Food conversion ratio was best in the control group. 4. Nitrogen intake was related to the protein concentration of the diet, the food intake being almost the same in the 3 experimental groups. Faecal nitrogen content significantly and linearly decreased with reduction in dietary protein content and was about 50% of the intake. Considering the nitrogen faecal/intake ratio, the 150 CP group showed better nitrogen utilisation at each sampling time.
Desulfonation and Degradation of the Disulfodiphenylethercarboxylates from Linear Alkyldiphenyletherdisulfonate Surfactants

ABSTRACT Earlier work showed that the biodegradation of a commercial linear monoalkyldiphenyletherdisulfonate surfactant as a carbon source for microbial growth leads to the quantitative formation of corresponding disulfodiphenylether carboxylates (DSDPECs), which were not degraded. α-Proteobacterium strain DS-1 (DSM 13023) catalyzes these reactions. These DSDPECs have now been characterized by high-pressure liquid chromatography coupled via an electrospray interface to a mass spectrometer. DSDPECs were a complex mixture of compounds which indicated catabolism via ω-oxygenation and β-oxidation. DSDPECs were subject to quantitative desulfonation in bacterial cultures in which they served as sole sulfur sources for bacterial growth. On average, one sulfonate group per DSDPEC species was removed, and the organism responsible for this desulfonation was isolated and identified as Rhodococcus opacus ISO-5. The products were largely monosulfodiphenylether carboxylate-phenols (MSDPEC-phenols). MSDPEC-phenols were subject to extensive dissimilation by bacteria from activated sludge.
Harnessing the Fc m Receptor for Potent and Selective Cytotoxic Therapy of Chronic Lymphocytic Leukemia

, Abstract Chronic lymphocytic leukemia (CLL) is a B-cell malignancy in need of new, effective, and safe therapies. The recently identi ﬁ ed IgM receptor Fc m R is overexpressed on malignant B cells in CLL and mediates the rapid internalization and lysosomal shuttling of IgM via its Fc fragment (Fc m ). To exploit this internalization and traf ﬁ cking pathway for targeted drug delivery, we engineered an IgM-derived protein scaffold (Fc m ) and linked it with the cytotoxic agent monomethylauristatin F. This Fc m – drug conjugate was selectively toxic for Fc m R-expressing cell lines in vitro and for CLL cells but not autologous normal T cells ex vivo . Notably, the cytotoxic activity of the Fc m – drug conjugate was maintained in CLL cells carrying a 17p deletion, which predicts resistance to standard chemotherapy. Next, we tested the possible therapeutic application of the Fc m – drug conjugate in immunode ﬁ cient NOD/SCID/IL-2R g null (NSG) mice engrafted with peripheral blood cells from patients with leukemia. Three intravenous injections of the Fc m – drug conjugate over a 10-day period were well tolerated and selectively killed the human CLL cells but not the coengrafted autologous human T cells. In summary, we developed a novel strategy for targeted cytotoxic therapy of CLL based on the unique properties of Fc m R. Fc m R-targeted drug delivery showed potent and speci ﬁ c therapeutic activity in CLL, thus providing proof of concept for Fc m R as a valuable therapeutic target in CLL and for IgM-based antibody – drug conjugates as a new targeting platform. Cancer Res; 74(24); 1 – 11. (cid:2) 2014 AACR.
Predictive validity of the Biomedical Admissions Test: An evaluation and case study

There has been an increase in the use of pre-admission selection tests for medicine. Such tests need to show good psychometric properties. Here, we use a paper by Emery and Bell [2009. The predictive validity of the Biomedical Admissions Test for pre-clinical examination performance. Med Educ 43:557–564] as a case study to evaluate and comment on the reporting of psychometric data in the field of medical student selection (and the comments apply to many papers in the field). We highlight pitfalls when reliability data are not presented, how simple zero-order associations can lead to inaccurate conclusions about the predictive validity of a test, and how biases need to be explored and reported. We show with BMAT that it is the knowledge part of the test which does all the predictive work. We show that without evidence of incremental validity it is difficult to assess the value of any selection tests for medicine.
A Tight Combinatorial Algorithm for Submodular Maximization Subject to a Matroid Constraint

We present an optimal, combinatorial 1-1/e approximation algorithm for monotone sub modular optimization over a matroid constraint. Compared to the continuous greedy algorithm (Calinescu, Chekuri, Pal and Vondrak, 2008), our algorithm is extremely simple and requires no rounding. It consists of the greedy algorithm followed by local search. Both phases are run not on the actual objective function, but on a related non-oblivious potential function, which is also monotone sub modular. In our previous work on maximum coverage (Filmus and Ward, 2011), the potential function gives more weight to elements covered multiple times. We generalize this approach from coverage functions to arbitrary monotone sub modular functions. When the objective function is a coverage function, both definitions of the potential function coincide. The parameters used to define the potential function are closely related to Pade approximants of exp(x) evaluated at x = 1. We use this connection to determine the approximation ratio of the algorithm.