Miracle-dz/UniFAR-FTUs huggingface dataset:
A Second Receptor Binding Site on Human Parainfluenza Virus Type 3 Hemagglutinin-Neuraminidase Contributes to Activation of the FusionMechanism

ABSTRACT The hemagglutinin-neuraminidase (HN) protein of paramyxoviruses carries out three discrete activities that each affect the ability of HN to promote viral fusion and entry: receptor binding, receptor cleaving (neuraminidase), and triggering of the fusion protein. The interrelationship between the receptor binding and fusion-triggering functions of HN has not been clear. For human parainfluenza type 3 (HPIV3), one bifunctional site on HN can carry out both receptor binding and neuraminidase activities, and this site's receptor binding can be inhibited by the small receptor analog zanamivir. We now report experimental evidence, complemented by computational data, for a second receptor binding site near the HPIV3 HN dimer interface. This second binding site can mediate receptor binding even in the presence of zanamivir, and it differs from the second receptor binding site of the paramyxovirus Newcastle disease virus in its function and its relationship to the primary binding site. This second binding site of HPIV3 HN is involved in triggering F. We suggest that the two receptor binding sites on HPIV3 HN each contribute in distinct ways to virus-cell interaction; one is the multifunctional site that contains both binding and neuraminidase activities, and the other contains binding activity and also is involved in fusion promotion.
Energy‐dependent degradation: Linkage between ClpX‐catalyzed nucleotide hydrolysis and protein‐substrate processing

ClpX requires ATP to unfold protein substrates and translocate them into the proteolytic chamber of ClpP for degradation. The steady‐state parameters for hydrolysis of ATP and ATPγS by ClpX were measured with different protein partners and the kinetics of degradation of ssrA‐tagged substrates were determined with both nucleotides. ClpX hydrolyzed ATPγS to ADP and thiophosphate at a rate (6/min) significantly slower than ATP hydrolysis (140/min), but the hydrolysis of both nucleotides was increased by ssrA‐tagged substrates and decreased by ClpP. KM and kcat for hydrolysis of ATP and ATPγS were linearly correlated over a 200‐fold range, suggesting that protein partners largely affect kcat rather than nucleotide binding, indicating that most bound ATP leaves the enzyme by hydrolysis rather than dissociation, and placing an upper limit of ≈15 μM on KD for both nucleotides. Competition studies with ClpX and fluorescently labeled ADP gave inhibition constants for ATPγS (≈2 μM) and ADP (≈3 μM) under the reaction conditions used for steady‐state kinetics. In the absence of Mg2+, where hydrolysis does not occur, the inhibition constant for ATP (≈55 μM) was weaker but very similar to the value for ATPγS (≈45 μM). Compared with ATP, ATPγS supported slow but roughly comparable rates of ClpXP degradation for two Arc‐ssrA substrates and denatured GFP‐ssrA, but not of native GFP‐ssrA. These results show that the processing of protein substrates by ClpX is closely coupled to the maximum rate of nucleotide hydrolysis.
Modification of the optical flow horn-schunck estimation incorporating exaustive search

Optical Flow is the pixels apparent movement pattern of two consecutives images. There are differents methods to estimate the optical flow: variational methods and exaustive methods. Exhaustive methods take a neighborhood around a point in the first image of the sequence and search for the most similar in the second image. This procedure is known as correspondency estimation. This work evaluate the effect of the incorporation of new correspondecies to a classical variational method to estimate the optical flow. With this goal a variational model is stated. This variational model considers a function k(x) to decide if a correspondency is incorporated or not to the variational model. Obtained results in a standar database show that the incorporation of new correspondencies improve the performance of the optical flow classical method. The obtained result combines the precision of the variational method with exhaustive search. This method was implemented in a GPU satisfactorily, and reducing the processing time to a few seconds.
Studies on production performance and toxin residues in tissues and eggs of layer chickens fed on diets with various concentrations of aflatoxin AFB1

1. An experiment on 1-week-old, White Leghorn female chicks was conducted to study the effect of aflatoxin AFB1 on weight gain, feed intake, feed gain ratio, age at sexual maturity, production and quality of eggs, retention of nutrients, pathoanatomical and histopathological parameters, and also on AFB1 residues in eggs and muscles of hens. The chicks were assigned to 4 dietary treatments: D1 (without AFB1), D2 (2·50 mg/kg AFB1), D3 (3·13 mg/kg AFB1), D4 (3·91 mg/kg AFB1) up to the age of 40 weeks. 2. At the end of the experiment, the mean body weight gain and feed intake were significantly lower in all aflatoxin-fed groups compared to control. The feed gain ratios were noted as 13·41, 13·59, 13·82 and 14·71, with the group fed the highest concentration of AFB1 showing a significantly poorer ratio than other groups. 3. Age at sexual maturity was also affected adversely by dietary AFB1: 193 d for D4 as compared to as early as 148 d for D1. Hen-d egg production was recorded as 96·92, 74·67, 65·98 and 50·75 in D1, D2, D3 and D4, respectively. 4. Average egg weights at the end of the experiment were 57·77, 57·49, 57·54 and 54·66 for D1, D2, D3 and D4, respectively. Shape index was significantly lower in D4 as compared to control. Contrary to this, albumen index was significantly higher in D4 as compared to D1. The values of yolk indices and eggshell thickness did not differ significantly among treatment groups. However, colour of yolk was reduced in all aflatoxin-fed groups compared to control. 5. Retentions of dry matter, crude protein, ether extract, calcium and metabolisable energy were adversely affected at various levels of AFB1 compared to control. 6. Pathoanatomical and histopathological studies showed various adverse changes in liver, kidney, heart, ovaries and bursa of Fabricius in AFB1-fed groups. 7. Different amounts of aflatoxin residues were detected in eggs and breast muscles of hen in all AFB1-fed groups.
Construcción del conocimiento didáctico del contenido biológico en formación inicial de profesores

Presentamos la sistematizacion de los datos obtenidos a partir de los documentos que presentaron dos grupos de futuros profesores de Biologia, a lo largo de un semestre, al disenar Unidades Didacticas para la ensenanza de dos tematicas relacionadas con el auto-mantenimiento de los organismos. Analizamos los referentes de los docentes en formacion acerca del Conocimiento Didactico del Contenido Biologico (contemplamos 9 categorias de investigacion) y los cambios de los mismos durante el proceso formativo en el que los estudiantes-profesores realizaron la propuesta.
Iron Regulatory Protein 1 Outcompetes Iron Regulatory Protein 2 in Regulating Cellular Iron Homeostasis in Response to Nitric Oxide*

In mammals, iron regulatory proteins (IRPs) 1 and 2 posttranscriptionally regulate expression of genes involved in iron metabolism, including transferrin receptor 1, the ferritin (Ft) H and L subunits, and ferroportin by binding mRNA motifs called iron responsive elements (IREs). IRP1 is a bifunctional protein that mostly exists in a non-IRE-binding, [4Fe-4S] cluster aconitase form, whereas IRP2, which does not assemble an Fe-S cluster, spontaneously binds IREs. Although both IRPs fulfill a trans-regulatory function, only mice lacking IRP2 misregulate iron metabolism. NO stimulates the IRE-binding activity of IRP1 by targeting its Fe-S cluster. IRP2 has also been reported to sense NO, but the intrinsic function of IRP1 and IRP2 in NO-mediated regulation of cellular iron metabolism is controversial. In this study, we exposed bone marrow macrophages from Irp1−/− and Irp2−/− mice to NO and showed that the generated apo-IRP1 was entirely responsible for the posttranscriptional regulation of transferrin receptor 1, H-Ft, L-Ft, and ferroportin. The powerful action of NO on IRP1 also remedies the defects of iron storage found in IRP2-null bone marrow macrophages by efficiently reducing Ft overexpression. We also found that NO-dependent IRP1 activation, resulting in increased iron uptake and reduced iron sequestration and export, maintains enough intracellular iron to fuel the Fe-S cluster biosynthetic pathway for efficient restoration of the citric acid cycle aconitase in mitochondria. Thus, IRP1 is the dominant sensor and transducer of NO for posttranscriptional regulation of iron metabolism and participates in Fe-S cluster repair after exposure to NO.
Mechanisms and novel approaches in overriding tyrosine kinase inhibitor resistance in chronic myeloid leukemia

Chronic myeloid leukemia is a stem cell-initiated but progenitor-driven disease induced by the BCR–ABL oncogene. Tyrosine kinase inhibitors (TKIs) were introduced in the late 1990s and have revolutionized the management of chronic myeloid leukemia in chronic phase. The majority of patients can now expect to live a normal life as long as they continue to comply with TKI treatment. However, in a significant proportion of cases TKI resistance develops over time, requiring a switch of therapy. The most frequent mechanism for drug resistance is the development of kinase domain mutations that reduce or completely ablate drug efficacy. Fortunately, the last 10 years have seen an impressive array of new drugs, some modeled on the mechanism of action of imatinib, others employing more novel approaches, for these patients.
Reinventing the wheel will not make it rounder: controlled trials of homeopathy reconsidered.

Ilove homeopathy—for the clinical effects I have noticed in myself, in my children, and in other people. These are sometimes so quick and strong that only the blind and intransigent could attribute them to chance, placebo, wishful thinking, or deceit. Sometimes these effects fail. At other times they are similar to miracle cures. Thus, I am also puzzled by homeopathy, by the many apparent contradictions, and paradoxes. I suggest that the following propositions are compatible with the known facts about homeopathy and with both formal and informal experience:
Low power cmos cell structures based on adiabatic switching

The dynamic power requirement of CMOS circuits is rapidly becoming a major concern in the design of personal information systems and large computers. In this paper, a new CMOS logic family called ADIABATIC LOGIC, based on the adiabatic switching principle is presented. The term adiabatic comes from thermodynamics, used to describe a process in which there is no exchange of heat with the environment. The adiabatic logic structure dramatically reduces the power dissipation. The adiabatic switching technique can achieve very low power dissipation, but at the expense of circuit complexity. Adiabatic logic offers a way to reuse the energy stored in the load capacitors rather than the traditional way of discharging the load capacitors to the ground and wasting this energy.
Neuropeptide-Y Neurons Projectioning to the Medial Septum-Diagonal Band Do Not Have Access to Fenestrated Capillaries in the Rat Brain

The aims of this study were to (1) determine the localization of neuropeptide-Y (NPY)-containing perikarya which project to the medial septum-diagonal band (MSDB), a brain region rich in gonadotropin-releasing hormone (GnRH) producing perikarya, and (2) determine if NPY neurons have access to fenestrated capillaries as well. Fluorescent retrograde tracing after microinjection of fluororuby (FR) into the MSDB, and peripheral injection of fluorogold (FG), was used in combination with immunofluorescence for NPY. Injection of FR into the MSDB resulted in retrograde labeling of neurons in the hypothalamic arcuate nucleus (ARC) and brainstem noradrenergic cell groups A1 and A2, as well as other regions. The largest populations of NPY neurons were located in the ventromedial ARC and several of these perikarya contained FR indicating that they project to the MSDB. Defined cell groups in the areas A1 and A2 of the brainstem also contained large numbers of NPY neuron perikarya, and several of these contained FR. In addition, we observed isolated incidences of FR-labeled NPY perikarya in the amygdala and hippocampus. A small population of NPY neurons in the ARC contained FG, indicating that they are in contact with fenestrated capillaries and hence are neuroendocrine cells; however, none of these neurons contained FR. We suggest that NPY neurons in the ARC modulate GnRH function via innervation of the MSDB and LH release via release into fenestrated capillaries of the hypophysial-portal system.
BAD Detects Coincidence of G2/M Phase and Growth Factor Deprivation to Regulate Apoptosis*

BAD, a member of the Bcl-2 protein family, promotes mitochondria-dependent apoptosis. Here, we report that BAD dissociates from 14-3-3ζ at each G2/M phase of proliferating lymphoid cells. The cell cycle-dependent dissociation of BAD was associated with phosphorylation at Ser-128, whereas mutant S128A-BAD, in which Ser-128 was converted to alanine, remained associated with 14-3-3ζ throughout the cell cycle. Although the cell cycle-dependent dissociation of BAD per se did not induce apoptosis, growth factor deprivation induced prompt apoptosis at the G2/M phase but not at the G1 phase. In cells expressing S128A-BAD, growth factor deprivation-induced apoptosis was markedly delayed and was accompanied by a delayed dephosphorylation of growth factor-dependent regulatory serine residues. These results indicate that BAD induces apoptosis upon detecting the coincidence of G2/M phase and growth factor deprivation.
Recoverable catalysts and reagents using recyclable polystyrene-based supports.

Contents 1.0Introduction 1.1 Polystyrene Supports as Carriers for Reagents and Catalysts 1.2 Catalyst and Reagent Attachment to Polymer Supports 2.0C-C Bond Formation Using Recyclable Resin-Based Reagents and Catalysts 2.1 Palladium-Catalyzed Coupling Reactions 2.2 Other Transition Metal Catalyzed Reactions 2.3 Resin-Supported Olefin Metathesis 2.4 Resin-Mediated Cycloaddition Reactions 2.4.1 Diels-Alder Cycloadditions 2.4.2 Resin-Based Catalysts for 1,3-Dipolar Cycloadditions 2.5 Immobilized Chiral Ligands for Diethylzinc Additions to Aldehydes 2.6 Miscellaneous: Other C-C Bond Forming Reactions 3.0Immobilized Oxidants 3.1Oxidation with Immobilized Transition Metal Complexes 3.2 Alcohol Oxidation 3.3 Alkene Oxidation 3.3. 1 Dihydroxylation 3.3.2 Epoxidation 3.3.3 Asymmetric Epoxidation 3.3.4 Other Alkene Oxidation Reactions 3.4 Potpourri: Other Immobilized Oxidants 4.0Immobilized Resin-Based Reductants 4.1 General Reduction Processes 4.2 Asymmetric Reduction of Ketones 4.3 Alkene Reduction 4.4 Resin-Based Tin and Germanium Reductants 5.0Conclusions 6.0Abbreviations 7.0Acknowledgments 8.0References
Retinoid X Receptor Agonists Modulate Foxp3+ Regulatory T Cell and Th17 Cell Differentiation with Differential Dependence on Retinoic Acid Receptor Activation

Retinoic acid (RA) enhances TGF-β–dependent differentiation of Foxp3+ inducible regulatory T cells (iTregs) and inhibits Th17 differentiation by binding to the RA receptor (RAR)/retinoid X receptor (RXR) heterodimer. The major physiologic RA, all-trans-RA, binds to RAR but not to RXR at physiological concentrations. It remained unclear whether RXR-mediated stimulation affected the iTregs and Th17 differentiation. We found in this study that the RXR agonists, PA024 and tributyltin, augmented the ability of all-trans-RA or the RAR agonist Am80 to enhance CD4+CD25− T cells to acquire Foxp3 expression and suppressive function. However, they failed to enhance Foxp3 expression in the presence of the RAR antagonist LE540, suggesting that the effect depends on RAR-mediated signals. They exerted the effect largely by augmenting the ability of all-trans-RA to suppress the production of IL-4, IL-21, and IFN-γ that inhibited Foxp3 expression. Agonists of peroxisome proliferator-activated receptors and liver X receptors (LXRs), permissive partners of RXR, failed to enhance Foxp3 expression. In contrast, RXR agonists and LXR agonists suppressed IL-17 expression. The RXR-mediated suppression was not canceled by blocking RAR stimulation but was likely to involve permissive activation of LXRs. All-trans-RA and an agonist of RXR or LXR additively suppressed IL-17 expression when the all-trans-RA concentration was low. RXR agonists also suppressed Ccr6 expression that is essential for Th17 cells to enter the CNS. Accordingly, tributyltin treatment of mice ameliorated experimental autoimmune encephalomyelitis through regulating Th17 cell activities. These results suggest that RXR stimulation modulates Foxp3+ iTreg and Th17 differentiation with differential dependence on RAR-mediated stimulation.
Statistical leakage current reduction in high-leakage environments using locality of block activation in time domain

This paper describes a new leakage current reduction methodology that can give a statistical leakage current reduction even if the chip is in active mode, as well as in sleep mode. The proposed scheme utilizes a time locality of activation probability of a given circuit block like cache memory characteristics. The leakage cut-off switch is operated by a self-timed sleep timer, which puts the block into sleep mode. By waiting for a certain number of cycles before entering sleep mode, power overhead associated with the sleep and wake-up process is optimized, and its conditional probability is also analyzed. The effectiveness of the proposed scheme is verified by an 8-bit RISC microprocessor using Verilog HDL with real firmware, and demonstrated by a 64-bit carry-look-ahead adder with the self-cut-off switch fabricated with dual-threshold voltage SOI technology. The criterion of the effectiveness of the proposed scheme is also discussed.
X-linked inhibitor of apoptosis protein as a therapeutic target

Dysregulation of apoptosis has been shown to contribute to many diseases, including cancer formation, development and resistance, as well as neurodegenerative and autoimmune disorders. One mechanism through which tumour cells are believed to acquire resistance to apoptosis is by overexpression of X-linked inhibitor of apoptosis protein (XIAP), which belongs to a family of inhibitor of apoptosis proteins. When XIAP is overexpressed, cancer cells are rendered resistant to apoptosis, both intrinsically and in response to chemotherapy and radiotherapy. Significant progress has been made in targeting XIAP therapeutically, both directly and indirectly through the modulation of other molecules involved in the apoptotic pathway. This review introduces XIAP from its molecular origins, discusses its modulation and potential as a novel drug target, and considers future therapeutic perspectives.
CDMA-based RFID Systems in Dense Scenarios: Concepts and Challenges

Radiofrequency identification (RFID) applications with large tag populations often require the fast identification of the tags present. Conventional RFID systems using framed ALOHA based medium access control algorithms waste bandwidth during the singulation process when tag replies collide on the shared wireless channel. In this paper, we investigate how code division multiplexing techniques can be used to decode tag replies in such collisions. Our analysis focusses on the choice of code set and detector for use in a spread spectrum RFID system. The paper also presents a method to estimate the number of tags in the range of such a spread spectrum RFID system.
ARMV8 debug and trace architectures

The ARM® processor family is the most widely used 32-bit processor family, and has consistently included debug features, starting from the ARM7TDMI® processor [1]. Embedded debug forms part of the ARMv7 architecture [2]. The most recent addition to the ARM architecture family is ARMv8 [3], which represents the biggest change in the architecture's history. This paper looks at the impact of the new architecture on debug and trace, and reviews some of the lessons learnt from previous architectures.
Nuclear competence for maturation and pronuclear formation in mouse oocytes.

BACKGROUND In response to gonadotrophins, a fully grown mouse oocyte matures to the metaphase of the second meiotic division and becomes competent for the development of female and male pronuclei after fertilization. The present study was carried out to clarify when during the growth period an oocyte nucleus acquires the ability to promote pronuclei formation after fertilization. METHODS Fully grown germinal vesicle (GV) oocytes were enucleated and fused with nuclei from growing oocytes from 1-20 day old mice by standard nuclear transfer technique. The reconstructed oocytes were matured and fertilized in vitro, and pronuclear formation was assessed. RESULTS The oocytes whose nuclei were exchanged for those of the non-growing-stage oocytes matured to the metaphase of the second meiotic stage, but no normal female pronuclei were formed. Female pronuclei first formed in 27% of the oocytes reconstituted with the nuclei of oocytes from 8 day old pups after fertilization. Recondensed sperm chromatin was detected in 27% of the oocytes reconstructed with oocyte nuclei from 8 day old mice, and a male pronucleus was first formed in 6% of the oocytes that had been reconstructed with the nuclei of oocytes from 15 day old mice. The sizes of the female and male pronuclei increased with oocyte donor age, and reached normal size when the oocytes from 15 and 20 day old mice respectively were used. An electron microscopic study using oocytes that had received the oocyte nuclei of 8 day old mice confirmed these results. CONCLUSION The factors required for pronuclear formation are derived from fully grown GV oocytes, and the transformation from decondensed sperm chromatin to a recondensed male pronucleus is governed by GV-derived factors.