Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-cytotoxic T lymphocyte antigen-4 antibodies in melanoma

Approaches aimed at enhancement of the tumor specific response have provided proof for the rationale of immunotherapy in cancer, both in animal models and in humans. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, is a new generation immunotherapeutic agent that has shown activity in terms of disease free and overall survival in metastatic melanoma patients. Its use was approved by the US Food and Drug Administration in March 2011 to treat patients with late stage melanoma that has spread or that cannot be removed by surgery. The mechanism of action of CTLA-4 antibodies in the activation of an antitumor immune response and selected clinical studies of ipilimumab in advanced melanoma patients are discussed. Ipilimumab treatment has been associated with immune related adverse events due to T-cell activation and proliferation. Most of these serious adverse effects are associated with the gastrointestinal tract and include severe diarrhea and colitis. The relationship between immune related adverse events and antitumor activity associated with ipilimumab was explored in clinical studies. Potential biomarkers predictive for clinical response and survival in patients treated with anti-CTLA-4 therapy are presently under investigation. Besides the conventional patterns of response and stable disease as defined by standard Response Evaluation Criteria in Solid Tumors criteria, in subsets of patients, ipilimumab has shown patterns of delayed clinical activity which were associated with an improved overall survival. For this reason a new set of response criteria for tumor immunotherapy has been proposed, which was termed immune related response criteria. These new criteria are presently used to better analyze clinical activity of immunotherapeutic regimens. Ipilimumab is currently under investigation in combination with other treatments, such as chemotherapy, target agents, radiotherapy, and other immuno-therapeutic regimens.
Higher-Order Statistics Based Iterative Space-Time FIR Precoder-Blind Equalizer

A higher-order statistics (HOS) based iterative FIR linear blind equalizer for block based transmission over FIR MIMO channels is proposed. With the precoder-equalizer struc- ture, the proposed blind equalization algorithm do not required a long guard period that is longer than or equal to the channel order, to be inserted in each block of transmitted signal to avoid inter-block interference. The signal transmitted during the guard period can be considered as redundancy which consumes channel bandwidth and transmission power. With the proposed algorithm, an FIR equalizer can be obtained based on the HOS of the received signal with minimal transmit redundancy required for FIR zero-forcing equalization. The simulation results showed that the proposed blind equalizer improves spectral efficiency while retaining good BER performance at high SNR. Simulation results also showed that the proposed equalizer can obtain good BER at low SNR due to the use of the HOS, which is robust towards Gaussian channel noise.
Three‐dimensional distribution of tyrosine hydroxylase, vasopressin and oxytocin neurones in the transparent postnatal mouse brain

Over the years, advances in immunohistochemistry techniques have been a critical step in detecting and mapping neuromodulatory substances in the central nervous system. The better quality and specificity of primary antibodies, new staining procedures and the spectacular development of imaging technologies have allowed such progress. Very recently, new methods permitting tissue transparency have been successfully used on brain tissues. In the present study, we combined whole‐mount immunostaining for tyrosine hydroxylase (TH), oxytocin (OXT) and arginine vasopressin (AVP), with the iDISCO+ clearing method, light‐sheet microscopy and semi‐automated counting of three‐dimensionally‐labelled neurones to obtain a (3D) distribution of these neuronal populations in a 5‐day postnatal (P5) mouse brain. Segmentation procedure and 3D reconstruction allowed us, with high resolution, to map TH staining of the various catecholaminergic cell groups and their ascending and descending fibre pathways. We show that TH pathways are present in the whole P5 mouse brain, similar to that observed in the adult rat brain. We also provide new information on the postnatal distribution of OXT and AVP immunoreactive cells in the mouse hypothalamus, and show that, compared to AVP neurones, OXT neurones in the supraoptic (SON) and paraventricular (PVN) nuclei are not yet mature in the early postnatal period. 3D semi‐automatic quantitative analysis of the PVN reveals that OXT cell bodies are more numerous than AVP neurones, although their immunoreactive soma have a volume half smaller. More AVP nerve fibres compared to OXT were observed in the PVN and the retrochiasmatic area. In conclusion, the results of the present study demonstrate the utility and the potency of imaging large brain tissues with clearing procedures coupled to novel 3D imaging technologies to study, localise and quantify neurotransmitter substances involved in brain and neuroendocrine functions.
Autotrophic CO2 Assimilation and the Evolution of Ribulose Diphosphate Carboxylase

From Heterotrophism to Autotrophism . 299 New Catalysts in CO.-Fixing Autotrophs . 300 RuDP carboxylase and phosphoribulokinase . 300 Properties of RuDP Carboxylase. 300 Kinetic response to substrates . 301 Metal ion requirement . 302 Specificity and mechanism of catalysis . 302 Inhibition . 303 Molecular size . 304 Quaternary structure, composition, terminal and tryptic peptides . 305
Evaluating Intervention Programs with a Pretest-Posttest Design: A Structural Equation Modeling Approach

A common situation in the evaluation of intervention programs is the researcher's possibility to rely on two waves of data only (i.e., pretest and posttest), which profoundly impacts on his/her choice about the possible statistical analyses to be conducted. Indeed, the evaluation of intervention programs based on a pretest-posttest design has been usually carried out by using classic statistical tests, such as family-wise ANOVA analyses, which are strongly limited by exclusively analyzing the intervention effects at the group level. In this article, we showed how second order multiple group latent curve modeling (SO-MG-LCM) could represent a useful methodological tool to have a more realistic and informative assessment of intervention programs with two waves of data. We offered a practical step-by-step guide to properly implement this methodology, and we outlined the advantages of the LCM approach over classic ANOVA analyses. Furthermore, we also provided a real-data example by re-analyzing the implementation of the Young Prosocial Animation, a universal intervention program aimed at promoting prosociality among youth. In conclusion, albeit there are previous studies that pointed to the usefulness of MG-LCM to evaluate intervention programs (Muthén and Curran, 1997; Curran and Muthén, 1999), no previous study showed that it is possible to use this approach even in pretest-posttest (i.e., with only two time points) designs. Given the advantages of latent variable analyses in examining differences in interindividual and intraindividual changes (McArdle, 2009), the methodological and substantive implications of our proposed approach are discussed.
Generation of microtubule stability subclasses by microtubule- associated proteins: implications for the microtubule "dynamic instability" model

We have developed a method to distinguish microtubule associated protein (MAP)-containing regions from MAP-free regions within a microtubule, or within microtubule sub-populations. In this method, we measure the MAP-dependent stabilization of microtubule regions to dilution-induced disassembly of the polymer. The appropriate microtubule regions are identified by assembly in the presence of [3H]GTP, and assayed by filter trapping and quantitation of microtubule regions that contain label. We find that MAPs bind very rapidly to polymer binding sites and that they do not exchange from these sites measurably once bound. Also, very low concentrations of MAPs yield measurable stabilization of local microtubule regions. Unlike the stable tubule only polypeptide (STOP) proteins, MAPs do not exhibit any sliding behavior under our assay conditions. These results predict the presence of different stability subclasses of microtubules when MAPs are present in less than saturating amounts. The data can readily account for the observed "dynamic instability" of microtubules through unequal MAP distributions. Further, we report that MAP dependent stabilization is quantitatively reversed by MAP phosphorylation, but that calmodulin, in large excess, has no specific influence on MAP protein activity when MAPs are on microtubules.
Prevalence of intestinal parasites among urban and rural population in Kancheepuram district of Tamil Nadu

Parasites are the organisms that live on other organisms or hosts to survive. Some parasites don’t affect their hosts, while others grow, reproduce or invade organs that make their hosts sick, resulting in a parasitic infection. There are 3 main classes of parasites which are capable of producing diseases in human beings. They are Protozoa, Helminthes and Ectoparasites. Protozoa are microscopic single celled organisms, can be free living or parasitic in nature. They can multiply in humans which contribute to their survival and also permit serious infections. Entamoeba histolytica is a protozoan which can cause amoebiasis and Giardia lamblia which causes giardiasis. Helminthes are large, multicellular, visible to the naked eye in their adult stage. They are also free living or parasitic in nature. Helminthes like Flukes and Tapeworm can cause diarrheal disorders and cyst in the visceral organs. Ectoparasites are the blood sucking arthropods such as mosquitoes, ticks, fleas, mites which acts as the vectors of malaria, Q fever, relapsing fever, plaque etc.
Sphingosine Kinase Modulates Microvascular Tone and Myogenic Responses Through Activation of RhoA/Rho Kinase

Background RhoA and Rho kinase are important modulators of microvascular tone. Methods and Results We tested whether sphingosine kinase (Sphk1) that generates the endogenous sphingolipid mediator sphingosine‐1‐phosphate (S1P) is part of a signaling cascade to activate the RhoA/Rho kinase pathway. Using a new transfection model, we report that resting tone and myogenic responses of isolated resistance arteries increased with forced expression of Sphk1 in smooth muscle cells of these arteries. Overexpression of a dominant negative Sphk1 mutant or coexpression of dominant negative mutants of RhoA or Rho kinase together with Sphk1 completely inhibited development of tone and myogenic responses. Conclusions The tone‐increasing effects of a Sphk1 overexpression suggest that Sphk1 may play an important role in the control of peripheral resistance. (Circulation. 2003;108:342‐347.)
Heavy Metals Contamination and Potential Human Health Risk via Consumption of Vegetables from Selected Communities in ONELGA, Rivers State, Nigeria

Background: Anthropogenic activities such as excessive oil exploration, automobile emissions with agricultural activities, etc tend to elevate the concentrations of heavy metals in the soil. These metals are accumulated by plant roots, thereby resulting to heavy metal contamination of such plants. Objectives: This study evaluated the concentration of heavy metals namely: Lead (Pb), Cadmium (Cd), Nickel (Ni), Arsenic (As), Iron (Fe), and Copper (Cu) in edible vegetables from selected communities in Ogba/Egbema/Ndoni Local Government Area (ONELGA), Rivers State, Nigeria, and the concentrations of these metals were used to assess the human health risk posed to the consumers of the edible vegetables. Materials and Methods: Sixteen different vegetable samples comprising Vernonia amygdalina, Talinum triangulare, Abelmoschus esculentus and Telfairia occidentalis were digested and analyzed for heavy metals using Flame Atomic Absorption Spectrophotometer (F-AAS). Results obtained from this study were used to estimate the human health risk of these heavy metals. Results: The results showed that the concentrations of Pb, Cd, Ni, As, Fe, and Cu ranged from 0.168-4.908; 0.364-2.977; 2.780-10.241; 0.157-2.633; 61.589-101.520 and 12.029-46.540 mg/kg, respectively. The concentrations of Pb, Cd, Ni and As in some of the analyzed vegetable samples exceeded the permissible limit as recommended by WHO/FAO, EC/CODEX and NAFDAC respectively. The concentration of Fe and Cu were below the permissible limit as recommended by WHO/FAO. The Estimated Daily Intake (EDI) of Pb and Cd exceeded the permissible tolerable daily intake of metals (TDI) but fall within the upper tolerable daily intake (UTDI) recommended by Institute of medicine, FDA, also Ni, Fe, and Cu fall within the recommended TDI and the UTDI. The EDI values of As exceeded the recommended TDI and the UTDI. The Target Hazard Quotient (THQ) and Hazard Index (HI) values of Pb, Cd, Cu and Ni were greater than 1. The Life Cancer Risk (LCR) of Pb were within the range of permissible predicted lifetime risks for carcinogens as recommended by US EPA. Conclusion: The result from the present study indicate that the exposed population may be at risk of Pb, Cd, Ni and Cu toxicity.
A memory efficient FPGA implementation of quasi-cyclic LDPC decoder

Low-Density Parity-Check (LDPC) code is one kind of prominent error correcting codes (ECC) being considered in next generation industry standards. The decoder implementation complexity has been the bottleneck of its application. This paper presents an implementation of Quasi-Cyclic Low-Density Parity-Check decoder by using FPGA. Modified Min-Sum decoding algorithm is applied to reduce the memory size needed for information storage. Partially parallel structures, memory management and pipelining schemes are discussed in this paper.
Specialized functions of MHC class I molecules. I. An N-formyl peptide receptor is required for construction of the class I antigen Mta

Maternally transmitted factor (Mtf) is a mitochondrial gene that controls the antigenic polymorphism of the MHC class I maternally transmitted antigen (Mta). Synthetic peptides from the NH2 terminus of the mitochondrially encoded NADH dehydrogenase subunit 1 (ND1) mimic Mtf peptide activity in an allele-specific manner. We show that the minimal ND1-alpha peptide length recognized by Mtaa-specific polyclonal CTLs was between 8 and 12 amino acids, while some Mtaa-specific CTL clones recognized a six amino acid peptide. The N-formyl group at the NH2 terminus of ND1 was essential for Mta activity. Competition experiments using N-substituted ND1-alpha peptides showed that an N- formyl peptide receptor on the target cell, which differs from the chemotactic peptide receptor, was required for Mta expression. The specificity of this receptor can account for the distinct immune restriction of Mta in which Mtf peptides are uniquely restricted by Hmt. It is possible that the Hmt gene product is the N-formyl peptide receptor itself and that it represents a class I antigen presentation molecule specialized for binding, transport, and immune presentation of N-formyl-peptide antigens of mitochondrial and prokaryotic origin.
Enzymes with lid-gated active sites must operate by an induced fit mechanism instead of conformational selection

The induced fit and conformational selection/population shift models are two extreme cases of a continuum aimed at understanding the mechanism by which the final key-lock or active enzyme conformation is achieved upon formation of the correctly ligated enzyme. Structures of complexes representing the Michaelis and enolate intermediate complexes of the reaction catalyzed by phosphoenolpyruvate carboxykinase provide direct structural evidence for the encounter complex that is intrinsic to the induced fit model and not required by the conformational selection model. In addition, the structural data demonstrate that the conformational selection model is not sufficient to explain the correlation between dynamics and catalysis in phosphoenolpyruvate carboxykinase and other enzymes in which the transition between the uninduced and the induced conformations occludes the active site from the solvent. The structural data are consistent with a model in that the energy input from substrate association results in changes in the free energy landscape for the protein, allowing for structural transitions along an induced fit pathway.
The “Old” Euonymus europaeus Agglutinin Represents a Novel Family of Ubiquitous Plant Proteins1[W][OA]

Molecular cloning of the “old” but still unclassified Euonymus europaeus agglutinin (EEA) demonstrated that the lectin is a homodimeric protein composed of 152 residue subunits. Analysis of the deduced sequence indicated that EEA is synthesized without a signal peptide and undergoes no posttranslational processing apart from the removal of a six-residue N-terminal peptide. Glycan array screening confirmed the previously reported high reactivity of EEA toward blood group B oligosaccharides but also revealed binding to high mannose N-glycans, providing firm evidence for the occurrence of a plant carbohydrate-binding domain that can interact with structurally different glycans. Basic Local Alignment Search Tool searches indicated that EEA shares no detectable sequence similarity with any other lectin but is closely related evolutionarily to a domain that was first identified in some abscisic acid- and salt stress-responsive rice (Oryza sativa) proteins, and, according to the available sequence data, might be ubiquitous in Spermatophyta. Hence, EEA can be considered the prototype of a novel family of presumably cytoplasmic/nuclear proteins that are apparently ubiquitous in plants. Taking into account that some of these proteins are definitely stress related, the present identification of the EEA lectin domain might be a first step in the recognition of the involvement and importance of protein-glycoconjugate interactions in some essential cellular processes in Embryophyta.
Total Synthesis of a Functional Designer Eukaryotic Chromosome

Designer Chromosome One of the ultimate aims of synthetic biology is to build designer organisms from the ground up. Rapid advances in DNA synthesis has allowed the assembly of complete bacterial genomes. Eukaryotic organisms, with their generally much larger and more complex genomes, present an additional challenge to synthetic biologists. Annaluru et al. (p. 55, published online 27 March) designed a synthetic eukaryotic chromosome based on yeast chromosome III. The designer chromosome, shorn of destabilizing transfer RNA genes and transposons, is ∼14% smaller than its wild-type template and is fully functional with every gene tagged for easy removal. A synthetic version of yeast chromosome III with every gene tagged can substitute for the original. Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871–base pair designer eukaryotic chromosome, synIII, which is based on the 316,617–base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATα allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.
Fatal cases of Theileria annulata infection in calves in Portugal associated with neoplastic-like lymphoid cell proliferation

This study was carried out to investigate fifteen cases of acute lethal infection of calves (≤ 4 months of age) by the protozoan parasite Theileria (T.) annulata in the south of Portugal. Calves developed multifocal to coalescent nodular skin lesions, similar to multicentric malignant lymphoma. Infestation with ticks (genus Hyalomma) was intense. Theileria was seen in blood and lymph node smears, and T. annulata infection was confirmed by isolation of schizont-transformed cells and sequencing of hypervariable region 4 of the 18S rRNA gene. At necropsy, hemorrhagic nodules or nodules with a hemorrhagic halo were seen, particularly in the skin, subcutaneous tissue, skeletal and cardiac muscles, pharynx, trachea and intestinal serosa. Histologically, nodules were formed by large, round, lymphoblastoid neoplastic-like cells. Immunohistochemistry (IHC) identified these cells as mostly CD3 positive T lymphocytes and MAC387 positive macrophages. A marker for B lymphocytes (CD79αcy) labeled very few cells. T. annulata infected cells in these nodules were also identified by IHC through the use of two monoclonal antibodies (1C7 and 1C12) which are diagnostic for the parasite. It was concluded that the pathological changes observed in the different organs and tissues were caused by proliferation of schizont-infected macrophages, which subsequently stimulate a severe uncontrolled proliferation of uninfected T lymphocytes.
Ionizing Radiation Induces a Stress Response in Primary Cultures of Rainbow Trout Skin

Abstract Lyng, F. M. , Lyons-Alcantara, M. , Olwell, P., Ní Shuilleabháin, S. , Seymour, C. , Cottell, D. C. and Mothersill, C. Ionizing Radiation Induces a Stress Response in Primary Cultures of Rainbow Trout Skin. Radiat. Res. 162, 226–232 (2004). Fish skin is very vulnerable to damage from physical and chemical pollutants because it is in direct contact with the aquatic environment. In this study, the effect of γ radiation on primary cultures of rainbow trout skin was investigated. Primary cultures containing two cell types, epidermal cells and goblet mucous cells, were exposed to doses ranging from 0.5–15 Gy 60Co γ radiation. Expression of PCNA, c-myc and BCL2 was investigated as well as growth and levels of apoptosis and necrosis. Morphological and functional changes were also studied. The irradiated cultures showed evidence of a dose-dependent increase in necrosis and enhanced proliferation as well as morphological damage. In addition, mucous cell area was found to decrease significantly after irradiation. The study shows the value of these primary cultures as in vitro models for studying radiation effects. They provide an effective alternative to whole-animal exposures for radiation risk assessment.
Rosmarinic Acid, a New Polyphenol from Baccaurea ramiflora Lour. Leaf: A Probable Compound for Its Anti-Inflammatory Activity

Despite several pharmacological applications of Baccaurea ramiflora Lour. , studies on the influence of its polyphenol content on pharmacological activity such as anti-inflammatory properties have been scarce. Here we evaluated in vitro antioxidant activity, poyphenolics by HPLC and the anti-inflammatory potential of the methanolic leaf extract of Baccaurea ramiflora (BME) and its protective effects in carrageenan-induced paw edema model of inflammation in rats. The BME extract contained 79.06 ± 0.03 mg gallic acid equivalent (GAE)/g total polyphenols, 28.80 ± 0.01 mg quercetin equivalent (QE)/g flavonoid and 29.42 ± 0.01 μg cathechin equivalent/g proanthocyanidin respectively and rosmarinic acid (8 mg/kg) as a main component was identified by HPLC. Results demonstrate that administration of BME at the dose of 200 mg/kg can reduce paw edema by over 63%, and it exhibits a dose-response effect. Depending on concentration, the extract exerted scavenging activity on DPPH radical (IC50 36.4 μg/mL), significantly inhibited IL-1β (4.4 pg/mg protein) and TNF-α (0.21 ng/μg protein). Therefore, we conclude BME causes a substantial reduction of inflammation in in vivo models. We propose that rosmarinic acid and similar phenolic compounds may be useful in the therapy of inflammation-related injuries.