Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Encapsulated Liver Cell Spheroids in a Fluidised-Bed Bioartificial Liver for Treatment of Ischaemic Acute Liver Failure in Pigs in a Translational Setting

Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL) comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4–6×1010cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL), and those connected to circuit containing alginate capsules without cells (Empty-bead BAL). Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells) had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without cells. In the +cell group, human proteins accumulated in pigs' plasma. Delivery of biomass using a short-term cold-chain enabled transport and use without loss of function over 3days. Thus, a fluidised-bed bioreactor containing alginate-encapsulated HepG2cell-spheroids improved important parameters of acute liver failure in pigs. The system can readily be up-scaled and transported to point-of-use justifying development at clinical scale.
Reduction of phosphorylated histone H3 serine 10 and serine 28 cell cycle marker intensities after DNA damage

Phosphorylated histone H3 at serine 10 and serine 28 (H3Ser10 and H3Ser28) have been recognized as cell cycle markers to evaluate the late‐G2/M status of cell and tissue samples. I report about the reduction phenomena of H3Ser10 and Ser28 phosphorylation (H3Ser10P and 28P) at the late‐G2 through M cell cycle phases in association with DNA damage caused by hydrogen peroxide (H2O2). The levels of H3Ser10P and Ser28P decreased between 15 and 60 min after H2O2 addition in an inverse correlation manner with H2AX Ser139 phosphorylation (γH2AX). Experiments using wortmannin suggested that the reduction events of H3Ser10P/28P are under the control of phosphatidylinositol 3‐kinase‐like kinases. Fluorescence microscopic observation showed that H3Ser10 and Ser28 on telomeric portions of condensed M‐phase chromosomes retained their strongly phosphorylated status even after 60 min of H2O2 treatment. In addition, these chromosome parts were poorly γH2AX positive showing mutually exclusive distribution patterns between H3Ser10P/28P and γH2AX. Considering these data, I hypothesize that the reduction of the H3Ser10P/28P is a part of the DNA damage response processes. It is advisable to pay careful attention to these phenomena at the time of designing cell cycle assay protocols with H3Ser10P or Ser28P mitosis markers when DNA damaging process is expected to occur. © 2008 International Society for Advancement of Cytometry
Enabling JSON Document Stores in Relational Systems

In recent years, “document store” NoSQL systems have exploded in popularity, largely driven by the adoption of the JSON data model in Web and mobile applications. The advantages of these NoSQL document store systems (like MongoDB and CouchDB) are tempered by a lack of traditional RDBMS features, notably a sophisticated declarative query language, rich native query processing constructs (e.g. joins), and transaction management providing ACID safety guarantees. With this paper, we hope to spark a discussion in the database community about how JSON data can be supported on top of a relational infrastructure, and how the best features of JSON document stores and relational databases can be combined. We present Argo, a proof-ofconcept mapping layer for storing and querying JSON data in a relational system with an easy-to-use SQL-like query language. We also present NoBench, a micro-benchmark suite for queries over JSON data in NoSQL and SQL systems. Our results point to directions of how one can marry the best of both worlds, combining the flexibility and interoperability of JSON with the rich query processing and transactional properties offered by a traditional RDBMS. Note: An extended version of this paper is available at [6]. The Argo source code is available at http://research.cs. wisc.edu/quickstep/argo/argo.tar. bz2
20-GHz Quadrature Injection-Locked LC Dividers With Enhanced Locking Range

Quadrature injection-lockedLC dividers with either a Miller topology or an injection-lockedLC VCO topology are coupled with transconductors to enhance their locking range. The effect of the transconductance coupling is analyzed theoretically and through circuit simulation. Both topologies were fabricated by 90-nm CMOS technology with a target input center frequency of 20 GHz and output frequency of 10 GHz. The measured locking range for the Miller topology with transconductance coupling is 25.3%, compared to 20.9% without coupling. The measured locking range for the injection-locked LC VCO topology with transconductance coupling is 18.1%, compared to 12.9% without coupling. Moreover, power consumption for both dividers is 6.4 mW with a 1.2-V supply.
Modeling Answer Constraints in Constraint Logic Programs

The constraint logic programming paradigm CLP(X) (CLP for short) has been proposed by Jaaar and Lassez in order to integrate a generic computational mechanism based on constraints with the logic programming framework. This paradigm retains the semantic properties of logic languages, namely the existence of equivalent operational, model theo-retic and xpoint semantics. Moreover, since computation is performed over the particular domain of computation X, CLP(X) programs have an equivalent \algebraic" semantics, i.e. a semantics which is deened directly on the algebraic structure of the domain X. In this paper we propose an extension of such a semantics, for the success set case, in order to fully characterize the operational behaviour of programs. We introduce a framework for deening various notions of models, each corresponding to a speciic operationally observable property. The construction is based on a new notion of interpretation (set of constrained atoms), on a natural extension of the standard notion of truth and on the dee-nition of various immediate consequences operators T i , whose least xpoints on the lattice of interpretations are models corresponding to various observable properties. Since within our framework the equivalence between the operational and the declarative semantics can be fully achieved, it can be taken as the basis of program transformation and analyses techniques. In particular, it is possible to deene suitable abstract immediate consequence operators and therefore a bottom-up abstract interpretation framework which generalizes to the CLP case an approach developed for pure logic programs.
A Two-Phase Expansion Protocol Combining Interleukin (IL)-15 and IL-21 Improves Natural Killer Cell Proliferation and Cytotoxicity against Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in children. Despite intensive research in recent decades the prognosis for patients with metastatic or relapsed diseases has hardly improved. New therapeutic concepts in anti-tumor therapy aim to modulate the patient’s immune system to increase its aggressiveness or targeted effects toward tumor cells. Besides surgery, radiotherapy and chemotherapy, immune activation by direct application of cytokines, antibodies or adoptive cell therapy are promising approaches. In the last years, adoptive transfer of natural killer (NK) cells came into the focus of translational medicine, because of their high cytotoxic potential against transformed malignant cells. A main challenge of NK cell therapy is that it requires a high amount of functional NK cells. Therefore, ex vivo NK cell expansion protocols are currently being developed. Many culturing strategies are based on the addition of feeder or accessory cells, which need to be removed prior to the clinical application of the final NK cell product. In this study, we addressed feeder cell-free expansion methods using common γ-chain cytokines, especially IL-15 and IL-21. Our results demonstrated high potential of IL-15 for NK cell expansion, while IL-21 triggered NK cell maturation and functionality. Hence, we established a two-phase expansion protocol with IL-15 to induce an early NK cell expansion, followed by short exposure to IL-21 that boosted the cytotoxic activity of NK cells against RMS cells. Further functional analyses revealed enhanced degranulation and secretion of pro-inflammatory cytokines such as interferon-γ and tumor necrosis factor-α. In a proof of concept in vivo study, we also observed a therapeutic effect of adoptively transferred IL-15 expanded and IL-21 boosted NK cells in combination with image guided high precision radiation therapy using a luciferase-transduced RMS xenograft model. In summary, this two-phased feeder cell-free ex vivo culturing protocol combined efficient expansion and high cytolytic functionality of NK cells for treatment of radiation-resistant RMS.
Vitamin B1 in marine sediments: pore water concentration gradient drives benthic flux with potential biological implications

Vitamin B1, or thiamin, can limit primary productivity in marine environments, however the major marine environmental sources of this essential coenzyme remain largely unknown. Vitamin B1 can only be produced by organisms that possess its complete synthesis pathway, while other organisms meet their cellular B1 quota by scavenging the coenzyme from exogenous sources. Due to high bacterial cell density and diversity, marine sediments could represent some of the highest concentrations of putative B1 producers, yet these environments have received little attention as a possible source of B1 to the overlying water column. Here we report the first dissolved pore water profiles of B1 measured in cores collected in two consecutive years from Santa Monica Basin, CA. Vitamin B1 concentrations were fairly consistent between the two years ranging from 30 pM up to 770 pM. A consistent maximum at ~5 cm sediment depth covaried with dissolved concentrations of iron. Pore water concentrations were higher than water column levels and represented some of the highest known environmental concentrations of B1 measured to date, (over two times higher than maximum water column concentrations) suggesting increased rates of cellular production and release within the sediments. A one dimensional diffusion-transport model applied to the B1 profile was used to estimate a diffusive benthic flux of ~0.7 nmol m−2 d−1. This is an estimated flux across the sediment-water interface in a deep sea basin; if similar magnitude B-vitamin fluxes occur in shallow coastal waters, benthic input could prove to be a significant B1-source to the water column and may play an important role in supplying this organic growth factor to auxotrophic primary producers.
The Galaxy Stellar Mass Function at 3.5 Greater Than or Equal to z Greater Than or Equal to 7.5 in the CANDLES/UDS, GOODS-South, and HUDF Fields

The galaxy stellar mass function (GSMF) at high-z provides key information on star-formation history and mass assembly in the young Universe. We aimed to use the unique combination of deep optical/NIR/MIR imaging provided by HST, Spitzer and the VLT in the CANDELS-UDS, GOODS-South, and HUDF fields to determine the GSMF over the redshift range 3.5 4. These results confirm the unique synergy of the CANDELS+HUDF, HUGS, and SEDS surveys for the discovery and study of moderate/low-mass galaxies at high redshifts.
Upstroke wing flexion and the inertial cost of bat flight

Flying vertebrates change the shapes of their wings during the upstroke, thereby decreasing wing surface area and bringing the wings closer to the body than during downstroke. These, and other wing deformations, might reduce the inertial cost of the upstroke compared with what it would be if the wings remained fully extended. However, wing deformations themselves entail energetic costs that could exceed any inertial energy savings. Using a model that incorporates detailed three-dimensional wing kinematics, we estimated the inertial cost of flapping flight for six bat species spanning a 40-fold range of body masses. We estimate that folding and unfolding comprises roughly 44 per cent of the inertial cost, but that the total inertial cost is only approximately 65 per cent of what it would be if the wing remained extended and rigid throughout the wingbeat cycle. Folding and unfolding occurred mostly during the upstroke; hence, our model suggests inertial cost of the upstroke is not less than that of downstroke. The cost of accelerating the metacarpals and phalanges accounted for around 44 per cent of inertial costs, although those elements constitute only 12 per cent of wing weight. This highlights the energetic benefit afforded to bats by the decreased mineralization of the distal wing bones.
Genetically essential and nonessential alpha-tubulin genes specify functionally interchangeable proteins

Microtubules in yeast are essential components of the mitotic and meiotic spindles and are essential for nuclear movement during cell division and mating. The relative importance in these processes of the two divergent alpha-tubulin genes of the budding yeast Saccharomyces cerevisiae, TUB1 and TUB3, was examined through the construction of null mutations and by increasing their copy number on chromosomes and on plasmids. Experiments with null alleles of TUB3 showed that TUB3 was not essential for mitosis, meiosis, or mating. Null alleles of TUB3, however, did cause several phenotypes, including hypersensitivity to the antimicrotubule drug benomyl and poor spore viability. On the other hand, the TUB1 gene was essential for growth of normal haploid cells. Even in diploids heterozygous for a TUB1 null allele, several dominant phenotypes were evident, including slow growth and poor sporulation. This functional difference between the two genes is apparently due to different levels of expression, because extra copies of either gene could suppress the defects caused by a null mutation in the other. We conclude that in spite of the 10% divergence between the products of the two genes, there is no essential qualitative functional difference between them.
Theophylline Restores Histone Deacetylase Activity and Steroid Responses in COPD Macrophages

Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease of the lungs with little or no response to glucocorticoids and a high level of oxidative stress. Histone deacetylase (HDAC) activity is reduced in cells of cigarette smokers, and low concentrations of theophylline can increase HDAC activity. We measured the effect of theophylline on HDAC activity and inflammatory gene expression in alveolar macrophages (AM) from patients with COPD. AM from normal smokers showed a decrease in HDAC activity compared with normal control subjects, and this was further reduced in COPD patients (51% decrease, P < 0.01). COPD AMs also showed increased basal release of IL-8 and TNF-α, which was poorly suppressed by dexamethasone. Theophylline induced a sixfold increase in HDAC activity in COPD AM lysates and significantly enhanced dexamethasone suppression of induced IL-8 release, an effect that was blocked by the HDAC inhibitor trichostatin A. Therefore, theophylline might restore steroid responsiveness in COPD patients.
Clinical Efficacy of Moringa oleifera Lam. Stems Bark in Urinary Tract Infections

Objective. Urinary tract infections (UTI) are the most common problem in clinical practice. Usually they are asymptomatic and are commonly present with distressing symptoms like pain and burning sensation on urination. Antibiotics are widely used to treat UTIs; however, they have their own limitations like resistance, reinfection, and relapses. The purpose of the current study was to evaluate the value of Moringa oleifera Lam. stem bark as a potential medicine for UTIs. Study Design. 30 patients with UTI were randomly divided into two groups with 15 patients in each group. Shigru bark was given to patients of the first group (trial group) and modern medicines were prescribed to the other group of patients. At least three follow-ups are taken in both groups at the end of every week of treatment. Results. After treatment 66.67 % were cured, 13.33 % improved, 13.33% patients have no change, and 6.67% relapsed in trial group and in control group 46.67% were cured, 26.66% improved, 6.67% patients have no change, and 20% relapsed. Interpretation and Conclusion. The trial drug is significant in the management of UTI. This study needs to be done on a large scale and for a long time.
Bone Marrow– or Vessel Wall–Derived Osteoprotegerin Is Sufficient to Reduce Atherosclerotic Lesion Size and Vascular Calcification

Objective—Osteoprotegerin (OPG) is a decoy receptor for the osteoclast differentiation factor receptor activator of NF-&kgr;B ligand. OPG regulates bone homeostasis, and its inactivation in mice results in severe osteoporosis. OPG deficiency in apolipoprotein E (ApoE)−/− mice results in increased atherosclerotic lesion size and calcification. Furthermore, receptor activator of NF-&kgr;B ligand enhances macrophage-dependent smooth muscle cell calcification in vitro. Here, we hypothesized that reconstitution of ApoE−/−OPG−/− mice with ApoE−/−OPG+/+ bone marrow (BM) would be sufficient to rescue lesion progression and vascular calcification. Conversely, reconstitution of ApoE−/−OPG+/+ mice with ApoE−/−OPG−/− BM may accelerate lesion progression and vascular calcification. Approach and Results—ApoE−/−OPG−/− mice transplanted with ApoE−/−OPG+/+ BM developed smaller atherosclerotic lesions and deposited less calcium in the innominate artery than that of ApoE−/−OPG−/− mice transplanted with ApoE−/−OPG−/− BM. There were no differences in lesion size and calcification in ApoE−/−OPG+/+ mice transplanted with BM from ApoE−/−OPG−/− or ApoE−/−OPG+/+ mice. The large lesions observed in the ApoE−/−OPG−/− mice transplanted with OPG−/− BM were rich in chondrocyte-like cells, collagen, and proteoglycans. Importantly, the ApoE−/−OPG−/− mice transplanted with OPG+/+ BM remained osteoporotic, and the ApoE−/−OPG+/+ mice did not show signs of bone loss regardless of the type of BM received. In coculture experiments, macrophages and mesenchymal stem cells derived from ApoE−/−OPG−/− BM induced more vascular smooth muscle cell calcification than cells derived from ApoE−/−OPG+/+ mice. Conclusions—These results indicate that OPG derived either from the BM or from the vessel wall is sufficient to slow down lesion progression and vascular calcification independent of bone turnover.
Fecundity compensation and tolerance to a sterilizing pathogen in Daphnia

Hosts are armed with several lines of defence in the battle against parasites: they may prevent the establishment of infection, reduce parasite growth once infected or persevere through mechanisms that reduce the damage caused by infection, called tolerance. Studies on tolerance in animals have focused on mortality, and sterility tolerance has not been investigated experimentally. Here, we tested for genetic variation in the multiple steps of defence when the invertebrate Daphnia magna is infected with the sterilizing bacterial pathogen Pasteuria ramosa: anti‐infection resistance, anti‐growth resistance and the ability to tolerate sterilization once infected. When exposed to nine doses of a genetically diverse pathogen inoculum, six host genotypes varied in their average susceptibility to infection and in their parasite loads once infected. How host fecundity changed with increasing parasite loads did not vary between genotypes, indicating that there was no genetic variation for this measure of fecundity tolerance. However, genotypes differed in their level of fecundity compensation under infection, and we discuss how, by increasing host fitness without targeting parasite densities, fecundity compensation is consistent with the functional definition of tolerance. Such infection‐induced life‐history shifts are not traditionally considered to be part of the immune response, but may crucially reduce harm (in terms of fitness loss) caused by disease, and are a distinct source of selection on pathogens.
Clinical characteristics and treatment of epilepsy in children with tuberous sclerosis complex

The aim of this study is to estimate the clinical characteristics and treatment of epileptic seizures in children with tuberous sclerosis complex and to determine if there is a correlation between brain CT/MRI findings and evolution of epilepsy in these patients. The medical data of 11 children diagnosed with tuberous sclerosis and epileptic seizures were retrospectively studied. Brain imaging was performed in all patients and revealed cortical tubers varying in number and location and/or intracranial calcifications. The children were treated employing different antiepileptic drugs single or add-on. Partial seizure control was achieved in 36.36% patients. In our study, there is no statistical relationship between epileptic seizures outcome and brain imaging abnormaties, but this conclusion, drawn from a small number of cases, represents only a starting point,remaining to be confirmed by further larger studies.
Intracoronary bone marrow cell application for terminal heart failure in children

Abstract Introduction In spite of tremendous progress in the medical and surgical treatment of children with congenital heart disease and dilated cardiomyopathy achieved during the past few decades, for some children a heart transplant remains the only option. Clinically relevant benefits of intracoronary injection of autologous stem cells on cardiac function and remodelling have been demonstrated in adult patients with acute myocardial infarction. Experience with autologous stem cell therapy in children with severe congenital or acquired pump failure is limited to a small number of case reports. Method and results Between 2006 and 2010, nine severely ill children were treated with intracoronary infusion of autologous bone marrow-derived mononuclear cells as part of a compassionate therapy in our centre. No procedure-related unexpected adverse events occurred. There was one patient on extracorporeal membrane oxygenation who died of haemorrhage unrelated to the procedure; three patients proceeded to heart transplantation once a donor heart became available. The other five patients showed an improvement with respect to New York Heart Association classification (greater than or equal to 1), brain natriuretic peptide serum levels, and ejection fraction. Conclusion Similar to adults, intracoronary injection of autologous bone marrow cell is technically feasible and safe for children. On the basis of our data, we propose to perform a pilot study for children with congestive heart failure, to formally assess the efficacy of intracoronary autologous bone marrow cell therapy.