Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracellular survival of Burkholderia pseudomallei

Burkholderia pseudomallei is the causative agent of melioidosis, a disease being increasingly recognized as an important cause of morbidity and mortality in many regions of the world. Several features of melioidosis suggest that B. pseudomallei is a facultative intracellular pathogen. This study was designed to assess the ability of B. pseudomallei to invade and survive in eukaryotic cells. We have shown that B. pseudomallei has the capacity to invade cultured cell lines, including HeLa, CHO, A549, and Vero cells. We have demonstrated intracellular survival of B. pseudomallei in professional phagocytic cells, including rat alveolar macrophages. B pseudomallei was localized inside vacuoles in human monocyte-like U937 cells, a histiocytic lymphoma cell line with phagocytic properties. Additionally, electron microscopic visualization of B. pseudomallei-infected HeLa cells and polymorphonuclear leukocytes confirmed the presence of intracellular bacteria within membrane-bound vacuoles. B. pseudomallei was found to be resistant to the cationic peptide protamine and to purified human defensin HNP-1.
Crystal structure of human ornithine transcarbamylase complexed with carbamoyl phosphate and L‐norvaline at 1.9 Å resolution

The crystal structure of human ornithine transcarbamylase (OTCase) complexed with carbamoyl phosphate (CP) and L‐norvaline (NOR) has been determined to 1.9‐Å resolution. There are significant differences in the interactions of CP with the protein, compared with the interactions of the CP moiety of the bisubstrate analogue N‐(phosphonoacetyl)‐L‐ornithine (PALO). The carbonyl plane of CP rotates about 60° compared with the equivalent plane in PALO complexed with OTCase. This positions the side chain of NOR optimally to interact with the carbonyl carbon of CP. The mixed‐anhydride oxygen of CP, which is analogous to the methylene group in PALO, interacts with the guanidinium group of Arg‐92; the primary carbamoyl nitrogen interacts with the main‐chain carbonyl oxygens of Cys‐303 and Leu‐304, the side chain carbonyl oxygen of Gln‐171, and the side chain of Arg‐330. The residues that interact with NOR are similar to the residues that interact with the ornithine (ORN) moiety of PALO. The side chain of NOR is well defined and close to the side chain of Cys‐303 with the side chains of Leu‐163, Leu‐200, Met‐268, and Pro‐305 forming a hydrophobic wall. C‐δ of NOR is close to the carbonyl oxygen of Leu‐304 (3.56 Å), S‐γ atom of Cys‐303 (4.19 Å), and carbonyl carbon of CP (3.28 Å). Even though the N‐ϵ atom of ornithine is absent in this structure, the side chain of NOR is positioned to enable the N‐ϵ of ornithine to donate a hydrogen to the S‐γ atom of Cys‐303 along the reaction pathway. Binding of CP and NOR promotes domain closure to the same degree as PALO, and the active site structure of CP‐NOR‐enzyme complex is similar to that of the PALO‐enzyme complex. The structures of the active sites in the complexes of aspartate transcarbamylase (ATCase) with various substrates or inhibitors are similar to this OTCase structure, consistent with their common evolutionary origin. Proteins 2000;39:271–277. © 2000 Wiley‐Liss, Inc.
Constructive edge of uridylation-induced RNA degradation

ABSTRACT RNA uridylation is a significant transcriptome-shaping factor in protists, fungi, metazoans, and plants. The 3′ U-additions are catalyzed by terminal uridyltransferases (TUTases), a diverse group of enzymes that along with non-canonical poly(A) polymerases form a distinct group in the superfamily of DNA polymerase β-like nucleotidyl transferases. Within and across studied organisms and subcellular compartments, TUTases differ in nucleotide triphosphate selectivity, interacting partners, and RNA targets. A general premise linking RNA uridylation to 3′–5′ degradation received support from several studies of small RNAs and mRNA turnover. However, recent work on kinetoplastid protists typified by Trypanosoma brucei provides evidence that RNA uridylation may play a more nuanced role in generating functional small RNAs. In this pathogen's mitochondrion, most mRNAs are internally edited by U-insertions and deletions, and subjected to 3′ adenylation/uridylation; guide RNAs (gRNAs) required for editing are U-tailed. The prominent role of uridylation in mitochondrial RNA metabolism stimulated identification of the first TUTase, RNA editing TUTase 1 (RET1). Here we discuss functional studies of mitochondrial uridylation in trypanosomes that have revealed an unorthodox pathway of small RNA biogenesis. The current model accentuates physical coupling of RET1 and 3′–5′ RNase II/RNB-type exonuclease DSS1 within a stable complex termed the mitochondrial 3′ processome (MPsome). In the confines of this complex, RET1 initially uridylates a long precursor to activate its 3′–5′ degradation by DSS1, and then uridylates trimmed guide RNA to disengage the processing complex from the mature molecule. We also discuss a potential role of antisense transcription in the MPsome pausing at a fixed distance from gRNA's 5′ end. This step likely defines the mature 3′ end by enabling kinetic competition between TUTase and exonuclease activities.
A 20 μV/°C digital offset compensation technique for comparators and differential amplifiers

Digital offset compensation has been widely used for start-up calibration of analog ICs. It can be valuable in the design of an offset control circuit that has a minimal dependence on temperature. This eliminates the need to recalibrate the circuit during normal operation when the temperature may randomly fluctuate. This paper presents a gm-tracking technique used in an offset correction loop that drifts only 20 μV/°C over a temperature range of 0°C to 100°C. Test circuits fabricated in a 40 nm CMOS technology confirm the performance of the proposed technique.
A Critical Role of Fc Receptor-Mediated Antibody-Dependent Phagocytosis in the Host Resistance to Blood-Stage Plasmodium berghei XAT Infection1

Plasmodium berghei XAT is an irradiation-induced attenuated variant derived from the lethal strain P. berghei NK65, and its blood-stage parasites are spontaneously cleared in immune competent mice. In the present study, we studied the mechanism of host resistance to blood-stage malaria infection using P. berghei XAT. Infection enhanced Ab-dependent phagocytosis of PRBC by splenic macrophages in wild-type C57BL/6 mice. In contrast, FcR γ-chain knockout (FcRγ−/−) mice, which lack the ability to mediate Ab-dependent phagocytosis and Ab-dependent cell-mediated cytotoxicity through FcγRI, FcγRII, and FcγRIII, could not induce Ab-dependent phagocytic activity. These FcRγ−/− mice showed increased susceptibility to the P. berghei XAT infection, with eventually fatal results, although they produced comparable amounts of IFN-γ by spleen cells and anti-XAT Abs in serum. In addition, passive transfer of anti-XAT IgG obtained from wild-type mice that had recovered from infection into FcRγ−/− mice could not suppress the increase in parasitemia, and almost all of these mice died after marked parasitemia. In contrast, passive transfer of anti-XAT IgG into control wild-type mice inhibited the increase in parasitemia. IFN-γ−/− mice, which were highly susceptible to the P. berghei XAT infection, failed to induce Ab-dependent phagocytic activity and also showed reduced production of serum anti-XAT IgG2a isotype compared with control wild-type mice. These results suggest that FcR-mediated Ab-dependent phagocytosis, which is located downstream of IFN-γ production, is important as an effector mechanism to eliminate PRBC in blood-stage P. berghei XAT infection.
Laquinimod prevents inflammation-induced synaptic alterations occurring in experimental autoimmune encephalomyelitis

Background There are two generally accepted strategies for treating multiple sclerosis (MS), preventing central nervous system (CNS) damage indirectly through immunomodulatory interventions and/or repairing CNS damage by promoting remyelination. Both approaches also provide neuroprotection since they can prevent, indirectly or directly, axonal damage. Objective Recent experimental and clinical evidence indicates that the novel immunomodulatory drug laquinimod can exert a neuroprotective role in MS. Whether laquinimod-mediated neuroprotection is exerted directly on neuronal cells or indirectly via peripheral immunomodulation is still unclear. Methods C57Bl/6 experimental autoimmune encephalomyelitis (EAE) mice, immunised with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide, were treated for 26 days with subcutaneous daily injections of laquinimod (from 1 to 25 mg/kg). Patch clamp electrophysiology was performed on acute brain striatal slices from EAE mice treated with daily (25 mg/kg) laquinimod and on acute brain striatal slices from control mice bathed with laquinimod (1–30 µM). Results Both preventive and therapeutic laquinimod treatment fully prevented the alterations of GABAergic synapses induced by EAE, the first limiting also glutamatergic synaptic alterations. This dual effect might, in turn, have limited glutamatergic excitotoxicity, a phenomenon previously observed early during EAE and possibly correlated with later axonal damage. Furthermore, laquinimod treatment also preserved cannabinoid CB1 receptor sensitivity, normally lost during EAE. Finally, laquinimod per se was able to regulate synaptic transmission by increasing inhibitory post-synaptic currents and, at the same time, reducing excitatory post-synaptic currents. Conclusions Our data suggest a novel neuroprotective mechanism by which laquinimod might in vivo protect from neuronal damage occurring as a consequence of inflammatory immune-mediated demyelination.
BRONCHIAL CASTS OF HUMAN LUNGS USING NEGATIVE PRESSURE INJECTION

Negative-pressure casting techniques have been used for obtaining silicone rubber casts of the avian respiratory system, which contains minute air capillaries, noncompressible hollow bones, and highly flexible air sacs. The possibilities of this technique for the study of human airway diseases, which present technical difficulties similar to those of avian lungs, are investigated here. Left lungs from patients with various obstructive lung diseases or with normal lungs were fixed at autopsy under 25 cm H2O airway pressure with 2.5% phosphate-buffered glutaraldehyde. Cannulated, isolated lobes were placed in a vacuum chamber, and Dow Corning 734 RTV silicone elastomer, diluted with 10% low viscosity silicone oil, was introduced into the airways at -10 kPa. Following complete polymerization, the tissue was microdissected to reveal the lung cast in situ, and histological sections were obtained for correlative studies. The tissue was then macerated in 5.25% sodium hypochlorite. The total time from fixation to finished cast was 3-4 days. Linear shrinkage of the elastomer was less than 1% in glutaraldehyde or water and between 1 and 2% in bleach. The negative-pressure injection technique enabled complete and accurate filling of airways to the alveolar duct level at physiological pressures and provided good delineation of blind cavities such as obstructed airways or ectatic mucous gland ducts. The technique proved useful for the study of obstructive lung disease and should also prove useful for modelling aerosol deposition in diseased lungs.
Métodos de Evaluación de Impacto de Políticas Públicas

Objetivo del curso Este curso tiene como objetivo estudiar las técnicas microeconométricas más comúnmente utilizadas para la evaluación de impacto de políticas públicas, con énfasis en programas sociales. Se estudiarán las distintas técnicas para evaluar programas con diseños experimentales y no experimentales, enfatizando los supuestos necesarios para la validez de cada técnica. Las principales metodologías de evaluación de impacto serán ilustradas con ejemplos tanto argentinos como internacionales. Evaluación: examen domiciliario a ser entregado en la última clase del curso. Para aprobar el curso también es necesario asistir como mínimo al 75% de las clases dictadas. Fecha de entrega: a confirmar Material del curso: Las filminas del curso pueden obtenerse de la página https://sites.google. com/a/cedlas.org/program_evaluation/ utilizando la clave eval_prog.
Dynamic simulation of renewable energy sources and requirements on fault ride through behavior

Currently, power generation from renewable energy sources is of global significance and will continue to grow during the coming years. The grid integration of intermitting renewable energy sources is not only an issue of distribution networks, but effects the transmission grids as well. The largest amount of new installations are connected to the transmission grid, especially into 110-kV. Further, large wind farms with some 100 MW have already been connected to the 400-kV-system. The renewable energy sources are connected to the power network via power electronic converters, and this type of connection schema can change the short circuit conditions in the network. Today, usually a tripping command is generated within the first period, but in the future contributions to the short circuit current by renewable sources are necessary to fulfil the selective clearing of faults. To investigate the new requirements some novel simulation models are necessary, and described in the paper, for: converter connected DC sources (fuel cell, PV plants), doubly fed induction generator, DFIG, converter connected synchronous generator. Using these models the simulation allows for investigating the behavior for various control design. Requested is the delivery of rated current up to voltage dips of 100% for the whole duration of the fault. The results of some simulations and discussion of them have led to new rules for grid access. These rules are implemented into the grid code
Associations of A-FABP and H-FABP Markers with the Content of Intramuscular Fat in Beijing-You Chicken

This study has assessed the association of single nucleotide polymorphisms (SNP) identified in the adipocyte fatty acid binding protein (A-FABP) and heart-type fatty acid binding protein (H-FABP) genes with the content of intramuscular fat (IMF) in a population of male Beijing-You chickens. A previously described SNP in the chicken A-FABP gene had a significant (P < 0.05) effect on IMF content. Chickens inheriting the homozygous BB genotype at A-FABP had a significantly higher content of IMF in thigh muscles and breast muscles than did those inheriting the AA and AB genotypes. A novel SNP, identified here, in the H-FABP gene was also significantly (P < 0.05) associated with IMF content in thigh and breast muscle. Chickens inheriting the genotypes of DD and CD had much higher content of IMF than those inheriting the homozygous genotype of CC. Markers at the A-FABP and H-FABP genes were associated with IMF content in the studied population. Chickens inheriting the BB genotype at A-FABP, along with the CD genotype at H-FABP, produced muscles with a much higher content of IMF when compared with all other genotypes. A weak interaction between A-FABP and H-FABP was detected (P < 0.09) for IMF content in the tested population. The statistical significance of interaction is tentative because of the limited number of observations for some genotypic combinations. Markers identified within the A-FABP and H-FABP genes are suitable for future use in identifying chickens with the genetic potential to produce more desirable muscle with higher IMF content, at least in the population of Beijing-You male chickens.
Kinesiophobia in patients with chronic musculoskeletal pain: differences between men and women.

OBJECTIVE To investigate the degree of kinesiophobia in patients with chronic pain, to examine differences in kinesiophobia and other pain-related characteristics between men and women, and to examine differences in pain-related characteristics between patients with high and low levels of kinesiophobia. DESIGN Postal survey. SUBJECTS/PATIENTS Eighty-eight men and 173 women with chronic musculoskeletal pain. METHODS Patients completed questionnaires covering background data, pain variables, disability and psychological characteristics. The Swedish version of Tampa Scale for Kinesiophobia (TSK-SV) was used to measure kinesiophobia. RESULTS Kinesiophobia (TSK-SV score >37) was found in 56% of patients, with men having a higher frequency (72%) than women (48%). Pain intensity was correlated with TSK-SV score in both men and women. No correlations were found between kinesiophobia and age, pain duration or probable depression/anxiety. Women with high kinesiophobia tended to be younger, had more pain and showed more tiredness, disability, stress, interference and life dissatisfaction compared with women with low kinesiophobia. These differences were not seen in men. CONCLUSION The results indicate differences between men and women with chronic pain. The use of the TSK-SV questionnaire might assist therapists to identify patients whose fear of movement may negatively impact their rehabilitation. There is some evidence to suggest that optimal cut-off scores may differ between male and female patients.
Mechanism of Human Telomerase Inhibition by BIBR1532, a Synthetic, Non-nucleosidic Drug Candidate*

Telomerase, a ribonucleoprotein acting as a reverse transcriptase, has been identified as a target for cancer drug discovery. The synthetic, non-nucleosidic compound, BIBR1532, is a potent and selective telomerase inhibitor capable of inducing senescence in human cancer cells (1). In the present study, the mode of drug action was characterized. BIBR1532 inhibits the native and recombinant human telomerase, comprising the human telomerase reverse transcriptase and human telomerase RNA components, with similar potency primarily by interfering with the processivity of the enzyme. Enzyme-kinetic experiments show that BIBR1532 is a mixed-type non-competitive inhibitor and suggest a drug binding site distinct from the sites for deoxyribonucleotides and the DNA primer, respectively. Thus, BIBR1532 defines a novel class of telomerase inhibitor with mechanistic similarities to non-nucleosidic inhibitors of HIV1 reverse transcriptase.
Changing Roles of Ability and Education in U.S. Intergenerational Mobility

Using data on young adults from the 1979 and 1997 National Longitudinal Survey of Youth, we investigate the changing roles of ability and education in the transmission of economic status across generations. We find that ability plays a substantially diminished role for the most recent cohort whereas education plays a much larger role. The first finding results primarily from a smaller effect of children's ability on status, the second from an increased correlation between parental status and educational attainment. A replication of the analysis by gender reveals that the changes in the role of ability are largely driven by men whereas the changes in education's role are largely driven by women.
Mutation analysis of the FRAS1 gene demonstrates new mutations in a propositus with Fraser syndrome

Fraser syndrome (OMIM 219000) is a rare, autosomal recessive condition with classical features of cryptophthalmos, syndactyly, ambiguous genitalia, laryngeal, and genitourinary malformations, oral clefting and mental retardation. Mutations causing loss of function of the FRAS1 gene have been demonstrated in five patients with Fraser syndrome. However, no phenotype–genotype correlation was established and there was evidence for genetic heterogeneity. Fraser syndrome is rare and the FRAS1 gene has 75 exons, complicating mutation screening in affected patients. We have screened two patients who fulfilled the diagnostic criteria for Fraser syndrome and three patients with related phenotypes (two patients with Manitoba oculotrichoanal syndrome and one patient with unilateral cryptophthalmos and labial fusion) for mutations in FRAS1 to increase the molecular genetic data in patients with Fraser syndrome and related conditions. We report two new mutations in a patient with Fraser syndrome, a frameshift mutation and a deletion of two amino acids that we consider pathogenic as both alter the NG2‐like domain of the protein. Although we are still unable to clarify a phenotype–genotype relationship in Fraser syndrome, our data add to the list of mutations associated with this syndrome. © 2006 Wiley‐Liss, Inc.
Signal Processing and Coding Techniques for 2-D Magnetic Recording: An Overview

Two-dimensional magnetic recording (TDMR) is an emerging storage technology that aims to achieve areal densities on the order of 10 Tb/in2, mainly driven by innovative channels engineering with minimal changes to existing head/media designs within a systems framework. Significant additive areal density gains can be achieved by using TDMR over bit patterned media (BPM) and energy-assisted magnetic recording (EAMR). In TDMR, the sectors are inherently 2-D with reduced track pitch and bit widths, leading to severe 2-D intersymbol interference (ISI). This necessitates the development of powerful 2-D signal processing and coding algorithms for mitigating 2-D ISI, timing artifacts, jitter, and electronics noise resulting from irregular media grain positions and read-head electronics. The algorithms have to be eventually realized within a read/write channel architecture as a part of a system-on-chip (SoC) within the disk controller system. In this work, we provide a wide overview of TDMR technology, channel models and capacity, signal processing algorithms (detection and timing recovery), and error-correcting codes attuned to 2-D channels. The innovations and advances described not only make TDMR a promising future technology, but may serve a broader engineering audience as well.
The Vector Control Strategies for Multiphase Synchronous Motor Drive Systems

This paper studies the multiphase synchronous motor with symmetrical windings and multi-Y-windings displaced in turn by ¿o separately, the mathematical descriptions about which can be concluded as two models: single-windings and multi-windings models in M,T frame. Based on these models, the multiphase vector control strategy and multiphase multi-ply vector control strategy are proposed, so as to achieve the gas-flux-oriented control for multiphase synchronous motor in two models of mathematic descriptions. The corresponding control frames are established for the multiphase synchronous motor drive systems. Taking the 12-phase synchronous motor with four Y-connected 3-phase symmetrical windings displaced in turn by 15° as an example, the 4-ply control principle is deduced. The experiment results show the system has perfect control and operation performance under such a control strategy.