Miracle-dz/UniFAR-FTUs huggingface dataset:
Allelic Diversity of the Plasmodium falciparum Erythrocyte Membrane Protein 1 Entails Variant-Specific Red Cell Surface Epitopes

The clonally variant Plasmodium falciparum PfEMP1 adhesin is a virulence factor and a prime target of humoral immunity. It is encoded by a repertoire of functionally differentiated var genes, which display architectural diversity and allelic polymorphism. Their serological relationship is key to understanding the evolutionary constraints on this gene family and rational vaccine design. Here, we investigated the Palo Alto/VarO and IT4/R29 and 3D7/PF13_003 parasites lines. VarO and R29 form rosettes with uninfected erythrocytes, a phenotype associated with severe malaria. They express an allelic Cys2/group A NTS-DBL1α1 PfEMP1 domain implicated in rosetting, whose 3D7 ortholog is encoded by PF13_0003. Using these three recombinant NTS-DBL1α1 domains, we elicited antibodies in mice that were used to develop monovariant cultures by panning selection. The 3D7/PF13_0003 parasites formed rosettes, revealing a correlation between sequence identity and virulence phenotype. The antibodies cross-reacted with the allelic domains in ELISA but only minimally with the Cys4/group B/C PFL1955w NTS-DBL1α. By contrast, they were variant-specific in surface seroreactivity of the monovariant-infected red cells by FACS analysis and in rosette-disruption assays. Thus, while ELISA can differentiate serogroups, surface reactivity assays define the more restrictive serotypes. Irrespective of cumulated exposure to infection, antibodies acquired by humans living in a malaria-endemic area also displayed a variant-specific surface reactivity. Although seroprevalence exceeded 90% for each rosetting line, the kinetics of acquistion of surface-reactive antibodies differed in the younger age groups. These data indicate that humans acquire an antibody repertoire to non-overlapping serotypes within a serogroup, consistent with an antibody-driven diversification pressure at the population level. In addition, the data provide important information for vaccine design, as production of a vaccine targeting rosetting PfEMP1 adhesins will require engineering to induce variant-transcending responses or combining multiple serotypes to elicit a broad spectrum of immunity.
TRAP-VACCINATE-RELEASE AND ORAL VACCINATION FOR RABIES CONTROL IN URBAN SKUNKS, RACCOONS AND FOXES

Two rabies control tactics, trap-vaccinate-release (T-V-R) and oral vaccination were used for the control of rabies in skunks (Mephitis mephitis), raccoons (Procyon lotor), and foxes (Vulpes vulpes) in metropolitan Toronto, Canada. Using T-V-R, a mean of 45% to 72% (95% confidence limits of 40% to 81%) of the skunks and a mean of 17% to 68% (95% confidence limits of 14% to 76%) of the raccoons in a 60 km2 area of Toronto were vaccinated against rabies between 1987 and 1991. The area has been free of skunk rabies from May 1989 to April 1992. Forty-five rabies cases were diagnosed during 1980 to 1986. In contrast, only three skunk cases have been reported since the vaccination program began in July 1987. The T-V-R area also remained rabies free during an epizootic of skunk rabies in metropolitan Toronto during 1991. Following distribution of rabies vaccine-baits throughout the ravines of metropolitan Toronto, June 1989 to December 1991, 46% to 80% of the Toronto fox population was immunized during 1989, 1990 and 1991. Only one case of fox rabies was reported in metropolitan Toronto since vaccination began, compared to 80 cases reported between 1982 and 1988. The area has been free of reported fox rabies from October 1990 to April 1992.
Regional variations in the distribution and colocalization of extracellular matrix proteins in the juvenile bovine meniscus

A deeper understanding of the composition and organization of extracellular matrix molecules in native, healthy meniscus tissue is required to fully appreciate the degeneration that occurs in joint disease and the intricate environment in which an engineered meniscal graft would need to function. In this study, regional variations in the tissue‐level and pericellular distributions of collagen types I, II and VI and the proteoglycans aggrecan, biglycan and decorin were examined in the juvenile bovine meniscus. The collagen networks were extensively, but not completely, colocalized, with tissue‐level organization that varied with radial position across the meniscus. Type VI collagen exhibited close association with large bundles composed of type I and II collagen and, in contrast to type I and II collagen, was further concentrated in the pericellular matrix. Aggrecan was detected throughout the inner region of the meniscus but was restricted to the pericellular matrix and sheaths of collagen bundles in the middle and outer regions. The small proteoglycans biglycan and decorin exhibited regional variations in staining intensity but were consistently localized in the intra‐ and/or peri‐cellular compartments. These results provide insight into the complex hierarchy of extracellular matrix organization in the meniscus and provide a framework for better understanding meniscal degeneration and disease progression and evaluating potential repair and regeneration strategies.
Survival and differentiation of neural progenitor cells derived from embryonic stem cells and transplanted into ischemic brain.

OBJECT Cell replacement therapy including the use of embryonic stem cells (ESCs) may represent a novel treatment for damage from stroke. In this study, the authors transplanted neural progenitor cells (NPCs) derived from ESCs into ischemic brain and analyzed their survival and differentiation. METHODS Multipotential NPCs were generated from ESCs by using the stromal cell-derived inducing activity method. These cells could differentiate in vitro into neurons, glia, and oligodendrocytes, thus revealing them to be neural stem cells. The NPCs were then transplanted into ischemic brain. At 2 weeks postischemia, the transplanted cells occupied 18.8 +/-2.5% of the hemispheric area; by 4 weeks postischemia, 26.5 +/- 4% of the hemisphere. At 4 weeks after transplantation, green fluorescent protein (GFP)-positive transplanted cells showed mature neuronal morphological features. The authors also investigated the expression of differentiation markers and various neurotransmitters. Transplanted cells were immunopositive for neuronal nuclei, beta-tubulin-III, and glial fibrillary acidic protein. Of the GFP-positive cells, 33.3 +/-11.5% were positive for glutamate decarboxylase, 13.3 +/- 5.8% for glutamate, 2.1 +/- 2.5% for tyrosine hydroxylase, 1.8 +/- 2% for serotonin, and 0.4 +/- 0.2% for choline acetyltransferase. CONCLUSIONS The authors confirmed the survival and differentiation of ESC-derived NPCs transplanted into the ischemic brain. Surviving transplanted cells expressed several neural markers and neurotransmitters. These findings indicate that these cells can function in the brain.
Differential Mobility of Pigment-Protein Complexes in Granal and Agranal Thylakoid Membranes of C3 and C4 Plants1[OA]

The photosynthetic performance of plants is crucially dependent on the mobility of the molecular complexes that catalyze the conversion of sunlight to metabolic energy equivalents in the thylakoid membrane network inside chloroplasts. The role of the extensive folding of thylakoid membranes leading to structural differentiation into stacked grana regions and unstacked stroma lamellae for diffusion-based processes of the photosynthetic machinery is poorly understood. This study examines, to our knowledge for the first time, the mobility of photosynthetic pigment-protein complexes in unstacked thylakoid regions in the C3 plant Arabidopsis (Arabidopsis thaliana) and agranal bundle sheath chloroplasts of the C4 plants sorghum (Sorghum bicolor) and maize (Zea mays) by the fluorescence recovery after photobleaching technique. In unstacked thylakoid membranes, more than 50% of the protein complexes are mobile, whereas this number drops to about 20% in stacked grana regions. The higher molecular mobility in unstacked thylakoid regions is explained by a lower protein-packing density compared with stacked grana regions. It is postulated that thylakoid membrane stacking to form grana leads to protein crowding that impedes lateral diffusion processes but is required for efficient light harvesting of the modularly organized photosystem II and its light-harvesting antenna system. In contrast, the arrangement of the photosystem I light-harvesting complex I in separate units in unstacked thylakoid membranes does not require dense protein packing, which is advantageous for protein diffusion.
Local climate zones and annual surface thermal response in a Mediterranean city

Beirut, a densely populated city along the Mediterranean coastline, has been witnessing temperature records well above thermal comfort levels especially during the past decade. The significant effect of existing urbanised materials on these rising urban temperatures has been verified through the previous modeling of the urban heat island phenomenon (UHI) of the city using the Town Energy Balance model (TEB). The predominantly dense mix of midrise buildings spread across the city with few trees has also been confirmed by previous local climatic zoning classification. The first aim of this paper was to compare different input data used for the classifications. Two Landsat 8 scenes (optical and thermal, acquired in 2013 and 2014) as well as one Sentinel-1, and one Sentinel-2 scene (both acquired in 2015) were tested as input data. The best results were achieved with both optical sensors, while thermal and SAR data alone did not perform as well. Secondly, the transferability of training area between Beirut and Damascus city was tested. It was found that the diverse biophysical and climatic backgrounds make this difficult resulting in poor accuracies. Finally, long-term surface temperature characteristics from thermal remote sensing images were compared to the LCZ classifications. Although the surface heat island effects could be seen in annual cycle parameters, the patterns were dominated by land cover and topo-climatic effects due to the high vertical extent of the region of interest.
FDTD analysis using constant parameter modeling for the calculation of transient responses and voltage profiles on multiconductor overhead transmission lines

FDTD models have been used since many years for the calculation of transients in overhead transmission lines (OHTLs), modeling them either as lossless or with frequency dependent parameters. Their major drawback, especially in the latter case, is their high computational cost. But FDTD models allow also the efficient calculation of voltage distributions with high discretization along OHTLs. This is significant in tracing transient overvoltages in short line segments in HV substations and in the calculation of signal voltage levels along transmission lines in Power Line Communication applications. Modal domain and phase domain frequency dependent transmission line models can provide accurate transient responses. However, when they are used in multi-segment configurations for the calculation of voltage distribution along transmission lines they may lead to error accumulations, combined with other limitations due to computational requirements or to the approaches in modal or phase domain analysis. In this paper, a constant parameter FDTD model for OHTLs is formulated, incorporating losses due to skin-effect and to the imperfect earth, capable to handle properly also non-homogeneous propagation. The proposed formulation is successfully checked against frequency dependent line models of the ATP/EMTP software, as well as against a formulated frequency dependent FDTD model. The proposed FDTD model proves to be numerically stable and is efficiently applied in voltage profile calculations.
Formation of Reactive Nitrogen Species during Peroxidase-catalyzed Oxidation of Nitrite

Involvement of peroxynitrite (ONOO−) in inflammatory diseases has been implicated by detection of 3-nitrotyrosine, an allegedly characteristic protein oxidation product, in various inflamed tissues. We show here that nitrite (NO2−), the primary metabolic end product of nitric oxide (NO·), can be oxidized by the heme peroxidases horseradish peroxidase, myeloperoxidase (MPO), and lactoperoxidase (LPO), in the presence of hydrogen peroxide (H2O2), to most likely form NO·2, which can also contribute to tyrosine nitration during inflammatory processes. Phenolic nitration by MPO-catalyzed NO2− oxidation is only partially inhibited by chloride (Cl−), the presumed major physiological substrate for MPO. In fact, low concentrations of NO2− (2-10 μM) catalyze MPO-mediated oxidation of Cl−, indicated by increased chlorination of monochlorodimedon or 4-hydroxyphenylacetic acid, most likely via reduction of MPO compound II. Peroxidase-catalyzed oxidation of NO2−, as indicated by phenolic nitration, was also observed in the presence of thiocyanate (SCN−), an alternative physiological substrate for mammalian peroxidases. Collectively, our results suggest that NO2−, at physiological or pathological levels, is a substrate for the mammalian peroxidases MPO and lactoperoxidase and that formation of NO2· via peroxidase-catalyzed oxidation of NO2− may provide an additional pathway contributing to cytotoxicity or host defense associated with increased NO· production.
Prion protein expression and functional importance in developmental angiogenesis: role in oxidative stress and copper homeostasis.

AIM It has been convincingly shown that oxidative stress and toxicity by deregulated metals, such as copper (Cu), are tightly linked to the development of pre-eclampsia and intrauterine growth retardation (IUGR), the most threatening pathologies of human pregnancy. However, mechanisms implemented to control these effects are far from being understood. Among proteins that bind Cu and insure cellular protection against oxidative stress is the cellular prion protein (PrP(C)), a glycosyl phosphatidyl inositol-anchored glycoprotein, which we reported to be highly expressed in human placenta. Herein, we investigated the pathophysiological role of PrP(C) in Cu and oxidative stress homeostasis in vitro using human placenta and trophoblast cells, and in vivo using three strains of mice (C57Bl6, PrP(C) knockout mice [PrP(-/-)], and PrP(C) overexpressing mice [Tga20]). RESULTS At the cellular level, PrP(C) protection against oxidative stress was established in multiple angiogenic processes: proliferation, migration, and tube-like organization. For the animal models, lack (PrP(-/-)) or overexpression (Tga20) of PrP(C) in gravid mice caused severe IUGR that was correlated with a decrease in litter size, changes in Cu homeostasis, increase in oxidative stress response, development of hypoxic environment, failure in placental function, and maintenance of growth defects of the offspring even 7.5 months after delivery. INNOVATION PrP(C) could serve as a marker for the idiopathic IUGR disease. CONCLUSION These findings demonstrate the stress-protective role of PrP(C) during development, and propose PrP(C) dysregulation as a novel causative element of IUGR.
Partial suppression of an Escherichia coli TonB transmembrane domain mutation (ΔV17) by a missense mutation in ExbB

Active transport of vitamin B12 and Fe(III)‐siderophore complexes across the outer membrane of Escherichia coli appears to be dependent upon the ability of the TonB protein to couple cytoplasmic membrane‐generated protonmotive force to outer membrane receptors. TonB is supported in this role by an auxiliary protein, ExbB, which, in addition to stabilizing TonB against the activities of endogenous envelope proteases, directly contributes to the energy transduction process. The topological partitioning of TonB and ExbB to either side of the cytoplasmic membrane restricts the sites of interaction between these proteins primarily to their transmembrane domains. In this study, deletion of valine 17 within the amino‐terminal transmembrane anchor of TonB resulted in complete loss of TonB activity, as well as loss of detectable in vivo crosslinking into a 59 kDa complex believed to contain ExbB. The ΔV17 mutation had no effect on TonB export. The loss of crosslinking appeared to reflect conformational changes in the TonB/ExbB pair rather than loss of interaction since ExbB was still required for some stabilization of TonBΔV17. Molecular modeling suggested that the ΔV17 mutation caused a significant change in the predicted conserved face of the TonB amino‐terminal membrane anchor. TonBΔV17 was unable to achieve the 23 kDa proteinase K‐resistant form in lysed sphaeroplasts that is characteristic of active TonB. Wild‐type TonB also failed to achieve the proteinase K‐resistant configuration when ExbB was absent. Taken together these results suggested that the ΔV17 mutation interrupted productive TonB–ExbB interactions. The apparent ability to crosslink to ExbB as well as a limited ability to transduce energy were restored by a second mutation (A39E) in or near the first predicted transmembrane domain of the ExbB protein. Consistent with the weak suppression, a 23 kDa proteinase K‐resistant form of TonBΔV17 was not observed in the presence of ExbBA39E. Neither the ExbBA39E allele nor the absence of ExbB affected TonB or TonBΔV17 export. Unlike the tonBΔV17 mutation, the exbBA39E mutation did not greatly alter a modelled ExbB transmembrane domain structure. Furthermore, the suppressor ExbBA39E functioned normally with wild‐type TonB, suggesting that the suppressor was not allele specific. Contrary to expectations, the TonBδV17, ExbBA39E pair resulted in a TonB with a greatly reduced half‐life (≅ 10 min). These results together with protease susceptibility studies suggest that ExbB functions by modulating the conformation of TonB.
Three element compact broadband parallel-coupled microstrip bandpass filter of simple configuration

A simple broadband parallel-coupled microstrip line (PCML) bandpass filter with compact design is proposed. A PCML structure with two feeding network of various widths is characterized by an equivalent J-inverter network. The extracted parameters indicate that the normalized J susceptance and equivalent electrical length are frequency dependent. A pair of PCML structure with centre resonator, without ground plane aperture at PCML structure and capacitive open-ended stub at the centre resonator, is proposed. The proposed design is further optimized by adjusting the length and width of the centre resonator. Three broadband bandpass filters with PCML structure of various couplings have been designed. It was found that the simulated and measured insertion and return losses responses showed good agreement with operating bandwidth of over 80%, return loss of better than -16 dB and 250% wide upper stopband.
Adaptive Regression

ABSTRACT Adjustment for prognostic covariates is recommended in clinical trials because relative to a t-test, it improves precision and adjusts for treatment imbalances caused by an “unlucky” randomization. But, inclusion of too many covariates can be counterproductive. In the quest to strike a balance between inclusion of all important variables and not going overboard, people have proposed methods such as stepwise regression, whereby the decision to include a covariate depends on post-randomization data. Covariate inclusion decisions are typically based on either the strength of its correlation with the outcome or the degree of treatment imbalance. Are these methods valid? Is there a valid way to analyze such data? These are some of the questions we address.
Induction of Adult T-Cell Leukemia-Like Lymphoproliferative Disease and Its Inhibition by Adoptive Immunotherapy in T-Cell-Deficient Nude Rats Inoculated with Syngeneic Human T-Cell Leukemia Virus Type 1-Immortalized Cells

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) has been shown to be the etiologic agent of adult T-cell leukemia (ATL), but the in vivo mechanism by which the virus causes the malignant transformation is largely unknown. In order to investigate the mechanisms of HTLV-1 leukemogenesis, we developed a rat model system in which ATL-like disease was reproducibly observed, following inoculation of various rat HTLV-1-immortalized cell lines. When previously established cell lines, F344-S1 and TARS-1, but not TART-1 or W7TM-1, were inoculated, systemic multiple tumor development was observed in adult nude (nu/nu) rats. FPM1 cells, newly established from a heterozygous (nu/+) rat syngeneic to nu/nurats, caused transient tumors only at the injection site in adult nu/nu rats, but could progressively grow in newborn nu/nu rats and metastasize in lymph nodes. The derivative cell line (FPM1-V1AX) serially passed through newbornnu/nu rats acquired the potency to grow in adultnu/nu rats. These results indicated that only some with additional changes but not all of the in vitro HTLV-1-immortalized cell lines possessed in vivo tumorigenicity. Using the syngeneic system, we further showed the inhibition of tumor development by transferring splenic T cells from immunized rats, suggesting the involvement of T cells in the regression of tumors. This novel and reproducible nude rat model of human ATL would be useful for investigation of leukemogenesis and antitumor immune responses in HTLV-1 infection.
Sumoylation Contributes to Timekeeping and Temperature Compensation of the Plant Circadian Clock

The transcriptional circadian clock network is tuned into a 24-h oscillator by numerous posttranslational modifications on the proteins encoded by clock genes, differentially influencing their subcellular localization or activity. Clock proteins in any circadian organism are subject to posttranslational regulation, and many of the key enzymes, notably kinases and phosphatases, are functionally conserved between the clocks of mammals, fungi, and plants. We now establish sumoylation, the posttranslational modification of target proteins by the covalent attachment of the small ubiquitin-like modifier protein SUMO, as a novel mechanism regulating key clock properties in the model plant Arabidopsis. Using 2 different approaches, we show that mutant plant lines with decreased or increased levels of global sumoylation exhibit shortened or lengthened circadian period, respectively. One known functional role of sumoylation is to protect the proteome from temperature stress. The circadian clock is characterized by temperature compensation, meaning that proper timekeeping is ensured over the full range of physiologically relevant temperatures. Interestingly, we observed that the period defects in sumoylation mutant plants are strongly differential across temperature. Increased global sumoylation leads to undercompensation of the clock against temperature and decreased sumoylation to overcompensation, implying that sumoylation buffers the plant clock system against differential ambient temperature.
Gender Wage Gap und Familienpolitik

Der durchschnittliche effektive Stundenlohnunterschied zwischen erwerbstatigen Frauen und Mannern zwischen 15 und 65 Jahren betrug im Jahr 2006 etwa 28 Prozent. Bei diesem Vergleich wird aber vernachlassigt, dass Frauen beispielsweise in anderen Branchen oder Berufen arbeiten oder dass es Unterschiede hinsichtlich des Qualifikationsniveaus gibt. Hinzu kommt, dass Manner haufiger eine Vollzeiterwerbstatigkeit ausuben. Werden die Lohnunterschiede zwischen Frauen und Mannern hinsichtlich dieser Einflussfaktoren korrigiert, so reduziert sich der Lohnabstand auf 15 Prozent. Ein wichtiger Grund fur die Lohnunterschiede sind auch die kindbedingten Erwerbsunterbrechungen, die haufiger die Frauen betreffen. Kehren Frauen nach einer Erwerbsunterbrechung jedoch moglichst schnell und mit einer hohen Stundenzahl in den Beruf zuruck, so reduziert dies die Lohnlucke zusatzlich. Der Lohnabstand dieser Gruppe zu den Mannern betragt nur noch 6 Prozent. Die Familienpolitik kann somit einen Beitrag zur Reduzierung der Lohnlucke leisten, indem die Vereinbarkeit von Familie und Beruf durch einen Ausbau der Kinderbetreuungsplatze erleichtert wird.