Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of reverse genetics in the development of vaccines against respiratory viruses

Despite their significance, the only available vaccines against respiratory viruses are those for the prevention of influenza. Attempts have been made to produce vaccines against other respiratory viruses using traditional techniques, but have met with little success. Reverse genetics, although still a r-elatively new tool for the manipulation of negative-strand RNA viruses, has great potential for the preparation of vaccines against many of the common respiratory viruses. In the preparation of live vaccines, reverse genetics s-ystems allow the direct modification of the specific regions in the genomes of negative-stranded RNA viruses concerned with attenuation; the ultimate goal is the introduction of site-specific mutations through a cDNA intermediate in order to develop strains with the requisite attenuation, antigenic and growth properties needed in a vaccine. These techniques can also be used to disarm potentially highly pathogenic viruses, such as emerging H5N1 avian influenza viruses, in order to facilitate large-scale preparation of viruses for use in inactivated vaccines under conditions of manufacturing safety. Before these vaccines become available, residual issues concerned with intellectual property rights to the technology and its application will need to be resolved.
Replication Proteins Influence the Maintenance of Telomere Length and Telomerase Protein Stability

ABSTRACT We investigated the effects of fission yeast replication genes on telomere length maintenance and identified 20 mutant alleles that confer lengthening or shortening of telomeres. The telomere elongation was telomerase dependent in the replication mutants analyzed. Furthermore, the telomerase catalytic subunit, Trt1, and the principal initiation and lagging-strand synthesis DNA polymerase, Polα, were reciprocally coimmunoprecipitated, indicating these proteins physically coexist as a complex in vivo. In a polα mutant that exhibited abnormal telomere lengthening and slightly reduced telomere position effect, the cellular level of the Trt1 protein was significantly lower and the coimmunoprecipitation of Trt1 and Polα was severely compromised compared to those in the wild-type polα cells. Interestingly, ectopic expression of wild-type polα in this polα mutant restored the cellular Trt1 protein to the wild-type level and shortened the telomeres to near-wild-type length. These results suggest that there is a close physical relationship between the replication and telomerase complexes. Thus, mutation of a component of the replication complex can affect the telomeric complex in maintaining both telomere length equilibrium and telomerase protein stability.
Targeted Irradiation of Mammalian Cells Using a Heavy-Ion Microprobe

Abstract Heiß, M. , Fischer, B. E. , Jakob, B. , Fournier, C. , Becker, G. and Taucher-Scholz, G. Targeted Irradiation of Mammalian Cells Using a Heavy-Ion Microprobe. Radiat. Res. 165, 231–239 (2006). The existing focusing heavy-ion microprobe at the Gesellschaft für Schwerionenforschung in Darmstadt (Germany) has been modified to enable the targeted irradiation of single, selected cells with a defined number of ions. With this setup, ions in the range from helium to uranium with linear energy transfers (LETs) up to ∼15,000 keV/μm can be positioned with a precision of a few micrometers in the nuclei of single cells that are growing in culture on a thin polypropylene film. To achieve this accuracy, the microbeam traverses a thin vacuum window with minimal scattering. Electron emission from that window is used for particle detection. The cells are kept in a specially designed dish that is mounted directly behind the vacuum window in a setup allowing the precise movement and the imaging of the sample with microscopic methods. The cells are located by an integrated software program that also controls the rapid deflection and switching of the beam. In this paper, the setup is described in detail together with the first experiments showing its performance. We describe the ability of the microprobe to reliably hit randomly positioned etched nuclear tracks in CR-39 with single ions as well as the ability to visualize the ion hits using immunofluorescence staining for 53BP1 as a marker of DNA damage in the targeted cell nuclei.
GETTING STRAIGHT ABOUT GRIEF

Acute grief is emotionally intense, cognitively preoccupying, and disruptive, but grief is not an illness; major depression and anxiety disorders are. Grief and mourning have a purpose. They provide an intense, focused opportunity to reregulate emotion and to engage in a learning process that is aimed at reconfiguring life without the deceased—both the internal life of the mind, and ongoing life in the world. A bereaved person needs to figure out how to find meaning, purpose, joy, and satisfaction in life without someone who has previously been central to these feelings. This reconfiguration is a very natural process that tends to occur in fits and starts as bereaved people move forward and deal with everyday life. Nevertheless, a knowledgeable, empathic and supportive clinician can foster good adjustment. Successful mourning is, however, not a given. For some people, the mourning process is derailed and acute grief is inordinately painful and prolonged. For others, the stress of bereavement triggers the onset or worsening of symptoms of MDD, an anxiety disorder or another psychiatric or medical condition, suicidality or negative health behaviors. Clinicians need to be alert to all of these problematic responses to loss. In the wake of bereavement, we need to both facilitate effective mourning and diagnose and treat co-occurring conditions.
Constitutive NF-κB Activation in Colorectal Carcinoma Plays a Key Role in Angiogenesis, Promoting Tumor Growth

Purpose: Nuclear factor κB (NF-κB) is an important transcription factor in various biological processes. Constitutive NF-κB activation has been noted in many tumors, including colorectal cancers. However, the precise role of this activation in colorectal cancer is unclear. Experimental Design: Constitutive NF-κB activation was evaluated in colorectal cancer tissues and cell lines. To inhibit NF-κB activation, we established cancer cells with stable knockdown of IκB kinase γ (NF-κB essential modulator), which is the regulatory subunit of the IκB kinase complex, by RNA interference. Cell growth and apoptosis were evaluated in wild-type cells (WT) and knocked-down cells (KD). Microarray and protein array analysis were also done. To determine involvement of angiogenesis, human umbilical vein endothelial cells were used. By s.c. transplantation of the cells into nude mice, tumor sizes, vascularity, and chemodrug sensitivity were analyzed. Results: Constitutive NF-κB activation was observed in 40% of colorectal cancer tissues and 67% of cell lines. Cell proliferation was not different between WT and KD in vitro, whereas apoptosis mediated by tumor necrosis factor-α and 5-fluorouracil were increased in KD. Several angiogenic chemokines were decreased in KD. Human umbilical vein endothelial cells incubated in WT supernatant showed more branch points than in KD, suggesting that constitutive NF-κB activation was involved in angiogenesis. Subcutaneous tumor expansion was suppressed to 23% in KD, and vessels were also decreased. By 5-fluoruracil treatment, tumor expansion was suppressed to a greater extent in KD (to 6%) than in WT (to 50%). Conclusion: NF-κB inhibition may represent a potent treatment modality in colorectal cancer, especially in cases with constitutive NF-κB activation.
Quantifying historical trends in the completeness of the fossil record and the contributing factors: an example using Aves

Abstract Improvements in the perceived completeness of the fossil record may be driven both by new discoveries and by reinterpretation of known fossils, but disentangling the relative effects of these processes can be difficult. Here, we propose a new methodology for evaluating historical trends in the perceived completeness of the fossil record, demonstrate its implementation using the freely available software ASCC (version 4.0.0), and present an example using crown-group birds (Aves). Dates of discovery and recognition for the oldest fossil representatives of 75 major lineages of birds were collected for the historical period ranging from 1910 to 2010. Using a comprehensive phylogeny, we calculated minimum implied stratigraphic gaps (MIG range) across these 75 lineages. Our results show that a reduction in global MIG values of 1.35 Ga (billion years) occurred over the past century in avian paleontology. A pronounced increase in the average rate of global MIG reduction is noted in the post-1970s interval (290.5 Myr per decade) compared to the pre-1970s interval (31.9 Myr per decade). Although the majority of the improvement in the fossil record of birds has come from new discoveries, substantial improvement (∼22.5%) has resulted from restudy and phylogenetic revision of previously described fossils over the last 40 years. With a minimum estimate indicating that at least 1.34 Gyr of gaps remain to be filled between the predicted and observed first appearances of major lineages of crown Aves, there is much progress to be made. However, a notable tapering off in the rate of global MIG reduction occurs between 1990 and 2010, suggesting we may be approaching an asymptote of oldest record discoveries for birds. Only future observations can determine whether this is a real pattern or a historical anomaly. Either way, barring the discovery of fossils that substantially push back the minimum age for the origin of crown-clade Aves, new discoveries cannot continue to reduce global MIG values at the average post-1970s rate over the long term.
Important Determinants of Bone Strength: Beyond Bone Mineral Density

Osteoporosis is a systemic skeletal disorder characterized by compromised bone strength that predisposes individuals to increased fracture risk. Bone strength is determined by its material and structural properties. Bone mineral density (BMD) is a useful tool for diagnosis; however, this parameter provides information regarding only the quantity of mineral in bone, which is only one component of bone strength. Osteoporosis treatments have been shown to have beneficial effects on bone turnover, microarchitecture, and/or mineralization, all of which can help account for the reductions in fracture risk above and beyond changes in BMD. Newer noninvasive imaging methods are being developed that assess bone strength independent of BMD, and these methods should improve the assessment of fracture risk and response to treatment. These imaging methods are not currently available for routine clinical use, and therefore, clinicians need to continue for now to rely on surrogate markers of bone fragility, including BMD, prevalent fracture, and other important risk factors for fracture.
Soils and frost boil ecosystems across the North American Arctic Transect

[1] We studied soil properties of frost boils at nine zonal-vegetation locations across the North American Arctic Transect (NAAT) in order to better understand arctic soils and their interaction with other biogeophysical components of frost boil ecosystems. Soil genetic horizons were analyzed for particle size, pH, electrical conductivity, total organic carbon (OC) and nitrogen (N), bulk density and volumetric water content. Surface soils (0–5 cm) across frost boil patterns were analyzed for of pH, OC, water content, extractable N and P, and exchangeable K, Ca and Na. Our results revealed that soil texture, pH, EC, P, Na and Ca contents are strongly influenced by local parent materials. Soil pH was acidic in the north going to alkaline in the midtransect and then again back to acidic in the south. Simple correlations between soil analytical data and observed frost boil properties across the NAAT support and are consistent with the laboratory and theoretical-conceptual models of pattern ground dynamics that have been developed by others. Soil water related well to texture. Soil horizon %OC and profile OC stocks under the pattern corresponded well to biomass and frost heave, respectively. Also soil water was closely related to biomass and heave. Nutrients in surface soils at sites corresponded to OC stocks. An interaction between soil water and segregation of Na and Ca between the pattern and interpattern was found for locations with high cation availability. At these sites, chemical as well as physical disruption of the pattern area could affect plant establishment. Overall there was a good linkage between properties relating to frost boil pattern dynamics and soil biogeochemical properties. Our study offers insight into the important process of cryoturbation for carbon sequestration in Gelisols across the Arctic.
Interpreting the magnitudes of correlation coefficients.

Copyright 2003 by the American Psychological Association, Inc. 0003-066X/03/$12.00 Vol. 58, No. 1, 78–80 monomethod correlation coefficients, which yield results that are artificially large compared with associations found between realworld, independently measured variables. Cohen (1988) provided perhaps the most widely known guidelines or “operational definitions” (p. 79) that are more realistic than those above for interpreting the magnitude of correlation coefficients typically found in the behavioral sciences. These guidelines are “offered as a convention . for use when no others suggest themselves” (Cohen, 1988, p. 79). According to Cohen, correlation coefficients in the order of . 10 are “small,” those of . 30 are “medium,” and those of . 50 are “large” in terms of magnitude of effect sizes (see pp. 77–81). Cohen seems to have arrived at these guidelines largely on the basis of his considerable experience with effect sizes and correlation coefficients. For this comment, an attempt was made to extend Cohen’s benchmarks by deriving empirical guidelines concerning the magnitude of correlation coefficients found among psychological studies.
SERUM TRACE MINERALS VARIATION DURING PRE AND POST-PARTUM PERIOD IN NILI-RAVI BUFFALOES

The present study was conducted with the objective to the iron, copper and zinc variations in serum of Nili-Ravi buffaloes during pre and post partum periods determine. The study was carried out on 35 pregnant Nili-Ravi buffaloes during June 2008 to October 2008 at Buffalo Research Institute, Pattoki, District Kasur. Blood samples were taken from these buffaloes during three, two and one week before parturition, at the time of parturition and then one, two and three weeks after parturition. Serum iron, copper and zinc were determined on Atomic Absorption Spectrophotometer. The mean serum iron and copper concentration differed significantly (P 0.05) decrease in zinc concentration between 1st and 2nd week after parturition where as a significant increased (P<0.05) in zinc concentration took place during 3 rd week after parturition. Serum zinc concentrations also dropped at the
Les méthodes mixtes en systèmes d’information: enjeux épistémologiques et méthodologiques

Les methodes mixtes rencontrent un succes croissant dans les sciences sociales aujourd’hui, succes en partie lie a leur capacite a generer des resultats de recherche qui different de ceux obtenus par les methodologies traditionnelles. A ce titre, les methodes mixtes semblent fecondes pour le domaine des Systemes d’Information (SI) notamment car elles offrent un large eventail de choix methodologiques (Mingers, 2001 ; Venkatesh et al., 2013). Cependant, nous disposons de peu de connaissance sur la facon dont les auteurs s’approprient justement ces methodes et sur les choix qu’ils effectuent. Dans cette perspective, cet article a pour objet de mieux comprendre l’utilisation des methodes mixtes faite par les chercheurs dans le domaine des SI afin d’apprehender s’il existe des tendances quant a l’usage de ce type de methode et si ces methodes sont rigoureusement mises en œuvre. Pour ce faire, a partir d’une revue de litterature comparative sur les methodes mixtes en sciences sociales et en SI, une analyse bibliographique sur sept journaux en SI a ete conduite sur la periode 2008-2016. Cette analyse nous permet d’apporter un regard critique sur l’utilisation des methodes mixtes en SI et de completer ainsi les deux etudes bibliographiques realisees par Mingers (2001) et Venkatesh et al. (2013). En ancrant sa reflexion dans l’epistemologie, cette analyse se distingue alors des precedentes ce qui en fait son originalite et sa force. Elle nous permet alors de proposer des recommandations pour les auteurs desireux de mettre en œuvre ce type de methode.
The Relationship between Current Account and Government Budget Balance: The Case of Kuwait

The aim of this study is to examine the twin deficits hypothesis for Kuwait for the quarterly period (1993:4 2010:4). The twin deficit hypothesis states that an increase in the budget deficit will cause a similar increase in current account deficit. To analyze the relationship between the two variables, the paper tests the stationarity of the two variables, estimates the cointegration regression (the Johansen cointegration test), applies the VAR model, estimates the IRF, and tests for existence and the direction of causality. The causality test shows that the direction of causality goes from current account to budget balance. The other direction was not confirmed for this study. In addition, the results of this paper find a negative long-run relationship between current account and budget balance that is an increase in current account causes a decrease in the government budget surplus or an increase in budget deficit. This finding fits the Kuwaiti economy; since an improvement in the current account driven primarily by the improvement in the trade balance will cause the central government to spend more than it receive in revenue causing a decrease in government budget surplus or an increase in government budget deficit. Therefore, this paper reached to a conclusion that the twin deficit hypothesis was not confirmed for the Kuwaiti case.
Prognostic value of vertebral lesions detected by magnetic resonance imaging in patients with stage I multiple myeloma

We assessed the role of spinal magnetic resonance imaging (MRI) and bone densitometry as prognostic factors in patients with asymptomatic stage I multiple myeloma (MM) and negative skeletal survey. 55 consecutive patients underwent spinal MRI and 41 of them underwent bone densitometry by dual‐energy X‐ray absorptiometry (DEXA).
Towards a practical clinical use of fractioned exhaled nitric oxide levels in chronic cough.

Fractioned exhaled nitric oxide (FeNO) is the amount of nitric oxide (NO) present in the airways detectable with chemiluminescent or electrochemical methods in the exhaled air. The exhaled NO measured is the sum of the constitutive gas produced by the neuronal and the endothelial isoforms of the NO synthases and the amount produced after activation of the inducible isoform of this enzyme (1). The inducible isoform produces a high quantity of NO, nM range, compared to the constitutive isoforms, which produce pM amount of the gas. The inducible isoform is mainly present in macrophages and epithelial cells in the airways and it accounts for most of the FeNO detected. One interesting characteristic of the inducible production of FeNO is that it is quite well down-modulated by corticosteroids compared to the NO produced by the constitutive isoforms (1).
Lymphoma discrimination by computerized triple matrix analysis of list mode data from three-color flow cytometric immunophenotypes of bone marrow aspirates.

BACKGROUND The goal of this study was to evaluate a self-learning algorithm for the computer classification of information extracted from flow cytometric immunophenotype list mode files from high-grade non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and multiple myeloma (MM). Materials and Methods Bone marrow aspirates (BMA) were obtained from untreated NHL (n = 51), HD (n = 9), or MM (n = 13) patients. Bone marrow aspirates were not infiltrated in NHL and HD patients as confirmed by thorough histologic and cytologic investigation; however, MM patients showed an infiltration rate >50% by malignant myeloma cells. Peripheral blood leukocyte (PBL) samples were taken from age-matched healthy volunteers (n = 44) as easily available control material. A second control group of 15 healthy volunteers, from whom BMA and PBL samples were available, allowed us to differentiate whether the observed classification results on malignant samples were due to the malignant process or simply to the inherent differences between BMA and PBL. Bone marrow aspirates and PBL were analyzed by the same immunophenotyping antibody panel (CD45/14/20, CD4/8/3, kappa/CD19/5, lambda/CD19/5). The acquired list mode data files were analyzed and classified by the self-learning triple matrix classification algorithms CLASSIF1 following a priori separation of the data into a learning set and unknown test set. After completion of the learning phase, known patient samples were reclassified and unknown samples prospectively classified by the algorithm. RESULTS Highly discriminatory information was extracted for the various lymphoma entities. The most discriminating information was encountered in antibody binding, antibody binding ratios, and relative antibody surface density parameters of leukocytes rather than in percentage frequencies of discrete leukocyte subpopulations. Samples from healthy controls were classified as normal in 97.2% of the cases, whereas those of NHL, HD, and MM patients were on average correctly classified in 80. 8% of the cases. CONCLUSIONS Although no detectable lymphoma cells were present in BMA of NHL and HD patients, the CLASSIF1 classification of the immunophenotypes of morphologically normal cells provided a surprisingly good disease discrimination equal or better than that obtained by examining pathological lymph nodes according to the respective literature. The results are suggestive for a lymphoma-related and disease-specific antigen expression shift on normal hematopoietic bone marrow cells that can be used to discriminate the underlying disease (specificity of unspecific changes), i.e., in this case NHL from HD. Multiple myeloma patients were discriminated by changes on malignant as well as on normal bone marrow cells.
Interactions Among Western Corn Rootworm (Coleoptera: Chrysomelidae), Yellow Foxtail, and Corn

Abstract Field studies at sites with two contrasting soil types investigated effects from the presence of yellow foxtail [Setaria pumila (Poir.) Roem. and Schult. ], established in bands parallel to corn rows, on western corn rootworm (Diabrotica virgifera virgifera LeConte) survival, corn root injury, lodging, biomass production, and yield. Results suggested that the presence of foxtail as an alternate host influenced the degree and progression of corn rootworm damage and adult emergence in a given locality. Rootworm adults emerged later from foxtail band areas and had smaller head capsule size than did individuals from areas without foxtail, consistent with earlier findings that foxtail in the diet of western corn rootworm was a poor nutritional substitute for corn. Lodging was reduced in the presence of yellow foxtail in some cases, but corn stover biomass and yield also were lower. Influences, if any, of soil type on rootworm survival were unclear because of differences in planting date between the two sites. Foxtail may function as a buffer to reduce rootworm damage to corn and serves as an alternate host that should be considered in the development of resistance management strategies for transgenic corn modified for rootworm resistance.