Informatisation of transport process using GPS navigation system

Nowadays, internal business processes are one of the crucial factors of firms’ competitive advantage achievement, which is becoming increasingly important, not only on local but also on global markets. Firms’ performance improvement depends to a large extent on its flexibility, adjustability and especially ability to manage internal business processes. Hence, use of information technology is among the fundamental elements of business process change, which not only improve competitiveness but also assure long term development and growth of the firm. For all these reasons, the main purpose of this article is firstly to establish that use of information technology is feasible in all industries, explain what possible obstacles for successful informatisation are, and which are major advantages after its implementation. Secondly, within theoretical aspect we present broaden view of informatisation in logistics, whilst practical example illustrates successful informatisation of transport process with adoption of GPS (Global Positioning System) in a transport firm. Furthermore, in this article we are also introducing a case study of three transport firms describing process flow before and after implementation identifying enhanced information quality, service quality and communication as a foremost advantages and achievements after informatisatio

Maternal Obesity and Incidence of Depression

Obesity is a national epidemic in the United States, which both directly and indirectly affects the social productivity of individuals, the American macro economy and individuals’ personal health and well being. Depression often interferes with an individual’s ability to work, sleep, study, eat, and enjoy life. A maternal state of both obesity and depression may cause serious adverse medical conditions in the mother’s child. Taking steps to treat depression and obesity are critical in the construct of modern medicine. This project yields results that have the potential to make treatment options better tailored, more efficient, effective and economically-sound for the obese, pregnant population. This study was conducted using a collaborative approach, combining retrospectively collected patient data from Syracuse University and SUNY Upstate Medical Center. Our data shows that morbid obesity is positively correlated with higher incidence of depression. This suggests that health care practioners should screen morbidly obese perinatal women for depression more frequently and assist these women in accessing psychological treatment and weight management options

Genome‐wide off‐target analyses of CRISPR/Cas9‐mediated T‐cell receptor engineering in primary human T cells

Objectives Exploiting the forces of human T cells for treatment has led to the current paradigm of emerging immunotherapy strategies. Genetic engineering of the T-cell receptor (TCR) redirects specificity, ablates alloreactivity and brings significant progress and off-the-shelf options to emerging adoptive T-cell transfer (ACT) approaches. Targeted CRISPR/Cas9-mediated double-strand breaks in the DNA enable knockout or knock-in engineering. Methods Here, we perform CRISPR/Cas9-mediated TCR knockout using a therapeutically relevant ribonucleoprotein (RNP) delivery method to assess the safety of genetically engineered T-cell products. Whole-genome sequencing was performed to analyse whether CRISPR/Cas9-mediated DNA double-strand break at the TCR locus is associated with off-target events in human primary T cells. Results TCRα chain and TCRβ chain knockout leads to high on-target InDel frequency and functional knockout. None of the predicted off-target sites could be confirmed experimentally, whereas whole-genome sequencing and manual Integrative Genomics Viewer (IGV) review revealed 9 potential low-frequency off-target events genome-wide. Subsequent amplification and targeted deep sequencing in 7 of 7 evaluable loci did not confirm these low-frequency InDels. Therefore, off-target events are unlikely to be caused by the CRISPR/Cas9 engineering. Conclusion The combinatorial approach of whole-genome sequencing and targeted deep sequencing confirmed highly specific genetic engineering using CRISPR/Cas9-mediated TCR knockout without potentially harmful exonic off-target effects

Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators

The cell intrinsic antiviral response of multicellular organisms developed over millions of years and critically relies on the ability to sense and eliminate viral nucleic acids. Here we use an affinity proteomics approach in evolutionary distant species (human, mouse and fly) to identify proteins that are conserved in their ability to associate with diverse viral nucleic acids. This approach shows a core of orthologous proteins targeting viral genetic material and species-specific interactions. Functional characterization of the influence of 181 candidates on replication of 6 distinct viruses in human cells and flies identifies 128 nucleic acid binding proteins with an impact on virus growth. We identify the family of TAO kinases (TAOK1, -2 and -3) as dsRNA-interacting antiviral proteins and show their requirement for type-I interferon induction. Depletion of TAO kinases in mammals or flies leads to an impaired response to virus infection characterized by a reduced induction of interferon stimulated genes in mammals and impaired expression of srg1 and diedel in flies. Overall, our study shows a larger set of proteins able to mediate the interaction between viral genetic material and host factors than anticipated so far, attesting to the ancestral roots of innate immunity and to the lineage-specific pressures exerted by viruses. Whether there are conserved nucleic acid (NA) binding proteins across species is not fully known. Using data from human, mouse and fly, the authors identify common binders, implicate TAOKs and show that these kinases bind NAs across species and promote virus defence in mammalian cells.We further thank Korbinian Mayr, Igor Paron, and Gaby Sowa for maintaining mass spectrometers and the MPI-B core facility, especially Judith Scholz, Leopold Urich, Sabine Suppmann, and Stephan Uebel, for support..

Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5

The 5'-cap-structures of higher eukaryote mRNAs are ribose 2'-O-methylated. Likewise, a number of viruses replicating in the cytoplasm of eukayotes have evolved 2'-O-methyltransferases to modify autonomously their mRNAs. However, a defined biological role of mRNA 2'-O-methylation remains elusive. Here we show that viral mRNA 2'-O-methylation is critically involved in subversion of type-I-interferon (IFN-I) induction. We demonstrate that human and murine coronavirus 2'-O-methyltransferase mutants induce increased IFN-I expression, and are highly IFN-I sensitive. Importantly, IFN-I induction by 2'-O-methyltransferase-deficient viruses is dependent on the cytoplasmic RNA sensor melanoma differentiation-associated gene 5 (MDA5). This link between MDA5-mediated sensing of viral RNA and mRNA 2'-O-methylation suggests that RNA modifications, such as 2'-O-methylation, provide a molecular signature for the discrimination of self and non-self mRNA

The role of GPS-enabled information in transforming operational decision making: an exploratory study

Although the impact of ICT-enabled information on firm performance has been well documented in the business value of IT literature, our understanding of how Global Positioning System (GPS) adoption can transform operational decision making and foster differential firm performance is limited. In response, we conduct an exploratory comparative case study of three transport firms that have implemented the same GPS during the same year in their operations. Our results highlight that increased use of GPS-enabled information can enhance information quality and make operational decision making more fact-based and collaborative. We also find that such transformations in operational decision making, driven by increased use of GPS-enabled information, can foster differential performance impacts. However, we warn scholars and practitioners that a firm’s information management capability (in terms of availability of quality information in decision making, software tools for connectivity and access to information, IT systems integration post-GPS adoption and adaptability of the infrastructure to emerging business needs) and organizational factors (such as top management support, project management of GPS implementation, financial support, end-user involvement, rewarding, training and employee resistance) can facilitate (or inhibit) effective use of GPS-enabled information in operational decision making, and thus moderate differential performance benefits of GPS adoption

Processing of Genome 5′ Termini as a Strategy of Negative-Strand RNA Viruses to Avoid RIG-I-Dependent Interferon Induction

Innate immunity is critically dependent on the rapid production of interferon in response to intruding viruses. The intracellular pathogen recognition receptors RIG-I and MDA5 are essential for interferon induction by viral RNAs containing 5′ triphosphates or double-stranded structures, respectively. Viruses with a negative-stranded RNA genome are an important group of pathogens causing emerging and re-emerging diseases. We investigated the ability of genomic RNAs from substantial representatives of this virus group to induce interferon via RIG-I or MDA5. RNAs isolated from particles of Ebola virus, Nipah virus, Lassa virus, and Rift Valley fever virus strongly activated the interferon-beta promoter. Knockdown experiments demonstrated that interferon induction depended on RIG-I, but not MDA5, and phosphatase treatment revealed a requirement for the RNA 5′ triphosphate group. In contrast, genomic RNAs of Hantaan virus, Crimean-Congo hemorrhagic fever virus and Borna disease virus did not trigger interferon induction. Sensitivity of these RNAs to a 5′ monophosphate-specific exonuclease indicates that the RIG-I-activating 5′ triphosphate group was removed post-transcriptionally by a viral function. Consequently, RIG-I is unable to bind the RNAs of Hantaan virus, Crimean-Congo hemorrhagic fever virus and Borna disease virus. These results establish RIG-I as a major intracellular recognition receptor for the genome of most negative-strand RNA viruses and define the cleavage of triphosphates at the RNA 5′ end as a strategy of viruses to evade the innate immune response

p53 Activation following Rift Valley Fever Virus Infection Contributes to Cell Death and Viral Production

Rift Valley fever virus (RVFV) is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production