Indirect fluorescent-antibody (IFA) staining methods with Ehrlichia equi (MRK or BDS strains) and West- ern blot analyses containing a human granulocytic ehrlichiosis (HGE) agent (NCH-1 strain) were used to con- firm probable human cases of infection in Connecticut during 1995 and 1996. Also included were other tests for Ehrlichia chaffeensis, the agent of human monocytic ehrlichiosis (HME), Babesia microti, and Borrelia burg- dorferi. Thirty-three (8.8%) of 375 patients who had fever accompanied by marked leukopenia or thrombocyto- penia were serologically confirmed as having HGE. Western blot analyses of a subset of positive sera confirmed the results of the IFA staining methods for 15 (78.9%) of 19 seropositive specimens obtained from different per- sons. There was frequent detection of antibodies to a 44-kDa protein of the HGE agent. Serologic testing also revealed possible cases of Lyme borreliosis (n 5 142), babesiosis (n 5 41), and HME (n 5 21). Forty-seven (26.1%) of 180 patients had antibodies to two or more tick-borne agents. Therefore, when one of these diseases is clinically suspected or diagnosed, clinicians should consider the possibility of other current or past tick-borne infections.
The data presented here have several important impli- cations for understanding and evaluating the treatment of human cancers with therapeutic agents. They con- firm some previous studies that have indicated that p53 mutations confer resistance to therapeutics (23–25). However, they significantly extend these results by demonstrating that while DNA-damaging and antimetabolic drugs both function in a p53-dependent manner, the outcomes of treatment are markedly dis- tinct. In particular, p53 disruption makes these human colorectal cancer cells more sensitive to apoptosis induced by adriamycin and radiation, but less sensitive to the apoptotic effects of 5-FU. Interestingly, our 5-FU results were in excellent accord with those on normal mouse intestinal cells. It has been shown that p53 defi- ciency leads to increased resistance to 5-FU in mice (26). Furthermore, the apoptosis induced in normal mouse colorectal epithelial cells by 5-FU was shown to be relat- ed to RNA metabolism rather than to DNA metabolism (26), just as in the human cells we studied (Figure 4a). The fact that similar 5-FU–related observations have been made in normal murine colorectal epithelial cells, as well as in malignant human colorectal epithelial cells, suggests that they are basic to p53 biology.
The aim of the study was to evaluate the ability of four topical desensitizing agents on dentinal tubule impediment utilizing confocal laser scanning microscopy (CLSM). Buccal cervical areas of 45 extracted human molars were smoothed and wet- cleaned with SiC paper, trialed by utilization of 17% ethylenedi- aminetetraacetic acid (EDTA) so as to mimic the clinical aspect of overly sensitive dentin of cervical surfaces.
noblot analysis (26). A recent study investigating serologic cross-reactions among Ehrlichia equi, E. phagocytophila, and the HGE agent showed that most sera reacted with antigens between approximately 56 and 75 kDa, presumably to HSP (5). Therefore, cross-reactivity between E. chaffeensis and HGE agent is probably due to HSP and 42- to 49-kDa proteins of the HGE agent other than the major outer membrane protein P44. Although the use of purified antigens provides information on molecular sizes of reacting proteins and the typical patterns of reaction are distinct between HME and HGE, cross-reac- tivity of patient sera with antigens of E. chaffeensis and the HGE agent by Western blotting may preclude definitive deter- mination of the specific ehrlichial agent. Previous studies showed that anti-E. chaffeensis sera do not react with rP44. However, sera from patients with HGE have antibodies that specifically recognize rP44 (25). In the present study, 16 sera (including 13 cross-reacting sera that reacted with rP30) did not react with rP44. Samples reactive only with the HGE agent by IFA reacted only with rP44, not with rP30. Therefore, the use of rP44 as an antigen would provide better differentiation of HME from HGE than purified whole HGE organisms. Although dually IFA-reactive HGE-confirmed sera such as the one previously described by us (14) were not included in the present study, use of rP44 and rP30 as antigens is expected to help in ascertaining the true identity of dually HME and HGE IFA-reactive sera. In this context, Western blotting and the use of recombinant major outer membrane proteins can be helpful in discriminating etiologic agents of ehrlichioses. For clinical application, a Western blot strip containing both rP30 and rP44 can be used to facilitate a time- and cost-effective analysis. Although the serologic test would not replace the PCR or culture isolation, it is the most convenient test for HME and HGE diagnosis. An improved serologic test using recombinant antigens would have enhanced utility.
Here, we identified potential novel drugs for LUAD by a network-based algorithm followed by experimental verification. Differentially expressed genes (DEGs) between LUAD tissues and nontumor tissues were identified. Then, known small molecular drugs were ranked according to the effect of their targets on DEGs of LUAD by a random walk with restart (RWR) algorithm. Finally, we experimentally verified that atracurium, one of the potential agents, could induce NSCLC-derived A549 cell death, and Western blot assay demonstrated that atracurium upregulated the proapop- totic Bad and Bax, and downregulated the antiapoptotic p-Bad and Bcl-2 proteins. Furthermore, atracurium also enhanced the caspase-3 activity and could also reduce the expression of p53 and p21 Cip1/Waf1 in A549 cells. In brief, the candidate
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There is a huge number of algorithms for machine learning (reinforced learning, deep learning, neural networks, …) which are used successfully for different technical problems. Their strength lies in solving a particular technical problem better than other solutions. The algorithms were refined over the years and are now more successfully than before and used in a lot of technical solutions. But they still lack of an overall general learning ability that can be compared to the way a human being learns maybe also because they are very limited in its functionality. For example, a chess computer can normally play any other board game just by changing some parameters in the program that are related to the rules of the game. Therefore, they don’t fit as an overall solution into our holistic functional model of the human mind. But there are still other projects in the area of artificial general intelligence that should be shortly discussed here by picking LIDA (Learning Intelligent Distribution Agent) as a representative concerning the similarity to SiMA  and the learning functions.
The protective effects of probiotics may be mediated by their own DNA rather than by their metabolites or ability to colonize the colon. Toll-like receptor 9 (LR9) signaling is essential in mediating the anti- inflammatory effect of probiotics, and DNA derived from probiotic bacteria can be sufficient to attenuate experimental colitis (48) . In a human and murine inflammatory model, VSL#3 DNA inhibited IL-8 secretion, reduced p38 mitogen-activated protein kinase activation, delayed nuclear factor kappa B activation, stabilized levels of IkappaB, and inhibited proteasome function (46) . Similarly, S. boulardii prevented enterohemorrhagic Escherichia coli infection by interfering with the transduction pathways that control tight- junction structure as well as inhibiting NF- kappaB and MAPK signaling pathways leading to the production of IL-8 (79) . A study by Petrof, et al demonstrated that probiotics inhibited the pro-inflammatory nuclear factorkappaB pathway and triggered the expression of cellprotective heat shock proteins in the intestinal cells. Furthermore, the probiotic produced factors that inhibited the breakdown of the heat shock proteins, which would normally occur through intracellular protein destroyers known as proteasomes. Proteasome inhibition was an early event that began almost immediately after exposure of the colonic cells to the probiotic. The resulting inhibition of nuclear factor-kappaB and increased expression of heat shock proteins may account for the anti-inflammatory and cytoprotective effects reported for probiotics and may be a novel mechanism of microbial-epithelial interaction (80) . Effect on Humoral Immunity
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Even if a number of clinical studies especially in terms of side effects of BAs used in our study exist, we could not find in vitro experimental studies indicating effects on the articular cartilage and bone tissue in lit- erature. In addition, to our best knowledge, any study comparing the effects of BAs on cell viability and prolifer- ation of chondrocytes and osteocytes lacks in the litera- ture. However, most reports up to date are based on experimental animal models, those comprising animal tis- sues . Although studies based on animal models high- light differences between human and animal tissues, researchers may interpret data differently and draw differ- ing conclusions .
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Applying the rules of state responsibility on attribution to Indonesian military and security forces, it is clear that they are agents of the state and, if they are violating human rights in the course of their operations, their violations should be considered as acts of state for which Indonesia is responsible. 37 Under the law of state responsibility if such forces are operating in the private sphere, but continue to use their status as state actors to do so then arguably their conduct remains an act of state. 38 It may be that Indonesia’s security services are not exceeding their authority or contravening instructions when acting for commercial gain, given that the state security forces have been enmeshed in private activities virtually since independence, 39 but that would make their actions wholly acts of state. Furthermore, even criminal activities engaged in by state security forces, including export smuggling, timber smuggling, illegal logging, illegal mining, extortion, racketeering in drugs, gambling and prostitution, 40 would be deemed acts of state if they are carried out by state agents purporting to act in that capacity. The fact that the Indonesian Government has at various points, albeit with little enthusiasm, tried to prohibit, or limit, state security forces for private commercial activities, 41 does not prevent such actions continuing to be classified as acts of state.
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Phenomenological inquiry is a descriptive method of interpretive understanding that seeks to explore the direct experiences of human beings as meaning-making agents in their life worlds (van Manen, 2003). From a relational-centred child and youth care perspective, the construction of meaning is central to life in that it enables human beings to make sense of their experiences. However, meaning-making requires a degree of intuitive integration of experience into consciousness at the individual level and as an element of shared meaning. This study presented an opportunity to 1) examine the process and the effects of the relational-centred international education partnership between MacEwan University and Athlone Institute of Technology and 2) to explore the effects of the study-abroad initiative on students, faculty, community sites, and international administrative personnel through a phenomenological guided exploration of lived experiences.
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A novel series of spiro[chroman-2,4′-piperidin]-4-one derivatives was synthesized and evaluated as cytotoxic agents against three human cancer cell lines; MCF-7 (human breast carcinoma), A2780 (human ovarian cancer) and HT-29 (human colorectal adenocarcinoma) using MTT assay. Compound 16 with a sulfonyl spacer exhibited the most potent activity with IC 50 values between 0.31 and 5.62 μM. However, the trimethoxyphenyl derivative 15 was the least potent with IC 50 values between 18.77 and 47.05 μM. The most active compound 16 was selected for further mechanistic studies, which revealed that it induced more than three folds early apoptosis in MCF-7 cells treated for 24 h. Addi- tionally, it increased MCF-7 cells in the sub-G1 and G2-M cell cycle phases, following the same treatment duration. Together, these compounds could be promising cytotoxic candidates, thus further structural optimization, in vitro and in vivo studies are recommended to be developed into potential cytotoxic agents.
Because human societies are complex and humans rely on resources that are scarce, we encounter complex resource allocation problems. Scarce resources might be dif- ferent under different circumstances, such as food, energy, medical care, clean water, etc. To solve these problems, human interact with each other, and the interaction or information flow among them forms different kinds of information systems. Together with the technical aspects that participate in the systems to help, the information systems are actually sociotechnical systems, as we will define later. There are various kinds of sociotechnical systems serving different purposes. Take a simple situation as an example, a patient is trying to find a doctor who could take care of him. He may have a goal to spend money as less as possible, or to cure him as soon as possible, but he has no idea which doctor fits his purpose best. Thus he turns to his friends, his friends’ friends if necessary, for recommendations, incorporate these information into consideration, and make a decision with the help of agents. In this example, the per- sons involved, the agents and the information flow form a sociotechnical system and the purpose is to find a doctor for the patient. There are more complex information systems like the ones in section 1.2.
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however, human motion was presented less frequently (where non-human movement was represented by both the Android and Robot conditions and thus was seen twice as often). Thus it is possible imitation of human movements may have involved more attention or eﬀort, which could result in overall increase in muscle tension. A related “aﬀective” explanation may be that viewing a human elicits greater arousal (but note that participants did not rate the human as eliciting more arousal than the other agents, see Supplementary Materials 2.1), which can inﬂuence muscle tone and be detected through EMG (Hoehn-Saric et al., 1997). However, we believe such generic accounts are insuﬃcient to account for the eﬀect. Corrugator activity (brow furrowing), an indicator of eﬀort (de Morree and Marcora, 2010), was greater for Non-Human Motion, particularly in the observation condition (see Supplementary Materials 2.2.3). If greater eﬀort were associated with correctly imitating human motion, we would expect the opposite pattern. A delay in reaction to human motion could be another potential indicator of eﬀort in the form of a speed-accuracy tradeoﬀ. However, both in an action prediction study (Saygin and Stadler, 2012), and an attentional capture and cueing study (Li et al., 2015) behavioral data were instead modulated by Non-Human Appearance (i.e., Robot condition) indicating generic eﬀort or arousal eﬀects are unlikely to underlie the EMG diﬀerences in the current study. Rather, we suggest the signiﬁcant interactions with Time in the data, and the comparisons of cross-correlation lags demonstrate that the results are better viewed as preserved dynamics between perceived movement and executed movement rather than a delay per se. This is a much more interesting possibility, is consistent with prior work (Bouquet et al., 2007; Watanabe, 2008), and should be a fruitful direction to explore in future studies of dynamics of imitation of human and non-human movements, ideally with motion capture along with EMG (Thoroughman and Shadmehr, 1999; Casile and Giese, 2006).
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In the context of human and self-avatar interaction with an embodied agent (H2EA and SA2EA), research showed that human realism in an embodied agent should reflect natural human behaviour, appearance, and emotion. It is important to ensure that all human realism dimensions are matched with actual human behaviour, emotion, and visual cues in order to avoid the uncanny valley effect (Groom et al., 2009), which means that unmatched human realism can irritate people and lead to disengagement (Mitchell et al., 2011). Human realism is an important aspect of embodied agents’ representation, to create a digital representation that has human-like features and also to create a sense of social cues in the interaction. This is because humans usually prefer to digitally interact with a representation that is similar to them. The perception of similarity here is not limited to physical appearance or gender between users and digital representations, but also includes ethnicity and culture (Tamborini et al., 2018). Human realism and psychological similarity can increase the sense of presence, immersion, and involvement with the embodied agent. These, in turn, will ensure enjoyment, information credibility, likeability, and trust between the interaction partners. Similarly, information provided by an embodied agent is more credible and believable if it exhibits human-like features (Kim & Sundar, 2012a), and if these features are consistent with actual human features. Expectedly, likeability of embodied agents hinges on matching human features realistically. In summary, human realism can induce trust (Riedl et al., 2014), which enables the interaction partners to share information or work collectively with the embodied agent.
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Abstract—Almost without exception, cyber-physical systems operate alongside, for the benefit of, and supported by hu- mans. Unsurprisingly, disregarding their social aspects during development and operation renders these systems ineffective. In this paper, we explore approaches to modelling and reasoning about the human involvement in socio-cyber-physical systems (SCPS). To provide an unbiased perspective, we describe both the opportunities afforded by the presence of human agents, and the challenges associated with ensuring that their modelling is sufficiently accurate to support decision making during SCPS development and, if applicable, at run-time. Using SCPS ex- amples from emergency management and assisted living, we illustrate how recent advances in stochastic modelling, analysis and synthesis can be used to exploit human observations about the impact of natural and man-made disasters, and to support the efficient provision of assistive care.
Further it is also assumed that this new strategy of ‘rural development’, concentrating on redistribution of benefits can realise the objective task of bringing about justice and equality, without basically changing the capitalist path of development which uses its developmental thrust to encourage, help, facilitate and even condone the lapses of the industrialists, traders, rich farmers and moneylenders as they are considered the main agents of development and growth… In fact the basic assumption underlying the analysis of ‘strategy of rural development’ is that Indian state is a non-class, welfare institution, capable of re-distributing incomes, providing justice, and bringing about equality of opportunities to all, even though it is wedded to the capitalist path of development.’ (Desai, 1987: 1295). After an experience of democratic governance of around forty years, the role and form of democracy and within it the ‘normative and political basis of local government’ (Mitra, 2001: 109) was being reconsidered. It was acknowledged that political decentralisation provides a more durable ‘rational legal’ framework and a basis of decentralised development and the panchayati raj model in this context, is well-suited to the Indian conditions. Apart from the demands of a democratic structure whose three fourth population resided in the villages, there was widespread concern amongst scholars and policy makers for ‘democratic deepening’ (Mathew, 2003: 156) and to infuse ‘legitimacy to India’s democratic institutions’ (Kohli, 2001: 12).
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It has been known for 27 yr that blood platelets contain IgG, yet its subcellular location and significance have never been clearly determined. In these studies, the location of IgG within human platelets was investigated by immunocytochemical techniques and by the response of platelet IgG to agents that cause platelet secretion. Using frozen thin-sections of platelets and an immunogold probe, IgG was located within the alpha-granules. Thrombin stimulation caused parallel secretion of platelet IgG and two known alpha-granule proteins, platelet factor 4 and beta-thromboglobulin, beginning at 0.02 U/ml and reaching 100% at 0.5 U/ml. Thrombin-induced secretion of all three proteins was inhibited by prostaglandin E1 and dibutyryl-cyclic AMP. Calcium ionophore A23187 also caused parallel secretion of all three proteins, whereas ADP caused virtually no secretion of any of the three. From these data and a review of the literature, we hypothesize that plasma IgG is taken up by
Vitamin A consists of retinoid molecule in the form of retinol, retinal, retinoic acid and other pro-vitamin A like carotenoids. Vitamin A is readily available in vegetables and animal sources which includes cod liver oil, egg, butter, milk, carrot, spinach as a precursor to retinol. Retinoids has a protective role in maintaining both physiological and pathological state of human body. It acts as a signal modifying factor in controlling the gene expression, which influences the enzymes, proteins, hormones and growth factors to maintain the activity between the disease and the normal being. 11 Retinoids have been widely studied as a chemopreventive agents since it is capable of inducing apoptosis, decrease the growth rate of epithelial cells and free radicals and also regulates transcription through receptors and suppresses the activity of Activator Protein (AP- 1).
Several factors are responsible for the failure of international law on this score. First, inter state mechanisms which could and should logically regulate the behaviour of non-state actors, which are in fact the principal agents of globalization, are weak and the political will to strengthen the and create new ones is missing. At present TNCs, IMF, World Bank and investment firms, largely operate outside the ambit of international law and are not amenable to the international rule of law and human rights. Secondly the legal text of the International Covenant on Economic, Social and Cultural Rights and the implementing mechanism envisaged under it are too weak. Thirdly, industrialized countries and the main agents of globalization attach too much importance to civil and political rights, but they do not care for social, economic and cultural rights. It may sound intriguing but is a fact that many developing countries are more responsive to the needs of TNCs and investment firms than to the needs of the poor, powerless and voice less sections of their own populations.
infected, or after admission to the nursery. It was also observed that HPV and EBV are sometimes found in breast milk and can be transmitted to the infant through breastfeeding . Some of the above mentioned viruses are also found to cause tumors in adults (i.e., HPV in the cervix and in anogenital cancers, human HHV-8 in Kaposi’s sarcoma, and EBV in Burkitt’s lymphoma). Many mechanisms are used by infectious agents to sur- vive in a host and create favorable conditions for neo- plastic transformation. It is also possible that a child can inherit mutations that occurred in the germ cells of the parents via viral mutagenesis. Partial sequences of HHV- 6A have been found in members of the same families . All of the mechanisms listed in Table 1 could be exploited in combination, synergistically creating favorable conditions for neoplastic lesions to develop. Disruption of tumor suppression, in combination with apoptosis, im- mune evasion, and low-grade inflammation could enhance the accumulation of mutations, and this would select for preneoplastic cells, which over time could lead to the de- velopment of a tumor. Infants are born with an undevel- oped immune system, and the prevalence of latent viral infections in adults that come in contact with newborns could facilitate the transmission of viruses. Thus, the chance of latent infections is likely.