Miracle-dz/UniFAR-FTUs huggingface dataset:
Special Topic: Mechanism of Bacterial Pathogenesis Cell Biology and Immunology Lessons Taught by Legionella Pneumophila Legionella and the Dot/icm Type Iv Secretion System

Legionella pneumophila is a facultative intracellular pathogen capable of replicating within a broad range of hosts. One unique feature of this pathogen is the cohort of ca. 300 virulence factors (effectors) delivered into host cells via its Dot/Icm type IV secretion system. Study of these proteins has produced novel insights into the mechanisms of host function modulation by pathogens, the regulation of essential processes of eukaryotic cells and of immunosurveillance. In this review, we will briefly discuss the roles of some of these effectors in the creation of a niche permissive for bacterial replication in phagocytes and recent advancements in the dissection of the innate immune detection mechanisms by challenging immune cells with L. pneu-mophila. (2016). Cell biology and immunology lessons taught by Legionella pneumophila. The discovery of Legionella pneumophila dates back to 1976, when a mysterious disease affected 221 American veterans attending the American Legion Convention in Philadelphia. The causative agent for this highly concerning outbreak was identified three year later and was designated as Legionella pneumophila, a gram-negative bacterium that belongs to the -proteobacteria (McDade et al., 1977). Subsequent studies revealed that L. pneumophila is an intracel-lular pathogen capable of replicating in highly diverse hosts, ranging from fresh water amoebae to mammalian alveolar macrophages (Stone et al., 1999). One salient feature associated with L. pneumophila infection is that the bacterial phagosome does not undergo the default phagosomal matu-ration process characterized by fusion with the lysosomal network, particularly in the early phase of infection; rather it develops into an organelle permissive for intracellular bacterial replication termed the Legionella-containing vacuole The capability of this bacterium to construct such a unique niche is mostly attributed to the activity of effectors translocated by the Dot/Icm type IV secretion system (Huang et al. These effectors function to re-orchestrate various host processes to allow intracellular bacterial growth. The infection biology of L. pneumophila provides an excellent example of the sophistication of the interactions between bacterial pathogens and their hosts. Further, investigations of the sensing of the Dot/Icm trans-located proteins and/or their activity by immune cells such as macrophages has allowed the identification of novel im-munosurveillance mechanisms often not seen in infections with more adapted pathogens.
Surgical Response to Multiple Casualty Incidents Following Single Explosive Events

Background:Modern publications on response to single explosive events are from non-US hospitals, predate current resuscitation guidelines and lack detail on surgical and intensive care unit (ICU) requirements. The objective of this study is to provide a contemporary account of surge response to multiple casualty incidences following explosive events managed at a US trauma hospital in Iraq. Methods:Observational study and retrospective chart review of 72-hour transfusion, operating room, and ICU resource utilization from 3 multiple casualty incidences managed at the US Air Force Theater Hospital, Balad AB, Iraq between February and April 2008. Results:Fifty patients were treated with a mean injury severity score of 19. Forty-eight percent (n = 24) of casualties required blood transfusion with 4 patients receiving 43% (N = 74 units) of the packed red blood cells (pRBC). An average of 3.5 and 3.8 units of pRBC and plasma, respectively, was transfused per casualty (pRBC:plasma ratio of 1:1.1). Seventy-six percent (n = 38) of patients required immediate operation upon initial presentation. A total of 191 procedures were performed in parallel during 75 operations (3.8 procedures per casualty). Fifty percent (n = 25) of patients required ICU admission with nearly the same number (n = 24) requiring mechanical ventilator support beyond that required for operation. All cause, in-hospital mortality was 8% (n = 4). Conclusions:Results from this study provide a contemporary assessment of transfusion, surgical, and intensive care resource requirements after a single explosive event. Data from this experience may translate into useful guidelines for emergency planners worldwide.
QUICKEST CHANGE DETECTION : ASYMPTOTIC OPTIMALITY UNDER A SPARSE SIGNAL

In multichannel sequential change detection, multiple sensors monitor a system in which an abrupt change occurs at some unknown time and is perceived by an unknown subset of sensors. The goal is to detect this change quickly, while controlling the rate of false alarms. In the traditional asymptotic analysis of this problem, the false alarm rate goes to 0 while all other parameters remain fixed. We argue that this framework is not very informative, as the corresponding asymptotic optimality property cannot differentiate between universal and parsimonious rules. We propose an asymptotic framework in which the number of sensors also goes to infinity, and we show that in this context universal rules may fail to be asymptotically optimal when the number of streams is not very small. On the other hand, parsimonious rules are shown to be asymptotically optimal under reasonable sparsity conditions.
The Mood Type Indicator as compared with the MMPI-2 and BDI-II: A Study of Validity and Reliability

ii Acknowledgements iii The Mood Type Indicator as compared with the MMPI-2 and BDI-II 1 Hypotheses 1 Method 2 Subjects 2 Procedure 2 Instruments 3 The MTI 3 The MMPI-2 5 The BDI-II 6 Results 7 Discussion 8 References 11 Appendix A Tables 13 Table 1: PILOT STUDY Validity Correlations 13 Table 2: Cell Design 14 TABLE 3: CONTENT DESCRIPTION OF THE MTI SCALE 1 MAJOR DEPRESSIVE EPISODE: an item by item comparison with the DSM-IV Diagnostic Criteria 15 TABLE 4: CONTENT DESCRIPTION OF THE MTI SCALE 2 MANIC EPISODE: an item by item comparison with the DSM-IV Diagnostic Criteria 16 TABLE 5: CONTENT DESCRIPTION OF THE MTI SCALE 3 DYSTHYMIA: an item by item comparison with the DSM-IV Diagnostic Criteria. 17 Appendix B Raw Data 18 Appendix C Demographic Survey 119 Appendix D Informed Consent Form 120 Vita 121 MTI vs. MMPI-2 & BDI-II 1 The Mood Type Indicator as compared with the MMPI-2 and BDI-II The Mood Type Indicator (MTI) was designed to fill the need for an instrument that would help clinicians screen for mood disorders, and act as an aid in differential diagnosis by the content of its answers. When developed, the questions were based on the DSM-IV diagnostic criteria for major depressive episodes, manic episodes, and Dysthymic Disorder (Hissom, 1997). Due to the lack of external validity found in the pilot study of the MTI because of norming issues, this thesis proposed to further study the validity and reliability of the MTI. The purpose of the thesis was to retest the reliability and validity on a larger sample size, and with an additional instrument, the MMPI-2. The study consisted of one hundred one adults, who were given the MTI forms A, and B, the BDI II and, the MMPI 2, in a four cell counterbalanced design to control instrument effects. One cell contained twenty-six subjects. The extra subject was retained since a minor deviation from the cell design was unlikely to skew the results.
Alpha-divergence bridges maximum likelihood and reinforcement learning in neural sequence generation

Neural sequence generation is commonly approached by using maximumlikelihood (ML) estimation or reinforcement learning (RL). However, it is known that they have their own shortcomings; ML presents training/testing discrepancy, whereas RL suffers from sample inefficiency. We point out that it is difficult to resolve all of the shortcomings simultaneously because of a tradeoff between ML and RL. In order to counteract these problems, we propose an objective function for sequence generation using α-divergence, which leads to an ML-RL integrated method that exploits better parts of ML and RL. We demonstrate that the proposed objective function generalizes ML and RL objective functions because it includes both as its special cases (ML corresponds to α→ 0 and RL to α→ 1). We provide a proposition stating that the difference between the RL objective function and the proposed one monotonically decreases with increasing α. Experimental results on machine translation tasks show that minimizing the proposed objective function achieves better sequence generation performance than ML-based methods.
Learn not to learn–a way of keeping budgets and deadlines in ERP projects?

This paper takes as its point of departure the conflict between the project as an organisational form for time-limited task execution and the project as an organisational form for triggering knowledge development and learning. The aim of the paper is to explore how knowledge developed in ERP projects can be managed, as well as to identify potential influences on the management of knowledge developed in the project process. Qualitative data has been collected through interviews, document studies, and participant observations. The paper presents evidence that problems of keeping to budgets and timelines in ERP projects can depend on the fact that knowledge developed in the project process is also exploited in the project process. In order to bridge the conflict between the project as a time-limited form for task execution and an organisational form for knowledge development and learning, three tentative strategies for exploiting knowledge developed in the project process are suggested.
The Proteomics of Colorectal Cancer: Identification of a Protein Signature Associated with Prognosis

Colorectal cancer is one of the commonest types of cancer and there is requirement for the identification of prognostic biomarkers. In this study protein expression profiles have been established for colorectal cancer and normal colonic mucosa by proteomics using a combination of two dimensional gel electrophoresis with fresh frozen sections of paired Dukes B colorectal cancer and normal colorectal mucosa (n = 28), gel image analysis and high performance liquid chromatography–tandem mass spectrometry. Hierarchical cluster analysis and principal components analysis showed that the protein expression profiles of colorectal cancer and normal colonic mucosa clustered into distinct patterns of protein expression. Forty-five proteins were identified as showing at least 1.5 times increased expression in colorectal cancer and the identity of these proteins was confirmed by liquid chromatography–tandem mass spectrometry. Fifteen proteins that showed increased expression were validated by immunohistochemistry using a well characterised colorectal cancer tissue microarray containing 515 primary colorectal cancer, 224 lymph node metastasis and 50 normal colonic mucosal samples. The proteins that showed the greatest degree of overexpression in primary colorectal cancer compared with normal colonic mucosa were heat shock protein 60 (p<0.001), S100A9 (p<0.001) and translationally controlled tumour protein (p<0.001). Analysis of proteins individually identified 14-3-3β as a prognostic biomarker (χ2 = 6.218, p = 0.013, HR = 0.639, 95%CI 0.448–0.913). Hierarchical cluster analysis identified distinct phenotypes associated with survival and a two-protein signature consisting of 14-3-3β and aldehyde dehydrogenase 1 was identified as showing prognostic significance (χ2 = 7.306, p = 0.007, HR = 0.504, 95%CI 0.303–0.838) and that remained independently prognostic (p = 0.01, HR = 0.416, 95%CI 0.208–0.829) in a multivariate model.
Calpain-Mediated Cleavage of Calcineurin in Puromycin Aminonucleoside-Induced Podocyte Injury

The calcineurin inhibitors cyclosporine A (CsA) and tacrolimus are widely used in the treatment of proteinuria diseases. As the direct target of these drugs, calcineurin has previously been demonstrated to play a role in proteinuria diseases. However, aside from its immune-related effects, the local status of calcineurin in renal inherent cells has not been fully explored in the settings of proteinuria disease and podocyte injury. In this study, calcineurin activity and protein expression in the well-known puromycin aminonucleoside (PAN)-induced podocyte injury model were examined. Interestingly, we found that calcineurin activity was abnormally increased in PAN-treated podocytes, whereas the expression of the full-length 60-kDa calcineurin protein was decreased. This result suggests that there may be another activated form of calcineurin that is independent of the full-length phosphatase. To investigate whether calpain is involved in regulating calcineurin, we exposed PAN-treated podocytes to both pharmacological inhibitors of calpain and specific siRNAs against calpain. Calpain blockade reduced the enhanced calcineurin activity and restored the down-regulated expression of 60-kDa calcineurin. In addition, purified calpain protein was incubated with podocyte extracts, and a 45-kDa fragment of calcineurin was identified; this finding was confirmed in PAN-induced podocyte injury and calpain inhibition experiments. We conclude that calcineurin activity is abnormally increased during PAN-induced podocyte injury, whereas the expression of the full-length 60-kDa calcineurin protein is down-regulated due to over-activated calpain that cleaves calcineurin to form a 45-kDa fragment.
Can Face Recognition Really be Dissociated from Object Recognition?

We argue that the current literature on prosopagnosia fails to demonstrate unequivocal evidence for a disproportionate impairment for faces as compared to nonface objects. Two prosopagnosic subjects were tested for the discrimination of objects from several categories (face as well as nonface) at different levels of categorization (basic, subordinate, and exemplar levels). Several dependent measures were obtained including accuracy, signal detection measures, and response times. The results from Experiments 1 to 4 demonstrate that, in simultaneous-matching tasks, response times may reveal impairments with nonface objects in subjects whose error rates only indicate a face deficit. The results from Experiments 5 and 6 show that, given limited stimulus presentation times for face and nonface objects, the same subjects may demonstrate a decit for both stimulus categories in sensitivity. In Experiments 7, 8 and 9, a match-to-sample task that places greater demands on memory led to comparable recognition sensitivity with both face and nonface objects. Regardless of object category, the prosopagnosic subjects were more affected by manipulations of the level of categorization than normal controls. This result raises questions regarding neuropsychological evidence for the modularity of face recognition, as well as its theoretical and methodological foundations.
Incidence of Chondral Lesions of Talar Dome in Ankle Fracture Types

Background: Although the surgical treatment of ankle fractures is well known, a paucity of literature exists correlating chondral lesions with ankle fracture types. Materials and Methods: This study is a retrospective review of patients with absence or presence of chondral lesions that underwent arthroscopically assisted open reduction and internal fixation between June 2002 and April 2005. There were 38 female and 48 male patients (mean age, 41.4 years; mean followup, 33.9 months), and all had an Ankle-Hindfoot Scale score. The relationship between fracture types and presence of lesions was evaluated. Results: Four of 27 fractures with chondral lesions consisted of the bimalleolar type, 6 of 15 fractures with chondral lesions consisted of the trimalleolar type, and 14 of 20 distal fibula fractures had chondral lesions. There was significant greater incidence of chondral lesions associated with distal fibula fractures. The mean AOFAS score was 95.6 among all fractures. Conclusion: There is clear evidence that despite anatomic reduction, postoperative results of ankle fracture repair are not free of complications. We believe inspection of the talar dome should be routinely considered in the surgical repair ankle fractures.
Increased Expression of Angiotensin II Type 2 Receptors in the Solitary–Vagal Complex Blunts Renovascular Hypertension

Angiotensin II increases and decreases arterial pressure by acting at angiotensin type 1 and type 2 receptors, respectively. Renovascular hypertensive rats exhibit a high level of activity of the peripheral and central renin–angiotensin system. Therefore, in the present study, we evaluated the effect of increasing the expression of angiotensin type 2 receptors in the solitary–vagal complex (nucleus of the solitary tract/dorsal motor nucleus of the vagus), a key brain stem region for cardiovascular regulation, on the development of renovascular hypertension. Holtzman normotensive rats were implanted with a silver clip around the left renal artery to induce 2-kidney 1-clip renovascular hypertension. Three weeks later, rats were microinjected in the solitary–vagal complex with either an adenoassociated virus to increase the expression of angiotensin type 2 receptors or with a control vector. We observed that increasing angiotensin type 2 receptor expression in the solitary–vagal complex attenuated the development of renovascular hypertension and also reversed the impairment of the baroreflex and the increase in the low-frequency component of systolic blood pressure observed in renovascular hypertensive rats. Furthermore, an observed decrease in mRNA levels of angiotensin-converting enzyme 2 in the solitary–vagal complex of renovascular hypertensive rats was restored to control levels after viral-mediated increases in angiotensin type 2 receptors at this site. Collectively, these data demonstrate specific and beneficial effects of angiotensin type 2 receptors via the brain of hypertensive rats and suggest that central angiotensin type 2 receptors may be a potential target for therapeutics in renovascular hypertension.
Profiling unauthorized natural resource users for better targeting of conservation interventions

Unauthorized use of natural resources is a key threat to many protected areas. Approaches to reducing this threat include law enforcement and integrated conservation and development (ICD) projects, but for such ICDs to be targeted effectively, it is important to understand who is illegally using which natural resources and why. The nature of unauthorized behavior makes it difficult to ascertain this information through direct questioning. Bwindi Impenetrable National Park, Uganda, has many ICD projects, including authorizing some local people to use certain nontimber forest resources from the park. However, despite over 25 years of ICD, unauthorized resource use continues. We used household surveys, indirect questioning (unmatched count technique), and focus group discussions to generate profiles of authorized and unauthorized resource users and to explore motivations for unauthorized activity. Overall, unauthorized resource use was most common among people from poor households who lived closest to the park boundary and farthest from roads and trading centers. Other motivations for unauthorized resource use included crop raiding by wild animals, inequity of revenue sharing, and lack of employment, factors that created resentment among the poorest communities. In some communities, benefits obtained from ICD were reported to be the greatest deterrents against unauthorized activity, although law enforcement ranked highest overall. Despite the sensitive nature of exploring unauthorized resource use, management‐relevant insights into the profiles and motivations of unauthorized resource users can be gained from a combination of survey techniques, as adopted here. To reduce unauthorized activity at Bwindi, we suggest ICD benefit the poorest people living in remote areas and near the park boundary by providing affordable alternative sources of forest products and addressing crop raiding. To prevent resentment from driving further unauthorized activity, ICDs should be managed transparently and equitably.
The Synthetic Caged Garcinia Xanthone Cluvenone Induces Cell Stress and Apoptosis and Has Immune Modulatory Activity

Several caged Garcinia xanthone natural products have potent bioactivity and a documented value in traditional Eastern medicine. Previous synthesis and structure activity relationship studies of these natural products resulted in the identification of the pharmacophore represented by the structure of cluvenone. In the current study, we examined the anticancer activity of cluvenone and conducted gene expression profiling and pathway analyses. Cluvenone was found to induce apoptosis in T-cell acute lymphoblastic leukemia cells (EC50 = 0.25 μmol/L) and had potent growth-inhibitory activity against the NCI60 cell panel, including those that are multidrug-resistant, with a GI50 range of 0.1 to 2.7 μmol/L. Importantly, cluvenone was approximately 5-fold more potent against a primary B-cell acute lymphoblastic leukemia compared with peripheral blood mononuclear cells from normal donors, suggesting that it has significant tumor selectivity. Comparison of cluvenone's growth-inhibitory profile to those in the National Cancer Institute database revealed that compounds with a similar profile to cluvenone were mechanistically unlike known agents, but were associated with cell stress and survival signaling. Gene expression profiling studies determined that cluvenone induced the activation of mitogen-activated protein kinase and NrF2 stress response pathways. Furthermore, cluvenone was found to induce intracellular reactive oxygen species formation. Lastly, the modulation in the expression of several genes associated with T cell and natural killer cell activation and function by cluvenone suggests a role as an immune-modulator. The current work highlights the potential of cluvenone as a chemotherapeutic agent and provides support for further investigation of these intriguing molecules with regard to mechanism and targets. Mol Cancer Ther; 9(11); 2869–78. ©2010 AACR.
Evolutionary trade–off between defence against grazing and competitive ability in a simple unicellular alga, Chlorella vulgaris

Trade–offs between defence and other fitness components are expected in principle, and can have major qualitative impacts on ecological dynamics. Here we show that such a trade–off exists even in the simple unicellular alga Chlorella vulgaris. We grew algal populations for multiple generations in either the presence (‘grazed algae’) or absence (‘non–grazed algae’) of the grazing rotifer Brachionus calyciflorus, and then evaluated their defence and competitive abilities. Grazed algae were better defended, yielding rotifer growth rate 32% below that of animals fed non–grazed algae, but they also had diminished competitive ability, with a growth rate under nutrient–limiting conditions 28% below that of non–grazed algae. Grazed algae also had a smaller cell size and were more concentrated in carbon and nitrogen. Thus, C. vulgaris genotypes vary phenotypically in their position along a trade–off curve between defence against grazing and competitive ability. This genetic variation underlies rapid algal evolution that significantly alters the ecological predator–prey cycles between rotifers and algae.
The Effect of Teacher Gender on Student Achievement in Primary School

Using data from a randomized experiment, we find that having a female teacher lowers the math test scores of female primary school students in disadvantaged neighborhoods. Moreover, we do not find any effect of having a female teacher on male students’ test scores (math or reading) or female students’ reading test scores, which seems to rule out explanations pertaining to the unobserved quality differences between male and female teachers. Finally, this negative effect seems to persist only for female students who were assigned to a female teacher with a limited math background.