Miracle-dz/UniFAR-FTUs huggingface dataset:
A Serine/Threonine-rich Motif Is One of Three Nuclear Localization Signals That Determine Unidirectional Transport of the Mineralocorticoid Receptor to the Nucleus*

The mineralocorticoid receptor (MR) is a tightly regulated nuclear hormone receptor that selectively transmits corticosteroid signals. Steroid treatment transforms MR from a transcriptionally inert state, in which it is distributed equally between the nucleus and cytoplasm, to an active completely nuclear transcription factor. We report here that MR is an atypical nuclear hormone receptor that moves unidirectionally from the cytoplasm to the nucleus. We show that nuclear import of MR is controlled through three nuclear localization signals (NLSs) of distinct types. Nuclear localization of naïve MR was mediated primarily through a novel serine/threonine-rich NLS (NL0) in the receptor N terminus. Specific amino acid substitutions that mimicked phosphorylation selectively enhanced or repressed NL0 activity, highlighting the potential for active regulation of this new type of NLS. The second NLS (NL2) within the ligand-binding domain also lacks a recognizable basic motif. Nuclear transfer through this signal was strictly dependent on steroid agonist, but was independent of the interaction of MR with coactivator proteins. The third MR NLS (NL1) is a bipartite basic motif localized to the C terminus of the MR DNA-binding domain with properties distinct from those of NL1 of the closely related glucocorticoid receptor. NL1 acted in concert with NL0 and NL2 to stimulate nuclear uptake of the agonist-treated receptor, but also directed the complete nuclear localization of MR in response to treatment with steroid antagonist. These results present MR as a nuclear hormone receptor whose unidirectional transfer to the nucleus may be regulated through multiple pathways.
Red cell distribution width and coronary artery bypass surgery.

OBJECTIVES The red cell distribution width (RDW) has been identified as an independent risk factor with regard to prognosis in patients with coronary artery disease with or without heart failure. We sought to investigate the role of RDW in patients undergoing isolated coronary artery bypass graft surgery (CABG). METHODS Analysis of consecutive patients on a validated prospective cardiac surgery database was performed for patients undergoing isolated CABG. Univariate and multivariate analysis was performed for in hospital mortality, long-term survival, length of hospital stay, length of intensive care unit stay and creatinine kinase muscle-brain (CKMB) release. RESULTS Overall mortality was 2.1% for all cases, N = 8615. Median follow up was 5.8 years. Univariate analysis demonstrated that the RDW has a significant effect on CKMB release, P = 0.001, in-hospital mortality, P < 0.0001, and long-term survival, P < 0.0001, but no significant effect on the ITU length of stay, P = 0.9, or hospital length of stay, P = 0.2. Multivariate analysis revealed that the RDW was a significant factor determining in-hospital mortality and long-term survival, but had no significant effect on CKMB release, ITU or hospital length of stay. Confounding factor analysis revealed that in the absence of anaemia, the RDW was still a significant factor determining in-hospital mortality and long-term survival. CONCLUSIONS The RDW is a significant factor determining in-hospital mortality and long-term survival in patients undergoing isolated CABG. The mechanism of association requires further study.
The Nexus between union membership and workplace climate

ABSTRACT This paper summarises findings from a study of the relationship between union membership and workplace climate. A survey of 1380 workers in three different Australian manufacturing firms found union membership to be negatively associated with workplace climate in one company, positively associated with workplace climate in another and to have no significant relationship to workplace climate in the third. These results, when linked to the findings from observational research and focus group discussions, indicated that when a business was only partially unionised, internal harmony and good workplace conditions were reasons for the existence of a positive relationship between workplace climate and union membership. However, when union-management relationships were fractious, the workplace climate was driven by that relationship with deleterious results for workplace harmony. The findings highlight the pivotal requirement for management to provide positive work environments and, when unions are involved, to work with them to achieve this outcome.
The pancreatitis‐associated protein induces lung inflammation in the rat through activation of TNFα expression in hepatocytes

The pancreatitis‐associated protein (PAP) is a pancreatic stress protein overexpressed during acute pancreatitis, a disease often accompanied by lung inflammation. We investigated whether PAP was involved in the occurrence of this remote complication of pancreatitis and whether the liver might be implicated in the process. PAP was injected into the vena cava of rats (40 or 400 µg/kg body weight). For comparison, pancreatitis was induced in rats by intraductal administration of sodium taurocholate. Three hours later, parameters of inflammation and mRNA concentrations of TNFα, P‐selectin, heat shock protein (HSP)‐70, and extracellular superoxide dismutase (EC‐SOD) were monitored in lung and liver. Significant increases in P‐selectin expression, neutrophil infiltration, and oxidative stress revealed that PAP treatment induced lung inflammation in rats and exacerbated inflammation in animals with pancreatitis. Plasma TNFα level was increased and TNFα mRNA was strongly overexpressed in liver, with concomitant activation of NF‐κB; in situ hybridization revealed that TNFα overexpression was mainly located to hepatocytes. Lung inflammation induced by PAP could be prevented by injection of anti‐TNFα antibodies. It was concluded that, during pancreatitis, PAP released by the pancreas could mediate lung inflammation through induction of hepatic TNFα expression and subsequent increase in circulating TNFα. Copyright © 2003 John Wiley & Sons, Ltd.
An empirical analysis of the effect of business incubation process on firm performance in Nigeria

Small and medium enterprises (SME), acknowledged as tools of economic development, are faced with size-related challenges. Governments around the world design institutions to support them. Business incubation is one of such frameworks for entrepreneurial promotion and SME development. This study predicts firm performance from the constructs of the business incubation process: selection performance, business assistance intensity, resource munificence and professional management services. Using hierarchical multiple regression, the overall model was significant explaining 13.5% of the variation in firm performance with a moderate effect size. Business assistance intensity and professional management services were significant predictors while incubator selection performance and resource munificence were not significant predictors of firm performance. Incubation should be promoted as a tool for entrepreneurial promotion to complement the broader strategic entrepreneurial framework for entrepreneurship promotion. The focus should be on evolving strategies to expand and deepen incubators capacity by intensifying business assistance and professional management services to their clients.
Overall equipment efficiency of Flexographic Printing process: A case study

This paper reports the efficiency improvement of a flexographic printing machine by reducing breakdown time with the help of a total productive maintenance measure called overall equipment efficiency (OEE). The methodology is comprised of calculating OEE of the machine before and after identifying the causes of the problems. Pareto diagram is used to prioritize main problem areas and 5-whys analysis approach is used to identify the root cause of these problems. OEE of the process is improved from 34% to 40.2% for a 30 days time period. It is concluded that OEE and 5-whys analysis techniques are useful in improving effectiveness of the equipment and for the continuous process improvement as well.
Chronic Testicular Pain: A Unique Presentation of Isolated Testicular Polyarteritis Nodosa (PAN) with Hepatitis B Infection: A Case Report and a Review of theLiterature

Polyarteritis Nodosa (PAN) is a vasculitis of unknown origin that affects the medium and small arteries of our organ system. Isolated Polyarteritis Nodosa is a rare condition that may be due to modulation of local immune reaction by exposure to certain local triggering agent without any systemic immune reaction. Symptomatic PAN confined to the testis in hepatitis B infection is extremely rare and not reported frequently. We report a case of isolated testicular PAN in hepatitis B infection with chronic unilateral testicular pain and successfully treated by interferon α, systemic steroid and cyclophosphamide for 7 month.
Symptomatic herniation pits of the femoral neck: anatomic and clinical study.

OBJECTIVE The purpose of this study was to investigate the pathogenesis of herniation pits of the femoral neck, which are frequently considered a normal variant, and to describe the imaging abnormalities of such pits in three symptomatic patients. CONCLUSION The changing relationship between the joint capsule and the iliopsoas muscle appears to be important in the pathogenesis of the herniation pit, especially in athletic persons. In some cases, these pits may enlarge, the overlying cortex may fracture, and significant clinical manifestations may be apparent.
Influence of financial management on sustainability of community managed water supply projects in Kieni West District, Nyeri County, Kenya

Water is the most important natural resource, indispensable for life and at the same time the backbone of growth and prosperity for mankind. In the last decade, the provision of potable water for domestic and rural livelihood needs has moved to centre stage on the international development agenda and in the interventions of many Non Government Organizations (NGO) and National Governments. The Government of Kenya Vision 2030 acknowledges the fact that Kenya is a water scarce country and underscores the central role water plays in the performance of key sectors of the economy and the livelihoods of Kenyans. Under the economic and social pillars of Vision 2030, improved access to safe water and sanitation in both rural and urban areas, and increasing the area under irrigation have been given prominence with the rehabilitation and expansion of water supply identified as some of the flagship projects. The purpose of the study was to investigate financial management factors that influence sustainability of community managed water supply projects in Kieni West District. The research adopted a survey research design. The target population for the study was 150 water committee officials and the sample size was 109 respondents who were selected using the stratified sampling method. Key findings are that adequate understanding, identification and estimation of the operation and maintenance costs is critical for the sustainable delivery of water supply services; transparency of financial management is a key issue in community management in water projects and that without water levies and fees charged for connection and usage, sustainability of the project will not be possible.
Mibefradil inhibition of the Cole-Moore shift and K+-conductance of the tumor-related Kv10.1 channel

The KCNH1 gene codes for the KC-selective, noninactivating, voltage-dependent channel, referred to as Kv10.1 or Eag1. Outside the central nervous system Eag1 expression is associated with a cancerous phenotype. This was first demonstrated by the laboratory of Luis A Pardo and Walter St€ uhmer who showed that CHO cells upon stably expressing Eag1, but not other KC channels, acquire the hallmark characteristic of cancer cells; and that injection of Eag1 expressing cells to immunosuppressed mice leads to the development of massive tumors in these animals. Naturally, the question arises as to what particular structural characteristic(s), as compared with other KC channels, endow(s) Kv10.1 with its tumor promoting features, and which of them could be pharmacologically targeted in an effort to lessen the tumorous effect of Kv10. The Eag family presents a unique structural characteristic, namely a cytoplasmic, Per-Arnt-Sim (PAS) domain, which interacts with the voltage-sensor (S1 to S4 segments) domain. PAS domains are present in proteins engaged in pathways that regulate cellular responses to environmental stimuli, as such these domains mediate protein-protein interactions and bind diverse chemical molecules. These properties suggest that PAS domain could be an interesting target to test drugs aimed to lessen the tumor promoting properties of Kv10.1. In addition, Eag1 channels present other unique structural, and functional, features, for example: 1) Eag1 channels present a long pore-loop that forms glycosylated helical structures which surround the pore opening. It has been proposed that this arrangement may hinder the binding of peptide toxins. This means that in the quest to find pharmacological tools against Kv10.1 studies using non-peptide compounds, as mibefradil, are instrumental. 2) The pore lumen presents a rather uniform diameter along its full length. In other words Eag1 channels do not present the pore widening, or central cavity of KscA and Shaker-related channels. The central cavity is the place where internally added TEA, and numerous hydrophobic cations, as for example quinidine (e.g., reference 12 and references therein cited), blocks the open-pore of Shaker-related channels. 3) Eag1 channels endure a voltage-dependent gating even in the absence of a covalent linkage between S4 and S5 segments. This shows that communication between voltage-sensor and pore modules presents characteristics not shared with canonical Kv channels. The aforementioned properties indicate that care must be taken to translate drug-interaction models, initially developed on canonical Shaker-related KC channels, to Eag1 channels. In addition to the above mentioned features, a functional hallmark of Eag channels is the presence of both, a noticeably lag or time-shift for current surge, and the development of a markedly sigmoidal time course of current activation, as the holding potential (HP) becomes more negative; the latter arises from a rate limiting transition that
Overactive prefrontal and underactive motor cortical areas in idiopathic dystonia

Regional cerebral blood flow was measured using H215O and positron emission tomography in a group of 6 patients with idiopathic torsion dystonia and in a group of 6 control subjects. Subjects were scanned while at rest and when performing paced joystick movements in freely chosen directions with the right hand. Patients with idiopathic torsion dystonia showed significant overactivity in the contralateral lateral premotor cortex, rostral supplementary motor area, Brodmann area 8, anterior cingulate area 32, ipsilateral dorsolateral prefrontal cortex, and bilateral lentiform nucleus. Significant underactivity was found in the caudal supplementary motor area, bilateral sensorimotor cortex, posterior cingulate, and mesial parietal cortex. These results are consistent with inappropriate overactivity of striatofrontal projections and impaired activity of motor executive areas in idiopathic torsion dystonia and may explain the simultaneous dystonic posturing and bradykinesia evident in these patients.
Preferences and willingness to pay for tablet news apps

ABSTRACT Media companies are facing the need to adjust their established business models owing to media convergence. Applications (apps) for mobile devices such as tablet computers offer the potential to enter new markets in order to overcome decreasing revenue from established distribution channels (i.e. selling printed newspapers). This study uses a choice-based conjoint analysis to investigate (a) whether consumers demonstrate willingness to pay (WTP) for tablet news apps and (b) whether online advertising is negatively related to consumers’ WTP. The results reveal that two segments of the market for tablet news apps can be distinguished: a large segment (about 60%) of our sample lacks WTP for tablet news apps, whereas a smaller segment (about 40%) of our sample exhibits moderate WTP.
Treatment of prosthetic osteoarticular infections

Introduction: Despite being relatively infrequent, prosthetic joint infections are a devastating medical complication. However, recent advances in surgical techniques, new antibiotics, and knowledge about pathogenic mechanisms have improved the outcome for affected patients. Areas covered: We have analyzed recent advances in pathogenesis, medical and surgical therapy of prosthetic joint infections, with special focus on new antibiotics useful for this disease. Recent studies focused on the important role of biofilms and intracellular bacteria in the pathogenesis of biomaterial-related infections. These advances must guide the management of the patients. Together with more classical antibiotics, linezolid and daptomycin have shown their usefulness for the treatment of these infections. Recently developed lipoglycopeptides have the potential to be used for these infections. In this sense, the possibility of treating patients with oral antibiotics without lack of efficacy is of great interest. Expert opinion: Individualized therapies that take into account the microbial etiology, pathogenesis of the disease, antimicrobial susceptibility, and efficacy of antibiotics against biofilms and intracellular organisms make it possible to treat even those infections caused by multidrug-resistant organisms. A multidisciplinary approach (including a surgeon, infectious diseases specialist and microbiologist) provides the best possible management of patients.
Pleiotropic Role of Quorum-Sensing Autoinducer 2 in Photorhabdus luminescens

ABSTRACT Bacterial virulence is an integrative process that may involve quorum sensing. In this work, we compared by global expression profiling the wild-type entomopathogenic Photorhabdus luminescens subsp. laumondii TT01 to a luxS-deficient mutant unable to synthesize the type 2 quorum-sensing inducer AI-2. AI-2 was shown to regulate more than 300 targets involved in most compartments and metabolic pathways of the cell. AI-2 is located high in the hierarchy, as it controls the expression of several transcriptional regulators. The regulatory effect of AI-2 appeared to be dose dependent. The luxS-deficient strain exhibited decreased biofilm formation and increased type IV/V pilus-dependent twitching motility. AI-2 activated its own synthesis and transport. It also modulated bioluminescence by regulating the synthesis of spermidine. AI-2 was further shown to increase oxidative stress resistance, which is necessary to overcome part of the innate immune response of the host insect involving reactive oxygen species. Finally, we showed that the luxS-deficient strain had attenuated virulence against the lepidopteran Spodoptera littoralis. We concluded that AI-2 is involved mainly in early steps of insect invasion in P. luminescens.
Making planning work: insights from business development

Planning for a growth opportunity's success remains a challenge. Under which conditions does planning work, then? This exploratory study investigates the business development tasks and processes that span a growth opportunity's planning phase and its implementation phase and their unique performance implications. On the basis of 73 CEO responses from growth SMEs, the results show that business development increases firm performance and that the effectiveness of business planning depends on business development. Business developer support is found to positively influence firm performance per se. Business development is presented as an important organisational capability to pursue growth opportunities and subsequently theoretically anchored in the resource-based view of the firm. Implications for managers and for future business development research are discussed.
Opinion: a case against the membership programme proposal of the west african college of surgeons.

Following the meeting held in Accra, Ghana in September 2012, a draft proposal on Harmonization of Surgical Training was submitted for final consideration by the four Colleges in the West African Sub-region. The Council of the West African College of Surgeons (WACS) was mandated to produce a Membership Curriculum separate from the Part 1 programme of the Fellowship Examination. This, in essence, means that there is a proposal to have a Membership Examination and certification in addition to the well established Fellowship Examination and certification. This means that there will be a lower standard of examination for Membership certification than the Fellowship Examination. nd The President of WACS in the presidential address in Liberia at the 52 annual meeting made an allusion to “the reluctance of Faculty of Surgery to go along with the Membership” plan. We fully support the reluctance of the Faculty of Surgery in this regard, and the following will explain our position.
Factors Affecting Job Turnover: A Case Study of Private Schools of District Swat

Several factors force employees to leave the organization. This study examines the relationship among job turnover intention , workload, low pay and job stress in private schools at district swat. For this purpose, the data has been collected from of two hundred and forty eight employees. The results of the study indicated that workload, low pay and job stress are significantly positive related to turnover intention. This study also suggested that for overcoming the turnover from the schools enough salary should be given to employees to motivate them and retained.
The Apolipoprotein E-Mimetic Peptide COG112 Inhibits NF-κB Signaling, Proinflammatory Cytokine Expression, and Disease Activity in Murine Models of Colitis*

Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis, is a source of substantial morbidity and remains difficult to treat. New strategies for beneficial anti-inflammatory therapies would be highly desirable. Apolipoprotein (apo) E has immunomodulatory effects and synthetically derived apoE-mimetic peptides are beneficial in models of sepsis and neuroinflammation. We have reported that the antennapedia-linked apoE-mimetic peptide COG112 inhibits the inflammatory response to the colitis-inducing pathogen Citrobacter rodentium in vitro by inhibiting NF-κB activation. We now determined the effect of COG112 in mouse models of colitis. Using C. rodentium as an infection model, and dextran sulfate sodium (DSS) as an injury model, mice were treated with COG112 by intraperitoneal injection. With C. rodentium, COG112 improved the clinical parameters of survival, body weight, colon weight, and histologic injury. With DSS, COG112 ameliorated the loss of body weight, reduction in colon length, and histologic injury, whether administered concurrently with induction of colitis, during induction plus recovery, or only during the recovery phase of disease. In both colitis models, COG112 inhibited colon tissue inducible nitric-oxide synthase (iNOS), KC, TNF-α, IFN-γ, and IL-17 mRNA expression, and reduced nuclear translocation of NF-κB, as determined by immunoblot and immunofluorescence confocal microscopy. IκB kinase (IKK) activity was also reduced, which is necessary for activation of the canonical NF-κB pathway. Isolated colonic epithelial cells exhibited marked attenuation of expression of iNOS and the CXC chemokines KC and MIP-2. These studies indicate that apoE-mimetic peptides such as COG112 are novel potential therapies for IBD.