Miracle-dz/UniFAR-FTUs huggingface dataset:
Suppressor Mutagenesis Identifies a Velvet Complex Remediator of Aspergillus nidulans Secondary Metabolism

ABSTRACT Fungal secondary metabolites (SM) are bioactive compounds that are important in fungal ecology and, moreover, both harmful and useful in human endeavors (e.g., as toxins and pharmaceuticals). Recently a nuclear heterocomplex termed the Velvet complex, characterized in the model ascomycete Aspergillus nidulans, was found to be critical for SM production. Deletion of two members of the Velvet complex, laeA and veA, results in near loss of SM and defective sexual spore production in A. nidulans and other species. Using a multicopy-suppressor genetics approach, we have isolated an Aspergillus nidulans gene named rsmA (remediation of secondary metabolism) based upon its ability to remediate secondary metabolism in ΔlaeA and ΔveA backgrounds. Overexpression of rsmA (OE::rsmA) restores production of sterigmatocystin (ST) (a carcinogenic SM) via transcriptional activation of ST biosynthetic genes. However, defects in sexual reproduction in either ΔlaeA or ΔveA strains cannot be overcome by OE::rsmA. An intact Velvet complex coupled with an OE::rsmA allele increases SM many fold over the wild-type level, but loss of rsmA does not decrease SM. RsmA encodes a putative bZIP basic leucine zipper-type transcription factor.
Attribution of menopause symptoms in human immunodeficiency virus-infected or at-risk drug-using women

Objective: To examine the relationship of human immunodeficiency virus (HIV) and attribution of menopausal symptoms. Design: Peri- and postmenopausal women participating in a prospective study of HIV-infected and at-risk midlife women (the Ms. Study) were interviewed to determine whether they experienced hot flashes and/or vaginal dryness and to what they attributed these symptoms. Results: Of 278 women, 70% were perimenopausal; 54% were HIV-infected; and 52% had used crack, cocaine, heroin, and/or methadone within the past 5 years. Hot flashes were reported by 189 women and vaginal dryness was reported by 101 women. Overall, 69.8% attributed hot flashes to menopause and 28.7% attributed vaginal dryness to menopause. In bivariate analyses, age 45 years and older was associated with attributing hot flashes and vaginal dryness to menopause, and postmenopausal status and at least 12 years of education were associated with attributing vaginal dryness to menopause, but HIV status was not associated with attribution to menopause. In multivariate analysis, significant interactions between age and menopause status were found for both attribution of hot flashes (P = 0.019) and vaginal dryness (P = 0.029). Among perimenopausal women, older age was independently associated with attribution to menopause for hot flashes (adjusted odds ratio = 1.2, 95% CI: 1.1-1.4, P = 0.001) and vaginal dryness (adjusted odds ratio = 1.3, 95% CI: 1.1-1.6, P = 0.011). None of the tested factors were independently associated with attribution to menopause among postmenopausal women. Conclusion: Tailored health education programs may be beneficial in increasing the knowledge about menopause among HIV-infected and drug-using women, particularly those who are perimenopausal.
Cathepsin S Is Involved in Th17 Differentiation Through the Upregulation of IL-6 by Activating PAR-2 after Systemic Exposure to Lipopolysaccharide from Porphyromonas gingivalis

Positive links have been found between periodontitis and numerous diseases in humans via persistent inflammation throughout the body. However, the main factors responsible for maintaining this pro-inflammatory condition are poorly understood. The spleen, the largest secondary immune organ, is a central hub regulating the immune response/inflammation due to the dendritic cell (DC) response to CD4+ T cell subtype differentiation, and lysosomal proteinase cathepsin S (CatS) is known to be involved in DC functions. In the present study, we found that CatS-induced IL-6 production by splenic DCs subsequently promotes Th17 differentiation, in response to systemic exposure to lipopolysaccharide derived from Porphyromonas gingivalis (PgLPS). The population of CD11c+ DCs was significantly increased in the splenic marginal zone (MZ) locally of wild-type (DBA/2) mice with splenomegaly but not in that of CatS deficient (CatS-/-) mice after systemic exposure to PgLPS for 7 consecutive days (5 mg/kg/day, intraperitoneal). Similarly, the population of Th17+CD4+ T cells was also significantly increased in the splenic MZ of wild-type mice but not in that of CatS-/- mice after PgLPS exposure. Furthermore, the increase in the Th17+ CD4+ T cell population paralleled increases in the levels of CatS and IL-6 in CD11c+ cells in the splenic MZ. In isolated primary splenic CD11c+ cells, the mRNA expression and the production of IL-6 was dramatically increased in wild-type mice but not in CatS-/- mice after direct stimulation with PgLPS (1 μg/ml), and this PgLPS-induced increase in the IL-6 expression was completely abolished by pre-treatment with Z-Phe-Leu-COCHO (Z-FL), the specific inhibitor of CatS. The PgLPS activated protease-activated receptor (PAR) 2 in the isolated splenic CD11c+ cells was also significantly inhibited by CatS deficiently. In addition, the PgLPS-induced increase in the IL-6 production by splenic CD11c+ cells was completely abolished by pre-treatment with FSLLRY-NH2, a PAR2 antagonist, as well as Akti, a specific inhibitor of Akt. These findings indicate that CatS plays a critical role in driving splenic DC-dependent Th17 differentiation through the upregulation of IL-6 by activating PAR2 after exposure to components of periodontal bacteria. Therefore, CatS-specific inhibitors may be effective in alleviating periodontitis-related immune/inflammation.
Intermittent Explosive Disorder in South Africa: Prevalence, Correlates and the Role of Traumatic Exposures

Background: The epidemiology of DSM-IV intermittent explosive disorder (IED) is not well characterized in developing country settings. In South Africa, given the high rates of violence and trauma, there is particular interest in traumatic exposures as potential risk factors for IED. Methods: We examined the prevalence and predictors of IED in a nationally representative sample of 4,351 South African adults. IED and other diagnoses based on DSM-IV criteria were assessed using the World Health Organization Composite International Diagnostic Interview (CIDI). A 28-item scale was constructed to measure exposure to traumatic events. Results: Overall, 2.0% of participants (95% CI: 0–4.9%) fulfilled criteria for the narrow definition of IED, and 9.5% (95% CI: 6.6–12.3%) fulfilled criteria for the broad definition of IED. Individuals with IED experienced high rates of comorbid anxiety, mood and substance use disorders compared to non-IED participants. In multivariate analysis, a diagnosis of IED was associated with Caucasian and mixed-race ethnicity, psychiatric comorbidity and exposure to multiple traumatic events. Conclusion: These data suggest a relatively high prevalence of IED in South Africa. By reducing violence and trauma, and by providing appropriate psychological support to trauma survivors, we may be able to reduce rates of IED.
BLEEDING TENDENCIES ASSOCIATED WITH PROFOUND‐HYPOTHERMIA TECHNICS IN NEUROLOGIC SURGERY *

Uncontrollable bleeding, although uncommon during or after operation with the aid of extracorporeal circulation, can be a frustrating and perplexing problem. The voluminous literature on the alterations in blood coagulation and on hemostasis after extracorporeal circulation indicates the magnitude of this problem. ' . 'l In the past three years we have used two methods in the clinical production of profound hypothermia (below 15" C.) through total-body cooling in order to reduce arterial flow or induce total circulatory arrest during operation. Forty-three patients with intracranial aneurysm were treated. "i In the first method (used in 18 cases) profound hypothermia was accomplished according to the method of Drew' median sternotomy and cardiac catheterization, with bypass through a heat exchanger, utilizing the patient's own lungs as oxygenator. This method provided flows of 2.2 l. /min./m. * of body surface and varying periods of total circulatory arrest up to 44 minutes. The second method, which we have recently used in 25 cases, is that described by Woodhall and associates" and by Patterson and Ray ;lo i t does not require thoracotomy, and utilizes peripheral cannulae in the femoral veins and artery. The extracorporeal circuit consists of a pumpoxygenator with incorporated heat exchanger. Flows with this method averaged 1.4 l. /min./m. ,* which roughly doubled the length of time needed to reach 15' C. and thereafter to rewarm the body. The total duration of circulatory arrest averaged 20 minutes. The advantages of the open-thorax method are that i t provides more abundant flows and permits more rapid cooling and rewarming. Its disadvantages include those of thoracotomy, the need for large amounts of blood for both perfusion and transfusion, and the need for the services of a cardiac surgical team. The closed-thorax technic significantly reduces the amount of perfusate and blood for both perfusion and transfusion. This is especially advantageous when unusual blood types are unavailable. Freshly drawn heparinized blood is preferable with the open-thorax
Structure and variability of human chromosome ends

Mammalian telomeres are thought to be composed of a tandem array of TTAGGG repeats. To further define the type and arrangement of sequences at the ends of human chromosomes, we developed a direct cloning strategy for telomere-associated DNA. The method involves a telomere enrichment procedure based on the relative lack of restriction endonuclease cutting sites near the ends of human chromosomes. Nineteen (TTAGGG)n-bearing plasmids were isolated, two of which contain additional human sequences proximal to the telomeric repeats. These telomere-flanking sequences detect BAL 31-sensitive loci and thus are located close to chromosome ends. One of the flanking regions is part of a subtelomeric repeat that is present at 10 to 25% of the chromosome ends in the human genome. This sequence is not conserved in rodent DNA and therefore should be a helpful tool for physical characterization of human chromosomes in human-rodent hybrid cell lines; some of the chromosomes that may be analyzed in this manner have been identified, i.e., 7, 16, 17, and 21. The minimal size of the subtelomeric repeat is 4 kilobases (kb); it shows a high frequency of restriction fragment length polymorphisms and undergoes extensive de novo methylation in somatic cells. Distal to the subtelomeric repeat, the chromosomes terminate in a long region (up to 14 kb) that may be entirely composed of TTAGGG repeats. This terminal segment is unusually variable. Although sperm telomeres are 10 to 14 kb long, telomeres in somatic cells are several kilobase pairs shorter and very heterogeneous in length. Additional telomere reduction occurs in primary tumors, indicating that somatic telomeres are unstable and may continuously lose sequences from their termini.
Using STATCOM to mitigate voltage fluctuations due to aerodynamic aspects of wind turbines

This paper investigates how a static compensator (STATCOM) mitigates the voltage fluctuations caused by the aerodynaimc aspects of a wind turbine in a wind power system (e.g., due to yaw error and turbulence). In this regard, a small wind farm equipped with fixed speed wind turbines driving conventional induction generators connected to a relatively weak distribution system is studied, where a STATCOM is utilized to improve the power quality. The paper describes how the aerodynamic and mechanical aspects of a wind turbine can be simulated using TurbSim, AeroDyn, and FAST, where the electrical parts of the wind turbine, STATCOM, and network are modelled by Simulink blocks. Moreover, the STATCOM control scheme implemented in a Simulink environment is explained. Simulation results obtained from the model are used to observe the effects of yaw error and turbulence on the power and voltage variations at point of common coupling (PCC). The performance of the STATCOM and its controller is then evaluated based on these observations.
Liquidity and Returns to Target Shareholders in the Market for Corporate Control: Evidence from the US Markets

In this paper we analyze how stock market liquidity affects the abnormal return to target firms in mergers and tender offers. We predict that target firms with poorer stock market liquidity receive larger announcement day abnormal returns based on the following considerations. First, target firms with poorer stock market liquidity receive greater liquidity improvements after a merger or tender offer. Second, deals that involve less liquid targets are less anticipated and/or more likely to be completed. Third, less liquid stocks have more diverse reservation prices across shareholders and thus require a higher takeover return. Consistent with these expectations, we show that abnormal returns to target firms’ shareholders are significantly and positively related to the difference in liquidity (measured by the bid‐ask spread) between acquirers and targets as well as the magnitude of target firms’ liquidity improvement.
Cultural perceptions of online learning: transnational faculty perspectives

Purpose The purpose of this paper is to investigate how university academics from three different cultural and linguistic backgrounds perceived their own cultural context and how it influences on online learning. Design/methodology/approach The views of 30 faculty members from Sri Lanka, Pakistan and Mauritius who engaged in a six-week professional development online course were gathered through a self-reflection questionnaire, posts on an asynchronous discussion forum and personal self-reflections in journal entries. Content analysis of three asynchronous discussion forums indicated the emergence of categories and themes related to traditional culture and the impact of culture on online learning that were triangulated with questionnaire data and journal entries. Findings Cultural perceptions of Sri Lankans and Pakistanis showed similar patterns in their recognition that their cultures exhibit characteristics of high power distance, collectivism and feminine values, while there were no definite dimensional perspectives from the Mauritians. The inability to define their own cultural context using bi-polar dimensions may reflect the sociocultural context of Mauritius. While these frameworks may explain more traditional cultures like those in Sri Lanka and Pakistan, they are unlikely to be useful to define cultural characteristics when the society is diverse, multiethnic, multicultural and multilingual like Mauritius. Research limitations/implications This study was based on a small sample of participants from three ethnic origins and cannot be generalized. It has generated questions for further research. Practical implications The findings have implications for accounting for culture in designing and delivering online courses. Originality/value This study will benefit instructional designers/curriculum designers/teachers to design culturally sensitive and culturally adaptive online courses.
Joint Effect of MLSE and Receiver Filters Optimization on Dispersion Robustness of IMDD, DPSK, DQPSK, and Duobinary Modulation

We analyze the effectiveness of a 32-state maximum-likelihood sequence-estimation (MLSE) receiver on chromatic dispersion robustness of optical transmission based on several binary modulation formats: intensity modulation direct detection, differential phase-shift keying, and duobinary line coding. Multilevel differential quadrature phase-shift keying modulation is also analyzed using a four-state 2-bit/symbol joint MLSE processor. For all modulation formats, receiver filters are optimized together with the use of the MLSE technique.
A normal mitochondrial protein is selectively synthesized and accumulated during heat shock in Tetrahymena thermophila

We have identified and purified a 58-kilodalton protein of Tetrahymena thermophila whose synthesis during heat shock parallels that of the major heat shock proteins. This protein, hsp58, was found in both non-heat-shocked as well as heat-shocked cells; however, its concentration in the cell increased approximately two- to threefold during heat shock. The majority of hsp58 in both non-heat-shocked and heat-shocked cells was found by both cell fractionation studies and immunocytochemical techniques to be mitochondrially associated. During heat shock, the additional hsp58 was found to selectively accumulate in mitochondria. Nondenatured hsp58 released from mitochondria of non-heat-shocked or heat-shocked cells sedimented in sucrose gradients as a 20S to 25S complex. We suggest that this protein may play a role in mitochondria analogous to the role the major heat shock proteins play in the nucleus and cytosol.
Impact of simulation‐based learning on immediate outcomes of temporary haemodialysis catheter placements by nephrology fellows

Traditional apprenticeship model (AM) of teaching in invasive procedures such as temporary haemodialysis catheter (THDC) insertion can result in propagation of errors and complications. Simulation‐based learning (SBL) offers standardization of skills and allows trainees to repeatedly practice invasive procedures prior to performing them on actual patient.
Product-Service Systems for servitization of the automotive industry: a literature review

Nowadays companies are facing several transformations of their activities, empowered and pulled by technological and social evolutions over the few past decades. As competitiveness is a leitmotiv in the market economy paradigm, it is necessary to improve activities through excellence and new offers. In a focus on the consumers’ needs, the limits between tangible and intangible offer are challenged through new kind of offers merging products and service under one common offer. Manufacturing companies, and more precisely the automotive industry, endeavour to integrate new constraints of sustainability, economic globalisation and new ways of consumption made possible with this new kind of offerings. This supports the opportunity to change consumption offers, historically driven by production and consumption of tangible assets. The paper explores a key concept to operate this shift towards a new type of offer gathering products and service into an integrated bundle entitled product-service system (PSS). This paper proposes a review of PSS definitions, methodologies and its applications to clarify the contribution of the literature in enabling its adoption. Requirements to adopt PSS are extracted from case studies and methodologies for servitization are evaluated as means to overcome barriers of PSS adoption. A specific focus is given on the automotive industry.
The Mitogen-activated Protein Kinase Phosphatases PAC1, MKP-1, and MKP-2 Have Unique Substrate Specificities and Reduced Activity in Vivo toward the ERK2 sevenmaker Mutation (*)

Mitogen-activated protein (MAP) kinases can be grouped into three structural families, ERK, JNK, and p38, which are thought to carry out unique functions within cells. We demonstrate that ERK, JNK, and p38 are activated by distinct combinations of stimuli in T cells that simulate full or partial activation through the T cell receptor. These kinases are regulated by reversible phosphorylation on Tyr and Thr, and the dual specific phosphatases PAC1 and MKP-1 previously have been implicated in the in vivo inactivation of ERK or of ERK and JNK, respectively. Here we characterize a new MAP kinase phosphatase, MKP-2, that is induced in human peripheral blood T cells with phorbol 12-myristate 13-acetate and is expressed in a variety of nonhematopoietic tissues as well. We show that the in vivo substrate specificities of individual phosphatases are unique. PAC1, MKP-2, and MKP-1 recognize ERK and p38, ERK and JNK, and ERK, p38, and JNK, respectively. Thus, individual MAP kinase phosphatases can differentially regulate the potential for cross-talk between the various MAP kinase pathways. A hyperactive allele of ERK2 (D319N), analogous to the Drosophila sevenmaker gain-of-function mutation, has significantly reduced sensitivity to all three MAP kinase phosphatases in vivo.
On the choice of the optimal periodic operation for a continuous fermentation process

In this contribution we investigate the impact of the forcing waveform on the productivity of a continuous bioreactor governed by an unstructured, nonlinear kinetic model. The (periodic) forcing is applied on the substrate concentration in the feed. To this end, some alternative waveforms commonly encountered in practice are evaluated and their performance is compared. An analytical/numerical approach is used. The preliminary analytical step is based on the π‐criterion that gives useful information for small amplitudes. The extension to larger amplitudes, when significant improvements are expected, is then performed through a continuation‐optimization procedure. It is found that the choice of the specific waveform has an impact on the performance of the process and there is no unique best forcing for any process condition, but its choice depends on the operating parameters and the forcing amplitude and frequency values. Further, the influence of the waveform functions on the wash‐out conditions are extensively examined. The analysis shows that all the waveforms examined in this work may lead to significant enlargement of the nontrivial regime with respect to a steady state operation. In particular, square‐wave forcing leads in practice to the extinction of the wash‐out conditions for any feed substrate concentration and for a well defined choice of the forcing parameters. © 2010 American Institute of Chemical Engineers Biotechnol. Prog. , 2010
Inter-annual variability in fossil-fuel CO2 emissions due to temperature anomalies

It is well known that short-term (i.e. interannual) variations in fossil-fuel CO2 emissions are closely related to the evolution of the national economies. Nevertheless, a fraction of the CO2 emissions are linked to domestic and business heating and cooling, which can be expected to be related to the meteorology, independently of the economy. Here, we analyse whether the signature of the inter-annual temperature anomalies is discernible in the time series of CO2 emissions at the country scale. Our analysis shows that, for many countries, there is a clear positive correlation between a heating-degree-person index and the component of the CO2 emissions that is not explained by the economy as quantified by the gross domestic product (GDP). Similarly, several countries show a positive correlation between a cooling-degree-person (CDP) index and CO2 emissions. The slope of the linear relationship for heating is on the order of 0.5–1 kg CO2 (degree-day-person)−1 but with significant country-to-country variations. A similar relationship for cooling shows even greater diversity. We further show that the inter-annual climate anomalies have a small but significant impact on the annual growth rate of CO2 emissions, both at the national and global scale. Such a meteorological effect was a significant contribution to the rather small and unexpected global emission growth rate in 2014 while its contribution to the near zero emission growth in 2015 was insignificant.