Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of apoptosis regulators in cutaneous T‐cell lymphoma (CTCL) cells

This study examined cutaneous T‐cell lymphoma (CTCL) cell lines and cutaneous lesions for the presence of Bcl‐2 gene family members and found that the two apoptosis‐inhibiting members Bcl‐xL and Mcl‐1 and the two apoptosis‐supporting members Bad and Bax were expressed. However, Bad was at least partially inactivated by phosphorylation. In skin lesions, the translocation of Bad from the nucleus to the cytoplasm may reflect the Bad inactivation by phosphorylation identified in vivo. Bax is also ineffective, as the non‐steroidal anti‐inflammatory drug sulindac, whose cytotoxic effect is mediated by Bax, could not induce apoptosis in CTCL cell lines. The expression of Bcl‐2, Bcl‐xL, and Mcl‐1 may therefore be sufficient to guarantee the survival of malignant CTCL cells. The Bcl‐x, Mcl‐1, Bad, and Bax proteins were also expressed in all CTCL skin lesions tested. In two patients from whom two biopsies from two different time points of the disease were available, a significant increase in Mcl‐1 expression was found in the later‐stage skin lesion. Overexpression of Mcl‐1 and synthesis of non‐functional Bax may be responsible for the resistance of CTCL cells to the anti‐cancer drugs chlorambucil and sulindac. Copyright © 2003 John Wiley & Sons, Ltd.
The Multifaceted Proprotein Convertases: Their Unique, Redundant, Complementary, and Opposite Functions*

The secretory proprotein convertase (PC) family comprises nine members: PC1/3, PC2, furin, PC4, PC5/6, PACE4, PC7, SKI-1/S1P, and PCSK9. The first seven PCs cleave their substrates at single or paired basic residues, and SKI-1/S1P cleaves its substrates at non-basic residues in the Golgi. PCSK9 cleaves itself once, and the secreted inactive protease escorts specific receptors for lysosomal degradation. It regulates the levels of circulating LDL cholesterol and is considered a major therapeutic target in phase III clinical trials. In vivo, PCs exhibit unique and often essential functions during development and/or in adulthood, but certain convertases also exhibit complementary, redundant, or opposite functions.
Population genomic structure and linkage disequilibrium analysis of South African goat breeds using genome-wide SNP data.

The sustainability of goat farming in marginal areas of southern Africa depends on local breeds that are adapted to specific agro-ecological conditions. Unimproved non-descript goats are the main genetic resources used for the development of commercial meat-type breeds of South Africa. Little is known about genetic diversity and the genetics of adaptation of these indigenous goat populations. This study investigated the genetic diversity, population structure and breed relations, linkage disequilibrium, effective population size and persistence of gametic phase in goat populations of South Africa. Three locally developed meat-type breeds of the Boer (n = 33), Savanna (n = 31), Kalahari Red (n = 40), a feral breed of Tankwa (n = 25) and unimproved non-descript village ecotypes (n = 110) from four goat-producing provinces of the Eastern Cape, KwaZulu-Natal, Limpopo and North West were assessed using the Illumina Goat 50K SNP Bead Chip assay. The proportion of SNPs with minor allele frequencies >0.05 ranged from 84.22% in the Tankwa to 97.58% in the Xhosa ecotype, with a mean of 0.32 ± 0.13 across populations. Principal components analysis, admixture and pairwise FST identified Tankwa as a genetically distinct population and supported clustering of the populations according to their historical origins. Genome-wide FST identified 101 markers potentially under positive selection in the Tankwa. Average linkage disequilibrium was highest in the Tankwa (r(2) = 0.25 ± 0.26) and lowest in the village ecotypes (r(2) range = 0.09 ± 0.12 to 0.11 ± 0.14). We observed an effective population size of <150 for all populations 13 generations ago. The estimated correlations for all breed pairs were lower than 0.80 at marker distances >100 kb with the exception of those in Savanna and Tswana populations. This study highlights the high level of genetic diversity in South African indigenous goats as well as the utility of the genome-wide SNP marker panels in genetic studies of these populations.
Altered emotional morality in frontotemporal dementia

Introduction. Frontotemporal dementia (FTD), a disorder characterised by abnormal social behaviour and potential sociopathy, provides a window to the neurobiology of moral behaviour. This study investigated the basis of altered moral judgements in patients with FTD. Methods. We administered an inventory of moral knowledge, five “reasoned” moral dilemmas, and five “emotional” moral dilemmas where subjects may cause direct harm to another through their own actions, to 21 patients with FTD compared to 21 comparably mildly impaired patients with Alzheimer's disease (AD) and 21 normal controls. Among the FTD patients, the results were compared to findings on functional neuroimaging. Results. All groups showed retention of knowledge for moral behaviour and the ability to make reasoned moral judgements. In contrast to the other groups, the FTD patients were altered in their ability to make emotional moral judgements. Among the FTD patients, the altered moral judgements corresponded to right hemisphere frontotemporal involvement. Conclusions. In FTD patients, these findings suggest a decreased emotional responsiveness to others and a tendency to respond to moral dilemmas in a calculated fashion. Such a disturbance may result from ventromedial frontal dysfunction in FTD and supports the presence of a “morality” network in the brain, predominantly in the right hemisphere.
Patients with fatigue in general practice: a prospective study.

OBJECTIVE--To describe the characteristics of patients attending their general practitioners and complaining of fatigue or being "tired all the time. " DESIGN--Prospective study of cohort aged 16 years and older with follow up at two weeks and by questionnaires at two and six months. SUBJECTS--220 patients (164 women) with mean age 43 years and an age-sex matched comparison group. SETTINGS--Doctors and patients in four practices in Lancashire, Mid Glamorgan, Suffolk, and Surrey. MAIN OUTCOME MEASURES--General clinical data, results from standard group of laboratory tests, fatigue questionnaire, and 12 item general health questionnaire. RESULTS--Over twice as many patients with fatigue had high scores on the health questionnaire compared with the comparison group (156 (75%) v 69 (34%)). Results of laboratory tests were abnormal and contributed to the diagnosis in 19 patients. 59 out of 102 patients who responded had high fatigue scores six months later. Patients with persistent fatigue were more likely to have a history of anxiety or depression and to have had fatigue for more than three months on entry to the study. CONCLUSIONS--Women are particularly at risk of fatigue. The outcome is better if patients have had symptoms for three months or less or there is no history of emotional illness.
Survival and neurodevelopmental outcome of young children with medulloblastoma at St Jude Children's Research Hospital.

PURPOSE Young children treated for medulloblastoma are at especially high risk for morbidity and mortality from their disease and therapy. This study sought to assess the relationship, if any, between patient outcome and M stage. Neuropsychologic and endocrine outcomes were also assessed. PATIENTS AND METHODS Twenty-nine consecutively diagnosed infants and young children were treated for medulloblastoma at St Jude Children's Research Hospital between November 1984 and December 1995. All patients were treated with the intent of using postoperative chemotherapy to delay planned irradiation. RESULTS The median age at diagnosis was 2.6 years. Six patients completed planned chemotherapy without progressive disease and underwent irradiation at completion of chemotherapy. Twenty-three children experienced disease progression during chemotherapy and underwent irradiation at the time of progression. The 5-year overall survival rate for the entire cohort was 51% +/- 10%. The 5-year progression-free survival rate was 21% +/- 8%. M stage did not impact survival. All patients lost cognitive function during and after therapy at a rate of -3.9 intelligence quotient points per year (P =.0028). Sensory functions declined significantly after therapy (P =.007). All long-term survivors required hormone replacement therapy and had growth abnormalities. CONCLUSION The majority of infants treated for medulloblastoma experienced disease progression during initial chemotherapy. However, more than half of these patients can be cured with salvage radiation therapy, regardless of M stage. The presence of metastatic disease did not increase the risk of dying from medulloblastoma. All patients treated in this fashion have significant neuropsychologic deficits. Our experience demonstrates that medulloblastoma in infancy is a curable disease, albeit at a significant cost.
Lipid Transport in the Developing Bovine Follicle: Messenger RNA Expression Increases for Selective Uptake Receptors and Decreases for Endocytosis Receptors

Abstract Differences in rates of steroid production and secretion will, eventually, determine the developmental rates of ovarian follicles. The major supply of cholesterol, the precursor for steroid and androgen biosynthesis, to ovarian cells is from circulating lipoproteins via membrane receptors from the low density lipoprotein receptor (LDL) superfamily. This occurs by either endocytosis, which has been described for very low density lipoprotein receptors (VLDLr), for LDL receptors (LDLr), and by the selective uptake pathway described for the scavenger receptor class B type 1 receptor (SRB1) and the recently described ovarian receptor, lipoprotein receptor-related protein 8 (LRP8). In this study, the mRNA expression of these four cholesterol receptors in bovine ovarian cells was determined at different stages of follicular development. In small antral follicles, mRNA expression of the endocytosis receptors was higher than in large antral follicles. Expression of LRP8 mRNA increased linearly with follicular size together with an increase in LDL, VLDL, and cholesterol concentrations in the follicular fluid. SRB1 mRNA expression tended to increase with follicular diameter. Because different mRNA expression patterns were found for the two types of receptor, this may imply different regulation of cholesterol supply at different stages of follicular development. Accumulation of LDL and VLDL particles in the follicular fluid of large antral follicles may enhance cholesterol availability for the intense steroidogenic activity that is essential at these stages.
Altered Neuronal Activity Rhythm and Glutamate Receptor Expression in the Suprachiasmatic Nuclei of Trypanosoma brucei‐infected Rats

The parasites Trypanosoma brucei cause African trypanosomiasis (sleeping sickness), a severe neuropsychiatric disease with marked disturbances of sleep-wake alternation. The sites of brain lesions are not well characterized. The present experimental investigation is focused on the hypothalamic suprachiasmatic nuclei, which play a role of a biological clock entraining endogenous rhythms in the mammalian brain. The electrophysiological properties of these neurons were analyzed in slice preparations from trypanosome-infected rats. The neuronal spontaneous activity, which shows a circadian oscillation, was markedly altered in the infected animals, displaying a reduced firing rate and phase advance of its circadian peak. The direct retinal fibers, which play a pivotal role in entrainment of the circadian pacemaker, displayed a normal density and distribution in the suprachiasmatic nuclei of infected animals after intraocular tracer injections in vivo. At the postsynaptic level, immunohistochemistry and Western blotting revealed in the suprachiasmatic nuclei of infected rats a selective decrease of the expression of glutamate AMPA GluR2/3 and NMDAR1 receptor subunits that gate retinal afferents. These data disclose an impairment of the neuronal functions in the biological clock in African trypanosomiasis, and may serve to unravel functional and molecular mechanisms behind endogenous rhythm disturbances.
Medium-chain versus long-chain triacylglycerol emulsion hydrolysis by lipoprotein lipase and hepatic lipase: implications for the mechanisms of lipase action.

To explore how enzyme affinities and enzyme activities regulate hydrolysis of water-insoluble substrates, we compared hydrolysis of phospholipid-stabilized emulsions of medium-chain (MCT) versus long-chain triacylglycerols (LCT). Because substrate solubility at the emulsion surface might modulate rates of hydrolysis, the ability of egg yolk phosphatidylcholine to solubilize MCT was examined by NMR spectroscopy. Chemical shift measurements showed that 11 mol % of [13C]carbonyl enriched trioctanoin was incorporated into phospholipid vesicles as a surface component. Similar methods with [13C]triolein showed a maximum solubility in phospholipid bilayers of 3 mol % (Hamilton & Small, 1981). Line widths of trioctanoin surface peaks were half that of LCT, and relaxation times, T1, were also shorter for trioctanoin, showing greater mobility for MCT in phospholipid. In assessing the effects of these differences in solubility on lipolysis, we found that both purified bovine milk lipoprotein lipase and human hepatic lipase hydrolyzed MCT at rates at least 2-fold higher than for LCT. With increasing concentrations of MCT, saturation was not reached, indicating low affinities of lipase for MCT emulsions, but with LCT emulsion incubated with lipoprotein lipase, saturation was reached at relatively low concentration, demonstrating higher affinity of lipase for LCT emulsions. Differences in affinity were also demonstrated in mixed incubations where increasing amounts of LCT emulsion resulted in decreased hydrolysis of MCT emulsions. Increasing MCT emulsion amounts had little or no effect on LCT emulsion hydrolysis. (ABSTRACT TRUNCATED AT 250 WORDS)
Maternal immune correlates of protection from human cytomegalovirus transmission to the fetus after primary infection in pregnancy

Immune control of primary human cytomegalovirus (HCMV) infection appears to depend on the interaction of humoral and T‐cell responses. In this review, we have separately explored the 2 arms of the immune response to primary HCMV infection in HCMV‐seronegative pregnant women transmitting (T) or not transmitting (NT) the infection to the fetus, with the objective of correlating the immune risk factors associated with vertical HCMV transmission. As for the humoral response, the following findings were documented: (i) in competitive binding assays, antibody titers to different antigenic sites of the gH pentamer complex were significantly lower in T compared with NT women; (ii) in addition, the number of neutralization sites recognized by T was significantly lower compared with NT women; (iii) the plaque formation inhibition assay showed a faster kinetics and a higher titer in NT women. As for T‐cell immunity, the delayed expression of 3 immunological parameters (lymphoproliferative response, CD45RA reexpression in both CD4+ and CD8+ HCMV‐specific T cells, and interleukin‐2 production by HCMV‐specific CD4+ T cells) were significantly associated with vertical transmission. This overview provides important information at the population level, which may help to inform the evaluation of interventions such as vaccination or treatments designed to interrupt intrauterine transmission of HCMV during primary infection. However, although we are waiting for an HCMV vaccination to become available, we emphasize that none of these parameters can be prognostically used on an individual basis because of the great variation in values among women.
Innovation Credit: When and why do group members give their leaders license to deviate from group norms?

Leaders of organizations, teams, and groups are often required to change the group’s direction or forge an innovative path. Examples can be seen in political and organizational arenas on a daily basis. The USA has seen the appointment of a new President, President Obama, who won with a slogan of “Change we can believe in”. Organizations also often face the challenge of change by bringing in a new leader or CEO. For example, the UK broadcaster Channel 4 have recently appointed a new CEO, David Abraham, who has been quoted as saying he will manage a period of uncertainty in the organization through “the biggest creative transformation” (Burrell, 2010). When and why do groups allow leaders to innovate? Why are new leaders often associated with changes in direction? This chapter will explore these issues and examine what happens when leaders resist the tide of opinion within their groups.
Artificial nutritional support in chronic hemodialysis patients: a narrative review.

OBJECTIVE Malnutrition is common in hemodialysis (HD) patients and is a powerful predictor of morbidity and mortality. While much progress has been made in identifying the causes and pathogenesis of malnutrition in patients on HD, no consensus has been reached on its management. Nutritional counseling, appetite stimulants, growth hormone, androgenic anabolic steroids, and anti-inflammatory drugs have been tested with contradictory and nonconclusive results. Oral nutritional supplements (ONSs) and intradialytic parenteral nutrition (IDPN) also have been studied. DESIGN/SETTING/PATIENTS We searched the MEDLINE and PubMed databases for randomized clinical trials, comparative nonrandomized clinical trials, studies with patients who were controls for themselves, and single-arm studies on ONS and IDPN. Thirty-four studies (3223 patients) have been identified and analyzed. Seventeen studies were on ONS (778 patients) and 17 were on IDPN (2475 patients). RESULTS ONS may improve serum albumin levels and/or other nutritional parameters, whereas there are insufficient data on clinical outcome. IDPN improves serum albumin and body weight. CONCLUSION Data on survival are conflicting but the only study with an adequate population sample shows that IDPN does not influence survival. Randomized, controlled studies are needed to clarify the role of ONS and IDPN in the treatment of malnutrition in HD.
Evaluation of A New Bolus Tracking–Based Algorithm for Predicting A Patient-Specific Time of Arterial Peak Enhancement in Computed Tomography Angiography

ObjectivesThe aim of this study was to evaluate the systematic and random errors of a new bolus tracking–based algorithm that predicts a patient-specific time of peak arterial enhancement and compare its performance with a best-case scenario for the current bolus tracking technique. Materials and MethodsAll local institutional review boards approved this retrospective study, in which the test bolus signals of cardiac computed tomography angiographies of 72 patients (46 men; median age, 62 years [range, 31–81 years]) were used to simulate contrast enhancement curves for a multitude of injection protocols with iodine delivery rates (IDRs) varying between 0.5 and 2.5 gI/s, injection durations between 4 and 30 seconds, and tube voltages of 100 and 120 kV. From these simulated curves, bolus tracking signals with statistical errors of 4 Hounsfield units (HU) (standard deviation) were derived with trigger values of 100 and 150 HU at 100 and 120 kV, respectively. The new algorithm then matched the actual bolus tracking signal with a database of expected enhancement curves for that particular injection protocol, taking into account population-averaged blood circulation characteristics with variations in patient weight and cardiac output. Posttrigger delays (PTDs) were calculated as the time difference between the last bolus tracking point and the time of peak enhancement. The systematic and random errors between the predicted and true PTDs were assessed and compared with a best-case scenario for the current bolus tracking method. ResultsWith the current bolus tracking technique, interpatient variations decrease with higher IDRs and earlier triggering (lower tube voltage and/or lower trigger value), and the true PTDs increase linearly with injection duration. Compared with the current bolus tracking method, the systematic and random errors of the algorithm-predicted PTDs are smaller, do not depend on the IDR, and are predictable over a large range of total iodine doses. The median difference between the true and algorithm-predicted PTD is less than ±1 second for all IDRs and injection durations, and the algorithm was able to predict patient-specific PTDs within ±2 seconds from the true PTD in more than 90% of patients for almost all injection protocols. ConclusionsThe new algorithm can robustly predict a patient-specific time of arterial peak enhancement and is better than a best-case scenario for the current bolus tracking technique because interpatient variations are taken into account. It offers a new framework for scan timing optimization and can potentially be used for personalized scan timing in real time.
Fast algorithm for statistical phrase/accent command estimation based on generative model incorporating spectral features

An important challenge in speech processing involves extracting non-linguistic information from a fundamental frequency (F0) contour of speech. We propose a fast algorithm for estimating the model parameters of the Fujisaki model, namely, the timings and magnitudes of the phrase and accent commands. Although a powerful parameter estimation framework based on a stochastic counterpart of the Fujisaki model has recently been proposed, it still had room for improvement in terms of both computational efficiency and parameter estimation accuracy. This paper describes our two contributions. First, we propose a hard expectation-maximization (EM) algorithm for parameter inference where the E step of the conventional EM algorithm is replaced with a point estimation procedure to accelerate the estimation process. Second, to improve the parameter estimation accuracy, we add a generative process of a spectral feature sequence to the generative model. This makes it possible to use linguistic or phonological information as an additional clue to estimate the timings of the accent commands. The experiments confirmed that the present algorithm was approximately 16 times faster and estimated parameters about 3% more accurately than the conventional algorithm.
A framework for analyzing coordination in agricultural value chains: Evidence from cereal markets in Mali

A FRAMEWORK FOR ANALYZING COORDINATION IN AGRICULTURAL VALUE CHAINS: EVIDENCE FROM CEREAL MARKETS IN MALI By Ryan Vroegindewey Firms, farmers, and development actors view improved value chain governance as part of the solution for coordinating the actions of African farmers with the demands of emerging market segments. An important diversity of vertical coordination governance structures (such as contracting arrangements) and horizontal coordination governance structures (such as farmer organizations) are possible for linking farmers with such segments. The objective of this thesis is to better understand these governance structures and the conditions under which each is most cost-effective for achieving coordination. Building on the transaction cost economics literature, a framework that represents buyers’ and farmers’ governance structure choice is first developed. The framework is then empirically tested using a unique dataset from fifteen rice, maize, and millet/sorghum value chain case studies from Mali. Results show that marketing contracts and marketing cooperatives is the dominant governance structure pair used to coordinate farmers with higher-revenue segments in these cases. Transaction cost characteristics do influence buyers’ and farmers’ governance structure choice; additionally, time, social incentives, and the presence of other transaction cost-reducing governance structures may also be significant. Copyright by RYAN VROEGINDEWEY 2015