Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Method for Prosody Prediction in Voice Conversion

Most of the published voice conversion schemes do not consider detailed prosody modeling but only control the F0 level and range. However, the detailed prosody can also carry a significant amount of speaker identity related information. This paper introduces a new method for converting the prosody in voice conversion. A syllable-based prosodic codebook is used to predict the converted F0 using not only the source contour but also linguistic information and segmental durations. The selection of the most suitable target contour is carried out using a trained classification and regression tree. The F0 contours in the codebook are represented in a transformed domain which allows compression and fast comparison. The performance of the prosodic conversion is evaluated in a real voice conversion system. The results indicate a significant improvement in speaker identity and naturalness when compared to GMM (Gaussian mixture model) based pitch prediction approach.
The electron microscope and the antibody: trends in the diagnosis of epidermolysis bullosa

The diagnosis of the congenital forms of epidermolysis bullosa (EB) by electron microscopy (EM) provides examples of both the usefulness and the limitations of EM in clinical dermatology. There is a vital need by clinicians and involved families for reliable information: though rare, even the milder forms of these mechanobullous disorders cause physical distress and developmental problems, whilst the severer forms are mutilating and even life-threatening. Precise differentiation between the forms with autosomal dominant and autosomal recessive inheritance is obviously essential for genetic counselling. However, the classification of EB varieties on clinical grounds is not universally agreed upon, and considerable overlap between physical signs exists, particularly in the early stages of the disease. Family histories are not always available and incomplete penetrance and spontaneous mutation are also possibilities. Electron microscopy has, therefore, come to be the most reliable means of establishing the main, genetically distinct, categories of EB. Numerous studies over the last 20 years (reviewed by Eady & Tidman, 1983, and Kero & Niemi, 1986) have shown that these categories can be identified by differences in the plane of separation within the basement membrane zone (BMZ), and in some cases by quantitative or quantitative modifications to BMZ components such as hemidesmosomes and anchoring fibrils (AF). The ultrastructural classification has been refined further by more recent applications of morphometric analysis (Tidman & Eady, 1985). These studies have exposed an area of uncertainty in the diagnosis of dystrophic EB (DEB), involving two variants with different modes of inheritance. One subgroup of recessive DEB (RDEB) which is relatively mild and localized has been shown to be clinically and ultrastructurally similar to typical dominant DEB (DDEB). Morphometric analysis extended this similarity to the distribution of AF, which were reduced in both cases. AF were, as previously reported, absent in the more severe RDEB form; however, the nature of AF and the sampling errors inherent in EM make even this distinction difficult to make. AF have no consistent ultrastructural features and their distribution even within a single biopsy is extremely heterogeneous (Tidman & Eady, 1984). Secondary degradation of AF following blister formation can also occur. As a result, even in an ideal biopsy the confirmation of total absence of AF (severe generalized RDEB) as opposed to their sparse occurrence (localized RDEB) may require the examination of considerable lengths of the dermal-epidermal junction. In the dystrophic category of EB, then, we have one distinction which it is technically difficult for EM to make, and another to which EM makes no contribution. For this reason, recent reports of monoclonal antibodies directed towards BMZ components involved in the dystrophic EB group have been particularly welcome. KF-i, which recognizes a non-collagenous
Users’ Knowledge About Adverse Effects of Non-steroidal Anti-inflammatory Drugs in Tirana, Albania

Aim: To assess the level of knowledge of the adult users of non-steroidal anti-inflammatory drugs (NSAIDs) regarding their side effects and the socio-demographic factors associated with the use of these drugs in the adult population of Albania. Methods: This was a cross-sectional study including a representative sample of 199 individuals aged ≥18 years (77% women; overall mean age: 30.3±10.0 years; overall response rate: 90%) who were users of NSAIDs recruited in ten different pharmacies in Tirana municipality during April-May 2015. A self-administered questionnaire contained basic socio-demographic information and questions about NSAIDs use, their types, participants’ knowledge about NSAIDs side effects and their interaction with other drugs. Results: In 56% of the cases, NSAIDs were taken by participants’ own decisions, whereas in about 29% of the cases these drugs were prescribed by physicians. Acetaminophen, ketoprofen and ibuprofen were the most frequently used NSAIDs. Overall, 51% of participants thought NSAIDs could cause allergic reactions, whereas one third or fewer were aware of each of the following side effects: upper and lower gastrointestinal bleeding, hypertension, gastritis, kidney failure, myopathy, osteoporosis. About one third of participants were aware of NSAIDs-other drug interactions, whereas some of them were already taking contraindicated drugs. No significant differences were noticed regarding sex, age, educational level, employment status and marital status, with very few exceptions. Conclusion: Our findings indicate limited knowledge about NSAIDs side effects and their interaction with other drugs among the Albania adult population, which is a cause of concern.
Subthreshold depression: Characteristics and risk factors among vulnerable elders

Objectives: This study examines symptoms of subthreshold depression among older adults in congregate housing, compared with their nondepressed peers, and tests a conceptual model of subthreshold depression. Hypotheses included that subthreshold depression would be characterized and distinguished by low energy, social withdrawal, and depletion, rather than sadness, and that subthreshold depressed elders would be distinguished by poorer health and functioning, loneliness, and grieving a recent loss. Method: A self-administered survey was followed by a diagnostic interview by telephone to (N = 166) white and African-American residents of independent and assisted living apartments from six retirement communities, average age 82.9 years. The Mini International Neuropsychiatric Interview (MINI) determined depression status. The 30-item Geriatric Depression Scale was used to measure symptoms. Results: Forty-six individuals (27.7%) were identified as subthreshold depressed, seven as suffering from major depression, and 113 as non-depressed. Subthreshold depression was characterized by low energy, difficulty with initiative, worries about the future, lack of positive affect, sadness and irritability. Negative affect symptoms such as sadness and irritability best discriminated the subthreshold group from the nondepressed. Risk factors for subthreshold depression in this sample included less education, lower socio-economic status, African-American race, grieving, and social loneliness. Conclusion: Subthreshold depression in this group of residents of congregate housing was similar to the depletion experienced by many nondepressed elders, but further characterized by negative affect and lack of hope for the future. Social factors, such as socioeconomic status and personal losses, constituted greater risks for subthreshold depression than did health and functioning.
A New Macroevolutionary Algorithm for Nonlinear Constrained Optimization Problems

A new macroevolutionary algorithm is proposed for complex nonlinear constrained optimization problems. The proposed algorithm combines uniform experimental design, simulated annealing and macroevolutionary algorithm such that it get a good balance between exploration and exploitation, therefore it has a very good performance. Constraints are handled by embodying them in an augmented Lagrangian function, where the penalty parameters and multipliers are adapted as the execution of the algorithm proceeds. The validity of the proposed algorithm is illustrated by solving some benchmark problems
Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer.

PURPOSE Breast cancer frequently overexpresses the product of the HER2 proto-oncogene, a 185-kd growth factor receptor (p185HER2). The recombinant humanized monoclonal antibody (rhuMAb) HER2 has high affinity for p185HER2 and inhibits the growth of breast cancer cells that overexpress HER2. We evaluated the efficacy and toxicity of weekly intravenous administration of rhuMAb HER2 in patients with HER2-overexpressing metastatic breast cancer. PATIENTS AND METHODS We treated 46 patients with metastatic breast carcinomas that overexpressed HER2. Patients received a loading dose of 250 mg of intravenous rhuMAb HER2, then 10 weekly doses of 100 mg each. Patients with no disease progression at the completion of this treatment period were offered a maintenance phase of 100 mg/wk. RESULTS Study patients had extensive metastatic disease, and most had received extensive prior anticancer therapy. Adequate pharmacokinetic levels of rhuMAb HER2 were obtained in 90% of the patients. Toxicity was minimal and no antibodies against rhuMAb HER2 were detected in any patients. Objective responses were seen in five of 43 assessable patients, and included one complete remission and four partial remissions (overall response rate, 11.6%; 95% confidence interval, 4.36 to 25.9). Responses were observed in liver, mediastinum, lymph nodes, and chest wall lesions. Minor responses, seen in two patients, and stable disease, which occurred in 14 patients, lasted for a median of 5.1 months. CONCLUSION rhuMAb HER2 is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers that had received extensive prior therapy. This is evidence that targeting growth factor receptors can cause regression of human cancer and justifies further evaluation of this agent.
Privacy-preserving data publishing

The success of data mining relies on the availability of high quality data. To ensure quality data mining, effective information sharing between organizations becomes a vital requirement in today’s society. Since data mining often involves person-specific and sensitive information like medical records, the public has expressed a deep concern about their privacy. Privacy-preserving data publishing is a study of eliminating privacy threats while, at the same time, preserving useful information in the released data for data mining. It is different from the study of privacy-preserving data mining which performs some actual data mining task. This thesis identifies a collection of privacy threats in real life data publishing, and presents a unified solution to address these threats.
The underwater GPS problem

It is well known that the ordinary Global Positioning System (GPS) fails to provide location and time information under water. The reason is that the electromagnetic signals from the orbiting satellites are heavily damped in water and hence can not be detected by the receiver in most cases of interest. Acoustic waves are the canonical alternative, and there exist a variety of acoustically based systems. It is important to estimate the accuracy of position estimates and if possible correct for the errors. This is done systematically in the GPS case by the concept of Dilution Of Precision (DOP), and is also the natural approach underwater. The main issue presented below is a discussion and analysis of the concept of DOP in the context of Underwater Positioning Systems (UPS). This includes statistical models that differ from the one canonically used. Some of the sources of errors in the UPS case differs substantially from the GPS case. It is in particular demonstrated that the maximum likelihood estimator is biased. Alternative estimators, including an unbiased estimator and an optimal estimator, are discussed. The results are also briefly discussed in the context of an actual model experiment with ultrasound in air. A side effect of this is the demonstration of certain issues which have been ignored in the previous general discussion. The experiment also indicates that the results are relevant in other contexts. Other important classes of examples are given by Real Time Locating Systems as defined by the standard ISO/IEC 24730, and by Wireless Personal Area Networks as described in the IEEE 802.15 standard. These other contexts also provide most useful sources for research publications with results of relevance for UPS, and more generally for underwater communication systems.
Excitotoxic lesions of the rhinal cortex in the baboon differentially affect visual recognition memory, habit memory and spatial executive functions

To specify the functional role of the rhinal cortex, baboons with bilateral excitotoxic lesions of the rhinal cortex (RH group) were tested on a series of computerized memory and learning tasks. Preoperatively, they were trained to and then tested on a delayed nonmatching‐to‐sample (DNMS) task with trial‐unique stimuli. Postoperatively, this visual recognition memory task was given twice. As compared to a sham‐operated group, the RH group showed good retention of rule learning and were unimpaired on the Delay memory subtest. Performance on the List Length memory subtest was, however, severely impaired at both postoperative evaluations, with a significant negative correlation between cognitive performance and neuronal loss in rhinal areas. Visual habit memory and spatial working memory were assessed postoperatively only, using a concurrent discrimination learning task and both a delayed‐response task (with a two‐ and four‐location choice) and a delayed alternation task, respectively. The RH group was unimpaired on the first two tasks and was even faster than the controls in learning the delayed‐response task with four locations. Finally, most RH baboons failed to learn the delayed alternation task within the limits of testing. These results indicate that neuronal loss in the rhinal cortex is sufficient to impair visual recognition memory, and extend the implication of this area to spatial executive functions. Furthermore, the observation of impaired recognition memory and executive processes with preserved procedural memory and retrograde memory suggests that damage to the rhinal cortex probably participates in the cognitive deficits typical of the early stages of Alzheimer's disease.
Acculturation, Dietary Acceptability, and Diabetes Management among Chinese in North America

Immigrants to a new country face many challenges when diagnosed with type 2 diabetes, a chronic disease with a complex treatment involving both medical and behavioral interventions. These challenges will depend upon the extent to which the patient has adapted to the new country’s social and cultural norms, as well as individual factors such as age, education, and gender. This adaptation is termed acculturation. With respect to nutritional interventions for type 2 diabetes, uptake and adherence over the long term will depend upon overall health literacy, the cultural acceptability of the recommended diet. This review has focused on acculturation and its effects on diabetes management in ethnic Chinese in North America as an example of one populous minority and the challenges faced in adopting nutritional recommendations. Research directions and practical considerations are suggested.
Serotonergic modulation of two potassium currents in the pleural sensory neurons of Aplysia.

1. The properties of membrane currents that were modulated by serotonin (5-HT) were investigated with two-electrode voltage-clamp techniques in sensory neuron somata isolated from the pleural ganglion of Aplysia californica. The modulatory effects of 5-HT were revealed by computer subtraction of current responses elicited in the presence of 5-HT from current responses elicited prior to the application of 5-HT. The complexities of the resulting 5-HT difference currents (I5-HT) suggested that 5-HT modulated more than one component of membrane current. 2. The 5-HT difference currents appeared to have at least two distinct components. One component was clearly evident at membrane potentials more negative than -10 mV was relatively voltage independent and did not inactivate. A second component was activated at membrane potentials more positive than -10 mV, had complex kinetics, and was highly voltage dependent. In an attempt to identify the membrane currents that were modulated by 5-HT, we compared the pharmacologic sensitivity of I5-HT to that of previously described K+ currents. 3. The two components of I5-HT had different sensitivities to agents that block K+ currents. The relatively voltage-independent component of I5-HT was not blocked by 2 mM 4-aminopyridine (4-AP) and was relatively insensitive to tetraethylammonium (TEA) (estimated Kd of 92 mM). In contrast, the voltage-dependent component of I5-HT was blocked by 4-AP (2 mM) and moderate concentrations of TEA (estimated Kd of 5 mM). 4. The K+ current blockers that were used to examine I5-HT were also used to examine voltage-activated membrane currents. Externally applied TEA blocked the delayed or voltage-dependent K+ current (IK.V) with an estimated dissociation constant (Kd) of 8 mM and a membrane current similar to the Ca2+-activated K+ current (IK.Ca) with an estimated Kd of 0.4 mM. In addition, externally applied 4-AP (2 mM) blocked IK.V. Thus TEA and 4-AP were equipotent in blocking both IK.V and the voltage-dependent component of I5-HT. 5. The suggestion that I5-HT contained multiple components was supported further by examining the modulatory effects of adenosine 3',5'-cyclic monophosphate (cAMP) that mediates some actions of 5-HT on membrane currents in these cells. cAMP difference currents (IcAMP) were similar to the relatively voltage-independent component of I5-HT. The subsequent addition of 5-HT to solutions already containing cAMP resulted in 5-HT difference currents similar to the voltage-dependent component of I5-HT. (ABSTRACT TRUNCATED AT 400 WORDS)
Three-Year Outcomes Associated With Embolic Protection in Saphenous Vein Graft Intervention: Results in 49 325 Senior Patients in the Medicare-Linked National Cardiovascular Data Registry CathPCI Registry

Background—Information is limited on contemporary use and outcomes of embolic protection devices (EPDs) in saphenous vein graft interventions. Methods and Results—We formed a longitudinal cohort (2005–2009; n=49 325) by linking National Cardiovascular Data Registry CathPCI Registry to Medicare claims to examine the association between EPD use and both procedural and long-term outcomes among seniors (65+ years), adjusting for clinical factors using propensity and instrumental variable methodologies. Prespecified high-risk subgroups included acute coronary syndrome and de novo or graft body lesions. EPDs were used in 21.2% of saphenous vein grafts (median age, 75; 23% women) and were more common in acute coronary syndrome (versus non–acute coronary syndrome; 22% versus 19%), de novo (versus restenotic; 22% versus 14%), and graft body lesions (versus aortic and distal anastomosis; 24% versus 20% versus 8%, respectively). EPDs were associated with a slightly higher incidence of procedural complications, including no reflow (3.9% versus 2.8%; P<0.001), vessel dissection (1.3% versus 1.1%; P=0.05), perforation (0.7% versus 0.4%; P=0.001), and periprocedural myocardial infarction (2.8% versus 1.8%; P<0.001). By 3 years, death, myocardial infarction, and repeat revascularization occurred in 25%, 15%, and 30% of cases, respectively. EPD use was associated with a similar adjusted risk of death (propensity score–matched hazard ratio, 0.96; 95% confidence interval, 0.91–1.02), myocardial infarction (propensity score–matched hazard ratio, 1.00; 95% confidence interval, 0.93–1.09), and repeat revascularization (propensity score–matched hazard ratio, 1.02; 95% confidence interval, 0.96–1.08) in the overall cohort and high-risk subgroups. Conclusions—In this contemporary cohort, EPDs were used more commonly among patients with high-risk clinical indications, yet there was no evidence of improved acute- or long-term outcomes. Further prospective studies are needed to support routine EPD use.
Gene repression by minimal lac loops in vivo

The inflexibility of double-stranded DNA with respect to bending and twisting is well established in vitro. Understanding apparent DNA physical properties in vivo is a greater challenge. Here, we exploit repression looping with components of the Escherichia coli lac operon to monitor DNA flexibility in living cells. We create a minimal system for testing the shortest possible DNA repression loops that contain an E. coli promoter, and compare the results to prior experiments. Our data reveal that loop-independent repression occurs for certain tight operator/promoter spacings. When only loop-dependent repression is considered, fits to a thermodynamic model show that DNA twisting limits looping in vivo, although the apparent DNA twist flexibility is 2- to 4-fold higher than in vitro. In contrast, length-dependent resistance to DNA bending is not observed in these experiments, even for the shortest loops constraining <0.4 persistence lengths of DNA. As observed previously for other looping configurations, loss of the nucleoid protein heat unstable (HU) markedly disables DNA looping in vivo. Length-independent DNA bending energy may reflect the activities of architectural proteins and the structure of the DNA topological domain. We suggest that the shortest loops are formed in apical loops rather than along the DNA plectonemic superhelix.
Insulin-like Growth Factor Binding Proteins from Cultured Human Fibroblasts

Specific, high affinity insulin-like growth factor (IGF) binding proteins are secreted by human fibroblasts in culture. By multiple criteria, the species of IGF binding proteins produced by human fibroblasts are distinct from the HepG2/amniotic fluid IGF binding protein, but share many characteristics with the growth hormone-dependent IGF binding protein forms predominant in normal adult human plasma. Treatment of cultured human fibroblasts with growth hormone produced an increase in IGF binding protein activity in the medium, while addition of glucocorticoids markedly diminished IGF binding activity. Insulin, epidermal growth factor, platelet-derived growth factor, and progesterone had no effect on IGF binding activity in fibroblast media. In comparison, HepG2 IGF binding activity was enhanced by progesterone, decreased by insulin, and unaffected by growth hormone or glucocorticoid treatment. Five molecular forms of IGF binding proteins were identified by Western ligand blots in human fibroblast conditioned medium, with Mr = 41,500, 37,000, 32,000, 28,000, and 23,000. In human fibroblast conditioned medium, the Mr = 41,500 and 37,000 IGF binding protein species were abundant, as in normal human plasma, with a major Mr = 23,000 form which was a minor component in plasma.
Boys’ underachievement – challenging some assumptions about boys

W Introduction There has been much interest in and debate about boys’ achievement in the past few years. Much of it has been focused on the results of boys in public examinations and key stage assessments in comparison with girls. Research has shown that girls are outperforming boys in national assessment outcomes at ages seven, eleven and fourteen, and do better in a wide range of subjects at GCSE level (Ellwood and Comber, 1995). The research is unclear about examination performance at age eighteen, but more girls are getting top grades and more are going on into higher education.