Miracle-dz/UniFAR-FTUs huggingface dataset:
Low-Jitter Design for Second-Order Time-to-Digital Converter Using Frequency Shift Oscillators

SUMMARY We present a low-jitter design for a 10-bit second-order frequency shift oscillator time-to-digital converter (FSOTDC). As described herein, we analyze the relation between performance and FSOTDC parameters and provide insight to support the design of the FSOTDC. Re-sults show that an oscillator jitter limits the FSOTDC resolution, particularly during the ﬁrst stage. To estimate and design an FSOTDC, the frequency shift oscillator requires an inverter of a certain size. In a standard 65-nm CMOS process, an SNDR of 64dB is achievable at an input signal frequency of 10kHz and a sampling clock of 2MHz. Measurements of the test chip conﬁrmed that the measurements match the analyses.
Repeat‐induced point mutation (RIP) in Magnaporthe grisea: implications for its sexual cycle in the natural field context

Repeat‐induced point mutation (RIP) is a process that detects DNA duplications and peppers their sequences with C:G to T:A transitions in the sexual phase of the life cycle. So far, this unique mechanism has been identified as a currently active process in only two fungal species, Neurospora crassa and Podospora anserina. To determine whether a RIP‐like process operates in the plant pathogenic fungus Magnaporthe grisea, the retrotransposon MAGGY and the hygromycin B phosphotransferase gene were introduced into the fungus as multiple transgenes and examined for sequence alterations after a cross. Frequent C:G to T:A transitions in the transgenes were found in the descendants, preferentially in (A/Tp)Cp(A/T) contexts, suggesting that a process similar to RIP functions in M. grisea. We also examined the sequence of another retrotransposon Pyret in six field isolates of M. grisea. Even though no perfect stage has been known in M. grisea under field conditions to date, RIP‐like transitions were found in all the field isolates tested. Interestingly, the frequency of the transitions mostly correlated with the fertility of the isolates examined under laboratory conditions. These results imply that the sexual cycle of this fungus exists or existed in the natural field context.
Therapeutic Drug Monitoring of Voriconazole in Children

Voriconazole is an extended-spectrum triazole antifungal with activity against a wide variety of pathogens, including Aspergillus, Candida, Cryptococcus neoformans, Fusarium, and Scedosporium. It exerts its antifungal activity by blocking the synthesis of fungal cell membranes and is considered the first-line treatment for invasive aspergillosis. Because the pharmacokinetics of voriconazole can demonstrate considerable variability, it has been suggested that monitoring plasma levels of voriconazole may play an important role in optimizing the efficacy and safety of the drug in complex patients like those at risk of or who have invasive aspergillosis. In this article, we review the criteria for therapeutic drug monitoring and assess the evidence for using plasma voriconazole concentrations to individualize doses in children.
Functional Synergism between the Most Common Polymorphism in Human Alanine:Glyoxylate Aminotransferase and Four of the Most Common Disease-causing Mutations*

The autosomal recessive disorder primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver-specific pyridoxal-phosphate-dependent enzyme alanine:glyoxylate aminotransferase (AGT). Numerous mutations and polymorphisms in the gene encoding AGT have been identified, but in only a few cases has the causal relationship between genotype and phenotype actually been demonstrated. In this study, we have determined the effects of the most common naturally occurring amino acid substitutions (both normal polymorphisms and disease-causing mutations) on the properties, especially specific catalytic activity, of purified recombinant AGT. The results presented in this paper show the following: 1) normal human His-tagged AGT can be expressed at high levels in Escherichia coli and purified in a correctly folded, dimerized and catalytically active state; 2) presence of the common P11L polymorphism decreases the specific activity of purified recombinant AGT by a factor of three; 3) AGTs containing four of the most common PH1-specific mutations (G41R, F152I, G170R, and I244T) are all soluble and catalytically active in the absence of the P11L polymorphism, but in its presence all lead to protein destabilization and aggregation into inclusion bodies; 4) naturally occurring and artificial amino acid substitutions that lead to peroxisome-to-mitochondrion AGT mistargeting in mammalian cells also lead to destabilization and aggregation in E. coli; and 5) the PH1-specific G82E mutation abolishes AGT catalytic activity by interfering with cofactor binding, as does the artificial K209R mutation at the putative site of cofactor Shiff base formation. These results are discussed in the light of the high allelic frequency (∼20%) of the P11L polymorphism and its importance in determining the phenotypic manifestations of mutations in PH1.
Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.

BACKGROUND We conducted a randomized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer. METHODS A total of 1207 patients with advanced non-small-cell lung cancer were randomly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens: cisplatin and gemcitabine, cisplatin and docetaxel, or carboplatin and paclitaxel. RESULTS The response rate for all 1155 eligible patients was 19 percent, with a median survival of 7.9 months (95 percent confidence interval, 7.3 to 8.5), a 1-year survival rate of 33 percent (95 percent confidence interval, 30 to 36 percent), and a 2-year survival rate of 11 percent (95 percent confidence interval, 8 to 12 percent). The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens. Treatment with cisplatin and gemcitabine was associated with a significantly longer time to the progression of disease than was treatment with cisplatin and paclitaxel but was more likely to cause grade 3, 4, or 5 renal toxicity (in 9 percent of patients, vs. 3 percent of those treated with cisplatin plus paclitaxel). Patients with a performance status of 2 had a significantly lower rate of survival than did those with a performance status of 0 or 1. CONCLUSIONS None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer.
Constrained Evolutionary Optimization by Means of ( + )-Differential Evolution and Improved Adaptive Trade-Off Model

This paper proposes a ( + )-differential evolution and an improved adaptive trade-off model for solving constrained optimization problems. The proposed ( + )-differential evolution adopts three mutation strategies (i.e., rand/1 strategy, current-to-best/1 strategy, and rand/2 strategy) and binomial crossover to generate the offspring population. Moreover, the current-to-best/1 strategy has been improved in this paper to further enhance the global exploration ability by exploiting the feasibility proportion of the last population. Additionally, the improved adaptive trade-off model includes three main situations: the infeasible situation, the semi-feasible situation, and the feasible situation. In each situation, a constraint-handling mechanism is designed based on the characteristics of the current population. By combining the ( + )-differential evolution with the improved adaptive trade-off model, a generic method named ( + )-constrained differential evolution (( + )-CDE) is developed. The ( + )-CDE is utilized to solve 24 well-known benchmark test functions provided for the special session on constrained real-parameter optimization of the 2006 IEEE Congress on Evolutionary Computation (CEC2006). Experimental results suggest that the ( + )-CDE is very promising for constrained optimization, since it can reach the best known solutions for 23 test functions and is able to successfully solve 21 test functions in all runs. Moreover, in this paper, a self-adaptive version of ( + )-CDE is proposed which is the most competitive algorithm so far among the CEC2006 entries.
Hybrid Control Model of Under Load Tap Changers

This paper proposes a hybrid control model of under load tap changer transformers. The proposed model is based on the well-known discrete and continuous control models of such device, and is designed so that it preserves the discrete behavior of the tap ratio while allowing solving small-signal stability and eigenvalue analysis. The proposed model is tested through the IEEE 14-bus test system and a real-world 1488-bus model of a sub-transmission and distribution system.
Reversal of naturally occuring diabetes in primates by unmodified islet xenografts without chronic immunosuppression.

BACKGROUND Isolated pancreatic islet transplantation (IPITx) is an attractive alternative for treatment of insulin-dependent diabetes mellitus (IDDM). However, IPITx has been difficult to implement clinically because islets frequently fail to function, have a high incidence of rejection, and are susceptible to autoimmune recurrence and damage by chronic immunosuppressive therapy. Tolerance induction may be a rational approach to resolve several of these limitations. Because anti-CD3 immunotoxin (IT) has been successful in promoting stable primate kidney transplant tolerance in our experience, we considered that tolerance induction with IT might be duplicated in IPITx. MATERIALS AND METHODS Three monkeys with spontaneous IDDM (two Macaca fascicularis and one Ceropithecus aethiops) were treated with xenogeneic pancreatic islets (Macaca mulatta). Intrahepatic islet transplantation was performed at a mean of 13136+/-3860 islet equivalents/kg. Islet xenograft acceptance was accomplished by tolerance induction with two injections of IT given on day 0 at 2 hr before transplantation and on day +1, respectively. IT treatment was supplemented with cyclosporine and steroids administered on days 0 through 4. No additional immunosuppression was given thereafter. Two additional control macaques with spontaneous IDDM received the immunosuppressive protocol without islet infusion. RESULTS All recipients were restored to stable euglycemia, off exogenous insulin, within 1-2 weeks after transplantation. Glucose tolerance, C-peptide, and glycosylated hemoglobin tests confirmed the restoration of normal glucose homeostasis after islet transplantation. All three islet recipients have remained euglycemic at 410, 255, and 100 days of follow-up despite recovery of peripheral T cells to normal levels. In contrast, none of the controls presented changes in the diabetic status 4 and 8 months after treatment. CONCLUSIONS These results represent the first demonstration in nonhuman primates of stable, long-term acceptance of nonencapsulated xenogeneic islets off all immunosuppression, suggesting operational tolerance. The findings have potential implications for islet transplantation as well as improved and more cost-effective therapy for IDDM.
Sleep problems and associated daytime fatigue in community-dwelling older individuals.

BACKGROUND Reported fatigue has been identified as a component of frailty. The contribution of nighttime sleep quality (duration and complaints) to fatigue symptoms in community-dwelling older adults has not been evaluated. METHODS We studied 2264 men and women, aged 75-84 years (mean 77.5 years; standard deviation [SD] 2.9), participating in the Year 5 (2001--2002) clinic visit of the Health, Aging, and Body Composition (Health ABC) study. Fatigue was determined using a subscale of the Modified Piper Fatigue Scale (0-50; higher score indicating higher fatigue). Hours of sleep per night, trouble falling asleep, waking up during the night, and waking up too early in the morning were assessed using interviewer-administered questionnaires. RESULTS The average fatigue score was 17.7 (SD 8.4). In multivariate models, women had a 3.8% higher fatigue score than men did. Individuals who slept < or = 6 hours/night had a 4.3% higher fatigue score than did those who slept 7 hours/night. Individuals with complaints of awakening too early in the morning had a 5.5% higher fatigue score than did those without these complaints. These associations remained significant after multivariate adjustment for multiple medical conditions. CONCLUSION The association between self-reported short sleep duration (< or = 6 hours), and waking up too early and fatigue symptoms suggests that better and more effective management of sleep behaviors may help reduce fatigue in older adults.
Do port security quality and service quality influence customer satisfaction and loyalty?

ABSTRACT This study uses Kaohsiung Port as a case study to evaluate the relationships between port security quality, port service quality, customer satisfaction, and customer loyalty. For this purpose, a survey was conducted with shipping companies and freight forwarders in Taiwan. The results indicate that port security quality has a direct and positive impact on both port service quality and customer satisfaction; port service quality has a direct and positive impact on both customer satisfaction and customer loyalty; and customer satisfaction has a direct and positive impact on customer loyalty. However, the impact from port service quality is more significant than that of port security quality. Accordingly, this study suggests that Kaohsiung Port should concentrate on improving its service quality in order to enhance customer satisfaction and customer loyalty.
Pituitary Resistin Gene Expression: Effects of Age, Gender and Obesity

Resistin is a new adipocytokine which is expressed in rat, mouse and possibly human adipose tissue. Its putative role as a mediator of insulin resistance is controversial. We hypothesized that resistin, like leptin, would have multiple roles in non-adipose tissues and we reported that resistin is expressed in mouse brain and pituitary. Moreover, resistin expression in female mouse pituitary is developmentally regulated and maximal expression occurs peripubertally. Although the role of endogenous resistin in mouse brain and pituitary has not been determined, our data suggest that resistin could be important in the postnatal maturation of the hypothalamic-pituitary system. In the present study we compared the ontogeny of resistin gene expression in the pituitary of male and female mice using semi-quantitative RT-PCR analysis. We show that resistin expression is developmentally regulated in the pituitary of male and female CD1 mice. However, significant gender differences were evident (male > female at postnatal day 28 and 42) and this was not modified by neonatal treatment of female pups with testosterone. Since resistin expression in adipose tissue is also influenced by obesity, we evaluated resistin expression in fat, brain and pituitary of the obese ob/ob mouse. Resistin mRNA was significantly increased in both visceral and subcutaneous adipose depots in postnatal day 28 ob/ob mice compared to controls, but pituitary resistin expression was significantly reduced. In contrast to the prepubertal levels, and in agreement with other reports, adipose resistin expression was reduced in adult ob/ob mice. In a third set of experiments we examined the influence of food deprivation on pituitary and fat resistin mRNA. Resistin gene expression was severely down-regulated by a 24-hour fast in adipose and pituitary tissue but not in hypothalamus. In conclusion, pituitary resistin expression is age- and gender-dependent. In ob/ob mice, and in fasted mice, resistin is regulated in a tissue-specific manner. Thus in visceral fat obesity increases but starvation decreases resistin mRNA. In contrast, pituitary levels are decreased in the presence of both high (ob/ob) and low (fasting) adipose stores. Further studies are required to define the unexpected hormonal regulation of resistin gene expression in the pituitary.
Prevalence of malocclusion, its association with occlusal interferences and temporomandibular disorders among the Saudi sub-population.

AIMS This Study was conducted to determine the incidence of malocclusion, occlusal interferences, temporomandibular Disorder (TMD) among the Saudi population and to evaluate the possible existence of an association between malocclusion, occlusal interferences and TMD. METHODS 250 patients attending dental clinics in Abha city, Saudi Arabia for treatment was clinically examined for the degree of malocclusion. Patients were further evaluated for the presence of occlusal interferences and TMD. Data was evaluated by person's correlation and logistic regression to evaluate the association between malocclusion, occlusal interference and TMD. RESULTS The results of the study indicate 42.8% of the evaluated subjects had a definitive degree of malocclusion. Among the occlusal interference observed, balancing side interferences were high (47.6%), followed by protrusive interferences (41.2%). The prevalence of TMD among the evaluated subjects was 41.6%, with mandibular deviation and joint sounds were most prevalent. Statistical Analysis (Pearson's correlation) showed the statistically significant correlation between malocclusion and centric slide (p-0.030), posterior missing teeth (p-000). The statistically significant correlation was observed between TMD and balanced side interferences (p-0.000), slide RCP-ICP (p-0.001), reduced occlusal contacts (0.033). Logistic regression analysis showed the strong association of TMD with anterior open bite, increased maxillary overjet, balanced side interferences, and centric slide. CONCLUSION The prevailing malocclusion and TMD among studied population is significantly higher. The preventive dental treatment and community dental education need to be more emphasized.
Levodopa response differs in Parkinson's motor subtypes: A task‐based effective connectivity study

Parkinson's disease (PD) is a circuit‐level disorder with clinically‐determined motor subtypes. Despite evidence suggesting each subtype may have different pathophysiology, few neuroimaging studies have examined levodopa‐induced differences in neural activation between tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtype patients during a motor task. The goal of this functional MRI (fMRI) study was to examine task‐induced activation and connectivity in the cortico‐striatal‐thalamo‐cortical motor circuit in healthy controls, TD patients, and PIGD patients before and after levodopa administration. Fourteen TD and 12 PIGD cognitively‐intact patients and 21 age‐ and sex‐matched healthy controls completed a right‐hand, paced tapping fMRI paradigm. Collectively, PD patients off medication (OFF) showed hypoactivation of the motor cortex relative to healthy controls, even when controlling for performance. After levodopa intake, the PIGD patients had significantly increased activation in the left putamen compared with TD patients and healthy controls. Psychophysiological interaction analysis revealed that levodopa increased effective connectivity between the posterior putamen and other areas of the motor circuit during tapping in TD patients, but not in PIGD patients. This novel, levodopa‐induced difference in the neural responses between PD motor subtypes may have significant implications for elucidating the mechanisms underlying the distinct phenotypic manifestations and enabling the classification of motor subtypes objectively using fMRI.
Analysis of sagittal profile of spine using 3D ultrasound imaging: a phantom study and preliminary subject test

ABSTRACT Radiographic Cobb’s angle is the gold standard for evaluation of spinal curvature, however, X-ray is ionising. In contrast, ultrasound is non-ionising and inexpensive. However, no study has reported the reliability and accuracy of ultrasound on sagittal curvature analysis. Ultrasound and X-ray scanning were conducted on 16 sets of spine phantoms with different deformities. Intra-rater and inter-rater reliability, correlations, mean absolute differences (MAD) and linear regression of ultrasound spinous process angles (USSPA), X-ray spinous process angles (XSPA) and X-ray Cobb’s angles (XCA) together with the intra-operator reliability of USSPA were investigated. In addition, USSPA and XCA of five AIS subjects were obtained using the ultrasound system. In the phantom study, excellent intra-rater and inter-rater reproducibility for the three angles and excellent intra-operator reproducibility for USSPA were demonstrated. Good to moderate or better correlations were obtained among the angles. All three angles indicated positive linear relationships with MAD ≤ 6.0°. The results of the preliminary study demonstrated a high intra-reliability for the ultrasound measurements. The measured difference between the USSPA and XCA methods was 6.3° ± 5.4°. The results showed that ultrasound is feasible for measuring sagittal curvature and has the potential for monitoring the curve progression and evaluating sagittal spinal profiles.
Technical, tactical and spatial indicators related to goal scoring in European elite soccer

The aim of this study was to describe the technical, tactical and spatial indicators related to goal scoring in elite European soccer, considering the type of defence and the positioning of the opponent. For the analysis, 8 tactical dimensions related to the final actions in 380 sequences that led to goal during the UEFA Champions League were evaluated by observational methodology. 75.9% of the goals were scored from open play and 24.1% were scored from set pieces. Collective actions produced 51.6% of the total goals while individual actions produced 10.5% of goals. Regarding the penultimate action, crosses were more frequent against organized defences, while passes in behind the defence, or actions as dribbling or running with the ball had a greater percentage of goals against circumstantial defences (X2=37.027; p>0.001). Besides, greater utilization of wide invasive spaces (70.2%) was observed to assist against organized defences, while this percentage was 53.1% (X2=5.501; p=0.015) against circumstantial defences. For the last action, 70.1% of the goals were scored by using only one contact to the ball in organized defences but 46.6% in circumstantial defences (X2=26.521; p>0.001). The technical and tactical actions that achieve goal and their spatial characteristics are related to the type of defence used by the opposing team.
Internal tremor in patients with Parkinson's disease

Although sensory symptoms were not originally described in Parkinson's disease (PD), in recent years it has been increasingly recognized that painful sensations and paresthesias occur in ∼40% of patients. It has been our observation that PD patients often describe a sensation of internal tremor, a feeling of tremor inside the chest, abdomen, arms, or legs that cannot be seen. We investigated the prevalence and characteristics of internal tremor by administering a questionnaire to 100 consecutive patients with PD and 50 age‐matched controls seen in our movement disorders center. A sensation of internal tremor was present in 44% of this sample of PD patients and in 6% of the control population (p < 0.0001). The presence of internal tremor was unrelated to Unified Parkinson's Disease Rating Scale score, Hoehn and Yahr stage, duration of disease, or the presence of observable tremor. The frequency of other sensory symptoms (aching, tingling, burning) was higher in the PD patients with internal tremor (73%) than in those without (45%; p = 0.005). Internal tremor is associated with anxiety in 64% of patients (p < 0.0001). It was described as uncomfortable and was unrelieved by antiparkinsonian medication in three quarters of patients. A sensation of internal tremor is commonly reported by PD patients and should be recognized as a useful diagnostic factor in PD.