Miracle-dz/UniFAR-FTUs huggingface dataset:
Preventing the transmission of mitochondrial DNA disorders using prenatal or preimplantation genetic diagnosis

Mitochondrial disorders are among the most common inborn errors of metabolism; at least 15% are caused by mitochondrial DNA (mtDNA) mutations, which occur de novo or are maternally inherited. For familial heteroplasmic mtDNA mutations, the mitochondrial bottleneck defines the mtDNA mutation load in offspring, with an often high or unpredictable recurrence risk. Oocyte donation is a safe option to prevent the transmission of mtDNA disease, but the offspring resulting from oocyte donation are genetically related only to the father. Prenatal diagnosis (PND) is technically possible but usually not applicable because of limitations in predicting the phenotype. For de novo mtDNA point mutations, recurrence risks are low and PND can be offered to provide reassurance regarding fetal health. PND is also the best option for female carriers with low‐level mutations demonstrating skewing to 0% or 100%. A fairly new option for preventing the transmission of mtDNA diseases is preimplantation genetic diagnosis (PGD), in which embryos with a mutant load below a mutation‐specific or general expression threshold of 18% can be transferred. PGD is currently the best reproductive option for familial heteroplasmic mtDNA point mutations. Nuclear genome transfer and genome editing techniques are currently being investigated and might offer additional reproductive options for specific mtDNA disease cases.
Multi-Feedback Successive Interference Cancellation with Multi-Branch Processing for MIMO Systems

In this paper, a new successive interference cancellation (SIC) strategy for multiple-input multiple output (MIMO) spatial multiplexing systems is developed to combat the error propagation (EP) in decision feedback systems. The proposed scheme employs a parallel multi-branch (MB) structure. Each branch employs a SIC with multi-feedback (MF) strategy to detects the signals according to their respective ordering pattern. The MF-SIC scheme considers the feedback diversity by using a number of selected constellation points as the feedback set if a previous decision is considered unreliable. The shadow area constraint (SAC) is proposed to reduce the computational complexity by avoiding redundant MF processing with reliable decisions. The MB-MF-SIC achieves a higher detection diversity by selecting the branch which yields the signal estimates with the best performance according to the maximum likelihood rule. The simulation results show that the MB-MF-SIC scheme successfully mitigates the EP and approaches the ML performance while requiring lower complexity than sphere decoders.
Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans.

OBJECTIVES To determine the critical oxygen delivery threshold for anaerobic metabolism and to compare its value between septic and nonseptic critically ill patients. DESIGN Cohort analytic study, consecutive sample. SETTING Two tertiary care medical and surgical intensive care units in university hospitals. PATIENTS Nine septic and nine nonseptic critically ill humans. A diagnosis of sepsis was established by the presence of sepsis syndrome, positive cultures obtained within 48 hours of study, and autopsy evidence of a source of infection. METHODS AND INTERVENTIONS The O2 consumption (determined by indirect calorimetry), O2 delivery (calculated from the Fick equation), and concentration of arterial plasma lactate were simultaneously determined at 5- to 20-minute intervals while life support was discontinued. MAIN OUTCOME MEASURES Critical O2 delivery, critical O2 extraction ratio, and maximal O2 extraction ratio. RESULTS In all septic and eight nonseptic patients, O2 delivery and O2 consumption displayed a biphasic relationship over the range of O2 delivery studied. There were no differences in critical O2 delivery threshold (3.8 +/- 1.5 vs 4.5 +/- 1.3 mL.min-1 x kg-1; P > .28), critical O2 extraction ratio (0.61 +/- 0.05 vs 0.59 +/- 0.16; P > .64), and maximal O2 extraction ratio (0.74 +/- 0.08 vs 0.80 +/- 0.11; P > .29) between septic and nonseptic patients. These data have greater than 90% power to detect a difference of 2 mL.min-1 x kg-1 in the critical O2 delivery and 0.1 in the critical and maximal O2 extraction ratios between the septic and nonseptic groups. CONCLUSIONS The critical O2 delivery for anaerobic metabolism was identified from the biphasic relationship between O2 delivery and O2 consumption in individual humans. The critical O2 delivery is considerably lower than previously reported in humans with the use of pooled group data. Sepsis does not alter the critical O2 delivery for anaerobic metabolism or tissue O2 extraction ability. Interventions to increase O2 delivery to supranormal levels in critically ill humans in the hope of increasing O2 consumption may be inappropriate.
Structural Stabilization of Tissue for Embryo Phenotyping Using Micro-CT with Iodine Staining

The International Mouse Phenotyping Consortium has been established to conduct large-scale phenotyping of the approximately 23,000 single-gene knockout mice generated by the International Knockout Mouse Consortium to investigate the role of each gene in the mouse genome. Of the generated mouse lines, 30% are predicted to be embryonic lethal, requiring the implementation of imaging techniques and analysis tools specific to late gestation mouse embryo phenotyping. A well-adopted technique combines the use of iodinated contrast solutions and micro-computed tomography imaging. This simple iodine immersion technique provides superior soft-tissue contrast enhancement, however, the hypertonic nature of iodine promotes dehydration causing moderate to severe tissue deformation. Here, we combine the stabilizing properties of a hydrogel mesh with the enhanced contrast properties of iodine. The protocol promotes cross linking of tissue through formaldehyde fixation and the linking of hydrogel monomers to biomolecules. As a result, the hydrogel supports tissue structure and preserves its conformation taking advantage of iodine-enhanced soft tissue contrast to produce high quality mouse embryo images with minimal tissue distortion. Hydrogel stabilization substantially reduces intersample anatomical variation of mature mouse embryos subjected to iodine preparation protocols. A 20% and 50% reduction in intersample variation of normalized brain and lung volume is achieved through hydrogel stabilization, as well as a 20% reduction in variation in overall embryo anatomy as measured through image registration methods. This increases the sensitivity of computer automated analysis to reveal significant anatomical differences between mutant and wild-type mice.
Cell Signaling : Proteins , Pathways and Mechanisms A novel mechanism of myostatin regulation by its alternative splicing variant during myogenesis in avian species

Shin S, Song Y, Ahn J, Kim E, Chen P, Yang S, Suh Y, Lee K. A novel mechanism of myostatin regulation by its alternative splicing variant during myogenesis in avian species. Am J Physiol Cell Physiol 309: C650 –C659, 2015. First published September 9, 2015; doi:10.1152/ajpcell.00187. 2015. —Myostatin (MSTN) is a key negative regulator of muscle growth and development, and an increase of muscle mass is achieved by inhibiting MSTN signaling. In the current study, five alternative splicing isoforms of MSTN mRNAs in avian species were identified in various tissues. Among these five, three truncated forms of myostatin, MSTN-B, -C, and -E created premature stop codons and produced partial MSTN prodomains encoded from exon 1. MSTN-B is the second dominant isoform following full-length MSTN-A, and their expression was dynamically regulated during muscle development of chicken, turkey, and quail in vivo and in vitro. To clarify the function of MSTN-B, two stable cell lines of quail myoblasts (QM7) were generated to overexpress MSTN-A or MSTN-B. Interestingly, MSTN-B promoted both cell proliferation and differentiation similar to the function of the MSTN prodomain to counteract the negative role of MSTN on myogenesis. The coimmunoprecipitation assay revealed that MSTN-B binds to MSTN-A and reduces the generation of mature MSTN. Furthermore, the current study demonstrated that the partial prodomain encoded from exon 1 is critical for binding of MSTN-B to MSTN-A. Altogether, these data imply that alternative splicing isoforms of MSTN could negatively regulate pro-myostatin processing in muscle cells and prevent MSTNmediated inhibition of myogenesis in avian species.
Amplitude control of the neutral-point voltage oscillations in the three-level converter

This paper presents a control method to regulate the amplitude of the voltage oscillations that appear in the neutral-point of the three-level diode-clamped converter for some operating conditions. The control is applied to the hybrid modulation technique, which is based on combining two modulation techniques. One of them is based on two modulation signals per phase, and can remove completely the low-frequency voltage oscillations on the neutral point. However, such a modulation strategy has an important drawback; it increases significantly switching losses on the converter. The hybrid modulation used here combines such a modulation with sinusoidal PWM. The main characteristic of this hybrid modulation is the capacity to reduce switching losses at the cost of having some low-frequency voltage oscillations on the neutral point. The amplitude of these oscillations can be regulated thanks to the proposed controller, which defines the exact degree of mixture between the two modulation strategies. Some simulation and experimental results are presented in this paper.
Long-term CCK-leptin synergy suggests a role for CCK in the regulation of body weight.

The gut peptide CCK is a nutrient-related signal important to the control of food intake. In the present studies, we observed that a single intraperitoneal injection of CCK (1-2 μg/kg) given 2-3 h after intracerebroventricular leptin (2-5 μg) reduced body weight and chow intake over the ensuing 48 h more than did leptin alone. CCK alone had no effect on either 48-h chow intake or body weight but significantly reduced feeding during a 30-min sucrose test. However, reduction of 30-min sucrose intake by CCK was not enhanced by prior intracerebroventricular leptin. The present data suggest that CCK can contribute to the regulation of body weight when central leptin levels are elevated.
Chronic Metoclopramide Therapy for Diabetic Gastroparesis

OBJECTIVE To review the safety and efficacy of chronic metoclopramide for diabetic gastroparesis. DATA SOURCES Medical literature was accessed through MEDLINE (1965 to October 2002) and PubMed (1965 to October 2002). Key search terms included metoclopramide; diabetic gastroparesis; and dyskinesia, drug induced. DATA SYNTHESIS Metoclopramide is often used for diabetic gastroparesis, despite the risk of tardive dyskinesia. Published information is limited regarding long-term efficacy and toxicity of metoclopramide. The literature was assessed concerning these topics. CONCLUSIONS Limited data do not provide sufficient evidence to conclude whether metoclopramide is efficacious for chronic use. Routine monitoring may mitigate the risk associated with metoclopramide therapy.
The hyperion project: from data integration to data coordination

We present an architecture and a set of challenges for peer database management systems. These systems team up to build a network of nodes (peers) that coordinate at run time most of the typical DBMS tasks such as the querying, updating, and sharing of data. Such a network works in a way similar to conventional multidatabases. Conventional multidatabase systems are founded on key concepts such as those of a global schema, central administrative authority, data integration, global access to multiple databases, permanent participation of databases, etc. Instead, our proposal assumes total absence of any central authority or control, no global schema, transient participation of peer databases, and constantly evolving coordination rules among databases. In this work, we describe the status of the Hyperion project, present our current solutions, and outline remaining research issues.
Logic Depth and Power Consumption: A Comparative Study Between Standard Cells and FPGAs

In large combinational datapaths, glitches generated in the first stages produce an avalanche effect in the activity of subsequent nodes. This problem can be avoided by registering every few gates. Thus, the propagation of glitches is blocked, and consequently, the datapath power is reduced. However, these extra registers increase the synchronization power. Therefore, for a given technology, the potential power saving will depend on the balance between synchronization and datapath consumption. In this paper, the relationship between logic depth and power consumption is analyzed for three semicustom options: Xilinx and Altera FPGAs, and 1μ CMOS Standard Cells from ES2. Main results show that, for all technologies, an intermediate value of logic depth that minimizes datapath power consumption exists. In FPGA-based prototypes, such reduction compensates the synchronization power overhead, but the reverse occurs in the cellbased circuits. In addition, the standard cell technology (SC) exhibits a relatively high off-chip consumption, making less significant any action to cut down other causes of power consumption.
On Teaching Computational Thinking

Jeannette Wing’s call for teaching Computational Thinking (CT) as a formative skill on par with reading, writing, and arithmetic places computer science in the category of basic knowledge. Just as proficiency in basic language arts helps us to effectively communicate and in basic math helps us to successfully quantitate, proficiency in computational thinking helps us to systematically and efficiently process information and tasks. But while teaching everyone to think computationally is a noble goal, there are pedagogical challenges. Perhaps the most confounding issue is the role of programming, and whether we can separate it from teaching basic computer science. How much programming, if any, should be required for CT proficiency? We believe that to successfully broaden participation in computer science, efforts must be made to lay the foundations of CT long before students experience their first programming language. We posit that programming is to Computer Science what proof construction is to mathematics, and what literary analysis is to English. Hence by analogy, programming should be the entrance into higher CS, and not the student’s first encounter in CS. We argue that in the absence of programming, teaching CT should focus on establishing vocabularies and symbols that can be used to annotate and describe computation and abstraction, suggest information and execution, and provide notation around which mental models of processes can be built. Lastly, we conjecture that students with sustained exposure to CT in their formative education will be better prepared for programming and the CS curriculum, and, furthermore, that they might choose to major in CS not only for career opportunities, but also for its intellectual content.
Is noninvasive hemodynamic monitoring appropriate for the elderly critically injured patient?

BACKGROUND Noninvasive hemodynamic monitoring in critically ill patients using bioimpedance technology has been shown to be a reliable alternative to invasive thermodilution techniques. However, there have been some concerns that the bioimpedance method may be unreliable in elderly patients with an atherosclerotic and rigid thoracic aorta. The purpose of the present study was to evaluate the effect of age on the reliability of noninvasive bioimpedance technology in measuring cardiac index. METHODS This is a retrospective analysis of prospectively collected data in critically injured patients admitted to the surgical intensive care unit. All patients had simultaneous measurement using thermodilution cardiac index (TDCI) and bioimpedance cardiac index (BICI). The population was divided into three age groups (<55 years, 55-70 years, and >70 years). The correlation between TDCI and BICI was calculated for each age group. RESULTS There were 1,138 simultaneous measurements of TDCI and BICI in 285 patients. The BICI correlated well with TDCI in all three age groups (r = 0.82 for group <55 years, r = 0.87 for group 55-70 years, and r = 0.80 for group >70 years). CONCLUSION Noninvasive cardiac index monitoring in elderly patients is reliable and correlates well with standard thermodilution techniques.
Shielding effectiveness of 1-D periodic composite screens in the presence of electric line sources: Full-wave analysis and limits of homogenization

The near-field shielding effectiveness of composite screens characterized by spatial periodicity along one dimension is investigated in the presence of an electric line source (i.e., an aperiodic source) placed in proximity of the screen. The metal strip grating and the wire-medium screen supported by a dielectric board are studied as examples of one-dimensional periodic screens. Both full-wave analyses and approximate homogeneous models are adopted in order to investigate the limits of the homogenization techniques for the study of the interaction between a finite source and a periodic screen. Moreover, differences in shielding-effectiveness values for such periodic structures are discussed when considering finite-source or plane-wave excitations.
Air pollution and its health impacts: the changing panorama

Urban air pollution levels are associated with increased mortality and cardiorespiratory morbidity. These health effects occur even at exposure levels below those stipulated in current air‐quality guidelines, and it is unclear whether a safe threshold exists. Air pollution in Australia and New Zealand comes primarily from motor vehicle emissions, electricity generation from fossil fuels, heavy industry, and home heating using wood and coal. In individual patients a direct link between symptoms and air pollution exposure may be difficult to establish and may not change their clinical management. However, avoiding exposure during periods of peak pollution may be beneficial. Although there is some evidence that urban air pollution in Australia and New Zealand has been decreasing (through reduced car use, improved emission‐control technology and use of more energy‐efficient devices in the household and in industry), pollution levels are still unsatisfactory. Further reductions may prevent hundreds of cardiorespiratory hospital admissions and deaths each year.
Rapid Collection of Biospecimens by Automated Identification of Patients Eligible for Pharmacoepigenetic Studies

Epigenetics plays an important role in regulating gene expression, and can be modified by environmental factors and physiological conditions. Studying epigenetics is a promising approach to potentially improving the diagnosis, prevention and treatment of human diseases, and to providing personalized medical care. However, the role of epigenetics in the development of diseases is not clear because epigenetic markers may be both mediators and outcomes of human diseases. It is particularly complicated to study pharmacoepigenetics, as medication use may modify the epigenetic profile. To address the challenges facing pharmacoepigenetic research of human diseases, we developed a novel design to rapidly identify, contact, and recruit participants and collect specimens for longitudinal studies of pharmacoepigenetics. Using data in real-time from electronic medical record systems, we can identify patients recently start on new medications and who also have a blood test. Prior to disposal of the leftover blood by the clinical laboratory, we are able to contact and recruit these patients, enabling us to use both their leftover baseline blood sample as well as leftover specimens at future tests. With treatment-naïve and follow-up specimens, this system is able to study both epigenetic markers associated with disease without treatment effect as well as treatment-related epigenetic changes.
The birefringence property of magnesium fluoride crystal in THz frequency region

The azimuthal angle dependent transmittance in 0.2-2.2 THz frequency region for magnesium fluoride (MgF2) crystal is measured by using a polarization sensitive detection method. The birefringence, absorption coefficient and refractive index have been studied. Based on the theory of crystal optics, the possibility of using magnesium fluoride (MgF2) crystal as a THz wave plate is investigated. The coincidence of experimental data and theoretical curve demonstrates that these optical properties are sufficient for being used as wave plate operating in 0.2-2.2 THz frequency region.
Ontologizing concept maps using graph theory

Given the new challenges of open and unsupervised information extraction, there is a need to identify important and relevant knowledge structures (concepts and relationships) in the vast amount of extracted data and to filter the noise that results from unsupervised information extraction. This is generally referred to as the ontologization task. This paper uses measures from graph theory to identify these key elements such as Page Rank, Betweenness, and Degree. We also propose a combination of metrics for ranking concepts and relationships. Our approach shows effective results in terms of precision compared to other standard measures for weighting concepts and relationships such as TF*IDF or frequency of co-occurrences.
Programming in natural language: “NLC” as a prototype

The state of the art in computational linguistics has progressed to the point where it is now possible to process simple programs written in natural language. This report describes a natural language programming system called NLC which enables a computer user to type English commands into a display terminal and watch them executed on example data shown on the screen. The system is designed to process data stored in matrices or tables, and any problem which can be represented in such structures can be handled if the total storage requirements are not excessive.
Migration in Afro-Brazilian Rural Communities: Crossing Demographic and Genetic Data

Abstract Many studies have used genetic markers to understand global migration patterns of our species. However, there are only few studies of human migration on a local scale. We, therefore, researched migration dynamics in three Afro-Brazilian rural communities, using demographic data and ten Ancestry Informative Markers. In addition to the description of migration and marriage structures, we carried out genetic comparisons between the three populations, as well as between locals and migrants from each community. Genetic admixture analyses were conducted according to the gene-identity method, with Sub-Saharan Africans, Amerindians, and Europeans as parental populations. The three analyzed Afro-Brazilian rural communities consisted of 16% to 30% of migrants, most of them women. The age pyramid revealed a gap in the segment of men aged between 20 to 30 yrs. While endogamous marriages predominated, exogamous marriages were mainly patrilocal. Migration dynamics are apparently associated with matrimonial customs and other social practices of such communities. The impact of migration upon the populations' genetic composition was low but showed an increase in European alleles with a concomitant decrease in the Amerindian contribution. Admixture analysis evidenced a higher African contribution to the gene pool of the studied populations, followed by the contribution of Europeans and Amerindians, respectively.