Miracle-dz/UniFAR-FTUs huggingface dataset:
Biomarker discovery in mass spectrometry‐based urinary proteomics

Urinary proteomics has become one of the most attractive topics in disease biomarker discovery. MS‐based proteomic analysis has advanced continuously and emerged as a prominent tool in the field of clinical bioanalysis. However, only few protein biomarkers have made their way to validation and clinical practice. Biomarker discovery is challenged by many clinical and analytical factors including, but not limited to, the complexity of urine and the wide dynamic range of endogenous proteins in the sample. This article highlights promising technologies and strategies in the MS‐based biomarker discovery process, including study design, sample preparation, protein quantification, instrumental platforms, and bioinformatics. Different proteomics approaches are discussed, and progresses in maximizing urinary proteome coverage and standardization are emphasized in this review. MS‐based urinary proteomics has great potential in the development of noninvasive diagnostic assays in the future, which will require collaborative efforts between analytical scientists, systems biologists, and clinicians.
[Inhibition of the in vitro interaction between hypoxia inducible factor 1alpha and p300 by mitogen-activated protein kinase phosphatase 1].

OBJECTIVE To investigate the effects of mitogen-activated protein kinase phosphatase-1 (MKP-1) on the interaction between hypoxia-inducible factor (HIF)-1alpha and coactivator p300. METHODS Prokaryotic expression vector PGEX-4T1 was constructed based on DNA recombination technology. GST fusion proteins were purified by glutathione-agarose beads and transfected into Escherichia coli BL-21. Effects of MKP-1 or PD98059 on in vitro interaction between HIF-1alpha and p300 was determined by Pull-down assay coupled with Western bloting. Effects of MKP-1 on the p300 expression level was detected using Western bloting. RESULTS (1) GST fusion proteins were expressed in BL-21 Escherichia coli and purified proteins were obtained. (2) Less amount of p300 was pulled down by GST fusion protein from SGC7901-MKP-1 cells than from control cells after 12 hours of exposure to hypoxia. (3) 12 hours after hypoxia, Less amount of p300 was pulled down by GST fusion protein from PD98059 treated cells than from DMSO treated cells or SGC7901 cells. (4) There were no significant differences in p300 expression levels between recombinant MKP-1 transfected cells and control cells after 12 hours of exposure to hypoxia. CONCLUSION MKP-1 inhibits the in vitro interaction between HIF-1alpha and p300.
Neurophysiological characterization of transpinal evoked potentials in human leg muscles

The objectives of this study were to characterize the neurophysiological properties of the compound muscle action potentials (CMAPs) evoked by transcutaneous electric stimulation of the spine (tsESS), and the effects of tsESS on the soleus H‐reflex in seated and standing healthy human subjects. In seated semi‐prone subjects with the trunk semi‐flexed, two re‐usable self‐adhering electrodes (cathode), connected to act as one electrode, were placed bilaterally on the iliac crests. A re‐usable pregelled electrode (anode) was placed on the thoracolumbar region at thoracic 10–lumbar 1 and held under constant pressure throughout the experiment. CMAPs were recorded bilaterally from ankle muscles with subjects seated semi‐prone at 1.0, 0.3, 0.2, 0.125, and 0.1 Hz following tsESS. The soleus H‐reflex, evoked by posterior tibial nerve stimulation via conventional methods, was measured following tsESS at inter‐stimulus intervals (ISIs) that ranged from −100 to 100 ms with the subjects seated semi‐prone and during standing. The tsESS‐induced CMAPs were not decreased at low stimulation frequencies, and the soleus H‐reflex excitability was profoundly decreased by tsESS at ISIs that ranged from −5 to 20 ms with the subjects seated semi‐prone and during standing. CMAPs induced by tsESS may be utilized to assess spinal‐to‐muscle conduction time while bypassing spinal motoneuron excitability and tsESS can be used as a modality to decrease spinal reflex hyper‐excitability in neurological disorders. Bioelectromagnetics 34:630–640, 2013. © 2013 Wiley Periodicals, Inc.
Physiological and genetic regulation of the aldohexuronate transport system in Escherichia coli

In Escherichia coli K-12, the specificity of the aldohexuronate transport system (THU) is restricted to glucuronate and galacturonate. There is a relatively high basal-level activity in uninduced wild-type or isomeraseless strains. Supplementary activity is obtained with the inducers mannonic amide (five-fold), galacturonate (fourfold), fructuronate (fivefold), and tagaturonate (sevenfold). Specific THU- mutants were selected as strains unable to grow on either aldohexuronate but able to grow on fructuronate or tagaturonate. The remaining transport activity in uninduced and induced THU- starins represents less than 20% of that found in the wild type. Conjugation and transduction experiments indicate that all of the THU- mutations are located in a unique locus, exuT, half-way between the tolC (59 min) and argG (61 min) markers. exuT is closely linked to the uxaC-uxaA operon (60 min) and to the regulatory gene exuR (60 min), which controls the above-mentioned operon and the uxaB operon (45 min). Growth on either aldohexuronate and transport activity are fully recovered when exuT mutants are allowed to revert to exuT+ on galacturonate or glucuronate. Reversion on glucuronate alone may lead to the mutational derepression of the 2-keto-3-deoxygluconate transport system, which is uninducible in the wild type, which also takes up glucuronate, and whose structural gene belongs to the kdg regulon. Such strains, which remain unable to grow on galacturonate, are exuT and kdgR (constitutive allele of the regulatory gene kdgR of the kdg regulon). THU activity is superrepressed in an exuR mutant in which the uxaC-uxaA operon and the uxaB operon are superrepressed; exuR+/exuR merodiploids are also superrepressed. In a thermosensitive exuR mutant in which the above-mentioned operons are constitutive at 42 degrees C, the THU activity is fully derepressed at this temperature. On the basis of these and other results, it is concluded that THU is coded for by the structural gene exuT, which is negatively controlled by the exuR gene product and which probably belongs to an operon distinct from the uxaA-uxaC operon.
Limited Predictability and the Greenhouse Effect – A Scientific Review

The concept of limited predictability is reviewed followed by simple examples illustrating the sensitivity to small changes in the initial state and/or the forcing of a non-linear system. Limited predictability applies to almost all non-linear systems, and the concept is therefore important to geophysical systems governed by non-linear model equations. The limited predictability determines the upper limit to operational weather forecasts, but it will also be demonstrated that it has an impact on the determination of the effect of changes in the forcing of the system. The general strategy applied by researchers to estimate the atmospheric greenhouse effect is reviewed. It will be demonstrated that the adopted strategy, due to prescribed changes in the forcing of the climate system, is also influenced by limited predictability in the sense that predicted changes are much larger than observed changes in the temperatures at the surface of the Earth. It is therefore very unlikely that the predictions are reliable. The inclusion of the sulphur-aerosol effects are also discussed with the conclusion that although these cooling agents reduce the greenhouse warming, they do not behave as expected in the sulphur-rich and sulphur-poor regions.
Integration of microfluidic system with silicon nanowires biosensor for multiplexed detection

This paper propose a novel method of integration microfluidic sample delivery system with silicon nanowire (SiNW) biosensor device, which provide multiplexed detection capability as well as protect the fragile sensing elements from mechanical shocks and surrounding impurities. The SiNWs and PDMS chips were fabricated with complementary metal oxide semiconductor (CMOS) compatibility and low cost methods. They were integrated together by using optimal O2 plasma parameters that enabled rapid and leakage-free bond formation, without additional heating or applied pressure. Capillary action enabled by the hydrophilicity of the channels using polyvinylpyrrolidone (PVP) was also demonstrated to allow analyte solution delivery onto the sensor array directly, exclude the need of using external pumping devices.
Outer Membrane Lipoprotein e (P4) ofHaemophilus influenzae Is a Novel Phosphomonoesterase

ABSTRACT Haemophilus influenzae exists as a commensal of the upper respiratory tract of humans but also causes infections of contiguous structures. We describe the identification, localization, purification, and characterization of a novel, surface-localized phosphomonoesterase from a nontypeable H. influenzaestrain, R2866. Sequences obtained from two CNBr-derived fragments of this protein matched lipoprotein e (P4) within the H. influenzae sequence database. Escherichia coli DH5α transformed with plasmids containing the H. influenzae helgene, which encodes lipoprotein e (P4), produced high levels of a membrane-associated phosphomonoesterase. The isolated ∼28-kDa enzyme was tartrate resistant and displayed narrow substrate specificity with the highest activity for arylphosphates, excluding 5-bromo-4-chloro-3-indolylphosphate. Optimum enzymatic activity was observed at pH 5.0 and only in the presence of divalent copper. The enzyme was inhibited by vanadate, molybdate, and EDTA but was resistant to inorganic phosphate. The association of phosphomonoesterase activity with a protein that has also been recognized as a heme transporter suggests a unique role for this unusual phosphohydrolase.
Economic growth and gender inequalities in labor force participation and Education In Kenya

The main development goal in Kenya’s Vision 2030 is to raise economic growth and reduce gender disparities. However, majority of the Kenyans still remain in poverty and gender inequality is widening. To achieve its vision 2030, the government need deliberate win-win policies that aim at dropping gender gaps and raising growth in the Gross Domestic Product (GDP). To provide the relevant information necessary for designing these policies, this study sought to probe how gender disparities in education and labor force participation impact on GDP growth using time series data for the period between 1990 and 2012. The research utilizes Autoregressive Distributed Lag model (ARDL) to examine how gender inequality is affected by the education system and labor force involvement on the growth of the economy. The key findings show that gender disparities in education had a depressing consequence on GDP growth in both short and long run. On the other hand, gender disparities in labor force involvement had no consequence on GDP growth. The study recommends that the Kenyan government should focus on policies that ensure that the girl child has access to not only primary and secondary education but also institutions of higher learning in order to increase gender equality.
Uniform looking vector plot with streamline fragmentation

Vector plot is a frequently used method for illustrating vector fields used in applications such as scientific visualization. Although the method is easy to implement and the resulting image captures the original vector field well, the streamlines are often positioned too closely or too sparsely to one another due to sources and sinks of the original vector field. This results in unevenness of visual density over the entire region, and some previous researches have treated the problem. Mebarki et al [1] proposed the improved strategy that the maximum vacant region should be given priority for a new streamline, but the results still lack uniformity. Other related works [2][3] suggested that both tapering streamlines and controlling intensity improve the visual uniformity of streamlines. We propose another approach for making streamlines look uniform with dotted and broken lines instead of tapering or intensity control. The results are binary images and consist of fixed width streamlines which preserve uniformity.
Genetic approaches to identify disease genes for birth defects with cleft lip/palate as a model.

BACKGROUND Understanding the etiology of birth defects is an important step toward developing improved treatment and preventive strategies. Most birth defects have an underlying genetic basis, ranging from single genes playing dominant or recessive roles in Mendelian disorders to a mixture of contributions from multiple genes and environmental triggers in complex traits. The purpose of this article is to provide an overview of genetic approaches to identifying disease genes for genetically complex birth defects. METHODS A review of the literature describing successes and limitations for identifying disease genes for complex traits was conducted. RESULTS Cleft lip and cleft palate are common congenital anomalies with significant medical, psychological, social, and economic ramifications. The Online Mendelian Inheritance in Man catalog (OMIM; http://www3.ncbi.nlm.nih.gov/Omim) lists more than 400 single-gene causes of clefts of the lip and/or palate. Genetic causes of clefting also include chromosomal rearrangements, genetic susceptibility to teratogenic exposures, and complex genetic contributions of multiple genes. CONCLUSIONS Genetic causes of birth defects can be identified using an increasingly powerful combination of careful sample collection, molecular analytic methods, and statistical evaluations. We will describe a range of approaches to search for genetic factors of birth defects and use our own work with cleft lip and palate as a model.
Current Gene‐Mapping Strategies in Experimental Models of Multiple Sclerosis

Both family‐based linkage analyses and population‐based association studies have failed to identify disease‐regulatory non‐human leucocyte antigen genes of importance in multiple sclerosis (MS). Instead, investigators have employed experimental models, which offer major advantages in genetic studies. We summarize the current main methodologies used and the status of both the human and experimental approaches. Why is it important to find genes regulating MS? There is an immense number of cellular and molecular interactions defined in the immunological field and it is very difficult to unravel those that are critical to an inflammatory disease, such as MS, by classical hypothesis‐driven research. Unbiased genetics defines evolutionary conserved gene polymorphisms and pathways regulated by these genes, which are central in the pathogenesis. These, in turn, are of interest as therapeutic targets and pharmacogenetic markers.
Single‐cell analysis using capillary electrophoresis: Influence of surface support properties on cell injection into the capillary

Capillary electrophoresis (CE) is an important tool of chemical cytometry. Whole‐cell analysis using CE starts with cell injection into the capillary by either siphoning or electroosmosis. However, strong adherence of the cell to the support surface can prevent efficient cell injection and lead to irreproducible analysis. Here we evaluated several surfaces as potential cell supports for HT29 cells (human colon adenocarcinoma). These cells strongly adhered to the surface of untreated glass or polystyrene. Hydrophobic coating with dimethyldichlorosilane (DMS) or Sigmacote® did not significantly reduce cell adhesion. In contrast, cell adhesion was reduced significantly when the surface was modified with hydrophilic polymers (hydrogels) such as poly(2‐hydrohyethyl methacrylate) (PHEMA) and polyvinyl alcohol (PVA). In addition to their pronounced antiadhesive properties, PHEMA and PVA coatings were the most biocompatible (had highest survival of cells in contact with surface). Hydrogel‐coated polystyrene plates were tested as a commercial alternative to hydrogel‐coated glass slides. The cell adhesive properties of such plates were similar to those of PHEMA and PVA. However, the biocompatibility of the plates was lower than that of the other surfaces tested. Moreover, in contrast to PHEMA‐ and PVA‐coated glass slides, the plates were sensitive to UV light and therefore should not be used when fluorescent image microscopy with UV excitation precedes CE. The analyses of the data obtained showed that PHEMA‐ and PVA‐coated glass slides were the most suitable cell supports for cell injection into the capillary.
Enduring effects of nurse home visitation on maternal life course: a 3-year follow-up of a randomized trial.

CONTEXT A home visitation program using nurses to improve maternal and child outcomes had favorable results in a randomized trial with a primarily white, semirural population. Many of the short-term findings have been replicated with urban blacks, but whether the program will continue to demonstrate effectiveness after its conclusion is uncertain. OBJECTIVE To determine the effectiveness of a prenatal and infancy home visitation program on the maternal life course of women in an urban environment 3 years after the program ended. DESIGN AND SETTING Three-year follow-up of a randomized controlled trial of women seen consecutively between June 1990 and August 1991 at an obstetrical clinic in Memphis, Tenn, who were enrolled in a visitation program for 2 years after the birth of their first child. PARTICIPANTS A cohort of 743 women who were primarily black, were pregnant for less than 29 weeks, had no previous live births, and had at least 2 sociodemographic risk factors (unmarried, <12 years of education, or unemployed). INTERVENTION An average of 7 (range, 0-18) home visits during pregnancy and 26 (range, 0-71) from birth to the child's second birthday. MAIN OUTCOME MEASURES Rate of subsequent pregnancy, mean interval between first and second birth, and mean number of months of welfare use. RESULTS Compared with the control group, women who received home visits by nurses had fewer subsequent pregnancies (1.15 vs 1.34; P=.03), fewer closely spaced subsequent pregnancies (0.22 vs 0.32; P=.03), longer intervals between the birth of the first and second child (30.25 vs 26.60 months; P=.004), and fewer months of using Aid to Families with Dependent Children (32.55 vs 36.19; P=.01) and food stamps (41.57 vs 45.04; P=.005). Compared with the effect of the program while the program was in operation, the effect after it ended was essentially equal for Aid to Families with Dependent Children, greater for food stamps, greater for rates of closely spaced subsequent pregnancies, and smaller for rates of subsequent pregnancy overall. CONCLUSIONS We found enduring effects of a home visitation program on the lives of black women living in an urban setting. While these results were smaller in magnitude than those achieved in a previous trial with white women living in a semirural setting, the direction of the effects was consistent across the 2 studies.
Site-Specific DNA Binding of the Schizosaccharomyces pombe Origin Recognition Complex Is Determined by the Orc4 Subunit

ABSTRACT The mechanism by which origin recognition complexes (ORCs) identify replication origins was investigated using purified Orc proteins from Schizosaccharomyces pombe. Orc4p alone bound tightly and specifically to several sites withinS. pombe replication origins that are genetically required for origin activity. These sites consisted of clusters of A or T residues on one strand but were devoid of either alternating A and T residues or GC-rich sequences. Addition of a complex consisting of Orc1, -2, -3, -5, and -6 proteins (ORC-5) altered neither Orc4p binding to origin DNA nor Orc4p protection of specific sequences. ORC-5 alone bound weakly and nonspecifically to DNA; strong binding required the presence of Orc4p. Under these conditions, all six subunits remained bound to chromatin isolated from each phase of the cell division cycle. These results reveal that the S.pombe ORC binds to multiple, specific sites within replication origins and that site selection, at least in vitro, is determined solely by the Orc4p subunit.
Preventing Progression and Improving Survival with BCG Maintenance

BCG immunotherapy provides a superior reduction in tumour recurrence compared with chemotherapy. Unlike chemotherapy, however, it also appears to reduce disease progression. The benefit of BCG is long-term, but protection from disease progression without maintenance therapy is lost when comparisons are made after 15 years. Data suggest that optimal maintenance therapy with BCG provides even better protection from tumour recurrence, reduces disease progression and improves survival. Maintenance BCG schedules using single instillations at 1–3 month intervals have not been proved to be better than induction alone. However, a Southwest Oncology Group (SWOG) study using three, weekly instillations of Connaught BCG, found this regimen to be markedly superior. Before the introduction of BCG, carcinoma in situ (CIS) would progress to muscle invasion in 52% of patients. In the SWOG study, the additional instillations increased the complete response rate in CIS from the expected 68% to 84%. With maintenance BCG, long-term (7 years) tumour recurrence in high-risk patients reduced from the expected 52% with a single 6-week course to only 25% (p < 0.000001). Worsening-free survival, defined as the absence of evidence of disease progression, including pathologic stage T2 or greater disease, or the need for systemic chemotherapy, radiation therapy or cystectomy, significantly increased (p < 0.049, log rank test). In 391 randomized patients, the already excellent 86% survival at 4 years observed with induction therapy improved to 92% in patients receiving maintenance BCG (p < 0.04). There is thus increasingly good evidence that BCG maintenance therapy, at the optimal treatment schedule, provides superior protection from tumour progression and recurrence, and improves long-term survival.
Influence of Radial Force Harmonics With Low Mode Number on Electromagnetic Vibration of PMSM

Permanent magnet synchronous machines (PMSM) have been widely used in a variety of applications. A strong electromagnetic force exists between the rotor magnets and the stator core in a PMSM. The force directly causes mechanical deformation and vibration of the stator. In small PM motors, mechanical vibration comes mainly from the electromagnetic force of the stator. This paper gives the general expression of the frequency and corresponding mode number of radial force harmonics for a PMSM with a three-phase symmetrical double-layer winding. The paper shows that the lowest mode number of radial force harmonics is the greatest common divisor of pole number and slot number. The force harmonics with a low mode number can induce a high mechanical vibration, especially for PMSMs with a fractional slot combination. This is simulated using a weak-coupling electromagnetic-mechanical finite element model. To illustrate the influence of radial force harmonics with a low mode number on vibration, a method to eliminate the lowest mode number force harmonics for the fractional slot combination motor is proposed. A test rig for the 12-slot 8-pole prototype motor is set up. The experimental and simulated results confirm that force harmonics with low mode number have a major impact on vibration.