Miracle-dz/UniFAR-FTUs huggingface dataset:
Growth-related Changes in Oxygen Uptake and Heart Rate during Progressive Exercise in Children

Summary: Although body size and muscle mass increase considerably during growth in children, certain aerobic responses to exercise appear to be regulated so that the delivery of oxygen to muscle is maintained at optimized levels. We proposed that the relationship between oxygen uptake, (VO2) and heart rate (HR) was one of the regulated responses. We further hypothesized that the increase in VO2 per increase in HR during progressive exercise would differ in subjects of different size, but when normalized to body weight would be constant since changes in muscle mass are highly correlated to changes in body mass. To test this, we performed a cross-sectional study of 107 normal children, 50 girls and 57 boys ranging in age from 6 to 17 years. The protocol consisted of a continuously increasing work rate on a cycle ergometer, to the limit of the child's tolerance (ramp forcing function). Gas exchange was measured breath-by-breath for the determination of VO2, and heart rate was measured beat-by-beat. We used linear regression techniques to determine M, the slope, and B, the y intercept of the equation: VO2=M x HR-B. In both boys and girls, M increased significantly with body weight, but when normalized for body weight (M /kg), there was no systematic change with increasing weight or age, the mean value being 0.33 ± 0.10 ml/min/kg (SD). The mean value for the boys was 0.37 ± 0.10 which was significantly greater than that of the girls (0.29 ± 0.08, p < 0.01). Using allometric equations, we found M, B, and the O2-pulse (VO2/HR) at a heart rate of 140 beats/min and at the anaerobic threshold, all scaled in direct proportion to body weight (i.e., to 1.0 power of body weight). We conclude that during growth, the output of the heart is closely tied to the size of the muscles so that delivery of oxygen during exercise is maintained at optimized levels from early in childhood.
A Low Cost Superregenerative Saw Stabilized Receiver

This paper describes a new superregenerative receiver that overcomes the frequency drift and excessive bandwidth problems of the present state-of-the-art devices with little or no sacrifice in receiver simplicity and cost. The receiver makes use of a new third generation surface acoustic wave device to stabilize the center frequency and decrease the bandwidth of the regenerative circuit.
The Effect of Gene Variants on Levonorgestrel Pharmacokinetics When Combined With Antiretroviral Therapy Containing Efavirenz or Nevirapine

Reduced levonorgestrel concentrations from the levonorgestrel contraceptive implant was previously seen when given concomitantly with efavirenz. We sought to assess whether single nucleotide polymorphisms (SNPs) in genes involved in efavirenz and nevirapine metabolism were linked to these changes in levonorgestrel concentration. SNPs in CYP2B6, CYP2A6, NR1I2, and NR1I3 were analyzed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV‐positive women using the levonorgestrel implant plus efavirenz‐ or nevirapine‐based antiretroviral therapy (ART), in comparison to ART‐naïve women using multivariate linear regression. Efavirenz group: CYP2B6 516G>T was associated with lower levonorgestrel log10 Cmax and log10 AUC. CYP2B6 15582C>T was associated with lower log10 AUC. Nevirapine group: CYP2B6 516G>T was associated with higher log10 Cmax and lower log10 Cmin. Pharmacogenetic variations influenced subdermal levonorgestrel pharmacokinetics in HIV‐positive women, indicating that the magnitude of the interaction with non‐nucleoside reverse transcriptase inhibitors (NNRTIs) is influenced by host genetics.
Stylized facts of real aggregate activity (1)

Figure 1 shows the U.S. price level from 1869-1996 on a proportionate scale. Over these almost 130 years, the price index has increased considerably. Also evident in Figure 1 are prolonged periods of increases and declines. We say, the ∗Department of Economics, University of Bern, Gesellschaftsstrasse 49, CH-3012 Bern, Switzerland. Email: manuel.waelti@vwi.unibe.ch, Homepage: www.vwi.unibe.ch/staff/waelti/.
Effects of varying levels of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure.

OBJECTIVE To determine the influence of positive end-expiratory pressure (PEEP) on intracranial pressure and cerebral perfusion pressure. DESIGN Neurosurgical intensive care patients requiring intracranial pressure monitoring and mechanical ventilation were studied in a randomized, controlled study. SETTING Tertiary care, neurosurgical intensive care unit. PATIENTS Eighteen patients were enrolled in the study. Patients had posttraumatic head injuries (n = 9), subarachnoid hemorrhage (n = 7), obstructive hydrocephalus (n = 1), and intracerebral hemorrhage of unknown cause (n = 1). INTERVENTIONS Patients had PEEP levels of 5, 10, and 15 cm H2O applied to their lungs. MEASUREMENTS AND MAIN RESULTS Changes in intracranial pressure, mean arterial pressure, and cerebral perfusion pressure were measured. The results were analyzed separately for patients with normal and increased intracranial pressure (> 15 mm Hg). PEEP at 5 cm H2O had no effect on intracranial pressure in the group with normal intracranial pressure. However, PEEP at 10 and 15 cm H2O produced a significant (p < .05) increase in intracranial pressure (1.9 and 1.5 mm Hg, respectively). In the group with increased intracranial pressure, no significant change in intracranial pressure occurred at any of the PEEP levels used. In both groups, cerebral perfusion pressure was unchanged throughout. CONCLUSIONS In patients with normal intracranial pressure, PEEP at 5 cm H2O did not significantly alter intracranial pressure. The clinical relevance of the intracranial pressure increase at PEEP levels of 10 and 15 cm H2O is questionable because cerebral perfusion pressure did not change and remained > 60 mm Hg. In patients with increased intracranial pressure, higher levels of PEEP did not significantly change intracranial pressure or cerebral perfusion pressure.
Optimization of closed-loop poles for robust constrained control

The presented paper introduces a relatively simple methodology for robust control system design in case of the limits on the control input signal. For this task efficient simulation and optimization tools of the MATLAB system are fruitfully exploited. The control system design is based on the algebraic approach resulting in the pole-placement problem to be solved. This task is addressed numerically using the standard MATLAB functions for nonlinear constrained optimization to meet both the constraints on the manipulated variable and robustness of the resultant closed-loop. Certain control quality criteria and a procedure are introduced for this purpose. The suggested algorithm is illustrated on the AMIRA DR300 servo-system controlled both in robust sense and with limited control action. Presented results show applicability of the suggested approach.
Escherichia coli ribosomal RNA transcription: regulatory roles for ppGpp, NTPs, architectural proteins and a polymerase‐binding protein

Ribosomal RNA transcription can limit the rate of Escherichia coli growth and is subject to complex regulation. Somehow, the cell is able to sense the general nutritional environment and adjust rRNA transcription so that an appropriate number of ribosomes is produced. This review discusses the current state of affairs, including recent information about the involvement of two nucleotide regulators, two architectural protein regulators, one new co‐regulator and stalled ribosomes.
Lenalidomide versus thalidomide based regimens as first-line therapy for patients with multiple myeloma

Abstract Thalidomide (T) and lenalidomide (R) have been used as first-line therapy for previously untreated myeloma. However, direct head-to-head comparison between them is lacking. We performed an indirect meta-analysis to assess the treatment effects of lenalidomide- versus thalidomide-based regimens using common comparators. A comprehensive literature search was undertaken. The initial search yielded 1345 citations, of which 11 randomized controlled trials (RCTs) enrolling 4162 patients met the inclusion criteria. Indirect comparison of lenalidomide versus thalidomide maintenance after autologous stem cell transplant (ASCT) showed a progression-free survival (PFS) benefit (hazard ratio [HR] 0.75, 95% confidence interval [CI] [0.67, 0.85], p < 0.001) but no survival difference (HR 0.83, [0.63, 1.09], p = 0.19) when using observation/placebo as the common comparator. Similarly, the indirect comparison of melphalan–prednisone plus lenalidomide followed by lenalidomide maintenance (MPR-R) versus melphalan–prednisone–thalidomide induction followed by thalidomide maintenance (MPT-T) showed a statistically significant PFS advantage for MPR-R (HR 0.53, 95% CI [0.46, 0.60], p < 0.001), but no difference for overall survival (OS) (HR 0.97, [0.81, 1.17], p = 0.74). Additionally, the significant heterogeneity among pooled studies for the outcome of discontinuation rate due to treatment-related adverse events between MPT-T and MPR-R subgroups (p = 0.007) indicated that the discontinuation rate from thalidomide trials seems to be higher than that from lenalidomide trials. In conclusion, lenalidomide seems to be a more potent and less toxic agent than thalidomide in the treatment of patients with multiple myeloma. Further, a direct head-to-head trial comparing lenalidomide versus thalidomide is clearly warranted.
Tris(1-ethyl-3-methylimidazolium) hexabromidoeuropate(III)

The crystal structure of the title compound, (C6H11N2)3[EuBr6], consists of 1-ethyl-3-methylimidazolium cations and centrosymmetric octahedral hexabromidoeuropate anions. The [EuBr6]3− anions are located at the corners and face-centres of the monoclinic unit cell. Characteristic hydrogen-bonding interactions can be observed between the bromide anions and the acidic H atoms of the imidazolium cations.
Molecular cytogenetic characterization of pancreas cancer cell lines reveals high complexity chromosomal alterations

Karyotype analysis can provide clues to significant genes involved in the genesis and growth of pancreas cancer. The genome of pancreas cancer is complex, and G-band analysis cannot resolve many of the karyotypic abnormalities seen. We studied the karyotypes of 15 recently established cell lines using molecular cytogenetic tools. Comparative genomic hybridization (CGH) analysis of all 15 lines identified genomic gains of 3q, 8q, 11q, 17q, and chromosome 20 in nine or more cell lines. CGH confirmed frequent loss of chromosome 18, 17p, 6q, and 8p. 14/15 cell lines demonstrated loss of chromosome 18q, either by loss of a copy of chromosome 18 (n = 5), all of 18q (n = 7) or portions of 18q (n = 2). Multicolor FISH (Spectral Karyotyping, or SKY) of 11 lines identified many complex structural chromosomal aberrations. 93 structurally abnormal chromosomes were evaluated, for which SKY added new information to 67. Several potentially site-specific recurrent rearrangements were observed. Chromosome region 18q11.2 was recurrently involved in nine cell lines, including formation of derivative chromosomes 18 from a t(18;22) (three cell lines), t(17;18) (two cell lines), and t(12;18), t(15;18), t(18;20), and ins(6;18) (one cell line each). To further define the breakpoints involved on chromosome 18, YACs from the 18q11.2 region, spanning approximately 8 Mb, were used to perform targeted FISH analyses of these lines. We found significant heterogeneity in the breakpoints despite their G-band similarity, including multiple independent regions of loss proximal to the already identified loss of DPC4 at 18q21.
Type IV secretion: intercellular transfer of macromolecules by systems ancestrally related to conjugation machines

Bacterial conjugation systems are highly promiscuous macromolecular transfer systems that impact human health significantly. In clinical settings, conjugation is exceptionally problematic, leading to the rapid dissemination of antibiotic resistance genes and other virulence traits among bacterial populations. Recent work has shown that several pathogens of plants and mammals –Agrobacterium tumefaciens, Bordetella pertussis, Helicobacter pylori and Legionella pneumophila– have evolved secretion pathways ancestrally related to conjugation systems for the purpose of delivering effector molecules to eukaryotic target cells. Each of these systems exports distinct DNA or protein substrates to effect a myriad of changes in host cell physiology during infection. Collectively, secretion pathways ancestrally related to bacterial conjugation systems are now referred to as the type IV secretion family. The list of putative type IV family members is increasing rapidly, suggesting that macromolecular transfer by these systems is a widespread phenomenon in nature.
Exploiting altered patterns of choline kinase-alpha expression on human prostate tissue to prognosticate prostate cancer

Aims Malignant transformation results in overexpression of choline-kinase (CHK) and altered choline metabolism, which is potentially detectable by immunohistochemistry (IHC). We investigated the utility of CHK-alpha (CHKA) IHC as a complement to current diagnostic investigation of prostate cancer by analysing expression patterns in normal (no evidence of malignancy) and malignant human prostate tissue samples. Methods As an initial validation, paraffin-embedded prostatectomy specimen blocks with both normal and malignant prostate tissue were analysed for CHKA protein and mRNA expression by western blot and quantitative reverse transcriptase PCR (qRT-PCR), respectively. Subsequently, 100 paraffin-embedded malignant prostate tumour and 25 normal prostate cores were stained for both Ki67 (labelling-index: LI) and CHKA expression. Results The validity of CHKA-antibody was verified using CHKA-transfected cells and siRNA knockdown. Immunoblotting of tissues showed good resolution of CHKA protein in malignant prostate, verifying use of the antibody for IHC. There was minimal qRT-PCR detectable CHKA mRNA in normal tissue, and conversely high expression in malignant prostate tissues. IHC of normal prostate cores showed mild (intensity) CHKA expression in only 28% (7/25) of samples with no Ki67 expression. In contrast, CHKA was expressed in all malignant prostate cores along with characteristically low proliferation (median 2% Ki67-LI; range 1–17%). Stratification of survival according to CHK intensity showed a trend towards lower progression-free survival with CHK score of 3. Conclusions Increased expression of CHKA, detectable by IHC, is seen in malignant lesions. This relatively simple cost-effective technique (IHC) could complement current diagnostic procedures for prostate cancer and, therefore, warrants further investigation.
Comparative distribution patterns of type I and III collagens and fibronectin in human arteriosclerotic aorta.

The distribution patterns of type I and III collagens and fibronectin were studied in arteriosclerotic lesions of human aortas as well as in the regions devoid of any macroscopic lesions of the same aortas. Frozen sections were analyzed for fibronectin and collagens by indirect immunofluorescence or immunoperoxidase analysis with specific antisera prepared in rabbits against human plasma fibronectin and against human type I and III collagens. Tissue samples were also stained for type I and III collagen distribution using Picro Sirius red according to the method described by Junqueira et al. (1979). In the regions devoid of any visible macroscopic lesions, there is a co-distribution in the media of the aortic wall of type I and III collagens, with a predominance of type I collagen. Type I collagen is also visible in the intima, as a continuous layer. This is attributed to an age-dependent change of the aorta (arteriosclerosis). Fibronectin can be demonstrated as a thin layer in the subendothelium and as a weak immunofluorescence over the media. In recent or evolutive arteriosclerotic plaques, fibronectin and type III collagen appear to be strongly increased and superimposed. There is also an increase of type I collagen in the intimal region of the plaque. The co-distribution of type III collagen and fibronectin in the arteriosclerotic plaques may suggest a tissue-repair-type of process, analogous to that which can be observed during wound healing. Our results suggest that in arteriosclerotic lesions, type III collagen and fibronectin are predominantly synthesized. (ABSTRACT TRUNCATED AT 250 WORDS)
IL-17RA in Intestinal Inflammation: Structure, Signaling, Function, and Clinical Application

Abstract:Interleukin-17 receptor A (IL-17RA) is responsible for both IL-17A and IL-25 (IL-17E) signaling pathways. Current evidences suggest distinct but interactive responses between IL-17A and IL-25 signaling, both of which are critical for intestinal immune homeostasis. IL-17RA is assumed to regulate this counterbalance and therefore becomes a crucial molecule in mucosal immunology. In this review, we will describe the structure of IL-17RA, compare IL-17A and IL-25 signaling pathways, and emphasize on the function of IL-17RA in intestinal inflammation and discuss current evidences of accomplished and ongoing clinical trials with monoclonal antibodies targeting Th17 pathway, especially IL-17RA.
Comparative metabolism and toxicity of dichlorobenzenes in Sprague-Dawley, Fischer-344 and human liver slices

1 Precision-cut liver slices, prepared from Sprague- Dawley and Fischer-344 rats and donated human liver tis sue, were used to identify differences in 1,2-dichloroben zene (1,2-DCB), 1,3-dichlorobenzene (1,3-DCB) and 1,4- dichlorobenzene (1,4-DCB) metabolism and how it may relate to toxicity. 2 Rat and human liver slices were incubated with 1 mM of either dichlorobenzene to determine metabolism and toxi city, at 2 and 6 h of organ culture. 3 The human liver slices metabolised the dichloroben zenes to a greater extent than those from either of the rat strains. Liver slices from the Fischer-344 strain had a higher metabolic rate than the slices from the Sprague- Dawley rat strain. 4 The metabolic rate of dichlorobenzene isomers did not consistently correlate with its toxicity. For example, human slices did not exhibit any hepatotoxicity, even though they metabolised these compounds to a greater extent than either rat strain. 5 Cross species covalent binding did not correlate with toxicity endpoints measured in this study. 6 The phase two metabolite profiles for each of the iso mers in human and rat slices were similar in that the glu tathione-cysteine conjugate was the major metabolite. 7 The use of an in vitro system which utilises human liver slices might provide an important bridge between animal derived data and the human situation.
Large-subunit ribosomal RNA systematics of symbiotic dinoflagellates: morphology does not recapitulate phylogeny.

Biochemical, histological, physiological, and genetic evidence indicates that dinoflagellates symbiotic with marine invertebrates are a heterogeneous complex of taxa, representing at least five genera in three orders. Despite a wealth of data regarding morphological, biochemical, and behavioral differences among symbiotic dinoflagellates, knowledge concerning patterns of diversification is limited. I analyzed approximately 900 bp of the 5' end of the large-subunit ribosomal RNA gene from 14 dinoflagellate isolates: six cultured Symbiodinium specimens, two cultured symbiotic Gymnodinium, two algal samples isolated from reef-building corals, an algal sample obtained from cultures of the jellyfish Cassiopea xamachana, and three free-living Gymnodinium isolates. Results show that morphological similarities among the examined symbiotic taxa do not necessarily correspond with molecular phylogeny. The included Symbiodinium taxa represent a paraphyletic assemblage while Gymnodinium is reconstructed as a polyphyletic assemblage. Analysis indicates that all the included symbiotic dinoflagellates descended from a common, symbiotic ancestor (though within the dinoflagellates, symbiosis is a polyphyletic trait). Additionally, two free-living dinoflagellates emerge within the symbiotic clade, suggesting that the symbiotic lifestyle has been lost at least once in this group. It has been hypothesized that rates of evolution within mutualistic endosymbioses should be reduced relative to free-living taxa. However, results indicate that rates of molecular, morphological, biochemical and behavioral change are similar among branches leading to symbiotic and free-living dinoflagellates.
Perioperative hyperoxygenation and wound site infection following surgery for acute appendicitis: a randomized, prospective, controlled trial.

OBJECTIVE To assess the influence of hyperoxygenation on surgical site infection by using the most homogeneous study population. DESIGN A randomized, prospective, controlled trial. SETTING Department of surgery in a government hospital. PATIENTS A total of 210 patients who underwent open surgery for acute appendicitis. In the study group, patients received 80% oxygen during anesthesia, followed by high-flow oxygen for 2 hours in the recovery room. The control group received 30% oxygen, as usual. INTERVENTION Open appendectomy via incision in the right lower quadrant of the abdomen. MAIN OUTCOME MEASURES Surgical site infection, mainly assessed by the ASEPSIS (additional treatment, serous discharge, erythema, purulent discharge, separation of deep tissues, isolation of bacteria, and stay in hospital prolonged >14 days) system score. RESULTS Surgical site infections were recorded in 6 of 107 patients (5.6%) in the study group vs 14 of 103 patients (13.6%) in the control group (P = .04). Significant differences in the ASEPSIS score were also found. The mean hospital stay was longer in the control group (2.92 days) compared with the study group (2.51 days) (P = .01). CONCLUSION The use of supplemental oxygen is advantageous in operations for acute appendicitis by reducing surgical site infection rate and hospital stay. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01002365.
Recent Advances in Research on Parkinson Disease: Synuclein and Parkin

Background: Until recently, most research effort on Parkinson disease (PD) was focused on possible environmental causes. With the discovery of mutations in two genes, synuclein and parkin, which are responsible for rare familial forms of the disease, there has been a major change in emphasis. Review Summary: The first genetic cause of PD to be identified was in the gene for synuclein, resulting in an alanine to threonine substitution at position 53. The likely pathogenetic significance of this mutation was supported by the discovery of a second mutation, and the presence of synuclein in Lewy bodies in sporadic PD cases. The synuclein protein has a tendency to self aggregate, and this tendency is increased in the mutants, and by oxidative injury to the protein. While there is growing evidence in animal models that overexpression of wildtype or mutant synuclein may lead to intracytoplasmic inclusions, and dysfunction of dopamine neurons, no animal models in rodents have yet replicated all important features of the disease. Deletions or point mutations in the gene for parkin cause an autosomal recessive, early onset form of parkinsonism. The parkin protein functions as an E3 ubiquitin-protein ligase, and it is involved in the degradation of cellular proteins by the proteasomal pathway. It is hypothesized that the loss of this function results in the toxic accumulation of its target proteins. Conclusions: Research on these inherited forms of PD is pointing towards a common theme, that disturbances of cellular protein handling can lead to the death of dopamine neurons in PD.