Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationship Between Blood Pressure, Cerebral Electrical Activity, Cerebral Fractional Oxygen Extraction, and Peripheral Blood Flow in Very Low Birth Weight Newborn Infants

There is uncertainty about the level of systemic blood pressure required to maintain adequate cerebral oxygen delivery and organ integrity. This prospective, observational study on 35 very low birth weight infants aimed to determine the mean blood pressure (MBP) below which cerebral electrical activity, peripheral blood flow (PBF), and cerebral fractional oxygen extraction (CFOE) are abnormal. Digital EEG, recorded every day on the first 4 d after birth, were analyzed a) by automatic spectral analysis, b) by manual measurement of interburst interval, and c) qualitatively. CFOE and PBF measurements were performed using near-infrared spectroscopy and venous occlusion. MBP was measured using arterial catheters. The median (range) of MBP recorded was 32 mm Hg (16–46). The EEG became abnormal at MBP levels below 23 mm Hg: a) the relative power of the delta (0.5–3.5 Hz) frequency band was decreased, b) interburst intervals were prolonged, and c) all four qualitatively abnormal EEG (low amplitude and prolonged interburst intervals) from four different patients were recorded below this MBP level. The only abnormally high CFOE was measured at MBP of 20 mm Hg. PBF decreased at MBP levels between 23 and 33 mm Hg. None of the infants in this study developed cystic periventricular leukomalacia. One infant (MBP, 22 mm Hg) developed ventricular dilatation after intraventricular hemorrhage. The EEG and CFOE remained normal at MBP levels above 23 mm Hg. It would appear that cerebral perfusion is probably maintained at MBP levels above 23 mm Hg.
Global transcriptional analysis of nuclear reprogramming in the transition from MEFs to iPSCs

Induced pluripotent stem cells (iPSCs) are flourishing in the investigation of cell reprogramming. However, we still know little about the sequential molecular mechanism during somatic cell reprogramming (SCR). Here, we first observed rapid generation of colonies whereas mouse embryonic fibroblasts (MEFs) were induced by OCT4, SOX2, KLF4 (OSK), and vitamin C for 7 days. The colony's global transcriptional profiles were analyzed using Affymetrix microarray. Microarray data confirmed that SCR was a process in which transcriptome got reversed and pluripotent genes expressed de novo. There were many changes, especially substantial growth expression of epigenetic factors, on transcriptome during the transition from Day 7 to iPSCs indicating that this period may provide ‘flexibility’ genome structure, chromatin remodeling, and epigenetic modifications to rebind to the transcriptional factors. Several biological processes such as viral immune response, apoptosis, cell fate specification, and cell communication were mainly involved before Day 7 whereas cell cycle, DNA methylation, and histone modification were mainly involved after Day 7. Furthermore, it was suggested that p53 signaling contributed to the transition ‘hyperdynamic plastic’ cell state and assembled cell niche for SCR, and small molecular compounds useful for chromatin remodeling can enhance iPSCs by exciting epigenetic modification rather than the exogenous expression of more TFs vectors.
Modeling Subgenomic Hepatitis C Virus RNA Kinetics during Treatment with Alpha Interferon

ABSTRACT Although replicons have been used to demonstrate hepatitis C virus (HCV) inhibition by alpha interferon (IFN-α), the detailed inhibition kinetics required to mathematically model HCV RNA decline have been lacking. Therefore, we measured genotype 1b subgenomic replicon (sg1b) RNA levels under various IFN-α concentrations to assess the inhibition kinetics of intracellular HCV RNA. During nine days of IFN-α treatment, sg1b RNA decreased in a biphasic, dose-dependent manner. Using frequent measurements to dissect these phases during IFN-α treatments of 100 and 250 U/ml revealed that the first-phase sg1b RNA decline began ∼12 h posttreatment, continued for 2 to 4 days, and then exhibited a distinct flat or slower second phase. Based on these data, we developed a mathematical model of IFN-α-induced intracellular sg1b RNA decline, and we show that the mechanism(s) mediating IFN-α inhibition of HCV acts primarily by reducing sg1b RNA amplification, with an additional effect on HCV RNA stability/degradation detectable at a dose of 250 U/ml IFN-α. While the extremely slow or flat second phase of viral RNA inhibition observed in vitro, in which there is little or no cell death, supports the in vivo modeling prediction that the more profound second-phase decline observed in IFN-α-treated patients reflects immune-mediated death/loss of productively infected cells, the second-phase decline in viral RNA with a dose of 250 U/ml IFN-α suggests that a further inhibition of intracellular HCV RNA levels may contribute as well. As such, dissection of HCV IFN-α inhibition kinetics in vitro has brought us closer to understanding the mechanism(s) by which IFN-α may be inhibiting HCV in vivo.
Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine

Halofantrine, an antimalarial drug that prolongs the QT interval, is metabolized into N‐debutyl‐halofantrine by cytochrome P450 (CYP) 3A4. Grapefruit juice increases the bioavailability of several orally administered CYP3A4 substrates by inhibiting CYP3A4 at the enterocyte level and could therefore increase the risk of halofantrine‐induced QT interval prolongation. We studied the effect of grapefruit juice on halofantrine bioavailability and on QT interval prolongation associated with its oral administration.
Echinococcus granulosus from Mexican pigs is the same strain as that in Polish pigs

Abstract Samples of Echinococcus granulosus from seven pigs from Mexico were compared with isolates of the parasite from pigs in Poland and representative strains and species of Echinococcus. Isolates from pigs in Mexico were found to be genetically identical to E. granulosus from Polish pigs and distinct from other major genotypes by sequencing part of the mitochondrial cytochrome c oxidase I (COI) mtDNA locus, restriction fragment length polymorphism (RFLP) of the polymerase chain reaction (PCR) amplified rDNA internal transcribed spacer (ITS) 1 using five different enzymes, and random amplified polymorphic DNA (RAPD) analysis. These results were complemented by data on hook morphology and together strengthen the view that Echinococcus maintained in a cycle involving pigs and dogs is a distinct strain that is conserved genetically in different geographical areas. The present study supports the close relationship of the cervid, camel and pig strains and raises the question of their taxonomic status.
A typology of non‐adherence in pediatric renal transplant recipients

Abstract: We reviewed 112 pediatric renal transplant recipients to document the rate of medication non‐adherence (NA) and to examine the relationships between NA, comorbid psychiatric illness, and the outcome variables of acute and chronic rejection and graft loss. A total of 32.5% of subjects had clinically significant NA with treatment based on review of serum immunosuppressant levels. NA was found to be significantly related to acute and chronic rejection, and graft loss (p < 0.001). NA was also related to the presence of comorbid psychiatric illness (p < 0.001). Logistic regression indicated that NA was a significant predictor for acute and chronic rejection, while psychiatric illness predicted graft loss. Adolescents had significantly higher rates of NA as well as shorter intervals between transplant date and onset of NA when compared with child patients (p < 0.001). Physician ratings of the primary reasons for NA suggested that lack of parental supervision and parent–child conflict were the major factors related to NA.
Guided Online or Face-to-Face Cognitive Behavioral Treatment for Insomnia: A Randomized Wait-List Controlled Trial.

STUDY OBJECTIVES To compare the efficacy of guided online and individual face-to-face cognitive behavioral treatment for insomnia (CBT-I) to a wait-list condition. METHODS A randomized controlled trial comparing three conditions: guided online; face-to-face; wait-list. Posttest measurements were administered to all conditions, along with 3- and 6-mo follow-up assessments to the online and face-to-face conditions. Ninety media-recruited participants meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for insomnia were randomly allocated to either guided online CBT-I (n = 30), individual face-to-face CBT-I (n = 30), or wait-list (n = 30). RESULTS At post-assessment, the online (Cohen d = 1.2) and face-to-face (Cohen d = 2.3) intervention groups showed significantly larger treatment effects than the wait-list group on insomnia severity (insomnia severity index). Large treatment effects were also found for the sleep diary estimates (except for total sleep time), and anxiety and depression measures (for depression only in the face-to-face condition). Face-to-face treatment yielded a statistically larger treatment effect (Cohen d = 0.9) on insomnia severity than the online condition at all time points. In addition, a moderate differential effect size favoring face-to-face treatment emerged at the 3- and 6-mo follow-up on all sleep diary estimates. Face-to-face treatment further outperformed online treatment on depression and anxiety outcomes. CONCLUSIONS These data show superior performance of face-to-face treatment relative to online treatment. Yet, our results also suggest that online treatment may offer a potentially cost-effective alternative to and complement face-to-face treatment. CLINICAL TRIAL REGISTRATION Clinicaltrials.gov, NCT01955850. COMMENTARY A commentary on this article appears in this issue on page 13.
In silico approach to ascertain the calcium dependent role of Plasmodium falciparum SERA5

The P. falciparum serine repeat antigen (PfSERA5) is the most abundantly expressed protein in the parasitophorous vacuole during the asexual blood stage and serves as both drug and vaccine target. The processed central fragment (56 KDa) of PfSERA5 is implicated to play an important role in parasite exit (egress) during schizont rupture from erythrocytes. Structural characterization of its enzymatic domain supports protease-like function for this central domain. The understanding of exact functional role of PfSERA5 in parasite egress remains unconfirmed as recent studies also indicate an indispensable non-catalytic role for PfSERA5 putative enzyme domain in the blood stage. No structural insight into PfSERA5 prodomain is available. Structure prediction of PfSERA5 prodomain using in silico approach in our study, showed it to have structural similarity with calcium-binding proteins. An earlier observation of steep rise in intracellular calcium concentration as an important factor in egress makes the prodomain calcium-binding role significant. The implication of calcium on structure and activity of PfSERA5 putative enzyme domain is also unknown, and such information would aid to substantiating any calcium-dependent effects on PfSERA5. To understand this, we performed molecular dynamic (MD) simulation both in the presence and absence of calcium. MD results show secondary structure conformational differences in local regions of protein structure. Our results support calcium to be an important parameter for stability and function of PfSERA5. This computational assessment suggest a need to design future experiments like calcium-dependent inhibition studies to reveal exact functional role of PfSERA5 in parasite egress.
A superior solution to control the connection repeatability of Coaxial Airline Impedance standards used for network analyzer verification

There have been many attempts with regard to mitigate the effects of pin gap when dealing with beadless (unsupported) airline impedance standards in order to improve calibration accuracy. This paper discusses common mechanical and electrical problems with the use of beadless airlines. Connection repeatability is a main concern since these errors cannot be corrected for. There are many aspects which can influence connection repeatability of beadless airlines. Pin gap of the mating connectors can greatly influence the center conductor's longitudinal position with respect to its outer conductor is one important example. Beaded Coaxial Airline Impedance standards can offer advantages over beadless versions. Some of these advantages are: known pin gap on each end when mated, good concentricity, ease of use and reduced risk in damage when mated with another connector, etc. When used as verification standards, beaded airlines can offer improved reproducibility and repeatability characteristics by eliminating the various connection repeatability problems associated with beadless airlines.
Solid-Phase Synthesis of the Lipopeptide Myr-HBVpreS/2-78, a Hepatitis B Virus Entry Inhibitor

Chronic HBV infection is the leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Synthetic peptides derived from the N-terminus of the large HBV envelope protein (L-protein) have been shown to efficiently block HBV entry. Myr-HBVpreS/2-78, the parent compound of these drugs, inhibits human HBV infection in vitro and in vivo. An efficient synthesis is required, as these peptides constitute a novel class of anti HBV drugs. Consequently, the solid phase synthesis of the N-terminal 77 amino acids of the viral L-protein was studied in detail. The peptide was N-terminally myristoylated to resemble the natural, postranslationally modified protein. The synthesis was monitored using the Fmoc cleavage pattern of the solid phase synthesis on a standard peptide synthesizer and by LC-MS analyses of the arising side products. “Difficult sequences” in the positions 42-47 of the peptide sequence complicate the efficient synthesis of the 77-mer peptide HBVpreS/2-78. Attempts were undertaken to optimize the synthesis by heating, double coupling or the use of pseudoproline dipeptides. HPLC-MS analyses showed that the efficiency of the synthesis could be increased best by temperature elevation. This resulted in a higher purity of the crude product after solid phase synthesis. It was possible to minimize the occurrence of side products due to the positive effects related to higher reaction temperature. In conclusion, the peptide is accessible by stepwise SPPS without the necessity of segment coupling.
High-Molecular-Weight Aggregates of Therapeutic Insulin: In Vitro Measurements of Receptor Binding and Bioactivity

On the basis of a monomeric insulin standard, ∼28% of total circulating immunoreactive insulin in insulin-dependent diabetes mellitus (IDDM) is a covalent aggregate of insulin. This aggregate probably originates in therapeutic insulin preparations. In this study, the activity of these aggregates was compared with that of monomeric insulin with regard to behavior in the radioimmunoassay, binding to insulin receptors, and biologic activity in isolated rat adipose cells. Molar activity of the aggregate in the insulin radioimmunoassay was approximately twice (240%) that of monomeric insulin, whereas the log-logit slope produced by the aggregate was indistinguishable from that of monomeric insulin. Insulin-receptor binding was determined by displacement of 125I-labeled A14-insulin by insulin or insulin aggregate (10−10–10−5 M). The free-insulin and aggregate concentrations required for half-maximal displacement of 125I-insulin were 4.0 × 10−10 and 2.25 × 10−9 M, respectively. [1-14C]glucose incorporation into 14CO2, glyceride-glycerol, and fatty acids was measured over a wide range of insulin monomer and aggregate concentrations (0–8 nM). In the bioassay, the maximal rates of glucose metabolism were equal (normal responsiveness). However, the concentration of insulin aggregates producing half-maximal stimulation of glucose metabolism was threefold greater than that of insulin (140 vs. 46 pM, respectively), indicating decreased sensitivity of the adipose cells to the aggregates. This was associated with a sixfold decrease in the Kd for binding of aggregates to adipose cell insulin receptors compared with binding of monomeric insulin. Taken together, these findings may partially explain the apparent discrepancies between measured concentrations of circulating immunoreactive insulin and bioactive insulin in IDDM. These data are consistent with the hypothesis that the aggregates are largely composed of insulin dimers.
An Investigation of Case-Based Instructional Strategies on Learning, Retention, and Ethical Decision-Making

Case-based instruction has been successfully employed by educators across various fields; Revised however, little is known about how individuals work with cases during the learning process. We examined two well-established instructional strategies: Elaboration and self-development of narratives. Participants were randomly assigned to (1) elaborate on a given case, (2) develop their own case, (3) elaborate on a self-developed case, or (4) a control condition. Findings indicated that those who elaborated on a given case and the control group outperformed the other treatment groups in terms of case-based knowledge acquisition, execution of sensemaking processes, utilization of ethical decision-making (EDM) strategies, and performance on two EDM measures. Implications for use of instructional strategies in ethics training programs are discussed.
Analysis of the extracellular matrix vesicle proteome in mineralizing osteoblasts

Many key processes central to bone formation and homeostasis require the involvement of osteoblasts, cells responsible for accumulation and mineralization of the extracellular matrix (ECM). During this complex and only partially understood process, osteoblasts generate and secrete matrix vesicles (MVs) into the ECM to initiate mineralization. Although they are considered an important component of mineralization process, MVs still remain a mystery. To better understand their function and biogenesis, a proteomic analysis of MVs has been conducted. MVs were harvested by two sample preparation approaches and mass spectrometry was utilized for protein identification. A total of 133 proteins were identified in common from the two MV preparations, among which were previously known proteins, such as annexins and peptidases, along with many novel proteins including a variety of enzymes, osteoblast‐specific factors, ion channels, and signal transduction molecules, such as 14‐3‐3 family members and Rab‐related proteins. To compare the proteome of MV with that of the ECM we conducted a large‐scale proteomic analysis of collagenase digested mineralizing osteoblast matrix. This analysis resulted in the identification of 1,327 unique proteins. A comparison of the proteins identified from the two MV preparations with the ECM analysis revealed 83 unique, non‐redundant proteins identified in all three samples. This investigation represents the first systematic proteomic analysis of MVs and provides insights into both the function and origin of these important mineralization‐regulating vesicles. J. Cell. Physiol. 210: 325–335, 2007. © 2006 Wiley‐Liss, Inc.
Role of interdomain and interplatelet boundaries on magnetic flux penetration in melt grown YBCO

The microstructure of a melt processed YBCO sample reveals the presence of random domains with aligned platelets separated by microcracks inside the domains. The lower critical field (H/sub c1/) and critical current density (J/sub c/) of these boundaries will be less than that of the grains, and their role in determining the bulk properties cannot be neglected. We have employed a sensitive lock-in flat-band detection technique and recorded the low field ac M-H loops at 33 Hz and 77 K and derived the flux profiles. The results show an enhancement in H/sub c1/ due to melt processing. Inclusion of Y/sub 2/BaCuO/sub 5/, and Ag enhances the H/sub c1/ further. The flux profiles show distinct slope changes at certain fields which reflect different coupling strengths of weaklinks that become operative for flux entry at different applied fields. While the low field flux profiles are found to reflect the effect of residual weaklinks (like liquid phase and micropores) and domain boundaries, those at higher fields might reflect the effect of platelet boundaries.
Sponge: an oversubscription strategy supporting performance interference management in cloud

Resource oversubscription optimizes the utilization of the computing resources. Many well-known virtual machine monitors (VMMs), such as Xen and KVM, adopt this approach to help maximize the yield of the cloud datacenters. That is, with proper resource oversubscription strategies, more virtual machines (VMs) can be supported by limited resources. However, performance interference among VMs hosting in the same physical machines (PMs) exists in cloud environment, and probably aggravated by resource oversubscription strategies, which aims to put more VMs into the same PM. In this paper, we present a resource oversubscription strategy called Sponge targeting cloud platforms. Sponge mitigates the issue of performance interference among the oversubscribed co-hosting VMs. Sponge also provides a VM association strategy for each PM to handle with its besteffort We performed our evaluation on a virtual datacenter simulated by Xen. Our evaluation results show that Sponge improves the resources utilization and manages to make each VM meet its performance requirement even hosting with other VMs in the same PM.
Disk|Crypt|Net: rethinking the stack for high-performance video streaming

Conventional operating systems used for video streaming employ an in-memory disk buffer cache to mask the high latency and low throughput of disks. However, data from Netflix servers show that this cache has a low hit rate, so does little to improve throughput. Latency is not the problem it once was either, due to PCIe-attached flash storage. With memory bandwidth increasingly becoming a bottleneck for video servers, especially when end-to-end encryption is considered, we revisit the interaction between storage and networking for video streaming servers in pursuit of higher performance. We show how to build high-performance userspace network services that saturate existing hardware while serving data directly from disks, with no need for a traditional disk buffer cache. Employing netmap, and developing a new diskmap service, which provides safe high-performance userspace direct I/O access to NVMe devices, we amortize system overheads by utilizing efficient batching of outstanding I/O requests, process-to-completion, and zerocopy operation. We demonstrate how a buffer-cache-free design is not only practical, but required in order to achieve efficient use of memory bandwidth on contemporary microarchitectures. Minimizing latency between DMA and CPU access by integrating storage and TCP control loops allows many operations to access only the last-level cache rather than bottle-necking on memory bandwidth. We illustrate the power of this design by building Atlas, a video streaming web server that outperforms state-of-the-art configurations, and achieves ~72Gbps of plaintext or encrypted network traffic using a fraction of the available CPU cores on commodity hardware.