Miracle-dz/UniFAR-FTUs huggingface dataset:
A 1.7 GHz Fractional-N Frequency Synthesizer Based on a Multiplying Delay-Locked Loop

Although multiplying delay-locked loops allow clock frequency multiplication with very low phase noise and jitter, their application has been so far limited to integer-N multiplication, and the achieved reference-spur performance has been typically limited by time offsets. This paper presents the first published multiplying delay-locked loop achieving fine fractional-N frequency resolution, and introduces an automatic cancellation of the phase detector offset. Both capabilities are enabled by insertion of a digital-to-time converter in the reference path. The proposed synthesizer, implemented in a standard 65 nm CMOS process, occupies a core area of 0.09 mm 2, and generates a frequency ranging between 1.6 and 1.9 GHz with a 190 Hz resolution from a 50 MHz quartz-based reference oscillator. In fractional-N mode, the integrated RMS jitter, including random and deterministic components, is below 1.4 ps at 3 mW power consumption, leading to a jitter-power figure of merit of -232 dB. In integer-N mode, the circuit achieves RMS jitter of 0.47 ps at 2.4 mW power and figure of merit of -243 dB. Thanks to the adoption of the automatic offset cancellation, the reference-spur level is reduced from -32 to -55 dBc.
Inhibition of the receptor‐binding function of clathrin adaptor protein AP‐2 by dominant‐negative mutant μ2 subunit and its effects on endocytosis

Although interactions between the μ2 subunit of the clathrin adaptor protein complex AP‐2 and tyrosine‐based internalization motifs have been implicated in the selective recruitment of cargo molecules into coated pits, the functional significance of this interaction for endocytosis of many types of membrane proteins remains unclear. To analyze the function of μ2–receptor interactions, we constructed an epitope‐tagged μ2 that incorporates into AP‐2 and is targeted to coated pits. Mutational analysis revealed that Asp176 and Trp421 of μ2 are involved in the interaction with internalization motifs of TGN38 and epidermal growth factor (EGF) receptor. Inducible overexpression of mutant μ2, in which these two residues were changed to alanines, resulted in metabolic replacement of endogenous μ2 in AP‐2 complexes and complete abrogation of AP‐2 interaction with the tyrosine‐based internalization motifs. As a consequence, endocytosis of the transferrin receptor was severely impaired. In contrast, internalization of the EGF receptor was not affected. These results demonstrate the potential usefulness of the dominant‐interfering approach for functional analysis of the adaptor protein family, and indicate that clathrin‐mediated endocytosis may proceed in both a μ2‐dependent and ‐independent manner.
Ion Channels and Transporters in Lung Function and Disease Positioning of extracellular loop 1 affects pore gating of the cystic fibrosis transmembrane conductance regulator

Daniel T. Infield, Guiying Cui, Christopher Kuang, and Nael A. McCarty Division of Pulmonology, Allergy and Immunology, Cystic Fibrosis, and Sleep, Department of Pediatrics, Center for Cystic Fibrosis and Airways Disease Research, Emory Children’s Pediatric Research Center, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia; and Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, Georgia
High accuracy pipelined ADC design for wireless LANs

Analog-to-digital converters (ADCs) are devices which accept entrance analog signals and generate digital signals corresponding to them, suitable for processing by microprocessors and other digital devices. Requirements to ADCs constantly become tougher: they should provide high frequency and accuracy of transformation, to have a wide bandwidth and the big dynamic range. That's why it is important to design ADC with high accuracy.
Dietary fiber intake and reduced risk of coronary heart disease in US men and women: the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study.

BACKGROUND Prospective studies suggest that dietary fiber intake, especially water-soluble fiber, may be inversely associated with the risk of coronary heart disease (CHD). METHODS We examined the relationship between total and soluble dietary fiber intake and the risk of CHD and cardiovascular disease (CVD) in 9776 adults who participated in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study and were free of CVD at baseline. A 24-hour dietary recall was conducted at the baseline examination, and nutrient intakes were calculated using Food Processor software. Incidence and mortality data for CHD and CVD were obtained from medical records and death certificates during follow-up. RESULTS During an average of 19 years of follow-up, 1843 incident cases of CHD and 3762 incident cases of CVD were documented. Compared with the lowest quartile of dietary fiber intake (median, 5.9 g/d), participants in the highest quartile (median, 20.7 g/d) had an adjusted relative risk of 0.88 (95% confidence interval [CI], 0.74-1.04; P =.05 for trend) for CHD events and of 0.89 (95% CI, 0.80-0.99; P =.01 for trend) for CVD events. The relative risks for those in the highest (median, 5.9 g/d) compared with those in the lowest (median, 0.9 g/d) quartile of water-soluble dietary fiber intake were 0.85 (95% CI, 0.74-0.98; P =.004 for trend) for CHD events and 0.90 (95% CI, 0.82-0.99; P =.01 for trend) for CVD events. CONCLUSION A higher intake of dietary fiber, particularly water-soluble fiber, reduces the risk of CHD.
Kinetics and thermodynamics of triple-helix formation: effects of ionic strength and mismatches.

Thermodynamic and kinetic parameters for the triplex-forming reactions between a homopurine-homopyrimidine 22-base-pair duplex (sequence of the purine strand: 5'd[AAAGGAGGAGAAGAAGAAAAAA]3') and the four 22-dN third strands (22 dN: 5'd[TTTCCTCCTCTNCTTCTTTTTT]3', where N = A, C, T, or G) were determined from thermal denaturation and renaturation UV absorbance profiles. Cooling and heating curves were not superimposable and thus allowed us to determine the rate constants of association (k(on)) and dissociation (k(off)) as a function of temperature, assuming a two-state model analogous to that developed for duplex-forming reactions. Experiments were performed in 10 mM cacodylate buffer (pH 6.8) in the presence of NaCl concentrations ranging from 20 to 300 mM. Within experimental accuracy, the main results are the following: (i) The rate constants k(on) and k(off) result in linear Arrhenius plots, consistent with the prediction of two-state association and dissociation (ii) k(on) is independent of the nature of the base N located in the center of the third strand. (iii) k(on) strongly decreases when the NaCl concentration is decreased. (iv) The activation energy, E(on), is always negative and becomes more negative when the NaCl concentration is decreased. (v) k(off) is independent of NaCl concentration but depends on the base N, with its magnitude following the order C greater than G greater than A much greater than T. (vi) The activation energy, E(off), is independent of the base N. All these results are discussed in the light of a nucleation-zipping model similar to that developed for the duplex-coil transitions [Craig, M. E. , Crothers, D. M. , & Doty, P. (1971) J. Mol. Biol. 62, 383-401; Pörschke, D. , Eigen, M. (1971) J. Mol. Biol. 62, 361-381].
Proteomic analysis of platelets treated with gamma irradiation versus a commercial photochemical pathogen reduction technology

Several strategies are currently being tested to reduce the risk of pathogen transmission associated with platelet (PLT) transfusion. Within the framework of the Italian Platelet Technology Assessment Study, we investigated the variations of the protein profiles (proteomics) of apheresis PLT concentrates (PCs) upon treatment with riboflavin and ultraviolet (UV) light (Mirasol; 6.24 J/mL; 280‐400 nm).
Evaluating differences in linkage disequilibrium between populations

We propose two methods to evaluate the statistical significance of differences in linkage disequilibrium (LD) between populations, where LD is measured by the standardised parameter D′. The first method is based on bootstrapping individuals within populations in order to test LD differences for each pair of loci. Using this approach we propose a solution to the problem of testing multiple locus‐pairs by means of a single test for the number of pairs that exhibit significant LD differences among populations. The second method provides the Bayesian posterior probability that one population has greater LD than the other for each locus pair. Both methods can handle genotypes with unknown phase, and are demonstrated using two data sets. For the purpose of demonstration, we apply the methods to two different sets of data from humans. First, we explore the issue of LD differences between reproductively isolated populations using a new data set of twelve Xq25 microsatellites, typed in four European populations. Second, we examine evidence for LD differences between Alzheimer cases and controls from the Icelandic population using 19 single nucleotide polymorphisms (SNPs) from a 97 kb region flanking the Apolipoprotein E (APOE) gene on chromosome 19.
Automated screening for at-risk drinking in a primary care office using interactive voice response.

OBJECTIVE Screening for alcohol misuse in primary care settings is strongly recommended but grossly underused. Using interactive voice response (IVR), we developed an automated screening tool (IVR Screen) for identifying alcohol misuse in outpatient primary care offices and evaluated its use rate and acceptability for both patients and providers. METHOD Patients (N = 101) presenting to a primary care clinic for scheduled, nonemergent health care visits called the IVR Screen by using a dedicated telephone in the waiting room and answered five questions about their health. Results were printed immediately for patient and provider to review during the visit. Medical assistants interviewed patients about the IVR Screen in the examination room. RESULTS Ninety-six percent of patients who were invited to participate in the study consented to do so. Of those, 26% met criteria for alcohol misuse. Feedback from patients and providers was positive and included constructive suggestions for revisions to the IVR Screen for future use. CONCLUSIONS IVR-based screening for at-risk drinking was feasible and did not interfere with the provider-patient interaction. The proportion of heavy drinkers identified by the IVR Screen was comparable to that of published reports of screening with written questionnaires. Implications for behavioral health screening, treatment, and clinical research are considerable because IVR-based screening assessments can be customized and targeted to different populations. Results suggest that continued development of IVR as a tool for health and alcohol screening in primary care settings is warranted.
Detection and quantification of mature circulating endothelial cells using flow cytometry and immunomagnetic beads: A methodological comparison

Summary Mature circulating endothelial cells (CECs) are novel cellular markers of endothelial damage/dysfunction. The two main techniques of CEC enumeration are flow cytometry (FC) and immunomagnetic bead (IB) isolation. Both quantify CECs accurately, but a direct comparison of both methods has not been reported. We sought to assess the agreement between the two methods in two patient populations, and a group of healthy subjects, with emphasis given to methodological issues. We included 34 patients with acute coronary syndrome (ACS), 60 patients with primary breast cancer (PBC) and 30 healthy controls (HC). We quantified CECs using the IB method [CD146 and FITCUlex europaeus lectin-1] and FC [CD45, CD34 and CD146]. Bland-Altman plots suggested reasonable agreement (<5% of events >2 standard deviations from the mean) between FC and the IB methods for CEC quantification in whole blood in the two disease groups (ACS and PBC), but not among the HCs. There were no statistically significant differences in CEC levels by the two methods amongst all three patient groups. There is reasonable agreement between the FC and the IB methods for mature CEC quantification in whole blood, especially amongst disease groups. The agreement between the two methods appears to weaken in healthy controls, and at lower and higher absolute CEC counts.
Vaccinia virus D10 protein has mRNA decapping activity, providing a mechanism for control of host and viral gene expression

Previous studies indicated that the vaccinia virus D10 protein, which is conserved in all sequenced poxviruses, participates in the rapid turnover of host and viral mRNAs. D10 contains a motif present in the family of Nudix/MutT enzymes, a subset of which has been shown to enhance mRNA turnover in eukaryotic cells through cleavage of the 5′ cap (m7GpppNm-). Here, we demonstrate that a purified recombinant D10 fusion protein possesses an intrinsic activity that liberates m7GDP from capped RNA substrates. Furthermore, point mutations in the Nudix/MutT motif abolished decapping activity. D10 has a strong affinity for capped RNA substrates (Km ≈ 3 nm). RNAs of 24–309 nt were decapped to comparable extents, whereas the cap of a 12-nt RNA was uncleaved. At large molar ratios relative to capped RNA substrate, competitor m7GpppG, m7GTP, or m7GDP inhibited decapping, whereas even higher concentrations of unmethylated analogs did not. High concentrations of uncapped RNA were also inhibitory, suggesting that D10 recognizes its substrate through interaction with both cap and RNA moieties. Thus far, poxviruses represent the only virus family shown to encode a Nudix hydrolase-decapping enzyme. Although it may seem self-destructive for a virus to encode a decapping and a capping enzyme, accelerated mRNA turnover helps eliminate competing host mRNAs and allows stage-specific synthesis of viral proteins.
Efficacy of tadalafil once daily in men with diabetes mellitus and erectile dysfunction

Aims Erectile dysfunction (ED) is a common comorbidity in men with diabetes mellitus. Tadalafil 10 or 20 mg taken on demand is efficacious and safe for men with diabetes and ED. Recently, continuous treatment with tadalafil has been proposed, addressing ED management as any other chronic condition. This study examined whether once‐daily tadalafil 2.5 and 5 mg is efficacious for men with diabetes and ED.
Yeast Peroxisomal Multifunctional Enzyme: (3R)-Hydroxyacyl-CoA Dehydrogenase Domains A and B Are Required for Optimal Growth on Oleic Acid*

The yeast peroxisomal (3R)-hydroxyacyl-CoA dehydrogenase/2-enoyl-CoA hydratase 2 (multifunctional enzyme type 2; MFE-2) has two N-terminal domains belonging to the short chain alcohol dehydrogenase/reductase superfamily. To investigate the physiological roles of these domains, here called A and B, Saccharomyces cerevisiae fox-2 cells (devoid of Sc MFE-2) were taken as a model system. Gly16 and Gly329 of the S. cerevisiae A and B domains, corresponding to Gly16, which is mutated in the human MFE-2 deficiency, were mutated to serine and cloned into the yeast expression plasmid pYE352. In oleic acid medium, fox-2 cells transformed with pYE352:: ScMFE-2(aΔ) and pYE352::ScMFE-2(bΔ) grew slower than cells transformed with pYE352::ScMFE-2, whereas cells transformed with pYE352::ScMFE-2(aΔbΔ) failed to grow. Candida tropicalis MFE-2 with a deleted hydratase 2 domain (Ct MFE- 2(h2Δ)) and mutational variants of the A and B domains (Ct MFE-2(h2ΔaΔ), Ct MFE- 2(h2ΔbΔ), andCt MFE- 2(h2ΔaΔbΔ)) were overexpressed and characterized. All proteins were dimers with similar secondary structure elements. Both wild type domains were enzymatically active, with the B domain showing the highest activity with short chain and the A domain with medium and long chain (3R)-hydroxyacyl-CoA substrates. The data show that the dehydrogenase domains of yeast MFE-2 have different substrate specificities required to allow the yeast to propagate optimally on fatty acids as the carbon source.
Identification of Genes Controlled by the Essential YycFG Two-Component System Reveals a Role for Biofilm Modulation in Staphylococcus epidermidis

Biofilms play a crucial role in the pathogenicity of Staphylococcus epidermidis, while little is known about whether the essential YycFG two-component signal transduction system (TCS) is involved in biofilm formation. We used antisense RNA (asRNA) to silence the yycFG TCS in order to study its regulatory functions in S. epidermidis. Strain 1457 expressing asRNAyycF exhibited a significant delay (~4–5 h) in entry to log phase, which was partially complemented by overexpressing ssaA. The expression of asRNAyycF and asRNAyycG resulted in a 68 and 50% decrease in biofilm formation at 6 h, respectively, while they had no significant inhibitory effect on 12 h biofilm formation. The expression of asRNAyycF led to a ~5-fold increase in polysaccharide intercellular adhesion (PIA) production, but it did not affect the expression of accumulation-associated protein (Aap) or the release of extracellular DNA. Consistently, quantitative real-time PCR showed that silencing yycF resulted in an increased transcription of biofilm-related genes, including icaA, arlR, sarA, sarX, and sbp. An in silico search of the YycF regulon for the conserved YycF recognition pattern and a modified motif in S. epidermidis, along with additional gel shift and DNase I footprinting assays, showed that arlR, sarA, sarX, and icaA are directly regulated by YycF. Our data suggests that YycFG modulates S. epidermidis biofilm formation in an ica-dependent manner.
CREBBP mutations in individuals without Rubinstein–Taybi syndrome phenotype

Mutations in CREBBP cause Rubinstein–Taybi syndrome. By using exome sequencing, and by using Sanger in one patient, CREBBP mutations were detected in 11 patients who did not, or only in a very limited manner, resemble Rubinstein–Taybi syndrome. The combined facial signs typical for Rubinstein–Taybi syndrome were absent, none had broad thumbs, and three had only somewhat broad halluces. All had apparent developmental delay (being the reason for molecular analysis); five had short stature and seven had microcephaly. The facial characteristics were variable; main characteristics were short palpebral fissures, telecanthi, depressed nasal ridge, short nose, anteverted nares, short columella, and long philtrum. Six patients had autistic behavior, and two had self‐injurious behavior. Other symptoms were recurrent upper airway infections (n = 5), feeding problems (n = 7) and impaired hearing (n = 7). Major malformations occurred infrequently. All patients had a de novo missense mutation in the last part of exon 30 or beginning of exon 31 of CREBBP, between base pairs 5,128 and 5,614 (codons 1,710 and 1,872). No missense or truncating mutations in this region have been described to be associated with the classical Rubinstein–Taybi syndrome phenotype. No functional studies have (yet) been performed, but we hypothesize that the mutations disturb protein–protein interactions by altering zinc finger function. We conclude that patients with missense mutations in this specific CREBBP region show a phenotype that differs substantially from that in patients with Rubinstein–Taybi syndrome, and may prove to constitute one (or more) separate entities. © 2016 Wiley Periodicals, Inc.
Hybrid delay-based congestion control for multipath TCP

Current algorithms for MPTCP (as LIA, OLIA, BALIA, or wVegas) present loss-based congestion control on the exception of wVegas. Delay-based congestion control allows a preventive action against congestion, capable to avoid loss up to some extent, unlike loss-based congestion control. Additionally delay-based congestion control induces lower delay and presents higher fairness, but poor performance interoperating with loss-based flows, as get a poor share of the available bandwidth. We propose DAIMD, a hybrid congestion control for Multipath TCP, based on the delay-based AIMD scheme, which benefits from better, preventive detection of congestion, a more responsive use of queues and consequently low induced delay, as well as the capability to coexist in fair conditions with loss-based flows in shared links. Our system presents its own analysis criteria for detecting incipient congestion that differs from other delay-based schemes on which it is based, such as CDG, delay-based AIMD and Vegas.
Health Literacy and Nurses’ Communication With Type 2 Diabetes Patients in Primary Care Settings

BackgroundThe use of the interactive communication loop has been recommended as an effective method to enhance patient understanding and recall of information. ObjectiveThe aim of the study was to examine the application of interactive communication loops, use of jargon, and the impact of health literacy (HL) when nurses provide education and counseling to patients with type 2 diabetes in the primary care setting in Alberta, Canada. MethodsEncounters between nurses and patients with type 2 diabetes were audio recorded, and a patient survey including a HL measure was administered. Topics within each interaction were coded based on five key components of the communication loop and categories of jargon. ResultsNine nurses participated in this study, and encounters with 36 patients were recorded. A complete communication loop was noted in only 11% of the encounters. Clarifying health information was the most commonly applied component (58% often used), followed by repeating health information (33% often used). Checking for understanding was the least applied (81% never used), followed by asking for understanding (42% never used). Medical jargon and mismatched language were often used in 17% and 25% of the encounters, respectively. Patients’ HL did not materially affect patterns of communication in terms of using communication loops; however, nurses used less jargon and mismatched words with patients with inadequate HL. DiscussionThe overuse of medical jargon accompanied with underuse of communication loop components jeopardizes patients’ comprehension and retention of information that they need to know to properly self-manage their diabetes. Nurses need to develop more effective ways to communicate concepts critical to chronic diabetes self-care education and management.
Characterization of Specific DNA-binding Factors Activated by Double-stranded RNA as Positive Regulators of Interferon α/β-stimulated Genes (*)

Viral infection results in transcriptional activation of the cellular interferon α/β-stimulated genes (ISGs) independent of the autocrine action of interferon α/β (IFN-α/β). Induction of ISG expression by virus appears to be mediated through production of viral double-stranded RNA (dsRNA). Previously, we identified two novel dsRNA-activated factors (DRAFs) that bind to the interferon-stimulated response element (ISRE), the DNA sequence that mediates transcriptional activation by IFN-α/β. In this report we define sequences that flank the classical ISRE to be necessary for DRAF1 binding. More significantly, it is shown that the sequences required to bind DRAF1 correlate with the ability to mediate ISG induction by virus. These results strongly suggest that DRAF1 is a positive regulator of ISG transcription. DRAF1 is shown to bind selectively to the promoters of those ISGs which are strongly induced by viral infection, again suggesting the functional significance of this factor. UV cross-linking experiments indicate that DRAF1 and DRAF2 share a common DNA-binding subunit of approximately 70 kDa which is referred to as the DRAF binding component (DRAFB). DRAFB is shown to preexist in the cytoplasm of unstimulated cells. Consistent with this observation, both DRAF1 and DRAF2 are activated in the cytoplasm prior to nuclear translocation.