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Aims LDL cholesterol (LDL-C) is the current lipid standard for cardiovascular disease (CVD)-risk assessment in type 1 diabetes. Apolipoprotein B (apoB) may be helpful to further stratify CVD risk. We explored the association between apoB and pulse wave velocity (PWV) to determine if apoB would improve CVD-risk stratification, especially in type 1 diabetes adolescents with borderline LDL-C (100–129 mg/dL). We hypothesized that type 1 diabetes adolescents with borderline LDL-C and elevated apoB (≥90 mg/dL) would have increased PWV compared to those with borderline LDL-C and normal apoB (<90 mg/dL), and that apoB would explain more of the variability of PWV than alternative lipid indices. Methods Fasting lipids, including apoB, were collected in 267 adolescents, age 12–19 years, with diabetes duration >5 years and HbA1c 8.9 ± 1.6 %. Triglyceride to HDL-C ratio (TG/HDL-C) and nonHDL-cholesterol (nonHDL-C) were calculated. PWV was measured in the carotid–femoral segment. Results ApoB, nonHDL-C and TG/HDL-C correlated with PWV ( p  < 0.0001). ApoB, nonHDL-C and TG/HDL-C remained significantly associated with PWV in fully adjusted models. In adolescents with borderline LDL-C ( n  = 61), PWV was significantly higher in those with elevated apoB than in those with normal apoB (5.6 ± 0.6 vs. 5.2 ± 0.6 m/s, p  < 0.01) and also remained significant after adjustment for CVD-risk factors ( p  = 0.0002). Moreover, in those with borderline LDL-C, apoB explained more of the variability of PWV than nonHDL-C and TG/HDL-C. Conclusion Elevated apoB is associated with increased arterial stiffness in type 1 diabetes adolescents. Measurement of apoB in addition to LDL-C may be helpful in stratifying CVD risk in type 1 diabetes adolescents, especially in those with borderline LDL-C.

Isochromosomal, respiratory-deficient yeast strains, such as a mit$^{-}$, a hypersuppressive petite, and a petite lacking mitochondrial DNA, are phenotypically identical in spite of differences in their mitochondrial genomes. Subtractive hybridizations of complementary DNA's to polyadenylated RNA isolated from derepressed cultures of these strains reveal the presence of nuclear-encoded transcripts whose abundance varies not only between them and their respiratory-competent parent, but among the respiratory-deficient strains themselves. Transcripts of some nuclear-encoded mitochondrial proteins, like cytochrome c and the $\\alpha $ and $\\beta $ subunits of the mitochondrial adenosine triphosphatase, whose abundance is affected by glucose or heme, do not vary. In the absence of major metabolic variables, yeast cells seem to respond to the quality and quantity of mitochondrial DNA and modulate the levels of nuclear-encoded RNA's, perhaps as a means of intergenomic regulation.

Abstract Context The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed. Objective The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures. Methods We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients. Results All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient. Conclusions Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.

Congenital arhinia (absent external nose) is an extremely rare mendelian disorder (<100 case reports in the past century) caused by heterozygous missense mutations in the gene SMCHD1. Arhinia is frequently accompanied by ocular and reproductive defects, a clinical triad which defines the Bosma arhinia microphthalmia syndrome (BAMS). The etiology and spectrum of reproductive defects in BAMS is unknown. We studied eleven subjects with arhinia or nasal hypoplasia (aged 18-53 yrs; 5 males) to assess endogenous luteinizing hormone (LH) secretion (n=11), a validated marker of GnRH, responsiveness to pulsatile GnRH (n=2), and non-reproductive phenotypes (n=11). Clinical data abstracted from questionnaires were analyzed in 33 additional international patients. Nearly every male demonstrated clinical and biochemical signs of severe congenital GnRH deficiency (CGD) including a history of microphallus and/or cryptorchidism, testicular volumes < 3 ml, hypogonadotropic hypogonadism (HH), low inhibin B levels, and apulsatile LH profiles; two young boys (studied from afar) had normal genitals but an absent mini-puberty of infancy was confirmed biochemically in one case. Pulsatile GnRH administered to one adult male and hCG to two others also revealed testicular resistance. Several females reported spontaneous breast bud development, but all had primary amenorrhea, small ovaries on pelvic ultrasound, HH, and apulsatile LH profiles. Pulsatile GnRH administered to one female induced ovulation on treatment day 21. Two females (studied from afar) reported normal thelarche and menstrual cycles. The 11 subjects studied in detail were completely anosmic with absent internal olfactory structures on brain MRI but normal hypothalamic-pituitary anatomy. Subjects with arhinia demonstrated some, but not all, non-reproductive phenotypes characteristic of Kallmann syndrome (KS) and/or CHARGE syndrome including dental agenesis (56%) and congenital mirror movements (CMMs; 50%); none had renal agenesis, severe congenital heart defects, or deafness. This study demonstrates for the first time that the hypogonadotropism observed in BAMS is indeed secondary to GnRH deficiency. In contrast to the male predominance (3-5:1) in KS, there is no sex bias in the incidence of BAMS. However, females may demonstrate partial or complete pubertal development whereas males are severely affected with some showing both hypothalamic and testicular defects. The combination of defects in the nasal skeleton, olfactory structures, and GnRH ontogeny point to aberrant development of the nasal placode in BAMS, yet the high prevalence of CMMs, a sign of misrouted commissural axons, suggests insults may occur even earlier in neurogenesis, at the neural plate border.

High dynamic range in today’s millimeter-wave systems is crucial. Stringent linearity requirements and increasing operating frequencies push these systems to their limits. Mixer performance has a predominant effect on how well a system will perform. Trade-offs in a mixer include conversion loss, LO drive, port-isolations, noise, VSWR, and linearity. Once in a system these mixer specifications will have a predominant influence on the overall system performance, especially the dynamic range. To this end a highly linear mixer with low conversion loss and low distortion characteristics is highly sought after. In this research both device level and system level linearization techniques are applied to III-V FET resistive mixers operating at millimeter wave frequencies. The benefits of device linearization applied to both GaAs and GaN 0.15 μm pHEMT based mixers have been investigated. Upon optimizing the third-order drain conductance with bias input 3rd order intercepts (IIP3) of up to 37.5 dBm have been achieved. The system level techniques in this research include second harmonic injection as well as modifying the LO drive waveform to the mixer. With second harmonic injection linearization an improvement of 3 dB in IIP3 has been demonstrated with no degradation in either conversion loss or noise figure at Ka-band. With the modified LO drive waveform improvements of 6 – 8 dB in IIP3 have been achieved as well. This leads to a mixer with high linearity and low conversion loss operating at millimeter wave frequencies. The combination of both system level and device level linearization techniques can further improve the linearity performance of the mixer.

Fever phobia can cause parents at times to be overly aggressive in treating fever, and they want to give their child a fever reducer right away. The body uses specific chemicals from the Immune system to create a fever, and the medicines that treat a fever interfere with the action of these chemicals.

Feeding of sorghum with a high level of tannin (high-tannin sorghum) to rats caused changes in gene expression in parotid glands similar to isoproterenol treatment. Within 3 days the parotid glands were enlarged about 3-fold and a series of proline-rich proteins were increased about 12-fold. Unlike isoproterenol treatment, no changes were observed in the submandibular glands, and a Mr220,000 glycoprotein in parotid glands was not induced. Amino acid analyses, electrophoretic patterns, and cell-free translations of mRNAs all confirmed that the proline-rich proteins induced by feeding high-tannin sorghum were identical to those induced by isoproterenol treatment. Binding curves for proline-rich proteins to tannins showed affinities 10-fold greater than bovine serum albumin and tannins.

We recognize that the impacts of Sept. 11 are significant, and that our industry will continue to be dynamic. However, Edmonton Airports operates in a city that leads the country in growth, and we are resolute in our vision to provide optimal air service and appropriate infrastructure to support that growth. We would appeal to [Wilson] to join the community in this endeavor. Air Canada has announced system-wide capacity reductions of 20 per cent: in Edmonton we have seen eight per cent of that reduction. Edmonton traffic in October is improving and is close to yearly norms.