On the Proportionality Between Area and Load in Line Contacts.

The relative contact area of rough surface contacts is known to increase linearly with reduced pressure, with proportionality factor κ . In its common definition, the reduced pressure contains the root-mean-square gradient (RMSG) of the surface. Although easy to measure, the RMSG of the entire surface does not coincide, at small loads, with the RMSG over the actual contact area g ¯ r , which gives a better description of the contact between rough surfaces. It was recently shown that, for Hertzian contacts, linearity between area and load is indeed obtained only if the RMSG is determined over the actual contact area. Similar to surface contacts, in line contacts, numerical data are often studied using theories that predict linearity by design. In this work, we revisit line contact problems and examine whether or not the assumption of linearity for line contacts holds true. We demonstrate, using Green's function molecular dynamics simulations, that κ for line contacts is not a constant: It depends on both the reduced pressure and the Hurst exponent. However, linearity holds when the RMSG is measured over the actual contact area. In that case, we could compare κ for line and surface contacts and found that their ratio is approximately 0.9. Finally, by analytically deriving the proportionality factor using g ¯ r in the original model of Greenwood and Williamson, a value is obtained that is surprisingly in good agreement with our numerical results for rough surface contacts.

Glycogenic hepatopathy is an under-recognised cause of hepatomegaly and elevated liver transaminases in type 1 diabetes mellitus.

Glycogenic hepatopathy (GH) is an under-recognised complication of type 1 diabetes mellitus (T1DM) not controlled to target resulting in hepatomegaly and elevated liver transaminases. We report the case of a 19-year-old man with T1DM not controlled to target who presented with abdominal pain, hepatomegaly and deranged liver transaminases. He was subsequently diagnosed with GH on liver biopsy, with the mainstay of treatment being reduction in caloric intake and insulin.

Severity of chronic pain affects health care utilization after kidney transplantation.

BACKGROUND: While the association between chronic pain and high health care utilization is a known issue in the general population, this relation has not been well studied among kidney transplantation patients. METHODS: The subjects were first-time kidney transplant recipients engrafted between 2003 and 2006 and 6 months to 5 years postoperatively. Using SF-36 Bodily Pain Scale, patients were categorized in three groups: group I, those with scores over 66.6; group II, between 66.6 and 33.3; and group III, over 33.3. The subjects' health care utilization was prospectively assessed by recording the number of hospital admission days and the frequency of home nurse visits, outpatient physician visits, and emergency department visits for any medical reason in a 6-month period. RESULTS: A stepwise increase in the frequency of patients admitted to the hospital (P=.017), and those referred to emergency departments (P=.007) was correlated with greater severity of pain in the three groups. However, the frequency of patients having outpatient physician visits (P=.30) or home nurse visits (P=.387) did not vary significantly. Similarly, with increased pain severity, an increase was observed in the number of emergency department visits (P=.005) and duration of hospital stays (P=.049), but not in the number of home nurse (P=.890) or physician visits (P=.112). CONCLUSION: The severity of pain seems to increase the amount of health care use among kidney transplant patients. To minimize associated costs, appropriate pain rehabilitation programs are suggested.

Improvement of the primary metabolism of cell cultures by introducing a new cytoplasmic pyruvate carboxylase reaction.

Continuous mammalian cell lines are important hosts for the production of biological pharmaceuticals. However, these cell lines show some severe disorders in primary metabolism, which they have in common with many cancer cells. This leads to a high throughput of substrates giving a low energy yield and ample toxic side products such as lactate and ammonia. Because the enzymatic connection between glycolysis and the tricarboxylic acid cycle (TCA) is very poor, glucose is mainly degraded via oxidative glycolysis. It will be shown that introducing a pyruvate carboxylase gene expressed in the cytoplasma into a continuous BHK-21 cell line, and thus reconstituting the missing link between glycolysis and TCA, can reduce this problem. Thus, glucose consumption could be reduced by a factor of four and glutamine utilization up to a factor of two, compared with control. Moreover, a 1.4-fold-higher adenosine triphosphate (ATP) content was achieved. The flux of labeled [(14)C]-glucose into the TCA is shown to be enhanced, indicating a higher rate of oxidative glucose degradation. Host cell lines with an improved energy metabolism will therefore result in better exploitation of substrates, an increasing yield by the more efficient use of carbon source, and higher product integrity combined with lower production costs.

Thymidine dinucleotides induce S phase cell cycle arrest in addition to increased melanogenesis in human melanocytes.

Although the induction of pigmentation following exposure of melanocytes to ultraviolet light in vivo and in vitro is well documented, the intracellular mechanisms involved in this response are not yet fully understood. Exposure to UV-B radiation leads to the production of DNA damage, mainly cyclobutane pyrimidine dimers, and it was recently suggested that the thymidine dinucleotide pTpT, mimicking small DNA fragments released in the course of excision repair mechanisms, could trigger melanin synthesis. We now report that the thymidine dinucleotide pTpT induces melanogenesis both in human normal adult melanocytes and in human melanoma cells. Thus, the SOS-like response suggested by Gilchrest's work to be evolutionary conserved, based primarily on work in murine cells and guinea pigs, is also apparently present in the human. Thymidine dinucleotide is nontoxic to melanoma cells and does not induce apoptosis in these cells, but induces S phase cell cycle arrest and a proliferation slow down. Because thymidine excess in culture medium leads to the synchronization of cells in S phase, we investigated whether this phenomenon was involved in the increase in melanin synthesis. We show that melanin synthesis is specifically triggered by the dimeric form of the thymidine and not by the monomeric form pT. Thus, our data strongly support that thymidine dinucleotides pTpT mimic at least part of the effects of ultraviolet irradiation, and may hence represent an invaluable model in the study of the molecular events involved in melanogenesis induction triggered through DNA damage.

Congenital anomalies and congenital adrenal hyperplasia.

Among 74 patients with congenital adrenal hyperplasia observed at Childrens Hospital, Los Angeles, in a 25-year period, 36 had the simple virilizing type and 38 the salt-losing type. During the same time, seven children with virilizing adrenal tumors were observed at the hospital. While virilization and dehydration were the most common presenting symptoms, some of the children first came to medical attention because of other symptoms, and 11 of them died before adrenal hyperplasia had been diagnosed. Twenty-eight additional congenital cardiovascular, genitourinary, and gastrointestinal anomalies were found in 16 of these 74 children. With proper management, the patients tolerated such stresses as surgical operation and infections without difficulty.