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Background. Our goal is to conduct a multicenter randomized controlled trial (RCT) to investigate whether exercise can reduce incident fractures compared with no intervention among women aged [greater than or equal to] 65 years with a vertebral fracture. Objectives. This pilot study will determine the feasibility of recruitment, retention, and adherence for the proposed trial. Design. The proposed RCT will be a pilot feasibility study with 1:1 randomization to exercise or attentional control groups. Setting. Five Canadian sites (1 community hospital partnered with an academic center and 4 academic hospitals or centers affiliated with an academic center) and 2 Australian centers (1 academic hospital and 1 center for community primary care, geriatric, and rehabilitation services). Participants. One hundred sixty women aged [greater than or equal to] 65 years with vertebral fracture at 5 Canadian and 2 Australian centers will be recruited. Intervention. The Build Better Bones With Exercise (B3E) intervention includes exercise and behavioral counseling, delivered by a physical therapist in 6 home visits over 8 months, and monthly calls; participants are to exercise [greater than or equal to] 3 times weekly. Controls will receive equal attention. Measurements. Primary outcomes will include recruitment, retention, and adherence. Adherence to exercise will be assessed via calendar diary. Secondary outcomes will include physical function (lower extremity strength, mobility, and balance), posture, and falls. Additional secondary outcomes will include quality of life, pain, fall self-efficacy, behavior change variables, intervention cost, fractures, and adverse events. Analyses of feasibility objectives will be descriptive or based on estimates with 95% confidence intervals, where feasibility will be assessed relative to a priori criteria. Differences in secondary outcomes will be evaluated in intention-to-treat analyses via independent Student t tests, chi-square tests, or logistic regression. The Bonferroni method will be used to adjust the level of significance for secondary outcomes so the overall alpha level is .05. Limitations. No assessment of bone mineral density will be conducted. The proposed definitive trial will require a large sample size. Conclusions. The viability of a large-scale exercise trial in women with vertebral fractures will be evaluated, as well as the effects of a home exercise program on important secondary outcomes., Osteoporotic fractures create a substantial human and economic burden. (1) Vertebral fractures are a common consequence of osteoporosis that can cause pain and are associated with increased mortality. (2) One [...]

Oral semaglutide is the first oral formulation of a glucagon-like peptide-1 (GLP-1) receptor agonist developed for the treatment of type 2 diabetes. We aimed to compare the efficacy and safety of flexible dose adjustments of oral semaglutide with sitagliptin 100 mg.

Ibrutinib, a recently approved inhibitor of Bruton’s tyrosine kinase (BTK), has shown great efficacy in patients with high-risk CLL. Nevertheless, there are few data regarding its use in patients who relapsed after allogeneic stem cell transplantation (alloSCT). We report clinical data from five CLL patients treated with ibrutinib for relapse after first or even second allogeneic transplantation. Additionally, we performed analyses on cytokine levels and direct measuring of CD4 Th1 and CD4 Th2 cells to evaluate possible clinically relevant immunomodulatory effects of ibrutinib. All patients achieved partial responses including one minimal residual disease (MRD)-negative remission. Within 1 year of follow-up, no relapse was observed. One patient died of severe pneumonia while on ibrutinib treatment. Beside this, no unexpected adverse events were observed. Flow cytometry and analyses of T cell-mediated cytokine levels (IL10 and TNFα) did not reveal substantial changes in T-cell distribution in favor of a CD4 Th1 T-cell shift in our patients. No acute exacerbation of GvHD was reported. In conclusion, these results support further evaluation of ibrutinib in CLL patients relapsing after alloSCT.

Recent advances in the realization of individual molecular‐scale devices [1,2] highlight the integration of individual devices into large‐scale functional circuits as the major challenge. DNA‐programmed assembly is a promising avenue in that direction due to the large amount of information that can be coded into the molecules and the ability to translate that information into physical constructs [3]. Large‐scale DNA‐templated electronics require, however, complex manipulation of double‐stranded DNA (dsDNA) molecules, as well as patterning of the electrical properties instilled to them by, e.g., metallization. To that end, sequence‐specific molecular lithography on single DNA molecules has been developed [4]. This was achieved by harnessing the exquisite homologous recombination process of the RecA protein. Sequence‐specific patterning of the metal coating of DNA molecules, localization of arbitrary labeled molecular objects at any desired dsDNA address without prior modifications, and generation of molecularly accurate stable dsDNA‐dsDNA junctions are demonstrated. The information encoded in the DNA molecules directs the lithographic process in analogy to the masks used in conventional microelectronics. The RecA protein provides the assembling capabilities, as well as the resist function.

Mutations in the transparent testa (tt) loci abolish pigment production in Arabidopsis seed coats. The TT4, TT5, and TT3 loci encode chalcone synthase, chalcone isomerase, and dihydroflavonol 4-reductase, respectively, which are essential for anthocyanin accumulation and may form a macromolecular complex. Here, we show that the products of the maize (Zea mays) C2, CHI1, and A1 genes complement Arabidopsis tt4, tt5, and tt3 mutants, restoring the ability of these mutants to accumulate pigments in seed coats and seedlings. Overexpression of the maize genes in wild-type Arabidopsis seedlings does not result in increased anthocyanin accumulation, suggesting that the steps catalyzed by these enzymes are not rate limiting in the conditions assayed. The expression of the maize A1 gene in the flavonoid 3' hydroxylase Arabidopsis tt7 mutant resulted in an increased accumulation of pelargonidin. We conclude that enzymes involved in secondary metabolism can be functionally exchangeable between plants separated by large evolutionary distances. This is in sharp contrast to the notion that the more relaxed selective constrains to which secondary metabolic pathways are subjected is responsible for the rapid divergence of the corresponding enzymes.

The relationship between kidney structure and diet was examined in several species of bats from the tropics. The trophic level of the bats was determined by their stable nitrogen isotopic composition (δ 15N). The results indicate that the relative thickness of the renal medulla is directly related to the trophic level of the bats. Additionally, we also determined the relationship between body mass and kidney structure. Relative medullary thickness was reciprocally related to body mass in animalivorous bats but no relationship was found in phytophagous bats. Stable isotope analysis provided a quantitative approximation of diet to test its relationship with kidney structure.

OBJECTIVE: We studied the significance of BsmI restriction enzyme polymorphism of the vitamin D receptor (VDR) gene and the XbaI and PvuII polymorphisms of the estrogen receptor (ER) gene in patients with type 2 diabetes (n=49), android type obesity with normal carbohydrate metabolism (n=29) and healthy controls (n=138). METHODS: The distribution of genotypes in the study groups, as well as their relationship to fasting and 1 h postprandial serum C-peptide levels were analyzed. RESULTS: Postprandial serum C-peptide levels of BB genotypes were significantly higher in the diabetes and obese groups (6.18+/-5.09 ng/ml) compared with other genotypes (2.71+/-2.45 vs. 1.72+/-1.97 ng/ml, respectively, P=0.05). Among patients with type 2 diabetes and obese subjects, the XX allelic variant of the ER gene was more frequent (P=0.00015). Postprandial C-peptide levels of subjects exhibiting XX genotype were significantly lower compared with those with Xx genotype (1.67+/-2.16 vs. 3.8+/-3.72 ng/ml, P=0.021). The BBXx allelic combination of the VDR/ER receptor genes was less frequent in diabetic patients than in healthy subjects or in obese patients. The BBXx genotype was associated with significantly elevated postprandial C-peptide levels in all subjects compared with other combinations (9.65+/-3.14 vs. 1.35+/-2.82 ng/ml, P=0.003). No difference was found in the distribution of the PvuII polymorphism of the ER gene or in the association with the C-peptide levels among study groups. CONCLUSION: Polymorphisms of the VDR/ER receptor genes might play a role in the pathogenesis of type 2 diabetes by influencing the secretory capacity of beta-cells.

Lipoxygenase (LOX) activity has been identified consistently during pathogen-induced defense responses. Here we report the involvement of a specific leaf LOX gene of potato (Solanum tuberosum), designated POTLX-3 (GenBank/EMBL accession no. U60202), in defense responses against pathogens. The sequence of POTLX-3 does not match any other LOX genes of potato and has the greatest match to a tobacco LOX gene that contributes to a resistance mechanism against Phytophthora parasitica var nicotianae. POTLX-3 transcript accumulation was not detected in untreated, healthy potato organs or in wounded mature leaves. POTLX-3 mRNA accumulation was induced in potato leaves treated with ethylene or methyl jasmonate or infected with either virulent or avirulent strains of Phytophthora infestans, the causal agent of late blight. During the resistance response, POTLX-3 was induced within 6 hours, increased steadily through 24 hours, and its mRNA continued to accumulate for a week after inoculation. In contrast, when a plant was susceptible to P. infestans, induction of mRNA accumulation in response to inoculation was inconsistent and delayed. LOX activity assayed during an incompatible interaction in leaves peaked 3 days earlier than during a compatible interaction. POTLX-3 mRNA accumulation also was induced during hypersensitive response development caused by the incompatible pathogen Pseudomonas syringae pv phaseolicola. Our results show that POTLX-3 may be involved specifically in defense responses against pathogen infection.

We report a large-scale comparison of sequence data from the filamentous fungus Neurospora crassa with the complete genome sequence of Saccharomyces cerevisiae. N. crassa is considerably more morphologically and developmentally complex than S. cerevisiae. We found that N. crassa has a much higher proportion of "orphan" genes than S. cerevisiae, suggesting that its morphological complexity reflects the acquisition or maintenance of novel genes, consistent with its larger genome. Our results also indicate the loss of specific genes from S. cerevisiae. Surprisingly, some of the genes lost from S. cerevisiae are involved in basic cellular processes, including translation and ion (especially calcium) homeostasis. Horizontal gene transfer from prokaryotes appears to have played a relatively modest role in the evolution of the N. crassa genome. Differences in the overall rate of molecular evolution between N. crassa and S. cerevisiae were not detected. Our results indicate that the current public sequence databases have fairly complete samples of gene families with ancient conserved regions, suggesting that further sequencing will not substantially change the proportion of genes with homologs among distantly related groups. Models of the evolution of fungal genomes compatible with these results, and their functional implications, are discussed.

The substrate specificity of the avian renal organic cation exchanger was examined in isolated renal brush-border membrane vesicles. Endobiotic and xenobiotic organic cations (OCs) were tested at a concentration of 100 microM for cis-inhibition of 14C-tetraethylammonium (TEA)/H+ exchange and at 1 mM for trans-stimulation of 14C-TEA efflux. The xenobiotic cations amiloride, cimetidine, mepiperphenidol, procainamide, quinidine, quinine, and ranitidine cis-inhibited TEA uptake >/= 80%; isoproterenol and unlabeled TEA inhibited uptake at least 30%. In contrast, the endogenous cations acetylcholine, choline, and guanidine did not inhibit TEA uptake; however, epinephrine, N1-methylnicotinamide, serotonin, and thiamine inhibited uptake as much as 60%. Each endogenous cation, except thiamine, trans-stimulated TEA efflux, and xenobiotic cations, excluding isoproterenol and TEA, trans-inhibited TEA efflux. The data suggest that the avian renal tubule luminal OC exchanger has greater affinity for xenobiotic cations than for endobiotic cations, but greater transport capacity for endobiotics than for xenobiotics.

Discusses the Scuola Romana, a group of artists active in Rome, Italy from 1930 through World War II. The author calls into question their art-historical label as a school and their identification as an anti-Fascist movement. Some of the artists discussed are: Antonietta Raphael Mafai, Giuseppe Capogross and Scipione (Gino Bonichi).

Measurements of specific heat (1.4–350 K), thermopower and thermal conducctivity (1.5–300 K), electrical resistivity (40 mK–300 K) and of the magnetic susceptibility (40 mK–300 K) on polycrystalline samples of CeInAu, CeInAu2and of the reference compounds LaInAu and LuInAu2are reported. The properties of the Ce-compounds are unusual due to phase transitions (magnetic ordering, martensitic) and crystalline electric field effects. There are only weak indications of a valence instability.

Abstract: The development of Fe-Ti oxide assemblages in basic rocks from the Penninic series of the southern Venediger rea, Austria, during polyphase Alpine metamorphism has been studied. Textural and compositional relations indicate thorough reequilibration of the opaque mineral assemblages during late Barrovian metamorphism at essentially static conditions of lower amphibolite to greenschist facies. In contrast, silicate mineralogy of the preceeding blueschist to eclogite facies metamorphism might still be preserved to a large extent. Chemical adjustment of the Fe-Ti oxide minerals to decreasing P-T conditions is characterized by (1) formation of complex intergrowths of ilmenite and hematite solid solutions (<550 C), (2) the decomposition of hemo-ilmenite 1 to ferrianilmenite2+magnetite+rutile and of ilmeno-hematite1 to titanhematite2+rutilemagnetite (<450 C), and (3) low-grade oxidation of ferrianilmenite2 to magnetite+hematite-rutile intergrowths or hematite +rutile and of titanhematite2 to hematite-rutile intergrowths (≦400 C). Chemical equilibrium is suggested by the regular partitioning of Cr, V, Mg and Mn between coexisting hemo-ilmenite, ilmeno-hematite, and magnetite. The hematite-ilmenite miscibility gap has been delimited on the basis of the bulk compositions of the exsolved phases and the temperature estimates obtained from Fe-Ti oxide thermometry.

The concentrations of cobalt and chromium have been measured in the urine of 22 patients who had received uncemented hip prostheses made from cobalt, chromium and molybdenum alloy, and in 21 patients who had not received prostheses, using absorption spectrophotometry. The results were statistically analysed using the Wilcoxon test.

The isolation and characterization of a new methanogen from a peat bog, Methanobacterium palustre spec. nov., strain F, is described. Strain F grew on H2/CO2 and formate in complex medium. It also grew autotrophically on H2/CO2. Furthermore, growth on 2-propanol/CO2 was observed. Methane was formed from CO2 by oxidation of 2-propanol to acetone or 2-butanol to 2-butanone, but growth on 2-butanol plus CO2 apparently was too little to be measurable. Similarly, Methanobacterium bryantii M. o. H. and M. o. H. G formed acetone and 2-butanone from 2-propanol and 2-butanol, but no growth was measurable.

A multistep self-assembly process is proposed for the preparation of nanometer-scale electronics. The process is based on the assembly of a DNA network that serves, in turn, as a template for the subsequent assembly of functional elements using different levels of molecular recognition ability. Inter-element connectivity and connection to the "macroscopic world" is achieved by instilling electrical functionality to the DNA network. The feasibility of this approach was demonstrated by the DNA-templated self-assembly of a 12 μm long, ca. 1000 Å wide, conductive silver wire connecting two macroscopic electrodes.

Abstract.: The aim of this study is to evaluate directly, using a reduced experimental system, the nature of interactions between voltage-gated potassium channels and the resting membrane potential. Xenopus oocytes were injected with various concentrations of cRNA coding for a delayed-rectifier potassium channel Shaker-IR. The effects of the density and kinetics of the expressed channels on resting membrane potential is explored in isolated (``inside-out'') patches. The channel density is given in terms of maximal conductance (G max), measured from the maximal slope of the I-V curve under voltage clamp conditions. The capacitance of the experimental setup is approximately 1 pF. At high channel densities (G max > 10 pA/mV) the mean membrane potential is stabilized at approximately −60 mV. This resting membrane potential is more than 35 mV positive to the reversal potential for potassium ions under the same experimental conditions. Analyses of voltage clamp experiments indicate that at high channel densities the mean membrane potential is determined by the rates of channel activation and deactivation, but is not affected by the rates involved in the process of slow (C-type) inactivation. In contrast, at lower channel densities membrane potential is very unstable, and its mean value and amplitude of fluctuations are strongly affected by the process of slow (C-type) inactivation.

We obtain the transport coefficients up to first order in the density for a system of particles interacting with nonadditive forces. To zeroth order in the density we recover the usual results obtained from the Boltzmann equation. To first order in the density one finds that the transport coefficients consist of two parts: the value of the corresponding quantities for a system with only additive forces, plus a contribution due to nonadditive forces.

The purpose of this paper is to obtain general expressions for the second-order terms of the transport coefficients of a dense gas. These expressions are obtained using the convergent kinetic theory proposed recently by Braun and Flores.

Growth and proliferation of microorganisms such as the yeast Saccharomyces cerevisiae are controlled in part by the availability of nutrients. When proliferating yeast cells exhaust available nutrients, they enter a stationary phase characterized by cell cycle arrest and specific physiological, biochemical, and morphological changes. These changes include thickening of the cell wall, accumulation of reserve carbohydrates, and acquisition of thermotolerance. Recent characterization of mutant cells that are conditionally defective only for the resumption of proliferation from stationary phase provides evidence that stationary phase is a unique developmental state. Strains with mutations affecting entry into and survival during stationary phase have also been isolated, and the mutations have been shown to affect at least seven different cellular processes: (i) signal transduction, (ii) protein synthesis, (iii) protein N-terminal acetylation, (iv) protein turnover, (v) protein secretion, (vi) membrane biosynthesis, and (vii) cell polarity. The exact nature of the relationship between these processes and survival during stationary phase remains to be elucidated. We propose that cell cycle arrest coordinated with the ability to remain viable in the absence of additional nutrients provides a good operational definition of starvation-induced stationary phase.

We present measurements of the specific heat and of the thermal expansion of the most prominent phases of the Bi and Tl high temperature superconductors (Bi-2212, Bi-2223, Tl-2212, Tl-2223) in the neighbourhood ofTc. In all these systems we observe small but sharp anomalies which have very little similarity with the mean field jump found in the conventional superconductors. The analysis of these anomalies shows clear evidence for the presence of strong fluctuations of the order parameter. For temperatures more than ˜ 5 K away fromTc,2D Gaussian fluctuations are found, while within ±5 K ofTc the fluctuation contribution is best fitted by critical fluctuations. The shape of the thermal expansion anomalies is similar to that of the specific heat. Combination of both measurements predicts dTc/dp˜+0.2 K/kbar for Bi- and Tl-2223 systems.

The magnetic susceptibility (?) of Th1-xTbx alloys (with 5c decrease. The contribution of the interconfigurational mixing on ? and the specific heat is also discussed.

The white-tailed prairie dog is an obligate hibernator that enters a heterothermic phase when maintained in the cold with low intensity light and ad libitum food and water. The black-tailed prairie dog (a facultative hibernator) will not hibernate under similar conditions. It has been suggested that the black tailed prairie dog remains active during the winter because it can conserve water more effectively due to a more efficient kidney. The present study revealed no significant differences between the species in renal morphology: relative medullary thickness, nephron heterogeneity, renal vasculature, or fornix dimensions, all of which are structures associated with the urinary concentrating mechanism. In addition, there was no difference in number of nephrons between the two species. The black-tailed prairie dog does produce a more concentrated urine when food and water deprived. However, this difference was not observed when the animals were salt loaded. The water-deprivation and salt-loading experiments suggest that the higher urine osmolality produced by the back-tailed prairie dog during fasting is a result of a higher urea load due to a greater protein catabolism and not because of a differential capacity to concentrate urine.

A new concept truck transmission for 800000 km durability, low life cycle cost and reduced driver effort is described, with emphasis on driver effort and truck performance comparisons, testing, and future trends.