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Aims: To determine whether there is an association between the insertion/deletion (I/D) polymorphism of the human angiotensin I converting enzyme (ACE) gene and malignant vascular injury (MVI). Methods: The polymerase [...]

Conflicting results have been reported on the relationship between familial predisposition to hypertension and development of diabetic nephropathy in IDDM. In our case-control study, we assessed the prevalence of hypertension [...]

The impact of microalbuminuria and macroalbuminuria on mortality was evaluated prospectively in 328 Caucasian patients with non-insulin-dependent diabetes mellitus (NIDDM) followed for 5 years. One hundred ninety-one (109 men and [...]

The BCL-2 inhibitor venetoclax combined with hypomethylating agents or low-dose cytarabine represents an important new therapy for older or unfit patients with acute myeloid leukemia (AML). We analyzed 81 patients receiving these venetoclax-based combinations to identify molecular correlates of durable remission, response followed by relapse (adaptive resistance), or refractory disease (primary resistance). High response rates and durable remissions were typically associated with NPM1 or IDH2 mutations, with prolonged molecular remissions prevalent for NPM1 mutations. Primary and adaptive resistance to venetoclax-based combinations was most commonly characterized by acquisition or enrichment of clones activating signaling pathways such as FLT3 or RAS or biallelically perturbing TP53. Single-cell studies highlighted the polyclonal nature of intratumoral resistance mechanisms in some cases. Among cases that were primary refractory, we identified heterogeneous and sometimes divergent interval changes in leukemic clones within a single cycle of therapy, highlighting the dynamic and rapid occurrence of therapeutic selection in AML. In functional studies, FLT3 internal tandem duplication gain or TP53 loss conferred cross-resistance to both venetoclax and cytotoxic-based therapies. Collectively, we highlight molecular determinants of outcome with clinical relevance to patients with AML receiving venetoclax-based combination therapies.

Segmental arterial mediolysis (SAM) is a rare, non-atherosclerotic, non-inflammatory vascular disease mostly affecting medium to large sized abdominal arteries which may cause aneurysms, stenosis, and haemorrhage.

Electronic defect states at material interfaces provide highly deleterious sources of noise in solid-state nanostructures, and even a single trapped charge can qualitatively alter the properties of short one-dimensional nanowire field-effect transistors (FET) and quantum bit (qubit) devices. Understanding the dynamics of trapped charge is thus essential for future nanotechnologies, but their direct detection and manipulation is rather challenging. Here, a transistor-based set-up is used to create and probe individual electronic defect states that can be coherently driven with microwave (MW) pulses. Strikingly, we resolve a large number of very high quality (Q ∼ 1 × 105) resonances in the transistor current as a function of MW frequency and demonstrate both long decoherence times (∼1 μs—40 μs) and coherent control of the defect-induced dynamics. Efficiently characterizing over 800 individually addressable resonances across two separate defect-hosting materials, we propose that their properties are consistent with weakly driven two-level systems.

Permafrost underlies about one fifth of the global land area and affects ground stability, freshwater runoff, soil chemistry, and surface‐atmosphere gas exchange. The depth of thawed ground overlying permafrost (active layer thickness) has broadly increased across the Arctic in recent decades, coincident with a period of increased streamflow, especially the lowest flows (baseflow). Mechanistic links between active layer thickness and baseflow have recently been explored using linear reservoir theory, but most watersheds behave as nonlinear reservoirs. We derive theoretical nonlinear relationships between long‐term average saturated soil thickness η‾$\overline{\eta }$(proxy for active layer thickness) and long‐term average baseflow. When applied to 38 years of daily streamflow data for the Kuparuk River basin on the North Slope of Alaska, the theory predicts η‾$\overline{\eta }$increased 0.17±0.22[2σ]$0.17\pm 0.22\,[2\sigma ]$cm a−1between 1983 and 2020 (6.4±8.4$6.4\pm 8.4$cm total). The rate of increase nearly doubled to 0.29±0.31$0.29\pm 0.31$cm a−1between 1990 and 2020, during which time local field measurements from Circumpolar Active Layer Monitoring sites indicate the active layer increased 0.31±0.22$0.31\pm 0.22$cm a−1. The predicted rate of increase more than doubled again between 2002 and 2020, outpacing a near doubling of observed active layer thickening, consistent with trends in terrestrial water storage inferred from Gravity Recovery and Climate Experiment satellite gravimetry and Modern‐Era Retrospective Analysis for Research and Applications climate reanalysis. Overall, hydrologic change is accelerating in the Kuparuk River basin, and we provide a theoretical framework for estimating basin‐scale changes in active layer water storage from streamflow measurements. Streamflow has increased in most areas of the Arctic in recent decades. This increase in streamflow has occurred along with a period of rising air temperatures and thawing permafrost. Permafrost is typically overlain by a layer of seasonally unfrozen ground referred to as active layer, which gets deeper as permafrost thaws. As active layer deepens, it can store more water. Water may also take more time to flow through a thicker active layer than it would atop frozen ground. Because there is more space to store water, thicker active layers lead to increased soil water storage which sustains streamflow during dry periods and enhances overall increased streamflow and subsurface flow. We developed an approach to measure how quickly the active layer thickness is changing using the rate of change of streamflow. This is useful because streamflow measurements are widely available and easy to obtain, whereas active layer thickness measurements are difficult to measure and less common than streamflow measurements. If the equations we developed accurately predict measured values, the pace at which active layer thickness changes can be estimated from streamflow measurements, which would expand the current knowledge of permafrost thaw rates and provide an independent way to validate computer simulations of active layer thickness. New relationships between active layer thickness and baseflow are developed for application to catchments underlain by permafrostTheoretical predictions of active layer thickness trends agree with measured trends on the North Slope of Arctic AlaskaNovel methods are developed to estimate nonlinear recession flow parameters and related hydrologic signatures using generalized Pareto distributions New relationships between active layer thickness and baseflow are developed for application to catchments underlain by permafrost Theoretical predictions of active layer thickness trends agree with measured trends on the North Slope of Arctic Alaska Novel methods are developed to estimate nonlinear recession flow parameters and related hydrologic signatures using generalized Pareto distributions

Adoptive T cell immunotherapy using cytomegalovirus‐specific T cells from a donor bank is used as salvage therapy in a case of ganciclovir‐resistant cytomegalovirus disease in a renal transplant recipient.

Cerenkov radiation is generated in optical fibers immersed in radiation fields and can interfere with signal transmission. We develop a theory for predicting the intensity of Cerenkov radiation generated within the core of a multimode optical fiber by using a ray optic approach and use it to make predictions of the intensity of radiation transmitted down the fiber in propagating modes. The intensity transmitted down the fiber is found to be dominated by bound rays with a contribution from tunneling rays. It is confirmed that for relativistic particles the intensity of the radiation that is transmitted along the fiber is a function of the angle between the particle beam and the fiber axis. The angle of peak intensity is found to be a function of the fiber refractive index difference as well as the core refractive index, with larger refractive index differences shifting the peak significantly toward lower angles. The angular range of the distribution is also significantly increased in both directions by increasing the fiber refractive index difference. The intensity of the radiation is found to be proportional to the cube of the fiber core radius in addition to its dependence on refractive index difference. As the particle energy is reduced into the nonrelativistic range the entire distribution is shifted toward lower angles. Recommendations on minimizing the quantity of Cerenkov light transmitted in the fiber optic system in a radiation field are given.

The XO project's first objective is to find hot Jupiters transiting bright stars (i.e., V<12) by precision differential photometry. Two XO cameras have been operating since 2003 September on the 10,000 foot Haleakala summit on Maui. Each XO camera consists of a 200 mm f/1.8 lens coupled to a 1024 × 1024 pixel, thinned CCD operated by drift-scanning. In its first year of routine operation, XO has observed 6.6% of the sky within six 7° wide strips scanned from 0° to +63° of declination and centered at R.A. = 0, 4, 8, 12, 16, and 20 hr. Autonomously operating, XO records 1 billion pixels per clear night, calibrates them photometrically and astrometrically, performs aperture photometry, archives the pixel data, and transmits the photometric data to the Space Telescope Science Institute for further analysis. From the first year of operation, the resulting database consists of photometry of ?100,000 stars at more than 1000 epochs per star, with differential photometric precision better than 1% per epoch. Analysis of the light curves of those stars produces transiting-planet candidates requiring detailed follow-up, described elsewhere, culminating in spectroscopy to measure radial velocity variation in order to differentiate genuine planets from the more numerous impostors, primarily eclipsing binary and multiple stars.

The monomeric precursor Zr-npropoxide was modified using chelating agents. The resulting sols were used to compose a consolidant sol that included coupling agents selected based on previous studies done by ourselves, the hydrophobic agent trimethyl methoxysilane (TMS) and mesitylene as drying control chemical additive (DCCA). The sols were studied by Fourier Transform Infrared Spectroscopy (FTIR). In a later stage calcite powder was impregnated with the sols and studied by Diffuse Reflectance Infrared Spectroscopy (DRIFT). According to the DRIFT results new bands appeared, that indicate interactions between the coupling agents and calcite. The Kratky plots obtained from the sols indicate that in all cases fiber-like oligomeric structures were obtained, having a fractal dimension value 1.60.

BackgroundAlcohol exposure during development can produce severe and long‐lasting central nervous system damage and consequent behavioral alterations. Recent evidence suggests that NMDA receptor‐mediated excitotoxicity during periods of withdrawal may contribute to this damage. We have demonstrated that blocking the NMDA receptor with MK‐801 during alcohol withdrawal can attenuate ethanol's adverse effects on behavioral development in the rat. This study examined the dose dependency of MK‐801's ability to mitigate ethanol's teratogenic effects.

The morphology of gibbsite, γ-Al(OH)3, crystals is predicted on the basis of a complete connected net analysis. It turns out that the morphology cannot be explained on the basis of the attachment energy. Instead, it is shown by a Monte Carlo algorithm based on a 2D nucleation model, that the edge (free) energy of the flat faces is the relevant parameter that determines the growth morphology. The algorithm reveals that the morphological importance of the faces follows the sequence:  {112}, {11&twomacr;} ≈ {101}, {10&onemacr;} &lt; {200} &lt; {110} ≪ {002}. At zero driving force, gibbsite has a hexagonal morphology with {002} basal faces, {200} and {110} side and {101}, {10&onemacr;}, {112} and {11&twomacr;} chamfered faces. At higher driving forces, the chamfered faces disappear first, followed by the {200} faces. This corresponds well to our experimental results and is explained in terms of the energies involved in the formation of 2D nuclei at the various surfaces. Thus, the various morphologies observed for gibbsite crystals depending on the driving force for crystallization can be explained.

Objectives:1) To survey all patients waiting for cardiac surgery to ascertain if patients wanted further education and support than was already being provided. 2) To use the results of this survey to plan future provision of services.

We experimentally observed two forms of subsideband generation in the soliton spectrum of a passively mode-locked fiber soliton ring laser. We found that the different forms of subsideband generation are related to the different strengths of the saturable absorption in the laser cavity. Analyzing featuring of the subsideband generations, we show that they are both modulational-instability lasings of the dispersive waves in the laser.

Computer modeling techniques provide a useful mechanism with which to model the morphology of defect crystals. In this work, a study of the incorporation of sodium and potassium cations into the morphologically important surfaces of gibbsite was conducted. Computation of the resulting changes in surfaces energies was achieved with the aid of a Born−Haber cycle. These calculations were then employed to determine the defect influenced morphologies for both cations. The resulting habits suggest that cation incorporation contributes to the elongation of the prismatic faces and also to the formation of diamond morphologies.

The protein ubiquitin (Ub) appears to be present in all eukaryotic cells. Its widespread presence and extremely conserved structure indicate that it may play a vital role in cell metabolism. The roles of Ub are mediated by its covalent attachment to target proteins, a process known as ubiquitylation, a form of protein modification which may lead to degradation of the modified protein. A number of proteins with similar structure to Ub but varying in function have been isolated. Recently, there has been much interest in the role of Ub and its related proteins in reproductive processes. Ub and Ub-related proteins may be involved in gametogenesis, modulation of steroid receptor concentrations, placental development and endometrial modification at the beginning of pregnancy. These wide-ranging effects have led to extensive research which will be reviewed in this article.

It has previously been demonstrated that stimulation of opiate receptors within the nucleus accumbens results in marked hyperphagia, perhaps reflecting enhancement of taste palatability. Rats that have received multiple morphine treatments also increase feeding in response to environmental stimuli that have been associated with the morphine injections. The present investigation further examined this phenomenon. In Experiment 1, it was shown that induction of conditioned feeding was dose-dependent; significant conditioned feeding was obtained with repeated (n= 5) intra-accumbens injections of 5 or 10 μg/μl morphine but not with saline or 1 μg. The conditioned feeding response was blocked by systemic naltrexone (5 mg/kg). In the second experiment, co-treatment with either a D-1 (SCH 23390, 0.1 mg/kg) or D-2 (haloperidol, 0.25 mg/kg) antagonist did not block the developmentof conditioned feeding, nor did these drugs block morphine-induced feeding. In Experiment 3, it was found that systemic naltrexone blocked the expressionof conditioned feeding (confirming Experiment 1), as did SCH-23390, whereas haloperidol did not affect expression of conditioned feeding. In the fourth experiment, we observed that significant conditioned feeding was induced with repeated treatment with the selective mu agonist D-Ala2, NMe-phe4, Glyol5-enkephalin (DAMGO, 2.5 μg), but not with the delta agonist D-Pen2,5-enkephalin (DPEN, 3.1 μg). The final experiment tested the diurnal variability of the expression of conditioned feeding, and it was found that the magnitude of the effect depended on time of day. In summary, the development of opioid-induced conditioned feeding depends on mu opiate receptor stimulation, but not dopamine receptor stimulation. Its expression, however, involves both opiate and D-1 receptor activation. These findings are considered in terms of putative neural mechanisms governing conditioned meal initiation, and implications for compulsive eating and bulimia are also discussed.

This study was designed to clarify whether orientation of the first polar body (PB) of the oocyte at 6 o'clock rather than 12 o'clock, during intracytoplasmic sperm injection (ICSI), significantly affects a number of clinically important outcome measures including fertilization, zygote cleavage, embryonic morphology, and clinical pregnancy and implantation rates. In all, 114 patients were allocated to one of two groups on the basis of strict alternation, both groups being treated by the same ICSI practitioner. In one group, all oocytes were injected with their first PB at 6 o'clock, whereas in the other, the orientation of the PB was reversed (12 o'clock). In all cases, a normally bevelled injection pipette was inserted into the oocyte in the 3 towards 9 o'clock direction. The orientation of the PB did not significantly affect the proportion of oocytes that failed to survive injection or the proportion scored as having either zero, one, two or three pronuclei. The proportion of normally fertilized zygotes that cleaved was not significantly different between the two groups, nor was the proportion of embryos classified as either grade 1, 2 or 3. However, the proportion of grade 4 embryos (the poorest grade) was significantly lower in the 12 o'clock, compared to the 6 o'clock group. Most importantly, there was no significant difference between the two groups in the proportion of patients having a positive clinical pregnancy test, nor in either the implantation rate or the mean number of fetal hearts detected per patient presenting with a clinical pregnancy.

Advances in our understanding of the genetic abnormalities that lead to the development of renal carcinomas have led to the formulation of a new histopathological classification. This classification is based on these genetic changes but can be implemented by the use of conventional histopathological methods. The most common renal carcinoma is the conventional or clear cell type associated with a mutation in the Von Hippel Lindau (VHL) gene and with loss of chromosome 3p. Papillary carcinoma, chromophobe and collecting duct carcinomas have distinctive morphology and clinical behaviour and a different set of genetic alterations. Sarcomatoid transformation is now defined as a progression factor common to all of the variants of renal carcinomas rather than a separate entity. Some benign neoplasms are also recognised including oncocytoma, renal adenoma and metanephric adenoma. The morphology of these various renal epithelial tumours is discussed.

AbstractA universal algebra is called congruence compactif every family of congruence classes with the finite intersection property has a non-empty intersection. This paper determines the structure of all right congruence compact monoids Sfor which Green's relations ? and coincide. The results are thus sufficiently general to describe, in particular, all congruence compact commutative monoids and all right congruence compact Clifford inverse monoids.

These authors gathered information that their users needed and built it into their company's new Intranet, therby improving their image within the organization. [ABSTRACT FROM AUTHOR]

4-aminobutyrate metabolism in Escherichia coli begins with transport across the cytoplasmic membrane via the GabP, which is encoded by gabP. Although GabP is specific and exhibits poor affinity for many cellular constituents such as the alpha-amino acids, the range of compounds recognized with high affinity has yet to be investigated. In order to address this gap in knowledge, we developed a gabP-negative host strain, which permits evaluation of test compounds for inhibitory effects on cloned GabP (expression inducible by isopropyl-1-thio-beta-D-galactopyranoside). Using this inducible expression system, three structurally distinct categories of high affinity transport inhibitor were identified. The structural dissimilarity of these inhibitors significantly alters our view of ligand recognition by GabP. Any complete model must now account for the observation that inhibition of 4-aminobutyrate transport can be mediated either (i) by open chain analogs of 4-aminobutyrate, (ii) by cyclic amino acid analogs, or (iii) by planar heterocyclic compounds lacking a carboxyl group. Such results do not support a previously sustainable view of GabP that features a restrictive ligand recognition domain, unable to accommodate structures that differ very much from the native substrate, 4-aminobutyrate.

Intestinal epithelial cell proliferation in young male F344 rats was measured in response to dietary protein content (5%, 10%, and 20% casein diets), energy restriction (energy intake was 60% of ad libitum energy intakes of animals consuming the 20% casein diet), total diet restriction (dietary intake was 60% of the ad libitum intake of 20% casein diet group), aflatoxin administration, and whole body irradiation. Cellular proliferation was measured in sections of jejunum, ileum, proximal colon, and distal colon with the [3H]thymidine technique. Restricting energy or total diet intakes by 40% from ad libitum levels reduced proliferation in epithelial cells throughout the intestine. In comparison to the 5% casein diet, the 20% casein diet resulted in modestly lower cellular proliferation in all intestinal segments. Radiation induced a decrease in cellular proliferation in the jejunum and ileum; this decrease was prevented by a 20% casein diet. Pretreatment with aflatoxin B1 decreased intestinal cell proliferation throughout the intestine, and this decrease was not influenced by the protein content of the diet.

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The 14C-triolein breath test, a recognised index of fat absorption, and the p-aminobenzoic acid (PABA) test, a ‘tubeless’ test of exocrine pancreatic function, have both been widely used in the diagnosis of malabsorption and exocrine pancreatic insufficiency. This study evaluates the potential of a combination of both tests in the investigation of fat absorption and exocrine pancreatic function. Combination of the tests has become technically feasible because of the introduction of high pressure liquid chromatography as the preferred method of analysis for PABA, and use of p-aminosalicylic acid (PAS) as the marker for PABA absorption and metabolismWe studied 25 healthy subjects, 11 patients with exocrine pancreatic disease and 12 patients with gastrointestinal disease. The combined test identified subjects with reduced fat absorption and distinguished subjects with exocrine pancreatic insufficiency from those with an intestinal cause of fat malabsorption. The test could be completed in 7 h and had high patient acceptibility. These findings suggest that the combined 14C-triolein breath test and PABA test can be used as a non-invasive, 1-day investigation of fat absorption and exocrine pancreatic function.

Utilizing real-time computer image analysis, individual spermatozoa were selected using microaspiration. Selection criteria were based on potential hyperactivation motility characteristics; the amplitude of lateral head displacement > 7.5 microns, curvilinear velocity > 70 microns/s and linearity of < 30%. For this pilot study, 16 patients (eight in each group) were recruited. Using subzonal insemination (SUZI), up to five (mean = 4.4 +/- 0.3) spermatozoa selected using computer-image sperm selection (CISS) were micro-injected, or up to 15 (mean = 12.8 +/- 1.3 SD) unselected spermatozoa. In the group which utilized CISS, 28 out of 49 (57%) oocytes were fertilized compared with 13 out of 52 (25%) utilizing conventional SUZI (P < 0.04); polyspermy was 20% (n = 10) and 2% (n = 1) respectively. CISS with SUZI showed increased efficiency in achieving fertilization and is a novel approach to studying individual sperm function in a sperm egg bioassay where gamete ratios are close to unity.

In this paper the authors examine the role of councillors at the committee stage of development-control decisions. Their rejection of officer recommendations is studied for Bracknell District Council between 1974 and 1981. In rejecting recommendations, the committee may act to facilitate the approval of an application, or it may attempt to block a proposal. The issues at stake and the consequences of their actions are discussed.

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The dream imagery of 30 first-year student nurses was monitored by self-report questionnaires before and during their first clinical placements. Students randomly assigned to the geriatric group (N = 14) trained on a ward in a large metropolitan geriatric hospital. The remaining students (N = 16) were assigned to the medical-surgical ward of a general hospital where exposure to dying is infrequent (the general clinical group). Analyses revealed no significant differences between the geriatric group and the general clinical group on death association and death symbolism content of their reported dreams. However, in contrast to the general clinical group, the geriatric group reported a significantly greater number of dream images associated with old age (geriatric association) in anticipation of their clinical experience. In addition, there was a significant decrease in geriatric associations for this group during the period of internship in the geriatric hospital.

The secretion of renin from granules stored in renal juxtaglomerular cells plays a key role in blood pressure homeostasis. The synthesis and release of renin and the extent of granulation is regulated by several mechanisms including signaling from the macula densa, neuronal input, and blood pressure. Through the use of a gene-targeting vector containing homology arms generated using the polymerase chain reaction, we have inactivated the Ren-1(d) gene, one of two mouse genes encoding renin, and report that lack of renin-1(d) results in altered morphology of the macula densa of the kidney distal tubule and complete absence of juxtaglomerular cell granulation. Furthermore, Ren-1(d-/-) mice exhibit sexually dimorphic hypotension. The altered growth morphology of the macula densa in Ren-1(d)-null mice should provide a tool for the investigation of the JG cell-macula densa signaling. Furthermore, the current data indicate that expression of the Ren-1(d) gene is a prerequisite for the formation of storage granules, even though the related protein renin-2 is present in these mice, suggesting that renin-1(d) and renin-2 are secreted by distinct pathways in vivo.