cssi/SciSciGPT-SciSciNet huggingface dataset:
Toleranzentstehung nach Langzeitnitraten? Eine kritische Übersicht

Nitroglyzerin und die langwirkenden Nitrat-Ester gewinnen zunehmend an Bedeutung. Sie werden fur die Behandlung einer Anzahl von kardiovaskularen Erkrankungen verwendet (Tabelle 1) und sind die tragende Saule der medikamentosen Therapie der Angina pectoris. Bei zahlreichen Patienten mit Herzinsuffizienz mittleren Schweregrades uben die Nitrate durch Senkung der linksventrikularen Fullungsdrucke und Aufrechterhaltung bzw. Erhohung des Herzzeitvolumens ihre gunstige Wirkung aus. Im Verlauf der letzten 5 bis 7 Jahre konnte uberzeugend nachgewiesen werden, das haufig eine hochdosierte Nitrattherapie erforderlich ist. Dies gilt insbesondere bei Herzinsuffizienz oder therapierefraktarer Angina pectoris. Heutzutage erhalten viele Patienten Nitratmengen, die fruher als ubertrieben hoch gegolten hatten, die aber in Wirklichkeit zum Erreichen einer angemessenen Bioverfugbarkeit und anhaltenden pharmakologischen Wirksamkeit erforderlich sind (1, 2).
Diagnostic pitfalls of infarcted Warthin tumor in frozen section evaluation

Warthin tumor (WT) is the second most common benign salivary gland neoplasm and has characteristic cytologic and histologic findings. Fine-needle aspiration is a common and useful preoperative diagnostic technique, which sometimes leads to ischemic injury resulting in the infarction of these lesions. Infarcted WT may demonstrate variable gross and histologic alterations that may render the diagnosis challenging, particularly during intraoperative frozen section evaluation. In this study, we collected 11 resection specimens from 9 patients with infarcted WT. Seven patients were men and 2 were women, ranging from 49 to 85 years (mean, 69). All the patients had fine-needle aspiration before the resection. Macroscopically, the tumors were tan-white and contained soft, yellow, exudative material. The histologic findings were variable and included necrosis, ghosts of papillae, squamous metaplasia, cholesterol clefts, foamy macrophages, multinucleated giant cell reaction, necrotizing granulomas, and fibrosis. Each case predominantly demonstrated 1 or 2 of these histomorphologic features. In the permanent sections, additional sampling revealed foci of residual viable WT in 8 cases. Three cases were completely infarcted; however, they all had ghost-like papillae in which the architecture of WT was evident. Infarcted WT may present a diagnostic challenge during intraoperative frozen section evaluation. Associated morphologic alterations may preclude a definitive diagnosis of WT and may mimic malignancy. Awareness of the gross and microscopic features associated with infarcted WT is important, particularly for accurate frozen section evaluation of these salivary gland tumors.
Rectal Anticonvulsant Therapy

The use of rectally administered antiepileptic drugs (AEDs) is reviewed by experts from the College of Pharmacy and Division of Pediatric Neurology, University of Minnesota, Minneapolis, Minn.
Sensor-Based Fast Thermal Evaluation Model For Energy Efficient High-Performance Datacenters

In this work, we propose an abstract heat flow model which uses temperature information from onboard and ambient sensors, characterizes hot air recirculation based on these information, and accelerates the thermal evaluation process for high performance datacenters. This is critical to minimize energy costs, optimize computing resources, and maximize computation capability of the datacenters. Given a workload and thermal profile, obtained from various distributed sensors, we predict the resulting temperature distribution in a fast and accurate manner taking into account the recirculation characterization of a datacenter topology. Simulation results confirm our hypothesis that heat recirculation can be characterized as cross interference in our abstract heat flow model. Moreover, fast thermal evaluation based on cross interference can be used in online thermal management to predict temperature distribution in real-time.
Inwardly rectifying K+ channels are major contributors to flow-induced vasodilatation in resistance arteries.

Key points Endothelial inwardly rectifying K+ (Kir2.1) channels regulate flow-induced vasodilatation via nitric oxide (NO) in mouse mesenteric resistance arteries. Deficiency of Kir2.1 channels results in elevated blood pressure and increased vascular resistance. Flow-induced vasodilatation in human resistance arteries is also regulated by inwardly rectifying K+ channels. This study presents the first direct evidence that Kir channels play a critical role in physiological endothelial responses to flow. Abstract Inwardly rectifying K+ (Kir) channels are known to be sensitive to flow, but their role in flow-induced endothelial responses is not known. The goal of this study is to establish the role of Kir channels in flow-induced vasodilatation and to provide first insights into the mechanisms responsible for Kir signalling in this process. First, we establish that primary endothelial cells isolated from murine mesenteric arteries express functional Kir2.1 channels sensitive to shear stress. Then, using the Kir2.1+/− heterozygous mouse model, we establish that downregulation of Kir2.1 results in significant decrease in shear-activated Kir currents and inhibition of endothelium-dependent flow-induced vasodilatation (FIV) assayed in pressurized mesenteric arteries pre-constricted with endothelin-1. Deficiency in Kir2.1 also results in the loss of flow-induced phosphorylation of eNOS and Akt, as well as inhibition of NO generation. All the effects are fully rescued by endothelial cell (EC)-specific overexpression of Kir2.1. A component of FIV that is Kir independent is abrogated by blocking Ca2+-sensitive K+ channels. Kir2.1 has no effect on endothelium-independent and K+-induced vasodilatation in denuded arteries. Kir2.1+/− mice also show increased mean blood pressure measured by carotid artery cannulation and increased microvascular resistance measured using a tail-cuff. Importantly, blocking Kir channels also inhibits flow-induced vasodilatation in human subcutaneous adipose microvessels. Endothelial Kir channels contribute to FIV of mouse mesenteric arteries via an NO-dependent mechanism, whereas Ca2+-sensitive K+ channels mediate FIV via an NO-independent pathway. Kir2 channels also regulate vascular resistance and blood pressure. Finally, Kir channels also contribute to FIV in human subcutaneous microvessels.
State of the Scholarship in Classics on Ancient Roman Rhetoric

ABSTRACTLimiting ourselves to scholarly books published in English from 2009–2016, we survey classics scholarship about rhetoric in ancient Rome from the late republic through the early empire. We seek traditional threads and growing trends across those works that advance our understanding of rhetoric’s practical, theoretical, and material manifestations during that time of tumult and transition. We begin broadly, using companion books to delineate three structural pillars in the scholarship: rhetoric as a formal cultural system, the republic as subject to ruptures and reinventions, and Cicero as a foremost statesman of the late republic. Then we move into scholarship that draws upon nontraditional rhetorical objects, such as art, and that moves into increasingly vibrant areas of interest in rhetoric, such as the senses. Overall, we find that classicists writing about ancient Roman rhetorical culture share with their counterparts in rhetoric an urge to test old verities and to add historical depth to larg...
Factorization for generic jet production

Factorization is the central ingredient in any theoretical prediction for collider experiments. We introduce a factorization formalism that can be applied to any desired observable, like event shapes or jet observables, for any number of jets and a wide range of jet algorithms in leptonic or hadronic collisions. This is achieved by using soft-collinear effective theory to prove the formal factorization of a generic fully differential cross section in terms of a hard coefficient, and generic jet and soft functions. In this formalism, whether a given observable factorizes in the usual sense, depends on whether it is inclusive enough, so the jet functions can be calculated perturbatively. The factorization formula for any such observable immediately follows from our general result, including the precise definition of the jet and soft functions appropriate for the observable in question. As examples of our formalism, we work out several results in two-jet production for both ${e}^{+}{e}^{\ensuremath{-}}$ and $pp$ collisions. For the latter, we also comment on how our formalism allows one to treat underlying events and beam remnants.
Arteriovenous Graft-Arteriovenous Fistula Conversion (Secondary Arteriovenous Fistula Creation)

Arteriovenous hemodialysis catheters have lower rates of primary and secondary patency than autologous arteriovenous fistulas in most patients. While emphasis has been placed on de novo construction of arteriovenous fistulae, grafts are still placed for primary access in a large population of end-stage renal disease placements. Unfortunately, once these grafts fail, patients are often left with no peripheral hemodialysis access and require central venous catheter placement. Construction of secondary arteriovenous fistulae prior to graft failure obviates the need for this period of hemodialysis catheter placement.
No Increased Risk of ASD, ADHD, or SGA with First-Trimester Antidepressant Use

This study found that maternal antidepressant use during the first trimester of pregnancy is associated with an increased risk of preterm birth, but not SGA, ASD, or ADHD. Another study in the same issue also reported no increased risk of ASD with in utero exposure to selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors.
The role of Atlantic overturning circulation in the recent decline of Atlantic major hurricane frequency.

Observed Atlantic major hurricane frequency has exhibited pronounced multidecadal variability since the 1940s. However, the cause of this variability is debated. Using observations and a coupled earth system model (GFDL-ESM2G), here we show that the decline of the Atlantic major hurricane frequency during 2005–2015 is associated with a weakening of the Atlantic Meridional Overturning Circulation (AMOC) inferred from ocean observations. Directly observed North Atlantic sulfate aerosol optical depth has not increased (but shows a modest decline) over this period, suggesting the decline of the Atlantic major hurricane frequency during 2005–2015 is not likely due to recent changes in anthropogenic sulfate aerosols. Instead, we find coherent multidecadal variations involving the inferred AMOC and Atlantic major hurricane frequency, along with indices of Atlantic Multidecadal Variability and inverted vertical wind shear. Our results provide evidence for an important role of the AMOC in the recent decline of Atlantic major hurricane frequency. The reason for the decline in frequency of Atlantic major hurricanes since 2005 is still debated. Here the authors combine observations with model simulations to show that this decline is largely due to changes in the Atlantic ocean meridional overturning circulation.
Regulation of T cell proliferation with drug-responsive microRNA switches

As molecular and cellular therapies advance in the clinic, the role of genetic regulation is becoming increasingly important for controlling therapeutic potency and safety. The emerging field of mammalian synthetic biology provides promising tools for the construction of regulatory platforms that can intervene with endogenous pathways and control cell behavior. Recent work has highlighted the development of synthetic biological systems that integrate sensing of molecular signals to regulated therapeutic function in various disease settings. However, the toxicity and limited dosing of currently available molecular inducers have largely inhibited translation to clinical settings. In this work, we developed synthetic microRNA-based genetic systems that are controlled by the pharmaceutical drug leucovorin, which is readily available and safe for prolonged administration in clinical settings. We designed microRNA switches to target endogenous cytokine receptor subunits (IL-2Rβ and γc) that mediate various signaling pathways in T cells. We demonstrate the function of these control systems by effectively regulating T cell proliferation with the drug input. Each control system produced unique functional responses, and combinatorial targeting of multiple receptor subunits exhibited greater repression of cell growth. This work highlights the potential use of drug-responsive genetic control systems to improve the management and safety of cellular therapeutics.
Paleomagnetic Records in Cave Sediments

The Earth’s magnetic field reverses polarity at irregular intervals in the range of a few hundred thousand years. Magnetic mineral grains suspended in cave waters orient themselves with respect to the prevailing field direction when they settle from the water and then become locked in place in the resulting pile of cave sediment. Because the time scale of magnetic reversals is well-established, measurement of magnetic orientation in cave sediments and the location of magnetic reversals within sediment piles can be used to date the deposits and thus provide a minimum age for the cave.
Use of in-field bioreactors demonstrate groundwater filtration influences planktonic bacterial community assembly, but not biofilm composition

Using in-field bioreactors, we investigated the influence of exogenous microorganisms in groundwater planktonic and biofilm microbial communities as part of the Integrated Field Research Challenge (IFRC). After an acclimation period with source groundwater, bioreactors received either filtered (0.22 μM filter) or unfiltered well groundwater in triplicate and communities were tracked routinely for 23 days after filtration was initiated. To address geochemical influences, the planktonic phase was assayed periodically for protein, organic acids, physico-/geochemical measurements and bacterial community (via 16S rRNA gene sequencing), while biofilms (i.e. microbial growth on sediment coupons) were targeted for bacterial community composition at the completion of the experiment (23 d). Based on Bray-Curtis distance, planktonic bacterial community composition varied temporally and between treatments (filtered, unfiltered bioreactors). Notably, filtration led to an increase in the dominant genus, Zoogloea relative abundance over time within the planktonic community, while remaining relatively constant when unfiltered. At day 23, biofilm communities were more taxonomically and phylogenetically diverse and substantially different from planktonic bacterial communities; however, the biofilm bacterial communities were similar regardless of filtration. These results suggest that although planktonic communities were sensitive to groundwater filtration, bacterial biofilm communities were stable and resistant to filtration. Bioreactors are useful tools in addressing questions pertaining to microbial community assembly and succession. These data provide a first step in understanding how an extrinsic factor, such as a groundwater inoculation and flux of microbial colonizers, impact how microbial communities assemble in environmental systems.
Topical beta-aminopropionitrile in the treatment of Peyronie's disease.

AbstractWe treated 9 patients with Peyronie’s disease for 1 to 8 years in duration with a 4-week course of beta-aminopropionitrile free base as the pure liquid. The drug was applied topically to the plaques twice daily. Patients were followed with ultrasound imaging of the plaques and saline inflations of the corpora cavernosa with photographic documentation of the deformity. No significant adverse effect was noted. Three patients experienced a subjective response but did not demonstrate objective change on the aforementioned studies. It was concluded that topical beta-aminopropionitrile was not effective in reversing the deformity of Peyronie’s disease. Further investigation into specific anti-collagen drugs for the treatment of this condition may be warranted.
Intestinal taurine and the enterohepatic circulation of taurocholic acid in the cat.

Taurine’s most well defined role is the conjugation of bile salts in the liver. After synthesis from cholesterol, bile salts are conjugated with taurine and/or glycine before secretion into the bile canaliculi1. When taurine is limiting, most mammals have the ability to conjugate bile salts with glycine, exceptions being the dog2 and the cat3,4, which conjugate bile salts almost exclusively with taurine. The percentage of total bile salts conjugated with taurine is determined by both the hepatic taurine concentration and the affinity of the bile salt conjugase for glycine and taurine2,5-7. Taurine is the preferred substrate in most species with 90 percent taurine conjugation occurring in the rat when hepatic taurine and glycine concentrations are equal7. Hepatic taurine depletion in rats, caused by the infusion of cholic acid7 or by feeding guanidinoethanesulfonic acid5, results in a substantial increase in the amount of bile salts conjugated with glycine. In species that cannot conjugate bile salts with glycine (the dog and cat), hepatic taurine depletion leads instead to an increase in the proportion of unconjugated bile salts, the majority being free cholic acid2,3.
Ultrasonic Evaluation of Dissimilar Solid-State Bonds

This paper discusses two special ultrasonic NDE problems of particular interest to dissimilar solid-state bonds. The first problem is the so-called “cold weld” effect which is a lack-of-bond type defect, but as opposed to other common types of defects in this category, it is very difficult to detect by ultrasound. The other problem, to be addressed in the second part of this paper, is the “blinding” effect of the strong interface reflection caused by acoustical impedance mismatch between dissimilar materials. Ultrasonic characterization of such bonds is rendered very difficult by the fact that the relatively weak signals generated by possible boundary imperfections are often overshadowed by this inherent reflection. A novel technique based on the symmetric part of the interface reflections from the opposite sides of the bond will be introduced to obtain quantitative information even from very good, apparently flawless bonds.
Newly diagnosed AIDS with neurosyphilis, Kaposi sarcoma, pancytopenia, oropharyngeal candidiasis, and pseudomonal pneumonia: We shouldn't be seeing this anymore.

Abstract The incidence of new human immunodeficiency virus (HIV) infections is declining and is half of what it was in the mid 1990s. We present a case of newly diagnosed HIV with acquired immune deficiency syndrome (AIDS), Neurosyphilis, Kaposi Sarcoma, and multiple opportunistic infections. Although this type of patient was not uncommon in the pre-antiretroviral era, we do not often see such a constellation of conditions in a single individual. The significance of this case lies not in the diagnosis, but rather in the number of the diagnoses and the thought process used to attain them.
Quantitative Analysis of Underivatized Amino Acids by Liquid Chromatography-Tandem Mass Spectrometry.

Quantitative amino acid analysis has diverse applications in clinical diagnostics, biomedical research, and agriculture. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) enables more rapid and specific detection of amino acids in comparison to traditional, gold-standard ninhydrin-based methods. However, triple quadrupole mass spectrometers are unable to definitively differentiate isomers and are susceptible to ion suppression, both of which prevent accurate quantitation. Therefore, appropriate chromatography must be applied before ionization.We have shown that two-dimensional LC enables rapid and specific amino acid quantitation without derivatization by resolving isomers, such as alloisoleucine, isoleucine, and leucine, and reducing matrix effects (Le et al., J Chromatogr B Analyt Technol Biomed Life Sci 944:166-174, 2014). In this clinically validated protocol, we provide an updated description of the chromatographic setup and selected reaction monitoring (SRM) transitions. Then, we describe sample processing for serum, plasma, urine, cerebral spinal fluid, and dried blood spots. Most importantly, we outline a singular quantitative design for efficient data analysis of the listed sample types and quality assurance strategies to ensure test fidelity. Lastly, we share extensive knowledge critical to the success of this method. A liquid sample can be processed and be ready for injection within 5 min, and each sample is analyzed by the MS in 14.5 min.
OC43 Impact of flash and continuous glucose monitoring on quality of life and disease burden in children with diabetes mellitus and their families

Introduction/Background Flash and continuous glucose monitoring technology has revolutionised the management of diabetes, particularly in paediatric populations. Recent government funding for flash glucose monitoring devices has enabled widespread usage in children and adolescents in the Republic of Ireland. We examined the impact of this novel technology on the lives of children with diabetes and their parents through the use of age modified questionnaires. Design/Methods Qualitative research was carried out using anonymised ‘Quality of Life’ questionnaires. All children and adolescents and their families attending the diabetes service in Children’s University Hospital were eligible for the study and were invited to contribute at routine outpatient visit. Those using the technology were divided into three groups; pre-school, primary school and secondary school. Together, children and their parents answered questions relating to ease of use, impact on schooling, independence, parent-child relationships and subjective burden of disease. Some sections were specific to the particular form of glucose monitoring [flash or continuous]; but those regarding impact on day-to-day management of diabetes and impact on quality of life were common to all. A separate questionnaire was used for patients not using either technology and explored the factors that influenced that decision. Results Preliminary data (n=39) shows that patient and parent experiences with flash and continuous glucose monitoring technology have been overwhelmingly positive. 90% of children surveyed are using one of these devices. Across all age groups, 100% of those using the technology reported subjective improvement in glycaemic control. All adolescents reported increased confidence in their ability to manage diabetes and a greater degree of personal independence. Parents reported significant reduction in frequency of hypoglycaemic events and > 80% reported reduction in anxiety surrounding hypoglycaemia. >85% of both patients and parents found a significant reduction in the day-to-day burden of diabetes. Those not using glucose-monitoring devices listed parental concern regarding device accuracy and attachment of the device on the skin as the major deterring factors. Conclusions This data demonstrates a positive impact of flash and continuous glucose monitoring on quality of life for children with diabetes mellitus. Government funding since 2018 has enabled equal access for all paediatric patients [over 4 years old] to this life-impacting technology which should now be offered to all children and adolescents, to include those with Type 2 Diabetes and other rarer sub-types, and those under 4 years old.
Developed Systems in the Mariana Islands Archipelago

Abstract This article represents a status assessment of the Mariana Islands developed system, including the current status, stressors, and future viability. Developed systems within the Marianas Archipelago exist where there are human populations, primarily focused on the coasts of Guam, Saipan, Rota, and Tinian Islands. The quality of the developed system is largely composed of a mixture of nonnative vegetation types, and predominantly nonnative wildlife. Our assessment of the developed system viability, defined as the likelihood of persistence over the long term, is based on the concepts of representation, redundancy, and resiliency. The main stressors to developed systems are effects of climate change, additional development, typhoons, pollution and invasive species. Ongoing conservation efforts are helping to protect plants and wildlife within developed systems, and the conservation depends largely on combined efforts of State, Federal, multiagency organizations, nonprofit organizations, and the voluntary support of private landowners. The Marianas developed system represents a unique land use type, whose composition is dynamic across its range. Due to growing human population numbers, the developed system is likely to decrease in size over the coming years, as development increases. Projections for the persistence of developed systems in the Marianas largely depends on the conservation actions taken, which should be implemented to safeguard pockets of biodiversity found within these systems.
Financial efficiency and accounting quality: The impact of institutional micro-factors on FDI

Abstract In this paper, we explore whether factors such as financial markets and accounting qualities contribute to foreign direct investment (FDI). We use a unique data source: the survey data from World Economic Forum, to measure the efficiency of the financial markets and the quality of accounting standards. With this unique data, we demonstrate that financial markets and accounting quality are important factors of FDI inflow into a country. In particular, FDI is positively correlated with the strength of financial audits and reporting standards and venture capital availability for all countries. We also show that accounting quality measures are more important for developing and emerging countries than for developed countries. On the other hand, financial market measures, especially the access to venture capital, have a bigger impact in attracting FDI flow into developed countries. These results support the hypothesis that local financial markets and accounting quality affect FDI. The results have strong policy implications for governmental regulatory agencies.
Facile synthesis of high surface area molybdenum nitride and carbide

Abstract The synthesis of high surface area γ-Mo2N and α-Mo2C is reported (116 and 120 m2/g) without the temperature programmed reduction of MoO3. γ-Mo2N was prepared in an NH3-free synthesis using forming gas (7 at% H2, N2-balance) as the reactive atmosphere. Three precursors were studied ((NH4)6Mo7O24·4H2O, (NH4)2 Mg(MoO4)2, and MgMoO4) along with the sacrificial support method (SSM) as a means of reducing the particle size of Mo2N and Mo2C. In situ X-ray diffraction (XRD) studies were carried out to identify reaction intermediates, the temperature at which various intermediates form, and the average domain size of the Mo2N products. Materials were synthesized in bulk and further characterized by XRD, HRTEM, XPS, and BET.
Labour Force Participation of Women: Empirical Evidence on the Role of Policy and Other Determinants in OECD Countries

This paper examines the determinants of female labour force participation in OECD countries, including a number of policy instruments such as the tax treatment of second earners (relative to single individuals), childcare subsidies, child benefits, paid maternity and parental leaves, and tax incentives to sharing market work between spouses. The econometric analysis uses a panel data set covering 17 OECD countries over the period 1985-1999, and distinguishes between part-time and full-time female participation rates. It shows a positive impact on female participation of a more neutral tax treatment of second earners (relative to single individuals), stronger tax incentives to share market work between spouses, childcare subsidies, and paid maternity and parental leaves Unlike childcare subsidies, child benefits reduce female participation due to an income effect and their lump-sum character. Finally, female education, the general labour market conditions, and cultural attitudes remain major determinants of female participation.
The Richard Grady Monsplasty: A vertical Z-plasty technique.

Summary Classic bladder exstrophy in the female results in an exstrophic bladder and urethra, an anterior introitus with a bifid clitoris and short labia minora. During closure, the lower abdominal wall is closed and the bifid clitori are brought into close apposition, but are often not completely closed to prevent injury to the clitoral bodies, thus leaving a persistent gap between the clitoral bodies that grows over time. We demonstrate a vertical z plasty closure to provide a 2 layer closure of the mons that decreases tension and improves cosmetic appearance by recreating a clitoral hood that provides a more normal appearance of the external genitalia for girls with bladder exstrophy.
Cortical ripples provide the conditions for consolidation during NREM sleep in humans

Hippocampal ripples index the reconstruction of spatiotemporal neuronal firing patterns essential for the consolidation of memories in the cortex during non-rapid eye movement (NREM) sleep. However, it is not known whether ripples are generated in the human cortex during sleep. Here, using human intracranial recordings, we show that ~70ms long ~80Hz ripples are ubiquitous in all regions of the cortex during NREM sleep as well as waking. During waking, cortical ripples occur on local high frequency activity peaks. During sleep, cortical ripples occur during spindles on the down-to-upstate transition, with unit-firing patterns consistent with generation by pyramidal-interneuron feedback. Cortical ripples mark the recurrence of spatiotemporal activity patterns from preceding waking, and they group co-firing within the window of spike-timing-dependent plasticity. Thus, cortical ripples guided by sequential sleep waves may facilitate memory consolidation during NREM sleep in humans.
A 5G 25–29 GHz 64-Element Phased-Array with 49–52 dBm EIRP, Integrated Up/Down-Converter and On-Chip PLL

A 25–29 GHz phased-array with embedded filter, driver, up/down-converter and mm-wave PLL is presented. This work is based on two separate chips, a 2×2 SiGe BiCMOS beamformer chip with 14–15 dBm of output power per channel and a wideband up/down-converter with low phase noise. These chips are assembled on a carrier printed-circuit board containing high efficiency stacked-microstrip antennas, a 16:1 low-loss Wilkinson network, a high-Q filter to remove any spurious harmonics and mixing spurs from the up/down-converter, and all other supporting components such as the reference crystal oscillator, voltage regulators, SPI drivers and IF and LO connectors. The phased-array system results in a measured EIRP of 49–52 dBm at 25–29 GHz, spurious radiation of <-42 dBc as compared to P1dB-10 dB power levels, and an EVM of 5% for a 100 MBaud 64QAM waveform with a PAPR of 7.7 dB, at an EIRP of 42 dBm. This work shows the highest integration level at mm-wave frequencies to-date and small-cell units for mm-wave 5G.
Synthetic plots: some history and examples

Jerzy Neyman and Elizabeth Scott developed the idea of synthetic plots. These plots are a display of the data values of an experiment side by side with a display of simulated data values, with the simulation-based on a considered stochastic model. The Neyman and Scott work concerned the distribution of galaxies on the celestial sphere. A review of their wo is presented here followed by personal examples from hydrology, neuroscience, and animal motion.
Ultrastructure and steroid-binding studies in leiomyomatosis peritonealis disseminata

Leiomyomatosis peritonealis disseminata (LPD) is characterized by the development of numerous leiomyomata throughout the peritoneal cavity which appear grossly malignant but histologically benign. The etiology of this disorder has been controversial. The tenth reported case of LPD is presented with ultrastructural evidence that these tumors arise from smooth muscle cells. The cytoplasmic estrogen and progesterone bindings by these tumors were ninefold and twofold greater than receptor concentrations in normal myometrium from the same patient. In addition to the steroid binding data, the strong association of this disorder with pregnancy or, as in this case, oral contraceptives suggests that the stimulus for neoplastic initiation and growth is hormonally related.
A Family of LIC Vectors for High-Throughput Cloning and Purification of Proteins

Fifteen related ligation-independent cloning vectors were constructed for high-throughput cloning and purification of proteins. The vectors encode a TEV protease site for removal of tags that facilitate pro tein purification (his-tag) or improve solubility (MBP, GST). Specialized vectors allow coexpression and copurification of interacting proteins, or in vivo removal of MBP by TVMV protease to improve screening and purification. All target genes and vectors are processed by the same protocols, which we describe here.
Pharmacoeconomics of Aztreonam-Clindamycin versus Gentamicin-Clindamycin in the Treatment of Penetrating Abdominal Injury

STUDY OBJECTIVE: To evaluate the pharmacoeconomic implications of using aztreonam-clindamycin (A-C) versus gentamicin-clindamycin (G-C) from the perspective of the hospital and pharmacy directors. DESIGN: Pharmacoeconomic analysis performed at one of the sites participating in the prospective, randomized, double-blind, comparative, multicenter efficacy study. SETTING: Referral hospital with level 1 trauma center. PATIENTS: Eight-five adults with a suspected penetrating intraabdominal injury requiring laparotomy. INTERVENTIONS: Patients were randomized to receive aztreonam 2 g intravenously every 8 hours or gentamicin 2 mg/kg intravenous load followed by 5 mg/kg/day intravenously initially adjusted to peak concentrations of 6-8 micrograms/ml. All patients received clindamycin 900 mg intravenously every 8 hours. MEASUREMENTS AND MAIN RESULTS: Charge data were gathered from the hospital billing system and converted to cost data using an institutional cost:charge ratio of 0.6. Study drug and aminoglycoside monitoring costs were also calculated. Overall, 43 (97%) of 44 patients receiving A-C had a favorable clinical response compared with 35 (85.4%) of 41 receiving G-C (p = 0.052). The mean hospital cost of $66,336 for 7 infected patients was significantly higher than that of $8014 in 78 noninfected patients (p 0.05) despite having only a single failure (total cost $162,666) in the A-C group. Similarly, mean pharmacy costs of $1411 and $1604, respectively, were not significantly different (p > 0.05). CONCLUSIONS: Hospital costs for infected patients with penetrating abdominal trauma exceed those of noninfected patients by 5-fold. Despite a lower infection rate in the A-C group, neither hospital nor pharmacy costs were significantly different compared with those in the G-C group.
NaV1.1 channels and epilepsy

Voltage-gated sodium channels initiate action potentials in brain neurons, and sodium channel blockers are used in therapy of epilepsy. Mutations in sodium channels are responsible for genetic epilepsy syndromes with a wide range of severity, and the NaV1.1 channel encoded by the SCN1A gene is the most frequent target of mutations. Complete loss-of-function mutations in NaV1.1 cause severe myoclonic epilepsy of infancy (SMEI or Dravet's Syndrome), which includes severe, intractable epilepsy and comorbidities of ataxia and cognitive impairment. Mice with loss-of-function mutations in NaV1.1 channels have severely impaired sodium currents and action potential firing in hippocampal GABAergic inhibitory neurons without detectable effect on the excitatory pyramidal neurons, which would cause hyperexcitability and contribute to seizures in SMEI. Similarly, the sodium currents and action potential firing are also impaired in the GABAergic Purkinje neurons of the cerebellum, which is likely to contribute to ataxia. The imbalance between excitatory and inhibitory transmission in these mice can be partially corrected by compensatory loss-of-function mutations of NaV1.6 channels, and thermally induced seizures in these mice can be prevented by drug combinations that enhance GABAergic neurotransmission. Generalized epilepsy with febrile seizures plus (GEFS+) is caused by missense mutations in NaV1.1 channels, which have variable biophysical effects on sodium channels expressed in non-neuronal cells, but may primarily cause loss of function when expressed in mice. Familial febrile seizures is caused by mild loss-of-function mutations in NaV1.1 channels; mutations in these channels are implicated in febrile seizures associated with vaccination; and impaired alternative splicing of the mRNA encoding these channels may also predispose some children to febrile seizures. We propose a unified loss-of-function hypothesis for the spectrum of epilepsy syndromes caused by genetic changes in NaV1.1 channels, in which mild impairment predisposes to febrile seizures, intermediate impairment leads to GEFS+ epilepsy, and severe or complete loss of function leads to the intractable seizures and comorbidities of SMEI.
Bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC): a review of the literature and a practical approach to therapy

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Bladder preservation therapies for muscle-invasive bladder cancer (MIBC) have been developed to address the needs of two cohorts: patients with severe medical co-morbidities for whom radical cystectomy is too high risk and patients with limited disease who wish to avoid aggressive surgery. There are multiple bladder preservation options, although the trimodal approach of maximal transurethral resection with chemoradiotherapy is the most strongly supported. While outcomes are worse for patients unfit for surgery than those otherwise fit for surgery, bladder preservation approaches still offer curative potential. We present a comprehensive review of the literature and outline a practical approach to bladder preservation therapy for MIBC. This review aims to help urologists easily navigate through the decision tree of therapeutic options. Radical cystectomy (RC) is associated with considerable morbidity. Aside from the perioperative period, RC with urinary diversion poses great potential for long-term complications and morbidity. Bladder preservation therapies for muscle-invasive bladder cancer (MIBC) have been developed to address the needs of two cohorts: patients with severe medical co-morbidities for whom a radical surgery is too high risk and patients with limited disease who wish to avoid radical surgery. The goal of achieving complete response to treatment while maintaining bladder form and function has led to the development of multimodal approaches to this disease. There are multiple bladder preservation options, although the trimodal approach of maximal transurethral resection with chemoradiotherapy is the most strongly supported. In medically operable patients ('fit' for surgery), there is abundant evidence to support trimodal therapy as an acceptable treatment option for highly selected patients with MIBC with favourable pathological parameters. While outcomes are worse for medically inoperable patients ('unfit' for surgery), bladder preservation approaches still offer curative potential. However, prospective trials comparing the above regimens to RC are still needed to better define their role in the treatment of MIBC. We present a comprehensive review of the literature and outline a practical approach to bladder preservation therapy for MIBC.
Control of neuroblast production and migration by converging GABA and glutamate signals in the postnatal forebrain.

The production of adult-born neurons is an ongoing process accounting for > 10 000 immature neurons migrating to the olfactory bulb every day. This high turnover rate necessitates profound control mechanisms converging onto neural stem cells and neuroblasts to achieve adequate adult-born neuron production. Here, we elaborate on a novel epigenetic control of adult neurogenesis via highly coordinated, non-synaptic, intercellular signalling. This communication engages the neurotransmitters GABA and glutamate, whose extracellular concentrations depend on neuroblast number and high affinity uptake systems in stem cells. Previous studies show that neuroblasts release GABA providing a negative feedback control of stem cell proliferation. Recent findings show an unexpected mosaic expression of glutamate receptors leading to calcium elevations in migrating neuroblasts. We speculate that stem cells release glutamate that activates glutamate receptors on migrating neuroblasts providing them with migratory and survival cues. In addition, we propose that the timing of neurotransmitter release and their spatial diffusion will determine the convergent coactivation of neuroblasts and stem cells, and provide a steady-state level of neuroblast production. Upon external impact or injury this signalling may adjust to a new steady-state level, thus providing non-synaptic scaling of neuroblast production.
6th Geneva Conference Announcement

The Conference main theme will be Person-centered Health Research. In connection with this, ten thematic symposia will be held covering various aspects of person-centered research on conceptual issues, clinical care and public health. A special session on Ethical Standards for Research will also be held. A Geneva Declaration on Person-centered Health Research will be organized as well.
Full contrast transfer function correction in 3D cryo-EM reconstruction

Over the past years electron cryo-microscopy (cryo-EM) has established itself as an important tool in studying the three dimensional structure of biological molecules up to the resolution of 6-9 /spl Aring/. However, as we pursue even higher resolution (i.e., 3-4 /spl Aring/), the depth-of-field problem inherent in the contrast transfer function emerges as a limiting factor. This problem has been previously addressed in the research community (Jensen, G.J., 2000; DeRosier, D.J., 2000; Zhou, Z.H. and Chiu, W., 2003; Cohen, H.A. et al., 1984). We develop a full theoretical solution to this problem. We show that the projected image from the electron microscope corresponds to neither a slice, nor an Ewald sphere, in the Fourier space, but a pair of quadratic surfaces in that space. The general solutions to this problem for both single and double defocus exposures are developed. Simulations show the correctness of the theory.
Deregulation of FoxO3a accelerates prostate cancer progression in TRAMP mice.

BACKGROUND Forkhead box, class “O” (FoxO) transcription factors are involved in multiple signaling pathways and possess tumor suppressor functions. Loss of PTEN and activation of PI3K/Akt is frequently observed in prostate cancer, which may potentially inactivate FoxO activity. We therefore investigated the role of FoxO transcription factors in prostate cancer progression, in particular FoxO3a, in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, which mimics progressive forms of human disease. METHODS Prostate cancer progression in TRAMP mice was followed from 8 to 28 weeks. Expression patterns of Akt, FoxO1a, FoxO3a, FoxO4, and their phosphorylated form, DNA binding activity and downstream signaling molecules during different stages of disease progression were examined by immunoblotting, immunoprecipitation, enzyme-linked immunoabsorbant assay (ELISA), and immunohistochemistry. Inhibition of FoxO3a activity was attained by using FoxO3a peptide treatment to TRAMP mice. RESULTS In TRAMP mice, FoxO3a activity is negatively regulated by Akt/PKB through post-translational modification. Progressive increase in Akt activation during prostate cancer progression led to increase phosphorylation of FoxO3a and binding with 14-3-3, which potentially affected its transcriptional activity in age-specific manner. Furthermore, blocking FoxO3a activity resulted in accelerated prostate cancer progression in these mice, which was associated with the loss of cell cycle control and increased proliferation and survival markers. CONCLUSIONS Restoration of FoxO3a activity represents an attractive therapeutic target in the chemoprevention and possibly in inhibition of progression of prostate cancer. Prostate 73: 1507–1517, 2013. © 2013 Wiley Periodicals, Inc.
Time and cost constrained optimal designs of constant-stress and step-stress accelerated life tests

Abstract By running life tests at higher stress levels than normal operating conditions, accelerated life testing quickly yields information on the lifetime distribution of a test unit. The lifetime at the design stress is then estimated through extrapolation using a regression model. To conduct an accelerated life test efficiently with constrained resources in practice, several decision variables such as the sample allocation proportions and the stress durations should be determined carefully at the design stage. These decision variables affect not only the experimental cost but also the estimate precision of the lifetime parameters of interest. In this work, under the constraint that the total experimental cost does not exceed a pre-specified budget, the optimal decision variables are determined based on C / D / A -optimality criteria. In particular, the constant-stress and step-stress accelerated life tests are considered with the exponential failure data under time constraint as well. We illustrate the proposed methods using two real case studies, and under the identical budget constraint, the efficiencies of these two stress loading schemes are compared in terms of the ratio of optimal objective functions based on the information matrix.
CO adsorption on ion-exchanged Ru zeolite catalyst

Abstract An infrared study of CO adsorption on ion-exchanged RuY catalysts was carried out. At least three types of Ru sites on the reduced catlayst have been identified. It is suggested that these three types of sites are associated with (a) highly dispersed (probably atomically) Ru, (b) Ru clusters, and (c) Ru particles greater than 1.0 nm.
Phylogenetic Analysis of theArenaviridae:Patterns of Virus Evolution and Evidence for Cospeciation between Arenaviruses and Their Rodent Hosts☆☆☆

Abstract Viruses of theArenaviridaecause hemorrhagic fevers and neurologic disease in humans. Historically, the arenaviruses have been divided into two complexes (LASV-LCMV, Tacaribe) through the use of antigenic typing. The phylogeny of theArenaviridaeas a whole has not been estimated previously due to a lack of sequence data for all members of the family. In this study, nucleocapsid protein gene sequence data were obtained for all currently known arenaviruses and used to estimate, for the first time, a phylogeny of the entire virus family. The LCMV-LASV complex arenaviruses are monophyletic and comprise three distinct lineages. The Tacaribe complex viruses also are monophyletic and occupy three distinct lineages. Comparisons of arenavirus phylogeny with rodent host phylogeny and taxonomic relationships provide several examples in which virus–host cospeciation is potentially occurring. The pathogenic arenaviruses do not appear to be monophyletic, suggesting that the pathogenic phenotype has arisen in multiple independent events during virus evolution.
Protective Factors Against Substance Use Among Multiethnic Gang-Affiliated Youth

Most gang research has focused on factors likely to increase adolescents’ likelihood of joining gangs and becoming involved in delinquency. The current study takes a protective factor approach to identify family, peer, and school-related factors to effectively reduce substance use among multiethnic gang-affiliated youth. Data from the National Longitudinal Study of Adolescent Health were used to determine the effectiveness of these factors for Asian, Mexican-heritage, White, and Black gang-affiliated youth. The protective effects varied by racial and ethnic group, with school attachment and family cohesion the most protective and peer attachment the least.