cssi/SciSciGPT-SciSciNet huggingface dataset:
Phase II study of temozolomide and thalidomide in patients with metastatic melanoma in the brain: high rate of thromboembolic events (CALGB 500102).

BACKGROUND. Preliminary studies suggesting that extended-dose temozolomide with thalidomide is safe and active in patients with metastatic melanoma have led to frequent use of this oral regimen. To confirm these observations the combination was tested in a multicenter Phase II trial in patients with melanoma brain metastases. METHODS. Eligible patients had melanoma brain metastases, with or without systemic metastases. The primary endpoint was response rate in brain metastases. Patients received temozolomide at a dose of 75 mg/m2/day for 6 weeks with a 2-week rest between cycles, and thalidomide (escalated to 400 mg/day for patients age <70 years or to 200 mg/day for patients age ≥70 years). A 2-stage design required ≥3 responses in the first 21 patients before enrolling 29 additional patients in the second stage. RESULTS. Sixteen eligible patients were enrolled. No objective responses were observed. The median survival was 23.9 weeks. Seven patients withdrew because of tumor progression; 7 were removed during Cycle 1 because of adverse events, including allergic reaction (1 patient), severe fatigue (1 patient), sudden death (1 patient), and thromboembolic events (pulmonary embolism in 3 patients and deep vein thrombosis in 1 patient); 2 patients withdrew when the study was suspended and subsequently closed. No associations could be established between baseline characteristics and toxicity. CONCLUSIONS. The proportion of patients with lethal or potentially life-threatening adverse events was high (0.31, 95% confidence interval, 0.11–0.59), and the absence of objective responses made it unlikely that further accrual would demonstrate the efficacy of the regimen. These observations provide little support for the use of this combination for melanoma brain metastases unless safe and effective methods to prevent thrombosis are developed. Cancer 2006. © 2006 American Cancer Society.
Rotational bands and isomeric states in 175Lu

Rotational bands in {sup 175}Lu have been extended through investigation with the (n,n{prime}{gamma}) reaction. Spallation neutrons bombarded Lu samples, and the resulting {gamma} rays were detected in a large-scale Compton-suppressed Ge detector array. Prompt- and delayed-{gamma}{gamma} coincidences have been used to extend most of the existing known bands, and to tentatively assign a new band, based on the 7/2{sup -}[523] configuration, from its band head to spin 13/2. The 3-quasiparticle K{sup {pi}} = 19/2{sup +} isomer is confirmed and its half life determined to be 984 {+-} 13(stat.) {+-} 30(sys.) {micro}s, in agreement with previous results.
Oxygen dynamics during in vitro seizures.

Oxygen is an essential element for brain activity. The brain is a metabolic engine that requires 20% of the body’s metabolic energy, despite being only 2% of the human body mass [1]. Two thirds of brain’s metabolic energy is dedicated to supporting neural spiking activity. Much of the O2 dependent ATP metabolism in single neurons is used by energetic Na/K-ATPase pumps that transport 3Na+ outwards with 2K+ inward against their concentration gradients for each ATP hydrolyzed [2,3]. However, understanding the relationship between seizures and real-time oxygen dynamics has been restricted by current technical limitations. Computational models can offer insight to help understand the measurements from experiments. We have performed experiments relating seizure activity at the cellular level with simultaneous real-time O2 microdomain measurements. In this paper, we build a mathematical neuron model that extends the Hodgkin-Huxley formalism containing leak currents for sodium, potassium and chloride ions, transient sodium currents, and delayed rectifier potassium currents. This neuron was embedded within an extracellular space and a simplified glia-endothelium system. The Na+ and K+ ion concentrations as well as extracellular oxygen density were continuously estimated. Hypoxia was modeled by reducing both neuron and glial Na/K-ATPase pump activities. During seizure events, the extracellular K+ and intracellular Na+ were increased, which further activated the Na/K-ATPase pump activity. Energy (ATP) and O2 demand were simultaneously increased. Therefore, local available [O2] decreased substantially during seizure events, and the apparent O2 debt substantially outlasts the intense electrical activity of a seizure, as shown in Figure ​Figure1.1. This result is consistent with experimental data [4]. We also observed that hypoxia alone can induce seizure like events, which occurs only in a narrow range of bath oxygen pressure, reflecting experimental observations. Lastly, we reproduced the interplay between excitatory and inhibitory neurons seen in experiments. Our model accounts for the different [O2] levels that we have observed during seizures in pyramidal cell layers vs. inhibitory (oriens lacunosum moleculare) cell layers. Our work suggests the critical importance of modeling extracellular ion concentration and oxygen dynamics to properly understand the underlying mechanisms behind seizure and related phenomena. Figure 1 Membrane potentials (top trace), extracellular potassium concentration (middle trace), and oxygen density (bottom trace) from a single model neuron during a seizure event. The time course of [O2] debt is qualitatively similar to that observed experimentally. ...
Transamniotic stem cell therapy (TRASCET) mitigates bowel damage in a model of gastroschisis.

Abstract Purpose We sought to determine whether intraamniotic delivery of concentrated amniotic-derived mesenchymal stem cells (afMSCs) could reduce damage to exposed bowel in experimental gastroschisis. Methods Rat fetuses (n=117) with surgically created gastroschisis were divided into three groups: untreated animals (n=62) and two groups receiving volume-matched intraamniotic injections of either saline (n=25) or 2×10 6 cells/mL of syngeneic, labeled afMSCs (n=30). Animals were killed before term, along with normal controls (NL). Blinded observers performed computerized measurements of total and segmental (serosa, muscularis, and mucosa) intestinal wall thicknesses. Statistical comparisons were by ANOVA (P Results Among survivors with gastroschisis, there were statistically significant decreases in total bowel wall, serosal, muscular, and mucosal thicknesses in the afMSC group vs. the untreated group (P=0.001/0.035/0.001/0.005, respectively) and vs. the saline group (P=0.003/0.05/ Conclusions Amniotic mesenchymal stem cells mitigate bowel damage in experimental gastroschisis after concentrated intraamniotic injection. Transamniotic stem cell therapy (TRASCET) may become a practical component of the treatment of gastroschisis.
Prostanoid biosynthesis and mechanisms of action

Prostanoids are local hormones formed from arachidonic acid that coordinate responses to circulating hormones which elicit prostanoid synthesis. For example, in the kidney, prostaglandin (PG) E2 synthesized by collecting tubule epithelia in response to arginine vasopressin (AVP) acts on the parent collecting tubule as well as the neighboring thick limb to modulate NaCl and water reabsorption occurring in response to AVP. Studies performed over the last 15 years have defined the major cellular and subcellular sites of PG synthesis in the kidney. In addition, it is now recognized that the multiple cellular actions of prostanoids in the kidney are mediated through receptors coupled to guanine nucleotide regulatory proteins. The goal of this review is to summarize recent biochemical and molecular biological studies on prostanoid biosynthetic enzymes and on prostanoid receptors. The major topics to be addressed are 1) phospholipid precursors of arachidonate, 2) membrane-associated and cytosolic phospholipase A2s, 3) PG endoperoxide (PGH) synthase isozymes, 4) thromboxane A (TxA) synthase, and 5) TxA/PGH and PGE receptors.
Personal health technology: A new era in cardiovascular disease prevention

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide yet the majority of related risk factors are largely preventable (primary prevention [PP]) and effectively treatable (secondary prevention [SP]) with healthy lifestyle behaviors. The use of information and communication technology (ICT) offers a unique approach to personal health and CVD prevention, as these mediums are relatively affordable, approachable, and accessible. The purpose of this review is to provide an overview of ICT-driven personal health technologies and their potential role in promoting and supporting self-care behaviors for PP and SP of CVD. In this review, we focus on technological interventions that have been successful at supporting positive behavior change in order to determine which tools, resources, and methods are most appropriate for delivering interventions geared towards CVD prevention. We conducted a literature search from a range of sources including scholarly, peer-reviewed journal articles indexed in PubMed and CINAHL, gray literature, and reputable websites and other Internet-based media. A synthesis of existing literature indicates that the overall efficacy of ICT-driven personal health technologies is largely determined by: 1) the educational resources provided and the extent to which the relayed information is customized or individually tailored; and 2) the degree of self-monitoring and levels of personalized feedback or other interactions (e.g. interpersonal communications). We conclude that virtually all the technological tools and resources identified (e.g. Internet-based communications including websites, weblogs and wikis, mobile devices and applications, social media, and wearable monitors) can be strategically leveraged to enhance self-care behaviors for CVD risk reduction and SP but further research is needed to evaluate their efficacy, cost-effectiveness, and long-term maintainability.
Chronic Marginal Vitamin A Status Reduces Natural Killer Cell Number and Function in Aging Lewis Rats

Natural killer (NK) cells function in the regulation of immune responses and in the surveillance of malignant or other abnormal cells. Little is known of the effects of chronic marginal vitamin A (VA) status or VA supplementation, or their interaction with age, on NK cell number and cytolytic activity. We have conducted a two-factor (diet, age) study in which male Lewis rats were fed AIN-93M diet, modified to contain either 0.3 (designated marginal), 4.0 (control) or 50 (supplemented) mg retinol equivalents (RE)/kg diet, from the time of weaning until the ages of 2.5 mo (young), 8-10 mo (middle-aged) or 18-20 mo (old). Natural killer cells were identified and quantified in peripheral blood mononuclear cells (PBMC) and spleen with the use of flow cytometry, and NK cell cytotoxicity was assayed. The number and percentage of PBMC NK cells increased with age (P < 0.0001 by two-way ANOVA). For all age groups, values were lowest in rats with marginal VA status (P < 0.0001 vs. controls). NK cell lytic activity also declined with age (P = 0. 0003). As a result, NK cell lytic efficiency (lytic activity per NK cell) decreased markedly with age (P < 0.0001). Regardless of the donor's age or VA status, PBMC NK cell cytotoxicity doubled (100 +/- 25% increase) after exposure to interferon-alpha (5 x 10(5) U/L for 1 h before assay), indicating that IFN-stimulated lytic activity was related directly to basal NK cell activity. If the relationships observed in this animal model can be applied to humans, these data suggest that elderly people consuming diets chronically low in VA may be at increased risk for infectious or neoplastic diseases.
Reflex inhibition and reflex elicitation by acoustic stimuli differing in abruptness of onset and peak intensity

The rat’s acoustic startle reaction to a loud tone (S2) was inhibited by white-noise preliminary stimuli (S1) varying in rise/decay time (5 and 100 msec) and intensity (70, 80, and 90 dB). The amount of inhibition was linearly related to the intensity of S1 but was unaffected by its rise/ decay time. In contrast, the response directly elicited by S1 was affected by both variables, being greater with greater intensity and with the more abrupt onset. These data reveal that reflex elicitation and reflex inhibition are the products of different neural mechanisms.
An active coupling mechanism with three modes of operation for modular mobile robotics

This paper presents a new design for a docking interface that enables rigid, reversible and non-back-drivable coupling between robotic modules in a chain architecture. The distinctive merit of the proposed interface is exhibited in its ability to operate in three independent modes. In the drive mode, the motor torque is directed to drive the host module. In the neutral mode, the motor torque aligns the coupling elements prior to docking. In the clamp mode, the motor torque actuates the revolute joint resulting from this docking process, thus allowing one module to revolve relative to its neighbors in the formation. In this paper, an optimality analysis of the unique kinematic properties of the dual-rod slider-rocker (DRSR) mechanism which enables this tri-state operation is presented. This analysis is supplemented by simulations and experimental results that validate these optimal kinematics, as well as the rigidity and the three operation modes of the docking interface.
Parallel computation over hyperbolic groups

Hyperbolic groups are a rich class of groups frequently encountered in mathematical research, particularly in topology. It has been the focus of intense study by many combinatorial group theorists and topologists recently. We present some computational results for infinite groups, especially for hyperbolic groups. It is shown that the word problem for hyperbolic groups is solvable in NC2. This is the first NC algorithm for a class of groups in combinatorial group theory. We also consider the isomorphism problem of randomly generated groups using a novel technique: the Alexander polynomial from knot theory. These randomly generated groups are almost always hyperbolic groups.
Effects of ongoing task context and target typicality on prospective memory performance: The importance of associative cueing

Two experiments examined whether prospective memory performance is influenced by contextual cues. In our automatic activation model, any information available at encoding and retrieval should aid recall of the prospective task. The first experiment demonstrated an effect of the ongoing task context; performance was better when information about the ongoing task present at retrieval was available at encoding. Performance was also improved by a strong association between the prospective memory target as it was presented at retrieval and the intention as it was encoded. Experiment 2 demonstrated boundary conditions of the ongoing task context effect, which implicate the association between the ongoing and prospective tasks formed at encoding as the source of the context effect. The results of this study are consistent with predictions based on automatic activation of intentions.
‘Building democracy’ through foreign aid: The limitations of United States political conditionalities, 1992–96

This article examines the record of the United States government in promoting democratic reform through the manipulation of development aid flows between 1992 and 1996. The first section reviews the origins of the policy of political conditionality and the subsequent changes in the US Agency for International Development. The next section evaluates the policy's execution by considering trends in the volume and distribution of US official development assistance, statistical linkages between that aid and recipient democratization, and the relationship with other potential foreign policy goals. The study finds that, contrary to the government's pledges, democratic and democratizing states have not received a greater share of aid. Instead, the distribution has been closely linked with security concerns ‐ a pattern consistent with the cold war record ‐ and US economic self‐interests have also been evident. Finally, three obstacles to the policy of ‘building democracy’ are considered: domestic ambivalence over ...
Should hyperlipidemia in children with the nephrotic syndrome be treated

The pathogenesis, clinical significance, and treatment options of the disturbances in lipid metabolism in children with persistent nephrotic syndrome are reviewed. The lipoprotein profile is characterized by elevations of total plasma cholesterol and often triglycerides, elevated very low-density lipoprotein and low-density lipoprotein cholesterol, whereas high-density lipoprotein-cholesterol levels are variable; plasma levels of the atherogenic and thrombogenic lipoprotein(a) are also elevated. The pathophysiology of nephrotic dyslipoproteinemia is multifactorial, including both an increased hepatic synthesis and a diminished plasma catabolism of lipoproteins. There is a rationale for treatment, since dyslipidemia may contribute to the development of atherosclerosis and the progression of chronic renal failure. However, the benefits of treatment with lipid-lowering drugs have not been proven. Short-term studies in adults with nephrotic syndrome have documented safety and efficacy of lipid-lowering drugs, including hydroxymethylglutaryl-CoA reductase inhibitors (”statins”), bile acid sequestrants, fibric acids, fish oil, and probucol. Statins are the most-effective medication, resulting in a decrease of total cholesterol levels by about 30%–40%. Prospective controlled studies in children evaluating efficacy and safety of lipid-lowering drugs are needed.
Resonant cavity coupled infrared detectors with high detectivity operating at room temperature

A spectrally selective uncooled long wave infrared detector with peak detectivity between 3×109 cm Hz1/2/W and 4.4×109 cm Hz1/2/W is reported. The detector is fabricated using silicon microfabrication techniques and integrates a thermoelectric readout with a resonant optical cavity to achieve wavelength selective absorption.
One of the Things We Know that Ain't so: Is U.S. Labor's Share Relatively Stable?

Robert Solow (1958) argued that, from 1929-1954, U.S. aggregate labor's share was not stable relative to what we would expect given individual industry labor's shares. I confirm and extend this result using data from 1958-1996 that includes 35 industries (roughly 2-digit SIC level) and spans the entire U.S. economy. Changes in industry shares in total value-added contribute negligibly to aggregate labor's share volatility. Industry labor's shares comovement actually adds to aggregate labor's share volatility. These findings highlight economists' imprecise understanding of one of the stylized facts of economic growth. If the great macroeconomic ratio is meaningful, it must be interpreted in terms of long-run, offsetting shifts in "services" industries versus "goods" industries, both in terms of their labor's shares and shares in total value-added.
Premaxillary movements in cyprinodontiform fishes: An unusual protrusion mechanism facilitates “picking” prey capture

Abstract Premaxillary protrusion is hypothesized to confer a number of feeding advantages to teleost fishes; however, most proposed advantages relate to enhanced stealth or suction production during prey capture. Cyprinodontiformes exhibit an unusual form of premaxillary protrusion where the descending process of the premaxilla does not rotate anteriorly to occlude the sides of the open mouth during prey capture. Instead, the premaxilla is protruded such that it gives the impression of a beak during prey capture. We quantified premaxillary kinematics during feeding in four cyprinodontiform taxa and compared them with three percomorph taxa to identify any performance consequences of this protrusion mechanism. Individual prey capture events were recorded using digital high-speed video at 250–500 frames per second (n⩾4 individuals, ⩾4 strikes per individual). Species differed in the timing of movement and the maximum displacement of the premaxilla during the gape cycle and in the contribution of the premaxilla to jaw closing. Cyprinodontiform taxa produced less premaxillary protrusion than the percomorph taxa, and were consistently slower in the time to maximum gape. Further, it appears cyprinodontiforms can alter the contribution of the premaxilla to mouth closure on an event-specific basis. We were able to demonstrate that, within at least one species, this variability is associated with the location of the prey (bottom vs. water column). Cyprinodontiform upper jaw movements likely reflect increased dexterity associated with a foraging ecology where prey items are “picked” from a variety of locations: the bottom, water column, or surface. We postulate that dexterity requires slow, precisely controlled jaw movements; thus, may be traded off for some aspects of suction-feeding performance, such as protrusion distance and speed.
Structured eIRA codes with low floors

In a recent paper, Yang et al. presented the class of extended irregular repeat-accumulate (eIRA) codes which are efficiently encodable LDPC codes possessing very low error-rate floors and are appropriate for code rates 1/2 or greater. While efficiently encodable, the left-most (n-k)-by-k submatrix of an eIRA code parity-check matrix is random in nature, making efficient decoder implementation problematic. In the present paper, we present structured eIRA codes. We first present some ensemble results for the general class of eIRA codes, after which the subclass of structured eIRA (SeIRA) codes is defined. Software- and hardware-based performance results for SeIRA code designs (rates 0.5 to 0.9) are then presented
Identification of Small Molecules that Disrupt Signaling between ABL and Its Positive Regulator RIN1

Constitutively active BCR-ABL kinase fusions are causative mutations in the pathogenesis of hematopoietic neoplasias including chronic myelogenous leukemia (CML). Although these fusions have been successfully targeted with kinase inhibitors, drug-resistance and relapse continue to limit long-term survival, highlighting the need for continued innovative drug discovery. We developed a time-resolved Forster resonance energy transfer (TR-FRET) -based assay to identify compounds that disrupt stimulation of the ABL kinase by blocking its ability to bind the positive regulator RIN1. This assay was used in a high throughput screen (HTS) of two small molecule libraries totaling 444,743 compounds. 708 confirmed hits were counter-screened to eliminate off-target inhibitors and reanalyzed to prioritize compounds with IC50 values below 10 μM. The CML cell line K562 was then used to identify five compounds that decrease MAPK1/3 phosphorylation, which we determined to be an indicator of RIN1-dependent ABL signaling. One of these compounds is a thiadiazole, and the other four are structurally related acyl piperidine amides. Notably, these five compounds lower cellular BCR-ABL1 kinase activity by blocking a positive regulatory interaction rather than directly inhibiting ABL catalytic function.
Acute renal failure due to bilateral pieloureteral stone impaction in a 10-month-old boy

Urolithiasis (UL) can present with its classic signs and symptoms, such as flank or abdominal pain and gross hematuria. However, atypical complaints can be more common in younger children. We report here a case of bilateral ureteropelvic junction (UPJ) stones in a 10-month-old boy who only showed nonspecific symptoms at the time of presentation. The initial blood test revealed renal failure (serum creatinine 3.4 mg/dl), hyperkalemia (6.4 mEq/l), hyperphosphoremia (9.4 mEq/l) and mild metabolic acidosis. Medical treatment for electrolyte disorders was started. The ultrasonography revealed impacted stones in both ureteropelvic junctions. A pigtail catheter was placed in each ureter. High urine flow was promptly achieved after the pigtail procedure, and the serum creatinine level dropped quickly from 4.5 to 0.32 mg/dl. Quantitative determination of urinary amino acids by ion exchange chromatography showed high cystine levels of 8.43 mmol/g creatinine. Outpatient follow-up was scheduled every 3 months to monitor patient compliance with potassium citrate. In the first 6 months, the patient underwent three febrile urinary tract infections (UTIs). Since both pigtail catheters were removed, he has been free of UTIs and stones. Our case emphasizes the need for considering UL in infants who complain with unclear signs, because UL can only show nonspecific symptoms in children younger than 1 year old. Since cystinuria can cause loss of renal function due to urinary system obstruction and UTI, an early diagnosis and a close follow-up are the key to achieving the best long-term outcome.
Scientific Evolution and Technical Innovation

Slow economies and uncertain political situations may often slow the pace of scientific evolution and technical innovation. Pharmaceutical manufacturers that embrace innovation and lead the inevitable evolution will maintain a competitive advantage in such challenging situations. The editorial advisory board of JPI continues its effort to provide high-quality papers calling attention to innovative research that will facilitate rapid development of pharmaceutical products from R&D to market. This issue of JPI provides examples of scientific evolution and technical innovation in the use of experimental design principles in dissolution method development and in predictive modeling for pharmaceutical processes. Formulation novelty is demonstrated in a paper on mucoadhesive tablets. A perspective article defines Japanese GMP/GQP regulations and their challenges, providing insight to international pharmaceutical manufacturers wishing to access the Japanese marketplace. Finally, an article on near infrared spectroscopy demonstrates a new approach to predicting powder flow interruptions, an analytical advance. I thank all of the authors, referees, editorial advisory board members, and others who have supported JPI during 2009, and with your continued support, we look forward to another successful year in 2010.
The influence of three-dimensional nanofibrous scaffolds on the osteogenic differentiation of embryonic stem cells

Embryonic stem cells represent a potentially unlimited cell source for tissue engineering applications. However, in order to be used for such applications, embryonic stem cells' differentiation must be controlled to only the desired lineages. In this study, we examine the effects of nanofibrous architecture and biochemical cues on the osteogenic differentiation of embryonic stem cells compared to the more traditional architecture without the nanofibrous features in two dimensions (thin matrix or flat films) and three dimensions (scaffolds) in vitro. After three weeks of culture the nanofibrous thin matrices were capable of supporting mRNA expression of osteogenic differentiation markers in embryonic stem cells without osteogenic supplements, while solid films required osteogenic supplements and growth factors to achieve mRNA expression of osteogenic differentiation markers. Nanofibrous scaffolds substantially enhanced mRNA expression of osteogenic differentiation markers compared to solid-walled scaffolds, nanofibrous thin matrices or solid films. After 4 weeks of culture, nanofibrous scaffolds were found to contain 3 times more calcium and stronger osteocalcin stain throughout the scaffolds than the solid-walled scaffolds. Overall, the nanofibrous architecture enhanced the osteogenic differentiation and mineralization of embryonic stem cells compared to the solid-walled architecture in both two and three-dimensional cultures.
A model of evolving damage bands in materials

Abstract This paper develops a model that incorporates damage band evolution at three levels: (i) at the mechanism level, the damage mechanisms, such as diffusive void growth and fatigue cracks, determine the damage growth rate; (ii) at an intermediate level, the damage band is modeled as springs connecting undamaged materials, and the spring constants change as damage develops; (iii) at the continuum level, the damage band is modeled as an array of dislocations to satisfy equilibrium. We demonstrate this model with an example of a band of microcracks subject to remote tensile cyclic stress. It is observed that damage rapidly grows at the weakest regions in the band, and a macroscopic crack nucleates while the overall damage level is still very low. The model shows that there exists a critical number of cycles for macroscopic crack nucleation, which depends on materials as well as the amplitude of applied cyclic stress. This critical number of cycles is insensitive to the size of damage cluster, but decreases rapidly as the local excess of damage increases.
Operator renormalization group and spin systems.

The results of a new hybrid method for calculating ground-state energies for lattice Hamiltonians are presented. This method combines the {ital t} expansion with the real-space renormalization-group approach, with the hope of extracting infinite-volume physics at {ital t}{r arrow}{infinity} from calculations of only a few powers of {ital t}. We calculate the ground-state energy for the (1+1)-dimensional anisotropic Heisenberg model and the (1+1)-dimensional Ising model. Using a blocking that treats the sites and links symmetrically, we were able to determine the exact critical point of the Ising system. In both of these systems we see that the operator renormalization-group method substantially improves upon the results of either the {ital t} expansion or real-space renormalization-group methods used separately.
Rational modification of a selection strategy leads to deoxyribozymes that create native 3'-5' RNA linkages

We previously used in vitro selection to identify several classes of deoxyribozymes that mediate RNA ligation by attack of a hydroxyl group at a 5'-triphosphate. In these reactions, the nucleophilic hydroxyl group is located at an internal 2'-position of an RNA substrate, leading to 2',5'-branched RNA. To obtain deoxyribozymes that instead create linear 3'-5'-linked (native) RNA, here we strategically modified the selection approach by embedding the nascent ligation junction within an RNA:DNA duplex region. This approach should favor formation of linear rather than branched RNA because the two RNA termini are spatially constrained by Watson-Crick base pairing during the ligation reaction. Furthermore, because native 3'-5' linkages are more stable in a duplex than isomeric non-native 2'-5' linkages, this strategy is predicted to favor the formation of 3'-5' linkages. All of the new deoxyribozymes indeed create only linear 3'-5' RNA, confirming the effectiveness of the rational design. The new deoxyribozymes ligate RNA with k(obs) values up to 0.5 h(-1) at 37 degrees C and 40 mM Mg2+, pH 9.0, with up to 41% yield at 3 h incubation. They require several specific RNA nucleotides on either side of the ligation junction, which may limit their practical generality. These RNA ligase deoxyribozymes are the first that create native 3'-5' RNA linkages, which to date have been highly elusive via other selection approaches.
Temperature Dependence of the Raman Spectrum of Barium Peroxide

The Raman spectra of barium peroxide (BaO2) in the O−O stretching region were studied at various temperatures between 22 and 850 °C in both O2 and He atmospheres. Although only one peroxide stretching band is expected for the crystal symmetry, three Raman bands, which were assigned to peroxide ions in different crystal environments due to the relative locations of oxide impurities, were observed at all temperatures. The temperature dependencies of the Raman frequencies, bandwidths, and the absolute and partial intensities were investigated in detail, and these were explained on the basis of the sample composition and structural changes.
The utility of repeated presence data as a surrogate for counts: a case study using butterflies

Abundance data are widely used to monitor long-term population trends for management and conservation of species of interest. Programs that collect count data are often prohibitively expensive and time intensive, limiting the number of species that can be simultaneously monitored. Presence data, on the other hand, can often be collected in less time and for multiple species simultaneously. We investigate the relationship of counts to presence using 49 butterfly species across 4 sites over 9 years, and then compare trends produced from each index. We also employed simulated datasets to test the effect of reduced sampling on the relationship of counts to presence data and to investigate changes in each index’s power to reveal population trends. Presence and counts were highly correlated for most species tested, and population trends based on each index were concordant for most species. The effect of reduced sampling was species-specific, but on a whole, sensitivity of both indices to detect population trends was reduced. Common and rare species, as well as those with a range of life-history and behavioral traits performed equally well. The relationship between presence and count data may break down in cases of very abundant and widespread species with extended flight seasons. Our results suggest that when used cautiously, presence data has the potential to be used as a surrogate for counts. Collection of presence data may be useful for multi-species monitoring or to reduce the duration of monitoring visits without fully sacrificing the ability to infer population trends.
Deep level effects in silicon and germanium after plasma hydrogenation

Deep level electron and hole trapping states are observed in n-and p-type silicon after plasma hydrogenation at 250 - 300°C. These defect states are not observed after exposure to a helium plasma. In contrast to these results, no hydrogen or helium plasma-induced levels are seen in n-or p-type germanium after similar heat treatment of up to 600°C. However, hydrogenation of p-type germanium at 600°C significantly enhances the solubility of the rapidly diffusing impurity copper, compared to untreated material. Reproducing the experiments using a helium plasma does not affect the copper solubility. A simple model which accounts for the experimental results is proposed.
Strategic Essentialism and Vatican Policy

Just as women's NGOs around the world use essentialism strategically—calling upon their assigned roles as mothers to create change for their children that they might not feel empowered to create for themselves—the most recent Vatican policy holds on to the remnants of essentialism as a policy for protecting exclusive male access to ordination, and therefore power in the church. Previously, essentialism had protected male superiority in existence, social roles, the family, and the church, but one by one, all of these have been conceded except male superiority in the church. The paper further proposes that the traditional male role, of which the church has been a principal support, has in fact now become detrimental to males.
The nature of O2 activation by the ethylene-forming enzyme 1-aminocyclopropane-1-carboxylic acid oxidase

Ethylene is a plant hormone important in many aspects of plant growth and development such as germination, fruit ripening, and senescence. 1-Aminocyclopropane-1-carboxylic acid (ACC) oxidase (ACCO), an O2-activating ascorbate-dependent nonheme iron enzyme, catalyzes the last step in ethylene biosynthesis. The O2 activation process by ACCO was investigated using steady-state kinetics, solvent isotope effects (SIEs), and competitive oxygen kinetic isotope effects (18O KIEs) to provide insights into the nature of the activated oxygen species formed at the active-site iron center and its dependence on ascorbic acid. The observed large 18O KIE of 1.0215 ± 0.0005 strongly supports a rate-determining step formation of an FeIVO species, which acts as the reactive intermediate in substrate oxidation. The large SIE on kcat/Km(O2) of 5.0 ± 0.9 suggests that formation of this FeIVO species is linked to a rate-limiting proton or hydrogen atom transfer step. Based on the observed decrease in SIE and 18O KIE values for ACCO at limiting ascorbate concentrations, ascorbate is proposed to bind in a random manner, depending on its concentration. We conclude that ascorbate is not essential for initial O2 binding and activation but is required for rapid FeIVO formation under catalytic turnover. Similar studies can be performed for other nonheme iron enzymes, with the 18O KIEs providing a kinetic probe into the chemical nature of Fe/O2 intermediates formed in the first irreversible step of the O2 activation.
Quantitative Thin-Layer Chromatography/Mass Spectrometry Analysis of Caffeine Using a Surface Sampling Probe Electrospray Ionization Tandem Mass Spectrometry System

Quantitative determination of caffeine on reversed-phase C8 thin-layer chromatography plates using a surface sampling electrospray ionization system with tandem mass spectrometry detection is reported. The thin-layer chromatography/electrospray tandem mass spectrometry method employed a deuterium-labeled caffeine internal standard and selected reaction monitoring detection. Up to nine parallel caffeine bands on a single plate were sampled in a single surface scanning experiment requiring 35 min at a surface scan rate of 44 μm/s. A reversed-phase HPLC/UV caffeine assay was developed in parallel to assess the mass spectrometry method performance. Limits of detection for the HPLC/UV and thin-layer chromatography/electrospray tandem mass spectrometry methods determined from the calibration curve statistics were 0.20 ng injected (0.50 μL) and 1.0 ng spotted on the plate, respectively. Spike recoveries with standards and real samples ranged between 97 and 106% for both methods. The caffeine content of three die...
Acetaldehyde: genotoxicity and cytotoxicity in human lymphocytes

We evaluated the DNA damaging effects of ethanol and its major metabolite, acetaldehyde. Freshly isolated human lymphocytes from two healthy donors were incubated with 0, 1.56, 6.25, 25, and 100 mM of ethanol or acetaldehyde in complete medium for 1 h. We used a newly developed, sensitive, alkaline microgel electrophoresis technique to quantitate single- and double-strand DNA breaks or alkali-labile sites in individual cells. Ethanol did not induce DNA strand breaks. However, acetaldehyde induced both single-strand (even at the lowest concentration of 1.56 mM) and double-strand breaks (only at the highest concentration of 100 mM). Following exposure to acetaldehyde, cells were incubated in complete medium for 30, 60, and 120 min. During this incubation period, most cells were unable to repair DNA single- and double-strand breaks caused by acetaldehyde. We also observed a significant cell loss after exposure to acetaldehyde. To our knowledge, this is the first study demonstrating DNA single- and double-strand breaks by acetaldehyde.
Endoplasmic reticulum bodies: solving the insoluble

Plant cells produce and accumulate insoluble triglycerides, proteins, and rubber that are assembled into inert, ER-derived organelles broadly termed as ER bodies. ER bodies appear to originate from tubular ER domains that are maintained by cytoskeletal interactions and integral ER proteins. ER bodies sequestering insoluble substances usually are transferred to the vacuole but sometimes remain as cytoplasmic organelles. Some otherwise soluble ER-synthesized proteins are converted to insoluble aggregates to produce ER bodies for transfer to the vacuole. This process constitutes an alternate secretory system to assemble and traffic transport-incompetent insoluble materials.
Excess enthalpies, heat capacities, and excess heat capacities as a function of temperature in liquid mixtures of ethanol + toluene, ethanol + hexamethyldisiloxane, and hexamethyldisiloxane + toluene

Abstract The heat capacities of liquid ethanol, toluene, and hexamethyldisiloxane, and of 14 binary mixtures of these were measured at atmospheric pressure at a series of temperatures between 298 and 348 K. In addition, the excess enthalpy was measured for each of the 14 mixtures at room temperature and corrected with the aid of the heat capacities to 298.15 K. The results were represented by empirical equations of a polynomial form. From these equations, the excess heat capacity was derived and the excess enthalpy was calculated, and fitted to equations, as a function of composition at temperatures between 298 and 348 K. All the mixtures are non-ideal as evidenced by the substantial excess enthalpy. The excess enthalpy for the mixtures containing ethanol showed a strong positive temperature dependence, while the variation of temperature between 298 and 348 K had little effect on the excess enthalpy of toluene + hexamethyldisiloxane.
Homicide in the High North: Alaska, 1999-2006

This article focuses on homicides (murders and nonnegligent manslaughter) in Alaska from 1999 to 2006, through a comparison of homicides in Anchorage and in the rest of the state. Data used include the Supplementary Homicide Reports of the FBI Uniform Crime Reporting Program Data for Alaska, newspaper surveillance, and Alaska Vital Statistics. Geographic, cultural and demographic factors are used to help provide an explanation of Alaska’s unusual homicide pattern, a relatively high rate of female homicide victims. In addition, the article compares the Alaska findings to those of the United States as a whole, to place homicide in the state within a larger context. The general theoretical framework is a consideration of disorganization theory, which is used to better understand homicides in Alaska and the particular vulnerability of Alaskan Native women who migrate to Anchorage from rural villages. Topics examined include the gender and race of victims, the relationship between the victim and perpetrator, the time of year of the homicide, the location (home or elsewhere), the region of Alaska, and the weapon used in the homicide. Negligent manslaughter and child witnesses to murder are also discussed. A number of suggestions are made for the reduction of homicides in Alaska.
Estrogen stimulation and tamoxifen inhibition of leiomyoma cell growth in vitro and in vivo

Uterine leiomyomas (fibroids) are the most common gynecological neoplasms and may be associated with significant morbidity. Recently, we described a rat model (Eker rat) of fibroid development in which reproductive tract leiomyomas develop spontaneously with high frequency. The present studies describe the estrogen and antiestrogen responsiveness of an Eker rat leiomyoma-derived cell line in vitro and a nude mouse xenograft system in vivo. In this cell line, estradiol stimulated growth in estrogen-depleted medium, whereas the nonsteroidal antiestrogen tamoxifen maximally inhibited cell proliferation in medium containing 10% charcoal-stripped serum. Proliferation was also decreased by the biologically active tamoxifen metabolite 4-hydroxytamoxifen; the metabolite was more effective than the parent compound in exerting this growth inhibition. Compared to placebo-treated controls, estradiol increased the size of tumors that developed in a nude mouse xenograft system, whereas tamoxifen increased tumor latency and decreased tumor size. This study of leiomyoma cells in a well defined system suggests that antiestrogens may prove efficacious in the treatment of this clinically important neoplasm.
Calmodulin and Calmodulin-dependent Kinase IIα Regulate Osteoblast Differentiation by Controlling c-fos Expression

Ca(2+)/calmodulin-dependent protein kinase IIalpha (alpha-CaMKII) was once thought to be exclusively expressed in neuronal tissue, but it is becoming increasingly evident that CaMKII is also expressed in various extraneural cells. CaMKII plays a critical role in regulating various signaling pathways leading to modulation of several aspects of cellular functions, including proliferation, differentiation, cytoskeletal structure, and gene expression. The purpose of this study was to examine the expression of CaMKII in osteoblast-like cells (MC4) and to elucidate its role in osteoblast differentiation. We demonstrated that CaMKII, specifically the alpha isoform, is expressed in osteoblasts both in vitro and in vivo. Inhibition of CaMKII by the calmodulin antagonist trifluoperazine or the CaMKII antagonist KN93 reduces alkaline phosphatase activity and mineralization, as well as causes 85 and 56% decreases in alkaline phosphatase and osteocalcin gene expression, respectively. CaM and CaMKII antagonists, using the newborn mouse calvaria in vivo model, cause a 50% decrease in osteoblast number (N.Ob-BS) and a 32% decrease in mineralization (BV/TV). Pharmacologic and genetic inhibition of alpha-CaMKII by using trifluoperazine, KN93, and alpha-CaMKII small interfering RNA decreases the phosphorylation of ERK and of cAMP-response element-binding protein, leading to a significant decrease in the transactivation of serum response element and cAMP-response element. Inhibition of alpha-CaMKII decreases the expression of c-fos, AP-1 transactivation, and AP-1 DNA binding activity. Our findings demonstrated that alpha-CaMKII is expressed in osteoblasts and is involved in c-fos expression via regulation of serum response element and cAMP-response element. Inhibition of alpha-CaMKII results in a decrease in c-fos expression and AP-1 activation, leading to inhibition of osteoblast differentiation.
Assessing the compatibility of work system factors through an integrative model: a case study.

Work Factor Compatibility (WFC) theory proposes that human performance is dependent on the interaction of various components (e.g., physical and mental task demands, physical environment, social environment) of the work system and integrates multiple human performance perspectives into a single mathematical model. Work Factor Analysis (WFA) is a comprehensive survey administered to employees to determine the WFC index. WFA also provides recommendations for targeting specific work system areas for improvement. Preliminary testing of the tool was conducted at a manufacturing operation of a Fortune 10 company. Results are discussed and recommendations for further study are made.
Interstitial defects in 316L austenitic stainless steel containing “colossal” carbon concentrations: An internal friction study

Carburization of 316L austenitic stainless steel under paraequilibrium conditions results in extremely hard (∼1100 HV) single-phase cases containing surface carbon concentrations of ∼15 mol.% and very high residual compressive stresses (⩾2 GPa). Carburization produced an anelastic relaxation peak at 543 K (1.0 Hz), due to a carbon-containing defect with a highly anisotropic strain field. Interstitial solid-solution strengthening theories can explain the approximate three-fold increase in hardness, using reasonable parameters for the strain ellipsoids of these defects.
Nonphagocytic release of neutral protease and β-glucuronidase from human neutrophils regulation by autonomic neurohormones and cyclic neucleotides

Human neutrophils released lysosome granule-associated neutral protease and β-glucuronidase, but not cytoplasmic lactate dehydrogenase, during cell contact with immobilized heat-aggregated human IgG treated with RA serum. Treatment of aggregated IgG with RA serum was more effective than treatment with normal serum with regard to stimulation of enzyme release. Epinephrine, isoproterenol, cyclic 3′,5′-adenosine monophosphate (cyclic AMP), and analogs of cyclic AMP inhibited the nonphagocytic release of enzyme. The action of epinephrine was blocked by propranolol but not by phentolamine. Acetylcholine, acetyl β-methylcholine, cyclic 3′,5′-guanosine monophosphate (cyclic GMP) and analogs of cyclic GMP enhanced lysosomal, but not cytoplasmic, enzyme release. The action of acetylcholine was blocked by atropine but not by hexamethonium. Calcium was required for both the nonphagocytic release of lysosome granule enzymes and for the stimulation of this enzyme release process by cholinergic agents and cyclic GMP. Thus it appears that human neutrophils are capable of responding to autonomic agents and to cyclic nucleotides by quantitative changes in the nonphagocytic release of lysosomal enzymes.