cssi/SciSciGPT-SciSciNet huggingface dataset:
A Double-Blind Randomized Discontinuation Phase-II Study of Sorafenib (BAY 43–9006) in Previously Treated Non–Small-Cell Lung Cancer Patients: Eastern Cooperative Oncology Group Study E2501

Introduction Sorafenib is a raf kinase and angiogenesis inhibitor with activity in multiple cancers. This phase-II study in heavily pretreated non–small-cell lung cancer (NSCLC) patients (≥ 2 prior therapies) used a randomized discontinuation design. Methods Patients received 400 mg of sorafenib orally twice daily for two cycles (2 months) (step 1). Responding patients on step 1 continued on sorafenib; progressing patients went off study, and patients with stable disease were randomized to placebo or sorafenib (step 2), with crossover from placebo allowed upon progression. The primary endpoint of this study was the proportion of patients having stable or responding disease 2 months after randomization. Results There were 299 patients evaluated for step 1; of these, 81 eligible patients were randomized on step 2 and received sorafenib ( n = 50) or placebo ( n = 31). The 2-month disease control rates after randomization were 54% and 23% for patients initially receiving sorafenib and placebo, respectively, p = 0.005. The hazard ratio for progression on step 2 was 0.51 (95% [confidence interval] CI 0.30, 0.87, p = 0.014) favoring sorafenib. A trend in favor of overall survival with sorafenib was also observed (13.7 versus 9.0 months from time of randomization), hazard ratio 0.67 (95% CI 0.40–1.11), p = 0.117. A dispensing error occurred, which resulted in the unblinding of some patients, but not before completion of the 8-week initial step 2 therapy. Toxicities were manageable and as expected. Conclusions The results of this randomized discontinuation trial suggest that sorafenib has single-agent activity in a heavily pretreated, enriched patient population with advanced NSCLC. These results support further investigation with sorafenib as a single agent in larger, randomized studies in NSCLC.
Theoretical analysis of selectivity mechanisms in molecular transport through channels and nanopores

Selectivity is one of the most fundamental concepts in natural sciences, and it is also critically important in various technological, industrial, and medical applications. Although there are many experimental methods that allow to separate molecules, frequently they are expensive and not efficient. Recently, a new method of separation of chemical mixtures based on utilization of channels and nanopores has been proposed and successfully tested in several systems. However, mechanisms of selectivity in the molecular transport during the translocation are still not well understood. Here, we develop a simple theoretical approach to explain the origin of selectivity in molecular fluxes through channels. Our method utilizes discrete-state stochastic models that take into account all relevant chemical transitions and can be solved analytically. More specifically, we analyze channels with one and two binding sites employed for separating mixtures of two types of molecules. The effects of the symmetry and the strength of the molecular-pore interactions are examined. It is found that for one-site binding channels, the differences in the strength of interactions for two species drive the separation. At the same time, in more realistic two-site systems, the symmetry of interaction potential becomes also important. The most efficient separation is predicted when the specific binding site is located near the entrance to the nanopore. In addition, the selectivity is higher for large entrance rates into the channel. It is also found that the molecular transport is more selective for repulsive interactions than for attractive interactions. The physical-chemical origin of the observed phenomena is discussed.
ANALYSIS OF THE STRUCTURE AND STABILITY OF OMEGA LOOP A REPLACEMENTS IN YEAST ISO-1-CYTOCHROME C

Omega (omega)-loop A, residues 18-32 in wild-type yeast iso-1-cytochrome c, has been deleted and replaced with loop sequences from three other cytochromes c and one from esterase. Yeast expressing a partial loop deletion do not contain perceptible amounts of holoprotein as measured by low-temperature spectroscopy and cannot grow on nonfermentable media. Strains expressing loop replacement mutations accumulate holoprotein in vivo, but the protein function varies depending on the sequence and length of the replacement loop; in vivo expression levels do not correlate with their thermal denaturation temperatures. In vitro spectroscopic studies of the loop replacement proteins indicate that all fold into a native-like cytochrome c conformation, but are less stable than the wild-type protein. Decreases in thermal stability are caused by perturbation of loop C backbone in one case and a slight reorganization of the protein hydrophobic core in another case, rather than rearrangement of the loop A backbone. A single-site mutation in one of the replacement mutants designed to relieve inefficient hydrophobic core packing caused by the new loop recovers some, but not all, of the lost stability.
Faculty Vitality and Institutional Productivity: Critical Perspectives for Higher Education edited by Shirley M. Clark and Darrell R. Lewis. New York: Teachers College Press, 1985, 293 pp., hardcover.

(1986). Faculty Vitality and Institutional Productivity: Critical Perspectives for Higher Education edited by Shirley M. Clark and Darrell R. Lewis. New York: Teachers College Press, 1985, 293 pp., hardcover. The Educational Forum: Vol. 50, No. 2, pp. 211-214.
"Arachnoid cysts" of the sylvian fissure versus "temporal lobe agenesis" syndrome.

Measurements of the two cerebral hemispheres in 2 brains with arachnoid cysts of the sylvian fissure indicate no differences in weight or volume and therefore give no support to the hypothesis that these could be examples of the “temporal lobe agenesis” syndrome.
Mediation of dehydration‐induced peptidergic gene expression in the rat lateral hypothalamic area by forebrain afferent projections

We have previously shown in dehydrated rats that cellular levels of the mRNAs encoding the precursor peptides for corticotropin-releasing hormone and neurotensin/neuromedin N significantly increase in a restricted region of the lateral hypothalamic area (Watts, 1992, Brain Res. 581:208–216). The experiments reported here address the role that forebrain osmosensitive cell groups or regions associated with autonomic regulation play in developing this mRNA response. The first experiment showed that unilateral knife cuts placed between the rostral forebrain and the lateral hypothalamic area (LHA) will unilaterally attenuate the mRNA response in the LHA to dehydration. In a second experiment, small injections of the retrograde tracer Fluorogold into the region of the LHA containing these mRNAs revealed a direct input from the osmosensitive median preoptic nucleus and subfornical organ and from the fusiform nucleus of the bed nuclei of the stria terminalis, which is part of a complex of cell groups associated with autonomic regulation. We found that at least 30% of the neurons in the median preoptic nucleus and subfornical organ and 14% of the neurons in the fusiform nucleus of the bed nuclei of the stria terminalis that project to the LHA responded to a rapid increase in plasma osmolality with increased c-fos mRNA levels. In the final experiment, injections of Fluorogold into the LHA were made simultaneously with ipsilateral rostral knife cuts. Here the numbers of neurons accumulating Fluorogold in the median preoptic nucleus, subfornical organ, and the fusiform nucleus were all significantly decreased concomitantly with attenuated mRNA responses in the LHA to dehydration. We conclude that the LHA receives direct and functional projections from the median preoptic nucleus, subfornical organ, and the fusiform nucleus. These projections appear capable of mediating a substantial part of the response of peptidergic mRNAs in the LHA to dehydration. © 1996 Wiley-Liss, Inc.
The effect of wastewater phosphorus removal on shagawa lake, Minnesota: phosphorus supplies, lake phosphorus and chlorophyll a

Abstract In early 1973, the phosphorus supply to Shagawa Lake, Minnesota, was reduced by about 80% when a tertiary wastewater treatment plant began operating. Significant reductions in total and soluble reactive phosphorus concentrations have occurred in the lake since that time. By 1976 the average (volume weighted over the entire lake) total and soluble reactive phosphorus concentrations had declined from about 51 and 21 μg l −1 to about 30 and 4.5 μg l −1 , respectively, corresponding to 40 and 80% reductions. During 1975 and 1976, chlorophyll a (averaged over the top 5 m) had decreased to less than 50% of the pretreatment level during May-June but during July-August little change had occurred. A phosphorus residence time model projected equilibrium total phosphorus concentrations of about 12 μg l −1 within 1.5 years. The fact that this level was not reached is attributed to a feedback of phosphorus from the sediments, primarily during summer. This phenomenon has been incorporated into a modified total phosphorus mass balance model which projects the phosphorus pattern through 1976 quite accurately. The close fit of the modified mass balance model implies that the phosphorus supply from the sediments has not diminished since treatment since treatment began, and that further recovery of the lake will depend upon how long this feedback of phosphorus from the sediments continues.
Reinventing Democrats: The Politics of Liberalism from Reagan to Clinton

When Bill Clinton declared in 1996 that "the era of big government is over," Republicans felt that he was stealing their thunder. But in fact, it was the culmination of a decade-long struggle for the heart and soul of the Democratic party. This book tells how a group of New Democrats reformed their enfeebled party's agenda, moved it toward the center, and recaptured the White House with their first two-term president since FDR. "Reinventing Democrats" is the story of the Democratic Leadership Council, an elite group of elected officials, benefactors, and strategists that let fresh air into the smoke-filled room of politics and changed the public philosophy of their party. Kenneth Baer tells who they are, where they came from, what they believe in, and how they helped elect Bill Clinton the DLC's former chairman to the presidency. Drawing on DLC archives and interviews with party insiders, Baer chronicles the increasing influence of the DLC from 1985 to the present. He describes battles waged between New Democrats and party liberals after the failed candidacy of Walter Mondale, and he takes readers behind the scenes in Little Rock to tell how DLC director Al From encouraged Clinton's run for the White House. He then explains how the DLC reshaped the party's agenda into a "third way" that embraced positions such as welfare reform, a balanced budget, free trade, a tough stance on crime, and a strong defense. In this revealing analysis of insider politics, Baer shows how a determined faction can consciously change a party's public philosophy, even without the impetus of a national crisis or electoral realignment. He also shows that the New Democrat stance exemplifies how ideas can work in sync with the political calendar to determine which specific policies find their way onto the national agenda. If Clinton has achieved nothing else in his presidency, says Baer, he has moved his party to the center, where it stands a better chance to succeed much to the dismay of conservatives, who feel victimized by the theft of many of their strongest issues. In a book that will engage any reader caught up in the fervor of an election year, Baer reveals the role of new ideas in shaping political stratagems and provides much food for thought concerning the future of the New Democratic philosophy, the Democratic party, and American party politics."
New thinking about the ‘New Man’: Developments in Soviet moral theory

Recent developments in Soviet thinking about morality are far more interesting than any which have occurred since the death of Stalin. In contrast to the traditional moral instrumentalism and consequentialism which judges government policies according to whether they promote the desired ends, a narrowing of the concept of acceptable or moral behavior on the part of the State is occurring, accompanied by signs of an emerging recognition of the sanctity of the individual. By contrast, the definition of moral behavior on the part of the individual is being expanded to include a variety of activities hitherto condemned as inimical to the moral code of the New Soviet Man.
The Transcription Elongation Factor NusA Is Required for Stress-Induced Mutagenesis in Escherichia coli

Stress-induced mutagenesis describes the accumulation of mutations that occur in nongrowing cells, in contrast to mutagenesis that occurs in actively dividing populations, and has been referred to as stationary-phase or adaptive mutagenesis. The most widely studied system for stress-induced mutagenesis involves monitoring the appearance of Lac(+) revertants of the strain FC40 under starvation conditions in Escherichia coli. The SOS-inducible translesion DNA polymerase DinB plays an important role in this phenomenon. Loss of DinB (DNA pol IV) function results in a severe reduction of Lac(+) revertants. We previously reported that NusA, an essential component of elongating RNA polymerases, interacts with DinB. Here we report our unexpected observation that wild-type NusA function is required for stress-induced mutagenesis. We present evidence that this effect is unlikely to be due to defects in transcription of lac genes but rather is due to an inability to adapt and mutate in response to environmental stress. Furthermore, we extended our analysis to the formation of stress-induced mutants in response to antibiotic treatment, observing the same striking abolition of mutagenesis under entirely different conditions. Our results are the first to implicate NusA as a crucial participant in the phenomenon of stress-induced mutagenesis.
The Lefschetz properties of monomial complete intersections in positive characteristic

Abstract Stanley proved that, in characteristic zero, all Artinian monomial complete intersections have the strong Lefschetz property. We provide a positive characteristic complement to Stanleyʼs result in the case of Artinian monomial complete intersections generated by monomials all of the same degree, and also for arbitrary Artinian monomial complete intersections in characteristic two. To establish these results, we first prove an a priori lower bound on the characteristics that guarantee the Lefschetz properties. We then use a variety of techniques to complete the classifications.
Biochemical, Structural and Molecular Dynamics Analyses of the Potential Virulence Factor RipA from Yersinia pestis

Human diseases are attributed in part to the ability of pathogens to evade the eukaryotic immune systems. A subset of these pathogens has developed mechanisms to survive in human macrophages. Yersinia pestis, the causative agent of the bubonic plague, is a predominately extracellular pathogen with the ability to survive and replicate intracellularly. A previous study has shown that a novel rip (required for intracellular proliferation) operon (ripA, ripB and ripC) is essential for replication and survival of Y. pestis in postactivated macrophages, by playing a role in lowering macrophage-produced nitric oxide (NO) levels. A bioinformatics analysis indicates that the rip operon is conserved among a distally related subset of macrophage-residing pathogens, including Burkholderia and Salmonella species, and suggests that this previously uncharacterized pathway is also required for intracellular survival of these pathogens. The focus of this study is ripA, which encodes for a protein highly homologous to 4-hydroxybutyrate-CoA transferase; however, biochemical analysis suggests that RipA functions as a butyryl-CoA transferase. The 1.9 A X-ray crystal structure reveals that RipA belongs to the class of Family I CoA transferases and exhibits a unique tetrameric state. Molecular dynamics simulations are consistent with RipA tetramer formation and suggest a possible gating mechanism for CoA binding mediated by Val227. Together, our structural characterization and molecular dynamic simulations offer insights into acyl-CoA specificity within the active site binding pocket, and support biochemical results that RipA is a butyryl-CoA transferase. We hypothesize that the end product of the rip operon is butyrate, a known anti-inflammatory, which has been shown to lower NO levels in macrophages. Thus, the results of this molecular study of Y. pestis RipA provide a structural platform for rational inhibitor design, which may lead to a greater understanding of the role of RipA in this unique virulence pathway.
The Treatment of Maxillofacial Trauma in Austere Conditions

Caring for severely injured patients, whether they be in the theater of combat or after natural disasters, can be a rewarding and even life-changing experience for all involved. Sound surgical principles and an attempt to achieve a high standard of care should still guide the treating surgeon. The surgical team undoubtedly face numerous obstacles, but with careful and considerate planning, many of these can be minimized.
The effect of exercise intensity and duration on salivary immunoglobulin A

Two experiments were performed to examine salivary immunoglobulin A (s-IgA) responses to varying levels of exercise intensity and duration. For experiment 1, 9 college men (mean age, SD=23.56, 1.64 years) completed treadmill runs of 15, 30, and 45 min at approximately 60% of maximum oxygen consumption (VO2max). For experiment 2, 9 other college men (mean age, SD=23.67, 2.0 years) ran for 20 min at approximately 50, 65 and 80% of VO2max. Unstimulated salivary samples were collected before, and immediately, 1 and 2 h after the exercise. Samples were assayed for s-IgA using an enzyme-linked immunosorbent assay. Mean s-IgA levels did not change significantly (P>0.05) at any of the post-exercise collection times when compared to pre-exercise levels. The results of this investigation indicated that running at intensities of 50–80% of VO2max and for durations of 15–45 min did not affect s-IgA levels.
A freeze-fracture study of sarcoplasmic reticulum from fast and slow muscle of the mouse.

Sarcoplasmic reticulum (SR) of fast extensor digitorum longus (EDL) and slow soleus (SOL) muscles of the mouse was examined by freeze-fracture techniques. A distinctive feature of sarcoplasmic reticulum from the EDL is the presence of hillocks on the A-face within the terminal cisterns. These hillocks are usually arranged in a single row which is deployed parallel to the long axis of the adjacent T-tubule. Center-to-center spacing of hillocks within a row is about 70–75 nm. Hillocks are also found scattered within the collar region. The EDL of ten week mice was characterized by sheet-like terminal and intermediate cisterns, the latter being replaced in 37 week animals by thin tubular longitudinal elements of the SR which contain no hillocks or dimples. Hillocks occur only occasionally in SR from 10 or 20 week SOL muscle. In such cases the hillocks occur singly rather than in rows as in the terminal cisterns of EDL. The predominant form of SR in the SOL contains no hillocks. Total particles in the A-face of EDL-SR (2996 particles/μ2; S.D. = ± 287) slightly exceeded that of SOL-SR (2558 particles/μ2; S.D. = ± 274 8 nm). Packing density of 8 nm particles was slightly higher for EDL (750/μ2) vs. SOL (700/μ2). The possible significance of these features of SR in fast and slow muscle is discussed.
Prognostic factors in minor salivary gland cancer

Background. Minor salivary gland cancer occurs infrequently and presents a diagnostic and therapeutic challenge. The purpose of this study was to determine prognostic factors for this disease. Methods. The medical records of 95 patients diagnosed and treated at the University of Alabama at Birmingham over a 35-year period were reviewed. Information concerning patient, disease, and treatment characteristics was compiled for each case. Multivariate analysis was conducted using a rank regression procedure. Results. Stage I or II cancer (p = .022), the absence of cervical lymph node metastases (p = .001), and surgical margins which were free of cancer (p < .001) were predictive of increased 4-year disease-free survival by multivariate analysis. Conclusion. Our findings emphasize the need for detection of early-stage disease combined with complete surgical extirpation of the cancer, which provide the patient with the best chance for locoregional control and long-term survival. © 1995 Jons Wiley & Sons, Inc.
Effects of diffusional barriers on the extent of presystemic and systemic intestinal elimination of drugs.

In the present study, a pharmacokinetic model to address the effects of the diffusional barrier between splanchnic bed and enterocytes on the extent of presystemic and systemic intestinal elimination of drugs was developed. The model is composed of five compartmentsi.e., gut lumen, enterocyte, splanchnic bed, liver and central compartments. The equations for various pharmacokinetic parameters important for estimating the quantitative differences between prresystemic and systemic intestinal and hepatic elimination of drugs were derived. A simulation study demonstrated that the diffusional barrier present between splanchnic blood and enterocytes can have significant effects on oral bioavailability and systemic clearance of drugs. In conclusion, the model can be useful for a better understanding of the effects of diffusional barrier on the extent of administration-route dependent intestinal and hepatic elimination of drugs, especially those with high hydrophilicity and/or charge(s) under physiological conditions.
Early-onset multiple myeloma: an illustrative case report.

Abstract Objective This case study describes a patient diagnosed with early manifestations of multiple myeloma and illustrates relevant aspects of differential diagnosis and the use of laboratory, radiologic, and advanced imaging techniques to aid in establishing the diagnosis and issues of management. Clinical Features A 36-year-old male student experienced midback pain that occurred primarily at night in conjunction with fever and unexplained weight loss. Minor trauma induced a significant fracture and an occult fracture in the upper extremity. Physical examination revealed an elevated temperature indicating a fever of undetermined etiology. Plain radiographs revealed diffuse osteoporosis of the thoracic spine. Laboratory tests revealed anemia, hypercalcemia, and abnormal monoclonal paraprotein. Magnetic resonance imaging revealed a fracture with poor healing and an occult fracture in the upper extremity. Intervention and Outcome The patient was initially assessed for fever of undetermined etiology in association with nocturnal midback pain. Although considered a disease of the geriatric population, subsequent laboratory and radiologic evaluations established a diagnosis of early-onset multiple myeloma. Early recognition and referral with comanagement by an oncologist provided optimum care. Early-onset cases of multiple myeloma tend to have a more favorable response to treatment as compared with cases diagnosed in the geriatric population. Conclusion Multiple myeloma should be a consideration when a patient presents with nocturnal back pain and fever of undetermined etiology. Differentiating multiple myeloma from other causes of back pain is especially important in making management decisions. With a precise history and physical diagnosis, the diagnosis may be suspected, but confirmation must rely on ancillary investigations. Multiple myeloma is frequently accompanied by a poor prognosis, but early-onset cases generally respond more favorably to interventions.
Two postprocessing techniques for the elimination of background autofluorescence for fluorescence lifetime imaging microscopy

The analysis of fluorescence lifetime imaging microscopy (FLIM) data under complex biological conditions can be challenging. Particularly, the presence of short-lived autofluorescent aggregates can confound lifetime measurements in fluorescence energy transfer (FRET) experiments, where it can become confused with the signal from exogenous fluorophores. Here we report two techniques that can be used to discriminate the contribution of autofluorescence from exogenous fluorphores in FLIM. We apply the techniques to transgenic mice that natively express yellow fluorescence protein (YFP) in a subset of cortical neurons and to histological slices of aged human brain tissue, where we study the misfolding of intracellular tau protein in the form of neurofibrillary tangles.
The Influence of Patient-related Variables in the Timing of Cataract Extraction

Data from a prospective study of quality of life after cataract extraction with intraocular lens implantation were used to examine associations between patient factors and the timing of cataract extraction. The 495 patients were drawn from 76 ophthalmologists' offices in three cities. Patients were categorized as waiting three months or less or four months or more to schedule their operations after their physicians' recommendations. Patients who delayed scheduling their operations were more likely to be younger, have higher incomes, be working full-time, have higher life satisfaction, have lower levels of depression and higher levels of vigor, have had a less than perfect previous operation, have lower scores for mid-range vision and higher scores for cataract symptoms, be fearful of nighttime driving, and be heavy drinkers. Conversely, patients who delayed their operations were less likely to be covered by Medicare and to expect excellent postoperative vision and a short recovery time. A discriminant analysis correctly classified 68.9% of the patients according to timing group.
Effect of agitation and Tween 80 addition in the continuous alcohol fermentation

While conducting glucose pulse experiments in the continuous production of ethanol byS. cerevisiae ATCC 4126 in a carbon-limited chemostat, a very poor response and incomplete glucose utilisation was observed. This paper reports the modifications made to the original experimental conditions in order to obtain an optimal behavior of the culture. These modifications include minor culture medium adjustments, Tween 80 addition and improved agitation. The new conditions allowed for a 71% increase in alcohol volumetric productivity and almost complete glucose consumption up to dilution rates of 0.2 h−1.
1-Anilino-8-naphthalenesulfonate: A fluorescent probe of ion and ionophore transport kinetics and trans-membrane asymmetry

The kinetics of the transport of the 1-anilino-8-naphthalenesulfonate (ANS−, an anionic fluorescent probe of the membrane surface) across phospholipid vesicle membranes have been studied using a stopped-flow rapid kinetic technique. The method has been used to gain detailed information about the mechanism of transport of this probe and to study ionophore-mediated cation transport across the membrane. The technique has also been exploited to study differences between the inside and outside surfaces of vesicles containing phosphatidyl choline (PC).
The management of hypercholesterolemia in patients with coronary artery disease: Guidelines for primary care

Abstract More than 10 million individuals in the United States currently have symptomatic coronary artery disease (CAD). Asymptomatic CAD is even more prevalent. CAD in the United States is responsible for approximately 1.5 million myocardial infarctions, 500, 000 deaths, and a total economic burden in excess of $120 billion annually. Fortunately, CAD is preventable in many individuals. Our understanding of CAD has steadily progressed throughout the 20th century, and now several lines of evidence support the importance of cholesterol in both the genesis and management of coronary atherosclerosis. Following identification of the presence of cholesterol in atheromas, Anitschkov early this century demonstrated that atherosclerotic lesions can be induced in susceptible animals by high-saturated-fat and cholesterol diets. These lesions regressed when low fat and cholesterol diets were resumed. In the 1970s and 1980s, findings from the landmark Framingham Heart, Seven Countries, and Multiple Risk Factor Intervention Trial studies firmly established that hypercholesterolemia was a major risk factor for cardiovascular morbidity and mortality. During the 1980s and 1990s, 21 of 22 angiographic trials demonstrated reduced progression of coronary andlor carotid artery disease using lifestyle, drug, and surgical means for reducing cholesterol. The later trials commonly employed hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), reflecting increasing clinical use of these drugs. In 1988, the Adult Treatment Panel of the National Cholesterol Education Program (NCEP) published guidelines on testing and treating hypercholesterolemic patients, which outlined a more aggressive approach to cholesterol lowering than was currently in practice. Since 1994, five large cardiovascular event trials and a large angiographic trial have shown that aggressive cholesterol lowering reduces both cardiac morbidity and mortality, largely substantiating the NCEP guidelines. Although important clinical questions remain regarding patient subsets and treatment goals, lifestyle changes and appropriate drug therapy have proved to be highly effective in preventing initial and recurrent cardiovascular events.
Modeling of an Explosively Driven Micro-Valve

An analysis is given which demonstrates how the performance of a well-characterized explosively actuated valve conguration (length L 2:5 cm) varies with a linear reduction in size. The analysis is based on a time-dependent, system-level model that tracks the evolution of explosive and product mass and energy within the actuator due to combustion, product gas o w from the actuator to an expansion chamber due to a pressure imbalance, work performed by gas within the expansion chamber in pushing a deformable piston into a constant area bore during stroke, and heat transfer with the surroundings. Predictions indicate that the baseline valve is signican tly overdriven by the 150 mg of HMX (C4H8N8O8) contained in the actuator; consequently, little variation in performance is predicted for a reduction in valve size over the range 0:44 s < 1, where s = l=L is a scale factor. Performance variations are predicted for approximately s < 0:44 due to unrestricted compressible gas o w through the actuator port that reduces the pressurization rate within both the actuator and expansion chamber, and results in irregular piston motion. The analysis demonstrates how product gas o w between internal valve components may adversely aect the performance of small valves.
Enzymatic preparation of 3H-labeled β-ureidoisobutyric acid and β-aminoisobutyric acid from 3H-thymidine

We have synthesized β-aminoisobutyric acid (3-amino-2-[3H]methyl-propanoic acid) and β-ureidoisobutyric acid (3-[(aminocarbonyl)amino]-2-[3H]methyl-propanoic acid) starting with [3]thymidine (1-(2-deoxy-β-D-ribo-furanosyl)-5-[3H]methyluracil). We have developed a simplified enzymatic preparation using a dialyzed supernatant of homogenized dog liver. The homogenate was incubated with [3H]thymidine (41 Ci/mmol) in the presence of NADPH, and β-ureidopropionic acid. After extraction the supernatant was purified by HPLC.
Synthesis of threshold logic circuits using tree matching

Threshold logic has been known to be an alternative to Boolean logic for over four decades now. However, due to the lack of efficient circuit implementations, threshold logic did not gain popularity until recently. This change is motivated by new and efficient alternative CMOS implementations for threshold logic and futuristic nano devices like RTDs and SETs which possess inherent threshold properties. This paper motivates the need for threshold logic, and justifies it as an alternative design technique in the post-CMOS era. We present a novel synthesis algorithm for threshold circuits based on tree matching. In comparison with the previous state of the art methods the proposed method demonstrates an improvement of 25% in the number of gates required (max improvement is 50%) and comparable circuit depth.
Interactions in and Interfacial Structure of Annealed Co / a-Si 3 N 4 Studied by Hrtem

Interactions between Co and a-Si3N4 films during Rapid Thermal Anneal (RTA) in N2 and Ar ambients, and during vacuum anneal, have been studied using plan-view and cross-sectional Transmission Electron Microscopy (TEM). Annealing in the temperature range 600 - 1000°C reveals agglomeration of the 12.5 nm Co layer and partial exposure of the nitride layer to the surface. Morphological damage of the Co/Si3N4 interface, and diffusion of Co into the nitride layer and possibly to the Si substrate, were observed after high temperature anneals. Phases of Co and CoSi2 were identified from the plan-view electron diffaction patterns. The Co/Si3N4 interaction seems to occur at lower temperature when annealed in vacuum. The microstructures and morphology of the layers and interfaces are presented. The mechanism for the diffusion of Co into the nitride layer is proposed.
Mitigation of acoustic noise and vibration in switched reluctance motor drive using neural network based current profiling

In order to optimize the performance of switched reluctance motor (SRM) drives, geometrical design of the motor as well as control strategies for its power converter should be adjusted. High levels of torque ripple and acoustic noise are the main drawbacks of SRM drives in many applications. This paper mainly focuses on control strategies to be used for minimizing the acoustic noise and vibration in SRM drives. Further, the major sources of acoustic noise and vibration have been addressed. In addition, the significance of various control variables (control angles and current profile) has been studied in detail. Furthermore, based on this analysis, a current shape optimization method has been introduced. Extensive simulations are given to support the proposed control strategies. Moreover, the impact of the noise reduction algorithm on the efficiency of the drive has been explored. In addition, artificial neural networks have been employed to generate optimized current profiles at various operating points. Finally, experimental results for an 8/6, 0.3 kW SRM drive are given.
Using the Rayleigh-Taylor instability for in situ measurements of thermal conductivity of warm dense matter

The Rayleigh-Taylor (RT) instability of a material with stratified density, temperature, and composition is considered. The variation of composition gives rise to the appearance of modes whose growth rate is directly related to the finite thermal conductivity. It is suggested that this effect could be used for in situ measurements of thermal conductivity of warm dense matter. Expressions for the RT growth rate for the general equation of state are derived and the modes most suitable for measurements are identified. A desired perturbation can be introduced by machining the package or by using masks during the surface deposition process. To visualize the evolution of the embedded perturbation, higher-Z tracers can be used. A concept for a laser-driven experiment where this approach could be realized is presented.
On-line ringing characterization as a PHM technique for power drives and electrical machinery

Embeddable features easily incorporated in traditional power drive systems are identified for prognostic health management (PHM) systems. This novel technique utilizes the original PWM waveform produced by the inverter to evaluate the power electronic circuit and electric machine against transistor degradation. Evaluation of the primary feature, ringing characterization, with experimental data demonstrates its viability as a practical real-time power device health-state indicator.
Identification of a TcpC-TcpQ outer membrane complex involved in the biogenesis of the toxin-coregulated pilus of Vibrio cholerae.

The toxin-coregulated pilus (TCP) of Vibrio cholerae and the soluble TcpF protein that is secreted via the TCP biogenesis apparatus are essential for intestinal colonization. The TCP biogenesis apparatus is composed of at least nine proteins but is largely uncharacterized. TcpC is an outer membrane lipoprotein required for TCP biogenesis that is a member of the secretin protein superfamily. In the present study, analysis of TcpC in a series of strains deficient in each of the TCP biogenesis proteins revealed that TcpC was absent specifically in a tcpQ mutant. TcpQ is a predicted periplasmic protein required for TCP biogenesis. Fractionation studies revealed that the protein is not localized to the periplasm but is associated predominantly with the outer membrane fraction. An analysis of the amount of TcpQ present in the series of tcp mutants demonstrated the inverse of the TcpC result (absence of TcpQ in a tcpC deletion strain). Complementation of the tcpQ deletion restored TcpC levels and TCP formation, and similarly, complementation of tcpC restored TcpQ. Metal affinity pull-down experiments performed using His-tagged TcpC or TcpQ demonstrated a direct interaction between TcpC and TcpQ. In the presence of TcpQ, TcpC was found to form a high-molecular-weight complex that is stable in 2% sodium dodecyl sulfate and at temperatures below 65°C, a characteristic of secretin complexes. Fractionation studies in which TcpC was overexpressed in the absence of TcpQ showed that TcpQ is also required for proper localization of TcpC to the outer membrane.
Cardiopulmonary Bypass Decreases Activation of the Signal Transducer and Activator of Transcription 3 (STAT3) Pathway in Diabetic Human Myocardium

Background Cardiopulmonary bypass (CPB) is associated with increased myocardial oxidative stress and apoptosis in diabetic patients. A mechanistic understanding of this relationship could have therapeutic value. To establish a possible mechanism, we compared the activation of the cardioprotective signal transducer and activator of transcription 3 (STAT3) pathway between patients with uncontrolled diabetes (UD) and nondiabetic (ND) patients. Methods Right atrial tissue and serum were collected before and after CPB from 80 patients, 39 ND and 41 UD (HbA 1c ≥6.5), undergoing cardiac operations. The samples were evaluated with Western blotting, immunohistochemistry, and microarray. Results On Western blot, leptin levels were significantly increased in ND post-CPB ( p p p p p = 0.05) in the UD patients. The oxidative stress marker nuclear factor-κB was significantly higher ( p Conclusions Compared with ND, UD myocardium demonstrated attenuation of the cardioprotective STAT3 pathway. Identification of this mechanism offers a possible target for therapeutic modulation.
A highly metamorphic virus generator

Metamorphic viruses modify their code to produce viral copies that are syntactically different from their parents. The viral copies have the same functionality as the parent but typically have no common signature. This makes signature-based virus scanners ineffective for detecting metamorphic viruses. But machine learning tool such as Hidden Markov Models (HMMs) have proven effective at detecting metamorphic viruses. Previous research has shown that most metamorphic generators do not produce a significant degree of metamorphism. In this project, we develop a metamorphic engine that yields highly diverse morphed copies of a base virus. We show that our metamorphic engine easily defeats commercial virus scanners. We then show that, perhaps surprisingly, HMM-based detection is effective against our highly metamorphic viruses. We conclude with a discussion of possible improvements to our generator that might enable it to defeat statistical-based detection methods, such as those that rely on HMMs.
Localization for robotic assemblies using probing and particle filtering

This paper deals with the class of robotic assemblies where position uncertainty far exceeds assembly clearance, and visual assistance is not available to resolve the uncertainty. Specifically, we focus on the assembly of a key in a lock, with uncertainty in the position of the lock in (x,y,z). Under this scenario, we implement a localization strategy that resolves the uncertainty using a pre-acquired map of key-lock contact configurations. Prior to assembly, the strategy explores the contact configuration space (C-space) by using the key to probe the stationary (fixtured) lock-surface at various different positions and matching the contact configurations thus recorded with the map. Thus, the strategy is progressively able to localize the lock-position in (x,y,z) and achieve assembly. However, with a sampled map of the contact C-space, discretization errors are introduced, and implementing deterministic matching (at the fine-grained level necessary for assembly) would soon become prohibitively expensive in terms of computation. Additionally, with global initial uncertainty, multiple solutions abound in our localization problem. Here, we use a particle filter implementation, which can not only handle the discretization errors in map-matching, but also track multiple solutions simultaneously. The particle filter implementation was highly successful in localizing the lock-position, reducing the uncertainty by more than 95% and making it easy for a compliant strategy to achieve assembly. Results from 50 trials of the lock-key assembly are reported
Binary Phase Diagram of the Manganese Oxide–Iron Oxide System

In this study, the MnOx-FeOx binary system was measured within a temperature range of 750 to 1590°C in an atmosphere of air. Multiple measurement methods were employed to accurately measure the phase boundaries, including isothermal heat-treatments followed by rapid quenching, dilatometery, differential thermal analyses with thermogravimetric analyses, and hot-stage X-ray diffraction (XRD). Phase assemblage in each sample was determined by XRD. Data were compared with literature, and a new, self consistent phase diagram was developed. The results are reported along with background information and a comparison with previously reported data.
Polarimetric microwave brightness signatures of ocean wind directions

The sensitivities of wind direction signals in passive microwave brightness temperatures of sea surfaces to wind speed, incidence angle, polarization, and frequency are presented in this paper. The experimental data were acquired from a series of aircraft flights from 1993 through 1996 by the Jet Propulsion Laboratory (JPL) using JPL 19 and 37 GHz polarimetric radiometers (WINDRAD). Fourier analysis of the data versus mind direction was carried out and the coefficients of Fourier series are illustrated against the wind speed at 45/spl deg/, 55/spl deg/, and 65/spl deg/ incidence angles. There is a good agreement between the JPL aircraft flight data and Wentz's Special Sensor Microwave/Imager (SSM/I) geophysical model function for the vertically polarized brightness temperatures, but Wentz's SSM/I wind direction model for horizontal polarization shows a significantly stronger upwind and downwind asymmetry than the aircraft flight data. Comparison of the dual-frequency WINDRAD data show's that the wind direction signals are similar at 19 and 37 GHz, although the 37 GHz data have slightly stronger signals than the 19 GHz data. In general, the azimuthal variations of brightness temperatures increase with increasing wind speed from low to moderate winds, then level off and decrease at high minds. The only exception is the U measurements at 65/spl deg/ incidence angle, which have a stronger than expected signal at low winds. An exponential function was proposed to model the sensitivities of wind direction signals to wind speeds. The coefficients of the empirical model are provided in this paper and are useful for the simulation of ocean brightness temperatures and for the development of geophysical retrieval algorithms.
The RNA Polymerase II Trigger Loop Functions in Substrate Selection and Is Directly Targeted by α-Amanitin

Structural, biochemical, and genetic studies have led to proposals that a mobile element of multisubunit RNA polymerases, the Trigger Loop (TL), plays a critical role in catalysis and can be targeted by antibiotic inhibitors. Here we present evidence that the Saccharomyces cerevisiae RNA Polymerase II (Pol II) TL participates in substrate selection. Amino acid substitutions within the Pol II TL preferentially alter substrate usage and enzyme fidelity, as does inhibition of transcription by α-amanitin. Finally, substitution of His1085 in the TL specifically renders Pol II highly resistant to α-amanitin, indicating a functional interaction between His1085 and α-amanitin that is supported by rerefinement of an α-amanitin-Pol II crystal structure. We propose that α-amanitin-inhibited Pol II elongation, which is slow and exhibits reduced substrate selectivity, results from direct α-amanitin interference with the TL.
The parasitophorous vacuole membrane surrounding intracellular Toxoplasma gondii functions as a molecular sieve.

Abstract The obligate intracellular protozoan parasite Toxoplasma gondii creates and enters into a unique membrane-bounded cytoplasmic compartment, the parasitophorous vacuole, when invading mammalian host cells. By microinjecting polar fluorescent molecules into individual T. gondii-infected fibroblasts, we show here that the parasitophorous vacuole membrane (PVM) surrounding the parasite functions as a molecular sieve. Lucifer yellow (457 Da) displayed free bidirectional flux across the PVM and distinctly outlined the parasites, which did not take up the dye, within the vacuole. This dye movement was not appreciably delayed by pretreatment of cells with 5 mM probenecid or chilling the monolayer to 5 degrees C, suggesting that dye movement was due to passive permeation through a membrane pore rather than active transport. Calcein, fluo-3, and a series of fluorescein isothiocyanate-labeled peptides up to 1291 Da crossed the PVM in a size-restricted fashion. A labeled peptide of 1926 Da and labeled dextrans and proteins (> or = 3000 Da) failed to transit the PVM. This putative channel in the PVM therefore allows exchange of molecules up to 1300-1900 Da between the host cell cytoplasm and the parasitophorous vacuolar space.
A case for magnetospheric research: President's Page

It has been nearly eighteen years since the initiation of the ‘spaceage’—an age characterized by the exploration and utilization of space by satellites. Satellite explorations now have ranged from within the orbit of Mercury to well beyond the orbit of Jupiter. The attractiveness of explorations to the outer reaches of the solar system, coupled with a depressed budgetary situation, may jeopardize smaller, yet productive, programs studying the near-earth environment. I recognize the difficult and often thankless task of program managers in funding agencies to make hard decisions concerning various research and exploration program priorities.
In vitro incorporation of serine into the staphylococcal cell wall.

Abstract A variant of Staphylococcus aureus 44A HJD was isolated by serial growth in Trypticase soy broth to which 2 M serine had been added (wt/vol). Amino acid analysis of hydrolysates of purified mucopeptides from the variant showed that they contained 1.266 serine and 2.156 glycine residues per glutamic acid residue, compared with 0.174 serine and 3.144 glycine residues per glutamic acid residue in the mucopeptide of the parent strain. In addition to this alteration in the chemical composition of the mucopeptide, the variant lost many of the biochemical and cultural characteristics of the parent organism. The variant was not sensitive to the lytic action of lysostaphin and was non-phage-typable. Moreover, in vitro tests indicated that the organism was coagulase negative, did not produce gelatinase or deoxyribonuclease, and did not hemolyze sheep erythrocytes. Apparently due to the change in the serine content in the cell wall of the parent S. aureus strain, the organism had become “epidermidis-like” in its properties.