cssi/SciSciGPT-SciSciNet huggingface dataset:
Codon equilibrium II: its use in estimating silent-substitution rates

We study the equilibrium in the use of synonymous codons by eukaryotic organisms and find five equations involving substitution rates that we believe embody the important implications of equilibrium for the process of silent substitution. We then combine these five equations with additional criteria to determine sets of substitution rates applicable to eukaryotic organisms. One method employs the equilibrium equations and a principle of maximum entropy to find the most uniform set of rates consistent with equilibrium. In a second method we combine the equilibrium equations with data on the man-mouse divergence to determine that set of rates that is most neutral yet consistent with both types of data (i.e., equilibrium and divergence data). Simulations show this second method to be quite reliable in spite of significant saturation in the substitution process. We find that when divergence data are included in the calculation of rates, even though these rates are chosen to be as neutral as possible, the strength of selection inferred from the nonuniformity of the rates is approximately doubled. Both sets of rates are applied to estimate the human-mouse divergence time based on several independent subsets of the divergence data consisting of the quartet, C- or T-ending duet, and A- or G-ending duet codon sets. Both rate sets produce patterns of divergence times that are shortest for the quartet data, intermediate for the CT-ending duets, and longest for the AG-ending duets. This indicates that rates of transitions in the duet-codon sets are significantly higher than those in the quartet-codon sets; this effect is especially marked for A→G, the rate of which in duets must be about double that in quartets.
Error Statistics and Coding for Binary Transmission over Telephone Circuits

About 2000 hours of noise data on various digital data telephone links are analyzed with respect to the applicability of coding theory to such links. The analysis indicates that coding for error correction is inefficient for such systems, but that coding for error detection, along with feedback, is remarkably simple and effective.
Metabolism of very low density lipoproteins in diet induced hypercholesterolemic pigtail monkeys (Macaca nemestrina)

Cholesterol-fed male pigtail monkeys were used to determine the metabolic mechanism of dietary hypercholesterolemia. Cholesterol feeding (200–400 mg/ day) in monkeys produced a moderate hypercholesterolemia, which progressed with time and after 15 months the plasma cholesterol levels were raised 8-fold. The initial rise in plasma cholesterol was due to an increase in low density lipoproteins (LDL), but later the increases in intermediate (IDL) and very low (VLDL) density lipoproteins were mainly responsible for the rise in plasma cholesterol. To determine the metabolic mechanism, animals, both before and after cholesterol feeding, were co-injected with 131I-labelled VLDL from normal and 125I-labelled VLDL from cholesterol-fed donors. The fractional catabolic rate of autologous VLDL apolipoprotein B, which decayed biphasically, depended upon the dietary status of the recipient animal. The decrease in fractional catabolic rate was due to more VLDL apolipoprotein B being metabolized by the slower second phase. Normal VLDL apolipoprotein B in cholesterol-fed animals was catabolized by the slower second phase to a greater proportion than that in normal animals, where it was mainly transferred to LDL.
Change is the New Normal: Access Services in a New Public Services Paradigm

As the academic library landscape evolves to meet new challenges, many libraries are rethinking their public services models. In 2009, the University of California, Santa Cruz (UCSC) Library began contemplating major changes to public services as a part of planning for a new service desk in a renovated library. With a history of embracing change, Access Services was a model for examining other services within the library. This article, authored by the then two Heads of Access Services at UCSC, provides a practical examination of the collaborative process implemented for rethinking public services and integrating service desks, as well as the benefits and challenges uncovered during the process.
Self-assembled microdevices driven by muscle

Current procedures for manual extraction of mature muscle tissue in micromechanical structures are time consuming and can damage the living components. To overcome these limitations, we have devised a new system for assembling muscle-powered microdevices based on judicious manipulations of materials phases and interfaces. In this system, individual cells grow and self-assemble into muscle bundles that are integrated with micromechanical structures and can be controllably released to enable free movement. Having realized such an assembly with cardiomyocytes we demonstrate two potential applications: a force transducer able to characterize in situ the mechanical properties of muscle and a self-assembled hybrid (biotic/abiotic) microdevice that moves as a consequence of collective cooperative contraction of muscle bundles. Because the fabrication of silicon microdevices is independent of the subsequent assembly of muscle cells, this system is highly versatile and may lead to the integration of cells and tissues with a variety of other microstructures.
Regeneration of Axons and Synaptic Complex Formation Rostral to the Site of Hemisection in the Spinal Cord of the Monkey

Historically, injury of the mammalian spinal cord resulted in abortive regeneration. Recent findings have shown regeneration of the spinal cord occurs by limited regrowth of severed nerve fibers and massive regrowth of axonal sprouts of normal axons. The foregoing study investigates the regenerative capacity of the spinal cord in 14 Rhesus monkeys (Macaca mulatto) following left hemisection at vertebral segment T2. In addition to three normals, animals were utilized 7, 14, 21 days and 1, 2, 3, and 4 months posthemisection. Tissue was prepared for Golgi impregnation, Protargol-cresyl violet-eosin staining, and electron microscopy. The motor horn rostral to the site of lesion was investigated. Dendrites of motor horn cells adjacent to and facing the lesion developed varicosities which formed at the terminal end of the dendrite by day 7 and progressed to include the entire dendrite by day 14–30 posthemisection. Motor horn cell dendrites (0–5 mm from lesion) were varicose and many possessed only two short, va...
Mass fire characteristics in large-scale tests

The suburban sprawl into rural and wildland areas increases the potential for damage from mass fires, either through nuclear attack or natural disaster. But defenses against the devastating effects of mass fires suffer from lack of quantitative information on behavior of large intense fires. Laboratory-scale testing is not enough —it is very likely that a different set of controlling factors take over when a fire grows to a certain size and intensity. A series of large-scale tests using woodland fuels in ordered piles simulating built-up residential areas has been started to provide the missing data. Preliminary tests in the series are reported here.
Limb loss due to transvenous endocardial pacemaker therapy.

Abstract Although Intravenous thrombosis frequently complicates placement of transvenous endocardial leads in patients with permanent pacemakers, clinical manifestations of upper extremity thrombosis are uncommon. Most, including upper extremity edema, cervical venous engorgement, and even superior vena cava syndrome, can be successfully managed with conservative therapy. In the patient described in the present report, clinical manifestations of pacemaker-electrode thrombosis were neither mild nor responsive to conservative therapies: in this patient, pacemaker-electrode thrombosis ultimately required amputation of the right upper extremity. Complications of the magnitude described in this patient emphasize the need for continual review of the indications for pacemaker therapy as understanding of the risk-benefit ratio of this procedure broadens.
Transient Long-Wave Response for a Multiple-Island System

Abstract An interpretation of the tsunami response at the Hawaiian island of Kauai has been carried out utilizing simple geometric representations which include the three-island system of Kauai, Niihau and Oahu. The response has been investigated in terms of constant-depth models with the islands represented as cylinders and with a model which have geometric approximations of the underwater topography. The constant-depth models have indicated the portion of the response at Kauai related to interactions of the scattered and incident waves while the topographic model additionally contains response modes associated with the transient trapping of long-wave energy by the island system. The enhancement of the computed response in the topographic model is studied both in terms of the local Kauai topography alone and for a complete geometric representation of the Kauai, Niihau and Oahu topography.
Nerve impulse propagation affected by sol-gel changes in axoplasm

Abstract Changes in temperature and pressure alter the gel-sol state of protoplasm. The degree of gelation relates to the structural properties of protoplasm and since the propagation velocity of a nerve impulse depends on the apparent modulus of elasticity, altering temperature and pressure changes the velocity of the impulse.
Abstract 3091: A sumoylation-dependent transcriptional subprogram is required for Myc-driven tumorigenesis

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Myc is an oncogenic transcription factor frequently dysregulated in human malignancies. While the transcriptional programs and other functions of Myc have been intensively studied, there remains no effective strategy for inhibiting Myc in patients. To search for pathways that support the Myc oncogenic program, we employed a next-generation RNAi screen for Myc-synthetic lethal (MySL) genes. Using this strategy, we have identified several cellular processes required to tolerate oncogenic Myc. Key among these is the core sumoylation machinery, and we define the Sumo-activating enzyme (SAE) as a central component in this MySL network. Loss of SAE drives synthetic lethality with Myc, and the enzymatic activity of SAE is required to support the Myc oncogenic state. Inactivation of SAE leads to mitotic catastrophe and cell death selectively upon Myc hyper-activation. Mechanistically, depletion of SAE switches a subprogram of Myc transcriptional targets governing mitotic spindle function from activated to repressed, a subprogram we term Sumoylation-dependent Myc Switchers, or SMS genes. Notably, SMS genes are required to tolerate Myc hyper-activation, and SAE and the SMS program are required for Myc-dependent breast cancer cell survival in vitro and tumor growth and progression in vivo. Importantly, patient survival significantly correlates with levels of SAE and SMS gene expression in Myc-high tumors. Collectively, these studies reveal a mitotic vulnerability of Myc-driven cancers and demonstrate that inhibiting sumoylation can selectively impair mitosis and survival in an oncogenic Myc-dependent manner. We propose that drugs targeting SAE and its downstream SMS targets may have therapeutic benefits for patients with Myc-driven cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3091. doi:1538-7445.AM2012-3091
Energy spectrum of delayed neutrons from the spontaneous fission of 252Cf

Abstract The energy spectrum of delayed neutrons from the spontaneous fission of 252Cf has been measured using a time-of-flight neutron spectrometer. The experimental timing conditions emphasized delayed neutrons of about 2 s half-life. Eleven peaks due to monoenergetic neutrons were observed in the energy range from 95 to 430 keV.
A general approach to the management of chronic hepatitis C

Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the United States. Although many will live a lifetime unaffected by the consequence of chronic infection, some will develop cirrhosis and end-stage liver disease. Given the broad spectrum of disease outcomes, developing a careful systematic approach to infected patients is fundamental. This allows the practitioner to provide accurate education, develop treatment plans, and determine appropriate health care maintenance and screening. Care for the patient with HCV must be individualized. In this regard,the purpose of this article is not to present a guideline, but to provide a foundation of information that will aid the provider and patient in developing an appropriate treatment strategy.
Differential inactivation and separation of homologous and heterologous antiviral activity of human leukocyte interferon by a proteolytic enzyme.

Abstract Human leukocyte interferon (HuLeIF) can express its antiviral activity on both human and bovine cells. The rates of inactivation of HuLeIF by α-chymotrypsin, as expressed on human and bovine cells, are not the same: the ability to induce activity on human cells is lost significantly more rapidly than the activity detected on bovine cells; usually a margin of greater than one hundred-fold exists after α-chymotrypsin treatment. HuLeIF, when subjected to analysis on 10% SDS-PAGE, can be separated into two molecular weight species, one having apparent molecular weight of approximately 21,000 daltons, the other 18,000 daltons. A more rapidly migrating form (molecular weight 16,500 daltons) can also be isolated, which is considerably more active on bovine cells than on human cells. α-chymotrypsin-treated samples analyzed by SDS-PAGE show a clear separation of the activities expressed on human and bovine cells. The residual activity detected on human cells is isolated only in the 21,000 component while the activity found on bovine cells is recovered only as the 16,500 dalton species.
Some data concerning the Vocational Preference Inventory scales and the Strong Vocational Interest Blank

Abstract Occupational scales of the Vocational Preference Inventory were correlated with the Basic Interest scales of the Strong Vocational Interest Blank . The 285 subjects were women freshman in a College of Education. The results indicate that the scales are not highly correlated.
Is there an intrinsic difference between bulk YBCO and a single unit-cell layer?☆

Abstract The reduction of Tc in ultrathin films of YBCO in multilayers has often been assumed to be the result of the absence of essential transverse coupling. Our work shows instead that the changes in Tc are correlated with changes in conductance, which are the result of extrinsic effects, such as charge transfer and defects at the interfaces. Except for these effects there seems to be no evidence for any change in the YBCO properties down to the thickness of a single unit-cell layer.
A systematic approach to the analysis of complex interaction patterns in two-level factorial designs

Analysis of data from two-level full factorial designs often ends up with a final prediction equation that gives only the significant main-effect and interaction terms. When the number of interactions is small, simple and useful interpretation of the equation can then be drawn immediately. This article addresses a different situation in which the number of significant interactions may be large so that additional efforts are needed to sort out the pattern and the relationship between them. In particular, we bring out a class of models in which most interactions can be attributed to just one or two (or very few) factors, and conditional on these factors, the models become essentially linear. We offer a strategy for uncovering this structure by linear domain splitting, whereby a complicated global model is replaced by a series of local domain-specific linear models. We present a recommended methodology (PHD—principal Hessian direction) for systematically proceeding from the global equation to local split-dom...
Children's Daily Fruit and Vegetable Intake: Associations with Maternal Intake and Child Weight Status.

Abstract Objective To evaluate associations between children’s and their mothers’ fruit and vegetable (FV) intake and children’s FV intake and weight status. Methods Mothers (n = 39) residing in Philadelphia, PA completed a subsection of the Diet History Questionnaire assessing their FV intake. Mothers also completed this questionnaire to estimate FV intake among their 5- or 6-year-old children (n = 39). Children’s height and weight were measured. Pearson correlation, Student t tests, and binary logistic regression analyses were performed. Results A significant positive mother-child association was found for FV intake ( P P = .02). Conclusions and Implications Efforts to promote FV consumption in mothers may help children achieve the recommended intake of FVs. Higher intakes of FVs in turn may help with child weight management.
Pre-operative CT angiography and three-dimensional image post processing for deep inferior epigastric perforator flap breast reconstructive surgery

Autologous breast reconstructive surgery with deep inferior epigastric artery (DIEA) perforator flaps has become the mainstay for breast reconstructive surgery. CT angiography and three-dimensional image post processing can depict the number, size, course and location of the DIEA perforating arteries for the pre-operative selection of the best artery to use for the tissue flap. Knowledge of the location and selection of the optimal perforating artery shortens operative times and decreases patient morbidity.
Predicting Yolk Weight in Quail Eggs

Abstract Avian toxicologists and immunologists may need to dose or innoculate eggs based upon the yolk weight. Equations predicting yolk weight of Japanese quail eggs from egg weight, shell length, and shell width were determined. A prediction equation using only egg weight: yolk weight = (.2155) egg weight1.175 is as reliable as equations using the other parameters. A simple and rapid technique for isolating the yolk from the albumen is also described.
SCIENCE‐BASED PRODUCT DEVELOPMENT: AN EMPIRICAL STUDY OF THE MAINFRAME COMPUTER INDUSTRY

This paper reports on the results of an empirical study of product development in a complex and novel environment. The work is based on field investigations of recent product development projects performed by all leading mainframe computer producers. The projects focused on the development of complex products based on advanced technologies and probed deeply into their science base. The results show striking differences in development lead time and research and development productivity between different projects. The analysis relates these performance differences to the process for the integration of new technology. Organizations that emphasize the accumulation of system-level knowledge of product and production process and its use in technology evaluation and selection are associated with high productivity and short development lead times. This appears to have a greater impact on development performance in this novel environment than more traditional factors, such as processes for effective crossfunctional integration and for overlapping problem solving.
Dilute solution studies of pyrrone prepolymers

Data on dilute solutions of a pyrrone “prepolymer” are presented and the tendency of this polymer to aggregate in certain solvents commonly used in dilute solution studies is discussed. It is concluded that reliable molecular weights can be determined if solvents that interact with the prepolymer through hydrogen bonding are used.
Energy changes in stressed bodies due to void and crack growth

It is demonstrated that the removal of material or the creation or extension of cracks always reduces the total potential energy of any non-linear or linear stable elastic body under fixed load and displacement boundary conditions. A weaker statement that crack extension releases potential energy in excess of plastic dissipation is established for stable elastic-plastic bodies, with certain strong but reasonable restrictions on the path of traction removal from the new surface. Crack healing, however, always absorbs energy. Implications for the Griffith theory of fracture, including its extension to inelastic materials, and the mechanical aspects of stress corrosion cracking are discussed.
Progress In Optical Recording At 428nm

Summary form only given, as follows. Experiments demonstrating high density optical recording at 428 nm using the recently developed compact, frequency doubled diode laser and optimized COPT multilayer media are described.
Age-related changes in the vestibular folds of the human larynx: A histomorphometric study

Summary Age-related changes were investigated in the human vestibular folds of the larynx. Twelve male Caucasian larynges were obtained from autopsy and studied via light microscopy. The donors were free from head-neck pathologies or laryngeal trauma. Specimens included a 6-week-old infant, and at least one each from the second through eighth decades. Each specimen was decalcified and prepared for paraffin embedding and subsequent sectioning in the coronal plane at 6 μm. Sections were stained alternately with safronphloxine-hematoxylin and iron gallien elastic stains. Descriptive and quantitative data were obtained from light microscopy and planar morphometry using a computer image analysis system. Tissue changes included fatty infiltration of serous and mucous glands, fibrotic changes in connective tissue, and alterations in the distribution of mixed glands specific to serous/mucous ratios. Potential implications of findings to vocal function are discussed.
Perception of movement in American Sign Language: effects of linguistic structure and linguistic experience.

In order to reveal the psychological representation of movement from American Sign Language (ASL), deaf native signers and hearing subjects unfamiliar with sign were asked to make triadic comparisons of movements that had been isolated from lexical and from grammatically inflected signs. An analysis of the similarity judgments revealed a small set of physically specifiable dimensions that accounted for most of the variance. The dimensions underlying the perception of lexical movement were in general different from those underlying inflectional movement, for both groups of subjects. Most strikingly, deaf and hearing subjects significantly differed in their patterns of dimensional salience for movements, both at the lexical and at the inflectional levels. Linguistically relevant dimensions were of increased salience to native signers. The difference in perception of linguistic movement by native signers and by naive observers demonstrates that modification of natural perceptual categories after language acquisition is not bound to a particular transmission modality, but rather can be a more general consequence of acquiring a formal linguistic system.
Discrete-time modeling of TCP Reno under background traffic interference with extension to RED-based routers

This paper introduces a discrete-time model which captures the essential protocol features of the congestion control mechanism used by the TCP Reno protocol, subject to interference from other sources. Under this model, a single target session is modeled according to the TCP Reno mechanism, including slow start, congestion avoidance, fast retransmit and fast recovery. At the same time, other sources are modeled as a background process using a discrete batch Markov arrival process (D-BMAP). The D-BMAP process has been modified such that the transitions between the phases are dependent on the number of lost packets from the background process. This introduces a feedback process, which can be used to model an aggregation of TCP sources. In order to capture all the TCP Reno protocol features, two levels of Markov process modeling are used: a microscopic level, at the packet transmission time boundaries, and a macroscopic one, at the start of the new transmission windows. In addition, it is shown how the model can be extended to model networks with RED-based routers. Several performance measures are derived, and numerical examples which demonstrate the protocol features are presented.
Hydralazine Modifies Aβ Fibril Formation and Prevents Modification by Lipids in Vitro

Lipid oxidative damage and amyloid β (Aβ) misfolding contribute to Alzheimer's disease (AD) pathology. Thus, the prevention of oxidative damage and Aβ misfolding are attractive targets for drug discovery. At present, no AD drugs approved by the Food and Drug Administration (FDA) prevent or halt disease progression. Hydralazine, a smooth muscle relaxant, is a potential drug candidate for AD drug therapy as it reduces Aβ production and prevents oxidative damage via its antioxidant hydrazide group. We evaluated the efficacy of hydralazine, and related hydrazides, in reducing (1) Aβ misfolding and (2) Aβ protein modification by the reactive lipid 4-hydroxy-2-nonenal (HNE) using transmission electron microscopy and Western blotting. While hydralazine did not prevent Aβ aggregation as measured using the protease protection assay, there were more oligomeric species observed by electron microscopy. Hydralazine prevented lipid modification of Aβ, and Aβ was used as a proxy for classes of proteins which either misfold or are modified by HNE. All of the other hydrazides prevented lipid modification of Aβ and also did not prevent Aβ aggregation. Surprisingly, a few of the compounds, carbazochrome and niclosamide, appeared to augment Aβ formation. Thus, hydrazides reduced lipid oxidative damage, and hydralazine additionally reduced Aβ misfolding. While hydralazine would require specific chemical modifications for use as an AD therapeutic itself (to improve blood brain barrier permeability, reduce vasoactive side effects, and optimization for amyloid inhibition), this study suggests its potential merit for further AD drug development.
Characterization of a Biomedical Titanium Alloy Using Various Surface Modifications to Enhance its Corrosion Resistance and Biocompatibility

Ti6Al4V titanium alloy has been characterized for its prospective applications as an implant material. The surface treatments performed have brought about enhanced surface properties of these alloys and have produced corrosion resistant oxide films with increased bioactive properties. Characterization of the alloy surface has revealed the presence of a duplex oxide structure over the surface treated specimens, composed of an inner barrier layer and an outer porous layer. The inner barrier layer has imparted a high corrosion resistance to the alloy while the outer porous layer which is responsible for the increased roughness of the surface treated alloy specimens, has encouraged formation and deposition of apatite into the oxide pores and further resulted in an increase in cell adhesion over the alloy surface. Anodization and heat treatment procedures have proved advantageous to titanium alloys in terms of producing oxide films that can offer these alloys an improved biological performance.
Eric Voegelin, Reflexive Distance, and Harnessing the Benefits of Metaxy: The Leader's Imperative to Participate in History and Becoming

The capacity to lead consciously is connected to the leader's knowledge of the self and one's environment. Eric Voegelin stipulated that gaining reflexive distance through comparative historical knowledge allowed for a deeper understanding of an individual's place in society. Citing his works, the current article explains the utility to leaders in understanding historiography, confronting narratives of the past, and criticizing previous normative structures. Leaders come to understand their place in the process of “becoming” by confronting the past. Harnessing the capacity to reflect, leaders can use history as a mirror to demand more of themselves and followers. Moreover, as leaders come to comprehend symbols of mankind's attempt to make sense of the universe and to establish some degree of order, disruptions to the “order” can paradoxically manifest growth. Conscious leaders thus become adaptive rather than reactive.
A Fast Stereo-based System for Detecting and Tracking Pedestrians from a Moving Vehicle

In this paper we describe a fully integrated system for detecting, localizing, and tracking pedestrians from a moving vehicle. The system can reliably detect upright pedestrians to a range of 40 m in lightly cluttered urban environments. The system uses range data from stereo vision to segment the scene into regions of interest, from which shape features are extracted and used to classify pedestrians. The regions are tracked using shape and appearance features. Tracking is used to temporally filter classifications to improve performance and to estimate the velocity of pedestrians for use in path planning. The end-to-end system runs at 5 Hz on 1,024 A 768 imagery using a standard 2.4 GHz Intel Core 2 Quad processor, and has been integrated and tested on multiple ground vehicles and environments. We show performance on a diverse set of datasets with groundtruth in outdoor environments with varying degrees of pedestrian density and clutter. In highly cluttered urban environments, the detection rates are on a par with state-of-the-art but significantly slower systems.
Observing and modeling the nocturnal park cool island of an arid city: horizontal and vertical impacts

We examined the horizontal and vertical nocturnal cooling influence of a small park with irrigated lawn and xeric surfaces (∼3 ha) within a university campus of a hot arid city. Temperature data from 0.01- to 3-m heights observed during a bicycle traverse of the campus were combined with modeled spatial temperature data simulated from a three-dimensional microclimate model (ENVI-met 3.1). A distinct park cool island, with mean observed magnitudes of 0.7–3.6°C, was documented for both traverse and model data with larger cooling intensities measured closer to surface level. Modeled results possessed varying but generally reasonable accuracy in simulating both spatial and temporal temperature data, although some systematic errors exist. A combination of several factors, such as variations in surface thermal properties, urban geometry, building orientation, and soil moisture, was likely responsible for influencing differential urban and non-urban near-surface temperatures. A strong inversion layer up to 1 m over non-urban surfaces was detected, contrasting with near-neutral lapse rates over urban surfaces. A key factor in the spatial expansion of the park cool island was the advection of cooler park air to adjacent urban surfaces, although this effect was mostly concentrated from 0- to 1-m heights over urban surfaces that were more exposed to the atmosphere.
Effects of erythromycin or rifampin on losartan pharmacokinetics in healthy volunteers

Background Losartan is metabolized by CYP2C9 and CYP3A4 to an active metabolite, E3174, which has greater antihypertensive activity than the parent compound. Coadministered drugs that inhibit or induce metabolic processes may therefore alter the pharmacokinetics and pharmacologic response of losartan and E3174. Objective and Methods Ten healthy volunteers were studied to assess the effects of CYP3A4 inhibition and nonspecific P450 enzyme induction on the pharmacokinetics of losartan and E3174. Subjects completed three 1-week phases separated by 6 days: 50 mg losartan every morning, losartan plus 500 mg erythromycin four times a day, and losartan plus 300 mg rifampin (INN, rifampicin) twice a day. On the eighth day of each phase, serial plasma concentrations of losartan and E3174 were obtained over 32 hours and steady-state pharmacokinetics were determined. Results Rifampin decreased the area under the concentration-time curve from time zero to 24 hours after the dose (AUC[0–24]) of losartan by 35% (349 ± 246 versus 225 ± 130; p = 0.0001) and decreased the AUC(0–24) of E3174 by 40% (1336 ± 445 versus 792 ± 302; p < 0.005). Losartan oral clearance was increased by 44% (p = 0.0001). The half-life values of both compounds were decreased by 50% (p < 0.005). In contrast, erythromycin did not significantly affect the AUC(0–24) or half-life of either losartan or E3174. Conclusions Rifampin is a potent inducer of losartan and E3174 elimination. Given the magnitude of the effect, this interaction is likely to be clinically significant. On the basis of the minimal inhibitory effects observed with erythromycin, CYP3A4 appears to play a minor role in the in vivo metabolism of losartan to E3174. Further studies are needed to define the contribution of other isozymes, particularly CYP2C9, to the pharmacokinetics of losartan and E3174. Clinical Pharmacology & Therapeutics (1998) 63, 316–323; doi:
Regional presentation of hepatic diseases: CT and MR imaging findings of differential diagnosis

Neoplastic and nonneoplastic diseases may involve the liver with a regional distribution, which is defined as a non-focal process without any specific anatomic predilection. In this pictorial essay we review hepatic diseases commonly presenting with a regional distribution in the liver and describe the CT and MR imaging findings helpful for differential diagnosis. Knowledge of the characteristic imaging manifestations of neoplastic and non-neoplastic diseases affecting the liver regionally will facilitate an accurate diagnosis and result in the appropriate clinical management of these liver diseases.
Treatment implications of the emerging molecular classification system for melanoma.

Summary Melanoma is an aggressive disease with few standard treatment options. The conventional classification system for this disease is based on histological growth patterns, with division into four subtypes: superficial spreading, lentigo maligna, nodular, and acral lentiginous. Major limitations of this classification system are absence of prognostic importance and little correlation with treatment outcomes. Recent preclinical and clinical findings support the notion that melanoma is not one malignant disorder but rather a family of distinct molecular diseases. Incorporation of genetic signatures into the conventional histopathological classification of melanoma has great implications for development of new and effective treatments. Genes of the mitogen-associated protein kinase (MAPK) pathway harbour alterations sometimes identified in people with melanoma. The mutation Val600Glu in the BRAF oncogene (designated BRAF V600E ) has been associated with sensitivity in vitro and in vivo to agents that inhibit BRAF V600E or MEK (a kinase in the MAPK pathway). Melanomas arising from mucosal, acral, chronically sun-damaged surfaces sometimes have oncogenic mutations in KIT , against which several inhibitors have shown clinical efficacy. Some uveal melanomas have activating mutations in GNAQ and GNA11 , rendering them potentially susceptible to MEK inhibition. These findings suggest that prospective genotyping of patients with melanoma should be used increasingly as we work to develop new and effective treatments for this disease.
16-QAM BICM-ID in fading channels with imperfect channel state information

We analyze the impact of imperfect channel state information (CSI) on the performance of bit-interleaved coded modulation with iterative decoding (BICM-ID) over fading channels. We develop a general, accurate and efficient theoretical error-free feedback bound (EF bound) to analyze the asymptotic bit-error rate (BER) of BICM-ID with imperfect CSI, and predict the BER floor due to channel estimation error. The convergence to the EF bound and the accuracy of the BER floor prediction are verified by simulation with various sets of code and channel parameters. These results are canonical, in that they apply to a variety of system configurations. Pilot symbol assisted modulation is used as a particular example for Rayleigh-fading channels.
Parsing Warlpiri—A Free Word Order Language

An important challenge for natural language parsers is the phenomenon of free word order. In languages exhibiting this phenomenon—and it seems that all languages do have free ordering to some extent—the words in a sentence may swap about freely with little effect on meaning. It also appears that no language is completely free, so for a parser to properly handle this phenomenon, it must be able to accept sentences that vary where they may and that do not vary where they may not. In this chapter, I will present a parser that works well for a part of Warlpiri, an Aboriginal language from central Australia, that exhibits a great deal of free word order. It is believed that the same underlying mechanism will also handle more fixed word order languages like English.
Why there are two cyclooxygenase isozymes.

Since the discovery in 1991 of a second isoform of prostaglandin endoperoxide H synthase (PGHS, or cyclooxygenase), there has been considerable interest in the question of why two isoforms of this enzyme are necessary and what roles they might play. PGHS-1–deficient (1) and PGHS-2–deficient (2, 3) mice and isoform-specific inhibitors have been developed and used to investigate the physiological functions of PGHS-1 and PGHS-2. These studies suggest that there are processes in which each isozyme is uniquely involved (e.g., platelet aggregation for PGHS-1, ovulation for PGHS-2) and others in which both isozymes function coordinately (e.g., carcinogenesis, inflammation). There are also physiological events in which one PGHS isozyme normally functions but for which the other can compensate when the first is lacking (e.g., parturition and remodeling of the ductus arteriosus). Biochemical studies indicate that each isoform can function independently; namely, that there are distinct PGHS-1 and PGHS-2 prostanoid biosynthetic pathways. Thus, the unique physiological roles for each isozyme can be rationalized by what is known about the biochemistry of the enzymes. To facilitate discussion of the physiological functions of PGHS-1 and PGHS-2 and to point out those functions for which PGHS-1 and PGHS-2 can substitute for one another, we describe the following in sequence: (a) physiological processes that depend solely or primarily on PGHS-1, (b) physiological processes that depend solely or primarily on PGHS-2, and (c) processes in which both PGHS-1 and PGHS-2 are involved and act coordinately. We then summarize the biochemical evidence for distinct PGHS-1 and PGHS-2 biosynthetic pathways.
Miller-Urey and Beyond: What Have We Learned About Prebiotic Organic Synthesis Reactions in the Past 60 Years?

The synthesis of amino acids in the Miller-Urey spark-discharge experiments in the early 1950s inspired a strong interest in experimental studies of prebiotic organic chemistry that continues today. Over the years, many of the basic building blocks of life as we know it have been synthesized in the laboratory from simple ingredients, including amino acids, sugars, nucleobases, and membrane-forming lipids. Questions remain, however, concerning whether the conditions that allow synthesis of these compounds in the laboratory accurately simulate those that might have been present on the early Earth, and a closer convergence between plausible prebiotic conditions and laboratory simulations remains a challenge for experimentalists.
Treatment of Large Brain Metastases With Stereotactic Radiosurgery

Introduction:We report our series of patients with large brain metastases, >3 cm in diameter, who received stereotactic radiosurgery (SRS) as a component of their treatment, focusing on survival and intracranial recurrence rates.Materials and Methods:The brain tumor database was queried for patients treated with SRS for large brain metastases. Local recurrence (LR) and distant brain recurrence (DBR) rates were calculated using cumulative incidence analysis, and overall survival (OS) was calculated using Kaplan-Meier analysis. Patients were classified into 1 of the 4 groups based on treatment strategy: SRS alone, surgery plus SRS, SRS plus whole-brain radiation therapy (WBRT), and salvage SRS from more remote WBRT and/or surgery.Results:A total of 153 patients with 164 lesions were evaluated. The SRS alone was the treatment approach in 62 lesions, surgery followed by SRS to the resection bed (S + SRS) in 33, SRS + WBRT in 19, and salvage SRS in 50. There was no statistically significant difference in OS be...
A model system for targeted drug release triggered by biomolecular signals logically processed through enzyme logic networks.

A new Sense-and-Act system was realized by the integration of a biocomputing system, performing analytical processes, with a signal-responsive electrode. A drug-mimicking release process was triggered by biomolecular signals processed by different logic networks, including three concatenated AND logic gates or a 3-input OR logic gate. Biocatalytically produced NADH, controlled by various combinations of input signals, was used to activate the electrochemical system. A biocatalytic electrode associated with signal-processing “biocomputing” systems was electrically connected to another electrode coated with a polymer film, which was dissolved upon the formation of negative potential releasing entrapped drug-mimicking species, an enzyme–antibody conjugate, operating as a model for targeted immune-delivery and consequent “prodrug” activation. The system offers great versatility for future applications in controlled drug release and personalized medicine.
Reconsidering Successful Aging A Call for Renewed and Expanded Academic Critiques and Conceptualizations

Many scholars now critique successful aging terminology. Nonetheless, there is incomplete analysis of the political motivations behind the development of and/or effects of widespread use of these terms. This article suggests that analysis of the people who developed the terms and the settings within which they work parallels an analysis of the terms themselves and illustrates the continuing negative perception of aging. This study fleshes out a more thorough critique of the sociopolitical contexts surrounding the successful aging paradigm so that it can help renew and expand existing critiques. The authors conclude that researchers need to be wary of adopting successful aging terminology without considering and expanding their understanding of the political motivations and results that accompanies it. New, expanded conceptualizations of successful aging are needed so that socially minded researchers and practitioners of gerontology do not contribute to ageism and discrimination against older adults.
A bound on the unequal error protection capabilities of rate k/n convolutional codes

In a previous paper by Mills and Costello (see ibid., p.114, 1993) the effective free distance vector of a convolutional encoder was defined. This paper presents a new bound relating two individual effective free distances. Evaluating the bound is a useful tool in determining the possible unequal error protection capabilities of encoders of specified rate and memory distribution. In addition, the bound allows a comparison between the effective free distance vector of a specific encoder and the theoretically optimal effective free distance vector. First, a bound on the Hamming weight of the sum of two vectors with known Hamming weights is presented. Then this bound is applied to effective free distances of encoders with both balanced and unbalanced memory distributions. >
AN ELECTRICAL RESISTIVITY PROFILE IN HAWAII WITH NOVEL ELEVATION CORRECTION

In order to locate relatively optimum sites for drilling exploratory holes for fresh water, an electrical resistivity survey was conducted along the new Mahukona-Kawaihae Road on the west flank of the Kohala Mountain. Two resistivity soundings made at the same stations, using the Schlumberger electrode configuration, determined an a spacing of 275 feet for horizontal profiling with the Wenner array. The correlation coefficient of the elevation to profile data was 0.41. A procedure for removing elevation effect from observed apparent resistivity was developed. Based on the reduced resistivity profile, four relatively optimum sites for additional exploration, such as by drilling, are specified. There is no specific interpretation of the data that can definitely indicate the occurrence of large underground reservoirs of fresh water anywhere along the profile. This is because the interpretation of horizontal profiling data is essentially relative and not absolute.
The blacksburg electronic village: a study in community computing

This paper discusses the development of Blacksburg Electronic Village, and several of the ICT projects for local development. The stake-holders and their interests are analyzed, as well as the results, dilemmas and prospects.
Error analysis of algorithms in linear prediction

Errors caused by the finite wordlength of the computer in several popular algorithms in linear prediction are studied. Both the classical algorithms and the split cases of the classical algorithms are superior to other algorithms since the errors of computation at each stage propagate more slowly than in the Levinson and Schur cases. The results of the Levinson and Schur algorithms are almost the same. For the split cases, the errors accumulate much faster than in the classical situations since the three-term recurrence is used. >
An interaction system for watch computers using tactile guidance and bidirectional segmented strokes

We introduce an input system that is based on bidirectional strokes that are segmented by tactile landmarks. By giving the user tactile feedback about the length of a stroke during input, we decrease the dependence of the GUI on the visual display. By concatenating separate strokes into multistrokes, complex commands may be entered, which may encode commands, data content, or both simultaneously. To demonstrate their power, we show how multistrokes can be used to traverse a menu hierarchy quickly. In addition, we show how inter-landmark segments of the sensor may be used for continuous and discrete parameter entry, resulting in a multifunctional interaction paradigm. We also introduce multiwidgets, which allow the direct control of multiple virtual widgets without the need to change the state of the device or use modifier buttons. This approach to input does not depend on material displayed visually to the user, and, thanks to tactile guidance, may be used by expert users as an eyes-free user interface. We believe that these benefits make this interaction system especially suitable for wearable computer systems that use a head-worn display and wrist-worn watch-style devices.
Extraneous information and extra steps in arithmetic word problems

Abstract To determine how middle school students cope with some of the demands imposed on them by arithmetic word problems, 140 eighth graders were asked to solve word problems modeled after those used by the National Assessment of Educational Progress. Processing demands were imposed on the students by adding extraneous information and extra steps to the problems. Results indicated that the presence of extraneous information and extra steps reduced the accuracy of students' solutions. Thinking-out-loud protocols also revealed several misconceptions that students have about solving word problems.