cssi/SciSciGPT-SciSciNet huggingface dataset:
Animal insulin therapy induces a biased insulin antibody response that persists for years after introduction of human insulin.

Administration of exogenous insulin for the treatment of diabetes is often accompanied by the development of insulin antibodies (IA). These antibodies may affect the patient’s requirement for insulin by acting as an insulin binding reservoir. The improvement of insulin purification in the 1970s and the development of human recombinant insulin both reduced the incidence of IA and their binding levels. This study investigates the parameters affecting IA frequency and binding levels in a cohort of type 1 diabetes (T1D) patients. All patients were treated with human recombinant insulin. About half of the patients had received animal insulin prior to the introduction of human recombinant insulin. We tested the IA frequency and binding level for all serum samples. IA were further analyzed for their epitope specificity comparing human and porcine insulin binding. We found that T1D patients who received animal insulin in the past show significantly higher IA binding levels as compared to patients treated exclusively with human recombinant insulin (IA binding level of 0.9 and 0.25 index, respectively, P = 0.005). T1D patients who received animal insulin in the past showed a relative bias towards porcine insulin, as compared to T1D patients who were treated with human recombinant insulin exclusively (P < 0.0001). We conclude that IA binding level and epitope specificity are biased by treatment with animal insulin. This bias remains for over 20 years after animal insulin treatment is terminated.
10 years later: assessing the impact of public health efforts on the collection of family health history.

In 2004, a nationwide survey found that the majority (96.3%) of Americans believed their family health history (FHx) was important for their own health; however, only a third (29.8%) of respondents had ever actively collected this information. Over the past decade, government agencies, advocacy groups, professional societies, and healthcare provider organizations have aimed to improve the collection rates and utilization of FHx. This study assesses the current attitudes, knowledge, and practices of Americans regarding their FHx and whether the interventions over the past 10 years have led to any FHx-related changes. We conducted a nationwide survey of 5,258 respondents using the same measures used in the 2004 survey. Overall, there was little change in Americans knowledge and use of FHx information. While there was a statistically significant increase in respondents who have actively collected their FHx (36.9%), respondents know roughly the same or less about his or her FHx today. Furthermore, only a small fraction (2.6%) had ever collected their FHx using a web-based FHx tool. Several factors were identified which influence whether an individual actively collects his or her FHx. New FHx tools and approaches may be necessarytopromoteclinicallymeaningfulimprovementinFHx collection among patients. 2015 Wiley Periodicals, Inc.
Clock Completion: An Objective Screening Test for Dementia

Objective To develop a simple, readily administered and scored screening test for dementia utilizing the clock-drawing task. Design Retrospective analysis of clock-drawing errors and prospective validations. Setting Hospital-based outpatient geriatric assessment clinic, rehabilitation service, apartment building for older adults, and long-term care facility. Participants Convenience sample of patients attending the geriatric assessment clinic, patients on the rehabilitation service, or residents of the above sites. Measurements Sensitivity and specificity of a clock-scoring system in identifying patients with dementia and the comparison of this system with the Short Blessed Test (SBT) in the diagnosis of dementia and in the prospective validation of the test. Results Of the 10 clock-drawing errors evaluated, placement of digits in a pre-drawn circle had the greatest sensitivity and specificity in distinguishing patients with irreversible dementia from patients with other disorders who did not meet NINCDS-ADRDA criteria for probable dementia. The derived scoring system had a sensitivity of 87% and a specificity of 82%, compared with a sensitivity of 82% and a specificity of 88% for the SBT in identifying dementia. Test-retest reliability for the distinction between demented and non-demented was 82%, with a Kappa of 0.63 for the clock completion, and 82%, with a Kappa of 0.62 for the SBT. Inter-rater reliability for clock completion was 0.90 to 0.93. Conclusion A simple, completely objective scoring system for a clock completion test has been developed which involves only the number of digits placed in the fourth quadrant of a pre-drawn circle. This readily administered test is as effective in screening for dementia as the longer six-item SBT.
A Microcomputer-based Routine for Robust Trend Surface Analysis

An interactive microcomputer-based routine was developed for trend surface analysis. The routine includes robust alternatives, along with the more typical least-squares procedure, and provides graphical as well as statistical output. The robust procedures are suitable for data that do not meet the assumptions implicit in the least-squares procedures, and can also be used for outlier detection. The routine was developed in the DOS environment, which makes it very portable. It allows for interactive data entry and the selective removal of trend surface coefficients. The use of the routine is demonstrated on several data sets.
Backscatter dose perturbation at high atomic number interfaces in megavoltage photon beams.

Most computer algorithms used clinically for photonbeamtreatment planning are unable to predict the effect of electron backscattering on dose distribution from high atomic number materials. It has been observed that there is a significant dose enhancement at such an interface. We define the dose enhancement in terms of backscatter dose factor (BSDF), which depends on the energy of the photonbeam, thickness and width of the inhomogeneity, distance from the interface, and the atomic number of the inhomogeneity. For all energies studied, the dose fall‐off is initially very rapid and disappears beyond a few millimeters upstream from the interface. Empirically derived equations are presented for dose calculation at the interfaces of various media, including bone and soft tissue, for photon energies in the range of Co‐60 gamma rays to 24 MV x rays.
Applications Of Polarized Light In Materials Research

An overview of materials research, utilizing the unique power of polarized light for the optical characterization of materials is presented. For ease of discussion, the article is divided into two parts as characterization of materials (a) in their natural state and (b) under the influence of external stresses.
“Proof” in Pictures: Visual Evidence and Meaning Making in the Ivory-Billed Woodpecker Controversy:

This case study focuses on images in three Science articles on the ivory-billed woodpecker, whose rediscovery was recently heralded. Because the primary piece of evidence is a frustratingly fuzzy four-second video, two groups of authors ultimately disagree on its interpretation and the same still video images that are used to argue for the sighting are used to argue against it. Given that the authors are making taxonomic arguments, images that closely resemble reality are employed. These images, like all images, are coded, and this analysis seeks to unlock these visual codes to reveal how meaning is made at the site of production, the site of the image, and the site of the audience. It also exposes how meaning making at the site of the image fueled the controversy.
Some consequences of estimating parameters for the M/M/1 queue

An important interface between stochastic models and actual systems comes in estimating values for model parameters using ''real world'' data. This interface between models and systems is studied for one of the most elementary stochastic systems, the M/M/1 queue. Estimating arrival rates and service rates results in a notable discrepancy between the state distribution for the model (estimated parameters) and the state distribution for the actual system (known parameters). Also, the expected number of customers in the model is infinite regardless of the (unknown) value of the actual traffic intensity. The truth of this assertion is obvious if one allows estimated traffic intensities to equal or exceed one. However, it is shown that the mean for the model is infinite even if the estimated traffic intensity is restricted to be strictly less than one.
Kinetics of Irreversible Protein Aggregation: Analysis of Extended Lumry−Eyring Models and Implications for Predicting Protein Shelf Life

A general phenomenological kinetic model of irreversible protein aggregation in aqueous solution proceeding via non-native conformations is examined with a view toward the development of techniques to predict in vitro protein shelf life quantitatively. Approximate analytical solutions are derived for interpreting experimental data and agree with explicit numerical simulations over a broad range of physically relevant conditions. Results are presented in terms of the observed kinetics of monomer loss to provide a basis for direct comparison with typical experimental measures of aggregation as well as to provide a basis for quantitative prediction of protein shelf life. Similar to classic Lumry−Eyring models, experimentally observed aggregation kinetics are described as a combination of reversible conformational transitions and the intrinsic kinetics of aggregation via non-native states. However, in contrast to classic models, the extended Lumry−Eyring model developed here includes a detailed description of...
Inflammatory protein profiling of pancreatic cyst fluid using EUS-FNA in tandem with cytokine microarray differentiates between branch duct IPMN and inflammatory cysts.

Background Diagnosis of pancreatic cystic neoplasms remains problematic. We hypothesize that inflammatory mediator proteins in pancreatic cyst fluid can differentiate branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) and pancreatic inflammatory cysts. We aim to 1) detect inflammatory mediator proteins (IMPs) using a multiplexed IMP-targeted microarray in pancreatic cyst fluid obtained during endoscopic ultrasound fine needle aspiration (EUS-FNA) and 2) compare IMP profiles in pancreatic cyst fluid from BD-IPMNs and inflammatory cysts. Pancreatic cyst fluid from ten patients (5 BD-IPMN and 5 inflammatory cysts) was obtained by EUS-FNA and analyzed directly with a multiplexed microarray assay to determine concentrations of 89 IMPs. Statistical analysis was performed using non-parametric methods.
The discriminative stimulus properties of the atypical antipsychotic olanzapine in rats.

Rationale: Analysis of the preclinical behavioral effects of atypical antipsychotic agents will provide a better understanding of how they differ from typical antipsychotics and aid in the development of future atypical antipsychotic drugs. Objectives: The present study was designed to provide information about the discriminative stimulus properties of the atypical antipsychotic olanzapine. Methods: Rats were trained to discriminate the atypical antipsychotic olanzapine (either 0.5 mg/kg OLZ or 0.25 mg/kg OLZ, i.p.) from vehicle in a two- lever drug discrimination procedure. The atypical antipsychotic clozapine fully substituted for olanzapine in both the 0.5-mg/kg OLZ group (99.3% drug lever responding [DLR]) and the 0.25-mg/kg OLZ group (99.9% DLR). The typical antipsychotic chlorpromazine also substituted for olanzapine in both the 0.5-mg/kg OLZ group (87.5% DLR) and in the 0.25-mg/kg OLZ group (98.9% DLR); whereas, haloperidol displayed partial substitution for olanzapine in the 0.5-mg/kg OLZ group (56.1% DLR) and in the 0.25-mg/kg OLZ group (76.4% DLR). The 5.0-mg/kg dose of thioridazine produced olanzapine-appropriate responding in the 0.5-mg/kg OLZ group (99.6% DLR), but only partial substitution was seen with the 0.25-mg/kg OLZ training dose (64.0% DLR). The atypical antipsychotics raclopride (53.9% DLR) and risperidone (60.1% DLR) displayed only partial substitution in the 0.5-mg/kg OLZ group. Both the muscarinic cholinergic antagonist scopolamine (90.0% DLR) and the 5-HT2A/2C serotonergic antagonist ritanserin (86.0% DLR) fully substituted for olanzapine in the 0.5-mg/kg OLZ group. Conclusions: In contrast to previous discrimination studies with clozapine-trained rats, the typical antipsychotic agents chlorpromazine and thioridazine and the serotonin antagonist ritanserin substituted for olanzapine. These results demonstrate that there are differences in the mechanisms underlying the discriminative stimulus properties of clozapine and olanzapine. Specifically, olanzapine’s discriminative stimulus properties appear to be meditated in part by both cholinergic and serotonergic mechanisms.
ENVELOP Antenna: A Class of Very Low Profile UWB Directive Antennas for Radar and Communication Diversity Applications

In this paper we present the concept of new electrically narrow very low profile (ENVELOP) directive antennas for low frequency radars and diversity communication applications. The basic structure consists of a short TEM horn combined with an inductive loop antenna. The proposed antenna height is 0.063 where is the minimum operating wavelength and has good matching and radiation characteristics over more than an octave. It is based on the principle of crossed electric and magnetic dipoles with a TEM horn as the electric dipole and a sheet loop as the magnetic dipole. However, unlike the standard structures, the proposed structure is designed to enhance the radiation in a direction perpendicular to the TEM horn axis. This limits the maximum pattern bandwidth to about one octave but allows the antenna height along the direction of maximum radiation to be very small which is very important for airborne radars and in low frequency military communications that require conformal antennas. Three different variations of the basic structure are also presented which offer improved pattern characteristics and/or pattern and polarization diversity. Two antennas were fabricated and measured. The measured results agreed well with the simulation results and both showed that the antenna can operate over 1-2 GHz with consistent radiation pattern, low dispersion and input impedance matching performance.
Subcarrier multiplexing with dispersion reduction

A novel dispersion-reduction technique using subcarrier multiplexing and optical prefiltering is described. Measured results from a data link demonstrate that a pair of independent 2.5 Gbit/s data channels can be transmitted over /spl ges/100 km of ordinary single-mode fibre-optic cable at 1550 nm with negligible dispersion.
Pulsed nanosecond laser ablation of gold in deionized water and aqueous chitosan solution

Abstract Gold nanoparticles (AuNP) are produced using a Nd:YAG laser in deionized water and aqueous chitosan solutions via 1064 nm nanosecond laser ablation and subsequent 532 nm nanosecond laser irradiation. AuNP produced in deionized water under single laser ablation and subsequent irradiation for 20–40 min time exhibited coalescence and the formation of nano-chains, with average particle diameters ranging from 34.3 to 18.8 nm and 37.2 to 27.3 nm, respectively. The introduction of chitosan as a bio-compatible surfactant yielded lesser average diameters and tighter size-distributions with a narrow range of UV-Vis absorption spectra values (514–525 nm). For instance, at 20 and 40 min, the single laser ablation and subsequent irradiation produced the average diameters of 12.3 and 5.3 nm and 5.7 and 4.3 nm, respectively. Increases in ablation and irradiation time decrease AuNP size. As time increased, the size-distributions of the AuNP produced in chitosan solution narrowed and the particle size monotonically decreased. Chitosan functionalized the AuNP surface, promoting hydrophobicity, preventing electrostatic attraction of the Au nanoparticles, thus inhibiting coalescence and agglomeration. UV-Vis absorption spectra, TEM and HR-TEM images are used to verify AuNP size distributions. X-ray diffraction measurements of AuNP produced in chitosan confirmed crystallite size and the absence of gold-oxide despite the high-energy laser ablation. Furthermore, samples prepared in chitosan solution showed minimal agglomeration after 24 months.
Conditional gauge theorem for non-local Feynman-Kac transforms

Feynman-Kac transforms driven by discontinuous additive functionals are studied in this paper for a large class of Markov processes. General gauge and conditional gauge theorems are established for such transforms. Furthermore, the L 2 -infinitesimal generator of the Schrodinger semigroup given by a non-local Feynman-Kac transform is determined in terms of its associated bilinear form.
Downstaging of advanced rectal cancer following combined preoperative chemotherapy and high dose radiation

Abstract Purpose: To assess the potential downstaging of advanced rectal cancer with combined preoperative chemoradiation. Methods and Materials: Thirty-one patients with fixed rectal cancers (stage ≥ cT3) were treated with concomitant preoperative chemotherapy and high-dose radiation in an effort to improve resectability. Three (10%) patients had partially fixed low rectal cancers, 24 (77%) patients had fixed tumors, and 4 (13%) had advanced fixation with pelvic sidewall invasion. Radiation was delivered to the whole pelvis using shaped anterior and posterior and lateral fields to 45 Gy followed by a boost to the tumor. Median total radiation dose was 55.8 Gy. Chemotherapy consisted of low dose continuous infusion of 5-FU (200–300 Mg/M 2 /day) for the duration of radiation treatment. All 31 patients underwent surgical resection of tumor 6–8 weeks following treatment. Median follow up is 24 months (range 9–60). Results: Twenty-three (74%) of the tumors were clinically downstaged following preoperative treatment. Of 24 fixed cancers, 11 (46%) became mobile, 6 (25%) became partially fixed, and 7 remained fixed. Of the four tumors with advanced fixation, two (50%) became mobile and two (50%) no longer had tumor extension to the pelvic sidewall. Two of the three initially partially fixed cancers became mobile and one remained partially fixed. Following surgery, the pathologic postradiation T-stages were as follows: TO: 10%, TI: 0%, T2: 32%, T3: 42%, and T4: 16%. Seven patients (230/v) were also node-positive (T0–2: 2, T3: 4, T4: 1), and two patients (6%) had liver metastases at surgery. Preoperative chemoradiation was well tolerated. There was no significant hematological toxicity. Acute grade 3 gastrointestinal toxicity was seen in six patients requiring a short hospitalization for dehydration and/or abdominal discomfort. No patient developed grade 4 toxicity. Five patients (16%) developed local recurrence of disease (T0–2: 0/13, T3: 1/13, and T4: 4/5). The actuarial 3-year survival is 68%. Conclusions: Concomitant preoperative chemoradiation using low dose continuous infusional 5-FU for advanced rectal cancer is relatively safe with acceptable morbidity. This approach is associated with considerable clinical and pathologic downstaging of cancer. Tumor resectability is improved with potential for improved local control of disease and survival.
The Mechanical Environment of Bone Marrow: A Review

Bone marrow is a viscous tissue that resides in the confines of bones and houses the vitally important pluripotent stem cells. Due to its confinement by bones, the marrow has a unique mechanical environment which has been shown to be affected from external factors, such as physiological activity and disuse. The mechanical environment of bone marrow can be defined by determining hydrostatic pressure, fluid flow induced shear stress, and viscosity. The hydrostatic pressure values of bone marrow reported in the literature vary in the range of 10.7–120 mmHg for mammals, which is generally accepted to be around one fourth of the systemic blood pressure. Viscosity values of bone marrow have been reported to be between 37.5 and 400 cP for mammals, which is dependent on the marrow composition and temperature. Marrow’s mechanical and compositional properties have been implicated to be changing during common bone diseases, aging or disuse. In vitro experiments have demonstrated that the resident mesenchymal stem and progenitor cells in adult marrow are responsive to hydrostatic pressure, fluid shear or to local compositional factors such as medium viscosity. Therefore, the changes in the mechanical and compositional microenvironment of marrow may affect the fate of resident stem cells in vivo as well, which in turn may alter the homeostasis of bone. The aim of this review is to highlight the marrow tissue within the context of its mechanical environment during normal physiology and underline perturbations during disease.
Identification of caffeic acid derivatives in Actea racemosa (Cimicifuga racemosa, black cohosh) by liquid chromatography/tandem mass spectrometry

Caffeic acid derivatives occurring in black cohosh [Cimicifuga racemosa (L.) Nutt., Actaea racemosa (Ranunculaceae)], some of which may have pharmacological activity, were analyzed using high-performance liquid chromatography (HPLC) electrospray ionization tandem mass spectrometry (ESI-MS/MS) with the aim of developing a methodology for their rapid identification in a complex plant matrix. Based on these studies, structurally characteristic product ions and neutral molecule losses were identified, which were then used during LC/MS/MS with product ion scanning, precursor scanning and constant neutral loss scanning to detect caffeic acid derivatives in a crude extract of black cohosh. Several caffeic acid derivatives were detected, and the identification of six of them were confirmed by comparison with authentic standards including caffeic acid, ferulic acid, isoferulic acid, fukinolic acid, cimicifugic acid A, and cimicifugic acid B. Four other compounds were detected that appeared to be caffeic acid derivatives based on LC/MS/MS retention times, molecular weights, and fragmentation patterns during MS/MS. Since standards were unavailable for these four compounds, they were tentatively identified using LC/MS/MS as cimicifugic acid E, cimicifugic acid F, dehydrocimicifugic acid A, and dehydrocimicifugic acid B. Dehydrocimicifugic acid A and dehydrocimicifugic acid B have not been reported previously to be constituents of black cohosh.
β-Subunits of the human liver Gs/Gi signal-transducing proteins and those of bovine retinal rod cell transducin are identical

The complete cDNA encoding the β-subunit of the human liver signal transducing proteins Gs/Gi (βG) has been cloned from a λgtll library using an oligonucleotide as a screening agent. The cDNA has 3088 nucleotides and an 11 nucleotide poly(A) tail, of which 280 nucleotides constitute the 5′-untranslated region, 1023 form the open reading frame (ORF) and its stop codon, and 1785 are the 3′-untranslated region with two AATAAA cleavage and polyadenylation signals separated by 1467 nucleotides. The ORF codes for a 340 amino acid polypeptide that is identical to that encoded by bovine retinal rod cell cDNA of the β-subunit of transducin. Yet, it does so by using 87 different codons. Curiously, the 280 nucleotide 5′ leader sequence obtained starts with an ATG that is part of another ORF encoding a putative peptide X of 75 amino acids (nucleotide 280 to 55). This work proves for the first time that the β-subunits of all signal-transducing G-proteins, including transducin, are the same.
Avian monocytic leukemia cells release fibroblast growth factor: Implications to associated myelofibrosis

Abstract The marrow of chicks with leukemia induced by avian ‘myeloblastosis’ virus (AMV) exhibited a 5–10-fold increase in the number of fibroblast colony-forming cells (CFU-F). The increased CFU-F correlated with a mild fibrosis which can be seen in the marrow of these animals. Fibroblast proliferation likely was not simply due to the presence of leukemic cells because addition of formaldehyde-fixed peripheral leukemic cells failed to initiate CFU-F growth. Conditioned medium (CM) from day-4 cultures of peripheral leukemic cells was markedly stimulatory to CFU-F growth. The stimulatory activity was not due to virus released from the leukemic cells as, (1) removal of virus by pelleting had no effect on the CM activity and (2) direct inoculation of CFU-F cultures with virus failed to stimulate CFU-F growth. Normal avian marrow macrophage monolayers also released high levels of a fibroblast growth factor and both the emacrophage-derived and leukemic cell-derived factors were heat-labile (65°, 30 min).
Genetic analysis of the N-terminal end of the glucocorticoid receptor hormone binding domain

Four site-directed missense mutations were constructed at the N-terminal end of the mouse glucocorticoid receptor (GR) hormone binding domain. This small subdomain is highly conserved among the steroid hormone receptors and is within a larger subregion believed to be important for hormone binding, transcriptional activation, and hsp90 binding. The ability of mutant and wild type GR to activate a reporter gene in response to various concentrations of dexamethasone was examined in transiently transfected COS-7 cells. Mutant GR species V544G (valine-544 changes to glycine) and V549G activated the reporter gene to approximately the same extent as wild type GR, but required approx. 7 and 23 times greater hormone concentrations, respectively. In contrast, double mutant LL541/2GG (leucines changed to glycines) could not activate transcription even at 10 microM dexamethasone or deacylcortivazol, while E543A (glutamic acid to alanine) was functionally indistinguishable from wild type GR. GR mutants LL541/2GG and V549G had reduced abilities to bind covalently to affinity label dexamethasone 21-mesylate. The partially and fully functional mutant GR species had no deficiency in transcriptional transactivation activity in the presence of saturating concentrations of agonist.
Neural spiking dynamics in asynchronous digital circuits

We implement a digital neuron in silicon using delay-insensitive asynchronous circuits. Our design numerically solves the Izhikevich equations with a fixed-point number representation, resulting in a compact and energy-efficient neuron with a variety of dynamical characteristics. A digital implementation results in stable, reliable and highly programmable circuits, while an asynchronous design style leads to energy-efficient clockless neurons and their networks that mimic the event-driven nature of biological nervous systems. In 65 nm CMOS technology at 1 V operating voltage and a 16-bit word length, our neuron can update its state 11,600 times per millisecond while consuming 0.5 nJ per update. The design occupies 29,500 μm2 and can be used to construct dense neuromorphic systems. Our neuron exhibits the full repertoire of spiking features seen in biological neurons, resulting in a range of computational properties that can be used in artificial systems running neural-inspired algorithms, in neural prosthetic devices, and in accelerated brain simulations.
Modeling the Process of Adoption of Telecommuting: Comprehensive Framework:

A comprehensive model of the telecommuting adoption process, incorporating employer and employee perspectives, is developed. A probabilistic modeling approach is taken. The employer decision to offer a telecommuting program is modeled as a function of motivations and constraints and of the perceived impacts of telecommuting on the organization's productivity and costs. The employee decision to adopt telecommuting is modeled as a function of motivations and constraints as well as of the impact of the program on lifestyle quality, work-related costs, and income. The results indicate that telecommuting has a significant potential to increase productivity and improve lifestyle quality, if the right program is designed for the right employee. The potential of telecommuting to reduce organization and employee work-related costs is perceived to be limited. An overall negative perception about the potential impact on productivity and lifestyle quality of telework center-based telecommuting programs is identified,...
Macroethical systems and sustainability science

The Industrial Revolution and associated economic, demographic, technological and cultural changes have resulted in what many scientists are beginning to refer to as “the Anthropocene” – roughly translated, the Age of Humans. One response to this development is the nascent field of “sustainability science,” a multidisciplinary and systemic attempt to perceive and understand this new era. In doing so, however, methodologies and intellectual frameworks must be developed which extend beyond existing, dominantly reductionist, approaches, and are intended to address emergent characteristics of complex systems that integrate cultural and social systems, the engineered and built environment and natural systems. In the area of ethics, this requires developing a capability for “macroethics,” or ethical systems and processes capable of addressing issues arising from the emergent behavior of the complicated systems that characterize the Anthropocene.
clopidogrel: A pharmacogenomic perspective on its Use in coronary Artery Disease

The thienopyridine antiplatelet agent clopidogrel is an effective drug for the prevention of vascular events. However, data has accumulated over time to suggest it is prone to significant interpatient variability. While there are several factors that contribute to this, one of the most important is variability in forming the active metabolite necessary for clopidogrel function. Several enzymes are involved in formation of this metabolite, and two, CYP2C19 and P-glycoprotein, appear to have alleles that both occur frequently in the population and have a clinically significant impact. Patients carrying these alleles can be identified, but it remains to be determined if this information is necessary or sufficient for risk stratification. Furthermore, if patients with high-risk alleles are identified, it is unclear how treatment should be adjusted.
Autonomous rendezvous, docking, and landing system using cruise missile technologies

General Dynamics has been developing an Autonomous Rendezvous Docking and Landing (ARD&L) system that utilizes cruise missile technologies. In November 1990 the Autonomous Rendezvous and Docking (AR&D) system was first demonstrated for members of NASA's Strategic Avionics Technology Working Group (SATWG). This simulation utilized prototype hardware from the Cruise Missile and Advanced Centaur Avionics systems. The objective was to show that all the accuracy, reliability, and operational requirements established for a spacecraft to dock with Space Station Freedom could be met by the proposed system. Rapid prototyping techniques were used to evaluate the proposed system in a real time, hardware in the loop simulation of the rendezvous and docking reference mission. The simulation is currently being upgraded to test an Autonomous Approach and Landing (AA&L) system. Both systems use inertial guidance and control systems supplemented by the Global Positioning System (GPS) and an Image Processing System (IPS), for target recognition and tracking. The IPS includes a general purpose multiprocessor computer and a selected suite of sensors that will provide the required relative position and orientation data. Graphic displays can provide the astronaut/operator with realtime guidance and navigation data with enhanced video or sensor imagery.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Activation of a Nuclear DNA-binding Protein Recognized by a Transcriptional Element, bcn-1, from the Laminin B2 Chain Gene Promoter

Treatment of mesangial cells with either phorbol 12-myristate 13-acetate (PMA) or interleukin-1β induces an increase in laminin B2 chain mRNA levels. In other systems, activation of gene expression by these agents is transcriptionally mediated. To identify transcription factors that control expression of laminin B2 chain gene, we employed a strategy consisting of a computer-based analysis of murine and human gene promoter sequences and gel shift assays. Although overall the laminin B2 chain promoters from the two species have low sequence similarity, the mouse promoter contained sequences that were also contained in one motif, 5′-CCCCGCCCACCTCGCGCGC-3′, designated bcn-1, from the human promoter. Treatment of mesangial cells with either PMA or interleukin-1β induced a transient increase in nuclear DNA binding activity, designated BCN-1, recognized the bcn-1 motif in a gel shift assay. A single nucleotide replacement in the bcn-1 motif abolished DNA binding, indicating that bcn-1·BCN-1 complex formation is highly specific. In transient transfections, the ability of PMA to induce the laminin B2 chain promoter was abolished by mutating the bcn-1 motif. These results suggest that the bcn-1 element and its cognate inducible BCN-1 protein regulate laminin B2 chain gene transcription.
EM motion segmentation based on MRF model

In our earlier work, a Two-Pass motion estimation Algorithm (TPA) was developed to estimate a motion field for two adjacent frames in an image sequence where contextural constraints are handeled by several Markov Random Fields (MRFs) and the most A Posteriori (MAP) configuration is taken to be the resulting motion field. Currently in the disciplines of digital library and video processing of utmost interest are the extraction and representation of visual objects. Instead of estimating motion field, in this paper we focus on segmenting out visual objects based on spatial and temporal properties present in two contiguous frames under the MRF-MAP-MFT scheme. To achieve object segmentation, within the framework of EM optimization a novel concept "motion boundary field" is introduced which can turn off interactions between different object regions and in the mean time remove spurious objerct boundaries. Furthermore, in light of the generally smooth and slow velocities in-between two contiguous frames, we found that in the process of calculating matching blocks, assigning different weights to different locations can result in better object segmentation.
Experimental signatures of composite quarks and leptons

Certain types of composite models of quarks and leptons are expected to lead to low-lying excited states of quarks and leptons, possibly of masses as low as 20 GeV. Production cross sections of such excited states in ${e}^{+}{e}^{\ensuremath{-}}$ annihilation and in inelastic lepton-nucleon scattering are calculated. Questions of observability of excited but confined quarks are discussed. It appears that excited quarks and leptons can be best seen in annihilation experiments at c.m.-system energies close to the mass of the ${Z}^{0}$ boson.
Should second trimester ultrasound be routine for all pregnancies

Ultrasound use has become ubiquitous in pregnancy. We review the evidence regarding the benefits of routine ultrasound use during pregnancy. Routine ultrasound use before 24 weeks improves detection of undiagnosed twins, reduces postdates inductions, and allows detection of fetal anomalies before birth. Wide variations exist in the sensitivity of ultrasound in detecting fetal anomalies. These may be related to equipment, training, and maternal characteristics, such as obesity. Standards have been developed for the performance of routine fetal ultrasonography in the second trimester. The benefits of routine first trimester ultrasound in the diagnosis of structural fetal anomalies or of routine ultrasonography after 24 weeks are not proven. As ultrasound technology improves and obstetrical care changes, new uses of routine ultrasonography may emerge.
UHRF1 binds G9a and participates in p21 transcriptional regulation in mammalian cells

UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is a multi-domain protein associated with cellular proliferation and epigenetic regulation. The UHRF1 binds to methylated CpG dinucleotides and recruits transcriptional repressors DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1) through its distinct domains. However, the molecular basis of UHRF1-mediated transcriptional regulation via chromatin modifications is yet to be fully understood. Here we show that UHRF1 binds histone lysine methyltransferase G9a, and both are co-localized in the nucleus in a cell-cycle-dependent manner. Concurrent with the cell-cycle progression, gradual deposition of UHRF1 and G9a was observed, which mirrored H3K9me2 accumulation on chromatin. Murine Uhrf1-null embryonic stem (ES) cells displayed a reduced amount of G9a and H3K9me2 on chromatin. UHRF1 recruited and cooperated with G9a to inhibit the p21 promoter activity, which correlated with the elevated p21 protein level in both human UHRF1 siRNA-transfected HeLa cells and murine Uhrf1-null ES cells. Furthermore, endogenous p21 promoter remained bound to UHRF1, G9a, DNMT1 and HDAC1, and knockdown of UHRF1 impaired the association of all three chromatin modifiers with the promoter. Thus, our results suggest that UHRF1 may serve as a focal point of transcriptional regulation mediated by G9a and other chromatin modification enzymes.
Connecting rare DNA conformations and surface dynamics using single-molecule resonance energy transfer.

A mechanistic understanding of single-stranded DNA (ssDNA) behavior in the near-surface environment is critical to advancing DNA-directed self-assembled nanomaterials. A new approach is described that uses total internal reflection fluorescence microscopy to measure resonance energy transfer at the single-molecule level, providing a mechanistic understanding of the connection between molecular conformation and interfacial dynamics near amine-modified surfaces. Large numbers (>105) of ssDNA trajectories were observed, permitting dynamic correlation of molecular conformation with desorption and surface mobility. On the basis of dynamic behavior, molecules could be designated as members of the more common coiled population or a rare, weakly bound conformation. Molecules in the coiled state generally exhibited slow diffusion and conformational fluctuations that decreased with increasing average end-to-end distance. Lattice simulations of adsorbed self-avoiding polymers successfully predicted these trends. In ...
Radial glial cells in the postnatal olfactory tubercle of hamsters.

Abstract A discrete population of radial glial cells whose fibers extend into the lateral part of the olfactory tubercle can be labeled with horseradish peroxidase (HRP) during the first week of postnatal life. Radial glial processes are also seen in electron micrographs of this region in young animals and appear to form guides for longitudinally-oriented bundles of axons.
Neutron chopper phasing for a quasi-periodic pulsed neutron source

Abstract A control system has been developed which phases a neutron chopper to a pulsed neutron source which has a randomly varying pulse repetition rate. The chopper is driven by an induction motor and stabilized by a high precision proportional derivative (PD) feedback circuit. A control theory is developed which relates the system response bandwidth to motor and driver characteristics and rotor moment of inertia. Experiments with choppers operating in a phase-locked loop with the Los Alamos pulsed neutron source, the WNR/PSR Facility, show that (1) the control system can hold the phase of the chopper within the band in which the pulsed source will accept trigger pulses; and (2) when the chopper is used to trigger the pulsed source within this hand, the phase between source and chopper can be controlled to less than 1 μs.
The effect of oxygen on void stability in nickel and austenitic steel

Surface energy values lower than those determined experimentally are often utilized in theories of void nucleation and growth in metals. Utilization of established surface energy values generally predicts no swelling in the absence of helium. However, swelling occurs in many metals even in the absence of helium. Surface active impurities, such as oxygen, can readily account for this discrepancy by reducing the surface energy of metals. This investigation shows that very low concentrations of oxygen in nickel and austenitic stainless steel can achieve the necessary decrease in surface energy. A model has been developed to calculate the requisite quantity of oxygen in solution to stabilize voids. The criterion for void stability is that the void be the most energetically stable vacancy cluster in the metal. Knowing the fraction of oxygen which chemisorbs and the surface coverage required permits the determination of initial oxygen concentration needed to promote void stability. Calculations have been performed for austenitic stainless steel and nickel. The model has been tested by irradiating nickel with 14-MeV Ni ions at 500 °C. Oxygen was preinjected into one sample to a concentration of 75 appm. The irradiation reached a fluence of 3 × 1020 Ni-ion/m2 (28 dpa at the damage peak). The irradiated foils were examined in cross section in the electron microscope.
Binding of SV40 a protein to the BK virus origin of DNA replication

Abstract The SV40 A protein (T antigen) binds to the putative origin of replication of the related BK virus (BKV). Protection studies with dimethyl sulfate identify multiple pentanucleotide contact sites in three distinct binding regions. In addition to the consensus family of recognition sequences, 5′-(G > T)(A > G)GGC-3′, previously identified in the origin of SV40, BKV contains a contact 5′-AAGGC-3′ site. As in the case of SV40, each binding region contains recognition sequences in different arrangements. The high affinity region I contains two sites arranged as direct repetitions covering a span of 17 base pairs (bp). In the intermediate affinity region II, four pentanucleotides are oriented as inverted repetitions with a span of 23 bp. Low affinity region III has a single contact site that can direct binding of the A protein. These different arrangements of DNA contact sites determine different patterns of protein binding and DNase protection in the three regions. The findings support a model of A protein binding to DNA previously proposed for the SV40 origin and establish a basis for future studies on regulatory phenomena at the BKV origin.
An exact solution to a problem of nonlinear electrotonus

Abstract An exact solution is presented for the problem of electrotonus along a dendrite whose passive membrane currents are governed by in-file permeation mechanisms. It is shown that, within 100 mV of the resting potential, electrotonus will not differ appreciably from that predicted by a linear approximation.
Rapid Method for Obtaining Anti-Rh Serum from Guinea Pigs.

SummaryA modified rapid method for the preparation of diagnostically suitable anti-Rh serum obtained from guinea pigs is described.
Sexuality in an azygosporic strain of mucor hiemalis. I. Breakdown of the azygosporic component.

Single-vegetative-sporangiospore isolations were carried out on a number of azygosporic cultures of Mucor hiemalis. The resulting cultures were predominantly azygosporic (+) and normal-appearing (+) while normal-appearing (-) and azygosporic (-) types were somewhat more rare. While the breakdown of the azygosporic condition is not entirely predictable, it is more evident in older cultures and cultures which have been sub-cultured. The azygosporic cultures are thought to be bisexual but not sexually heterokaryotic. Sexual heterokaryosis may occur, if briefly, once the breakdown process has been initiated. The production of azygospores is thought to be an expression of the bisexual nature of the azygosporic mycelium. DURING THE COURSE of a study on zygospore
Buoyancy Arrest and Bottom Ekman Transport. Part II: Oscillating Flow

Abstract The effects of a sloping bottom and stratification on a turbulent bottom boundary layer are investigated for cases where the interior flow oscillates monochromatically with frequency ω. At higher frequencies, or small slope Burger numbers s = αN/f (where α is the bottom slope, N is the interior buoyancy frequency, and f is the Coriolis parameter), the bottom boundary layer is well mixed and the bottom stress is nearly what it would be over a flat bottom. For lower frequencies, or larger slope Burger number, the bottom boundary layer consists of a thick, weakly stratified outer layer and a thinner, more strongly stratified inner layer. Approximate expressions are derived for the different boundary layer thicknesses as functions of s and σ = ω/f. Further, buoyancy arrest causes the amplitude of the fluctuating bottom stress to decrease with decreasing σ (the s dependence, although important, is more complicated). For typical oceanic parameters, arrest is unimportant for fluctuation periods shorter ...
Acute regulation of hematocrit and acid-base balance in chicken embryos in response to severe intrinsic hypercapnic hypoxia

The regulation of blood acid-base balance and hematology in day 15 chicken embryos in response to partial water submersion (with egg's air cell in air) and complete submersion producing severe intrinsic hypercapnic hypoxia and recovery in air was studied. The acid-base disturbance during submersion was characterized by initial rapid respiratory changes and then superseded by metabolic processes, resulting in a large progressive hysteresis. Throughout submersion and recovery, blood lactate concentration changed swiftly along with the changes in bicarbonate concentration ([HCO3(-)]), indicating that anaerobic glycolysis determined overall acid-base disturbances. Both partial and complete submersion produced large, rapid increases in hematocrit through proportional increases in mean corpuscular volume and red blood cell concentration. Death ensued once the internal pool of O2 was exhausted and/or the acid-base disturbance became too severe for survival (i.e., [HCO3(-)]a<∼10mmolL(-1)). However, embryos recovered from acid-base and hematological disturbances within 120min recovery in air after short bouts of complete (20min) or partial (60min) submersion, suggesting that shorter severe intrinsic hypercapnic hypoxia does not compromise viability of embryos.
Stark mapping of H 2 Rydberg states in the strong-field regime with dynamical resolution

We have acquired spectra of high Rydberg states of molecular hydrogen in a static external field, in the energy region from below the energy at which field ionization becomes classically possible (${\mathit{E}}_{\mathit{c}}$) to well above this energy. Simultaneous spectra of ionization and dissociation were acquired, thereby allowing direct information on the excited-state decay dynamics to be obtained. We have found that states with energies below ${\mathit{E}}_{\mathit{c}}$ undergo field-induced predissociation, while states with energies well above ${\mathit{E}}_{\mathit{c}}$ decay predominantly by field ionization. Field ionization and dissociation compete effectively as decay channels for states with energies in a restricted region just above ${\mathit{E}}_{\mathit{c}}$. Comparison of our ionization spectra to the results of a single-channel quantum-defect theory Stark calculation shows quantitative agreement except near curve crossings, indicating that inclusion of different core rotational state channels will be required to properly account for coupling between the Stark states. Several states in the spectra undergo pronounced changes in their dynamical properties over a narrow range of field values, which we interpret as being due to interference cancellation of the ionization rates for these states.