cssi/SciSciGPT-SciSciNet huggingface dataset:
Genetics and Autoimmunity: Non-MHC Genes

Publisher Summary This chapter focuses on the contribution of non-major histocompatiblity complex (MHC) genes to the genetic susceptibility to autoimmune diseases. Several non-MHC immune regulatory genes have been shown to be susceptibility genes for autoimmunity. As expected, these genes are not specific for one autoimmune disease but predispose to several autoimmune conditions. However, some variability does exist with certain immune regulatory genes showing a much stronger association with some autoimmune conditions than with others. For example, the (cytotoxic T-lymphocyte antigen-4) CTLA-4 gene shows the strongest association with Graves' disease and a much weaker association with Hashimoto's disease and T1D. Furthermore, whole genome screening is a powerful genetic tool with which to identify loci or genetic regions that might be linked with disease. When a locus, which is linked with disease, is identified, the region can be fine mapped and the gene identified. This strategy has been used successfully in a number of complex diseases, most notably in the mapping and identification of NOD2 as a susceptibility gene for Crohn's disease.
Modeling Self-Organization in the Visual Cortex*

Publisher Summary This chapter talks about how the self-organizing map (SOM) architecture was originally motivated by the topological maps and the self-organization of sensory pathways in the brain. The standard SOM algorithm, where a global supervisor finds the maximally responding unit and determines the weight-change neighborhood, is a computationally powerful abstraction of the actual biological mechanisms. Such an abstraction has turned out extremely useful in many real-world tasks from visualization and data mining to robot control and optimization. To gain insight into biological knowledge organization and development, the self-organizing map architecture is extended with anatomical receptive fields, lateral connections, Hebbian adaptation, and spiking neurons. The resulting RF-SLISSOM model shows how the observed receptive fields, columnar organization, and lateral connectivity in the visual cortex can arise through input-driven self-organization, and how such plasticity can account for partial recovery following retinal and cortical lesions. The self-organized network forms a redundancy-reduced sparse coding of the input that allows it to process massive amounts of information efficiently, and explains how various low-level visual phenomena such as tilt aftereffects, and segmentation and binding can emerge. Such models allow understanding biological processes at a very detailed computational level, and are likely to play a major role in cognitive neuroscience in the future.
HERD IMMUNITY: BASIC CONCEPT AND RELEVANCE TO PUBLIC HEALTH IMMUNIZATION PRACTICES

Specific immunization has long been a basic tool in medical practice and in local, state, national and international public health. However, the protection afforded by such immunization has been largely limited to the persons immunized because: 1) the usual sources of infection are extra-human (tetanus, yellow fever); 2) spread is primarily by indirect means (typhoid); or 3) those immunized may remain at least partially susceptible to infection and, hence, continue as potential links in the future spread of agents transmitted by contact (diphtheria, pertussis, Salk-type inactivated polio vaccine). An important exception has been vaccination against smallpox which does induce solid though temporary resistance to infection. Presumably as the result of systematic vaccination, endemic smallpox has disappeared from large areas
Innervation and regeneration in orbitally transplanted limbs of Amblystoma larvae

There is a widespread belief that innervation is an indispensible requirement for regeneration in salamander limbs. Several independent investigations have indicated that this view is too rigid. In this laboratory it was observed that regeneration proceeds in orbitally transplanted limbs, but the signs of innervation are few when the tissues are stained with ordinary histological procedures. The present study was conducted to find out if orbitally transplanted limbs do, in fact, possess nerve fibers and if their presence is, indeed, required for regeneration to proceed. Forelimbs of Amblystoma larvae were transplanted to the orbit. In one series, transplants were amputated two weeks after transplantation. Amputated segments were stained with protargol and revealed very few signs of innervation. Nevertheless, regeneration proceeded and reached a typical outcome within the usual time required for completion of the process normally. Full-term transplant regenerates exhibited innervation at levels of about one-third of normal values. In another series of experiments, limbs were subjected to distal amputation either before or shortly after transplantation. Regeneration proceeded normally in these experiments providing that the transplant was rapidly vascularized. When vascularization was delayed or failed, regeneration was retarded or did not occur at all. These findings, taken in light of those of other works, suggest that the function of nerves under ordinary conditions may be assumed by other tissues under circumstances produced by transplantation. This in turn suggests that nerves influence regeneration in a generalized manner and that the specificity ordinarily associated with them may be quantitative rather than qualitative in nature.
Fluorescence and Rotational Dynamics of Dityrosine

We have examined the lifetimes and rotational correlation times of dityrosine emission by time-correlated single-photon counting. We first noticed dityrosine fluorescence in samples of tyrosine and tyrosine dipeptides by its characteristic red-shifted emission at 400 to 430 nm. The longer rotational correlation time relative to tyrosine proved that this fluorescence emanated from a distinct species. Comparison with the fluorescence properties of synthesized dityrosine established the identity of the emitting species. Fluorescence intensity decays of dityrosine are generally characterized by two decay components, one with a lifetime in the range of 150 to 800 ps and another between 2.5 and 4.5 ns. We found no evidence for an excited-state reaction, since a rising phase (negative-amplitude component) was not observed. In the pH range from 4 to 10, two ground-state species exist in equilibrium with pKa ≈ 7. Both species exhibit two fluorescence decays. The average fluorescence lifetime increases gradually with pH over the pH range from 4 to 10 and decreases at pH 2. Anisotropy decays were measured for dityrosine and the alanine–dityrosine–alanine and leucine–dityrosine–leucine dipeptides. The rotational correlation times of dityrosine and dityrosine dipeptides increase linearly with van der Waals volumes. The slope indicates a stronger solute–solvent interaction than predicted with “stick” boundary conditions. It is suggested that these interactions result from the presence of two zwitterionic pairs.
Lexical acceleration coincides with the onset of combinatorial speech

Five children whose ages at the beginning of the study ranged from 12 to 17 months were observed weekly for 8-10 months. For each subject the cumulative numbers of both new words and new word- combinations were plotted as a function of week of observation. An exponential function was fitted to the lexical curves, and lexical acceleration was defined as an upward deviation of the observed curves from the fitted curves. It was found that lexical accelerations occurred at the time the subjects began to produce word- combinations. It is suggested that combinatorial speech, requiring greater specificity of expression (than holophrastic speech), motivates the learning of new words. At the same time, the sensitivity to sentential speech facilitates the mapping of word meanings.
An Investigation of Certain Factors Relating to the Nature of Children with Functional Defects of Articulation

THIS STUDY was concerned with an effort to gain a better under standing of children with functional articul?tory defects of speech by an investigation of (1) personal adjustment and social behavior, (2) school progress, (3) school attendance, (4) health, (5) intelligence and (6) leisure-time interests and activities. Inclusion of the foregoing factors in the study was motivated by the following tentative observations: First, there is conflicting evidence in the current literature regarding social adjustment of such children; second, there is a possibility of invalidity of previous findings regard ing mental abilities of these children in cases of scores derived from instruments possessing a prominent verbal factor; third, there is incon clusive evidence from previous investigations regarding the health of speech defectives; fourth, there is apparently no objective evidence regarding the school attendance and leisure-time interests and activ ities of such children, and fifth, all six factors are pertinent to a study of the nature of the speech defective child. Representative of inquiries into the nature of the social adjustment behavior of speech defectives are the investigations reported by Van Riper (9), Berry and Eisenson (2), Reid (6), McAllister (5) and Beckey (1). That the speech defective may present a distinct person ality portrait is inferred from descriptions of such individuals offered by most authors of textbooks in speech correction. However, certain controlled studies of elementary school children tend to cast some doubt on the assumption that the speech defective differs significantly from the normal speaker in emotional and social adjustment. Reid and McAllister, using personality inventories with elementary school children, found no significant difference between personal and social adjustment scores of speech defectives and those of normal speakers with whom they were compared. Likewise, Beckey, employing a case history approach, compared fifty speech defectives with controls and failed to find any significant difference between the groups in frequency of behavior problems.
Live mass, water content, nitrogen and mineral levels in some insects from south-central lower michigan

Abstract 1. 1. Live and dry mass, water content, nitrogen, sodium, potassium, magnesium, calcium and total iron concentrations are reported (or are available from the authors or the Faculty/Staff Collection of The University of Michigan-Flint Library) for members of 16 orders (360 species) of mostly adult, flying insects from south-central lower Michigan. 2. 2. Compared to published nutritional requirements (when meeting caloric requirements) for growth and reproduction in birds and mammals, insects are excellent sources of nitrogen, potassium and magnesium, highly variable sources of sodium and iron, and, very rarely, adequate calcium sources. 3. 3. Elemental composition of some insects differs by size, sex, season and after culling.
Identification of N-(hydroxymethyl) norcotinine as a major product of cytochrome P450 2A6, but not cytochrome P450 2A13-catalyzed cotinine metabolism.

Cotinine formation is the major pathway of nicotine metabolism in smokers, and the primary pathway of cotinine metabolism is trans-3‘-hydroxylation. trans-3‘-Hydroxycotinine and its glucuronide conjugate account for up to 50% of the nicotine metabolites excreted by smokers. Minor metabolites of cotinine excreted by smokers include norcotinine and cotinine N-oxide, each of which account for <5% of the nicotine dose. It has been reported that P450 2A6 is the catalyst of cotinine metabolism. However, we report here that the major product of P450 2A6-catalyzed cotinine metabolism is N-(hydroxymethyl)norcotinine, a previously unknown human metabolite of cotinine. N-(Hydroxymethyl)norcotinine was chemically synthesized, and its stability under the conditions of the enzyme reactions was confirmed. The products of P450 2A6-catalyzed [5-3H]cotinine metabolism were quantified by radioflow HPLC. The identification of N-(hydroxymethyl)norcotinine as the major metabolite was based on HPLC analysis on three unique syst...
Riding to the Rescue While Holding On By a Thread: Physical Activity in the Schools

The public health burden of obesity, overweight, and physical inactivity suggests schools be actively involved in prevention and treatment. Schools were challenged to take action by the Surgeon General in 2001. Few resources have been allocated to support the schools and in the presence of budget and high stakes testing pressure, resources are decreasing. Sources of support (research, professional organizations, government, coalitions/foundations) often criticize schools and teachers while providing erroneous information and no support. Teachers have responded to recommendations by including lifetime activities, health related fitness, and increasing MVPA. Approximately half the recommended minutes per week are provided in schools where there is any PE, many (5-33%) schools have no PE for their students. Three recommendations for scholars and leaders in the field include the following: Provide clear and consistent messages and interpretation of the scientific and theoretical information about physical act...
TH-A-214-07: Evaluation of Potential Effective Dose Estimates Using Values Included in CT Dose Reports

Purpose: CT Dose reports include several values (CTDIvol, DLP) for each series in an exam and often the Total DLP. The purpose of this work was to examine potential methods to calculate effective dose (ED) estimates from these reported values and to assess the accuracy of these ED estimates. Method: ED estimates for three types of CT exams were obtained for an adult female patient (who was slightly larger than reference woman size) using region‐specific DLP‐to‐ED coefficients (k‐factors) by: (A) summing the ED calculated for each scan component in each study, and, (B) calculating ED using the total DLP and the average k‐factor across all anatomical regions included in the exam. ED estimates were obtained for a routine abdomen, a three‐phase liver, and a trauma exam. For each exam, ED estimates were compared to reference values obtained using Monte Carlo simulations to estimate organ doses and then applying ICRP Publication 103 definitions. Results: The routine abdomen exam consists of only one scan, thus methods A and B both resulted in an ED estimate of 5.0mSv which underestimated the reference ED by 37%. For a three‐phase liver exam, both methods A and B estimated an ED of 27.9mSv, which also had an error of −37%. For the trauma exam, method A resulted in an ED estimate of 32.2mSv, which had error of −20% and method B produced an ED estimate of 36mSv, which had a smaller error of 10%. Conclusions: In theory, ED estimates should be obtained by multiplying the DLP for each series by the region‐specific k‐factor and summing (Method A); however, for the trauma exam Method B resulted in an ED with lower error. Regardless of what method is used, the ED estimates from k‐factors differed from the reference method for several reasons including not adjusting for patient size.
Antibodies against a 23Kd heparin binding fragment of thrombospondin inhibit platelet aggregation

Antiserum against a 23Kd heparin binding fragment of thrombospondin inhibits the aggregation of platelets in response to ADP, collagen or thrombin. The antiserum inhibits the secretion-dependent second phase, but not the primary phase of aggregation of platelets responding to ADP. Although immune serum added during the second phase of ADP-induced aggregation causes some inhibition of secretion, it also causes reversal of aggregation to the level produced during primary aggregation. Since thrombospondin is the endogenous lectin of human platelets, these results support the conclusion that the endogenous lectin mediates, at least in part, the secretion-dependent aggregation of platelets. Our data suggest that the region of thrombospondin which contains the heparin binding domain(s) present in the 23Kd fragment play(s) a critical role in secretion-dependent aggregation of platelets.
Cost analysis of objective structured clinical examinations

Background The costs of objective structured clinical examinations (OSCEs) and other patient-centered examinations have not been well established. The published literature contains cost estimates ranging from $21 to over $1,000 per examinee. This wide range in cost estimates is due in part to both a lack of a consistent definition as to what should be included as an expense and a lack of understanding of how these expenses can be minimized. Method In 1993-94 the authors conducted a literature review and defined and subcategorized costs related to the production and implementation of an OSCE into costs for personnel, standardized patients (SPs), and administration. An analysis was undertaken of how each of the subcategory costs can be minimized. Results Costs for physicians, patient trainers, support personnel, and data analysis are negligible if the personnel who perform these duties do so as part of their overall academic responsibilities. Costs for SPs can be minimized by developing a cadre of experienced patients as well as professional personnel who participate in a comprehensive program in which SPs are used in both teaching and evaluative modes. This contributes to the development of a psychometrically valid OSCE with a minimum number of stations and decreased costs. Administrative costs are fixed and not amenable to significant cost saving. A detailed cost analysis of a comprehensive OSCE given at the end of an Introduction to Clinical Medicine course at one institution is presented, illustrating the practical aspects of these cost-containment methods. Conclusion Based on these considerations it appears financially feasible for an individual academic institution to develop and implement an OSCE.
Influence of the Route of Infection on Development of T-Cell Receptor β-Chain Repertoires of Reovirus-Specific Cytotoxic T Lymphocytes

It is well established that the route of infection affects the nature of the adaptive immune response. However, little is known about the effects of the route of exposure on development of cytotoxic T-lymphocyte (CTL) responses. Alternative antigen-presenting cell populations, tissue-restricted expression of class I major histocompatibility complex-encoded molecules, and unique T-cell receptor (TCR)-bearing cells in mucosal tissues could influence the selection and expansion of responder T cells. This study addresses the question of whether the route of virus infection affects the selection and expansion of subpopulations of virus-specific CTLs. Mice were infected orally or in the hind footpads with reovirus, and the repertoires of TCR beta-chains expressed on virus-specific CD8(+) T cells in Peyer's patches or lymph nodes and spleens were examined. CD8(+) cells expressing the variable gene segment of the TCR beta-chain 6 (Vbeta6) expanded in the spleens of mice infected by either route and in CTL lines established from the spleens and draining lymphoid tissues. Adoptively transferred Vbeta6(+) CD8(+) T cells from orally or parenterally infected donors expanded in reovirus-infected severe combined immunodeficient recipient mice and mediated cytotoxicity ex vivo. Furthermore, recovered Vbeta6(+) cells were enriched for clones utilizing uniform complementarity-determining region 3 (CDR3) lengths. However, sequencing of CDR3beta regions from Vbeta6(+) CD8(+) cells indicated that Jbeta gene segment usage is significantly more restricted in CTLs from orally infected mice, suggesting that the route of infection affects selection and/or subsequent expansion of virus-specific CTLs.
Muscling in: Gene therapies for muscular dystrophy target RNA

Muscle diseases can take many forms, from the progressive muscle degeneration of dystrophies to the childhood cancer rhabdomyosarcoma. In 'Bench to Bedside', Joel R. Chamberlain and Jeffrey S. Chamberlain discuss studies using antisense oligonucleotides to treat Duchenne muscular dystrophy and myotonic dystrophy. In 'Bedside to Bench', Simone Hettmer and Amy J. Wagers examine the implications of clinical studies describing a type of rhabdomyosarcoma that resembles acute leukemia. The findings dovetail with other studies suggesting that some of these cancers might originate outside of muscle tissue and highlight the need for a better understanding of the cells that give rise to this condition.
A disordered two-dimensional system in a magnetic field: Borel-Padé analysis

Abstract We report on a calculation of the density of states and the diffusion constant for the lowest Landau level for an electron moving in two dimensions in a random potential, and under a strong magnetic field. The calculation is based on renormalized perturbation expansion carried out to very high orders, which is summed using the method of Borel-Pade analysis. The results are obtained from an extensive series analysis involving 45 terms in the white noise case and 36 terms in the case of a spatially correlated random potential.
Detecting nonuniformity in small welds and solder seams using optical correlation and electronic processing

Using holographic matched filtering and electronic processing, small variations in surface displacement along the seam of a hermetic microcircuit package can be detected when the seam is stressed. Destructive analysis of a solder-sealed package reveals a strong correlation between optical signal variations and nonuniformity of solder adhesion and wetting along the seam. The technique promises potential application as a means of nondestructively inspecting for flaws in small welded or soldered seams.
Congenital unilateral renal tubular dysgenesis and severe neonatal hypertension

Severe arterial hypertension rarely occurs in the neonatal period but may have life-threatening consequences. It is most often caused by renal parenchymal or vascular abnormality, which, to be accurately diagnosed, may require a combination of imaging modalities. We report on a case of neonatal hypertension presenting as cardiac failure. Initial imaging suggested unilateral renal artery stenosis, but this was not corroborated by magnetic resonance angiography. Surgical nephrectomy was curative for the hypertension and also allowed diagnosis of renal tubular dysgenesis. Unilateral congenital tubular dysgenesis without renal infarction has not been previously reported. We speculate that the condition was secondary to a period of localised hypoperfusion during early foetal life.
The effect of electrode shape on the voltage of hall/heroult cells—I. carbon anodes/wetted cathodes

Abstract Two-dimensional profiles assumed by carbon anodes suspended over shaped, wetted cathodes in the Hall process for aluminum production and the cell voltage of each configuration were calculated. Cathodes shaped as square waves, sine waves and triangular waves were used. Designation of a region of lower conductivity adjacent to the anode simulated the presence of carbon dioxide bubbles. The profile of the anode did not penetrate the shape of the cathode. A dimensionless group characterizing the response of the anode profile to a wave sculpted into the cathode is where s | is the stoichiometric coefficient, p is the reaction order, n is the number of electrons transferred, b o is the amplitude of the cathode wave, h o is the minimum separation of anode from the cathode, and γ o is the wavelength of the cathode wave. Cell voltages in all cases were greater than the voltage of a cell having the same amount of gas spread uniformly over a flat plane. Voltage reduction can be achieved if the shape cut into the anode aids removal of gas from the interelectrode region.
Paraspecific protection by elapid and sea snake antivenins

Abstract Seventeen elapid antivenins and one sea snake antivenin were tested for neutralizing activity against a panel of fifteen elapid venom samples (eight Naja, three Bungarus, one each of Ophiophagus, Hemachatus, Walterinnesia and Micrurus) and one sea snake (Enhydrina) sample. Assays were made by injecting mice subcutaneously with 2–10 ld 50 of venom and injecting antivenin intravenously immediately thereafter. Antivenins against venoms of certain Australian snakes (tiger snake, death adder, taipan) protected animals against at least fifteen of the venoms used. Tiger Snake Antivenene neutralized ten of the venoms at a dose of 10 ld 50. Sea Snake Antivenene showed at least some protective effect against fourteen of the fifteen elapid venoms used, but most elapid antivenins failed to neutralize sea snake venom. Cobra antivenins proved largely genus specific and showed considerable variation in neutralizing capacity. Venoms of Naja n. atra and N. nigricollis were less well neutralized than other cobra venoms. Krait antivenins were relatively ineffective even in homologous systems. Coral snake (Micrurus fulvius) venom proved very difficult to neutralize. Certain implications of these findings are discussed and suggestions made for utilizing the paraspecific effect of elapid antivenins in clinical situations.
Protein synthesis in cultured muscle cells: Methylation of nascent proteins

Abstract Protein methylation was examined in primary cultures of rat leg muscle cells between 7 and 9 days of culture. Methyl[ 14 C]- or [ 3 H]-methionine was introduced into the culture medium and the cells were sampled for radioactive methylated protein residues. Incorporation of the total radioactivity was linear for at least 4 hr after introduction of the methionine label. When labeling was studied for periods between 10–30 min, the methylation of polyribosome-bound, presumably nascent, proteins was unaffected by addition of cycloheximide to the culture medium. The antibiotic, however, inhibited incorporation of methionine, and consequently increased the ratios of the incorporated methylated, to methionine residues and the ratio of ribosome-bound to free radioactivity. The methylated, polyribosome-bound proteins were decreased when puromycin was added to the culture medium. It is proposed that selective methylation of nascent proteins, such as myosin, can begin at the level of polyribosomes and be completed in the cytosol of muscle cells cultured in vitro .
The sources of continuity and change of Ukraine’s incomplete state

Abstract This article examines the evolution of the state in Ukraine from an object of elite predation in early 1990s into a dominant actor in relations with non-state actors under Kuchma, an instrument of elite struggles for power and rents under Yushchenko and a return to a centralized state authority under Yanukovych. Despite its different transformations the state in Ukraine has been continuously characterized by the prevalence of informal levers of power and the absence of strong formal institutional foundations. As a result, after twenty years it still lacks the prerequisites of effective governance in a modern state – an impersonal bureaucracy, rule of law and mechanisms of accountability. This institutional void produces Ukraine’s vicious cycling between hybrid types of authoritarianism and democracy leaving the state dysfunctional and incomplete.
Disruption of circadian rhythm increases the risk of cancer, metabolic syndrome and cardiovascular disease

Abstract Incidents of non-communicable diseases (NCD) like cardiovascular diseases, cancer, diabetes, and chronic respiratory disease have increased dramatically and are currently the leading causes of death worldwide. Their rising incidents coincide with the dramatic changes in industrialization and development of societies over the past few hundred years. Therefore, current lifestyle practices should be further explored to uncover novel risk factors for certain cancers (i.e. colon, prostate, and breast cancer), metabolic syndrome (i.e. diabetes and obesity), and cardiovascular disease (i.e. coronary artery disease). This review discusses how a disruption of the “biological clock” or circadian rhythms could be involved in the development of these diseases as circadian rhythms control multiple physiological processes such as wake/sleep cycles, hormonal levels, body temperature, metabolism, and immune system. Several environmental factors that disrupt circadian rhythms can be identified including exposure ...
The promise of bolometers for CMB polarimetry

Bolometers currently offer the best sensitivity for measuring the anisotropy and polarization of the Cosmic Microwave Background (CMB). The next generation of CMB instruments intended to search for faint 'curl-mode' polarization require bolometer focal plane arrays with significantly higher sensitivity than current temperature anisotropy receivers, and unprecedented control of systematic errors. Bolometers for the ESA/NASA Planck experiment, thermally optimized for the photon background from the sky and instrument, approach the fundamental photon noise from the CMB with defined allocations for systems level noise contributions. Ground-based CMB polarimeters will soon field focal planes with approximately the instantaneous sensitivity of Planck HFI to deeply probe limited regions of sky. Future CMB polarimeters require large-format arrays of bolometers. Antenna-coupled bolometers with superconducting transition-edge readouts promise large-format arrays with well-controlled beam patterns and integral lithographed transmission-line filters.
Telemeter carrier channels

THE POWER SYSTEM operated by the Tennessee Valley Authority is centrally located in the vast network of power systems serving the south Atlantic and central United States and its generation, furnished by 32 major plants, represents about 14 per cent of the total interconnected pool capacity. The Authority's 6,666-mile transmission system is interconnected with neighboring power companies by 17 major transmission lines at 12 locations. For efficient control of generation and tie-line loadings, it has been found imperative to furnish the power system load dispatchers with a clear picture of power flowing at vital points. To secure maximum benefits from the intersystem tie lines, 68 carrier terminals are installed at 25 locations to establish the major portion of a 6,500-mile telemeter and automatic load-frequency control system. The quantity and direction of power flowing in the intersystem tie lines is telemetered an average distance of 172 miles to an operating office where the tie-line loadings are totalized.
NMRES: an artificial intelligence expert system for quantification of cardiac metabolites from 31phosphorus nuclear magnetic resonance spectroscopy

The application of high-resolution 31Phosphorus Nuclear Magnetic Resonance (31P NMR) Spectroscopy in biology and medicine has provided new insights into biochemical processes and also a unique assessment of metabolites. However, accurate quantification of biological NMR spectra is frequently complicated by: (a) non-Lorentzian form of peak lineshapes, (b) contamination of peak signals by neighboring peaks, (c) presence of broad resonances, (d) low signal-to-noise ratios, and (e) poorly defined sloping baselines. Our objectives were to develop an expert system that captures and formalizes 31P NMR spectroscopists' expert knowledge, and to provide a reliable, efficient, and automated system for the interpretation of biological spectra. The NMR Expert System (NMRES) was written in the C and OPS5 programming languages and implemented on a Unix-based (Ultrix) mainframe system with XWindows bit-map graphics display. Expert knowledge was acquired from NMR spectroscopists and represented as production rules in the knowledge base. A heuristic weights method was employed to determine the confidence levels of potential peaks. Statistical and numerical methods were used to facilitate processing decisions. NMR spectra obtained from studies of ischemic neonatal and immature hearts were used to assess the performance of the expert system. The expert system performed signal extraction, noise treatment, resonance assignment, intracellular pH determination, and metabolite intensity quantitation in about 10 s per 4 KB (kilobyte) spectrum. The peak identification success rate was 98.2%. Peak areas and pH estimated by the expert system compared favorably with those determined by human experts. We conclude that the expert system has provided a framework for reliable and efficient quantification of complex biological 31P NMR spectra.
On the Lagrange interpolation for a subset of C k functions

We study the optimal order of approximation forC k piecewise analytic functions (cf. Definition 1.2) by Lagrange interpolation associated with the Chebyshev extremal points. It is proved that the Jackson order of approximation is attained, and moreover, ifx is away from the singular points, the local order of approximation atx can be improved byO(n −1). Such improvement of the local order of approximation is also shown to be sharp. These results extend earlier results of Mastroianni and Szabados on the order of approximation for continuous piecewise polynomial functions (splines) by the Lagrange interpolation, and thus solve a problem of theirs (about the order of approximation for |x|3) in a much more general form.
Design-driven, multi-use research agendas to enable applied synthetic biology for global health

Many of the synthetic biological devices, pathways and systems that can be engineered are multi-use, in the sense that they could be used both for commercially-important applications and to help meet global health needs. The on-going development of models and simulation tools for assembling component parts into functionally-complex devices and systems will enable successful engineering with much less trial-and-error experimentation and laboratory infrastructure. As illustrations, I draw upon recent examples from my own work and the broader Keasling research group at the University of California Berkeley and the Joint BioEnergy Institute, of which I was formerly a part. By combining multi-use synthetic biology research agendas with advanced computer-aided design tool creation, it may be possible to more rapidly engineer safe and effective synthetic biology technologies that help address a wide range of global health problems.
The effects of cilostazol on insulin-induced proliferation and migration of human diabetic infragenicular arterial smooth muscle cells

Introduction: The pattern of atherosclerotic diabetic vascular disease in the lower extremities typically involves occlusive disease of the infrageniculate arteries. Accelerated proliferation and migration of arterial smooth muscle cells (ASMCs) occurs as an early event in atherosclerotic plaque formation particularly in patients with type II diabetes. The purpose of this study is to examine the effects of cilostazol, a substance that improves claudication distance in patients with lower extremity atherosclerosis, on the insulin-induced proliferation and migration of human infragenicular ASMCs harvested from diabetic patients. Methods: Human infragenicular ASMCs isolated from the tibial arteries of male diabetics undergoing lower extremity amputation were harvested and grown to subconfluence. This was followed by exposure to deprived media with and without insulin at 100 ng/ml and cilostazol (5 μM and 10 μM). Cellular proliferation was assayed at 24 hours using [methyl-3H]-thymidine incorporation. Migration assays were performed using a modified Boyden chamber. Cell viability was assessed by trypan blue assay. Results: ASMCs exposed to insulin had a significantly increased rise in thymidine incorporation (P < 0.05). When both the control (deprived media alone) and insulin groups were exposed to cilostazol (10 μM), there was a significant decrease in thymidine incorporation (P < 0.05). In the migration assay, insulin induced a significant increase (P < 0.05) in the mean number of cells per high-powered field compared to control. The addition of cilostazol (5 μM and 10 μM) resulted in a significant decrease (P < 0.05) in cell migration in all groups. Viability was not significantly different between control group, the group receiving cilostazol, and the group exposed to drug vehicle (DMSO). Conclusions: Cilostazol significantly reduces the rate of cell proliferation and migration in human diabetic ASMCs exposed to elevated concentrations of insulin without affecting cell viability. Therefore, cilostazol may have an even broader effect on ASMCs that will assist in the prevention of atherosclerotic lesion development. This may be particularly true for the type II diabetic patient.
A perithecial color mutant of Neurospora crassa

A mutation, per-1, was found in N. crassa which caused orange instead of black perithecia when the protoperithecial parent contained the per-1 allele. No effect of per-1 was found on vegetative morphology or nutritional requirements. The per-1 locus was mapped proximal to iv (?6201) in the right arm of linkage group V.
Enzyme Activities of Some Cultured Human Cells.

SummaryThe data presented here allow a comparison of the activity of 3 enzymes in diploid and heteroploid human cell cultures derived from both normal and neoplastic tissues. In general, acid phosphatase activity is similar in all of these cultures, although there is evidence that diploid cultures approaching or in phase III (decreased capacity for proliferation) have higher activities of this enzyme. Alkaline phosphatase activity was high in the cultures derived from neoplastic tissue, and low in the diploid cultures derived from normal tissues. Cultures derived from normal tissues and transformed in vitro by an oncogenic virus show activities lower than any of the diploid cultures.Cultures derived from neoplastic tissues show lactate dehydrogenase activities 1.5- to 2-fold higher than the normal diploid or transformed cultures.
Glutamate decarboxylase side reactions catalyzed by the enzyme

A homogeneous glutamate decarboxylase isolated from pig brain contains 0.8 mol of tightly bound pyridoxal 5-phosphate/enzyme dimer. Upon addition of exogenous pyridoxal 5-phosphate (pyridoxal-5-P), the enzyme acquires maximum catalytic activity. Preincubation of the enzyme with l-glutamate (10 mM) brings about changes in the absorption spectrum of bound pyridoxal-5-P with the concomitant formation of succinic semialdehyde. However, the rate of this slow secondary reaction, i.e. decarboxylative transamination, is 10−4 times the rate of normal decarboxylation. It is postulated that under physiological conditions enzymatically inactive species of glutamate decarboxylase, generated by the process of decarboxylative transamination, are reconstituted by pyridoxal-5-P produced by the cytosolic enzymes pyridoxal kinase and pyridoxine-5-P oxidase. The catalytic activity of resolved glutamate decarboxylase is recovered by preincubation with phospho-pyridoxyl-ethanolamine phosphate. The experimental evidence is consistent with the interpretation that the resolved enzyme binds the P-pyridoxyl analog, reduces the stability of the covalent bond of the phospho-pyridoxyl moiety, and catalyzes the formation of pyridoxal-5-P.
Dynamic duty cycle control for end-to-end delay guarantees in wireless sensor networks

It is well known that periodically putting nodes into sleep can effectively save energy in wireless sensor networks, at the cost of increased communication delays. However, most existing work mainly focuses on static sleep scheduling, which cannot guarantee the desired delay when the network conditions change dynamically. In many applications with user-specified end-to-end delay requirements, the duty cycle of every node should be tuned individually at runtime based on the network conditions to achieve the desired end-to-end delay guarantees and energy efficiency. In this paper, we propose DutyCon, a control theory-based dynamic duty cycle control approach. DutyCon decomposes the end-to-end delay guarantee problem into a set of single-hop delay guarantee problems along each data flow in the network. We then formulate the single-hop delay guarantee problem as a dynamic feedback control problem and design the controller rigorously, based on feedback control theory, for analytic assurance of control accuracy and system stability. DutyCon also features a queuing delay adaptation scheme that adapts the duty cycle of each node to unpredictable packet rates, as well as a novel energy balancing approach that extends the network lifetime by dynamically adjusting the delay requirement allocated to each hop. Our empirical results on a hardware testbed demonstrate that DutyCon can effectively achieve the desired tradeoff between end-to-end delay and energy conservation. Extensive simulation results also show that DutyCon outperforms two baseline sleep scheduling protocols by having more energy savings while meeting the end-to-end delay requirements.
Digital breast tomosynthesis: application of 2D digital mammography CAD to detection of microcalcification clusters on planar projection image

Computer-aided detection (CAD) has the potential to aid radiologists in detection of microcalcification clusters (MCs). CAD for digital breast tomosynthesis (DBT) can be developed by using the reconstructed volume, the projection views or other derivatives as input. We have developed a novel method of generating a single planar projection (PPJ) image from a regularized DBT volume to emphasize the high contrast objects such as microcalcifications while removing the anatomical background and noise. In this work, we adapted a CAD system developed for digital mammography (CADDM) to the PPJ image and compared its performance with our CAD system developed for DBT volumes (CADDBT) in the same set of cases. For microcalcification detection in the PPJ image using the CADDM system, the background removal preprocessing step designed for DM was not needed. The other methods and processing steps in the CADDM system were kept without modification while the parameters were optimized with a training set. The linear discriminant analysis classifier using cluster based features was retrained to generate a discriminant score to be used as decision variable. For view-based FROC analysis, at 80% sensitivity, an FP rate of 1.95/volume and 1.54/image were achieved, respectively, for CADDBT and CADDM in an independent test set. At a threshold of 1.2 FPs per image or per DBT volume, the nonparametric analysis of the area under the FROC curve shows that the optimized CADDM for PPJ is significantly better than CADDBT. However, the performance of CADDM drops at higher sensitivity or FP rate, resulting in similar overall performance between the two CAD systems. The higher sensitivity of the CADDM in the low FP rate region and vice versa for the CADDBT indicate that a joint CAD system combining detection in the DBT volume and the PPJ image has the potential to increase the sensitivity and reduce the FP rate.
Domain-engineered pyroelectric radiometer

We built a large-area domain-engineered pyroelectric radiometer with high spatial and spectral response uniformity that is an excellent primary transfer standard for measurements in the near- and the mid-infrared wavelength regions. The domain engineering consisted of inverting the spontaneous polarization over a 10-mm-diameter area in the center of a uniformly poled, 15.5 mm x 15.5 mm square, 0.25-mm-thick LiNbO(3) plate. Gold black was used as the optical absorber on the detector surface, and an aperture was added to define the optically sensitive detector area. Our results indicate that we significantly reduced the acoustic sensitivity without loss of optical sensitivity. The detector noise equivalent power was not exceptionally low but was nearly constant for different acoustic backgrounds. In addition, the detector's spatial-response uniformity variation was less than 0.1% across the 7.5-mm-diameter aperture, and reflectance measurements indicated that the gold-black coating was spectrally uniform within 2%, from 800 to 1800 nm. Other detailed evaluations of the detector include detector responsivity as a function of temperature, electrical frequency response, angular response, and field of view.
Abstract A31: Differential processing of let-7a precursors influences gemcitabine chemosensitivity in pancreatic cancer: Role of ribonucleotide reductase subunit M2

Abstract Ribonucleotide reductase subunit M2 (RRM2) involved in deoxyribonucleotide synthesis acts as a key determinant of chemoresistance to nucleoside drugs (e.g., gemcitabine) used in treating pancreatic cancer. While silencing RRM2 expression by synthetic means (e.g., siRNA) improves the chemosensitivity of pancreatic cancer cells to gemcitabine, targeting endogenous molecules to advance gemcitabine chemotherapeutic responses has never been explored. Based on existing evidence and computational predictions, we hypothesized that the let-7 tumor suppressor microRNAs will inhibit RRM2-mediated gemcitabine chemoresistance in pancreatic cancer. Reduced expression of the majority of let-7 miRNAs with an inverse relationship to RRM2 expression was identified in inherently gemcitabine-resistant pancreatic cancer cells. Direct binding of let-7 miRNA to the 3′-UTR of RRM2 transcripts identified post-transcriptional repression of RRM2 as a novel phenomenon influencing gemcitabine chemosensitivity. Intriguingly, overexpression of human precursor-let-7 miRNAs led to differential RRM2 expression and gemcitabine chemosensitization in a poorly differentiated gemcitabine-resistant pancreatic cancer cell line MIA PaCa-2. Defective processing of the let-7a precursors to mature forms explained, in part, the discrepancies observed with let-7a expressional outcomes. Screening putative regulators of let-7a biogenesis in MIA PaCa-2 cells identified LIN-28 and SET oncoprotein to differentially modulate let-7 biogenesis and chemosensitivity in gemcitabine-sensitive versus-resistant pancreatic cancer cells. Additionally, acquired gemcitabine chemoresistance was found to be independent of let-7 alterations. These data demonstrate an intricate post-transcriptional regulation of RRM2 expression by let-7 and that the manipulation of let-7 processing machinery may provide a mechanism for improving gemcitabine chemosensitivity in innately-resistant pancreatic cancer cells. Citation Format: Rajgopal Govindarajan. Differential processing of let-7a precursors influences gemcitabine chemosensitivity in pancreatic cancer: Role of ribonucleotide reductase subunit M2 [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A31.
Warmth from skin-to-skin contact with mother is essential for the acquisition of filial huddling preference in preweanling rats.

During a single, 2-hr session with a scented foster dam, preweanling rat pups form an affiliative attraction to an odor associated with the maternal caregiver, manifest as a huddling preference. To identify maternal stimuli that induce this filial preference, we quantitatively examined behavioral interactions during odor conditioning. Bout duration of skin-to-skin (STS) contact was positively associated with the preference. In contrast, simple physical contact and anogenital licking were not significantly related to the preference. The frequency of nonanogenital licking was negatively associated with the preference as well as with bout duration of STS contact. When odor conditioning was conducted with a warm cylinder, ambient warmth, or stroking as the unconditioned stimulus, only pups exposed to the warm cylinder exhibited a preference for the conditioned odor. These results suggest a positive, affiliative effect of maternal STS contact on pup filial preference, which may be disrupted by maternal licking. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 53:813–827, 2011.
Extension of lens-system model of holography*

The angular extent of a hologram’s zero-order light is derived from that of a set of collimating lenses. The effect of a reference source of nonzero area is obtained from the Airy disk of a lens. The finite temporal coherence of the reference source is modeled in terms of the depth of field of a lens. Finally, sampled holograms, such as those usually obtained in microwave or acoustical work, are modeled by a lens with a complicated pupil function. For the first time, these disparate topics in holography are treated in terms of simple lens properties; such a treatment is extremely useful for gaining an increased intuitive understanding of holography.