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Whole-cell biosensors are useful for monitoring heavy metal toxicity in public health and ecosystems, but their development has been hindered by intrinsic trade-offs between sensitivity and specificity. Here, we demonstrated an effective engineering solution by building a sensitive, specific, and high-response biosensor for carcinogenic cadmium ions. We genetically programmed the metal transport system of Escherichia coli to enrich intracellular cadmium ions and deprive interfering metal species. We then selected 16 cadmium-sensing transcription factors from the GenBank database and tested their reactivity to 14 metal ions in the engineered E. coli using the expression of the green fluorescent protein as the readout. The resulting cadmium biosensor was highly specific and showed a detection limit of 3 nM, a linear increase in fluorescent intensities from 0 to 200 nM, and a maximal 777-fold signal change. Using this whole-cell biosensor, a smartphone, and low-tech equipment, we developed a simple assay capable of measuring cadmium ions at the same concentration range in irrigation water and human urine. This method is user-friendly and cost-effective, making it affordable to screen large amounts of samples for cadmium toxicity in agriculture and medicine. Moreover, our work highlights natural gene repositories as a treasure chest for bioengineering.

Shine-Dalgarno sequences (SD) in prokaryotic mRNA facilitate protein translation by pairing with rRNA in ribosomes. Although conventionally defined as AG-rich motifs, recent genomic surveys reveal great sequence diversity, questioning how SD functions. Here, we determined the molecular fitness (i.e., translation efficiency) of 49 synthetic 9-nt SD genotypes in three distinct mRNA contexts in Escherichia coli. We uncovered generic principles governing the SD fitness landscapes: (1) Guanine contents, rather than canonical SD motifs, best predict the fitness of both synthetic and endogenous SD; (2) the genotype-fitness correlation of SD promotes its evolvability by steadily supplying beneficial mutations across fitness landscapes; and (3) the frequency and magnitude of deleterious mutations increase with background fitness, and adjacent nucleotides in SD show stronger epistasis. Epistasis results from disruption of the continuous base pairing between SD and rRNA. This “chain-breaking” epistasis creates sinkholes in SD fitness landscapes and may profoundly impact the evolution and function of prokaryotic translation initiation and other RNA-mediated processes. Collectively, our work yields functional insights into the SD sequence variation in prokaryotic genomes, identifies a simple design principle to guide bioengineering and bioinformatic analysis of SD, and illuminates the fundamentals of fitness landscapes and molecular evolution.

We present Taiji, a new system for managing user traffic for large-scale Internet services that accomplishes two goals: 1) balancing the utilization of data centers and 2) minimizing network latency of user requests. Taiji models edge-to-datacenter traffic routing as an assignment problem---assigning traffic objects at the edge to the data centers to satisfy service-level objectives. Taiji uses a constraint optimization solver to generate an optimal routing table that specifies the fractions of traffic each edge node will distribute to different data centers. Taiji continuously adjusts the routing table to accommodate the dynamics of user traffic and failure events that reduce capacity. Taiji leverages connections among users to selectively route traffic of highly-connected users to the same data centers based on fractions in the routing table. This routing strategy, which we term connection-aware routing, allows us to reduce query load on our backend storage by 17%. Taiji has been used in production at Facebook for more than four years and routes global traffic in a user-aware manner for several large-scale product services across dozens of edge nodes and data centers.

Previous studies of anemia epidemiology have been geographically limited with little detail about severity or etiology. Using publicly available data, we estimated mild, moderate, and severe anemia from 1990 to 2010 for 187 countries, both sexes, and 20 age groups. We then performed cause-specific attribution to 17 conditions using data from the Global Burden of Diseases, Injuries and Risk Factors (GBD) 2010 Study. Global anemia prevalence in 2010 was 32.9%, causing 68.36 (95% uncertainty interval [UI], 40.98 to 107.54) million years lived with disability (8.8% of total for all conditions [95% UI, 6.3% to 11.7%]). Prevalence dropped for both sexes from 1990 to 2010, although more for males. Prevalence in females was higher in most regions and age groups. South Asia and Central, West, and East sub-Saharan Africa had the highest burden, while East, Southeast, and South Asia saw the greatest reductions. Iron-deficiency anemia was the top cause globally, although 10 different conditions were among the top 3 in regional rankings. Malaria, schistosomiasis, and chronic kidney disease-related anemia were the only conditions to increase in prevalence. Hemoglobinopathies made significant contributions in most populations. Burden was highest in children under age 5, the only age groups with negative trends from 1990 to 2010.

International audience; BACKGROUND: Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. METHODS: We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. FINDINGS: In 2010, there were 52*8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24*9% of deaths worldwide in 2010, down from 15*9 million (34*1%) of 46*5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2*5 to 1*4 million), lower respiratory infections (from 3*4 to 2*8 million), neonatal disorders (from 3*1 to 2*2 million), measles (from 0*63 to 0*13 million), and tetanus (from 0*27 to 0*06 million). Deaths from HIV/AIDS increased from 0*30 million in 1990 to 1*5 million in 2010, reaching a peak of 1*7 million in 2006. Malaria mortality also rose by an estimated 19*9% since 1990 to 1*17 million deaths in 2010. Tuberculosis killed 1*2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34*5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1*5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12*9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1*3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5*1 million deaths) was marginally higher in 2010 (9*6%) compared with two decades earlier (8*8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1*3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. INTERPRETATION: Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. FUNDING: Bill & Melinda Gates Foundation.

Theoretical quantum mechanical methods for the characterization of molecular reactivity are applied to a series of hydroxy substituted indolealkylamines. A correlation is sought between the reactivity characteristics of these molecules and their biological activity on the LSD/serotonin receptor. The calculations are based on ab initio lcao-scf-mo wave functions. For the analysis of the early stages of drug-receptor interaction, the electrostatic potential fields calculated for the various congeners are compared to the field generated by the most active compound: 5-hydroxytryptamine. A model for the comparative orientation of the active molecules in the series is obtained on the basis of a requirement for matching electrostatic interaction fields. This requirement can be translated into observed differences in the affinity of the molecules for the biological receptor. The hypotheses for subsequent interactions with the receptor at shorter distances are analyzed in terms of the comparative ability of the molecules to interact in polarization-type complexes. The analysis focuses on the different localization of the most active sites in the various molecules. The largest single-orbital contribution to a polarization term E2 in a perturbation expansion of the interaction between the molecule and an attacking charge is shown to come from the highest occupied molecular orbital (homo). This illustrates the relation between the well established frontier density criteria for reactivity and a perturbation representation of the interaction. The localization of homo density is found to match the sites at which the highest percentile contribution to the polarization is calculated. These findings provide a theoretical background for previously obtained correlations between biological activity and electronic structure and answer some of the questions raised by correlations with charges on atoms and frontier densities. All the findings are in excellent qualitative agreement with the biological data on the specific binding of hydroxy substituted indolealkylamines to the LSD receptor, and with data on the pharmacological activity of these compounds.

To demonstrate the benefit of an institutionally implemented glucose control intervention based on serum and plasma glucose values in the acute inpatient setting.In a retrospective analysis, all serum and plasma glucose values from the laboratory information system database from 1999 through 2005 were used to assess implementation of 2 new hospital-wide intravenous and subcutaneous protocols aimed at lowering blood glucose values without increasing the number of hypoglycemic events. In our analysis, we used both a per-patient hyperglycemic index (HGI), an area-under-the-curve analysis, and hospital-wide geometric mean blood glucose to assess glucose control. Bedside capillary blood glucose measurements were not included.More than 630,000 serum and plasma glucose results were available for analysis. The percentage of results above the protocol target of 180 mg/dL decreased from 16.4% before the intervention to 10.0% after the intervention (P.00001), and we found no change in the proportion of "critical" hypoglycemic results (50 mg/dL). The hospital-wide geometric mean decreased significantly and coincided with a significant decrease in the fraction of patients with poor glucose control (based on the HGI) from 27.6% to 18.7% (P.00001). The geometric mean blood glucose was found to be an excellent marker for the HGI (r2 = 0.99).We are the first to report improvements in glucose control over an extended period with use of both hospital-wide intravenous and subcutaneous insulin protocols in an academic hospital setting. Furthermore, hospital-wide mean blood glucose levels are excellent surrogates for the more comprehensive calculation of per-patient HGI.

Infrastructure refers to those resources and items required to successfully support and operate information systems. These items include, but are not limited to, security, networks, computers and closely associated hardware, their operation and management, data centers, and desktop computers. In many cases, these items may be purchased as services from a vendor, or are a part of services supported by groups within an organization. Infrastructure items often require large capital and operational expenditures, lengthy lead times, and highly technical skills. The internal versus the acquisition of these services from commercial suppliers is usually decided by economic tradeoffs and availability of local skills. Infrastructure also refers to hardware and software for the use and management of information systems. These include software to manage identity management (users and their passwords), logins (such as single sign-on or SSO), anti-virus software, firewalls, and software for remote access. Infrastructure plays a large role in supporting the security of information systems to protect data against accidental or inappropriate destruction, alteration, or access.

Importance Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. Objectives To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. Design We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. Results US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. Conclusions and Relevance From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.

A taste and odor questionnaire was sent to 826 water utilities. A total of 377 usable responses were received from across the United States and Alberta, Canada. Sixteen percent of the utilities considered their taste and odor problems to be serious, and 43 percent had experienced a taste and odor event lasting longer than one week. The major odor problems reported by the utilities were characterized as chlorine, earthy, fishy, and medicinal; major taste problems were reported as sour, metallic, and chlorine. There were differences between the taste and odor problems encountered by utilities treating groundwater and those treating surface water. Most utilities attributed taste and odor problems to the distribution system. In addition, groundwater plants identified the disinfectant used and mineral residuals as other sources of taste and odor problems. Surface water systems blamed plankton and decaying vegetation in the influent water, the disinfectant used, and conditions at reservoirs.

How has funding to developing countries for health improvement changed in the wake of the global financial crisis? The question is vital for policy making, planning, and advocacy purposes in donor and recipient countries alike. We measured the total amount of financial and in-kind assistance that flowed from both public and private channels to improve health in developing countries during the period 1990-2011. The data for the years 1990-2009 reflect disbursements, while the numbers for 2010 and 2011 are preliminary estimates. Development assistance for health continued to grow in 2011, but the rate of growth was low. We estimate that assistance for health grew by 4 percent each year from 2009 to 2011, reaching a total of $27.73 billion. This growth was largely driven by the World Bank's International Bank for Reconstruction and Development and appeared to be a deliberate strategy in response to the global economic crisis. Assistance for health from bilateral agencies grew by only 4 percent, or $444.08 million, largely because the United States slowed its development assistance for health. Health funding through UN agencies stagnated, and the Global Fund to Fight AIDS, Tuberculosis, and Malaria announced that it would make no new grants for the next two years because of declines in funding. Given the international community's focus on meeting the Millennium Development Goals by 2015 and persistent economic hardship in donor countries, continued measurement of development assistance for health is essential for policy making.

Publisher Summary Infrastructure refers to those resources and items required to successfully support and operate information systems. Security refers to policies, procedures, software, and hardware designed to insure that data in information systems are protected against accidental or inappropriate destruction, alteration, or access. Properly supported, infrastructure competency allows an organization to maintain agility in responding to strategic directives and tactical changes. Infrastructure and security together provide the day-to-day operational support for the hardware and software, thus forming a critical component of the organization. Proper management of security requires attention to infrastructure and information system designs, as well as the organization adhering to strict and appropriate personnel practices. Both infrastructure and security are among the many invisible processes and resources required to implement and sustain a successful clinical computing system. Some resources, such as a data center, must be available prior to implementation of these systems; many other resources, such as those supporting security, should be available prior to implementation, but are often deferred until problems occur. Most infrastructure requirements continue and expand after the system is in use. Although organizations can purchase services through outside contracted vendors, those developing skills in their own personnel can use resources more cost effectively, saving as much as 25–40%, particularly in areas such as disaster management. In the longer term, the use of contracted services can result in the loss of skills necessary for making strategic decisions, putting into question whether the estimated savings of contracting can be achieved.

Background: Training of clinical pathologists is evolving and must now address the 6 core competencies described by the Accreditation Council for Graduate Medical Education (ACGME), which include patient care. A substantial portion of the patient care performed by the clinical pathology resident takes place while the resident is on call for the laboratory, a practice that provides the resident with clinical experience and assists the laboratory in providing quality service to clinicians in the hospital and surrounding community. Documenting the educational value of these on-call experiences and providing evidence of competence is difficult for residency directors. An online database of these calls, entered by residents and reviewed by faculty, would provide a mechanism for documenting and improving the education of clinical pathology residents. Methods: With Microsoft Access we developed an online database that uses active server pages and secure sockets layer encryption to document calls to the clinical pathology resident. Using the data collected, we evaluated the efficacy of 3 interventions aimed at improving resident education. Results: The database facilitated the documentation of more than 4 700 calls in the first 21 months it was online, provided archived resident-generated data to assist in serving clients, and demonstrated that 2 interventions aimed at improving resident education were successful. Conclusions: We have developed a secure online database, accessible from any computer with Internet access, that can be used to easily document clinical pathology resident education and competency.

Automobile design increasingly relies upon CAE (computer aided -engineering) technology to sim ulate vehicle performance. Simulation of NVH (Noise, Vibration and Harshness) provides d esigners and analysts with insights into their designs which not only advance produ ct competitiveness but also i m- prove pa ssenger comfort. An important area of NVH is assessing the response of the veh icle as it traverses a road that contains bumps. Power Spectral Density (PSD) methods can be used to characterize the r e- sponse of the vehi cle in the frequency domain due to input PSD information that characterizes the roug h- ness of the road by the energy present across a range of freque ncies. This paper discusses the addition of a design cap ability for this type of analysis within MSC.Nastra n. PSD and RMS responses have been added to those available in opt imization. Semi - analytical methods are utilized to compute the sens i- tivities of PSD and RMS responses for the optimiz a- tion in MSC.Nastran. An introduction to the techno l- ogy underlying r oad r esponse optimization is followed by a brief theoretical discussion and some comments on the implement ation of the capability in MSC.Nastran. Two exa mples are provided in this paper to illustrate the new capability. The first exa m- ple is a small ideal ized vehicle model which demo n- strates the potential of the new technique deve loped. The second example is a large full vehicle model. In this exa mple, engine mounts, modeled with springs, masses and dampers, are s elected as design variables. Different o bjectives are explored and di scussed.

You have just completed a patient history and physical exam. You determine that the patient needs laboratory tests to rule out secondary hypertension. You pull out and fill out paper requisition forms for basic blood work. You send the patient to the laboratory phlebotomist servicing the practice with a requisition for a basic seven-test chemistry profile (CHEM7) and a complete blood count (CBC). The patient goes home with filled-out request form and instructions for a 24-hour urine collection for metanephrine and is asked to return when he has completed the collection. You receive the results for the CHEM7 and CBC next morning. The patient returns to the laboratory satellite one week later with the 24-hour urine, but leaves the request forms at home. The phlebotomist calls your office for instructions on how to handle the urine jug while the patient is waiting. After 15 minutes with an angry patient, the phlebotomist receives a copy of the requisition faxed by your office. The metanephrine is ordered and results arrive two days later. You hunt down the laboratory results received a week earlier from the stack of paper on your desk and compare them with the metanephrine results.

Background Anaemia is associated with increased maternal and neonatal mortality, with young children most at risk of developing long-term ramifications. Most previous studies have been geographically limited with little detail about severity or aetiology. In this analysis, we completed the most comprehensive survey of anaemia burden to date. Methods Using publicly available data, we estimated mild, moderate, and severe anaemia in 1990 and 2010 for 187 countries, both sexes, and 20 age groups. We then performed cause-specific attribution to 17 conditions using data and resources of the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2010. Findings Global anaemia prevalence in 2010 was 32·9%, causing 68·36 million years lived with disability (95% CI 40·98–107·54 million; 8·8% of the total for all conditions, 95% CI 6·3–11·7). Prevalence dropped for both sexes from 1990 to 2010, though more so for males. Females' prevalence was higher in most regions and age groups. South Asia and central, west, and east sub-Saharan Africa had the highest burden, while east, southeast, and south Asia saw the greatest reductions. Ten different conditions were among the top three in prevalence, depending on the region. Malaria, schistosomiasis, and chronic kidney disease-related anaemia were the only conditions to increase in prevalence. Haemoglobinopathies made significant contributions to the anaemia burden in both sexes, most regions, and all time periods. Burden was highest in children under 5 years old, the only age groups with negative trends from 1990 to 2010. Interpretation Anaemia is a heterogeneous and complex condition. Despite significant progress, many challenges remain. Regional differences remain stark, some conditions are growing as a proportion of overall anaemia, the gender gap is widening, and the total disease burden remains high. Worryingly, young children, the most vulnerable group, appear to be doing worse over the past 20 years. Targeted surveillance and intervention in high-risk populations should be a greater priority. Funding Funding for GBD 2010 was provided by the Bill & Melinda Gates Foundation.

Harrison’s Principles of Internal Medicine (McGraw-Hill, New York, 2001) has been a standard textbook in internal medicine for more than four decades. The current edition is a hefty 8.5-pound book with authoritative descriptions on the diagnosis and management of diseases and is an excellent reference for anyone in laboratory medicine. Harrison’s Manual of Medicine , at 1.25 pounds, condenses Principles into a more convenient form. This book and the Washington Manual of Medical Therapeutics (Lippincott, Philadelphia, 2001) are both used by interns to help them through daily activities. Harrison’s focuses on diseases, whereas the Washington Manual focuses on …

von Karman equations are used for the analysis of rectangular window glass plates subjected to lateral pressures. A previously reported model that used a finite difference method solved the glass plate problem with simply supported boundary conditions. Here, this model is modified to include conditions where the plate is elastically supported on the boundary. Both linear and nonlinear elastic supports are considered. An efficient iterative procedure is used to solve the nonlinear equations.

A multiple perturbation method for the treatment of molecular reactivity is generalized to describe the simultaneous interaction of a molecule containing several reactive sites with a second molecule and a point charge. The modification of the reactivity properties of the main molecule by electrostatic interaction, polarization, dispersion and correlation corrections due to the presence of the second molecule, is identified from the effect of these corrections on the interaction energy with the point charge. The decomposition of interaction energies inherent to the perturbation expansion facilities this analysis. The method is applied to a simple molecule containing two reactive sites (formyl flouride — HCOF), interacting with HF at hydrogen-bond distances. The results are very good agreement with super-molecule LCAO SCF calculations with gaussian basis functions and indicate that the redistribution of the electron density caused by the interaction of the two molecules is adequately represented by the perturbation method.

An insulating glass (IG) unit consists of two glass plates, normally rectangular, placed parallel to each other using a spacer and sealed with a sealant to an extent that the whole unit is considered air tight after manufacture. Desiccants are used inside the spacer to absorb any moisture in the air trapped inside. The structural behavior of these units when subjected to lateral pressures induced by wind loads and variations of temperatures is not very well understood. A theoretical model is presented here to analyze the sharing of the loads between the two plates using a nonlinear plate analysis theory.

Both ab initio and INDO molecular orbital calculations on histamine show that the histamine N(3)H tautomer is preferred for the monocationic form, whereas in the neutral state the N(1)H tautomer is favored. This implies that upon neutralization of the protonated histamine which is predominant in the neutral aqueous solution the tautomeric shift occurs from the N(3)H to the N(1)H form. Although the total electronic energy term makes the N(1)H tautomer of the monocation more favorable, it is the nuclear repulsion term that results in the N(3)H tautomer for the monocation being more stable. The tautomeric energy difference for both the neutral and protonated histamines is independent of the side chain conformations.

It is shown that an electrophilic attack on the ring nitrogen in pyrrole or tryptamine produces an electron charge redistribution that is qualitatively different from the redistribution caused by an attack on the oxygen in furan. The electrophilic attacks are represented theoretically as interactions with a positive point charge and calculated by an ab-initio LCAO-SCF method with gaussian basis sets. Results show that an attacked nitrogen responds to the perturbation by moving electronic charge to the adjacent carbons whereas oxygen retains most of the charge polarized by the interaction. The nitrogen also acts as a charge transducer in other systems that are structurally very different. As a consequence of the charge redistribution, the comparative susceptibility of various sites in the heterocyclic molecules to an electrophilic attack may also depend on the response of the molecule to a prior attack on the heteroatom. The results indicate the need for dynamical reactivity considerations which reflect the variability in the molecular response to an incipient attack and the possibility that enhanced reactivity can be induced at certain sites by this response.