cssi/SciSciGPT-SciSciNet huggingface dataset:
Strong correlation of ferrochelatase enzymatic activity with Mitoferrin-1 mRNA in lymphoblasts of patients with protoporphyria.

Abstract Accumulation of protoporphyrin IX (PPIX) and Zn-PPIX, are the clinical hallmarks of protoporphyria. Phenotypic expression of protoporphyria is due to decreased activity of ferrochelatase (FECH) or to increased activity of aminolevulinic acid synthase (ALAS) in red blood cells. Other genetic defects have been shown to contribute to disease severity including loss of function mutations in the mitochondrial AAA-ATPase, CLPX and mutations in the Iron-responsive element binding protein 2 (IRP2), in mice. It is clear that multiple paths lead to a common phenotype of excess plasma PPIX that causes a phototoxic reaction on sun exposed areas. In this study we examined the association between mitochondrial iron acquisition and utilization with activity of FECH. Our data show that there is a metabolic link between the activity FECH and levels of MFRN1 mRNA. We examined the correlation between FECH activity and MFRN1 mRNA in cell lines established from patients with the classical protoporphyria, porphyria due to defects in ALAS2 mutations. Our data confirm MFRN1 message levels positively correlated with FECH enzymatic activity in all cell types.
Narcissism and Devaluing Others: An Exploration of Impaired Control Over Drinking as a Mediating Mechanism of Alcohol-Related Problems.

Abstract Devaluing or diminishing the worth of others is how many individuals destroy their relationships, such as by drinking beyond limits at inappropriate times and letting others down. Impaired control over drinking (IC) reflects consuming alcohol beyond predetermined limits. This investigation sought to determine whether facets of vulnerable narcissism (e.g., entitlement-rage, hiding-the-self, contingent-self-esteem, and devaluing) or narcissistic grandiosity (e.g. grandiose-fantasy, self-sacrificing-for-self-enhancement, and exploitativeness) were directly related to IC and indirectly related to drinking outcomes. We examined a path model of 759 university student drinkers. Our results show that while grandiose-fantasy (i.e., desire for special recognition) was negatively linked to IC, devaluing was positively linked to IC. In addition, men scored higher on exploitativeness (i.e., interpersonally manipulative for personal gain) than women. We conducted mediational analysis with asymmetric confidence intervals and a bias-corrected bootstrap technique. Mediational tests showed that higher levels of grandiose-fantasy were indirectly related to fewer alcohol-related problems through less IC and less heavy-episodic drinking. In contrast, higher levels of devaluing were indirectly related to more alcohol-related problems through more IC and heavy-episodic-drinking. Our results suggest that targeting thought processes in which people with Alcohol Use Disorders (AUDs) are actively devaluing others may be a good target for therapeutic intervention.
Protein structure aids predicting functional perturbation of missense variants in SCN5A and KCNQ1.

Abstract Rare variants in the cardiac potassium channel KV7.1 (KCNQ1) and sodium channel NaV1.5 (SCN5A) are implicated in genetic disorders of heart rhythm, including congenital long QT and Brugada syndromes (LQTS, BrS), but also occur in reference populations. We previously reported two sets of NaV1.5 (n = 356) and KV7.1 (n = 144) variants with in vitro characterized channel currents gathered from the literature. Here we investigated the ability to predict commonly reported NaV1.5 and KV7.1 variant functional perturbations by leveraging diverse features including variant classifiers PROVEAN, PolyPhen-2, and SIFT; evolutionary rate and BLAST position specific scoring matrices (PSSM); and structure-based features including “functional densities” which is a measure of the density of pathogenic variants near the residue of interest. Structure-based functional densities were the most significant features for predicting NaV1.5 peak current (adj. R2 = 0.27) and KV7.1 + KCNE1 half-maximal voltage of activation (adj. R2 = 0.29). Additionally, use of structure-based functional density values improves loss-of-function classification of SCN5A variants with an ROC-AUC of 0.78 compared with other predictive classifiers (AUC = 0.69; two-sided DeLong test p = .01). These results suggest structural data can inform predictions of the effect of uncharacterized SCN5A and KCNQ1 variants to provide a deeper understanding of their burden on carriers.
Web-Based Platform for Evaluation of Resilient and Transactive Smart-Grids

Today’s smart-grids have seen a clear rise in new ways of energy generation, transmission, and storage. This has not only introduced a huge degree of variability, but also a continual shift away from traditionally centralized generation and storage to distributed energy resources (DERs). In addition, the distributed sensors, energy generators and storage devices, and networking have led to a huge increase in attack vectors that make the grid vulnerable to a variety of attacks. The interconnection between computational and physical components through a largely open, IP-based communication network enables an attacker to cause physical damage through remote cyber-attacks or attack on software-controlled grid operations via physical- or cyber-attacks. Transactive Energy (TE) is an emerging approach for managing increasing DERs in the smart-grids through economic and control techniques. Transactive Smart-Grids use the TE approach to improve grid reliability and efficiency. However, skepticism remains in their full-scale viability for ensuring grid reliability. In addition, different TE approaches, in specific situations, can lead to very different outcomes in grid operations. In this paper, we present a comprehensive web-based platform for evaluating resilience of smart-grids against a variety of cyber- and physical-attacks and evaluating impact of various TE approaches on grid performance. We also provide several case-studies demonstrating evaluation of TE approaches as well as grid resilience against cyber and physical attacks.
Reprocessing Cross-linked Polyurethanes by Catalyzing Carbamate Exchange

The reprocessing or recycling of cross-linked polymers by incorporating dynamic covalent cross-links has the potential to increase their usable lifetimes and reduce their environmental impact. Polyurethanes (PUs) are among the largest class of cross-linked polymers, making up 31% of the thermosetting materials market in 2012; however, their direct recycling into similar value materials is not well developed. We demonstrate that several Lewis acid catalysts mediate urethane exchange, likely via a dissociative mechanism, selectively and under mild conditions. Incorporating these catalysts into cross-linked polyether and polyester PUs with structures similar to commercial PU thermosets gives cross-linked materials that can completely relax stress in 100 s at temperatures as low as 140 °C. The dynamic polymers were reprocessed via compression molding to provide materials with similar cross-linking densities to as-synthesized materials. Because these systems are based on commercially available PU monomers and ...
MEMS-Based Battery-Less RFID Infrared Sensor Tag with Memory Function

In this paper we demonstrate for the first time, a battery-less radio frequency identification (RFID) infrared (IR) sensor tag capable of detecting and recording the presence of a specific IR signature associated with an event of interest. Unlike existing passive sensor tags that can only perform sensing and recording functions when wirelessly powered by a reader, the proposed IR sensor tag uses a zero-power latching micromechanical photoswitch (MP) to continuously monitor the environment and record an event occurrence without requiring any electrical power. The MP's contacts are engineered to remain latched by adhesion forces after the device is exposed to above-threshold IR irradiation, thereby forming a physical memory bit (open/closed). An integrated auto-reset functionality is also implemented to unlatch and erase the memory bit after every reading. The prototype reported here represents the first demonstration of a battery-less RFID sensor tag suitable for long-term, continuous monitoring for IR signatures indicative of failure events (e.g. overheating/fires in power infrastructure).
Models of a New World: towards a Synthesis

Three alternative world orders can be imagined in the post-World War II international relations. During most of the Cold War a bipolar order, centered on the possession of nuclear weapons, existed. This world order was incomplete, however. The United States and the Soviet Union faced each other with equal capacity to destroy each other, but in terms of economic and global influence the United States was superior. The strengthening of economic and technological dynamics increased further the U.S. influence, but also sparked the power of non-states actors, including transnational corporations and banks, independent of states. Simultaneously with the globalization of the world, one could witness the rise of non-state actors in the military and political fields. The emergence of the world order of the third type has sometimes been called the neomedieval world in which some central tenets of feudalism has re-emerged. None of these world order models can be said to dominate in today’s world and none of them is likely to emerge victorious any time soon. In recent times., globalization has suffered from various setbacks and state-centric relations have reemerged. Their focus is not, however, any more on the military competition between the United States and Russia, although some of its elements remain in the arms competition between them. Globalization has brought in new ingredients in the rivalries between states and it has appeared most visibly in the U.S.-Chinese rivalry for economic and technological dominance of the globalized world economy. In other words, a new type of economic bipolarity is winning ground and is only secondarily manifesting itself in military relations. Patterns of warfare has in recent decades been colored by fighting of non-state military forces and the rise of new feudal patterns of behavior, but they have not been pronounced enough to justify the labeling of the entire world order by the name.
Indian womb — German baby: transnational gestational surrogacy in the film Monsoon Baby (2014)

The film Monsoon Baby (2014) by Andreas Kleinert sympathetically shows the needs of the German couple seeking parenthood by gestational carrier in India. I argue that it also takes a strong stand against commercial surrogacy abroad because it points out legal issues and—more importantly—shows how surrogacy work can exploit women’s bodies, emotions, mental and physical health and even lives. From a postcolonial perspective, it is also problematic because it contains neo-colonial topoi and attitudes. Surrogacy with foreign intended parents has in the meantime been banned in India, but it may just move to other countries. Monsoon Baby remains an important contribution to the public debate about reproductive rights and choices as well as global reproductive justice.
How to starve cancer cells when nutrients are abundant.

Metabolic flexibility represents a potential point of attack for novel cancer treatments. We recently described the signaling mechanism inducing a metabolic shift in response to metformin and phenf...
Primary Aortic Root Replacement Outcomes and Risk Factors in Pediatric Patients.

Background The study sought to identify the optimal aortic root replacement (ARR) strategy for pediatric patients, and a single-center experience was analyzed. Methods Retrospective review of patients undergoing ARR from 1995 to 2018 was performed. Patients were stratified by surgical strategy (pulmonary autograft [Ross procedure], aortic homograft, mechanical valve conduit [Bentall procedure], or porcine xenograft [Freestyle bioprosthesis]) and aortic annulus size. Results ARR was performed in 206 patients with a median follow-up of 5.0 (interquartile range, 1.4-11.4) years. Root replacements included Ross procedure (n = 98), homograft (n = 83), Bentall procedure (n = 18), and Freestyle bioprosthesis (n = 7). Overall survival was 92%, and freedom from reoperation or death was 81%. Reoperation-free survival was superior in the Ross group when compared with other groups. Because surgical options differ based on the size of the aortic annulus, the analysis was arbitrarily stratified. When the aortic annulus diameter was greater than 19 mm (n = 74), procedures included Ross procedure (n = 23), homograft (n = 29), Bentall procedure (n = 17), and Freestyle bioprosthesis (n = 5). Reoperation-free survival at median follow-up (5 years) was 86%, 58%, 100%, and 100%, respectively. The Bentall procedure offered the longest freedom from reoperation. In the subset with aortic annulus diameter less than 19 mm and a pulmonary valve suitable for a Ross procedure, patients underwent the Ross procedure (n = 75) or homograft ARR (n = 36). At median follow-up (3.8 years), reoperation-free survival was longer after the Ross procedure than after homograft ARR (88% vs 46%; P Conclusions In patients with a large aortic annulus, a Bentall ARR offers the longest reoperation-free survival. For patients with small aortic roots, a Ross procedure provides better a reoperation-free survival than does homograft ARR.
The European Union as a Christian democracy: a heuristic approach

While the historical role played by Christian Democrats in the construction of the European Union (EU) is well-known and amply documented, the impact this has had on the EU as it exists today has r...
Detecting m6A methylation regions from Methylated RNA Immunoprecipitation Sequencing.

Motivation The post-transcriptional epigenetic modification on mRNA is an emerging field to study the gene regulatory mechanism and their association with diseases. Recently developed high-throughput sequencing technology named Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) enables one to profile mRNA epigenetic modification transcriptome-wide. A few computational methods are available to identify transcriptome-wide mRNA modification, but they are either limited by over-simplified model ignoring the biological variance across replicates or suffer from low accuracy and efficiency. Results In this work, we develop a novel statistical method, based on an empirical Bayesian hierarchical model, to identify mRNA epigenetic modification regions from MeRIP-seq data. Our method accounts for various sources of variations in the data through rigorous modeling, and applies shrinkage estimation by borrowing informations from transcriptome-wide data to stabilize the parameter estimation. Simulation and real data analyses demonstrate that our method is more accurate, robust and efficient than the existing peak calling methods. Availability Our method TRES is implemented as an R package and is freely available on Github at https://github.com/ZhenxingGuo0015/TRES. Supplementary information Supplementary data are available at Bioinformatics online.
Transmission Electron Microscopy

The ultimate resolution of any imaging technique is limited to about the wavelength of the radiation which carries the information. For light, the wavelength is on the order of 500 nm. However, modern science demands information from samples at far higher resolution—in the limit, it would be ideal to image individual atomic positions in crystals, requiring a resolution of about 0.1 nm.
Hemoglobin A1c Is a Predictor of New Insulin Dependence After Partial Pancreatectomy: A Multi-Institutional Analysis

Pancreatic diseases have long been associated with impaired glucose control. This study sought to identify the incidence of new insulin-dependent diabetes mellitus (IDDM) after pancreatectomy and the predictive accuracy of hemoglobin A1c (HbA1c) or blood glucose. Patients who underwent partial pancreatectomy and had preoperative HbA1c available at two academic institutions were assessed for new IDDM on discharge in relation to complication rates and survival. Of the 267 patients analyzed, 67% had abnormal HbA1c levels prior to surgery (mean 6.8%, glucose 135 mg/dL). Two hundred eight (77.9%) were not insulin-dependent prior to surgery, and 35 (16.8%) developed new IDDM after resection. On multivariable regression, increasing HbA1c and preoperative glucose were the only significant predictors for new IDDM. Optimal predictive cutoffs (HbA1c of 6.25% and glucose of 121 mg/dL) were determined in a discovery group (n = 143) and confirmed in a validation group (n = 124) with a diagnostic sensitivity of 72.7% and specificity of 84.8%. Patients with new IDDM after resection had higher rates of severe complications (OR 3.39), increased TPN at discharge (OR 4.32), and increased rates of discharge to nursing facilities (OR 2.57) (all P < 0.05). New IDDM was also associated with a decreased cancer-specific survival. Preoperative HbA1c ≥ 6.25% and blood glucose ≥ 121 mg/dL can accurately identify patients at increased risk of IDDM. These diagnostics may help identify patients in a preoperative setting that may benefit from interventions such as diabetes education or enhanced glucose control preoperatively.
Development and Implementation of a Real-time Bundle-adherence Dashboard for Central Line-associated Bloodstream Infections

Introduction Central line-associated bloodstream infections (CLABSIs) are the most common hospital-acquired infection in pediatric patients. High adherence to the CLABSI bundle mitigates CLABSIs. At our institution, there did not exist a hospital-wide system to measure bundle-adherence. We developed an electronic dashboard to monitor CLABSI bundle-adherence across the hospital and in real time. Methods Institutional stakeholders and areas of opportunity were identified through interviews and data analyses. We created a data pipeline to pull adherence data from twice-daily bundle checks and populate a dashboard in the electronic health record. The dashboard was developed to allow visualization of overall and individual element bundle-adherence across units. Monthly dashboard accesses and element-level bundle-adherence were recorded, and the nursing staff's feedback about the dashboard was obtained. Results Following deployment in September 2018, the dashboard was primarily accessed by quality improvement, clinical effectiveness and analytics, and infection prevention and control. Quality improvement and infection prevention and control specialists presented dashboard data at improvement meetings to inform unit-level accountability initiatives. All-element adherence across the hospital increased from 25% in September 2018 to 44% in December 2019, and average adherence to each bundle element increased between 2018 and 2019. Conclusions CLABSI bundle-adherence, overall and by element, increased across the hospital following the deployment of a real-time electronic data dashboard. The dashboard enabled population-level surveillance of CLABSI bundle-adherence that informed bundle accountability initiatives. Data transparency enabled by electronic dashboards promises to be a useful tool for infectious disease control.
Analytical Maneuver Library for Remote Inspection with an Underactuated Spacecraft

This paper presents an analytical library for maneuvering of an underactuated spacecraft around a central target with application to remote inspection. Free-flying small spacecraft are an attractiv...
Ribonucleotide Reductase Regulatory Subunit M2 as a Driver of Glioblastoma TMZ-Resistance through Modulation of dNTP Production

Glioblastoma (GBM) remains one of the most resistant and fatal forms of cancer. Previous studies have examined primary and recurrent GBM tumors, but it is difficult to study tumor evolution during therapy where resistance develops. To investigate this, we performed an in vivo single-cell RNA sequencing screen in a patient-derived xenograft (PDX) model. Primary GBM was modeled by mice treated with DMSO control, recurrent GBM was modeled by mice treated with temozolomide (TMZ), and during therapy GBM was modeled by mice euthanized after two of five TMZ treatments. Our analysis revealed the cellular population present during therapy to be distinct from primary and recurrent GBM. We found the Ribonucleotide Reductase gene family to exhibit a unique signature in our data due to an observed subunit switch to favor RRM2 during therapy. GBM cells were shown to rely on RRM2 during therapy causing RRM2-knockdown (KD) cells to be TMZ-sensitive. Using targeted metabolomics, we found RRM2-KDs to produce less dGTP and dCTP than control cells in response to TMZ (p<0.0001). Supplementing RRM2-KDs with deoxycytidine and deoxyguanosine rescued TMZ-sensitivity, suggesting an RRM2-driven mechanism of chemoresistance, established by regulating the production of these nucleotides. In vivo, tumor-bearing mice treated with the RRM2-inhibitor, Triapine, in combination with TMZ, survived longer than mice treated with TMZ alone (p<0.01), indicating promising clinical opportunities in targeting RRM2. Our data present a novel understanding of RRM2 activity, and its alteration during therapeutic stress as response to TMZ-induced DNA damage.
Technology and Control of the Labor Process

Longshoring on the U.S. West Coast has undergone a technological transformation over the past quarter century. Perhaps the most critical effect of mechanization is the more than nine-fold increase in labor productivity since 1960. Furthermore, the effects of technological change and attendant productivity gains on industrial relations have been considerable. Most obviously, the replacement of men by machines has had a drastic impact on employment levels. In addition, we will argue that a less apparent, but by no means insignificant, implication of the transformation has been a major shift in control of the labor process from the workers to management.
Temperate Bacteriophages of Bacillus subtilis

Bacillus subtilis is a gram-positive sporulating soil eubacterium. Like its gram-negative counterpart in molecular biology, Escherichia coli, it is prototrophic, easy to cultivate, and relatively harmless. Genetic exchange mechanisms are known for B. subtilis: DNA transformation, either “natural” (in strain 168 or its derivatives) or using protoplasts; generalized transduction, usually carried out by the very large bacteriophage PBS1; and specialized transduction. A number of useful plasmids have been described or constructed, although most of them originated in other gram-positive bacteria; shuttle vectors useful both in B. subtilis and in E. coli have been produced. A transposon, Tn917, can be used for shotgun mutagenesis; it has been engineered in ways that make it useful for producing transcriptional fusion insertions (with the E. coli β-galactosidase gene, for example; see Youngman et al., 1985). A useful system for studying phage infections in minicells has been developed (Reeve, 1977) Almost one-half as many genes have been identified in B. subtilis as in E. coli. The sporulation process is considered a useful analogue of developmental and cellular differentiation in higher organisms and has been subjected to extensive study. B. subtilis has been known for some time to make use of what was originally thought to be a unique mechanism of metabolic control: it produces multiple RNA polymerases, which differ from each other in the polypeptides they use as o-factor. Useful reviews of these and other aspects of B. subtilis molecular biology can be found in Dubnau (1982, 1985).
ALLELIC RECOMBINATION AND ITS RELATION TO RECOMBINATION OF OUTSIDE MARKERS IN YEAST.

N recent years a number of examples have been reported in which crosses Ibetween allelic mutants of Saccharomyces cerevisim (ROMAN 1956a; ROMAN and JACOB 1958) produce nonmutant progeny with a frequency which is higher than is expected from reverse mutation. Such revertants can be shown to result from an event which does not have the characteristics of crossing over. ROMAN and JACOB (1958) have described one such case in mitotically dividing diploid yeast cells involving two allelic isoleucine-requiring mutants of different origin. This system has been examined further in the present study by including two more allelic mutants at this locus. The relationship between allelic recombination and the recombination of outside markers among spontaneous revertants has been examined in detail and the mutant sites of the four alleles have been ordered on the chromosome. MATERIALS AND METHODS
What is Simulated Annealing

Beginning in 1983, simulated annealing was marketed as a global optimization methodology that mimics the physical annealing process by which molten substances cool to crystalline lattices of minimal energy. This marketing strategy had a polarizing effect, attracting those who delighted in metaphor and alienating others who found metaphor insufficient at best and facile at worst. In fact, the emotional outbursts that accompany many discussions of simulated annealing are an unfortunate distraction. Whatever its pros and cons, simulated annealing can be grounded in rigorous mathematics. Here we provide an elementary, self-contained introduction to simulated annealing in terms of Markov chains.
An undergraduate software engineering program . . . within electrical engineering

For the past two years, the Department of Electrical Engineering has offered a specialty within electrical engineering to help prepare graduates for careers in embedded software engineering. This program offers a unique blend of software science and engineering within an ABET-accredited electrical engineering program.
Radiation damage in metals and semiconductors

A survey of our present knowledge about radiation damage in crystalline solids is presented. The subject matter is specially selected to facilitate comparisons between metals and semiconductors. The damage pattern produced by different kinds of irradiation and the experimental techniques available for the investigation of radiated-induced defects are described. It is emphasized that the key problems in the understanding of radiation damage in the most thoroughly investigated materials (i.e., fee metals and elemental semiconductors) center around the nature of the self-interstitials. Theoretical reasons for the complex behaviour of these defects are discussed. An interpretation for radiation damage annealing in silicon is suggested.
The space of multibody fundamental matrices: rank, geometry and projection

We study the rank and geometry of the multibody fundamental matrix, a geometric entity characterizing the two-view geometry of dynamic scenes consisting of multiple rigid-body motions. We derive an upper bound on the rank of the multibody fundamental matrix that depends on the number of independent translations. We also derive an algebraic characterization of the SVD of a multibody fundamental matrix in the case of two or odd number of rigid-body motions with a common rotation. This characterization allows us to project an arbitrary matrix onto the space of multibody fundamental matrices using linear algebraic techniques.
Cognitive Behavioral Analysis System of Psychotherapy

The Cognitive Behavioral Analysis System of Psychotherapy (CBASP; Keller, McCullough, Klein, Arnow, Dunner, Gelenberg et al., 2000; McCullough, 1984, 2000, 2006) is a psychological treatment program developed specifically for chronically depressed patients (Klein, in press; McCullough, Klein, Borian, Howland, Riso, Keller, et al., 2003). In the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR; American Psychiatric Association, 2000), chronic depression is a unipolar affective disorder lasting a minimum of two years; without adequate treatment, and the patient more often than not faces a lifetime of psychosocial disability. Early (prior to age 21) and late-onset are the diagnostic descriptors indicating when the disorder began. The clinical course among chronically depressed patients includes several types of profiles. Two of the more common ones are (1) an early-onset of dysthymia beginning at 12–13 years of age followed by a continuing course that includes one or more episodes of major depression—a clinical profile labeled “double depression”; and (2) a late-onset course exacerbated at age 25–26 with a major depressive episode that almost never fully remits. Approximately 23% of late-onset adults who have their first episode do not recover, and the course becomes chronic. Without adequate regimes of medication and psychotherapy, prognosis for recovery for both types is poor, and even with treatment, the ever-present danger of relapse and recurrence remains a serious threat throughout the lifespan. Keywords: chronic depression; psychotherapy; CBASP; psychopathology; disciplined personal involvement
Riboflavin-methotrexate interactions: Photochemical reaction and competition for transport in the L1210 mouse leukemia cell

Abstract Methotrexate transport in the L1210 mouse leukemia cell is a carrier-mediated process. Riboflavin competitively inhibits the unidirectional influx of methotrexate and possibly utilizes this carrier, at least in part, for its own transport. The apparent affinity of riboflavin for this transport mechanism is, however, much lower than that of methotrexate. In addition to their competition at the cell membrane for the transport mechanism, riboflavin and methotrexate undergo a time-dependent, photochemical reaction, which results in the formation of methotrexate derivatives that are separable by column chromatography. The compounds were not identified, but some of their properties were characterized. The labeled methotrexate derivatives do not significantly bind to the intracellular enzyme, dihydrofolate reductase. Their transport occurs by a route different from that for methotrexate, since uptake is more rapid, temperature sensitivity is markedly different, and inhibitors of methotrexate uptake are without effect on these derivatives. Other flavin-folate interactions were demonstrated by the reaction between riboflavin and the parent compound, folic acid, and by the reaction between methotrexate and ethanol lumiflavin, a congener of riboflavin.
The search for the genetic lesion in Ashkenazi Jews with Classic Tay-Sachs disease.

Publisher Summary This chapter gives an overview on the search for the genetic lesion in Askenazi Jews with Classic Tay-Sachs diseases (TSD). Elucidation of the mutation underlying classic TSD in the Ashkenazi Jewish population posed more of a challenge. Restriction enzyme digestion patterns of the mutant α-chain gene were identical to those of the normal gene, indicating that the mutation involved a small deletion or single base change. Amplification of the region encompassing the mutation by polymerase chain reaction followed by digestion of the amplified product with Dde1, then Southern analysis of the sample, reveals a 120-base-pair DNA (deoxyribonucleic acid) fragment from the normal allele in contrast to an 85-base pair piece from the mutant. It has generally been assumed that only one mutation gives rise to the classic form of TSD in the Ashkenazi Jewish population. PCR-based assay for the insertion mutation which involved amplification of a segment of exon 11 inclusive of the region of insertion and detection of the lesion by probing duplicate samples of the amplified product with oligonucleotides specific for either the normal or mutant sequence was developed.
The Surprising Kinetics of the T Cell Response to Live Antigenic Cells

Cooperation between CD4+ and CD8+ T cells is required for the proper development of primary effector and memory CD8+ T cells following immunization with noninflammatory immunogens. In this study, we characterized murine CD4+ and CD8+ T cell responses to male-specific minor histocompatibility (HY) Ags following injection of live male cells into females of the same strain. Male cells are rejected 10–12 days after transfer, coinciding with the expansion and effector function of CD8+ CTLs to two H-2Db-restricted epitopes. Although anti-HY CD4+ T cell responses are readily detectable day 5 posttransfer, CD8+ responses are undetectable until day 10. The early CD4+ response is not dependent on direct presentation of Ag by donor male cells, but depends on presentation of the male cells by recipient APC. The CD4+ T cell response is required for the priming of CD8+ T cell effector responses and rejection of HY-incompatible cells. Unexpectedly, HY-specific CD4+ T cells are also capable of efficiently lysing target cells in vivo. The delay in the CD8+ T cell response can be largely abrogated by depleting T cells from the male inoculum, and donor male CD8+ T cells in particular suppress host anti-HY CD8+ responses. These data demonstrate dramatic differences in host T cell responses to noninflammatory Ags compared with responses to pathogens. We explain the delayed CD8+ response by proposing that there is a balance between cross-presentation of Ag by helper cell-licensed dendritic cells, on the one hand, and veto suppression by live male lymphocytes on the other.
8-Spinor Quantum Gravity

Quantum gravity has been so elusive because we have tried to approach it by two paths which can never meet: quantum mechanics and general relativity. These contradict each other not only in superdense regimes, but also in the vacuum. We explore a straight road to quantum gravity here--the one mandated by Clifford-algebra covariance. This bridges the gap from microscales--where the massive Dirac propagator is a sum over null zig-zags--to macroscales--where we see the energy-momentum current, *T and the resulting Einstein curvature, *G. For massive particles, *T flows in the "cosmic time" direction, y^0--centrifugally in an expanding universe. Neighboring centrifugal currents of *T present opposite spacetime vorticities *G to the boundaries of each others' worldtubes, so they advect--i.e. attract, as we show here by integrating a Spin^c-4 Lagrangian by parts in the spinfluid regime. This boundary integral not only explains why stress-energy *T is the source for gravitational curvature *G, but also gives a value for the gravitational constant, kappa(x^0) that depends on the current scale factor of our expanding Friedmann 3-brane. On the microscopic scale, quantum gravity appears naturally as the statistical mechanics of null zig-zags of massive particles in "imaginary time," y^0.
Strategic planning for the 1990s: a challenge for change

Strategic planning is presented as a vehicle for change. Essential characteristics include definition of goals, assessment of external opportunities and pressure, analysis of existing capabilities and potential resources, formulation of a strategic plan, and implementation of an appropriate course of action. Specific problems in strategic planning within the context of schools of information and library studies are discussed. Questions raised dur4J,g a strategic planning session are offered as typical concerns facing our educational institutions.
THE YEAR‐END EFFECT IN MONEY MARKET YIELDS: BEYOND ONE MONTH AND BEYOND THE CRISIS

U.S. money market yields up to one month have shown changes consistent with year-end liquidity preferences. I find that three- and six-month negotiable certificate of deposit (CD), Eurodollar deposit (ED), and banker's acceptance (BA) yields are also affected by year-end liquidity preferences. Two- and three-month financial commercial paper (CP) yield changes are less pronounced. Banks—CD, ED, and BA issuers—have increased year-end liquidity needs, unlike finance companies—predominant CP issuers. The year-end effect disappears after the 2007–2008 crisis as depositories' cash holdings increase. CD, ED, and CP yields diverge postcrisis, suggesting that investors no longer consider them close substitutes.
Alterations in the Outer Membrane of the Cell Envelope of Heptose-Deficient Mutants of Escherichia coli

The composition of the cell envelope of a heptose-deficient lipopolysaccharide mutant of Escherichia coli, GR467, was studied after fractionation into its outer and cytoplasmic membrane components by means of sucrose density gradient centrifugation. The outer membrane of GR467 had a lower density than that of its parent strain, CR34. Analysis of the fractionated membranes of GR467 indicated that the phospholipid-to-protein ratio had increased 2.4-fold in the outer membrane. The ratio in the mutant cytoplasmic membrane was also increased, although to a lesser extent. By employing a third parameter, the lipid A content of the outer membrane, it was found that the observed phospholipid-to-protein change in the outer membrane was due predominantly to a decrease in the relative amount of protein. This decrease in protein was particularly significant, since it was concomitant with a 68% decrease in the lipid A recovered in the outer membrane of GR467 relative to the lipid A recovered in the outer membrane of CR34. Similar findings were observed in a second heptose-deficient mutant of E. coli, RC-59. The apparent protein deficiency in GR467 was further studied by subjecting solubilized envelope proteins to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was found that major envelope proteins which were localized in the outer membrane were greatly diminished in GR467. Two revertants of GR467 with the wild-type amounts of heptose had wild-type relative levels of protein in their outer membranes. A partial heptose revertant had a relative level of protein in its outer membrane between those of the mutant and wild type. Images
tert‐Butylmagnesium Chloride

(X = Cl) [672-22-5] C4H9ClMg (MW 116.87) InChI = 1S/C4H9.ClH.Mg/c1-4(2)3;;/h1-3H3;1H;/q;;+1/p-1 InChIKey = ZDRJSYVHDMFHSC-UHFFFAOYSA-M (X = Br) [2259-30-5] C4H9BrMg (MW 161.32) InChI = 1S/C4H9.BrH.Mg/c1-4(2)3;;/h1-3H3;1H;/q;;+1/p-1 InChIKey = VPFPCNQBOYUQRG-UHFFFAOYSA-M (adds to many unsaturated functional groups; tert-butyl can displace halide and like groups; can function as a strong base and a Lewis acid1b–f) Physical Data: NMR observations indicate that tert-BuMgCl in Et2O and THF and tert-BuMgBr in THF are in fact mixtures of tert-BuMgX, tert-Bu2Mg, and MgX2.2, 3 Although essentially monomeric in THF, tert-BuMgCl is mainly dimeric in Et2O.4 A solid of composition tert-BuMgBr(Et2O)2, probably having a dimeric structure, has been isolated.5 Solubility: sol Et2O and THF; insol hydrocarbons. Form Supplied in: solutions of tert-BuMgCl in Et2O and THF are commercially available. Analysis of Reagent Purity: see entry for Methylmagnesium Bromide. Preparative Methods:1c,e,6 in spite of the commercial availability of tert-BuMgCl solutions, tert-BuMgCl3, 7 and tert-BuMgBr are often prepared from reaction of a tert-butyl halide and Magnesium, usually in Et2O or THF. Handling, Storage, and Precautions: see entry for Methylmagnesium Bromide tert-Butyl Grignard reagents do not significantly attack Et2O or THF at normal reaction temperatures.
Attributive types for proof erasure

Proof erasure plays an essential role in the paradigm of programming with theorem proving. In this paper, we introduce a form of attributive types that carry an attribute to determine whether expressions assigned such types are eligible for erasure before run-time. We formalize a type system to support this form of attributive types and then establish its soundness. In addition, we outline an extension of the developed type system with dependent types and present some examples to illustrate its use in practice.
Using capture-recapture models to make objective post-inspection decisions

Problem Definition: Project managers manage the development process by enabling software developers to perform inspection of early software artifacts. However, an inspection can only detect the presence of defects; it cannot certify the absence of defects or indicate how many defects remain post inspection. Managers need objective information to help them decide when they can safely stop the inspection process. A reliable estimate of the number of defects remaining in software can aid mangers in determining whether there is a need for additional inspections.
Enzyme affinity in the acylation of lysophosphatidylcholine

Analogues of 1-palmitoyl-sn-glycero-3-phosphorylcholine were used to ascertain the respective roles of the 1-palmitoyl-sn-glycero and choline groups in binding this substrate to the transferase catalyzing the acylation reaction. 1-Palmitoyl-sn-glycero-3-phosphorylhomocholine proved to be an effective competitive inhibitor whereas 1-palmitoyl-2-deoxyglycero-3-phosphorylcholine was totally ineffective. The data support the view that the 1-palmitoyl-sn-glycero group plays the major role in determining enzyme affinity whereas the choline group functions primarily in the subsequent steps of the acylation reaction.
Electron microscopy supports a fibrous substructure for lens intermediate filaments

The substructure of intermediate filaments from bovine lens cortical fiber cells was investigated by electron microscopy. Native filaments and synthetic ones regenerated from the total cytoskeletal extract and from the three purified subunits were examined. The morphologies from these various sources were essentially identical, with the exception that filaments reconstituted from one of the purified polypeptides were much shorter, very contorted and showed strings of aggregated protein. The solid cylindrical, unbranching filaments consisted of a helical arrangement of at least two, 5 nm diameter strands. The evidence indicated that each strand was composed of two, 2 nm diameter protofilaments which were also helically constructed (right-handed) with a periodicity of 11.6 nm. Intermediate filament diameter varied widely (8–14.8 nm, average 11.3 nm) and in a direct, linear manner relative to the apparent progression (helical) angle of the strands across the filament face. These conclusions were obtained fro...
Developing Student's Innovation Skills for Globalized Electronic Industry

One of the very dynamic and demanding industries is, with no question, the electronic industry. It is also one of industries strongly shaped by globalization and therefore requires that it's engineers to carry multi-faceted training. To be hired and capable to keep the job the today and future engineer must demonstrate innovative skills or, in more general terms, to be resourceful. This 10 years long study presents the results of training of two groups of electrical engineering students selected each academic year to develop design projects. The requirement of each two semester long project is to develop novel circuitry (amplifiers, switches, etc.) or novel component (transistor, photodetector, etc.). Both groups were provided with commercial design packages. The difference however is that students of one group were supported by internships and worked at the sites of electronic companies and the other group was supported by university research assistantships. Every year based on scholastic achievements 10-15 students were selected for the project oriented course. Students were given the freedom to select a project topic. In current presentation we discuss the development of specific skills which undergraduate and graduate students of UMass do acquire in development of RF technology working closely with engineering teams of companies such as MACOM Technology Solutions, RF Microdevices, Raytheon and others.
A fluorescent substrate for the assay of phosphatidylinositol-specific phospholipase C: 4-(1-pyreno)butylphosphoryl-1-myo-inositol

Racemic 4-(1-pyreno)butylphosphoryl-1-myo-inositol was synthesized from a pentaprotected inositol-1-dimethylphosphite by phosphite coupling with 4-(1-pyreno)butanol. It is a good substrate for a very sensitive assay of phosphatidylinositol-specific phospholipase C.
Strength, endurance, and work capacity after muscle strengthening exercise in postpolio subjects

Abstract Objective: To determine whether a 12-week home quadriceps muscle strengthening exercise program would increase muscle strength, isometric endurance, and tension time index (TTI) in postpolio syndrome subjects without adversely affecting the surviving motor units or the muscle. Design: A longitudinal study to investigate the effect of a 12-week exercise program on neuromuscular function and electromyographic variables. Setting: Neuromuscular laboratory of a university hospital. Subjects: Seven subjects were recruited from a cohort of 12 subjects who had participated in a previous exercise study. All subjects had greater than antigravity strength of the quadriceps. Upon completion of a postpolio questionnaire, all acknowledged common postpolio syndrome symptoms such as new fatigue, pain, and weakness; 6 of the 7 acknowledged new strength decline. Intervention: On Mondays and Thursdays subjects performed three sets of four maximal isometric contractions of the quadriceps held for 5 seconds each. On Tuesdays and Fridays subjects performed three sets of 12 dynamic knee extension exercises with ankle weights. Main Outcome Measures: Neuromuscular variables of the quadriceps muscles were measured at the beginning and completion of the exercise program and included: isokinetic peak torque (ISOKPT, at 60°/sec angular velocity) and total work performed of four contractions (ISOKTW), isometric peak torque (MVC), endurance (EDUR, time subject could hold isometric contraction at 40% of the initial MVC), isometric tension time index (TTI, product of endurance time and torque at 40% of MVC), and initial and final ankle weight (WGT, kg) lifted. Electromyographic variables included: fiber density (FD), jitter (MCD), and blocking (BLK) from single fiber assessment and median macro amplitude (MACRO). Serum creatine kinase (CK) was also measured initially and at 4-week intervals throughout the study. Results: The following variables significantly ( p p > .05) change: FD, MCD, BLK, MACRO, and CK. Conclusions: This home exercise program significantly increased strength, endurance, and TTI without apparently adversely affecting the motor units or the muscle, as the EMG and CK variables did not change.
Leiomyoepithelioma of Iris Pigment Epithelium

• A 4-year-old boy had a jet-black, nodular lesion growing in his right iris. Detailed clinical and histopathologic studies of this unusual tumor showed the lesion to be derived from the anterior iris pigment epithelium. The tumor cells appeared to be benign and exhibited characteristics of both pigment epithelium and smooth muscle. We have called this tumor "leiomyoepithelioma of iris pigment epithelium."
Interactions among endocrine control systems in the regulation of ovarian function.

During sequential physiologic maturation of an individual follicle, the number of granulosa cells increases in excess of 1000-fold, while intra-ovarian concentrations of sex steroids escalate by 100-fold. The recent development of several in vitro ovarian systems has permitted a more extensive and direct assessment of specific mechanisms that control growth and steroidogenesis in granulosa and thecal cells. For example. estradiol and follicle stimulating-hormone seem to promote the production by ovarian cells of low-molecular-weight growth factors, that may participate in granulosa cell proliferation. Luteinizing hormone stimulates the de novo synthesis of prostacyclin by granulosa cells in vitro . Prostacyclin, in turn, may regulate the microvasculature of the maturing follicle and directly stimulate steroidogenesis. The effects of individual hormones are markedly modified by other intraovarian endocrine factors, and by the precise status of cytodifferentiation of the ovarian cells. For example, the actions of prolactin on granulosa-cell steroidogenesis are influenced strikingly by both agonistic and antagonistic interactions between prolactin and estradiol, as well as by the level of granulosa-cell cytodifferentiation attained in vivo . Similar bihormonal intrafollicular interactions are recognizable between estrogen and follicle-stimulating hormone in the early follicle, and between estradiol and luteinizing hormone in the maturing follicle. These interactions are susceptible to more precise examination under defined in vitro conditions. Overall, recent advances in biomedical research continue to elucidate basic molecular mechanisms of hormone action in ovarian cell physiology. Such advances are likely to continue to provide important insights into the pathophysiology of clinical disorders of human reproduction.