cssi/SciSciGPT-SciSciNet huggingface dataset:
Arylisothiocyanate-Containing esters of caffeic acid designed as affinity ligands for HIV-1 integrase

Integrase is an enzyme found in human immunodeficiency virus, which is required for the viral life cycle, yet has no human cellular homologue. For this reason, HIV integrase (IN) has become an important target for the development of new AIDS therapeutics. Irreversible affinity ligands have proven to be valuable tools for studying a number of enzyme and protein systems, yet to date there have been no reports of such affinity ligands for the study of IN. As an initial approach toward irreversible ligand design directed against IN, we appended isothiocyanate functionality onto caffeic acid phenethyl ester (CAPE), a known HIV integrase inhibitor. The choice of isothiocyanate as the reactive functionality, was based on its demonstrated utility in the preparation of affinity ligands directed against a number of other protein targets. Several isomeric CAPE isothiocyanates were prepared to explore the enzyme topography for reactive nitrogen and sulfur nucleophiles vicinal to the enzyme-bound CAPE. The preparation of these CAPE isothiocyanates, required development of new synthetic methodology which employed phenyl thiocarbamates as latent isothiocyanates which could be unmasked near the end of the synthetic sequence. When it was observed that β-mercaptoethanol (β-ME), which is required to maintain the catalytic activity of soluble IN (a F185KC280S mutant), reacted with CAPE isothiocyanate functionality to form the corresponding hydroxyethylthiocarbamate, a variety of mutant IN were examined which did not require the presence of β-ME for catalytic activity. Although in these latter enzymes, CAPE isothiocyanate functionality was presumed to be present and available for acylation by IN nucleophiles, they were equally effective against Cys to Ser mutants. One conclusion of these studies, is that upon binding of CAPE to the integrase, nitrogen or sulfur nucleophiles may not be properly situated in the vicinity of the phenethyl aryl ring to allow reaction with and covalent modification of reactive functionality, such as isothiocyanate groups. The fact that introduction of the isothiocyanate group onto various positions of the phenethyl ring or replacement of the phenyl ring with naphthyl rings, failed to significantly affect inhibitory potency, indicates a degree of insensitivity of this region of the molecule toward structural modification. These findings may be useful in future studies concerned with the development and use of HIV-1 integrase affinity ligands.
Functional differences among the six Saccharomyces cerevisiae tRNATrp genes

The Saccharomyces cerevisiae haploid genome includes six copies of the gene encoding tRNATrp which are scattered on five chromosomes. Other, non-functional tDNATrp fragments also occur in the genome. The segments of all six genes which encode the 72-nucleotide mature tRNATrp, as well as a 34-nucleotide intervening sequence, are identical. However, the 5' and 3' flanking sequences diverge virtually at the boundaries of the coding region. We have used an assay based on suppression of UGA mutations by multi-copy clones of tDNATrp to search for functional differences among these genes. Previous studies with one tDNATrp had demonstrated that moderate suppression of a UGA mutation, leu2-2, resulted from introduction of a multi-copy clone of the gene. Attempts to use this assay to select tDNATrp clones from a yeast genomic library yielded only four of the six different clones. The other two genes were amplified by PCR and cloned in pRS202, a 2 mu vector also used for the genomic library. Plasmids bearing the six tRNA genes were transformed into S. cerevisiae strain JG369.3B and scored for their ability to suppress the leu2-2 mutation as well as his4-260, another UGA marker. Two of the six tRNATrp clones were unable to suppress either marker, two evidenced weak suppression of the Leu auxotrophy, and two were able to suppress both markers. Growth rates in liquid media requiring suppression were measured for cell lines carrying each of the clones. Differences greater than 50-fold were observed in media lacking histidine. An evolutionary tree based on 5'-flanking sequence corresponds reasonably well with suppressor activity, while a similar analysis of 3'-flanking sequence does not. This suggests that the functional differences are based on divergence in the 5'-flanking sequences of the tRNATrp genes.
Hormone‐defined cell system for studying G‐protein coupled receptor agonist‐activated growth modulation: δ‐Opioid and serotonin‐5HT2C receptor activation show opposite mitogenic effects

G-protein-coupled receptor (GPCR) agonist-activated transformation of NIH/3T3 fibroblast cells has been documented by many workers. Our present interest is in the growth control exerted by these agonists. The mechanisms involved in GPCR agonist-activated growth regulation are not known and investigations using existing cell lines are complicated by the endogenous expression of numerous different GPCRs as well as by the fact that these cell lines are cultured in serum that contains naturally occurring agonists for these receptors. To study the agonist induced growth response of cells transfected with either δ-opioid or serotonin-5HT2C neurotransmitter receptor genes, we have developed new clonal cell lines derived from NIH/3T3 mouse fibroblast cells. These new cell lines, designated with the suffix 3T3DA, can be cultured stably in serum-free, hormone-defined medium: insulin is the only exogenous growth factor added to the culture medium of proliferating 3T3DA cell lines, and their proliferation can be stopped and started by the respective removal or addition of insulin. Micromolar concentrations of agonists were used to activate the corresponding opioid and serotonin receptors over periods extending to 6 days. We observed distinct patterns of GPCR-specific, agonist-activated growth regulation in serum-free cultures, but not in serum-supplemented cultures. At concentrations > 10 μM, morphine inhibits growth of δ-opioid receptor-expressing cells by 40% with respect to normal 3T3DA cells. Opioid agonist induced inhibition of cyclic AMP (cAMP) production as well as growth down-regulation are pertussis toxin sensitive indicating that the exogenously expressed δ-opioid receptors demonstrate classical opioid receptor signaling. The presence of 1 μM serotonin stimulates growth of serotonin-5HT2C receptor-expressing cells by approximately 100% with respect to normal 3T3DA cells. Neither the untreated nor the agonist-treated cells form colonies in soft agar, indicating that they retain anchorage-dependent growth control. These cell lines provide a simple system that could be used as a tool for probing the complex molecular mechanisms associated with GPCR agonist-activated growth control. J. Cell. Physiol. 171:61–74, 1997. © 1997 Wiley-Liss, Inc.
When encoding fails: instructions, feedback, and registration without learning.

Four experiments replicated and extended the registration-without-learning effect, in which there is little improvement in the ability to discriminate an old target (X) from a highly similar test item (Y) after the first few presentations of X, even though judgments of frequency continue to rise in an openended fashion. Forced-choice testing revealed the anomalous form of the learning curve for X-Y discrimination (faster and then slower than the exponential). Effects of several different learning instructions were compared, but these appeared to affect only the level of initial learning, and to do little to promote X-Y discrimination learning on later presentations. The opportunity for self-testing with feedback during study provided no benefits when responding was covert, but did when overt anticipation was required. The findings are discussed in relation to the roles of bottom-up and topdown processing in memory encoding, and to the importance of error-correcting feedback in further structural learning of materials, once the materials have become familiar.
Fracto-emission from single fibres of Kevlar

Fracto-emission (FE) is the emission of particles (e.g. electrons, ions and photons) during and following fracture. In this paper, we present data on electron emission (EE) and positive ion emission (PIE) from the tensile fracture of Kevlar single fibers. The fibers were initially fractured in pure tension, where a stranded form of fracture was observed, often with multiple peaks spread over several hundred microseconds. The loading condition was then changed by stretching and breaking the fibers over a dull metal edge. With this change in the loading, different forms of fracture were observed, each with distinctive forms of emission curves. When fracture was accompanied by extensive fibril formation, total emission was high and both EE and PIE decay times were long relative to fractures in which little fibril formation occurred. The results of this study suggest that FE has some applicability as a tool for the detection of fracture mechanisms of single fibers.
Value Theory for Virtue Ethics: Rational, Objective, and Human Criteria

This paper is an attempt at framing Virtue Ethics in a manner that it is not derivative of either deontological or utilitarian ethics. The purpose in doing this is to avoid certain pitfalls in the other two approaches, and the argument hinges on a holistic treatment of values in a social community, as well as the role of practical rationality as the means to edify such a system. There follows an examination of John Dancy and John McDowell’s work on this, with a critical perspective on where these clarifications have currency, and where these fall short.
Stener lesion after lateral dislocation of the proximal interphalangeal joint—Indication for open reduction

The management of lateral dislocations of the proximal interphalangeal joint is controversial. Absolute indications for operative management are few, and most dislocations can be treated nonoperatively. In this case, the ulnar collateral ligament was trapped between the lateral band and central slip of the dorsal apparatus and required open reduction for a satisfactory functional result.
PDGF-BB regulates IGF-mediated IGFBP-4 proteolysis in fetal lung fibroblasts.

Insulin-like growth factor (IGF)-stimulated lung fibroblast proliferation may be regulated by locally produced IGF-binding proteins (IGFBPs) during lung development. Recent evidence has shown that many growth factors participate in the regulation of cell proliferation by regulating IGFBPs. Because platelet-derived growth factor-BB (PDGF-BB)is highly expressed during lung development and is known to regulate IGFBP-4 production bylung cells, we examined the mechanisms by which PDGF-BB regulates IGFBP-4 production using primary cultures of 19-day gestation rat lung fibroblasts. Exposure of fetal rat lung fibroblasts to PDGF-BB increased IGFBP-4 mRNA transcript abundance by 3.6- and 2.4-fold at 18 and 40 hours, respectively. Addition of Rp-adenosine 3'-5'-cyclic monophosphothioa tetriethylamine (rp-cAMPS),a competitive inhibitor of protein kinase A, blunted the PDGF-BB-stimulated increase in conditioned medium (CM)IGFBP-4 and the increase in IGFBP-4 mRNA. Proteolysis of IGFBP-4 was detected in aliquots of cel...
Effects of dihydrotestosterone on cardiac inward rectifier K(+) current.

UNLABELLED There are well-described sexually dimorphic differences both in the electrocardiogram and in the propensity to develop drug-induced arrhythmias. The QT interval and the risk of ventricular proarrhythmia are reduced in males compared with females. Inward rectifier potassium current (IK(1)) is a primary determinant of the ventricular resting membrane potential, and an important contributor to myocardial excitability. METHODS AND RESULTS Using the whole-cell patch-clamp technique, we evaluated the effects of dihydrotestosterone (DHT) on IK(1) in ventricular myocytes from castrated rabbits that were treated with either replacement DHT or vehicle-control for 3 weeks. Compared with the DHT-treated group, myocytes from the control animals had a significant reduction in inward IK(1) conductance (p < 0.005) and rectification ratio (RR) (p < 0.04) with no significant change in peak outward current. Acute DHT superfusion of the myocytes increased inward IK(1) conductance from baseline (p < 0.05) and increased the RR (p < 0.05). Testosterone has been reported to increase intracellular ornithine decarboxylase activity in ventricular tissue, which would increase intracellular polyamines, known modulators of IK(1) rectification. We found that inclusion of the intracellular polyamines spermidine and putrescine in the pipette solution caused a decrease in inward IK(1), accompanied by an increase in peak outward current and a reduction in the RR. CONCLUSION In summary, DHT modulates IK(1) in a chronic, as well as, an acute fashion. These effects are not because of altered intracellular polyamines. DHT may modulate myocardial excitability through effects on IK(1).
Response to Comments by Paul P. Craig

Keywords: energy policy; environmental objectives; environmental policy; environmental values; prioritization; resource depletion
Phylogenetic tree analysis of G protein-coupled 5-HT receptors: implications for receptor nomenclature.

Abstract The nomenclature system used to characterize 5-hydroxytryptamine receptor subtypes remains controversial. To date, the majority of nomenclature systems have been based on the differential pharmacological properties of the receptors. However, the availability of molecular biological data allows for a nomenclature system based on the structural properties of the receptors. The evolutionary relationships between the known G protein-coupled 5-HT receptor subtypes were determined by a phylogenetic tree analysis. The data indicate that 2 major classes of G protein-coupled 5-HT receptors have evolved. Each of the 2 branches differentiate into additional 5-HT receptor subtypes. The most recent branching of 5-HT receptor subtypes occurs at the level of individual species. These data also indicate that the degree of structural similarity (e.g. 93% identify between human and rat 5-HT 1B receptors) does not necessarily correlate with pharmacological similarity. Phylogenetic tree analysis allows for a nomenclature framework that can be easily expanded to incorporate additional 5-HT receptor subtypes that have yet to be identified.
The Influence of Vorticity on Free Convection.

Abstract We inquire into the limits of validity of Priestley's theory of free convection when vorticity influences the dynamics of the convective elements. On the assumption that plumes and vortices (dust devils) are alternative forms envolving from the same triggering process, we conclude that the replacement of plumes by vortices results in the virtual suppression of free convection as a heat transport mechanism. Reasoning from the observed properties of plumes and vortices we make the hypothesis that the transformation from plume to vortex is the result of the inhibition by rotation of lateral diffusion near the core. This leads to a transformation condition Ω02>−N2, where Ω0 is one-half the ambient vorticity and N is the imaginary Brunt-Vaisala frequency. We conclude that the inequality is satisfied most easily by the existence of a very deep unstable layer. Ball's model of an unstable layer indicates that the critical difference between dust devil and plume conditions is that the inversion above the ...
Increasing Social Engagement Among Lonely Individuals: The Role of Acceptance Cues and Promotion Motivations

Lonely individuals typically fear negative evaluation and engage in overly cautious social behaviors that perpetuate their social isolation. Recent research has found analogous security-oriented (i.e., prevention-focused) responses following experiences highlighting concerns with social loss but differing growth-oriented (i.e., promotion-focused ) responses, such as attempts at social engagement, following experiences highlighting concerns with social gain. The present studies thus investigated whether fostering a promotion focus among lonely individuals through subtle primes of acceptance could reduce their self-protective social avoidance. This hypothesis was supported across four studies in which the links between primed acceptance and promotion-focused motivations were first established, and the impact of such primes on lonely individuals' social thoughts, intentions, and behaviors were then tested. Implications of observed differences between effects of acceptance primes on lonely versus nonlonely individuals are discussed in terms of deficits versus satiation with feelings of belonging.
Identification of a Second Dynamic State During Stick-Slip Motion

Stick-slip, or interrupted, motion rather than smooth uninterrupted motion occurs in many different phenomena such as friction, fluid flow, material fracture and wear, sound generation, and sensory "texture." During stick-slip, a system is believed to undergo transitions between a static (solid-like) state and a kinetic (liquid-like) state. The stick-slip motion between various types of pretreated surfaces was measured, and a second, much more kinetic state that exhibits ultra-low friction was found. Transitions to and from this super-kinetic state also give rise to stick-slip motion but are fundamentally different from conventional static-kinetic transitions. The results here suggest practical conditions for the control of unwanted stick-slip and the attainment of ultra-low friction.
Proactive Planning for Vascular Access Therapy: One Hospital's Plan for Success

Abstract Background Vascular access is a critical component of care for patients in neonatal intensive care units (NICUs). Our NICU had only a small number of nurses cross-trained to perform peripherally inserted central catheter (PICC) insertions and was not able to provide coverage 24 hours a day, 7 days a week. We combined the vascular access team (VAT) and NICU PICC team to improve the timeliness of NICU PICC insertions, standardize care, and use ultrasound for all PICC placements. Methods A paper guide tool was developed to prioritize PICC placements as emergent, same-day, or nonemergent. NICU nurses were trained to insert PICCs using ultrasound. Catheter insertion and care processes were standardized for the new centralized PICC team. NICU and VAT staff worked together to improve daily communication, hand-offs, and referrals. Criteria were developed to determine the appropriate hospital location for PICC insertions. Charge nurses began capturing information about patients with PICCs on daily planning sheets. Results Following implementation of the new combined VAT, the average wait time for emergent and same-day insertions decreased 10%. No adverse events were reported due to a delay in PICC placement or the PICC referral process. Conclusions Combining the NICU PICC insertion nurses and the VAT into a new centralized PICC team provided an opportunity for growth in both areas. NICU PICCs are now placed efficiently based on patient acuity and referral prioritization throughout the hospital. NICU and VAT physicians and nurses have developed a strong partnership for the provision of PICC services for NICU patients.
Sexual medicine: Online risks to health--the problem of counterfeit drugs.

Counterfeit medicines sold online are a global scourge. Although erectile dysfunction drugs are well known to be heavily counterfeited, illicit vendors are rapidly expanding to other drugs and devices in the sexual health arena. International multidisciplinary cooperation is needed to address key patient safety concerns resulting from such markets.
The Yang-Mills flow near the boundary of Teichmüller space.

We study the behavior of the Yang-Mills flow for unitary connections on compact and non-compact oriented surfaces with varying metrics. The flow can be used to define a one dimensional foliation on the space of \(SU(2)\) representations of a once punctured surface. This foliation universalizes over Teichmuller space and is equivariant with respect to the action of the mapping class group. It is shown how to extend the foliation as a singular foliation over the augmented boundary of Teichmuller space obtained by adding nodal Riemann surfaces. Continuity of this extension is the main result of the paper.
The human D1A dopamine receptor gene promoter directs expression of a reporter gene to the central nervous system in transgenic mice.

Dopamine receptors are involved in many aspects of dopaminergic neurotransmission including regulation of motor control, cognition, affect and neuroendocrine function. The D1A receptor is the most widely distributed dopamine receptor in the brain and is expressed at high levels in the striatum and nucleus accumbens, but is also found throughout cortical, limbic, hypothalamic and thalamic brain regions. We have cloned a 6.4 kb fragment 5′ of the human D1A dopamine receptor gene and shown that this region activates transcription of the chloramphenicol acetyltransferase (CAT) gene in a cell-specific manner. To study the expression of these sequences in vivo we analyzed the expression of the E. coli lac Z gene under the regulation of the 6.4 kb fragment in transgenic mice. Expression of the transgene was primarily detected in the brain, with only low levels detected in peripheral tissues. The 5′ flanking sequences were able to direct the tissue-specific expression of lac Z in three different lines of transgenic mice, to a number of brain regions including the caudate-putamen, thalamus, amygdala, cerebral cortex, hippocampus and hypothalamus. Greatest expression of the lac Z gene was detected in areas of the thalamus and amygdaloid complex. In the striatum, β-galactosidase activity was restricted to neurons within the matrix and was not detected within striosomes. Results of this study demonstrate that the 6.4 kb region upstream of the human D1A receptor gene is sufficient to confer tissue-specific expression in the CNS of transgenic mice. Furthermore, expression of the transgene to neurons within the matrix of the striatum, but not the striosomes suggests that expression of the D1A receptor may be regulated differently within these areas.
Writing for Publication While in Graduate School: An Accessible Reality

The purpose of this Writer's Forum is to share eight tips about writing for publication as a graduate student. These tips demonstrate writing for publication as an accessible reality for students. This Writer's Forum advances ideas, advice, and anecdotes focused on helping graduate students to see themselves as valued experts who are capable of writing, dealing with feedback and criticism, and using time in a thoughtful and productive manner.
Mixed tumors of the vagina: an immunohistochemical study of 13 cases with emphasis on the cell of origin and potential aid in differential diagnosis

Mixed tumors of the vagina (MTsV) are rare benign neoplasms characterized by an admixture of well-differentiated epithelial cells and stromal-type cells in various proportions. In contrast to mixed tumors in other anatomic sites, the histogenesis of the vaginal tumors is unclear. We studied the immunohistochemical profile of 13 examples to explore their histogenesis and determine whether their immunohistochemical profile might be useful in the differential diagnosis. The panel of antibodies used and the number of cases studied were: AE1/3 (12), cytokeratin 7 (CK7) (13), cytokeratin 20 (CK20) (13), epithelial membrane antigen (EMA) (13), muscle actin (MA) (12), desmin (11), h-Caldesmon (13), CD10 (13), CD34 (11), CD99 (8), and S-100 (7). Eight out of 12 tumors were positive for AE1/3, 7/13 for CK7, 2/13 for CK20, and 6/13 for EMA. MA was positive in 11/12 mixed tumors, desmin in 10/11 tumors and h-Caldesmon in 5/13. All tumors were extensively positive for CD10; CD34 was positive in 7/11; and none out of eight tumors showed membranous CD99 staining. Focal S-100 immunoreactivity was seen in 1/7 tumors. These results show that MTsV coexpress epithelial and mesenchymal markers. The expression of muscle actin (usually extensive), and focal desmin and h-Caldesmon positivity suggests the presence of a smooth muscle or myoepithelial component; however, the S-100 negativity and diffuse CD10 expression argue against it. Positivity for muscle markers does not help distinguish MTsV from smooth muscle or skeletal muscle tumors. The frequent expression of CD10 negates its use in the differential diagnosis with endometrial stromal tumors, and the CD10 and CD34 expression suggests that mixed tumors may arise from a primitive pluripotential cell. MTsV are positive for h-Caldesmon and CD10, two markers that have been used in gynecologic pathology primarily to aid in establishing the smooth muscle or endometrial stromal phenotype of a neoplasm.
Big data visualization engines for understanding the development of countries, social networks, culture and cities

Big data can be used for more than improving the targeting of marketing campaigns. In this talk I will present five big data visualization engines we have created at the MIT Media Lab's Macro Connections group and will show how we can use big data and visualizations to improve our understanding of the development of economies, cultures and cities. The data visualization engines I will demo include (i) the Observatory of Economic Complexity (atlas.media.mit.edu), which is the most comprehensive tool for exploring international trade data created to date; (ii) DataViva (dataviva.info), which is a tool we created to open up data for the entire formal sector economy of Brazil, including data on all of the working force, municipalities, industries, and occupations of Brazil; (iii) Pantheon (pantheon.media.mit.edu), a dataset and visualization engine we created to explore global patterns of cultural production; (iv) Immersion (immersion.media.mit.edu), which is a tool that inverts the email interface, by focusing it on people rather than messages; and (v) Place Pulse and StreetScore (pulse.media.mit.edu & streetscore.media.mit.edu), which are crowd-sourcing and machine learning tools we have developed to help understand the aesthetic aspects of cities and their evolution.
Impression technique for maxillary removable partial dentures.

T he preferred design for major connectors of maxillary removable partial dentures is a broad palatal plate or anterior and posterior palatal bars.‘” Regardless of which design is selected, intimate contact between the major connector and the palatal mucosa is essential to obtain maximum stability and prevent food entrapment under the major connector. The cast recovered from the master impression must be an accurate duplication of both the teeth and the palatal tissues. Irreversible hydrocolloid has been recommended as an acceptable material to use in making impressions for metal framework fabrication.‘* ‘, 5 A recent study has demonstrated that properly manipulated irreversible hydrocolloid will provide adequate accuracy in the region of the teeth. However, a clinically significant amount of distortion would be expected in the hard palate.6 The amount of distortion that occurs in this region is of sufficient magnitude to prevent contact of the major connector with the palatal mucosa. Techniques tal compensate for this inaccuracy of the impression have been suggested. One alternative is to use a slightly thicker mix of alginate (irreversible hydrocolloid) in an attempt to minimize the amount of distortion attributed to “slumping” of the impression material.’ Alter:ing the water/powder ratio of the irreversible hydrocolloid from that recommended by the manufacturer can impair certain characteristics of the gel and weaken the final set material.’ Another suggestion has been to place a mound of utility wax in the palatal part of the tray to support the impression material and prevent slumping or distortion5 A potential problem witb this technique is uneven application of the wax, resulting in impression material that is either too thick or too thin in the palatal area. The potential for adhesive failure between the wax and the irreversible hydrocolloid exists and would result in a lack of accurate (duplication. Further, distortion of the
Dehydrogenation of nanocrystalline TiH2 and consequent consolidation to form dense Ti

Dehydrogenation of nanocrystalline TiH2, produced by pulverization of commercially available powder, has been examined in detail by a combination of thermal analysis, X-ray diffraction (XRD), and transmission electron microscopy (TEM). The dehydrogenation to form Ti occurs as a two-step process involving the formation of an intermediate phase, TiH. In-situ experiments on dehydrogenation inside a transmission electron microscope reveal the possibility of a powder-metallurgy process for consolidation of Ti components by vacuum annealing of nanocrystalline TiH2 at ∼0.5Tm, where Tm is the melting point of Ti. Near-full densification of Ti has been achieved by sintering nanocrystalline TiH2 under vacuum at ∼0.5Tm.
Stress, race, and APOE: understanding the interplay of risk factors for changes in cognitive functioning.

Objectives: Biological and environmental factors are thought to contribute to the development of cognitive decline (CD). The Apolipoprotein E (APOE) ϵ4 allele is the greatest known genetic risk factor. The current study focused on the extent to which environmental factors, specifically stress, influence the relationship between the APOE allele and cognitive functioning and whether this relationship is stronger for African-Americans compared to Caucasians.Methods: Participants consisted of community-dwelling older adults from the Duke Established Populations for Epidemiologic Studies of the Elderly (N = 4,162). Data were drawn from two waves, which were three years apart. Cognitive functioning was assessed at both waves using the Short Portable Mental Status (SPMSQ).Results: Whereas there was no main effect of stress, there was a significant interaction between APOE status and stressful life events, such that increased stress in individuals with an ϵ4 allele lead to more errors on the SPMSQ than individual...
Classroom films for medical geography

Abstract A number of available films on disease ecology and health care delivery are useful for leaching medical geography. Twenty-five films are described and rental information provided here.
Use of Formal and Informal Work–Family Policies on the Digital Assembly Line

This study compares work–family policy use among low wage, predominately female call center workers and their more highly paid managers. Both formal policies and the informal work–family arrangements that employees negotiate with their supervisors were examined. Consistent with the work devotion perspective, it was found that formal work–family policies are more widely used among hourly workers than managers, and those with better performance evaluations are less likely than their otherwise similar coworkers to use formal work–family policies. The ability to negotiate informal work–family arrangements and use them as a supplement to formal policies is also important to workers in this study, especially women with children and those providing care to people with special needs. Access to informal arrangements may be limited to the high performers, however. Overall, this research suggests that the work devotion framework, which derives from studies of elite workers, may be more broadly applicable than previo...
The Philosophical Foundations of a Radical Austrian Approach to Entrepreneurship

The equilibrium-based approaches that dominate entrepreneurship research offer useful insights into some aspects of entrepreneurship, but they ignore or downplay many fundamental entrepreneurial phenomena such as individuals’ creative imaginations, firms’ resource (re)combinations, and markets’ disequilibrating tendencies—and the genu ine uncertainty and widespread heterogeneity these imply. To overcome these limitations, scholars have recently introduced a nonequilibrium approach to entrepreneurship based on Ludwig Lachmann’s “radical subjectivist” brand of Austrian economics. Here, this radical Austrian approach is extended beyond Lachmann to include the work of radical subjectivism’s other noted theorist: George Shackle. More important, the article extends entrepreneurship research by systematically comparing and contrasting the nascent, radical Austrian approach to entrepreneurship with three dominant equilibrium-based approaches: neoclassical, Kirznerian, and Schumpeterian economics. Specifically, the article (a) explicates the paradigmatic philosophical assumptions about the nature of individuals, firms, and markets that underlie these approaches; (b) demonstrates how metaphor is employed as a device to concretize these assumptions; (c) examines the research questions that arise from the assumptions these metaphors reflect; and (d) uses the Jap anese “beer wars” of the 1980s and 1990s to illustrate one methodological approach (hermeneutics) researchers can adopt to apply these assumptions, metaphors, and questions to study entrepreneurial phenomena from a radical subjectivist perspective.
MOLES: malicious off-chip leakage enabled by side-channels

Economic incentives have driven the semiconductor industry to separate design from fabrication in recent years. This trend leads to potential vulnerabilities from untrusted circuit foundries to covertly implant malicious hardware Trojans into a genuine design. Hardware Trojans provide back doors for on-chip manipulation, or leak secret information off-chip once the compromised IC is deployed in the field. This paper explores the design space of hardware Trojans and proposes a novel technique, "Malicious Off-chip Leakage Enabled by Side-channels" (MOLES), which employs power side-channels to convey secret information off-chip. An experimental MOLES circuit is designed with fewer than 50 gates and is embedded into an Advanced Encryption Standard (AES) cryptographic circuit in a predictive 45nm CMOS technology model. Engineered by a spread-spectrum technique, the MOLES technique is capable of leaking multi-bit information below the noise power level of the host IC to evade evaluators' detections. In addition, a generalized methodology for a class of MOLES circuits and design verification by statistical correlation analysis are presented. The goal of this work is to demonstrate the potential threats of MOLES on embedded system security. Nevertheless, MOLES could be constructively used for hardware authentication, fingerprinting and IP protection.
Using a Senior Seminar for Assessing the Major

We designed a senior seminar to address many theoretical and practical issues involved with, multidimensional assessment. We describe the structure of the course and various assessment measures used to tap student knowledge and student experiences. This course allowed us to accomplish several assessment and pedagogical goals. The course served as an integrative and self-reflective vehicle for students. As students became actively involved in identifying the body of knowledge that defines psychology, they also gained a better sense of the intricacies of assessment. Faculty gained information that can be directly applied to improving teaching and learning. We provide recommendations for using a seminar for assessment.
QTLs for bone mineral density of femurs and tibias in recombinant inbred strains derived from C57BL/6J and DBA/2J inbred strains

Background Quantitative trait loci (QTLs) for bone mineral density (BMD) are defined as regions of the genome that contain sequence variations that cause differences in either bone deposition or rates of resorption. In this study, we investigate QTLs for BMD of whole bones using femurs and tibiae from the BXD family of recombinant inbred (RI) strains derived by crossing C57BL/6J (B6) and DBA/2J (D2) inbred strains.
Modifications of the Brandel Superfusion 600 system and other revisions in superfusion technique improve the measurement of endogenous dopamine release in vitro

The Brandel Superfusion 600 is an automated system designed for the simultaneous measurement of neurotransmitter release from tissue slices from six chambers. In optimizing a technique for the measurement of endogenous dopamine (DA) with this system, a number of factors were identified which affected adversely both the accuracy and the precision of within and between experiments. These factors included bubbles in the perfusion chamber, an apparent loss of tissue viability during preparation of the slices, depletion of DA stores after multiple stimulations and degradation of DA in the perfusate after collection. The method was substantially improved with modifications in the Superfusion 600 system and by the addition of high Mg2+ to the preparation buffer. The addition of tyrosine to the perfusion buffer and the prevention of analyte degradation with antioxidant agents also improved accuracy and precision of measurements.
THE EFFECTS OF THE TWO OVARIAN HORMONES ON CASTRATED HUMAN FEMALES

Interest in the physiology of menstruation and its associated phenomena in the human female has been given impetus since the isolation and purification of two ovarian hormones. The present communication is concerned with the effects produced by the ovarian hormones on five castrated human females. The observations include: 1) the correlation of the histology of the endometrium produced by estrin alone, and estrin plus progestin; 2) the time relations of bleeding following the use of estrin alone, and of estrin plus progestin; 3) the effect of these hormones on menopausal symptoms. The estrin (Progynon-B), prepared from mare or stallion urine, was furnished by Schering Corporation. It contained 10,000 R. U. per cc. (50,000 international units) in oil and was used throughout this study. Chemically it is the benzoic acid ester of dihydroestrin.
Erythrocyte insulin‐like growth factor‐I binding in younger and older males

OBJECTIVE Insulin-like growth factor-I (IGF-I) levels are lower in older compared with younger subjects. We tested the hypothesis that the reduction in circulating IGF-I would be accompanied by upregulation in tissue IGF-I binding in at least some tissues. We tested erythrocyte IGF-I binding since blood is an accessible tissue in humans, and there is growing evidence to suggest that erythrocyte IGF-I binding is influenced by circulating IGF-I. DESIGN AND PATIENTS We compared 9 healthy older males (61–68 years old) with 9 healthy younger males (15–19 years old). MEASUREMENTS Standard techniques were used to assay circulating IGF-I and IGF binding proteins 1–5 (IGFBPs 1–5). Erythrocyte IGF-I binding was first measured by studies in which native [125I]-IGF-I was displaced with unlabelled native IGF-I. In order to determine a possible role for IGF binding proteins (IGFBP), native [125I]-IGF-I was displaced with des-(1-3)IGF-I, which binds with IGF receptors but not IGFBPs. RESULTS As expected, circulating IGF-I was significantly lower in the older compared with the younger subjects. In addition, IGFBP-3 and 5 were significantly lower, and IGFBP-4 higher, in older compared with younger subjects. When native [125I]-IGF-I was displaced with unlabelled native IGF-I, the number of IGF-I binding sites per erythrocyte was higher in the older subjects (43 ± 5 vs. 18 ± 2, older vs. younger, respectively; P < 0.05). In contrast, when native [125I]-IGF-I was displaced with des-(1-3), IGF-I binding capacity was not different between the two age groups. CONCLUSIONS Erythrocyte IGF binding was increased in older compared with younger subjects. Surprisingly, the mechanism of the increase may not be a simple up regulation of IGF-I receptors in response to reduced circulating IGF-I, but possibly by an increase in the levels of as yet unidentified erythrocyte membrane-associated IGF binding proteins.
Measuring Perceptual Skills That Are Related to the Learning Task

A brief review of the literature related to perceptual skills required in reading acquisition and the literature on the validity of current perceptual measures to tap these task-related perceptual abilities is presented. An informal task-related measure is proposed to overcome the drawbacks of more formal measures of visual perception.
Discrete differential form subdivision and vector field generation over volumetric domain

This thesis presents a new method to construct smooth l- and 2-form subdivision schemes over the 3D volumetric domain. Based on the subdivided 1- and 2-form coefficient field, smooth vector fields can be constructed using Whitney forms. To obtain stencils in the regular setting, classical 0-form subdivision and linear 1- and 2-form subdivision over the octet mesh are introduced. Then, convoluting with a smooth operator, smooth 1- and 2-form subdivision schemes in the regular case can be determined up to one free parameter. This parameter can be determined by a novel technique based on spectrum and momentum considerations. However, artifacts exist in boundary regions because of the incomplete regular support and the shrinking feature of the original 0-form subdivision scheme. To address these problems, the projection-scaling method and the expansion method are introduced and compared. The former method projects arbitrary discrete differential forms to a subspace spanned by low-order potential fields. The algorithm subdivides these potential fields and reconstructs the discrete form in the refined level using linear combinations. Scaling is included for elements near the boundary to offset the effect of mesh shrinkage. Alternatively, for the expansion method, a compatible nonshrinking 0-form subdivision scheme is constructed first. Based on the new 0-form subdivision method, extending 1- and 2-forms beyond the boundary becomes natural. In the experiment, no noticeable artifacts, including attenuation, enlarging or undesirable bend, are found in practice.
Brain dysfunctions during facial discrimination in schizophrenia: Selective association to affect decoding

Schizophrenia patients exhibit impaired facial affect perception, yet the exact nature of this impairment remains unclear. We investigated neural activity related to processing facial emotional and non-emotional information and complex images in 12 schizophrenia patients and 15 healthy controls using functional magnetic resonance imaging. All subjects performed a facial information processing task with three conditions: matching facial emotion, matching facial identity, and matching complex visual patterns. Patients and controls showed comparable behavioral performance in all task conditions. The neural activation patterns in schizophrenia patients and healthy controls were distinctly different while processing affect-related facial information but not other non-emotional facial features. During emotion matching, orbital frontal cortex and left amydala activations were found in controls but not in patients. When comparing emotion versus identity matching, controls activated the fusiform and middle temporal gyri, left superior temporal gyrus, and right inferior and middle frontal gyrus, whereas schizophrenia patients only activated the middle and inferior frontal gyri, the frontal operculi and the right insular cortex. Our findings suggest that schizophrenia patients and healthy controls may utilize different neural networks when processing facial emotional information.
Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks

Histone H2AX is rapidly phosphorylated in the chromatin micro-environment surrounding a DNA double-strand break (DSB). Although H2AX deficiency is not detrimental to life, H2AX is required for the accumulation of numerous essential proteins into irradiation induced foci (IRIF). However, the relationship between IRIF formation, H2AX phosphorylation (γ-H2AX) and the detection of DNA damage is unclear. Here, we show that the migration of repair and signalling proteins to DSBs is not abrogated in H2AX−/− cells, or in H2AX-deficient cells that have been reconstituted with H2AX mutants that eliminate phosphorylation. Despite their initial recruitment to DSBs, numerous factors, including Nbs1, 53BP1 and Brca1, subsequently fail to form IRIF. We propose that γ-H2AX does not constitute the primary signal required for the redistribution of repair complexes to damaged chromatin, but may function to concentrate proteins in the vicinity of DNA lesions. The differential requirements for factor recruitment to DSBs and sequestration into IRIF may explain why essential regulatory pathways controlling the ability of cells to respond to DNA damage are not abolished in the absence of H2AX.
An alkaline α-galactosidase transcript is present in maize seeds and cultured embryo cells, and accumulates during stress

Raffinose family oligosaccharides (RFO) accumulate in many developing seeds and are degraded during seed germination. However, acidic α-galactosidase (AGAL) activity and subcellular location do not correlate with raffinose depletion; alkaline α-galactosidases (AGA) may be responsible for RFO hydrolysis in germinating seeds. Three cDNA clones for AGA/SEED IMBIBITION PROTEIN were obtained from the Pioneer Hi-Bred maize expressed sequence database. Two of the clones were expressed in Escherichia coli, and the recombinant proteins, when incubated with naturally occurring galactosides or p-nitrophenyl α-d-galactose, exhibited AGA activity with maximum catalysis at pH 7.5 (ZmAGA1) or pH 8.5 (ZmAGA3). No raffinose biosynthetic capacity was observed with either enzyme. Maximal α-galactosidase activity in mature dehydrated, germinating and germinated maize (Zea mays) seeds occurred at pH 7.5. ZmAGA1 was the sole family member detected in seeds and maize Hi-II, embryo-derived, callus cells. Its transcript accumulated when seed germination was interrupted by heat, cold or dehydration stress, but not in response to NaCl. Tissue prints localized transcripts to the scutellum or the embryo axis, depending on the stress applied. In maize Hi-II callus cells, transcripts accumulated when callus was subjected to heat stress (42 °C), during which ZmAGA1 transcript accumulation was further induced by sucrose. Galactosides in a variety of forms, including raffinose, partially repressed the sucrose-induced accumulation of transcript in heat-stressed callus.
Steroid structure and pharmacological properties determine the anti-amnesic effects of pregnenolone sulphate in the passive avoidance task in rats

Pregnenolone sulphate (PREGS) has generated interest as one of the most potent memory-enhancing neurosteroids to be examined in rodent learning studies, with particular importance in the ageing process. The mechanism by which this endogenous steroid enhances memory formation is hypothesized to involve actions on glutamatergic and GABAergic systems. This hypothesis stems from findings that PREGS is a potent positive modulator of N-methyl-d-aspartate receptors (NMDARs) and a negative modulator of gamma-aminobutyric acid(A) receptors (GABA(A)Rs). Moreover, PREGS is able to reverse the amnesic-like effects of NMDAR and GABA(A)R ligands. To investigate this hypothesis, the present study in rats examined the memory-altering abilities of structural analogs of PREGS, which differ in their modulation of NMDAR and/or GABA(A)R function. The analogs tested were: 11-ketopregnenolone sulphate (an agent that is inactive at GABA(A)Rs and NMDARs), epipregnanolone ([3beta-hydroxy-5beta-pregnan-20-one] sulphate, an inhibitor of both GABA(A)Rs and NMDARs), and a newly synthesized (-) PREGS enantiomer (which is identical to PREGS in effects on GABA(A)Rs and NMDARs). The memory-enhancing effects of PREGS and its analogs were tested in the passive avoidance task using the model of scopolamine-induced amnesia. Both PREGS and its (-) enantiomer blocked the effects of scopolamine. The results show that, unlike PREGS, 11-ketopregnenolone sulphate and epipregnanolone sulphate failed to block the effect of scopolamine, suggesting that altering the modulation of NMDA receptors diminishes the memory-enhancing effects of PREGS. Moreover, enantioselectivity was demonstrated by the ability of natural PREGS to be an order of magnitude more effective than its synthetic enantiomer in reversing scopolamine-induced amnesia. These results identify a novel neuropharmacological site for the modulation of memory processes by neuroactive steroids.