cssi/SciSciGPT-SciSciNet huggingface dataset:
Performance-Based Wind Engineering for Wood-Frame Buildings

The majority of buildings and the vast majority of residential structures in North America are constructed using light-frame wood. Many of these structures are subjected to high winds along the eastern seaboard and gulf coast, and as a result routinely suffer damage resulting in financial losses. A relatively new paradigm in the field of earthquake engineering is performance-based design. This paper presents the concept of performance-based wind engineering for wood-frame buildings through the development and application of fragilities to form different owner/user performance expectations, namely, occupant comfort, continued occupancy, life safety, and structural integrity. The approach includes the development and application of fragility curves. An example analysis and design for a simple light-frame wood building for all four performance expectations is presented. The final design of the building needed to achieve the specified levels of structural performance are discussed for each performance expectation level.
Feasibility, safety and accuracy of regadenoson–atropine (REGAT) stress echocardiography for the diagnosis of coronary artery disease: an angiographic correlative study

Regadenoson (REG), a selective A2A receptor vasodilator, has not been widely evaluated in stress echocardiography (SE). We report results of 45 patients participating in REG + atropine (REGAT) SE protocol conducted in a single-center prospective trial. The REGAT study enrolled subjects before a clinically indicated cardiac catheterization for suspected coronary artery disease (CAD). After rest imaging, a 2 mg Atropine (AT) bolus followed by 400 mcg of REG was given. Standard stress imaging views were obtained and interpreted in blinded fashion. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated using cardiac catheterization >70 % stenosis as gold standard. Additional endpoints included major adverse cardiac events (MACE) and patient questionnaire responses. The mean duration of REGAT was 18 ± 7.2 min. There were no MACE, with only transient side-effects of dry mouth, shortness of breath, and headache. The incidence of significant CAD was 51.1 %. The sensitivity and specificity for significant stenosis was 60.9 and 86.4 %, with a PPV and NPV of 82.4 and 67.9 %. By coronary territories, the sensitivity, specificity, PPV, and NPV were: left anterior descending artery 58.8, 92.9, 83.3, and 78.8 %; left circumflex artery 6.7, 93.3, 33.3, and 67.7 %; and right coronary artery 16.7, 93.9, 50, and 75.6 %. Over 90 % of subjects reported feeling comfortable, with 83 % preferring REGAT as a future stress modality. The REGAT protocol is fast, safe, and well-tolerated with good specificity for CAD detection, but its low sensitivity and NPV precludes it from being an imaging modality for routine use.
From Despair to Resistance: Maya Workers in the Maquilas of Guatemala

Based on ethnographic research among industrial workers in the export processing plants of highland Guatemala, this article explores the meanings given to the high incidence of labor turnover. The sample is composed of mostly young workers between the ages of 16 and 25, the age of the majority of maquila workers. The study shows that turnover exemplifies worker agency, specifically in resistance to oppressive forms of production in global capitalism. Global processes in this study are illustrated through the eyes and words of local participants.
Rapid Multistep Synthesis of a Bioactive Peptidomimetic Oligomer for the Undergraduate Laboratory.

Peptidomimetic compounds are increasingly important in drug-discovery applications. We introduce the synthesis of an N-substituted glycine oligomer, a bioactive “peptoid” trimer. The six-step protocol is conducted on solid-phase resin, enabling the synthesis to be performed by undergraduate organic chemistry students. This synthesis lab was successfully completed within one 4-h session by second-year students. The procedures are relatively inexpensive and versatile, enabling modifications to generate a variety of oligomer sequences from commercially available reagents including bromoacetic acid and a diverse set of primary amines.
Effects of topography on facies and compositional zonation in caldera-related ignimbrites

Large-scale fluid dynamical processes during explosive eruptions within calderas are examined numerically by solving the full set of two-phase hydrodynamic equations with a topographic barrier, representing the rim of a caldera. The effect of the caldera rim on eruption dynamics depends on the relative locations of the rim and the impact zone where tephra collapsing from the eruption column strikes the ground. The distance of the impact zone from the vent is proportional to the collapse (fountain) height of the eruption column. Three significantly different eruption patterns have been observed in the simulations: (1) If the impact zone is outside the caldera rim, relatively continuous pyroclastic flow occurs outside the caldera. (2) If the impact zone is on or near the caldera rim, an initial pyroclastic current flow out of the caldera and is followed by a lapse in outflow during which the cladera fills up with ash. (3) If the impact zone is inside the rim, all initial pyroclastic flows are contained within the caldera unless the flows have sufficiently high initial densities and velocities to carry them over the rim. In most cases, recirculation of pyroclasts into the base of the column causes fountain height to decrease dramaticallymore » with time due to the {open_quotes}choking{close_quotes} effect of the ash. This recycling of ash in turn reduces the ability of pyroclastic flows to surmount the rim. The numerical models suggest several processes that cause the formation of multiple cooling and flow units in deposits outside a caldera from a single eruption of steady discharge. Compositional gaps may occur in outflow ignimbrite due entirely to interaction of eruption and emplacement dynamics with topography; sharp compositional gradients within a magma chamber are not necessarily implied by compositional gaps in outflow units. 35 refs., 10 figs., 1 tab.« less
Experimental Study of Direct Contact Condensation in the Presence of Noncondensable Gas

A series of direct contact condensation tests of mixture of saturated steam and nitrogen has been carried out in a subcooled pool of water. Nitrogen is used as the noncondensable gas. A mixture of nitrogen and steam is discharged into the subcooled water pool through a vertical nozzle. The apparatus is equipped with appropriate instruments and flow visualization. Pre-heaters and super-heaters are used to heat up nitrogen and steam before they are mixed. Tests have been preformed with variations of the liquid temperature, system pressure, nozzle size and the concentration of noncondensable gas. Images of bubble behaviors are captured with high speed video camera and downloaded into a PC in digital format. Information on bubble size variation and formation frequency is obtained from the image analysis. Detaching bubble size, surface area and frequency are correlated with the various dimensionless numbers.Copyright © 2002 by ASME
Support for Steiger's policies.

Jocelyn Kaiser's article on William Steiger, the point person on international health for U.S. Health and Human Services (HHS) Secretary Tommy Thompson (“The man behind the memos,” News Focus, 10 Sept., p. [1552][1]), is decidedly one-sided. She interviewed me at length, and although I support his policies and admire his professionalism, none of my views, or those of other supporters, are mentioned. Scientists cry “academic freedom” when their travel is cut, as happened with the AIDS conference in Bangkok. Steiger, as well as journalists and health experts, knew this conference had become unruly and unproductive ([1][2]). Kaiser writes that Steiger's support of the Bush administration's “controversial” position on abstinence in HIV prevention programs “ruffled feathers” among researchers. She neglects to mention how promotion of abstinence is dramatically reducing HIV/AIDS infections in Uganda ([2][3]). Furthermore, Steiger is doing his job when refusing to fund any conference that undermines the administration's approach to procuring safe and effective AIDS drugs. Kaiser fails to mention how the administration's position has been supported by the World Health Organization's (WHO) removal of five AIDS drugs from its list because of unproven quality. South Africa has banned at least one of the drugs that the Administration refused to buy until tested. The fact that Steiger approves HHS staff involvement in WHO activities may upset some researchers. Yet all government agencies routinely approve which researchers attend meetings as U.S. representatives. It is Steiger's job to coordinate the U.S. position with inputs from many agencies with expertise most appropriate for any particular conference. He does this job in the best interests of the country, and does it well. 1. 1.[↵][4] 1. S. Mallaby , For example, see these op-ed pieces: “AIDS activists misfiring,” Washington Post , 18 July 2004, p. A17; L. Garrett, “Bragging in Bangkok,” N.Y. Times , 16 July 2004, p. A21. 2. 2.[↵][5] 1. E. C. Green , Rethinking AIDS Prevention (Praeger, Westport, CT, 2003). [1]: /lookup/doi/10.1126/science.305.5690.1552 [2]: #ref-1 [3]: #ref-2 [4]: #xref-ref-1-1 "View reference 1. in text" [5]: #xref-ref-2-1 "View reference 2. in text"
Comparative study of plasma protein binding of diphenylhydantoin.

Abstract 1. Plasma protein binding of 14 C-labelled diphenylhydantoin (DPH) was determined in vitro by equilibrium dialysis (37° C.) and liquid scintillation spectroscopy. 2. Binding was studied in the goat, sheep, ox, horse, pony, swine, dog, cat, rabbit, opossum, and human plasmas. Extensive binding was observed in all species. 3. The percentage DPH bound decreased biphasically with increase in drug concentra-(2.4–40.0 μg. per ml.). 4. Highly significant interspecies variation was found in the unbound fraction of DPH. 5. Nephrectomy caused a significant decrease in DPH binding in goats. 6. Lower binding capacity may be due to a qualitative change in drug-binding proteins.
Milestones for Internal Medicine Sub-interns

Abstract Background As residency programs move toward measuring milestones for competency-based education assessment, medical schools will need to collaborate with residencies to determine competencies for graduating students. The objective of this study is to define the educational milestones for fourth-year medical students during an Internal Medicine sub-internship. Methods A cross-sectional Internet-based survey (with attention to validity evidence) was developed in early 2013 and administered to Internal Medicine attendings and Internal Medicine sub-interns working on an inpatient team at 3 academic medical centers. With the purpose to determine the milestones for sub-interns, items asked respondents what responsibilities a sub-intern could be entrusted to perform without direct supervision. Results Faculty responded that behaviors sub-interns could perform with indirect supervision were mostly at the "reporter" level, including completing a history and physical examination and collecting data such as test results. Other skills such as venipuncture and some communication skills such as calling consults, providing patient counseling, responding to pages, and creating discharge instructions were examples of tasks in which the majority of faculty felt that students were progressing toward unsupervised practice. Behaviors where the majority of faculty would always supervise a medical student performance included performance on the "interpreter" level, including interpreting electrocardiograms, significant physical examination findings, and laboratory results. Medical students less commonly noted needing supervision on the majority of the items when compared with faculty. Conclusion Tasks in the reporter domain such as taking a history, collecting medical records, and reporting results can be characterized as medical student milestones.
Thermal Effects on Hydrothermal Biomass Liquefaction

Batch pressure vessels commonly used for hydrothermal liquefaction have typical heating times in the range of 30 to 60 min. Thermodynamically, the complex set of reactions are path dependent, so that the heating rate can possibly affect yields and the composition of the resultant liquid products. It is postulated that the mode of heat transfer becomes an uncontrolled variable in kinetic studies and can seriously impact scale-up. To confirm this hypothesis and minimize these heat-transfer-related artifacts, we designed a batch pressure vessel equipped with an induction heating system, which allows the reduction of heat-up times by about two orders of magnitude to several seconds, compared to tens of minutes with standard pressure reactors. This system was used to study the direct liquefaction of corn stover and aspen wood with a pretreatment. The heating rate was found to have no significant effect on the composition of the liquid products. However, the liquid yields are dependent on the heating rate. Varying the cooling rate does not show obvious effects. The results confirm that the heating rate, as governed by the mode of heat transfer, is an important factor that needs to be considered during scale-up.
Computers, the media and multicultural education: seeking engagement and political literacy

This paper meshes Carr's research on media literacy with Porfilio's research on computer literacy, with both of these areas being focused on the central notion of social justice within a multicultural society. Both researchers teach pre‐service teachers, and have an interest in extending multicultural education, which often equates, overlaps with, and complements intercultural education. The key issue probed throughout this paper relates to the potential for (critical) multicultural education to take place in and through attempts to inculcate a media and computer literacy that surpasses simplistic notions of tolerance, respect and basic knowledge of the ‘Other’. The research underscores the need for formal and informal approaches to inculcating media and computing literacy in the classroom, which, ultimately, support a more robust critical multiculturalism in schools.
Herpes simplex virus entry is associated with tyrosine phosphorylation of cellular proteins.

Abstract The initial step in herpes simplex virus (HSV) entry is binding of virion glycoprotein (g)C and/or gB to cell surface heparan sulfate. After this initial attachment, gD interacts with cell surface receptor or receptors, and the virion envelope fuses with the cell membrane. Fusion requires viral glycoproteins gB, gD, gL, and gH, but the cellular factors that participate in or the pathways activated by viral entry have not been defined. To determine whether signal transduction pathways are triggered by viral–cell fusion, we examined the association of viral entry with tyrosine phosphorylation of cellular proteins. Using immunoprecipitation and Western blotting, we found that at least three cytoplasmic host cell proteins, designated p80, p104, and p140, become tyrosine phosphorylated within 5–10 min after exposure to HSV-1 or HSV-2. However, no phosphorylation is detected when cells are exposed to a mutant virus deleted in gL that binds but fails to penetrate. Phosphorylation is restored when the gL-deletion virus is grown on a complementing cell line. Viral entry and the phosphorylation of p80, p104, and p140 are inhibited when cells are infected with virus in the presence of protein tyrosine kinase inhibitors. Taken together, these studies suggest that tyrosine phosphorylation of host cellular proteins is triggered by viral entry.
Fungal adhesion protein guides community behaviors and autoinduction in a paracrine manner.

Microbes live mostly in a social community rather than in a planktonic state. Such communities have complex spatiotemporal patterns that require intercellular communication to coordinate gene expression. Here, we demonstrate that Cryptococcus neoformans, a model eukaryotic pathogen, responds to an extracellular signal in constructing its colony morphology. The signal that directs this community behavior is not a molecule of low molecular weight like pheromones or quorum-sensing molecules but a secreted protein. Znf2, a master regulator of morphogenesis in Cryptococcus, is necessary and sufficient for the production of this signal protein. Cfl1, a prominent Znf2-downstream adhesion protein (adhesin), was identified to be responsible for the paracrine communication. Consistent with its role in communication, Cfl1 is highly induced during mating colony differentiation, and some of the Cfl1 proteins undergo shedding and are released from the cell wall. The released Cfl1 is enriched in the extracellular matrix and acts as an autoinduction signal to stimulate neighboring cells to phenocopy Cfl1-expressing cells via the filamentation-signaling pathway. We further demonstrate the importance of an unannotated and yet conserved domain in Cfl1’s signaling activity. Although adhesion proteins have long been considered to be mediators of microbial pathogenicity and the structural components of biofilms, our work presented here provides the direct evidence supporting the signaling activation by microbial adhesion/matrix proteins.
Accreditation council for graduate medical education (ACGME) annual anesthesiology residency and fellowship program review: a "report card" model for continuous improvement

Background: The Accreditation Council for Graduate Medical Education (ACGME) requires an annual evaluation of all ACGME-accredited residency and fellowship programs to assess program quality. The results of this evaluation must be used to improve the program. This manuscript describes a metric to be used in conducting ACGMEmandated annual program review of ACGME-accredited anesthesiology residencies and fellowships. Methods: A variety of metrics to assess anesthesiology residency and fellowship programs are identified by the authors through literature review and considered for use in constructing a program “report card.” Results: Metrics used to assess program quality include success in achieving American Board of Anesthesiology (ABA) certification, performance on the annual ABA/American Society of Anesthesiology In-Training Examination, performance on mock oral ABA certification examinations, trainee scholarly activities (publications and presentations), accreditation site visit and internal review results, ACGME and alumni survey results, National Resident Matching Program (NRMP) results, exit interview feedback, diversity data and extensive program/rotation/ faculty/curriculum evaluations by trainees and faculty. The results are used to construct a “report card” that provides a high-level review of program performance and can be used in a continuous quality improvement process. Conclusions: An annual program review is required to assess all ACGME-accredited residency and fellowship programs to monitor and improve program quality. We describe an annual review process based on metrics that can be used to focus attention on areas for improvement and track program performance year-to-year. A “report card” format is described as a high-level tool to track educational outcomes.
A Trio of Books Applying the Ethic of Care: Personal, Institutional, and Global Dimensions

Books reviewed in this article: Towards a Caring Society: Ideas into Action, by Pearl M. Oliner and Samuel P. Oliner Caring in an Unjust World: Negotiating Borders and Barriers in Schools, edited by Deborah Eaker-Rich and Jane Van Galen Learning Peace: The Promise of Ecological and Cooperative Education, edited by Betty Reardon and Eva Nordland with the assistance of Peter Zuber
An electron-transfer induced migratory insertion reaction originating from a 19-electron cobaltacyclic anion

Abstract The cyclopentadienyl cobaltafluorenyl carbonyl complex Cp(CO)CoC 12 H 8 ( 3 ) is reduced in THF in a one-electron irreversible process. The reduction products include the fluorenone radical anion, Fl − , which is proposed to arise through migratory insertion of the CO ligand into the metallacyclic CoC bond of the 19-electron complex 3 − . Electrochemical and IR analyses show that bulk electrolysis under N 2 gives 1/3 equiv. each of Fl − and CpCo(CO) 2 and 2/3 equiv. of a 17-electron anion [CpCoC 12 H 8 ] − ( 2 − ) Under CO the yield of Fl − is quantitative. The insertion product is also formed when the reduction of the analogous phosphine complex Cp(PPh 3 )CoC 12 H 8 is performed under CO. An equilibrium between 17- and 19-electron compounds is postulated to account for the synthetic and voltammetric observations. When the cobaltacycle Cp(PPh 3 )CoC 4 Ph 4 ( 5 ) is reduced under carbon monoxide, the CO-insertion product is the π-cyclopentadienone complex CpCo(η 4 -C 4 Ph 4 O) ( 8 ).
G-protein-coupled receptors function as oligomers in vivo

Abstract Hormones, sensory stimuli, neurotransmitters and chemokines signal by activating G-protein-coupled receptors (GPCRs) [1]. Although GPCRs are thought to function as monomers, they can form SDS-resistant dimers, and coexpression of two non-functional or related GPCRs can result in rescue of activity or modification of function [2–10]. Furthermore, dimerization of peptides corresponding to the third cytoplasmic loops of GPCRs increases their potency as activators of G proteins in vitro [11], and peptide inhibitors of dimerization diminish β 2 -adrenergic receptor signaling [3]. Nevertheless, it is not known whether GPCRs exist as monomers or oligomers in intact cells and membranes, whether agonist binding regulates monomer–oligomer equilibrium, or whether oligomerization governs GPCR function. Here, we report that the α-factor receptor, a GPCR that is the product of the STE2 gene in the yeast Saccharomyces cerevisiae , is oligomeric in intact cells and membranes. Coexpression of receptors tagged with the cyan or yellow fluorescent proteins (CFP or YFP) resulted in efficient fluorescence resonance energy transfer (FRET) due to stable association rather than collisional interaction. Monomer–oligomer equilibrium was unaffected by binding of agonist, antagonist, or G protein heterotrimers. Oligomerization was further demonstrated by rescuing endocytosis-defective receptors with coexpressed wild-type receptors. Dominant-interfering receptor mutants inhibited signaling by interacting with wild-type receptors rather than by sequestering G protein heterotrimers. We suggest that oligomerization is likely to govern GPCR signaling and regulation.
Estimation of bloch model MT spin system parameters from Z‐spectral data

Previous studies have described magnetization transfer (MT) Z-spectra in terms of a two-pool Bloch model, with six spin-system parameters KA, F, T1A, T1B, T2A, and T2B. By simulation, we show that a process including nonlinear constrained optimization can be used to accurately and uniquely estimate spin-system parameters from MT Z-spectra prepared by continuous wave (CW) RF irradiation. Experiments producing Z-spectra by pulsed RF irradiation give substantially different magnetization values, relative to MT acquisitions obtained by CW RF irradiation, at small offset frequencies, with a consequence that only T2B can be uniquely determined. However, several equalities and bounds involving four of the other parameters (KA, F, T1A, and T1B) are derived, which are applicable to pulsed data. These relationships allow calculation of "free pool" magnetization corresponding to complete saturation of the restricted pool, without requiring that this complete saturation be experimentally achieved. MT experimental data from pulsed RF irradiation on boiled egg albumin, obtained using a clinical whole-body MRI system, are analyzed using an optimization algorithm and the derived expressions.
Restoring right relations among privileged and poor people: A case study of the Center for New Creation

Privileged people can work for restorative justice in their relations with poor and oppressed people. They do this by circumventing their class insulation through mutually respectful new relations with those struggling for their liberation. The author of this article argues for public spaces where oppressed and privileged people come together in conscious ways, to rebalance power relations, learn to bridge differences and work together for social justice. Faith‐based organisations, rather than an impediment to democracy, can be a significant site for building such political solidarity. The case study presented here examines an upper middle‐class faith community in the 1980s, the Center for New Creation, as it developed a culture based on democratic relations between the powerful and the poor. Its success was rooted in a conscious ‘caring for difference’ and a sense of personal and collective empowerment and responsibility among its privileged members. Out of this process evolved a new and radical approach...
Redefining Hijab: American Muslim Women's Standpoints on Veiling

Feminist standpoint theory suggests that, although powerful discourses attempt to define women on the “margins” of society, women's cultural positions provide them with heightened understandings of the contradictions between their experiences and the ways the dominant group defines them. Thus, while many Americans believe hijab—also called a “veil” or “headscarf”—functions to oppress women, veiled women probably possess alternative understandings. In this study, 13 veiled American Muslim women share their experiences, and under the lens of standpoint theory, the participants’ definition of hijab emerges. Specifically, the women inscribe hijab with meanings shaped by their unique cultural standpoints. Hijab functions to define Muslim identity, perform a behavior check, resist sexual objectification, afford more respect, preserve intimate relationships, and provide freedom.
Comparison of Home Lunches in Hawaii with Required Grade Nutrient Standards and Meal Pattern Requirements of the USDA School Lunch Program

Abstract Our objective was to determine whether lunches brought from home by children attending public elementary school in Hawaii met the grade nutrient standards and meal pattern requirements of the USDA National School Lunch Program for grades K-6. At least two schools from each of Hawaii's 7 public school districts were chosen and 323 students were interviewed. The average home lunch met the grade nutrient standards of the School Lunch Program for energy, saturated fat, protein, iron, and vitamin C, but 20 to 42% of the lunches didn't meet the standards for those nutrients. The average home lunch contained 9.8% of calories from saturated fat, but 42% of the lunches exceeded the maximum for saturated fat. The average home lunch did not meet the standards for fat, vitamin A or calcium. Home lunches contained more sodium and less cholesterol on average than Hawaii school lunches. Sugar provided 42% of the carbohydrate calories in home lunches. Home lunches did not meet the meal pattern requirements for d...
Facilitation of appetitive conditioning with naturalistic conditioned stimuli: CS and US factors

Adding limited female cues to a conditioned stimulus (CS) facilitates conditioned male sexual responding. In two experiments, we examined the mechanisms of this facilitation effect. The color of the female cues on the CS was varied in Experiment 1. Similarity between the CS plumage color and the color of the live female (the unconditioned stimulus [US]) could only partially account for the results. The extent to which the facilitation effect represents a specialization of sexual behavior was examined in Experiment 2 by comparing conditioning with either food or copulation as the US. The CSs with female cues elicited more approach and grab responses regardless of which US was used. However, uniquely sexual conditioned responses (mounts and cloacal contacts) were enhanced only when sexual reinforcement served as the US. These findings suggest that the facilitation effect of female cues represents a general feature of appetitive behavior systems.
Some Reflections on Medical Diagnosis by Electronic Data Processing Machines

The Vanderbilt University School of Medicine study of the feasibility of electronic data processing in medical diagnosis emphasizes a coordinated engineering and medical scientific effort. All needed technical modalities exist. Decisions have to be made about obtaining and encoding input patient information, size of memory, nature of access, the organization of data stored in it, the arithmetic of comparison, the format of a useful output. Diagnosis of health is a worthwhile long-term objective. Government services, large industries, and major medical centers are primary sites. Administrative, personnel and financing problems are difficult but not insurmountable.
Detection of antigen to herpes simplex virus in cerebrospinal fluid from patients with herpes simplex encephalitis.

Cerebrospinal fluid (CSF) specimens were obtained from patients with presumed herpes simplex encephalitis who underwent brain biopsy for diagnostic confirmation. Coded CSF specimens were fixed on nitrocellulose filter paper and probed with a pool of monoclonal antibodies directed against four herpes simplex virus glycoproteins (gB, gC, gD, and gE). Herpes simplex virus antigen was detected in 35 of 40 specimens obtained from 26 biopsy-positive patients. In contrast, only three of 25 specimens from 17 biopsynegative patients gave positive results by this assay. An additional 30 CSF specimens from patients with proven bacterial and fungal infections were all negative by this assay. For all specimens tested, the sensitivity and specificity of the assay were both 88^0. However, when results were evaluated by patient, the sensitivity was 92^0 (24 of 26) with a specificity of 829/0 (14 of 17). Among specimens collected one week or later after disease onset, the sensitivity was 100^0, with a specificity of 93^0.
Precocious mammary gland development in P-cadherin-deficient mice.

To investigate the functions of P-cadherin in vivo, we have mutated the gene encoding this cell adhesion receptor in mice. In contrast to E- and N-cadherin– deficient mice, mice homozygous for the P-cadherin mutation are viable. Although P-cadherin is expressed at high levels in the placenta, P-cadherin–null females are fertile. P-cadherin expression is localized to the myoepithelial cells surrounding the lumenal epithelial cells of the mammary gland. The role of the myoepithelium as a contractile tissue necessary for milk secretion is clear, but its function in the nonpregnant animal is unknown. The ability of the P-cadherin mutant female to nurse and maintain her litter indicates that the contractile function of the myoepithelium is not dependent on the cell adhesion molecule P-cadherin. The virgin P-cadherin–null females display precocious differentiation of the mammary gland. The alveolar-like buds in virgins resemble the glands of an early pregnant animal morphologically and biochemically (i.e., milk protein synthesis). The P-cadherin mutant mice develop hyperplasia and dysplasia of the mammary epithelium with age. In addition, abnormal lymphocyte infiltration was observed in the mammary glands of the mutant animals. These results indicate that P-cadherin–mediated adhesion and/or signals derived from cell–cell interactions are important determinants in negative growth control in the mammary gland. Furthermore, the loss of P-cadherin from the myoepithelium has uncovered a novel function for this tissue in maintaining the undifferentiated state of the underlying secretory epithelium.
Abstract 2378: Involvement of leptin-activated canonic and non-canonic kinases in VEGF regulation in breast cancer

We have previously reported that in vitro and in vivo leptin signaling up-regulates VEGF in mouse and human mammary tumor cells (MT) but the specific molecular mechanisms involved are largely unknown. Here we describe how leptin activated canonic and non-canonic signaling pathways to induce specific transcription factors (TF) essential for the transcriptional activation of VEGF gene in mouse MT (4T1, EMT6 and MMT). Basal expression of VEGF/VEGFR2, leptin/OB-R and ER-α was initially investigated in MT. Leptin dose-response and time-course effects on VEGF levels were determined by ELISA. Several pharmacological inhibitors for key leptin-target kinases and TF were used to dissect the signaling pathways involved in leptin-induced levels of VEGF protein and mRNA in MT. A series of VEGF-promoter Luc-reporters [full-length & transcription factor (TF)-binding deletions: HRE, AP1, AP2, NFκB and SP1] were transfected into MT to analyze leptin regulation of VEGF transcription. Our data show that MAPK, PI-3K (canonic) and PKC, JNK and p38 MAP kinase (non-canonic) signaling pathways were generally involved in leptin regulation of VEGF. Analysis of cis-acting elements of VEGF promoter shows that leptin activation of HIF-1α is essential for transcription in all MT. This was mainly linked to MAPK, PI-3K, PKC, JNK and p38 signaling. Leptin-induced MAPK, JNK and p38 to activate NFκB that was essential for VEGF expression in high producer MT (EMT6 and MMT). Leptin through all canonic signaling pathways activates SP1 required for VEGF regulation in 4T1 cells. In contrast, AP1 was not involved but AP2 repressed leptin-mediated transcription of VEGF. Overall, these data suggest that leptin signaling regulates VEGF gene in MT cells mainly through HIF-1α and NFκB. These results delineate for first time the mechanisms for leptin regulation of VEGF and, reinforce the idea that the disruption of leptin signaling could impact breast cancer growth by inhibiting MT proliferation and angiogenesis. This work was supported in part by NIH/NCI 1SC1CA138658-02; NIH/UAB Breast SPORE Career Development Award; BC 504370 Susan G. Komen Foundation for the Cure and the Georgia Cancer Coalition Distinguished Cancer Scholar Award (to RRGP). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2378.
Hyporheic exchange flow around constructed in-channel structures and implications for restoration design

In-channel rock vane structures are widely used in stream restoration as a way to reduce stream channel erosion and create pool or riffle features. When these structures change hydraulic gradients they may affect ecological stream functions, such as hyporheic exchange flow (HEF) patterns. A study of constructed in-channel structure controls on HEF was conducted in the third-order Batavia Kill, New York using stream and hyporheic temperature amplitude analysis and computational fluid dynamics (CFD) hydraulic simulations. Temperature monitors were installed in the water column and channel bed at six locations around each of seven in-channel restoration structures (three cross-vanes and four J-hooks) at baseflow in 2007. Elevation surveys of the structures were then used to simulate HEF using CFD. The results indicate a pattern of pronounced upwelling in the run section just below the structure, upwelling transitioning to downwelling within the pool, and pronounced downwelling in the glide out of the pool. This pattern is consistent with natural riffle pool sequences. The direction of HEF inferred from the temperature amplitude analysis agreed with the direction of flow simulated with CFD at 80% of the locations, and the few disagreements were expected due to model limitations. CFD simulation demonstrated that increasing stream flows result in changes in HEF spatial patterns and magnitude at each structure. This work illustrates how CFD simulations can guide design of in-channel restoration structures for HEF function. Copyright © 2009 John Wiley & Sons, Ltd.
Structure of the metal clusters in rabbit liver metallothionein.

Abstract Cadmium-113 nuclear magnetic resonance (113Cd NMR) has been used to determine the structures of the multiple cadmium binding sites in the two major isoproteins of rabbit liver metallothionein. The isotopically 113Cd-labeled metallothionein used in these studies was isolated from the livers of rabbits that had been subjected to repeated injections of 113CdCl2. The native protein isolated from these livers contains an appreciable amount of Zn in addition to Cd, ranging from 2-3 mol per mol of protein out of a total metal content of 7 mol per mol of protein. The 113Cd NMR spectrum of Cd, Zn-containing metallothionein is quite complex, reflecting the fact that the native protein is a heterogeneous mixture of species containing different relative amounts of Zn and Cd. Replacement of the native Zn with 113Cd in vitro gave a protein whose 113Cd NMR spectrum was much simpler, containing eight distinct multiplets with chemical shifts ranging from 611-670 ppm. The origin of the multiplet structures has been shown to be 113Cd-113Cd scalar coupling arising from two-bond interactions between 113Cd ions linked to one another by bridging cysteine thiolate ligands. The size and structures of the metal clusters in the protein were determined by the application of selective homonuclear 113Cd decoupling techniques. Analysis of these data showed that rabbit liver metallothionein contains two separate metal clusters, one containing four Cd2+ ions and the other containing three. These two clusters, whose structures are the same in both isoproteins, have been designated “cluster A” and “cluster B,” respectively. Structures for the clusters are proposed that account for the 113Cd spin coupling data and the participation of all 20 of the cysteine residues in metal ligation, 11 in cluster A and 9 in cluster B. The appearance in the spectrum of eight multiplets rather than the seven that would be expected on the basis of the number of metal binding sites in the protein is an indication of some residual heterogeneity in the 113Cd-labeled metallothionein sample. The origin of this heterogeneity is suggested to be the presence of a protein species that lacks metal ions at its cluster B binding sites.
Modifications for disk diffusion susceptibility testing criteria of clinafloxacin (CI-960, AM-1091, PD127371) and fleroxacin (Ro 23-6240, AM-833) following studies with a challenge panel of ciprofloxacin-resistant clinical isolates.

Abstract A collection of ciprofloxacin-resistant organisms (200 strains) was developed among 300 total test strains to "challenge" the initial interpretive criteria developed for clinafloxacin (formerly CI-960), fleroxacin (formerly Ro 23–6240, AM-833), and ciprofloxacin. Generated results indicate the necessity for modified criteria for disk diffusion tests (5-μg disks) as follows: for clinafloxacin, susceptible at ⩾21 mm (⩽1 μg/ml) and resistant at ⩽17 mm (⩾4 μg/ml), or susceptible at ⩾19 mm (⩽2 μg/liter) and resistant at ⩽15 mm (⩾8 μg/ml); for fleroxacin, susceptible at ⩾16 mm (⩽2 μg/ml) and resistant at ⩽11 mm (⩾8 μg/ml); and for ciprofloxacin, resistant at ⩽17 mm ⩾4 μg/ml). These modifications maximize total absolute interpretive accuracy between the standardized test methods, especially minimizing the potential for false susceptibility (very major errors) when testing truly resistant isolates. The clinafloxacin spectrum was widest against these resistant isolates, and the other two tested fluoroquinolones (ciprofloxacin, fleroxacin) possessed comparable overall spectrums of activity, although ciprofloxacin was generally more active on a weight basis. We urge the rapid acceptance of these criteria to improve the accuracy of the widely used National Committee for Clinical Laboratory Standards method for disk diffusion tests.
TitaniQ: a titanium-in-quartz geothermometer

Titanium is one of many trace elements to substitute for silicon in the mineral quartz. Here, we describe the temperature dependence of that substitution, in the form of a new geothermometer. To calibrate the “TitaniQ” thermometer, we synthesized quartz in the presence of rutile and either aqueous fluid or hydrous silicate melt, at temperatures ranging from 600 to 1,000°C, at 1.0 GPa. The Ti contents of quartz (in ppm by weight) from 13 experiments increase exponentially with reciprocal T as described by: $$ {\text{Log}}{\left( {X^{{{\text{qtz}}}}_{{{\text{Ti}}}} } \right)} = (5.69 \pm 0.02) - \frac{{(3765 \pm 24)}} {{T(K)}}. $$ Application of this thermometer is straightforward, typically requiring analysis of only one phase (quartz). This can be accomplished either by EPMA for crystallization temperatures above 600°C, or by SIMS for temperatures down to at least 400°. Resulting temperature estimates are very precise (usually better than ±5°C), potentially allowing detailed characterization of thermal histories within individual quartz grains. Although calibrated for quartz crystallized in the presence of rutile, the thermometer can also be applied to rutile-absent systems if TiO2 activity is constrained.
Neodymium isotopic study of Baffin Bay water: sources of REE from very old terranes

Water samples were collected from Baffin Bay and surrounding areas in order to evaluate this region as a potential source of Nd from old continental material to Atlantic water. The isotopic data ranged from e_(Nd)(0) = −9.0 to −26 with most of the data around e_(Nd)(0) = −20 compared with values of North Atlantic Deep Water (NADW) with e_(Nd)(0) = −13.5. The concentration of Nd in Baffin Bay waters was as high as 6 × 10^(−12) g/g compared with 2.5 × 10^(−12) g/g for NADW. The combination of low e_(Nd) and high Nd concentration indicates that Baffin Bay may be a significant source of Nd from very old crustal material. A simple box model was used to evaluate the contribution to the Nd budget of NADW and it was concluded that a substantial fraction of the Nd from ancient crustal sources that is required to maintain the isotopic composition of NADW could be supplied by Baffin Bay outflow.
A hybrid optimization method and its role in computer-aided design

Abstract The variable metric methods have been analyzed and exploited in the past to achieve a superlinear rate of convergence in unconstrained optimization. Recently, the update formulas used in these methods have been extended for constrained optimization. The update formulas construct approximate second order derivatives using first order information. These are referred to as constrained variable metric (CVM) methods. Higher order of convergence is often accompanied by a smaller domain of convergence. To overcome this limitation of CVM methods, a hybrid optimization algorithm is presented in this paper. It uses a cost function bounding concept initially and a CVM method in later stages of the search process. In addition, the algorithm uses an active set strategy and is globally convergent. An improved active set strategy is suggested. Besides developing a superlinear optimization algorithm, an efficient programming structure for computer-aided design of engineering systems is suggested and implemented. A number of mathematical programming problems, and small and large scale engineering design problems are solved to test numerical aspects of the algorithm. The algorithm has performed extremely well on the test problems.
The prevalence, characteristics and metabolic consequences of renal insufficiency in very old hospitalized diabetic patients.

Abstract Aims We aimed to characterize the determinants and characteristics of renal disease in very old diabetic patients in geriatric care. Methods Consecutive diabetic patients (96 women, 38 men) admitted to a geriatric service were studied. Glomerular filtration rate (GFR), albuminuria, vascular and general comorbidities, glycaemic control, malnutrition (using the Mini-Nutritional Assessment [MNA], serum albumin and cholesterol levels), haemoglobin and inflammation (CRP levels) were assessed. Results (a) 51.2 and 12.4% patients had moderate or severe renal insufficiency. The prevalence of normo-, micro- and macroalbuminuria was 45.0, 38.9 and 16.0% in the whole population, and was similar in patients with or without moderate renal insufficiency. Renal insufficiency was associated with previous stroke ( P =0.024), heart failure ( P =0.024), and atrial fibrillation ( P =0.008), and possibly myocardial infarction ( P =0.059, Mann-Whitney test). (b) Albuminaemia was associated with albuminuria, MNA scores, haemoglobin, total and HDL-cholesterol and CRP. However, in multiple linear regression analysis CRP was the only robust determinant of albuminaemia ( P Conclusion Renal insufficiency often occurs without albuminuria, suggesting aetiologies distinct from classical diabetic nephropathy, and is strongly associated with vascular comorbidities. Hypoalbuminaemia is more strongly associated with inflammation than with albuminuria and malnutrition. Malnutrition, hypoalbuminaemia, low cholesterol levels and anaemia are not associated with renal insufficiency, likely due to the very high prevalence of these abnormalities in the whole population. These features must be taken into account when organizing the global care of elderly diabetic patients.
Some observations on the nature of recovery in global aphasia after stroke.

Abstract A small group of patients who were still classified as global aphasic at 3 months poststroke were systematically studied according to a rigorous timetable. The study patients received intensive speech therapy and were characterized as alert in spite of severe, pervasive linguistic deficits. All of the patients improved, with the greatest progress noted in auditory comprehension and the least in the use of propositional speech. There was an increased use of nonlinguistic skills for communication (i.e., gestures) noted beyond 6 months. Patients remained, nevertheless, severely defective in communication skills. The results suggest that time since onset is a critical variable in the evolution of global aphasia since the greatest changes occurred in the 6- to 12-month period.
Evaluating the Role of Physical, Operant, Cognitive, and Affective Factors in the Pain Behaviors of Chronic Pain Patients:

Behavioral manifestations of pain, distress, and suffering have been characterized as pain behaviors. Although acquisition and maintenance of pain behaviors have been considered to occur through reinforcement contingencies, empirical evidence suggests that pain behavior is better understood as a multidimensional entity. The present study was designed to evaluate the contributions of physical, operant, cognitive, and affective factors to individual differences in pain behaviors. A total of 63 chronic pain patients diagnosed with the disorder fibromyalgia underwent medical, physical, and psychological evaluations. Hierarchical regression analyses revealed that the physical, cognitive, and affective factors, but not operant factors, were significantly related to observed pain behaviors. The set of all factors accounted for 53% of the variance in observed pain behavior. The results in this study suggest that pain behaviors should be conceptualized as behavioral manifestation of pain based on a complex interaction of various psychological and physical factors.