cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract ES2-2: Triple Negative Breast Cancer: Subtypes, Molecular Targets, and Therapeutic Approaches

The term “triple negative breast cancer” (TNBC) is used to classify 10%–20% of all breast cancers that lack estrogen receptor (ER) and progesterone receptor expression as well as amplification of the human epidermal growth factor receptor 2 (HER2)1. Disease heterogeneity and the absence of well-defined molecular targets have made treatment of TNBC challenging. To make significant clinical advances for TNBC patients, integrative and comprehensive genomic and molecular analyses of TNBC are required to understand the complexity of the disease as well as to allow identification of homogeneous subsets and ‘driver pathways’ that can then be therapeutically targeted. In response to this need, we compiled an extensive number of TNBC gene expression (GE) profiles and initiated molecular subtyping of the disease2. We identified two basal-like TNBC subtypes with cell cycle and DDR GE signatures (BL1 and BL2); two mesenchymal subtypes with high expression of genes involved in differentiation and growth factor pathways (M and MSL); an immunomodulatory (IM) type; and a luminal subtype driven by androgen signaling (LAR). Differential GE was used to designate 25 TNBC cell line models representative of these subtypes. Predicted ‘driver’ signaling pathways were pharmacologically targeted in these preclinical models as proof of concept that analysis of distinct GE signatures can inform therapy selection. Representative BL1 and BL2 subtype cell lines preferentially respond to cisplatin. Mesenchymal, basal, and luminal subtype lines with aberrations in PI3K signaling have the greatest sensitivity, in general, to phosphatidylinositol 3-kinase (PI3K) inhibitors. The LAR subtype cell lines express AR and are uniquely sensitive to bicalutamide (AR antagonist). We have also developed “TNBCtype,” a web-based subtyping tool for candidate TNBC tumor samples using our GE metadata and classification methods3. The approaches used and data generated have value for biomarker selection, drug discovery, and clinical trial design that will enable alignment of TNBC patients to appropriate targeted therapies. 1. Dent, R., Trudeau, M., Pritchard, K.I., Hanna, W.M., Kahn, H.K., Sawka, C.A., Lickley, L.A., Rawlinson, E., Sun, P., and Narod, S.A. (2007). Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13, 4429–4434. 2. Lehmann, B.D., Bauer, J.A., Chen, X., Sanders, M.E., Chakravarthy, A.B., Shyr, Y., and Pietenpol, J.A. (2011). Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 121: 2750–67. 3. Chen, X., Li, J., Gray, W.H., Lehmann, B.D., Bauer, J.A., Shyr, Y., and Pietenpol, J.A. (2012). TNBCtype: A Subtyping Tool for Triple-Negative Breast Cancer. Cancer informatics 11, 147–156. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES2-2.
A paradigm to investigate the self-regulation of cocaine administration in humans.

Introduction Current laboratory paradigms of human cocaine administration generally dictate the timing of drug access in ways that may limit assessing aspects of cocaine-taking behavior. Patient-controlled analgesia (PCA) methods, which allow individuals less restricted access to narcotic (i.e., opiate) analgesics, have proven safe and clinically effective for self-regulated treatment of pain. The current study assessed the feasibility, safety, and validity of a model of ad libitum cocaine self-administration, in which participants self-selected the timing of cocaine infusions, using PCA techniques.
Disability and Orientation-Specific Performance during a Reciprocal Tapping Task

Reciprocal tapping tasks have frequently been used to quantify user performance and motor control system function. This experiment used a reciprocal tapping task to examine differences in performance for participants oriented both in front and to the side of a touch screen. Evaluating performance in different orientations for touch screen users is important because public spaces and workplaces may have barriers which preclude touch screens from always being operated from directly in front. Additionally, building design standards may require a wheelchair user in a public building to operate a touch screen from the side because there may not be enough clearance to orient their wheelchair in a manner which allows them to only operate the screen from the front. Participants with motor control impairments affecting the upper extremity and participants without upper extremity motor control impairments completed a study examining reciprocal tapping performance while using a touch screen. Both groups included whe...
EUROCENTRISM AND AFRICAN URBANIZATION: THE CASE OF ZANZIBAR'S OTHER SIDE

A number of geographers have recently championed the struggle against Eurocentric theoretical categorizations in geographical research on African cities. At the same time, many whose work has concentrated on African urban geography have felt left out in the more abstract theoretical debates of their colleagues based in the West. I argue for the possibility of confronting Western bias and contributing to broader theoretical debates by creating theoretical constructs derived from the African experience. I develop my argument through an analysis of urban development in Ng'ambo, the African “Other Side” of Zanzibar city, and work toward the creation of meso-level conceptual guides for understanding Ng'ambo's development derived from the ideas of Ng'ambo residents themselves.
Synthesis of a Negatively Charged Dibenzofuran-Based β-Turn Mimetic and Its Incorporation into the WW Miniprotein-Enhanced Solubility without a Loss of Thermodynamic Stability

A versatile synthesis has been developed to functionalize the 4-(2-aminoethyl)-6-dibenzofuran propionic acid residue (1a) at the 2 and 8 positions with a variety of different substructures. The unfunctionalized version of this peptidomimetic (1a) is known to facilitate β-hairpin formation in a variety of small peptides and proteins in aqueous solution when incorporated in place of the i + 1 and i + 2 residues of a β-turn. In this study, we append propionate substituents on 1a at the 2 and 8 positions to successfully overcome solubility problems encountered with the incorporation of 1a in place of the i + 1 and i + 2 residues of the β-turn in loop 1 of the WW domain. The thermodynamic stability of several WW domain analogues incorporating residues 1a and 1b was compared to that of the wild-type sequence revealing comparable ΔG(H2O) unfolding values at 4 °C ranging from 3 to 3.6 kcal/mol. WW domains incorporating residue 1b exhibit improved solubility (exceeding 100 μM) and resistance to aggregation without...
An ErbB2-Muc4 complex in rat ocular surface epithelia.

Purpose. To show the presence and localization of type 1 growth factor receptors (ErbB2, ErbB3 and ErbB4) in rat corneal and conjunctival epithelia and investigate the association of ErbB2 with its intramembrane ligand Muc4. Methods. Methacarn-fixed, paraffin-embedded sections of corneas and eyelids from female adult rats were immunocytochemically stained using antibodies against the ErbB receptors and Muc4. Sequential immunoprecipitation and immunoblot analyses were performed on epithelial lysates to investigate the presence of a complex of Muc4 and ErbB2 in corneal and conjunctival epithelia. Results. Immunocytochemical staining demonstrated the presence of ErbB2, ErbB3 and ErbB4 growth factor receptors throughout the rat corneal and conjunctival epithelia. Co-immunoprecipitation of the epithelial lysates demonstrated that Muc4 and ErbB2 are present as a complex. Conclusions. The three type 1 growth factor receptors (ErbB2, ErbB3 and ErbB4) are present in the rat corneal and conjunctival epithelia, and ...
Early cell proliferative and cytotoxic effects of phenacetin on rat nasal mucosa

Abstract The oral analgesic drug phenacetin is known to cause nasal and renal tumors in rats when fed in the diet for 2 years at 1.25 or 2.5%. Long-term exposure to chemicals at cytotoxic concentrations may lead to tumor formation secondary to chronic restorative cell proliferation. In the present experiments, cell proliferative and cytotoxic effects on the nasal mucosa were examined after short-term phenacetin administration. One week of daily gavage treatment of rats with phenacetin at doses comparable to those used in oncogenicity studies resulted in doserelated increases in DNA synthesis in both respiratory and olfactory mucosa. The increase in respiratory mucosa was due to inflammatory cells in the lamina propria and not proliferation of the respiratory epithelial cells. This observation demonstrates a potentially serious artifact in analytical approaches to DNA synthesis using tissue homogenates. One or two weeks of daily phenacetin treatment resulted in degenerative changes in the olfactory epithelium and necrosis of Bowman's glands. These changes were associated with increases in cell proliferation only in the olfactory epithelium. Two-week daily gavage treatment of rats with phenacetin at 100, 625, or 1250 mg/kg/day increased olfactory epithelial cell replication 62.4, 174, or 763%, respectively. The dose-response relationship for cell proliferation was similar to that of nasal tumor formation. These data suggest that the primary site of phenacetin toxicity within the nose is the olfactory mucosa, with restorative cell proliferation being confined to the epithelial cell layer. The data indicated that early cell proliferative responses may be important in the genesis of nasal tumors and that cell proliferation data may be useful for setting dose levels for oncogenicity studies.
Aggression and family size.

Summary The aggression displayed under controlled conditions by 56 inner-city Hispanic boys ages 7-8 was measured to test the hypothesis that Ss from large families will display less antisocial aggression than Ss from small families. The results indicate that aggression and family size were related in a linear manner: decreasing aggression was linked to increasing family size. These behavioral results may be, in part, the result of increased accelerated development of social skills within children living in large families.
Maintenance of highly contractile tissue-cultured avian skeletal myotubes in collagen gel

Highly contractile skeletal myotubes differentiated in tissue culture are normally difficult to maintain on collagen-coated tissue culture dishes for extended periods because of their propensity to detach as a sheet of cells from their substratum. This detachment results in the release of mechanical tension in the growing cell “sheet” and, consequently, loss of cellular protein. We developed a simple method of culturing high density contractile primary avian myotubes embedded in a collagen gel matrix (collagel) attached to either a stainless steel mesh or nylon support structure. With this system the cells are maintained in a highly contractile state for extended periods in vitro under tension. Structural integrity of the myotubes can be maintained for up to 10 d in basal medium without serum or embryo extract. Total cellular protein and myosin heavy chain accumulation in the cells can be maintained for weeks at levels which are two to three times those found in timematched controls that are under little tension. Morphologically, the myotubes are well differentiated with structural characteristics of neonatal myofibers. This new collagel culture system should prove useful in the analysis of in vitro gene expression during myotube to myofiber differentiation and its regulation by various environmental factors such as medium growth factors, innervation, and mechanical activity.
gln3 Mutations Dissociate Responses to Nitrogen Limitation (Nitrogen Catabolite Repression) and Rapamycin Inhibition of TorC1

The GATA family transcription activator, Gln3 responds to the nitrogen requirements and environmental resources of the cell. When rapidly utilized, "good" nitrogen sources, e.g., glutamine, are plentiful, Gln3 is completely sequestered in the cytoplasm, and the transcription it mediates is minimal. In contrast, during nitrogen-limiting conditions, Gln3 quickly relocates to the nucleus and activates transcription of genes required to scavenge alternative, "poor" nitrogen sources, e.g., proline. This physiological response has been designated nitrogen catabolite repression (NCR). Because rapamycin treatment also elicits nuclear Gln3 localization, TorC1 has been thought to be responsible for NCR-sensitive Gln3 regulation. However, accumulating evidence now suggests that GATA factor regulation may occur by two separate pathways, one TorC1-dependent and the other NCR-sensitive. Therefore, the present experiments were initiated to identify Gln3 amino acid substitutions capable of dissecting the individual contributions of these pathways to overall Gln3 regulation. The rationale was that different regulatory pathways might be expected to operate through distinct Gln3 sensor residues. We found that C-terminal truncations or amino acid substitutions in a 17-amino acid Gln3 peptide with a predicted propensity to fold into an α-helix partially abolished the ability of the cell to sequester Gln3 in the cytoplasm of glutamine-grown cells and eliminated the rapamycin response of Gln3 localization, but did not adversely affect its response to limiting nitrogen. However, overall wild type control of intracellular Gln3 localization requires the contributions of both individual regulatory systems. We also found that Gln3 possesses at least one Tor1-interacting site in addition to the one previously reported.
Carryover effects of cyclical stretching of the digits on hand function in stroke survivors.

Abstract Objective To investigate the longevity and cumulative impact of multiple sessions of passive, cyclical stretching of the digits on hand function in subacute stroke survivors. Design Before-after trial with intervention repeated on 3 consecutive days. Setting Research laboratory. Participants Individuals (N=27) with moderate to severe hand impairment, 2 to 6 months (subacute, n=12) and >7 months (chronic, n=15) poststroke. Interventions Subjects wore an actuated glove orthosis that cyclically moved their fingers and thumb from a relaxed/flexed posture into neutral extension for 30 minutes on 3 consecutive days. Main Outcome Measures Three hand-specific tasks from the Graded Wolf Motor Function Test, Box and Block Test (BBT), grip strength, and lateral pinch strength. Recordings were taken before stretching and at 3 time points, each separated by 30 minutes after completion of stretching on each day. Results Significant improvement was observed immediately after the stretching for both groups. Improvements in the subacute group were largely maintained up to 1 hour poststretching, with significant carryover from day to day for some outcomes measures such as the BBT ( P =.006) and grip strength ( P =.012). In contrast, improvements after stretching for the chronic group were transient, with the changes largely dissipating over time and no significant cumulative effect across days. Conclusions Cyclical stretching of the digits had a lasting and reinforcing effect on improving hand motor control for subacute stroke survivors. Incorporation of cyclical stretching before active hand therapy may prove to be a beneficial treatment for stroke survivors, especially during the subacute phase of recovery.
Sodium tracer diffusion in glasses of the type (Na2O)0.2[(BO1.5)x(SiO2)1 − x]0.8

Abstract Sodium tracer diffusion coefficients, D Na *, have been measured in sodium borosilicate glasses of the type (Na 2 O) 0.2 [(BO 1.5 ) x (SiO 2 ) 1 − x ] 0.8 as a function of temperature and the composition parameter x. In these glasses, which can alternatively also be described by using the formula Na 2 O·(2B 2 O 3 ) x ·(4SiO 2 ) 1 − x , one network former unit, SiO 2 , is replaced by another one, BO 1.5 , while keeping the sodium concentration constant. At constant temperature, the tracer diffusion coefficient of sodium as a function of x has a shallow minimum at about x = 0.7. At temperatures below about 310 °C the temperature dependences of the measured tracer diffusion coefficients are of Arrhenius-type; at higher temperatures one observes an increase in the temperature dependence with increasing temperature. The activation energy derived from sodium tracer diffusion data for temperatures up to about 310 °C increases about linearly with increasing x from about 70 to 80 kJ/mol. The pre-exponential factor as a function of x varies by about one order of magnitude and has a minimum at about x = 0.4. Values derived for the Haven-ratio are smaller than one and show a shallow minimum as a function of x at around x = 0.75. Furthermore, it was investigated whether there is a significant, directly measurable uptake of water during annealing in moist atmospheres and whether water taken up from moist atmospheres can influence the diffusion of sodium.
Issues in Transracial Adoption and Foster Care

(2001). Issues in Transracial Adoption and Foster Care. Adoption Quarterly: Vol. 5, No. 2, pp. 1-4.
Suppurative complications of acute otitis media: changes in frequency over time.

Objective To review the experience at the Children's Hospital of Philadelphia in the management of suppurative complications of acute otitis media from 2000 to 2007, with an emphasis on changes in frequency over time. Design Retrospective cohort study. Setting Academic, tertiary care children's hospital. Patients The study population comprised 87 children (age Main Outcome Measure Frequency of cases of acute mastoiditis per year. Results The frequency of cases of acute mastoiditis at our institution was positively correlated with calendar time, both for all cases of acute mastoiditis (Spearman rank correlation, r = 0.73; P = .04) and for cases of mastoid subperiosteal abscess ( r = 0.96; P Conclusions We observed an increase in the frequency of cases of acute mastoiditis with subperiosteal abscess seen at our institution over the study period, controlling for case volume. These findings suggest an increase in incidence, although further population-based studies are required to definitively evaluate this possibility.
Practice and Privilege: Social Change and the Structure of Large Law Firms

Despite dramatic changes in size and specialization, large law firms have remained remarkably unchanged in other respects. Introducing research on major Chicago law firms, this article examines how large law firms have changed so much by changing so little. It proposes a theory of law firm growth emphasizing the relationship between changes in the market for sophisticated legal services and changes in the approach law firms have taken to organizing their practices. The author discusses the organizational structure of large law firms, giving particular attention to the various roles that lawyers play in such firms. After speculating on trends affecting large law firms, he points to implications of these trends for law and social change.
Non-Target Effects of Transgenic Blight-Resistant American Chestnut (Fagales: Fagaceae) on Insect Herbivores

ABSTRACT American chestnut [Castanea dentata (Marshall) Borkhausen], a canopy dominant species across wide swaths of eastern North America, was reduced to an understory shrub after introduction of the blight fungus [Cryphonectria parasitica (Murrill) Barr] in the early 1900s. Restoration of American chestnut by using biotechnology is promising, but the imprecise nature of transgenesis may inadvertently alter tree phenotype, thus potentially impacting ecologically dependent organisms. We quantified effects of genetic engineering and fungal inoculation of trees on insect herbivores by using transgenic American chestnuts expressing an oxalate oxidase gene and wild-type American and Chinese (C. mollissima Blume) chestnuts. Of three generalist folivores bioassayed, only gypsy moth [Lymantria dispar (L.)] was affected by genetic modification, exhibiting faster growth on transgenic than on wild-type chestnuts, whereas growth of polyphemus moth [Antheraea polyphemus (Cramer) ] differed between wild-type species, ...
The desmoplastic round cell tumor: A new solid tumor of childhood

Three patients with a new, pathologically distinct solid tumor of childhood have been treated recently. The disease is characterized by male predominance, adolescent onset, an extensive abdominal primary tumor, and aggressive metastases to regional lymph nodes, liver, and lung. Two patients presented with vague abdominal pain and the third with testicular pain. All three noted fatigue and malaise of less than two months' duration with minimal associated weight loss. Computed tomography (CT) scans of the abdomen and chest were obtained for initial preoperative staging, and then all three underwent surgical exploration. Widespread disease was found in each case. In no instance was complete tumor extirpation possible because of extensive peritoneal spread and lymphatic and hepatic metastases. Histologically, all three tumors consisted of round blue cells with a dense desmoplastic reaction and focal rhabdoid features. Immunohistochemical markers for epithelial, neural, and muscle elements were positive. Aggressive multidrug chemotherapeutic regimens were used in each case, and all three patients are alive and well but with known residual disease. We conclude that in cases of the desmoplastic round cell tumor of childhood, CT scans underestimate the extent of disease, and exploratory laparotomy is necessary for diagnosis and appropriate staging. Surgery is usually palliative because of extensive spread. Awareness of this newly recognized aggressive solid tumor of childhood is essential to define its natural history and guide the development of effective multidisciplinary therapeutic regimens.
Mediating Lipid Biosynthesis: Implications for Cardiovascular Disease

Dysregulation of lipid homeostasis is a risk factor for cardiovascular disease (CVD). Thus, understanding the molecular mechanisms of maintaining lipid homeostasis may aid the discovery of novel targets for treating CVD. MED15 and cyclin-dependent kinase-8 (CDK8) are subunits of the Mediator complex, which contains multiple proteins and functions as a transcriptional cofactor. Mediator can positively or negatively regulate gene expression, depending on the contexts and its associated transcription factors. Recent studies revealed a critical role of MED15 and CDK8 in regulating sterol regulatory element-binding protein (SREBP) transcription factors, which are master activators for genes that are responsible for lipid biosynthesis. Here, we review the function of MED15 and CDK8 in regulating lipid homeostasis and discuss the implications for CVD.
The effects of anatomic variations on stereotactic laser amygdalohippocampectomy and a proposed protocol for trajectory planning.

Background Stereotactic laser amygdalohippocampectomy (SLAH) is a promising minimally invasive alternative for mesial temporal lobe epilepsy. As seizure outcome has been associated with the extent of amygdalar and hippocampal ablation, it is important to select a safe trajectory optimizing involvement of both structures; however, variations in temporal anatomy significantly affect the overall complexity of planning. Objective To quantify anatomic variables of SLAH and facilitate stereotactic planning by developing a protocol for optimally targeting the amygdalohippocampal complex (AHC). Methods We performed a retrospective analysis of 19 SLAHs. Anatomic measurements from preoperative magnetic resonance imaging and laser trajectory measurements from coregistered postoperative magnetic resonance imaging were taken in 11 patients. Simple linear regression analysis was performed to identify significant predictor variables determining ablation extent. Based on these data, a protocol for optimal trajectory planning was developed and subsequently implemented in 8 patients. Results The medial angle of the laser trajectory correlated with the medial angle of the AHC. The length of amygdalar cannulation was predictive of its ablation volume. All trajectories passed through a posteroinferior corridor formed by the lateral ventricle superiorly and collateral sulcus inferiorly. Our protocol facilitated planning and increased the volume of AHC ablation. Conclusion The medial AHC angle dictates the medial trajectory angle and a path from the posteroinferior corridor through the hippocampus and the center of the amygdala dictates the caudal angle. These observations led to a protocol for long-axis AHC cannulation that maintains an extraventricular trajectory to minimize hemorrhage risk and targets the center of the amygdala to optimize ablation volumes.
The Management of Diabetic Neuropathy in CKD

Diabetic nephropathy is the leading cause of end stage renal disease (ESRD) requiring renal replacement therapy in the U.S.1A The progression of diabetes to advanced stages of chronic kidney disease is associated with the progression of multiple other micro and macrovascular complications of diabetes including diabetic neuropathies1. Diabetic peripheral neuropathy is a common complication of diabetes associated with high morbidity, poor quality of life and high risk of lower-extremity amputation. Similarly, cardiac autonomic neuropathy is associated with life-threatening consequences, such as silent myocardial ischemia and high mortality 2-4. In this review we will examine the characteristics of cardiac autonomic neuropathy and diabetic peripheral neuropathy in diabetic patients with stage 4-5 chronic kidney disease (CKD) or end stage renal disease (ESRD) undergoing dialysis. We will describe the evidence supporting the available therapeutic options and the challenges associated with providing adequate care for these patients and discuss future directions for investigation.
Serum Amyloid A and High Density Lipoprotein Participate in the Acute Phase Response of Kawasaki Disease

In this study we report changes in HDL concentration and composition in acute and convalescent Kawasaki disease. Notable reductions in plasma HDL-cholesterol (0.54 +/- 0.2 mmol/L, normal level 0.7-1.81 mmol/L) and apolipoprotein A-I (apoA-I) (56 +/- 28 mg/dL, normal level 141 +/- 22 mg/dL) were observed in all 24 patients studied during the acute phase of Kawasaki disease. These changes were accompanied by the marked appearance of serum amyloid A (SAA) protein in the plasma, associated with HDL3-like lipoprotein particles. The distribution of apoA-I was analyzed in five patients and showed a significant increase in lipid-free apoA-I in the bottom fraction (28.8 +/- 4.1%, normal range 10-15%), suggesting displacement of apoA-I from the HDL particles by SAA. Within 2 wk after acute Kawasaki disease, levels of HDL-cholesterol and apoA-I returned to the normal range, and SAA disappeared from the plasma. The HDL of patients with Kawasaki disease was markedly enriched in triglyceride even in the absence of changes in total plasma triglyceride. The core composition of HDL returned to the normal range more slowly than the plasma HDL-cholesterol and apoA-I levels. This suggests that Kawasaki disease has a profound effect on the lipoprotein profile acutely and a more subtle sustained effect on the HDL composition. We interpret these changes as manifestations of the acute phase response in Kawasaki disease.
Detection of Intravascular Epidural Catheters Using 2-Chloroprocaine: Influence of Local Anesthetic Dose and Nalbuphine Premedication

Background and Objectives Detecting the intravascular placement of epidural catheters is essential to avoid local anesthetic toxicity. Small doses of intravenous local anesthetics produce changes in sensorium and are often used to test newly placed epidural catheters. Many parturients receive nalbuphine for analgesia prior to epidural catheter placement. This study examines how nalbuphine premedication influences symptoms following intravenous 2-chloroprocaine. Methods Thirty-one volunteers were randomized to receive premedication with placebo or 0.15 mg/kg of nalbuphine intravenously. Starting 10 minutes later, intravenous injections of 0.0, 0.3, 0.6, 0.9, 1.2, and 1.5 mg/kg of 2-chloroprocaine were given in random order at 10 minute intervals. After each injection, volunteers were asked to report changes in hearing, taste, or other symptoms. Results Symptoms reported (in decreasing order of frequency) were auditory changes, taste changes, dizziness/lightheadedness, tingling in the extremities, and visual changes. The probability that volunteers will report symptoms is proportional to the dose of 2-chloroprocaine administered (auditory symptoms, P Conclusions This study suggests that patients who receive nalbuphine for analgesia prior to epidural placement will be more likely to report symptoms after receiving intravenous 2-chloroprocaine during epidural test dosing.
Drug-related problems and quality of life in arthritis and low back pain sufferers.

Abstract Objective The objective of this study was to determine the relationship between drug-related problems (DRPs) and health-related quality-of-life (HRQoL) in ambulatory, community-dwelling patients with musculoskeletal disorders. Methods A 12-month, prospective, observational study was conducted in 12 independent community pharmacies in eastern Iowa. Ambulatory patients with self-reported diagnoses of osteoarthritis, rheumatoid arthritis, or low back pain were invited to participate. During quarterly visits to the pharmacy, patients used touch-screen computers to fill out the Short Form-36 (SF-36) general health survey. Using the results of these point-of-service health status assessments, community pharmacists interviewed patients to assess for DRPs. To examine the influences of different DRP characteristics on HRQoL and controlling for potential confounders, both univariate and multivariate analyses were performed using the change in physical component summary (PCS) score and mental component summary (MCS) score of the SF-36 from baseline to 12 months as the dependent variables. In each regression, the independent variables were those significant variables from the univariate analyses, as well as the types of DRPs and their outcomes. Results A total of 461 patients were enrolled in the study. Through 12 months, 926 cumulative DRPs were identified. Overall regression models were significant for the PCS and MCS scores, respectively. Two types of DRPs showed significant negative associations with change in PCS: wrong drug and needs additional drug therapy. One type of DRP showed significant negative association with change in MCS: needs additional drug therapy. Resolution or improvement in DRPs showed a significant positive correlation with change in MCS but not PCS. Conclusions Two DRPs, needs additional drug therapy and wrong drug, are associated with reduced self-reported physical health in arthritis and low back pain, while the DRP needs additional drug therapy is also associated with reduced self-reported mental health. Resolution of DRPs is associated with improvement in mental health in this cohort.
Revision of vagal nerve stimulator electrodes: technical approach

Background. As the number of implanted vagal nerve stimulators grows, the need for removal or revision of the devices will become more frequent. Our purpose was to demonstrate the feasibility of complete removal of the vagal nerve stimulator electrode using microsurgical technique. Methods. Operative databases at the University of Utah (1995 through 2002), Westchester Medical Center (1995 through 2001), and University of Arizona Health Sciences Center (1995 through 1999) were retrospectively reviewed. Patients who had undergone removal or revision of a previously placed vagal nerve stimulator electrode were identified. Patients who had a vagal nerve stimulator device removed but had the lead trimmed and incompletely removed were excluded. Findings. Seven patients underwent complete removal of the lead. Microsurgical dissection allowed removal of the helical electrode from the vagus nerve without apparent physiological consequences. Four patients had a new electrode placed just proximal to the original lead site. The operative procedure required an additional 30 minutes to complete compared with initial device placement. The four patients who underwent replacement of the electrode demonstrated normal device function and lead resistance at the time of postoperative follow-up. Each experienced a return to prior stimulation response and seizure control. Conclusions. This series suggests that the electrode can be removed from the vagus nerve and repositioned without significant consequence in most cases.
Role of the mitochondrial ATP-sensitive K+ channels in cardioprotection.

The mitochondrial ATP-sensitive K + (mitoKATP) channel was discovered more than a decade ago. Since then, several pharmacological studies have identified agents that target this channel some of which selectively target mitoK ATP . These and other studies have also suggested that mitoK ATP plays a key role in the process of ischemic preconditioning (IPC) and prevention of apoptosis. The mechanism by which mitoK ATP exerts its protective effects is unclear, however, changes in mitochondrial Ca 2+ uptake and levels of reactive oxygen species, and mitochondrial matrix swelling are believed to be involved. Despite major advances, several important issues regarding mitoK ATP remain unanswered. These questions include, but are not limited to: the molecular structure of mitoK ATP , the downstream and upstream mechanisms that leads to IPC and cell death, and the pharmacological profile of the channel. This review attempts to provide an up-to-date overview of the role of mitoKATP in cardioprotection.
Nonlinear behavior of composite sandwich beams in three-point bending

The load-deflection behavior of a composite sandwich beam in three-point bending was investigated. The beam was made of unidirectional carbon/epoxy facings and a polyvinyl chloride closed-cell foam core. The load-deflection curves were plotted up to the point of failure initiation. They consist of an initial linear part followed by a nonlinear portion. A nonlinear mechanics of materials analysis that accounts for the combined effect of the nonlinear behavior of the facings and core materials (material nonlinearity) and the large deflections of the beam (geometric nonlinearity) was developed. The theoretical predictions were in good agreement with the experimental results. It was found that the effect of material nonlinearity on the deflection of the beam is more pronounced for shear-dominated core failures in the case of short span lengths. It is due to the nonlinear shear stress-strain behavior of the core. For long span lengths, the observed nonlinearity is small and is attributed to the combined effect of the facings nonlinear stress-strain behavior and the large deflections of the beam.
Role of acid-base interfacial bonding in adhesion

The strength of macroscopic adhesive bonds of polymers is known to be directly proportional to the microscopic exothermic interfacial energy changes of bond formation, as measured by Dupre's 'work of adhesion'. Since the work of adhesion can be very appreciably increased by interfacial acid-base bonding with concomitant increases in adhesive bond strength, it is important to understand the acid-base character of polymers and of the surface sites of substrates or of the reinforcing fillers of polymer composites. The best known acid-base bonds are the hydrogen bonds; these are typical of acid-base bonds, with interaction energies dependent on the acidity of the hydrogen donor and on the basicity of the hydrogen acceptor. The strengths of the acidic or basic sites of polymers and of inorganic substrates can be easily determined by spectroscopic or calorimetric methods, and from this information one can start to predict the strengths of adhesive bonds. An important application of the new knowledge of interfac...
Variation in specific gravity of potato tubers.

Specific gravity of tubers from the Irish Cobbler, Kennebec, Norgold Russet, Norland, Red Pontiac, Russet Burbank, Snowflake, and Viking varieties grown at 2 locations over 3 years were determined by the brine solution method. The usual differences in specific gravity were noted between varieties and locations. There was a narrow range in specific gravity of individual tubers within lots of Norland and Russet Burbank, and a wide range within lots of Kennebec and Snowflake, with the remaining varieties intermediate. Low variation of tubers within a variety as measured by standard deviation did not indicate low or high specific gravity. Varieties with low variation tended to remain low from one year to the next.
ALWAYS LEADING OUR MEN IN SERVICE AND SACRIFICE

This article focuses on the most important woman in Garveyism: Amy Jacques Garvey, Marcus Garvey's second wife. Amy Jacques Garvey's true value in the Garvey movement has rarely been acknowledged; most authors and scholars have misleadingly depicted her as Marcus's “helpmate.” This article proposes that Amy Jacques Garvey was a key architect of Garveyism and a lifelong advocate of social justice in her own right. The author also examines the relationship among race, class, and gender as it pertains to Amy Jacques Garvey's life and social thought.
Mechanism of Metalorganic MBE Growth of High Quality AlN on Si (111).

AlN constitutes the buffer layer of choice for the growth of GaN on all common substrates and its crystalline quality and surface morphology determine many of the properties of the overgrown epitaxial structure. This work systematically investigates the MOMBE growth of high quality AlN on Si (111) using trimethylaluminum and ammonia as sources of aluminum and nitrogen, respectively. Metalorganic MBE represents a hybrid growth technique that offers a combination of growth precision, in-situ monitoring and ease of source management with the promise of high material quality. We demonstrate very efficient growth, with the growth rate in excess of 500 nm/h and low ammonia consumption of less than 1 sccm. Over the entire domain of growth parameters, the surface roughness remained in the range from 12 to 53 A rms for AlN layers up to 1000 nm thick. Here, the low values of the roughness are associated to the low growth temperature (760 °C), behavior that contrasts with that usually observed in gas source MBE with elemental Al source. X-ray diffraction linewidth as narrow as 141 arcsec has been demonstrated for samples grown under stoichiometric conditions. High temperature of the ammonia injector promotes the transition to the two-dimensional growth, while reducing the growth rate, pointing out the importance of surface hydrogen. We demonstrate that hydrogen plays an important role in the MOMBE process acting as a surfactant and passivating surface nitrogen bonds.
Mindful M&M’s Mindfulness and Parent Training for a Preschool Child With Disruptive Behavior Disorder

Disruptive behavior problems are the primary reason for referral of preschool-aged children to mental health care settings and significantly interfere with social and academic functioning. Furtherm...
A Genome-Scale RNA–Interference Screen Identifies RRAS Signaling as a Pathologic Feature of Huntington's Disease

A genome-scale RNAi screen was performed in a mammalian cell-based assay to identify modifiers of mutant huntingtin toxicity. Ontology analysis of suppressor data identified processes previously implicated in Huntington's disease, including proteolysis, glutamate excitotoxicity, and mitochondrial dysfunction. In addition to established mechanisms, the screen identified multiple components of the RRAS signaling pathway as loss-of-function suppressors of mutant huntingtin toxicity in human and mouse cell models. Loss-of-function in orthologous RRAS pathway members also suppressed motor dysfunction in a Drosophila model of Huntington's disease. Abnormal activation of RRAS and a down-stream effector, RAF1, was observed in cellular models and a mouse model of Huntington's disease. We also observe co-localization of RRAS and mutant huntingtin in cells and in mouse striatum, suggesting that activation of R-Ras may occur through protein interaction. These data indicate that mutant huntingtin exerts a pathogenic effect on this pathway that can be corrected at multiple intervention points including RRAS, FNTA/B, PIN1, and PLK1. Consistent with these results, chemical inhibition of farnesyltransferase can also suppress mutant huntingtin toxicity. These data suggest that pharmacological inhibition of RRAS signaling may confer therapeutic benefit in Huntington's disease.
Few channel models of nuclear reactions: Distorted-wave Born approximation for light-ion-induced transfer processes.

Standard derivations of the distorted wave Born approximation amplitudes for particle-transfer reactions have always left unanswered two fundamental questions: How can one justify cancellation of the typical, one-body, absorptive-potential counter term, and, which Pauli-principle exchange amplitudes correspond to the standard, nonexchange distorted-wave Born approximation amplitude? This paper provides an answer to these questions. This is accomplished by using a particular type of antisymmetrized, N-particle collision theory to describe the transfer processes. For the reaction (b,a), with the mass of a greater than the mass of b, the extended Faddeev theory of the preceding paper is used, while its time-reversal partner, the precursor form of the Bencze-Redish-Sloan equations, is used for the (a,b) case. They lead to almost identical first-order amplitudes. For all the reactions studied herein, it is found that the form of the nonexchange distorted-wave amplitudes---those that are commonly referred to as distorted-wave Born approximation amplitudes---are essentially the same as are used to fit data. This result is achieved without any need to account for cancellation of a counter term, since none appears, implying an absence of so-called core-excitation effects in first order.No formalism other than the extended Faddeev--Bencze-Redish-Sloan--type has yet been found to yield such results. In addition, none of the first-order, Pauli-principle exchange amplitudes predicted by the formalism are of the conventional knockon type: all are either heavy-particle type of exchange amplitudes or heavy-particle plus additional, non-knockon types. There is also no need to cancel a counter term in the exchange amplitudes. For the (p,d) reaction, and certain others, the occurrence of a pure heavy-particle pickup amplitude helps to explain why direct reaction data analyses that rely on a distorted-wave Born approximation amplitude alone, i.e., one without an exchange amplitude, have been successful.The lack of a knockon term also helps to understand the empirical fact that three-particle pickup and not knockon is the mechanism for direct (p,\ensuremath{\alpha}) reactions. In addition to treating first-order amplitudes, a general expression is given for a two-step correction, and an expression for the nonexchange part of the (p,d)-(d,t) portion of the (p,t) two-step amplitude is derived. It is found to contain the same interactions as occur in a similar amplitude recently derived by Austern and Kawai.
The effect of plastic deformation on the martensite-to-austenite transition in an iron-nickel alloy

The effect of plastic deformation introduced by rolling at room temperature on the austenite start temperature of an Fe-30.3 wt pct Ni-0.005 wt pct C alloy has been determined. The austenite start temperature increases monotonically with deformation. Microhardness measurements show that the austenite start temperature increases with the yield strength of the martensite. The temperature at which martensite reversal initiates is not affected by the amount of martensite present, and, therefore, is not dependent on the martensite plate size. It is suggested that the reverse martensite transformation initiates at the martensite-austenite interface and is controlled by interface propagation.
New proofing process for making ink-on-paper prepress color proofs

This paper will review the needs of prepress proofing, then, point out some limitations of current proofing methods. After this, DuPont's new technology aimed at providing a modular "ink-on-paper" proofing system, will be described first, the concept, then the overall process and components of this system. And finally, the capabilities of this technology will be summarized
Acetylcholine-induced initiation of thymic lymphoblast DNA synthesis and proliferation†

Low (5 times 10-9 M to 10-7 M) acetylcholine concentrations cause a calcium-independent stimulation of the initiation of DNA synthesis and proliferation of lymphoblasts which are part of rat thymocyte populations suspended in vitro. A much higher (5 times 10-5 M) acetylcholine concentration also stimulates lymphoblast DNA synthesis and proliferation, but this action is calcium-dependent. This proliferogenic response to acetylcholine is however not clearly mediated by either cyclic GMP or cyclic AMP.
Short TpA-rich segments of the zeta-eta region induce DNA methylation in Neurospora crassa.

The mechanisms that establish DNA methylation in eukaryotes are poorly understood. In principle, methylation in a particular chromosomal region may reflect the presence of a "signal" that recruits methylation, the absence of a signal that prevents methylation, or both. Experiments were carried out to address these possibilities for the 1.6 kb zeta-eta (zeta-eta) region, a relict of repeat-induced point mutation (RIP) in the fungus Neurospora crassa. The zeta-eta region directs its own de novo methylation at a variety of chromosomal locations. We tested the methylation potential of a nested set of fragments with deletions from one end of the zeta-eta region, various internal fragments of this region, chimeras of eta and the homologous unmutated allele, theta (theta), and various synthetic variants, integrated precisely in single copy at the am locus on linkage group (LG) VR or the his-3 locus on LG IR. We found that: (1) the zeta-eta region contains at least two non-overlapping methylation signals; (2) different fragments of the region can induce different levels of methylation; (3) methylation induced by zeta-eta sequences can spread far into flanking sequences; (4) fragments as small as 171 bp can trigger methylation; (5) methylation signals behave similarly, but not identically, at different chromosomal sites; (6) mutation density, per se, does not determine whether sequences become methylated; and (7) neither A:T-richness nor high densities of TpA dinucleotides, typical attributes of methylated sequences in Neurospora, are essential features of methylation signals, but both promote de novo methylation. We conclude that de novo methylation of zeta-eta sequences does not simply reflect the absence of signals that prevent methylation; rather, the region contains multiple, positive signals that trigger methylation. These findings conflict with earlier models for the control of DNA methylation, including the simplest version of the collapsed chromatin model.
Estimation of Incident Propensity for Reliability Analysis in the Highway Capacity Manual

This paper presents the method used to generate the incident probabilities required by the freeway scenario generator for travel time reliability analysis in the Highway Capacity Manual. The freeway scenario generator requires the estimation of monthly probabilities of different levels of incident severity during specified study periods. Incident probability in this context is the fraction of time that an incident of a specific level of severity is active somewhere on the freeway facility during the study period for the month considered. The proposed method is designed to recognize and deal with the varying levels of incident and facility data availability at the implementing agencies. A queuing model is proposed for the conversion of incident frequencies into incident probabilities when agencies have access only to frequencies instead of probabilities.