cssi/SciSciGPT-SciSciNet huggingface dataset:
A concepts-first introduction to computer science

We present a unique "concepts-first" curriculum that exposes students without programming experience to the intellectual depth and breadth of computer science through hands-on experience with software development. The curriculum is supported by JPie, a tightly integrated programming environment that enables live construction of Java applications through direct manipulation of graphical representations of programming abstractions. The curriculum, projects, and classroom experience are described.
Human eccrine sweat contains tissue kallikrein and kininase II

We attempted to determine the level of sweat kallikrein (kininogenase) and to purify and characterize it using sweat collected over a white petrolatum barrier. Thermally induced eccrine sweat obtained from 24 healthy subjects showed kallikrein activity of 24.4 ng kinins generated/1 mg of sweat protein when heated plasma was used as the substrate and 16.1 ng kinin when purified low molecular weight bovine kininogen was used as the substrate. Sweat was sequentially purified by Sephacryl S-200, diethyaminoethyl Sephacel, and fast flow liquid chromatography Mono Q chromatography. Sweat kallikrein had a M(r) of 40,000 and was inhibited by aprotinin but not by soybean trypsin inhibitor. The peptide generated by sweat kallikrein was identified as lys-bradykinin using reverse phase high-performance liquid chromatography and by its amino acid sequence. Anti-human urinary kallikrein immunoglobulin G neutralized the sweat kallikrein activity completely, indicating that the sweat kallikrein is the glandular type. Purified sweat and salivary kallikrein showed similar M(r) and responses to inhibitors and antibodies. Using immunohistochemistry, kallikrein activity was localized in luminal ductal cells and in the peripheral rim of secretory coil segments, presumably the outer membrane of the myoepithelium. We also observed kininase activity in sweat at M(r) 160,000, which was inhibited by ethylenediamine tetraacetic acid, captopril, and angiotensin converting enzyme inhibitor peptide, indicating that it is kininase II (or angiotensin converting enzyme). Sweat also contains abundant non-kallikrein hydrolases for S-2266 and S-2302. The demonstration of glandular kallikrein, its tissue localization, and the presence of kininase II in sweat provide the basis for future studies on the physiologic role of the kallikrein/kinin system in the eccrine sweat gland.
Short-Term Cigarette Smoke Exposure Predisposes the Lung to Secondary Injury

Brief exposure to cigarette smoke is not generally associated with pulmonary injury and may adversely affect the lung only if underlying disease is present. To test this hypothesis, our laboratory performed a series of experiments involving exposure of hamsters to second-hand cigarette smoke (2 h/day for 5 days), either immediately before or after induction of acute pulmonary injury by intratracheal administration of amiodarone. Compared to controls receiving amiodarone alone, hamsters pretreated with smoke showed significant increases in the following parameters: (1) lung inflammation graded on a scale of 0-4 (3.4 vs. 1.6; p < 0.001), (2) percentage of neutrophils in bronchoalveolar lavage fluid (BALF) (75.0 vs. 1.3; p < 0.001), (3) percentage of TNFR1-positive BALF macrophages (44.7 vs. 2.7; p < 0.001), and (4) apoptotic lung parenchymal cells per ten high-power microscopic fields (7.3 vs. 0.7; p < 0.001). Animals post-treated with smoke also showed significant increases in these parameters compared to controls but to a lesser degree than pre-exposed animals. With regard to human disease, such synergistic interactions may account for a significant portion of the morbidity associated with second-hand smoke exposure.
Functional Decline in the Elderly: Evidence for Direct and Stress-buffering Protective Effects of Social Interactions and Physical Activity

Advances in medical technology and improvements in health behavior have greatly increased the proportion of Americans who survive into old age. Consequently, identifying environmental and behavioral factors that enhance or protect the health and functional capacity of older adults is an important goal. This study investigated the extent to which social interactions and physical activity can protect older adults from the declines in functional ability that typically occur with age and the extent to which they buffer the negative effects of widowhood on physical functioning. Data were from the Longitudinal Study of Aging, a six-year follow-up of over 7,000 respondents in the 1984 National Health Interview Survey. Using individual growth curve models which examine the effects of predictor variables on change over time, this study investigated how physical activity, social interactions, and widowhood are related to the rate of change in functional health over a six-year period. Results suggested that physical activity and social interactions each exerted independent effects on functional decline. In addition, physical activity and social interactions buffered the effects of widowhood on functional decline, especially in men who died before the end of the study. Results suggest a need for health promotion programs to encourage both physical and social activities in the elderly.
A curved array photoacoustic tomography system for small animal imaging

We have developed and tested a photoacoustic imaging system based on a 128 element curved-phased ultrasonic array, which spans a quarter of a complete circle with a radius of curvature equal to 25mm. The center frequency of the array is 5 MHz with 60% bandwidth. The physical dimensions of the elements are 10x0.3mm (elevation x azimuth) with an elevation focus of 19mm. Earlier we reported acoustic measurements of the axial and lateral resolutions of the system that were limited by the impulse response of the narrowband source used in the test. In this paper we discuss photoacoustic characterization of the system including resolution and sensitivity. The array forms the building block for a 512-element ring designed for complete tomographic imaging of small animals. Imaging results of phantoms will be compared with simulations.
Richard Anderson: Cardiothoracic Surgeon Personified

Richard Anderson epitomized the best of the specialty of cardiothoracic surgery. A superb technical surgeon, he spent the majority of his career at the Virginia Mason Clinic in Seattle where he headed a highly regarded cardiac surgery program. His no nonsense work ethic and integrity were widely respected and resulted in multiple professional leadership roles: President of the Western Thoracic Surgical Association, Chairman of the American Board of Thoracic Surgery Examination Committee, President of the Society of Thoracic Surgeons, and President of CTSNet. Richard Anderson will be remembered for his strength of character and his enormous selfless contributions of time and energy to our specialty.
β‐Amyloid‐Induced Neurotoxicity of a Hybrid Septal Cell Line Associated with Increased Tau Phosphorylation and Expression of β‐Amyloid Precursor Protein

Recent evidence suggests that beta-amyloid peptide (beta-AP) may induce tau protein phosphorylation, resulting in loss of microtubule binding capacity and formation of paired helical filaments. The mechanism by which beta-AP increases tau phosphorylation, however, is unclear. Using a hybrid septal cell line, SN56, we demonstrate that aggregated beta-AP(1-40) treatment caused cell injury. Accompanying the cell injury, the levels of phosphorylated tau as well as total tau were enhanced as detected immunochemically by AT8, PHF-1, Tau-1, and Tau-5 antibodies. Alkaline phosphatase treatment abolished AT8 and PHF-1 immunoreactivity, confirming that the tau phosphorylation sites were at least at Ser(199/202) and Ser396. In association with the increase in tau phosphorylation, the immunoreactivity of cell-associated and secreted beta-amyloid precursor protein (beta-APP) was markedly elevated. Application of antisense oligonucleotide to beta-APP reduced expression of beta-APP and immunoreactivity of phosphorylated tau. Control peptide beta-AP(1-28) did not produce significant effects on tau phosphorylation, although it slightly increased cell-associated beta-APP. These results suggest that betaAP(1-40)-induced tau phosphorylation may be associated with increased beta-APP expression in degenerated neurons.
DRL training and performance following anterior, posterior, or complete septal lesions in infant and adult rats ☆

Abstract Animals received septal lesions, caudate lesions, electrode punctures, or skin incisions at seven days of age while their litter mates were allowed to develop normally until 119 days of age before receiving septal lesions. When trained to bar press on DRL schedules of reinforcement all animals with septal lesions which included the posterior septum and columns of the fornix were very inefficient. Animals with electrode punctures, caudate lesions or anterior septal lesions performed as efficiently as control animals. Age at the time of lesion did not effect the severity of the behavioral deficit; however, minor recovery of function was displayed following the 119 day recovery period.
Links Between Business Strategy and Human Resource Management Strategy in U.S.-Based Japanese Subsidiaries: An Empirical Investigation

This study examines linkages between business strategy and human resource management (HRM) strategy in Japanese subsidiaries in the U.S. It investigates whether or not fit between a subsidiary's business strategy and its HRM strategy is associated with higher performance. The data show that subsidiaries with matched strategies performed better than unmatched ones in terms of HRM-related performance measures such as rates of promotion and turnover. Japanese subsidiaries with a business strategy/HRM strategy match were also more likely to experience better business performance versus competitors than were unmatched ones.
Sizing Up the Search for Autism Spectrum Disorder (ASD) Risk Markers During Prenatal and Early Postnatal Life

The symptom-based diagnosis of autism spectrum disorder (ASD) is characterized by early-emergent impairments of social communication alongside patterns of restricted interests and repetitive behavior. The preschool emergence of ASD symptoms and their strong association with known genetic disorders of early brain development motivate searching for ASD risk markers during prenatal and early postnatal life. Three studies in this month’s Journal contribute to this search, namely those by Campbell et al.,1 Zwaigenbaum et al.,2 and Cheslack-Postava et al.3
Is EPA's radium-226 drinking water standard justified?

Abstract The U.S. Environmental Protection Agency's (EPA) proposed drinking water standard for radium-226 ( 226 Ra) of 5 pCi/1 is evaluated according to its health basis and carcinogenic implications. Proposed health risks of 226 Ra in drinking water by other leading theoreticians (Evans, Gofman-Tamplin and Peterson) are also considered in light of the EPA proposal. It is concluded that the EPA proposal to raise the standard for 226 Ra in drinking water is not justified on the basis of present knowledge of 226 Ra carcinogenic effects.
Compliance of a microfibril subjected to shear and normal loads

Many synthetic bio-inspired adhesives consist of an array of microfibrils attached to an elastic backing layer, resulting in a tough and compliant structure. The surface region is usually subjected to large and nonlinear deformations during contact with an indenter, leading to a strongly nonlinear response. In order to understand the compliance of the fibrillar regions, we examine the nonlinear deformation of a single fibril subjected to a combination of shear and normal loads. An exact closed-form solution is obtained using elliptic functions. The prediction of our model compares well with the results of an indentation experiment.
Evaluation and Treatment of Pediatric Gastroesophageal Reflux and Its Effects on Voice

Abstract Voice disorders in the pediatric population are common, but have been understudied. Inflammation, trauma, neurologic, and congenital anomalies can all result in childhood dysphonia. Laryng...
Host and Parasite Populations After a Ten Year Flood: Manayunkia speciosa and Ceratonova (syn Ceratomyxa) shasta in the Klamath River

Abstract Manayunkia speciosa is the obligate invertebrate host of Ceratonova (syn Ceratomyxa) shasta (Myxozoa), the parasite that causes ceratomyxosis (enteronecrosis) in salmon and trout. High peak discharge has been correlated with reduced ceratomyxosis in salmon hosts but how it may influence parasite dynamics in the invertebrate host is unknown. We sampled M. speciosa populations from three sections of the Klamath River, California, in spring and summer months in 2006, a water year that was characterized by i) winter and spring discharge equivalent in magnitude to a 10 year flood and ii) low risk of ceratomyxosis for salmon. M. speciosa were observed in all river sections and months but densities were highest in the upper section, where peak discharge was lowest. Populations were dominated by immature individuals in all river sections and months, followed by progeny and mature individuals. Prevalence of C. shasta infection was 0.25% (SE 0.09) in June; 0.13% (SE 0.09) in July; 0% (SE 0) in August, and ...
Sensitivity of Atlantic Tropical Storm Frequency to ENSO and Interdecadal Variability of SSTs in an Ensemble of AGCM Integrations

A significant reduction (increase) of tropical storm activity over the Atlantic basin is observed during El Nino (La Nina) events. Furthermore, the number of Atlantic tropical storms displays an interdecadal variability with more storms in the 1950s and 1960s than in the 1970s and 1980s. Ensembles of simulations with an atmospheric general circulation model (AGCM) are used to explore the mechanisms responsible for this observed variability. The interannual variability is investigated using a 10-member ensemble of AGCM simulations forced by climatological SSTs of the 1980s everywhere except over the tropical Pacific and Indian Oceans. Significantly fewer tropical storms are simulated with El Nino SSTs imposed over the tropical Pacific and Indian Oceans than with La Nina conditions. Increased simulated vertical wind shear over the Atlantic is the most likely explanation for the reduction of simulated tropical storms during El Nino years. SST forcing from different El Nino events has distinct impacts on Atlantic tropical storms in the simulation: simulated tropical storms are significantly less numerous with 1982 SSTs imposed over the tropical Pacific and Indian Oceans than with 1986 SSTs. The interdecadal variability of tropical storm activity seems to coincide with an interdecadal variability of the North Atlantic SSTs with colder SSTs in the 1970s than in the 1950s. Ensembles of AGCM simulations produce significantly more tropical storms when forced by observed SSTs of the 1950s than when forced by SSTs of the 1970s. This supports the theory that the interdecadal variability of SSTs has a significant impact on the expected number of Atlantic tropical storms and suggests that Atlantic tropical storms may be more numerous in coming years if North Atlantic SSTs are getting warmer. A significant increase of vertical wind shear and a significant decrease in the convective available potential energy over the tropical Atlantic in the 1970s may explain the simulated interdecadal variability of Atlantic tropical storms.
Photochemical reactions of aqueous plutonium systems—II

Abstract The photochemical shift of the Pu 4+ disproportionation equilibrium in aqueous perchloric acid solutions has been measured and shown to be reversible. Ratios of equilibrium quotients between light and dark conditions have been measured for 0.01 M Pu ion concentrations in 0.53 to 1.24 N acid solutions exposed to 0.5 Watt of UV light. The photodecomposition of time- and temperature-aged Pu(IV) polymers in perchloric and nitric acid solutions have been examined as a function of aging conditions. Effects similar to those seen previously for fresh polymers have been observed in the aged perchloric acid solutions.
Proinflammatory cytokine signaling required for the generation of natural killer cell memory

Although natural killer (NK) cells are classified as innate immune cells, recent studies demonstrate that NK cells can become long-lived memory cells and contribute to secondary immune responses. The precise signals that promote generation of long-lived memory NK cells are unknown. Using cytokine receptor-deficient mice, we show that interleukin-12 (IL-12) is indispensible for mouse cytomegalovirus (MCMV)-specific NK cell expansion and generation of memory NK cells. In contrast to wild-type NK cells that proliferated robustly and resided in lymphoid and nonlymphoid tissues for months after MCMV infection, IL-12 receptor–deficient NK cells failed to expand and were unable to mediate protection after MCMV challenge. We further demonstrate that a STAT4-dependent IFN-γ–independent mechanism contributes toward the generation of memory NK cells during MCMV infection. Understanding the full contribution of inflammatory cytokine signaling to the NK cell response against viral infection will be of interest for the development of vaccines and therapeutics.
LATE LOGARITHMIC SALMONELLA TYPHIMURIUM HEp‐2 CELL ASSOCIATION AND INVASION RESPONSE TO SHORT‐CHAIN FATTY ACID ADDITION

The entry of Salmonella into the intestinal epithelial cells is essential for its pathogenesis. In the present study, late logarithmic growth (12 h) in Luria Bertani broth supplemented (25, 50, or 100 mM) with acetate, propionate, butyrate, or a mixture of the three short-chain fatty acids (SCFA), influenced the ability of S. typhimurium to associate and invade cultured HEp-2 cells. The response to SCFA addition was dependent on the concentration and the pH of the medium. Cell-association was decreased 4 to 100-fold at pH 6 and 2 to 20-fold at pH 7. At pH 7, invasion was increased 2-fold when bacteria were cultured in the presence of all concentrations of acetate and 25 mM propionate or butyrate; however, a 1.5 to 163-fold decrease in invasion occurred at pH 6 for all SCFA. The SCFA concentration also affected cell-association and invasion of S. typhimurium, especially at pH 6. In general, for each of the SCFA at pH 6 a lower percentage of cell-association and invasion was observed as the SCFA concentration was increased while at pH 7 decreases did not consistently occur as SCFA concentration was increased. These differences among the SCFA along with the pH effects suggest that the concentration of SCFA and the pH of the intestinal lumen may influence the expression of the invasion phenotype of S. typhimurium.
Severe, Uncontrolled Hypertension and Adult-Onset Seizures: A Case-Control Study in Rochester, Minnesota

Summary: Purpose: Hypertension is an established risk factor for clinically detected stroke, which is in turn a risk factor for epilepsy. This relation suggested that hypertension, particularly severe and uncontrolled, might increase the risk of epilepsy in the absence of prior clinically detected stroke. Methods: Subjects in this population-based case-control study were the 145 incident cases of first unprovoked seizure aged 55 years or older and 290 controls matched to cases on age, gender, and duration of medical follow-up. Using the records-linkage system of the Rochester Epidemiology Project, we obtained, for both cases and matched controls, all blood pressure readings before each case's first seizure came to medical attention. Subjects were classified as hypertensive if they had at least two readings of 160/95 mm Hg or if there was electrocardiographic evidence for left ventricular hypertrophy. Results: Severe uncontrolled hypertension increased the risk of unprovoked seizure. Left ventricular hypertrophy without diuretic treatment was associated with an 11-fold increased risk of unprovoked seizure: left ventricular hypertrophy treated with diuretics did not increase the risk. Conclusions: In the absence of clinically detected stroke, left ventricular hypertrophy without diuretic use may increase the risk of unprovoked seizures, and diuretic treatment may protect against this increased risk.
Tu1672 Final Cytopathologic Diagnosis of Initially “Indeterminate” Pancreatic Mass Lesions

Tu1672 Final Cytopathologic Diagnosis of Initially “Indeterminate” Pancreatic Mass Lesions Nigeen F. Hessami, Stuart R. Gordon, Timothy B. Gardner* Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH Background & Aims: Endoscopic Ultrasound (EUS)-guided Fine Needle Aspiration (FNA) of pancreatic masses is generally very accurate; occassionally however, cytology is classified as atypical or suspicious. These “indeterminate” results often lead to repeat procedures along with patient and provider uneasiness. We aimed to determine the final pathologic diagnosis in patients with pancreatic masses undergoing EUS-FNA whose initial cytology report was characterized as “atypical” or “suspicious”. Methods: A retrospective chart review was performed on patients referred for EUS-FNA of a pancreatic mass at our medical center from 2000-11. Initial cytology results were characterized as “benign”, “atypical”, “suspicious”, or ”malignant”. Reports were then compared to the final pathology of the pancreatic mass which was obtained from a repeat EUS-FNA or a subsequent surgical specimen. The following lesions were considered malignant: lymphoma, adenocarcinoma, islet cell tumor, and metastatic disease. Results: 619 patients met the inclusion criteria. On initial EUS-FNA, 448 had a “malignant” cytology, 26 had “suspicious” cytology, 29 were “atypical”, and 88 were “benign”. Of the 26 with “suspicious” cytology, 92.3% eventually were found to have a malignant diagnosis. In the 29 patients with “atypical” cytology, 65.5% eventually were eventually deemed malignant. In the 448 patients with an initial “malignant” report, 99.3% had the malignancy subsequently confirmed. The probability of an initial “suspicious” diagnosis being negative and an initial “malignant” diagnosis being negative were equivalent (pZ0.23). Linear regression demonstrated that a “suspicious” cytology was most likely in lesions from the neck (OR Z 2.01, 95% CI 1.23-2.79) and body (OR Z 2.23, 95% CI 1.78-2.67) and “atypical” cytology from the uncinate (OR Z 3.05, 95% CI 2.47-3.64). Conclusion: EUS-FNA of pancreas masses with an initial “suspicious” cytology are almost always found eventually to be malignant. These findings suggest that “suspicious” cytology may be treated as if the result were malignant. Probability that a Pancreatic Mass was Malignant given the EUSguided FNA Cytology Results
The role of complement in ocular pathology

Functionally active complement system and complement regulatory proteins are present in the normal human and rodent eye. Complement activation and its regulation by ocular complement regulatory proteins contribute to the pathology of various ocular diseases including keratitis, uveitis and age-related macular degeneration. Furthermore, a strong relationship between age-related macular degeneration and polymorphism in the genes of certain complement components/complement regulatory proteins is now well established. Recombinant forms of the naturally occurring complement regulatory proteins have been exploited in the animal models for treatment of these ocular diseases. It is hoped that in the future recombinant complement regulatory proteins will be used as novel therapeutic agents in the clinic for the treatment of keratitis, uveitis, and age-related macular degeneration.
Identification and characterization of nuclear microsatellite loci for multiple species of chorus frogs (Pseudacris) for population genetic analyses

Microsatellites were developed from an enriched genomic library of Pseudacris feriarum and P. nigrita. For 85 P. feriarum, six loci averaged 59 alleles, with loci ranging from 42–71 alleles. Observed heterozygosity averaged 0.72/locus (range: 0.42–0.84). In 142 P. maculata, seven additional loci (plus two loci above) averaged 8 alleles, with loci ranging from 3–16 alleles. Observed heterozygosity averaged 0.60/locus (range: 0.35–0.81).
Properties of distinct ventral tegmental area synapses activated via pedunculopontine or ventral tegmental area stimulation in vitro

Anatomical studies indicate that synaptic inputs from many cortical and subcortical structures converge on neurons of the ventral tegmental area (VTA). Although in vitro electrophysiological studies have examined synaptic inputs to dopamine (DA) and non-DA neurons in the VTA, they have largely relied upon local electrical stimulation to activate these synapses. This provides little information regarding the distinct properties of synapses originating from different brain areas. Using whole-cell recordings in parasagittal rat brain slices that preserved subcortical axons from the pedunculopontine nucleus (PPN) to the VTA, we compared these synapses with those activated by intra-VTA stimulation. PPN-evoked currents demonstrated longer latencies than intra-VTA-evoked currents, and both VTA and PPN responses were mediated by GABAA and AMPA receptors. However, unlike VTA-evoked currents, PPN currents were exclusively mediated by glutamate in 25–40% of the VTA neurons. Consistent with a cholinergic projection from the PPN to the VTA, nicotinic acetylcholine receptors (nAChR) were activated by endogenous acetylcholine released during PPN, but not VTA, stimulation. This was seen as a reduction of PPN-evoked, and not VTA-evoked, synaptic currents by the α7-nAChR antagonist methyllycaconitine (MLA) and the agonist nicotine. The β2-nAChR subunit antagonist dihydro-β-erythroidine had no effect on VTA- or PPN-evoked synaptic currents. The effects of MLA on PPN-evoked currents were unchanged by the GABAA receptor blocker picrotoxin, indicating that α7-nAChRs presynaptically modulated glutamate and not GABA release. These differences in physiological and pharmacological properties demonstrate that ascending PPN and presumed descending inputs to VTA utilize distinct mechanisms to differentially modulate neuronal activity and encode cortical and subcortical information.
Living into the imagined body: how the diagnostic image confronts the lived body

In this paper I will show how the medical image, presented to the patient by the physician, participates in medicine's cold culture of abstraction, objectification and mandated normativity. I begin by giving a brief account of the use of anatomical imaging since the Renaissance to show how images have historically functioned in contrast to how they are currently used in medical practice. Next, I examine how contemporary medical imaging techniques participate in a kind of knowledge production that objectifies the human body. Finally, I elucidate how physicians ought to place the medical image within the context of the lived body so as to create a healing relationship with the patient. In all this I hope to show that the medical image, far from a piece of objective data, testifies to the interplay of particular beliefs, practices and doctrines contemporary medicine holds dear. To best treat her patient, the physician must appreciate the influence of these images and appropriately place them within the context of the patient's lived experience.
History-Based Email Prioritization

The rise of email as a communication medium raises several issues. A majority of email messages sent are spam. Also, the amount of legitimate email received by many users is overwhelming. In this paper, we propose two new methods of performing email prioritization. Both techniques rank users inboxes using models created from email history. With them, lower priority email messages may be dealt with so that the use of email remains a net productivity gain.
Psychological Foundations of Trust

Trust lies at the foundation of nearly all major theories of interpersonal relationships. Despite its great theoretical importance, a limited amount of research has examined how and why trust develops, is maintained, and occasionally unravels in relationships. Following a brief overview of theoretical and empirical milestones in the interpersonal-trust literature, an integrative process model of trust in dyadic relationships is presented.
Concentrative sorting of secretory cargo proteins into COPII-coated vesicles

Here, we show that efficient transport of membrane and secretory proteins from the ER of Saccharomyces cerevisiae requires concentrative and signal-mediated sorting. Three independent markers of bulk flow transport out of the ER indicate that in the absence of an ER export signal, molecules are inefficiently captured into coat protein complex II (COPII)-coated vesicles. A soluble secretory protein, glycosylated pro-alpha-factor (gpalphaf), was enriched approximately 20 fold in these vesicles relative to bulk flow markers. In the absence of Erv29p, a membrane protein that facilitates gpalphaf transport (Belden and Barlowe, 2001), gpalphaf is packaged into COPII vesicles as inefficiently as soluble bulk flow markers. We also found that a plasma membrane protein, the general amino acid permease (Gap1p), is enriched approximately threefold in COPII vesicles relative to membrane phospholipids. Mutation of a diacidic sequence present in the COOH-terminal cytosolic domain of Gap1p eliminated concentrative sorting of this protein.
Inappropriate Activation of the Androgen Receptor by Nonsteroids: Involvement of the Src Kinase Pathway and Its Therapeutic Implications

The inappropriate activation of androgen receptor (AR) by nonsteroids is considered a potential mechanism in the emergence of hormone-refractory prostate tumors, but little is known about the properties of these "pseudoactivated" AR. Here, we present the first comprehensive analysis closely examining the properties of AR activated by the neuropeptide bombesin that distinguish it from androgen-activated AR. We show that bombesin-activated AR (a) is required for bombesin-induced growth of LNCaP cells, (b) has a transcriptional profile overlapping with, but not identical to, androgen-activated AR, (c) activates prostate-specific antigen by preferentially binding to its proximal promoter, and (d) assembles a distinct coactivator complex. Significantly, we found that Src kinase is critical for bombesin-induced AR-mediated activity and is required for translocation and transactivation of AR. Additionally, we identify c-Myc, a Src target gene, to be activated by bombesin and a potential coactivator of AR-mediated activity specific to bombesin-induced signaling. Because Src kinase is often activated by other nonsteroids, such as other neuropeptides, growth factors, chemokines, and cytokines, our findings have general applicability and provide rationale for investigating the efficacy of the Src kinase pathway as a target for the prevention of relapsed prostate cancers.
Mechanism of current-induced early afterdepolarizations in guinea pig ventricular myocytes

We investigated possible ionic mechanisms that cause early afterdepolarizations (EADs) following the injection of constant inward current in guinea pig ventricular myocytes by several interventions that affect failure of action potential repolarization. The amount of constant current was adjusted to measure the threshold potential (Vth) associated with the minimum inward current required for inducing EADs [threshold current (Ith)] and also the magnitude of EADs at Vth and following adjustment of current to generate takeoff potentials of -30 and -20 mV. Interventions associated with either inhibition of Ca2+ release from the sarcoplasmic reticulum (ryanodine 5 x 10(-6) M) or L-type membrane Ca2+ channel current (verapamil 1.1 x 10(-5) M and nisoldipine 5 x 10(-7) M) reduced or abolished EADs arising from -30 or -20 mV. Cells that generated delayed afterdepolarizations (DADs) in the absence of depolarizing current after 20 stimulations at 5 Hz either in control solution or following interventions associated with Ca2+ loading (reduced extracellular [K+] or increased extracellular [Ca2+]) also developed a marked shift in Vth of current-induced EADs at 1-Hz stimulation to more negative potentials [60.3 +/- 10.7 mV (mean +/- SD, n = 17) vs. -41.7 +/- 6.4 mV in cells without DADs in control solution (n = 25), P < 0.001]. Ca2+ loading also increased the magnitude of EADs arising from Vth and -20 mV. Exposure to quinidine (1.23 x 10(-5) M), which blocks both Na+ and delayed rectifier K+ channels, significantly reduced Ith but had only minimal effect on the magnitude of EADs. Our results suggest that L-type Ca2+ channel current and [Ca2+]-sensitive inward current associated with release of Ca2+ from the sarcoplasmic reticulum are the major currents that cause this form of EADs, and that Ca2+ loading promotes the development of large EADs likely to propagate to normal tissue.
Short Interest and Aggregate Tobin’s Q Dynamics

This study investigates the dynamic response of the change in short interest ratio in the equity market (SIR) to the change in aggregate Tobin’s q ratio (∆TBQ). Looking at the quarterly data from 1951Q4 to 2012Q4, the VAR results show that SIR drops following the shock to ∆TBQ after one quarter. The causality test results also confirm that the ∆TBQ causes the SIR to decrease. The variance decomposition analysis shows that the ∆TBQ forecasts ∆SIR about 7.26% at the 3-quarter horizon and around 7.51% at the 6-quarter horizon. The findings imply that when firms in the economy are generating more values or have more investment opportunities, investors, on average, are more optimistic and ride along the momentum thus significantly reducing their short-selling trade activity in the equity market.
Towards next generation wlans: exploiting coordination and cooperation

Wireless Local Area Networks (WLANs) operating in the industrial, scientific and medical (ISM) radio bands have gained great popularity and increasing usage over the past few years. The corresponding MAC/PHY specification, the IEEE 802.11 standard, has also evolved to adapt to such development. However, as the number of WLAN mobile users increases, and as their needs evolve in the face of new applications, there is an ongoing need for the further evolution of the IEEE 802.11 standard. In this thesis we propose several MAC/PHY layer protocols and schemes that will provide more system throughput, lower packet delivery delay and lessen the power consumption of mobile devices. Our work investigates three approaches that lead to improved WLAN performance: 1) cross-layer design of the PHY and MAC layers for larger system throughput, 2) exploring the use of implicit coordination among clients to increase the efficiency of random media access, and 3) improved packets dispatching by the access points (APs) to preserve the battery of mobile devices. Each proposed solution is supported by theoretical proofs and extensively studied by simulations or experiments on testbeds.
CLINICAL IMPORTANCE OF COMPLEX AORTIC PLAQUE IN THE CHA2DS2-VASC SCORING SYSTEM IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION

Although complex aortic plaque (≥4mm, mobile or ulceration) is a significant risk factor for thromboembolism and a component of CHA2DS2-VASc score, the clinical importance of complex aortic plaque in CHA2DS2-VASc score has not been well investigated. Transesophageal echocardiography finding of
Deep neural networks – a developmental perspective

There is a recent surge in research activities around “deep neural networks” (DNN). While the notion of neural networks have enjoyed cycles of enthusiasm, which may continue its ebb and flow, concrete advances now abound. Significant performance improvements have been shown in a number of pattern recognition tasks. As a technical topic, DNN is important in classes and tutorial articles and related learning resources are available. Streams of questions, nonetheless, never subside from students or researchers and there appears to be a frustrating tendency among the learners to treat DNN simply as a black box. This is an awkward and alarming situation in education. This paper thus has the intent to help the reader to properly understand DNN, not just its mechanism (what and how) but its motivation and justification (why). It is written from a developmental perspective with a comprehensive view, from the very basic but oft-forgotten principle of statistical pattern recognition and decision theory, through the problem stages that may be encountered during system design, to key ideas that led to the new advance. This paper can serve as a learning guide with historical reviews and important references, helpful in reaching an insightful understanding of the subject.
A mechanistic PK/PD model for two anti-IL13 antibodies explains the difference in total IL-13 accumulation observed in clinical studies

IMA-638 and IMA-026 are humanized IgG1 monoclonal antibodies (mAbs) that target non-overlapping epitopes of IL-13. Separate first-in-human single ascending dose studies were conducted for each mAb. These studies had similar study designs, but mild to moderate asthmatics were recruited for the IMA-638 study and healthy subjects were recruited for the IMA-026 study. IMA-638 and IMA-026 showed similar pharmacokinetic (PK) profiles, but very different total IL-13 (free and drug bound IL-13) profiles; free IL13 was not measured. IMA-026 treatment induced a dose-dependent accumulation of total IL-13, while IMA-638 treatment led to a much smaller accumulation without any clear dose-response. To understand the differences between the two total IL-13 profiles and to predict the free IL-13 profiles for each mAb treatment, a mechanistic PK/pharmacodynamic model was developed. PK-related parameters were first fit to the mean PK profiles of each mAb separately; thereafter, the target-related parameters were fit to both total IL-13 profiles simultaneously. The IL-13 degradation rate was assumed to be the same for asthma patients and healthy subjects. The model suggests that an approximately 100× faster elimination of IL-13-IMA-638 complex than IL-13-IMA-026 complex could be responsible for the differences observed in total IL-13 profiles for the two mAbs. Furthermore, the model predicts that IMA-638 administration results in greater and more prolonged free IL-13 inhibition than equivalent dosing of IMA-026 despite similar binding KD and PK profile. In conclusion, joint modeling of two similar molecules provided mechanistic insight that the elimination rate of mAb-target complex can regulate the degree of free target inhibition.
Real-Time Observation of Local Strain Effects on Nonvolatile Ferroelectric Memory Storage Mechanisms

We use in situ transmission electron microscopy to directly observe, at high temporal and spatial resolution, the interaction of ferroelectric domains and dislocation networks within BiFeO3 thin films. The experimental observations are compared with a phase field model constructed to simulate the dynamics of domains in the presence of dislocations and their resulting strain fields. We demonstrate that a global network of misfit dislocations at the film-substrate interface can act as nucleation sites and slow down domain propagation in the vicinity of the dislocations. Networks of individual threading dislocations emanating from the film-electrode interface play a more dramatic role in pinning domain motion. These dislocations may be responsible for the domain behavior in ferroelectric thin-film devices deviating from conventional Kolmogorov-Avrami-Ishibashi dynamics toward a Nucleation Limited Switching model.
Workers Compensation Reform Past and Present: An Analysis of Issues and Changes in Benefits

This research uses national data to analyze the effects of two cycles of workers compensation reform. One, during the 1970s, raised benefits for injured workers. The second, in the 1990s, was aimed at cutting workers' compensation costs. The research decomposes workers compen sation costs into variables directly controlled by legislatures, and vari ables that legislatures have no control over, to more easily analyze the direction that each reform took. The central finding of this research is that reforms of the nineties primarily effected medical care and access to the system. Consequently, they were not a direct reaction to the reform movement initiated by the National Commission in the early seventies. The economic recession of 1990-1991 appears to have been the primary economic motive that contributed to the timing of reform. These results indicate that workers compensation, because it is administered by the states, can be weakened in response to national economic events such as health care crisis and ...
Placental Transmission of Immunity to St. Louis Encephalitis Virus Inoculated Intraperitoneally in Mice.

ConclusionsPlacental transmission of specific immunity to the virus of St. Louis encephalitis has been demonstrated. Mice between 7 and 9 days of age and 13 to 14 days of age born of mothers immunized by the subcutaneous inoculation of active virus show no increased resistance to the virus of St. Louis encephalitis inoculated intracerebrally but are more resistant than control mice of the same age to virus inoculated intraperitoneally.
Predicting End-of-Career Transitions for Baby Boomers Nearing Retirement Age

Retirement has traditionally been conceptualized as a point-in-time decision to physically and psychologically withdraw from the workforce on reaching a certain age. However, the expectations of older workers demonstrate a new retirement paradigm, with many more retirement trajectories. The purpose of this study was to examine actual career decisions being made by older workers and to understand sociodemographic factors that might differentiate their career trajectories. Data from the Health and Retirement Study (Juster & Suzman, 1995) were analyzed using multinomial logistic regression to compare 4 retirement trajectories (i.e., no retirement, full retirement, bridge employment, and encore career). Gender, age, education, marital status, health, and wealth differentially predicted the odds of pursuing each of the 4 retirement decisions. Career practitioners may use these results to help baby boomers make retirement decisions and provide them with appropriate education, guidance, and resources. Additional research is needed to examine other factors salient to each of the retirement trajectories.
Doxorubicin and cyclosporin A affect murine lymphoid cells expressing different antigenic determinants.

Cyclosporin A (CsA) enhances the antitumor activity of doxorubicin (Dox) as well as that of some other cytotoxic drugs against drug-resistant tumor variants. In some cases, however, such combination treatments result in severe unexplained toxicities. In this study the possibility was explored that the effects of CsA and Dox on lymphoid cells may be instrumental, at least in part, in determining their toxicological effects. Subsets of spleen and thymus lymphoid cells, from mice with or without Dox or CsA treatment, were identified by flow cytometry based upon their plasma membrane antigenic determinants. The results indicate that there is essentially no cross-sensitivity/resistance between the two agents. The most Dox-susceptible cells were immature (non-proliferating) CD4 + CD8 + thymocytes and CD3 - B220 - as well as CD3 - B220 + splenocytes. These populations were intact following CsA treatment, but the numbers of mature CD4 + CD8 - and CD4 - CD8 + cells were substantially reduced. Similar mirror image differences were found for other populations examined. When considered together, these findings suggest that in combination Dox and CsA would affect nearly all subsets of lymphoid cells, providing one possible explanation of why increased leukopenia, toxicity and immunosuppression are found after their combined administration. Since leukemias, lymphomas and, to a more limited extent, certain solid tumors express these same phenotypic markers, similar analyses should be considered for monitoring and perhaps even predicting neoplastic cell sensitivity to treatment with such agents.
Reviews of Academic English Listening Tests for Non-Native Speakers

This article presents a review of 20 tests designed for assessing the academic English listening skill of second or foreign language learners. The available test information has been systematically condensed in purpose, listening construct, task characteristics, and validity evidence. It was found that most of the tests were developed for proficiency and placement purposes in academic contexts, with few of the tests serving for making workplace decisions. Also, global, local, and inferential skills constitute the construct in most listening comprehension tests. A practical approach for justifying the uses of these tests for different stakeholders is discussed. This review is a valuable resource for educators, administrators, test developers, and researchers looking for a comprehensive analysis of existing English tests that assess listening comprehension in second or foreign language learners.
Targeting Reactive Carbonyls for Identifying Natural Products and Their Biosynthetic Origins.

Natural products (NPs) serve important roles as drug candidates and as tools for chemical biology. However, traditional NP discovery, largely based on bioassay-guided approaches, is biased toward abundant compounds and rediscovery rates are high. Orthogonal methods to facilitate discovery of new NPs are thus needed, and herein we describe an isotope tag-based expansion of reactivity-based NP screening to address these shortcomings. Reactivity-based screening is a directed discovery approach in which a specific reactive handle on the NP is targeted by a chemoselective probe to enable its detection by mass spectrometry. In this study, we have developed an aminooxy-containing probe to guide the discovery of aldehyde- and ketone-containing NPs. To facilitate the detection of labeling events, the probe was dibrominated, imparting a unique isotopic signature to distinguish labeled metabolites from spectral noise. As a proof of concept, the probe was then utilized to screen a collection of bacterial extracts, le...
Identification of Antibody Against SNRPB, Small Nuclear Ribonucleoprotein-Associated Proteins B and B', as an Autoantibody Marker in Crohn's Disease using an Immunoproteomics Approach.

Background Current non-invasive biomarkers for Crohn's disease are limited in their utility. Progress in identifying individual autoantigens and autoantibodies in Crohn's disease has been challenging due to limitations of available immunoassays. Aims Our aim was to identify autoantibodies associated with Crohn's disease that may be useful in diagnosis and management using an innovative protein array technology, namely nucleic acid programmable protein arrays [NAPPA]. Methods Serum samples of 96 patients with established Crohn's disease and 96 healthy controls were included and evenly split into discovery and validation sets randomly. Autoantibodies of both IgG and IgA classes were profiled against ~1900 human proteins in the discovery set on NAPPA. Autoantibodies discovered to be Crohn's disease-specific were further validated in the independent validation set by enzyme-linked immunosorbent assay. Results Overall, reactivity of IgG autoantibodies was stronger than that of IgA autoantibodies; however, IgA autoantibodies showed greater differential reactivity between cases and controls. Four IgA autoantibodies against SNRPB, PRPH, PTTG1 and SNAI1 were newly identified with sensitivities above 15% at 95% specificity, among which anti-SNRPB-IgA had the highest sensitivity of 24.0%. Autoantibodies associated with specific disease subtypes were also found. Conclusions As one of the first studies to use immunoproteomics for the identification of autoantibodies in Crohn's disease, our results support the utility of NAPPA in implementing future expanded studies with better coverage of the human proteome and microbial proteomes relevant to Crohn's disease and identifying antibody markers that may have clinical impact in diagnosis and management.