cssi/SciSciGPT-SciSciNet huggingface dataset:
How low must you go? Effects of low-level noise on cochlear neural response.

Abstract Prolonged exposure to low-level noise has often been used scientifically as well as clinically to induce neuroplastic changes within the central auditory pathway in order to reduce central gain, suppress tinnitus and hyperacusis, and modulate different features of central auditory processing. A fundamental assumption underling these studies is that the noise exposure levels are so low that they have no effect on the neural output of the cochlea. Therefore, functional changes occurring in the central auditory pathway must be the results of central rather than peripheral changes. In an attempt to identify long-term noise exposures that did not cause peripheral changes, we measured the compound action potential (CAP) input/output functions from control rats and rats exposed for 6-weeks to 18–24 kHz noise presented at 25, 45, 55, 65, 75 or 85 dB SPL. Exposures >65 dB SPL significantly increased CAP thresholds; the critical intensity (Ct) below which no threshold shift occurred was estimated to be 55 dB SPL. Exposures >55 dB SPL significantly reduced suprathreshold CAP amplitudes; the critical intensity (Ca) below which no amplitude change was predicted to occur was a remarkably low level of 19 dB SPL. These results demonstrate that even extremely low-intensity long duration exposures can disrupt the neural output of the cochlea; these peripheral modifications are likely to contribute to the extensive compensatory changes observed at multiple levels of the central auditory pathway, neural network changes aimed at re-establishing homeostasis.
Improving process decisions in COTS-based development via risk-based prioritization: Research Sections

Good project planning requires the use of appropriate process models as well as effective decision support techniques. However, current software process models provide very little Commercial Off-the-Shelf (COTS)-specific insight and guidance on helping COTS-based application developers to make better decisions with respect to their particular project situations. This article presents a risk-based prioritization approach that is used in the context of a COTS Process Decision Framework. This method is particularly useful in supporting many dominant decisions during a COTS-based development (CBD) process, such as establishing COTS assessment criteria, scoping and sequencing development activities, prioritizing features to be implemented in incremental development, etc. In this way, the method not only provides a basis for optimal COTS selection but also helps focus limited development resources on more critical tasks that represent greater risks. The article also shows the evaluation results of applying this approach on the COTS Process Decision Framework through an experiment. Copyright © 2007 John Wiley & Sons, Ltd.
Voice quality differences between American English speakers and Korean learners of English

Various features have been examined as markers of foreign accent including segment-level errors, deviation in subsegmental acoustic properties, as well as prosodic patterns such as intonation, rhythm, and speaking rate. Features that characterize voice quality may also be useful but they have been investigated less extensively in the literature. The present study explores the utility of voice quality features by analyzing and comparing speech samples from American English speakers and Korean learners of English documented in the Wildcat Corpus of Native- and Foreign-Accented English. Measures of jitter, shimmer, and harmonics-to-noise ratio (HNR) were extracted from vowels and compared between the two speaker groups. Overall, Korean learners produced English vowels with less jitter and shimmer as well as higher HNRs than English speakers. The pattern was consistently found in both scripted and unscripted speech and was more salient among male speakers than female speakers. Furthermore, the same trend, although weaker, was also found when the Korean and English speakers produced vowels in their respective L1s while reading comparable scripts. However, the Korean speakers showed more shimmer while reading scripts in Korean (L1) than English (L2).
Presentation of Borderline Personality Disorder Symptoms in Adulthood: Development of Depression Mediates the Effect of Childhood and Adolescent Exposure to Violence.

ABSTRACT Past research has linked the development of borderline personality disorder to earlier exposure to violence. However, the causal link by which this relationship exists has not yet been fully identified. The present study sought to examine how exposure to violence predicted heterogeneity in the development of depressive systems and results in the arousal of borderline personality disorder symptoms in adulthood. The Pathways to Desistance data were used in the analyses. This data set consisted of the responses of 1354 juvenile offenders followed across 7 years. Group-based trajectory modeling was used to identify latent trajectories of depressive symptoms. Ordinary least squares regression was used to model covariate effects on borderline personality disorder symptoms in adulthood. Results indicated that a three-group depression trajectory model best fit the data. Direct victimization early in life was associated with increased borderline personality disorder symptoms in adulthood. When trajectory group assignment was accounted for in the model, the relationship between direct victimization and borderline personality disorder symptoms was attenuated by around 30%. Implications are discussed.
Negotiating relationships with powerfulness: using femme theory to resist masculinist pressures on feminist femininities

Finding power within femininity, typically through masculinised dimensions of femininity, has long been a mechanism through which to recuperate feminised identities, experiences, and aesthetics wit...
Underreported Risk of Lisinopril-Induced Angioedema in a Veteran Population.

Background:Lisinopril-induced angioedema (LIA) is a rare but serious adverse drug event (ADE) with a published incidence of 0.1% to 0.7%. It is well known that ADEs are widely underreported; howeve...
Three-dimensional bladder ultrasound to measure daily urinary bladder volume in hospitalized dogs

Background Urinary bladder volume (UBV) and urine residual volume (URV) provide important information for hospitalized dogs and might allow recognition of urine retention. Objective Using 3-dimensional (3D) ultrasound to monitor daily URV is a safe and effective way to recognize urinary retention. Animals Twenty-five client-owned hospitalized dogs. Methods Prospective, observational study. UBV and URV were measured using 3D ultrasound daily at approximately the same time. UBV was measured, the dog was taken for a 5-minute controlled leash walk, then URV was estimated. Concurrent use of opioids, anesthetics, and fluids administered IV were recorded. Results Daily URVs were >0.4 mL/kg in 22 of 25 dogs on at least 1 day of hospitalization. Seventeen of 25 dogs had an abnormal URV at the time of discharge. Of 18 dogs that were anesthetized while hospitalized, 16 had a URV >0.4 mL/kg with a mean of 4.34 mL/kg (range, 0.5-13.4 mL/kg). No statistical difference in degree of URV was found based on the use of anesthesia, administration of fluids IV, or opioids. Weight was significantly associated with URV; dogs 10 kg (P = .001). Conclusions and clinical importance Use of a 3D ultrasound device to measure daily UBV and URV in hospitalized dogs provides a safe estimate of bladder volume in real-time. Monitoring daily URV might help in early identification of patients that are retaining urine, thereby preventing potential adverse effects of urethral catheterization or prolonged urinary retention.
Term Newborn with Corneal Opacity.

A term male newborn with respiratory distress at birth was noted to have central corneal opacity of the right eye. ### Prenatal and Birth Histories ### Presentation (Day 1) In the NICU, the neonate continued to require CPAP. Initial chest radiography showed diffuse pulmonary opacities concerning for surfactant deficiency. When the neonate remained on CPAP at 6 hours of age, the primary team evaluated him for sepsis and started antibiotics. On examination at the time of admission, a right corneal opacity (Fig 1) was noted with a normal left eye (Fig 2). Figure 1. Right eye. Central corneal opacity with surrounding 360-degree vascularization. Figure 2. Left eye. Clear …
Five Conservative Principles to Apply Against Weaponized Antitrust

Some legislators, especially on the far Left, have set their sights on making radical changes to federal antitrust law. They seek to weaponize antitrust law, such as by making it much easier for the federal government to wield antitrust power to reshape industries and the entire economy. This is a serious threat that could give the far Left its most powerful tool to radically change the American economic system and even to achieve non-economic ideological objectives. Conservatives are right to be concerned with Big Tech and its chilling of speech, but weaponized antitrust will not solve the speech problems. Conservatives must stick to their core principles. This includes rejecting central planning, defending the consumer welfare standard, and fighting efforts to punish economic success. Conservatives should also aggressively push an agenda that reduces government intervention that hinders competition in the first place, and fight cronyism and corporate welfare at every turn.
Low Energy Carbon Capture via Electrochemically Induced pH Swing with Electrochemical Rebalancing

We demonstrate a carbon capture system based on pH swing cycles driven through proton-coupled electron transfer of sodium (3,3’-(phenazine-2,3-diylbis(oxy))bis(propane-1-sulfonate)) (DSPZ) molecules. Electrochemical reduction of DSPZ causes an increase of hydroxide concentration, which absorbs CO2; subsequent electrochemical oxidation of the reduced DSPZ consumes the hydroxide, causing CO2 outgassing. The measured electrical work of separating CO2 from a binary mixture with N2, at CO2 inlet partial pressures ranging from 0.1 to 0.5 bar, and releasing to a pure CO2 exit stream at 1.0 bar, was measured for electrical current densities of 20 to 150 mA/ cm2. The work for separating CO2 from a 0.1 bar inlet and concentrating into 1 bar exit is 61.3 kJ/molCO2 at a current density of 20 mA/cm2 and extrapolates to 57.1 kJ/molCO2 in the low-current-density limit. At this limit, the cycle work for capture from 0.4 mbar extrapolates to 108-212 kJ/ molCO2 depending on the initial composition of the electrolyte. We also introduce an electrochemical rebalancing method that extends cell lifetime by recovering the initial electrolyte composition after it is perturbed by side reactions. We discuss the implications of these results for future low-energy electrochemical carbon capture devices.
Association Pattern Mining

The classical problem of association pattern mining is defined in the context of supermarket data containing sets of items bought by customers, which are referred to as transactions. The goal is to determine associations between groups of items bought by customers, which can intuitively be viewed as k-way correlations between items. The most popular model for association pattern mining uses the frequencies of sets of items as the quantification of the level of association.
Reasoning about Unknown, Counterfactual, and Nondeterministic Actions in First-Order Logic

This paper extends previous work on axiomatizing actions and their effects in standard first-order logic. We show how to accommodate complex types of reasoning about action, including distinguishing between actual and hypothetical actions, drawing conclusions based on counterfactual assumptions, and reasoning about actions whose effects are nondeterministic. We also discuss in some detail the connections between the method proposed here and other methods based on nonmonotonic logics.
Reading for the End: Prescriptive Writing and the Practice of Genre

This article considers how genre categories marshal forms of social consensus through close examination of a late-fifteenth/early-sixteenth-century compilation, San Marino, Huntington Library, HM 144. Best known for its versions of Chaucer’s Tale of Melibee and Monk’s Tale, HM 144 also offers insight into the ways that successive generations of authors, scribes, and readers make and remake literary categories according to their intersecting — and at times competing — interests. I argue that much contemporary debate in genre theory implicitly concerns not simply the taxonomic features that divide one category from another but the bases upon which readers come into agreement about texts. By making explicit their own “terms of agreement,” medieval prescriptive texts, in particular, make visible the mechanisms of generic practice — the ways in which writing seeks to mold readers and the ways that readers, in turn, seek to mold miscellanies, compilations, and other literary objects according to their spiritual and social aspirations. Examining HM 144’s array of didactic material, the essay shows how prescriptive writing both elicits consensus from its readers and depends equally upon the failure of its own task.
Justice, Instruction, and the Good: The Case For Public Education in Aristotle and Plato's Laws

This paper develops an interpretation and analysis of the arguments for public education which open Book VIII of Aristotle's Politics, drawing on both the wider Aristotelian corpus and on examination of continuities with Plato's Laws.
A non-skiving tape head with sub-ambient air pressure cavities

A small head-medium spacing is crucial for achieving high linear densities in magnetic tape recording. Traditional contoured (cylindrical) tape heads have been superseded by flat-profile tape heads with sharp skiving edges to remove the natural air bearing that forms between tape and a contoured head, to reduce the head-tape spacing [1]. This means that tape is in contact with the head surface and that the spacing is determined predominantly by the tape surface roughness. To further reduce the head-medium spacing, the tape surface roughness needs to be reduced, which however results in increased head-medium friction. High friction is problematic for tape durability, for reliable operation of the data channel, and for accurate track-follow control. Although friction is lower for smaller tape wrap angles, reducing the wrap angle in a skiving configuration is not desirable because it results in an unacceptable increase in head-medium spacing. Furthermore, recent research has shown that a substantial amount of the friction originates at the skiving edges of the head. In this work, we present a new tape head design which allows dispensing with the skiving edges to reduce friction, while simultaneously maintaining tape-head contact above the read/write transducers.
Miniaturized GPS Tags Identify Non-breeding Territories of a Small Breeding Migratory Songbird.

Miniaturized GPS Tags Identify Non-breeding Territories of a Small Breeding Migratory Songbird
Accurate calculation of eye diagrams and error rates in long-haul transmission systems

We found the distribution of phase and timing jitter in a DMS system to be Gaussian-distributed. After their removal, the residual noise Fourier components obey a multivariate-Gaussian distribution, allowing us to accurately calculate eye diagrams and error rates.
The Mutated Androgen Receptor and Its Implications for the Treatment of Metastatic Carcinoma of the Prostate

Androgen deprivation is the most effective therapy for patients with advanced prostatic carcinoma. The lack of androgen stimulation on these cells causes them to become apoptotic. Although therapeutic efficacy of initial androgen deprivation in prostate cancer is high, the emergence of androgen-independent cancer is inevitable. Withdrawal of the antiandrogen flutamide elicits surprising activity in these cancers. In numerous studies the response rates cell line harbors a mutation in codon 877 of the androgen receptor. The mutant receptor loses androgen specificity and is activated by various steroids as well as flutamide. Identical and similar mutations have now been isolated from human prostate cancer tissue. The discovery of the mutated androgen receptor sheds light on the emergence of androgen-independent cancer and should facilitate the development of more efficacious therapies.
Distribution of hypertrophied locus coeruleus projection to adult cerebellum after neonatal 6-hydroxydopamine.

Abstract Following treatment as neonates with a high subcutaneous dose of 6-hydroxy-dopamine (6-OHDA), the projections of the locus coeruleus were mapped in the brains of adult rats. This was done using the technique of unilateral lesions in the nucleus followed by simultaneous determinations of norepinephrine (NE) levels, dopamine-β-hydroxylase (DBH) activity and synaptosomal [ 3 H]NE uptake in various terminal areas. In particular the cerebellum was subdivided into 3 areas in order to assess any changes from normal in the distribution of the hypertrophied noradrenegic projections here. In vehicle-control rats the lesions resulted in an 80–85% loss of NE in the parietal cortex ipsilateral to the lesion and a 15–20% loss contralaterally. In the control cerebellum the locus coeruleus projection, based upon changes in all 3 markers, is distributed 23 ipsilaterally and 13 contralaterally with the same pattern present in all 3 subregions. The neonatal 6-OHDA treatment resulted in virtually complete loss of noradrenergic terminals in the cerebral cortex. Following neonatal 6-OHDA treatment cerebellar levels of NE, DBH and [ 3 H]NE uptake increased by between 20–60%, with the smallest increases occurring in [ 3 H]NE uptake. In these rats the locus coeruleus accounted for at least 75–80% of the cerebellar noradrenergi parameters. Unlike control rats however, the lesions in these rats produced only ipsilateral decreases in NE and DBH. On the other hand changes in [ 3 H]NE uptake indicated a normal 23 ipsilateral, 13 contralateral pattern. It is suggested that two separable events occur in the noradrenergic projection to the cerebellum. The first is the regeneration of an increased number of nerve terminals, or sprouting, and the second is a build-up of synaptic vesicles, or collateral accumulation. The sprouting, judging from the [ 3 H]NE uptake data, occurs with apparently normal distribution, but the accumulation of NE and DBH is confined predominantly to the ipsilaterally projecting axon terminals. This may be the consequence of collateral accumulation resulting from the degeneration of the largely ipsilateral coeruleocortical projection.
A Hierarchical Anonymous Routing Scheme for Mobile Ad-Hoc Networks

Privacy and anonymity are critical security issues to many large-scale MANET applications such as military communication networks. These applications are more likely deploying the networks heterogeneously and hierarchically due to administrative needs or routing efficiency. When the size of the network scales up, the routing overhead incurred by existing flat anonymous routing protocols increases fast as the required number of public key operations increases. This results in deteriorated routing and data communication performance. In this paper, we introduce a novel hierarchical anonymous on-demand routing protocol tackling this limitation. In addition to guaranteeing routing and data delivering security, the scheme provides two levels of anonymity: intra-group and inter-group. By exploiting the hierarchical network structure, it effectively controls computational overhead while preserving anonymity, hence accommodates to larger-scale MANETs.
Identifying the Isomers of Octahedral Complexes with 119Sn and 207Pb NMR Spectroscopy: A Computational Exercise

In this computational exercise, the 119Sn and 207Pb NMR spectra (data provided to the students) of the octahedral complexes [SnClnF6−n]2− and [PbClnF6−n]2−, respectively, are examined. The pairwise-additivity model is applied to the NMR spectra of the complexes [MClnF6−n]2− (n = 0, 1, 5, 6) to obtain the Cl−Cl, Cl−F, and F−F pairwise-additivity parameters for each set of complexes; these parameters then are employed to predict the appropriate chemical shift for each pair of isomers of the complexes [MClnF6−n]2− (n = 2, 3, 4). By comparing the chemical shifts predicted by the pairwise-additivity model with the experimental values, the students are able to identify the one isomer of each pair that either is the only one that exists in solution or is the more abundant isomer. Molecular modeling (semiempirical PM3) is employed to see which geometric isomer of each pair is more stable. For both series of complexes, the only isomer in solution or the more abundant isomer proves to be the more stable one.
The influence of site conditions on the spatial incoherence of ground motions

Abstract We have found evidence for large differences in the spatial incoherence of ground motions under different site conditions. At sites located on flat-lying alluvial sequences, such as the Imperial Valley, California and Lotung, Taiwan, the spatial incoherence increases smoothly as a function of station separation and wave frequency. This uniform behavior is consistent with wave scattering in an otherwise laterally homogeneous seismic velocity structure. In contrast, on sites located on folded sedimentary rocks, such as the Coaling anticline in California, the spatial incoherence does not show a strong dependence on station separation and wave frequency, and is higher at close station spacing and low frequency than in flat-lying alluvial sites. This chaotic behavior is consistent with wave propagation in a medium having strong lateral heterogeneities in seismic velocity. We have modeled this behavior using synthetic seismograms calculated for a basin structure in which overlying sedimentary material is separated from basement rock by an undulating interface. Even simple undulations in a smooth interface produce caustics, giving rise to ground motions whose spatial incoherence characteristics resemble those of the Coalinga data. We conclude that the spatial incoherence measured on flat-lying sedimentary sites such as the Imperial Valley and Lotung may not provide a good description of the spatial incoherence at sites where there is significant lateral heterogeneity. These include folded sedimentary rocks exposed at the surface, basins generated by the folding of sedimentary rocks, and alluviated river valleys. At present, we do not have measurements of spatial incoherence at enough sites to know whether the spatial incoherence characteristics of ground motions can be readily correlated with simplified categories of site conditions. In order to obtain reliable estimates of the spatial incoherence of ground motion at a particular site, it may be necessary to use accelerograms of a small earthquake or explosion recorded on a small array at the site.
OPERANT TREATMENT OF DEPRESSION: A CASE STUDY

A case study of chronic depression is presented. It is argued that in some cases of depression, the appropriate treatment may focus on the social contingencies (such as attention and comfort) which maintain depressive behavior, rather than on the events which elicit depression. Depression may thus be considered an operant and manipulated much as any other operant. The present treatment consisted of self-administered aversive consequences for onset of depression, and self-administered positive consequences for the termination of depression. Results clearly support the notion that the subjective experience of depression may be successfully modified by operant self-control techniques.
Sequential and synergistic modification of human RPA stimulates chromosomal DNA repair.

Abstract The activity of human replication protein A (RPA) in DNA replication and repair is regulated by phosphorylation of the middle RPA2 subunit. It has previously been shown that up to nine different N-terminal residues are modified in vivo and in response to genotoxic stress. Using a novel antibody against phospho-Ser29, a moiety formed by cyclin-Cdk, we observed that RPA2 was phosphorylated during mitosis in nonstressed cells. Robust phosphorylation of Ser29 was also seen in interphase cells following treatment with the DNA-damaging agent camptothecin, a rare example of stress stimulating the modification of a repair factor by cyclin-Cdk. RPA2 phosphorylation is regulated both in cis and trans. Cis-phosphorylation follows a preferred pathway. (That is, the initial modification of Ser33 by ATR stimulates subsequent phosphorylation of Cdk sites Ser23 and Ser29). These events then facilitate modification of Thr21 and extreme N-terminal sites Ser4 and Ser8, probably by DNA-PK. Our data also indicate that the phosphorylation of one RPA molecule can influence the phosphorylation of other RPA molecules in trans. Cells in which endogenous RPA2 was “replaced” with a double S23A/S29A-RPA2 mutant were seen to have an abnormal cell cycle distribution both in normal and in stressed cells. Such cells also showed aberrant DNA damage-dependent RPA foci and had persistent staining of γH2AX following DNA damage. Our data indicate that RPA phosphorylation facilitates chromosomal DNA repair. We postulate that the RPA phosphorylation pattern provides a means to regulate the DNA repair pathway utilized.
A semiempirical estimate of the micrometeorite flux at the earth's surface and its implications

Fe-Ni unmelted and unablated micrometeorites number at earth surface calculated, using space density of interplanetary particles and micrometeoritic theory
Citrobacter meningitis and brain abscess in infancy: Epidemiology, pathogenesis, and treatment

Le Citrobacter (notamment diversus) est une cause de frequence croissante de meningite epidemique ou sporadique du nouveau-ne ou du jeune nourrisson, compliquee dans 77% des cas d'abces du cerveau. L'experimentation sur le rat pourrait aider a expliquer cette frequence et avoir des implications pour l'epidemiologie, la prevention et le traitement de ces meningites
A Novel DNA-binding Protein, HS2NF5, Interacts with a Functionally Important Sequence of the Human β-Globin Locus Control Region

We have identified a previously unreported DNA-binding protein, HS2NF5, which interacts with a conserved sequence within hypersensitive site II (HS2) of the human β-globin locus control region. A minimal DNA recognition sequence of TGTTCTCA was defined. The binding site for HS2NF5 overlaps an E box, which is a preferred recognition site in vitro for the erythroid-specific transcription factor TAL1 (SCL). No evidence for TAL1 (SCL) binding was found using nuclear extracts from K562 and MEL erythroleukemia cells. Mutations that prevent HS2NF5 binding reduce the enhancer activity of HS2 by 40 and 38% in transient and stable transfection assays, respectively. Analytical gel filtration and velocity centrifugation studies revealed a Stokes' radius of 23.0 A and an s20,w of 3.45 for HS2NF5. Based on these parameters, a native molecular mass of 34,679 Da was calculated. An ultraviolet light cross-linking assay was used to cross-link HS2NF5 to a minimal oligonucleotide. The cross-linking results are consistent with a protein of 33,396-38,309 Da. We propose that HS2NF5 is a novel DNA-binding protein that modulates the transcriptional activation property of the β-globin locus control region.
Frozen Wild Blueberry-Tofu-Soymilk Desserts

Both wild (lowbush) blueberries (Vaccinium angustifolium Ait.) and soybeans (Glycine max L.) possess a variety of antioxidants, and both foods appear to have multiple health benefits. Our objectives were to identify whether wild blueberry juice concentrate was more acceptable than puree in frozen desserts with a soy milk-tofu base; to determine whether fat-free products were as acceptable as those with 10% added fat; and to compare several levels of blueberry juice concentrate. Four frozen dessert formulations were prepared in duplicate from soy milk, silken tofu, sucrose, stabilizer, BJC or puree, soybean oil or polydextrose, sweetened dried blueberries, salt, and lemon juice. Samples were assayed for total anthocyanins, antioxidant activity using the DPPH method, color, overrun, and solids. Fifty-five persons evaluated the samples using a 9-point hedonic scale for color, flavor, texture, and overall acceptability. Samples containing blueberry juice concentrate were darker and less blue. Anthocyanin levels were highest in the puree sample and the fat-free product with 7.8% blueberry juice concentrate. However, antioxidant activity was highest (28 Trolox equivalents per gram) in the samples made with soybean oil and 7.4% blueberry juice concentrate. The puree formulation received higher hedonic scores than did the low-fat blueberry juice concentrate formulations. The puree formulation received overall acceptability scores of like very much or like extremely by 45% of the consumers. These findings may aid processors in defining potential formulations that combine 2 healthful food ingredients.
Targeting Cytotoxic Conjugates of Somatostatin, Luteinizing Hormone- Releasing Hormone and Bombesin to Cancers Expressing Their Receptors: A “Smarter” Chemotherapy

Chemotherapy is one of the main modalities in the therapy of cancer. However, an improvement in the efficacy and a reduction in the toxicity of chemotherapeutic agents remains a great challenge to oncologists. A specific delivery of cytotoxic drugs to cancerous cells may help improving both aspects. Peptide hormones, for which receptors have been found in various human cancers, can serve as carriers for a local delivery of cytotoxic agents or radiopharmaceuticals to the tumors, as demonstrated by the successful clinical use of radiolabeled somatostatin analog Octreoscan for the detection and treatment of some somatostatin receptor-positive tumors. Thus, in recent years we developed a series of cytotoxic peptide hormone conjugates based on derivatives of hypothalamic hormones such as somatostatin and luteinizing hormone-releasing hormone (LHRH), and the brain-gut hormone bombesin. To create targeted conjugates with high cytotoxic activity, a derivative of doxorubicin (DOX), 2-pyrrolino-DOX (AN-201), which is 500-1, 000 times more active than its parent compound, was developed. This agent was coupled to somatostatin octapeptide RC-121 to form cytotoxic conjugate AN-238, and to [D-Lys 6 ]LHRH carrier to produce analog AN-207. Cytotoxic bombesin hybrid AN-215 also contains AN-201. DOX was likewise linked to [D-Lys 6 ]LHRH to form AN-152. A comprehensive testing of these cytotoxic conjugates in experimental models of various human and rodent cancers led to their selection as candidates for clinical trials.
Depression and Medication Adherence in Outpatients With Coronary Heart Disease: Findings From the Heart and Soul Study

Background Depression leads to adverse outcomes in patients with coronary heart disease (CHD). Medication nonadherence is a potential mechanism for the increased risk of CHD events associated with depression, but it is not known whether depression is associated with medication nonadherence in outpatients with stable CHD. Methods We examined the association between current major depression (assessed using the Diagnostic Interview Schedule) and self-reported medication adherence in a cross-sectional study of 940 outpatients with stable CHD. Results A total of 204 participants (22%) had major depression. Twenty-eight (14%) of 204 depressed participants reported not taking their medications as prescribed compared with 40 (5%) of 736 nondepressed participants (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.7-4.7; P P P = .01). The relationship between depression and nonadherence persisted after adjustment for potential confounding variables, including age, ethnicity, education, social support, and measures of cardiac disease severity (OR, 2.2; 95% CI, 1.2-3.9; P = .009 for not taking medications as prescribed). Conclusions Depression is associated with medication nonadherence in outpatients with CHD. Medication nonadherence may contribute to adverse cardiovascular outcomes in depressed patients.
Long-term cognitive impairments and pathological alterations in a mouse model of repetitive mild traumatic brain injury

Mild traumatic brain injury (mTBI, also referred to as concussion) accounts for the majority of all TBIs. The consequences of repetitive mTBI have become of particular concern for individuals engaged in certain sports or in military operations. Many mTBI patients suffer long-lasting neurobehavioral impairments. In order to expedite pre-clinical research and therapy development, there is a need for animal models that reflect the long-term cognitive and pathological features seen in patients. In the present study, we developed and characterized a mouse model of repetitive mTBI, induced onto the closed head over the left frontal hemisphere with an electromagnetic stereotaxic impact device. Using GFAP-luciferase bioluminescence reporter mice that provide a readout of astrocyte activation, we observed an increase in bioluminescence relative to the force delivered by the impactor after single impact and cumulative effects of repetitive mTBI. Using the injury parameters established in the reporter mice, we induced a repetitive mTBI in wild-type C57BL/6J mice and characterized the long-term outcome. Animals received repetitive mTBI showed a significant impairment in spatial learning and memory when tested at 2 and 6 months after injury. A robust astrogliosis and increased p-Tau immunoreactivity was observed upon post-mortem pathological examinations. These findings are consistent with the deficits and pathology associated with mTBI in humans and support the use of this model to evaluate potential therapeutic approaches.
SINGLE: a program to control single‐crystal diffractometers

SINGLE, a program that runs under Windows operating systems, can be used to control a variety of four-circle Eulerian-cradle single-crystal diffractometers including Huber instruments equipped with Huber motor controllers, the Stoe Stadi-4 and the Siemens P4. The software can be configured, via variables set by the user, to operate any of these diffractometers with a variety of environmental devices including furnaces and diamond-anvil pressure cells. It is specifically designed to determine unit-cell parameters to a precision of 1 part in 30 000.
Analytic and heuristic processing influences on adolescent reasoning and decision-making

The normative/descriptive gap is the discrepancy between actual reasoning and traditional standards for reasoning. The relationship between age and the normative/descriptive gap was examined by presenting adolescents with a battery of reasoning and decision-making tasks. Middle adolescents (N = 76) performed closer to normative ideals than early adolescents (N = 66), although the normative/descriptive gap was large for both groups. Correlational analyses revealed that (1) normative responses correlated positively with each other, (2) nonnormative responses were positively interrelated, and (3) normative and nonnormative responses were largely independent. Factor analyses suggested that performance was based on two processing systems. The "analytic" system operates on "decontextualized" task representations and underlies conscious, computational reasoning. The "heuristic" system operates on "contextualized," content-laden representations and produces "cognitively cheap" responses that sometimes conflict with traditional norms. Analytic processing was more clearly linked to age and to intelligence than heuristic processing. Implications for cognitive development, the competence/performance issue, and rationality are discussed.
Moxonidine, an antihypertensive agent, is permissive to α1-adrenergic receptor pathway in the rat-tail artery

To investigate whether alpha1-adrenergic receptors were involved in the contractile response of tail arteries to moxonidine, isolated ring segments of tail arteries from male adult Sprague-Dawley rats were studied. Moxonidine (EC50 = 1.3 microM) and the alpha1-agonist phenylephrine (EC50 = 2.5 microM) increased tension development in the rat-tail artery similarly. The response to moxonidine (1 microM) could be blocked by both alpha1-adrenoceptor blockers prazosin (IC50 = 1 nM), and urapidil (IC50 = 14 nM), and also by alpha2-adrenoceptor blockers, yohimbine (IC50 = 49 nM) and efaroxan (IC50 = 49 nM). Combination drug treatment (urapidil and yohimbine, or yohimbine and prazosin) was more effective in blocking the contractile response to moxonidine, than treatment with prazosin or urapidil alone. Comparison of pA2 values for prazosin in the presence of moxonidine (9.35) or phenylephrine (10.2) confirm that alpha1-adrenergic receptors are involved in the contractile response of rat-tail artery to moxonidine.
A Theory of the Discovery and Predication of Relational Concepts.

Relational thinking plays a central role in human cognition. However, it is not known how children and adults acquire relational concepts and come to represent them in a form that is useful for the purposes of relational thinking (i.e., as structures that can be dynamically bound to arguments). The authors present a theory of how a psychologically and neurally plausible cognitive architecture can discover relational concepts from examples and represent them as explicit structures (predicates) that can take arguments (i.e., predicate them). The theory is instantiated as a computer program called DORA (Discovery Of Relations by Analogy). DORA is used to simulate the discovery of novel properties and relations, as well as a body of empirical phenomena from the domain of relational learning and the development of relational representations in children and adults.
Inference of interactions in cyanobacterial-heterotrophic co-cultures via transcriptome sequencing.

We used deep sequencing technology to identify transcriptional adaptation of the euryhaline unicellular cyanobacterium Synechococcus sp. PCC 7002 and the marine facultative aerobe Shewanella putrefaciens W3-18-1 to growth in a co-culture and infer the effect of carbon flux distributions on photoautotroph–heterotroph interactions. The overall transcriptome response of both organisms to co-cultivation was shaped by their respective physiologies and growth constraints. Carbon limitation resulted in the expansion of metabolic capacities, which was manifested through the transcriptional upregulation of transport and catabolic pathways. Although growth coupling occurred via lactate oxidation or secretion of photosynthetically fixed carbon, there was evidence of specific metabolic interactions between the two organisms. These hypothesized interactions were inferred from the excretion of specific amino acids (for example, alanine and methionine) by the cyanobacterium, which correlated with the downregulation of the corresponding biosynthetic machinery in Shewanella W3-18-1. In addition, the broad and consistent decrease of mRNA levels for many Fe-regulated Synechococcus 7002 genes during co-cultivation may indicate increased Fe availability as well as more facile and energy-efficient mechanisms for Fe acquisition by the cyanobacterium. Furthermore, evidence pointed at potentially novel interactions between oxygenic photoautotrophs and heterotrophs related to the oxidative stress response as transcriptional patterns suggested that Synechococcus 7002 rather than Shewanella W3-18-1 provided scavenging functions for reactive oxygen species under co-culture conditions. This study provides an initial insight into the complexity of photoautotrophic–heterotrophic interactions and brings new perspectives of their role in the robustness and stability of the association.
The Role of TRP Channels In Mechanosensitive Somatosensory Neurons

The somatosensory system underlies our ability to detect touch and pain. To understand the molecular and cellular processes governing somatosensation, it is necessary to identify receptors that detect physical stimuli, such as temperature and touch, and determine how they transduce environmental signals into action potentials. TRP channels that mediate sensitivity to heat and cold have been identified from somatosensory neurons. But the role of TRP channels in mammalian mechanosensitive sensory neurons remains controversial. We used a variety of in vitro assays to characterize responses of distinct subsets of mechanosensitive sensory neurons. Using calcium imaging in combination with radial stretch, osmotic stimuli or natural products that target mechanosensitive neurons, we assessed mechanosensitivity of nociceptors and low-threshold mechanoreceptors. The role of various TRP channels in these responses will be discussed.
Accuracy and test characteristics of ancillary tests of cerebrospinal fluid for predicting acute bacterial meningitis in children with low white blood cell counts in cerebrospinal fluid.

Objectives To determine whether ancillary tests of cerebrospinal fluid (CSF), specifically, the total protein concentration, glucose concentration, and percent neutrophils, provide information for diagnosing acute bacterial meningitis among children with low white blood cell (WBC) count in CSF. Methods The authors retrospectively reviewed CSF from children aged 1 month to 18 years undergoing lumbar puncture at Children's Hospital in Boston from 1993 to 1999. Data were supplemented with CSF test results obtained from children with 0-30 WBCs/mm(3) in CSF diagnosed with acute bacterial meningitis at the same institution from 1984 to 1992. For each test, the incremental value of ancillary tests was estimated by calculating indices of performance such as the area under receiver operator characteristic curves (AUC) and interval likelihood ratios that are relatively insensitive to disease prevalence. Results Among children with 0-30 WBCs/mm(3) in CSF who met study criteria, acute bacterial meningitis was identified in ten of 7,701 (0.1%) for the period from 1993 to 1999 and supplemented with 11 additional cases for the period from 1984 to 1992. AUC values for ancillary tests were 0.61 for total protein concentration, 0.69 for glucose concentration, and 0.90 for percent neutrophils. Interval likelihood ratios were unremarkable for mildly abnormal test results. In contrast, interval likelihood ratios for markedly abnormal test results were higher: 22 for total protein concentration >120 mg/dL, 57 for neutrophils >75%, 15 for glucose concentration 120 mg/dL. Conclusions When markedly abnormal, results of CSF total protein concentration, glucose concentration, and percent neutrophils have value for diagnosing acute bacterial meningitis, even among children with a low WBC count in CSF.
Shear effects on enzymes

Abstract Shear inactivation of enzymes has been found to be associated with flow, pumping and mixing. From data taken in a viscometer, shear inactivation in flow could be calculated. Among the materials experiencing this effect are catalase, rennet, carboxypeptidase A, interferon, heparin, fibrinogen, and phage lysozyme. Turbulent flow has greater losses than would be expected from streamline flow under the same dynamic and geometric conditions. Shear conditions also cause changes in the kinetics of reactions by reducing the reaction rate. It is thought that the shear field causes molecular distortions that result in breaking molecular bonds (inactivation) or stretching without breaking within an elastic limit that permits recovery when the shear field is removed (causing reduction of reaction rate.) There are conflicting data from different laboratories in that shear effects are not observed to the same extent. It may be that the presence of oxygen and metal ions and their reactions with disulphide bonds have an influence.
Correction of temporal misregistration artifacts in jet flow by conventional phase‐contrast MRI

Purpose To show that accuracy of jet flow representation by magnetic resonance (MR) phase-contrast (PC) velocity-encoded (VE) cine imaging is dominated by error terms resulting from the temporal distribution of data, and to present a generally applicable data interpolation-based approach to correct for this phenomenon. Materials and Methods Phase-contrast data were acquired in a stenotic orifice flow phantom using a physiologic pulsatile flow waveform. A temporally registered scan, acquired without data segmentation or interleaving was obtained (17 minutes) and taken as the reference (REF). Conventional PC data sets were acquired using segmentation and data interleaving. An enhanced temporal registration (ETR) algorithm was applied to the acquired data to temporally interpolate component sets and output data at matching time points, thereby reducing temporal dispersion. Results Compared to the REF data, conventionally processed PC data consistently overestimated peak velocities in laminar jet flow regions (127% ± 28%) and exhibited relatively weak correlations (r = 0.67 ± 0.23). The ETR-processed data better represented peak velocities (101% ± 13%, P < 0.001) and correlated more closely with the REF data (r = 0.94 ± 0.05, P < 0.001). Conclusion The temporal distribution of PC data impacts the accuracy of velocity representation in pulsatile jet flow. A temporal registration postprocessing algorithm can minimize loss of accuracy. J. Magn. Reson. Imaging 2007;25:1256–1262. © 2007 Wiley-Liss, Inc.
Growth hormone-binding protein in human lymph

The high affinity GH-binding protein (GHBP) is a soluble circulating ectodomain of the GH receptor (GHR). In humans, it is thought to be released from the plasma membrane-bound GHR by proteolysis at or near the transmembrane domain. GHBP modulates GH action by 1) intravascular complex formation, and 2) competing with the GHR for ligand in tissues (interstitial complex formation). Little is known about the tissue source(s) of GHBP, the local regulation of GHBP generation, or its concentration in the interstitium. To begin addressing these questions, we studied GHBP levels in peripheral lymph, whose composition approximates that of interstitial fluid. Lymph was collected in 13 healthy adult men from cannulated lymphatic vessels in the calf. Venous and arterial blood samples were collected from the femoral vein and radial artery contemporaneously with lymph collection. Potential GHBP production by endothelial or blood cells was assessed by examining conditioned medium from in vitro cell cultures. GHBP activi...
Eigenfunctions of the small oscillations about the double-sine-Gordon kink

We investigate the spectrum of the small oscillations about the 4..pi.. double-sine-Gordon (DSG) kink. Our method makes use of the supersymmetry which naturally arises in any one-dimensional Schroedinger equation for which the ground-state wave function is exactly known. We provide for what we believe to be the first time analytical expressions for the unnormalized eigenfunctions of the internal and continuum modes. Our result improves previous numerical investigations. Its relevance for the dynamics and thermodynamics of kinks is discussed.