cssi/SciSciGPT-SciSciNet huggingface dataset:
Elliptic Localization: Performance Study and Optimum Receiver Placement

Range based localization often relies on TOA that creates a circular contour or TDOA that yields hyperbolic surface to determine the position of an emitting object. Another approach that has gained attention recently is elliptic localization. Elliptic localization uses an active transmitter to send out a signal and several receivers to acquire the reflected or relayed signal from an object to obtain its location. This paper performs a fundamental investigation on the performance of elliptic localization, for both the synchronous and asynchronous cases between the transmitter and the receivers. Their performance is also characterized with respect to the hyperbolic localization. The study is based on the Cramer-Rao lower bound (CRLB) for the object location under Gaussian measurement noise as well as Gaussian errors in the transmitter and receiver positions. When the receiver positions are controllable, we derive the optimum receiver placement for elliptic positioning to improve the localization accuracy. We conclude the study with simulation results to demonstrate the elliptic localization performance using the CRLBs and the Maximum Likelihood estimators.
Gender difference in susceptibility to picrotoxin-induced seizures is seizure- and stimulation-dependent.

Abstract In a dose-response study, the pattern of sex-associated susceptibility to picrotoxin-induced myoclonic, focal, akinetic, and generalized tonic-clonic (GTC) seizures was investigated in rats to determine whether the reported heightened susceptibility of females to seizures was a general phenomenon in rats or whether it was limited to specific types of seizures. The latency to and incidence of specifically categorized seizures were used as indices of susceptibility after male and female rats had been injected with picrotoxin (3–10 mg/kg). The results revealed that at low doses of picrotoxin (4 mg/kg), female rats had significantly shorter latencies to myoclonic seizures and significantly shorter latencies and higher incidences of GTC seizures. At higher doses of picrotoxin (8 and 10 mg/kg), the pattern of relative susceptibility of males and females to myoclonic seizures was reversed, with males having shorter latencies than females. There were no significant sex differences in the incidence of or latency to focal or akinetic seizures at any of the doses tested. These findings indicate 1) that there are significant sex differences in seizure susceptibility only for specific seizure categories in rats; and 2) that for seizure categories where significant sex differences were identified, the observed pattern of relative susceptibility of males and females depends on the dose of picrotoxin tested. Thus, patterns of sex-associated seizure susceptibility favoring either males or females are both seizure- and stimulation-limited and do not reflect general dispositions to seizures in either sex. The possibility that the seizure- and stimulation-dependent features of sex-associated seizure susceptibility was due to sex differences in selected mechanisms underlying picrotoxin activity and in selected anatomical pathways mediating specific seizures was discussed.
Assessing what is cultural about Asian Americans’ academic advantage

Scholars have long debated the reasons underlying Asian Americans’ exceptional educational outcomes. Psychologists emphasize individual cognitive ability and the effects of stereotypes on performance (1). Culturalists point to values, beliefs, norms, and behavioral patterns unique and intrinsic to ethnicity (2). Structuralists focus on socioeconomic status within and beyond the family, including a group’s position in a society’s status hierarchy (3, 4). Data limitations and quantitative modeling constraints, combined with contentious ethnic politics, have rendered social scientists at an intellectual stalemate. This standstill has consequences: The lack of a strong social science voice in the debate has lead pundits to liberally evoke culture to explain poor or exceptional group outcomes (5, 6); the simplistic framing of group culture has fanned fury, pitted groups against each other, and led Civil Rights activists to advocate for group interests to promote a political agenda. Meanwhile, the general public has remained deprived of knowledge generated from rigorous scientific research. However, Amy Hsin and Yu Xie propel the debate forward with their refreshing analyses and insight in their PNAS report, “Explaining Asian Americans’ academic advantage over whites” (7). Based on nationally representative cohort longitudinal surveys, Hsin and Xie (7) use sophisticated statistical techniques to develop multilayer decomposition models that simultaneously test three competing hypotheses: psychological (individual cognitive ability), cultural (belief in academic effort), and structural (family socioeconomic background). The authors use Asian–white gaps in educational outcomes (rather than outcomes per se) as their dependent variable, and control for factors that differ across schools. Hsin and Xie find a persistent Asian–white gap in educational outcomes. They also find that the difference in academic effort, rather than in cognitive ability or socio-demographic characteristics, explains the Asian–white gap. Hsin and Xie then press forward to address why Asian American students put more effort into their schoolwork … [↵][1]1To whom correspondence should be addressed. E-mail: ZhouMin{at}ntu.edu.sg. [1]: #xref-corresp-1-1
Non-self recognition and programmed cell death in filamentous fungi

Non-self recognition resulting in programmed cell death is a ubiquitous phenomenon in filamentous ascomycete fungi and is termed heterokaryon incompatibility (HI). Recent analyses show that genes containing predicted HET domains are often involved in HI; however, the function of the HET domain is unknown. Autophagy is induced as a consequence of HI, whereas the presence of a predicted transcription factor, VIB-1, is required for HI. Morphological features associated with apoptosis in filamentous fungi are induced by various stresses and drugs, and also during HI. Future analyses will reveal whether common or different genetic mechanisms trigger death by non-self recognition and death by various environmental onslaughts.
Chilling-sensitive mutants of arabidopsis

Twenty-one mutants ofArabidopsis thaliana were isolated that developed chlorosis or necrosis upon incubation at low temperature (10°C to 15°C). Crosses among mutants in different phenotypic classes showed that mutants in three of four classes were found in a small number of loci.
The formation of bioactive amyloid species by prion proteins in vitro and in cells

Abstract Amyloid proteins are a group of proteins that can polymerize into cross β-sheeted amyloid species. We have found that enhancing cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formazan exocytosis is a common property of bioactive amyloid species formed from all of the amyloid proteins tested to date. In this report, we show that the infectious amyloid species of the prion protein HET-s of the filamentous fungus Podospora anserina, like other amyloidogenic proteins, also enhances MTT formazan exocytosis. More strikingly, cellular MTT formazan exocytosis revealed the formation of bioactive amyloid species in prion-infected mouse N2a neuroblastoma cells. These findings suggest that cellular MTT formazan exocytosis can be useful for studying the roles of bioactive amyloid species in prion infectivity and prion-induced neurodegeneration.
A tune in "a minor" can "b major": a review of epidemiology, illness course, and public health implications of subthreshold depression in older adults.

Abstract Background With emphasis on dimensional aspects of psychopathology in development of the upcoming DSM-V, we systematically review data on epidemiology, illness course, risk factors for, and consequences of late-life depressive syndromes not meeting DSM-IV-TR criteria for major depression or dysthymia. We termed these syndromes subthreshold depression, including minor depression and subsyndromal depression. Methods We searched PubMed (1980–Jan 2010) using the terms: subsyndromal depression, subthreshold depression, and minor depression in combination with elderly, geriatric, older adult, and late-life. Data were extracted from 181 studies of late-life subthreshold depression. Results In older adults subthreshold depression was generally at least 2–3 times more prevalent (median community point prevalence 9.8%) than major depression. Prevalence of subthreshold depression was lower in community settings versus primary care and highest in long-term care settings. Approximately 8–10% of older persons with subthreshold depression developed major depression per year. The course of late-life subthreshold depression was more favorable than that of late-life major depression, but far from benign, with a median remission rate to non-depressed status of only 27% after ≥ 1 year. Prominent risk factors included female gender, medical burden, disability, and low social support; consequences included increased disability, greater healthcare utilization, and increased suicidal ideation. Limitations Heterogeneity of the data, especially related to definitions of subthreshold depression limit our ability to conduct meta-analysis. Conclusions The high prevalence and associated adverse health outcomes of late-life subthreshold depression indicate the major public health significance of this condition and suggest a need for further research on its neurobiology and treatment. Such efforts could potentially lead to prevention of considerable morbidity for the growing number of older adults.
Adapter Protein Shc Regulates Janus Kinase 3 Phosphorylation

Although constitutive activation of Janus kinase 3 (Jak3) leads to different cancers, the mechanism of trans-molecular regulation of Jak3 activation is not known. Previously we reported that Jak3 interactions with adapter protein p52ShcA (Shc) facilitate mucosal homeostasis. In this study, we characterize the structural determinants that regulate the interactions between Jak3 and Shc and demonstrate the trans-molecular mechanism of regulation of Jak3 activation by Shc. We show that Jak3 autophosphorylation was the rate-limiting step during Jak3 trans-phosphorylation of Shc where Jak3 directly phosphorylated two tyrosine residues in Src homology 2 (SH2) domain and one tyrosine residue each in calponin homology 1 (CH1) domain and phosphotyrosine interaction domain (PID) of Shc. Direct interactions between mutants of Jak3 and Shc showed that although FERM domain of Jak3 was sufficient for binding to Shc, CH1 and PID domains of Shc were responsible for binding to Jak3. Functionally Jak3 was autophosphorylated under IL-2 stimulation in epithelial cells. However, Shc recruited tyrosine phosphatases SHP2 and PTP1B to Jak3 and thereby dephosphorylated Jak3. Thus we not only characterize Jak3 interaction with Shc, but also demonstrate the molecular mechanism of intracellular regulation of Jak3 activation where Jak3 interactions with Shc acted as regulators of Jak3 dephosphorylation through direct interactions of Shc with both Jak3 and tyrosine phosphatases.
Justice vs justification effects on productivity: Reconciling equity and dissonance findings

Abstract It was hypothesized that (a) subjects given a choice (high-choice) to work on a task would be more productive than subjects given little choice (low-choice) and (b) higher reward would lead to decreased productivity for high-choice subjects but to increased productivity for low-choice subjects. Subjects were either given a choice or not given a choice to work on a task for a specified level of reward (either equitable reward, under-reward, or over-reward). Results indicated that high-choice subjects produced more than low-choice subjects, and that higher reward tended to lead to lower productivity for high-choice subjects, while higher reward tended to lead to greater productivity for low-choice subjects. These results were discussed in terms of alternative responses to inequitable rewards.
University and community hospital medical student emergency medicine clerkship experiences.

Objective: To determine whether there is a significant difference between educational opportunities for fourth-year medical students rotating at a university hospital (UH) compared with several community hospitals (CHs) during a mandatory emergency medicine (EM) clerkship. Methods: A self-reported clinical tool was completed in real time by each student rotating for 2 weeks at the UH and 2 weeks at 1 of 4 CHs (3 affiliated and 1 unaffiliated). Students are required to document the number of patients seen and the number of procedures performed on each of 20 six-hour shifts. They rated the EM attending clinical teaching by site using a 5-point scale at the end of the clerkship. Results: Most (95%) of the 87 students in the 7 clerkship blocks of the 1996–97 academic year rotated at the UH and a CH. Most (71%) students rated both the UH and the CH for the quality of teaching by attendings. There was a significant difference in the mean number of patients evaluated/shift (2.2 ± 0.10 vs 2.8 ± 0.10, UH vs CH; p < 0.001) and the mean number of procedures performed/shift (0.36 ± 0.04 vs 0.56 ± 0.05, UH vs CH; p < 0.001). Attending clinical teaching scores were significantly higher (p = 0.03) at the CHs. Conclusions: The educational opportunities for students in an EM clerkship to evaluate patients and perform procedures were significantly greater at the community hospitals. Inclusion of community hospital settings in a medical student EM clerkship may optimize the clinical experience.
Cognitive Foundations of Musical Pitch

1. Objectives and Methods 2. Quantifying Tonal Hierarchies and Key Distances 3. Musical Correlates of Perceived Tonal Hierarchies 4. A Key-Finding Algorithm Based on Tonal Hierarchies 5. Perceived Relations Between Musical Tones 6. Perceptual Organization and Pitch Memory 7. Quantifying Harmonic Hierarchies and Key Distances 8. Perceived Harmonic Relations 9. Perceiving Multiple Keys: Modulation and Polytonality 10. Tonal Hierarchies in Atonal and Non-Western Tonal Music 11. Music Cognition: Theoretical and Empirical Generalizations
Thyroid Function Studied in Paired Maternal-Cord Sera and Sequential Observations of Thyrotropic Hormone Release during the First 72 Hours of Life

Thyroid Function Studied in Paired Maternal-Cord Sera and Sequential Observations of Thyrotropic Hormone Release during the First 72 Hours of Life
Regulation of the norepinephrine transporter by chronic administration of antidepressants

Abstract Background Downregulation of serotonin transporter was observed previously after chronic treatment with selective serotonin reuptake inhibitors (SSRIs) but not selective norepinephrine reuptake inhibitors (NRIs). This study investigated if chronic treatment of rats with selective NRIs or SSRIs also affected the norepinephrine transporter (NET). Methods Rats were treated for 3 to 6 weeks by osmotic minipumps with either the selective NRIs, desipramine, or the SSRI paroxetine. Results [ 3 H]nisoxetine binding sites as well as [ 3 H]norepinephrine uptake were decreased in hippocampus and cortex after treatment with desipramine. By contrast, paroxetine-treated rats showed no alteration in either [ 3 H]nisoxetine binding or [ 3 H]norepinephrine uptake. NET messenger RNA levels in the locus coeruleus were unchanged by desipramine treatment. Conclusions These results demonstrate that the marked decrease in NET density 1) is not a consequence of a decrease in gene expression; 2) was caused only by a selective NRI; and 3) was associated with a parallel decrease in norepinephrine uptake.
Amplification In A XeCl Excimer Gain Module Of 200-Fsec UV Pulses Derived From A Colliding Pulse Mode-Locked (Cpm) Laser System

Amplification in a XeC1 excimer gain module of 200-fsec UV pulses derived from a colliding pulse mode-locked (CPM) laser system was achieved, and the system producing the pulses was fully characterized. In an auxiliary experiment, the pulse width of -2.4-μm pulses generated by Raman shifting the 200-fsec UV pulses in Ba vapor was measured to be -160 fsec.
Sedimentation patterns of pulse-labeled RNA in the mitotic cycle of Physarum polycephalum

Abstract Plasmodia of the synchronously dividing myxomycete Physarum polycephalum have been exposed to short pulses of [ 3 H]uridine at different stages of the mitotic cycle. RNA was extracted by a modified phenol procedure and separated on sucrose density gradients. At all times of the cycle investigated, ribosomal and soluble RNA were made. After a 3-min pulse followed by a 60-min chase, the absorbance and activity patterns coincided at all times of the cycle. No significant differences were seen in the sedimentation pattern of 10-min pulse-labeled RNA made at different times of the mitotic cycle. Peaks with sedimentation values of about 33 S and 19 S were always observed; these may be precursors of ribosomal RNA. With 3-min pulse-labeling polydisperse RNA was obtained. Sedimentation values ranged from about 4 S to more than 50 S with two peaks at about 6 S and 13 S. The patterns were very similar at different times of the mitotic cycle; however, 1 h before mitosis the 13-S peak seemed particularly high, and in mitosis there was partial shift of the labeling pattern to the lighter side.
THE INTERNET AND DEMOCRACY: THE CAUSAL LINKS BETWEEN TECHNOLOGY AND POLITICS

Abstract This paper strives to explicate the causal links between changing technology and democratic governance. Its overarching goal is to define the relevant concepts of communication and governance and more importantly, to focus empirical observations on the critical dimensions of a multifaceted phenomenon. The analysis focuses on three key links in this causal chain. The first is the effects of technological in novation on different communication activities. The second link involves the role communication and information play in democratic governance. The final is the social and political mechanisms by which technological innovations are introduced within and transform democratic processes and institutions. We argue that a sharper understanding of these three essential links will enable the growing numbers of researchers interested in electronic democracy to employ the massive social experiment the Internet represents to clarify and further democratic theory itself. The rise of the Internet has led to...
Electrophysiology in Guillain-Barré syndrome

Clinical electrophysiological studies are important in the evaluation of patients with Guillain-Barre syndrome. Physiological evidence of demyelination occurs in almost all patients with Guillain-Barre syndrome, especially if serial studies are performed. Criteria for demyelination are proposed. Prognostic information concerning patient outcome can be deduced from computation of the mean of the summed motor evoked compound muscle action potential amplitudes from distal stimulation. Future studies of the electrophysiology of Guillain-Barre syndrome should allow increased use of the data for prognostication and should enhance our understanding of the mechanisms of the disease.
A serial position effect in recall of United States presidents

College students asked to recall the names of all the presidents of the United States, either in their order of occurrence or in any order, produce a classical serial position curve with best performance at the beginning and end of the series. Except for extraordinarily high recall of Lincoln, memorability of presidents is strongly related to their chronological position in history. This result extends generality of the serial position effect to semantic memory and, if one seeks a general explanation of serial position effects in semantic and long-term episodic memory experiments, rules out several theoretical candidates. It appears most congruent with the hypothesis that end points of a series serve as distinct positional cues around which memory search is begun.
Anatrophic nephrotomy and plastic calyrhaphy

SummaryA technique of nephrotomy is described in which the kidney is not bivalved, rather the nephrotomy incision is placed between the junction of the anterior and posterior arterial segments. A new method utilizing vertical mattress sutures and water-tight closure is discussed. Correction of calyceal stenosis is achieved by calycoplasty. The results of this procedure in 138 patients as it has evolved in the last 12 years are reviewed.
VIRUSES OF POLIOMYELITIS AN IMMUNOLOGICAL COMPARISON OF SIX STRAINS

Qualitative immunological differences exist between early passage strains or so called human strains of the virus of poliomyelitis. These differences show a relationship to the epidemic source of the virus and are exemplified in this study by 4 strains isolated in different years during an eastern and western epidemic of poliomyelitis.
Delivery of Catalytic Metal Species onto Surfaces with Dendrimer Carriers for the Synthesis of Carbon Nanotubes with Narrow Diameter Distribution

Polyamidoamine (PAMAM) dendrimers are used as carriers to deliver complexed Fe(III) ions uniformly onto silicon oxide substrates for the formation of iron oxide nanoparticles with a narrow diameter in the range of 1−2 nm. Chemical vapor deposition (CVD) synthesis with these nanoparticles affords single-walled carbon nanotubes (SWNTs) with a diameter distribution in the range of 1−2 nm, much narrower than that for SWNTs grown from commonly used powder-supported catalyst (1−5 nm) and from artificial ferritin derived nanoparticles (1−3 nm). Thus, the current work represents a step further toward the synthesis of monodispersed SWNTs via the approach of chemically controlling the formation of discrete catalyst nanoparticles.
Technique for Simultaneous Sampling of Planktonic Fish Eggs and Larvae at Three Depths

Abstract We describe the apparatus and a method for sampling planktonic fish eggs and larvae and macrozooplankton by using multiple plankton nets at two or three depths. This method proved to be efficient for collecting most pelagic life stages that occur in the Hudson River and various nearby inland lakes. The rigging was used on small boats that can be hauled to any accessible body of water by trailer. The setting and retrieval of nets was relatively easy, and was facilitated by the use of a gasoline-powered winch.
Microfabricated Implants for Applications in Therapeutic Delivery, Tissue Engineering, and Biosensing

By adapting microfabrication techniques originally developed in the microelectronics industry novel devices for drug delivery, tissue engineering and biosensing have been engineered for in vivo use. Implant microfabrication uses a broad range of techniques including photolithography, and micromachining to create devices with features ranging from 0.1 to hundreds of microns with high aspect ratios and precise features. Microfabrication offers device feature scale that is relevant to the tissues and cells to which they are applied, as well as offering ease of en masse fabrication, small device size, and facile incorporation of integrated circuit technology. Utilizing these methods, drug delivery applications have been developed for in vivo use through many delivery routes including intravenous, oral, and transdermal. Additionally, novel microfabricated tissue engineering approaches propose therapies for the cardiovascular, orthopedic, and ocular systems, among others. Biosensing devices have been designed to detect a variety of analytes and conditions in vivo through both enzymatic-electrochemical reactions and sensor displacement through mechanical loading. Overall, the impact of microfabricated devices has had an impact over a broad range of therapies and tissues. This review addresses many of these devices and highlights their fabrication as well as discusses materials relevant to microfabrication techniques.
Porcine Carbonyl Reductase STRUCTURAL BASIS FOR A FUNCTIONAL MONOMER IN SHORT CHAIN DEHYDROGENASES/REDUCTASES

Abstract Porcine testicular carbonyl reductase (PTCR) belongs to the short chain dehydrogenases/reductases (SDR) superfamily and catalyzes the NADPH-dependent reduction of ketones on steroids and prostaglandins. The enzyme shares nearly 85% sequence identity with the NADPH-dependent human 15-hydroxyprostaglandin dehydrogenase/carbonyl reductase. The tertiary structure of the enzyme at 2.3 A reveals a fold characteristic of the SDR superfamily that uses a Tyr-Lys-Ser triad as catalytic residues, but exhibits neither the functional homotetramer nor the homodimer that distinguish all SDRs. It is the first known monomeric structure in the SDR superfamily. In PTCR, which is also active as a monomer, a 41-residue insertion immediately before the catalytic Tyr describes an all-helix subdomain that packs against interfacial helices, eliminating the four-helix bundle interface conserved in the superfamily. An additional anti-parallel strand in the PTCR structure also blocks the other strand-mediated interface. These novel structural features provide the basis for the scaffolding of one catalytic site within a single molecule of the enzyme.
Onset and persistence of daily smoking: The interplay of socioeconomic status, gender, and psychiatric disorders

Abstract Gains in reducing the prevalence of smoking observed over the past 40 years have been substantially lower among lower socioeconomic status (SES) groups and women. In parallel, there have been strong and consistent associations of psychiatric disorders with SES, gender, and smoking. Yet few studies have examined the interrelations among these factors to identify their unique and shared contributions. In this study we examine (1) to what degree SES and gender predict new onset of daily smoking and persistence during the current period when rates of smoking have been stable overall; and (2) given the association of psychiatric disorders with gender, SES, and cigarette smoking, to what degree psychiatric disorders explain or alter the associations between gender, SES, and cigarette smoking. Methods Longitudinal data for U.S. adults come from Waves 1 (2001–2002) and 2 (2003–2004) of the National Epidemiologic Study of Alcohol and Related Conditions ( N = 34,653). DSM-IV mood, anxiety, and substance use disorders were assessed with AUDADIS-IV. Logistic regression was used to estimate risk of transitions to daily smoking and persistence over the 3-year follow-up. Results Gender, education, occupation, anxiety disorders, and substance use disorders (SUDs) independently predicted the onset of daily smoking at W2, with greater gender differences observed at lower levels of education. However, no interactions were found between active psychiatric disorders and either gender or SES in predicting the onset of daily smoking. Only being Native American/Alaskan, having an active SUD, and number of cigarettes smoked per day predicted persistence of daily smoking at W2.
Second or "Recurrent" Diaphragmatic Hernia Associated with Haemophilus influenzae Pneumonia and Sepsis

The following report describes an infant with a second right sided diaphragmatic hernia associated with Haemophilus influenzae type b sepsis
Middie mercury: an ambient music generator for relaxation

We describe a computer application for relaxation that is based on music generation following users' actions with a simulated drop of mercury. Rationale for the approach as well as architectural, algorithmic and technical details of the implementation are included. We also provide results of a user survey evaluating qualities of application usage experience.
Addition compounds of methyl substituted cyclic ethers with boron trifluoride

Abstract A manometric method was used to study the addition compounds of boron trifluoride with 2-methyltetrahydrofuran, 2,5-dimethyltetrahydrofuran, 2-methyltetrahydropyran and 2,6-dimethyltetrahydropyran. Physical characteristics are given. Methyl substitution in both tetrahydrofuran and tetrahydropyran causes the addition compound to be more highly dissociated, with the effect being much more pronounced for the latter. In spite of the increased dissociation, the addition compounds formed with the substituted five-membered ring ethers have higher enthalpies and entropies of dissociation than does that formed with the unsubstituted ether. In the six-membered ring system, however, all the thermodynamic values for the dissociation process are largest for the unsubstituted case.
The vestibuliferan ciliate Balantidium acanthuri n. sp. from two species of the surgeonfish, genus Acanthurus

Summary The surgeonfishes Acanthurus xanthopterus and A. leucosternon collected from the Indian ocean Durban, off South Africa, appear to have gut symbionts of the same species of Balantidium. The specificity of species of Balantidium in herbivorous marine fish is discussed.
Immortalized cells as experimental models to study cancer

The development of cancer is a multi-step process in which normal cells sustain a series of genetic alterations that together program the malignant phenotype. Much of our knowledge of cancer biology results from the detailed study of specimens and cell lines derived from patient tumors. While these approaches continue to yield critical information regarding the identity, number, and types of alterations found in human tumors, further progress in understanding the molecular basis of malignant transformation depends upon the generation and use of increasingly sophisticated experimental models of cancer. Over the past several years, the recognition that telomeres and telomerase play essential roles in regulating cell lifespan now permits the development of new models of human cancer. Here we review recent progress in the use of immortalized human cells as a foundation for understanding the molecular basis of cancer.
Abstract 5690: Validating sigma-2 receptor ligand as a novel tumor-targeted drug delivery agent for treating ovarian cancer

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL The sigma-2 receptor is overexpressed in various human tumors. Sigma-2 receptor selective radiotracers have been shown to target various solid tumors in rodents and in human patients using positron emission tomography. Sigma-2 receptor ligands can be internalized into tumor cells by the endocytotic pathway. Therefore, sigma-2 receptor ligands are excellent candidates as tumor-targeted delivery agents when covalently attached to drugs. Smac is a protein released from mitochondria into the cytosol in response to apoptotic stimuli. Small-molecule Smac mimetic compounds (SMC) have been developed by several laboratories as anticancer drugs. In this study we validate sigma-2 ligand as a tumor-targeting drug delivery agent for treating ovarian cancer. We have synthesized sigma-2 ligand-conjugated SMC (SSMC), SW III-123. Our data show that SW III-123 has adequate sigma-2 receptor binding affinities (Kiα2 =190 nM and Kiα1 =2046 nM). SW III-123 exhibits potent antitumor activities with EC50 values at 4.0 μM, 2.3 μM and 2.4 μM in human ovarian cancer cell lines SKOV-3, CaOV-3, and BG-1, respectively. In contrast, unconjugated SMC, SW IV-52s, shows little cytotoxicity in these cell lines (EC50 > 200 μM). These results suggest that the sigma-2 ligand has successfully delivered SMC into ovarian cancer cells. Western blot results show that SW III-123 degrades inhibitor of apoptosis proteins (IAPs), XIAP and cIAP-1, in SKOV-3 cells, possibly by interacting with the baculovirus IAP repeat (BIR) domains of IAPs. SW III-123 cleaves caspase-3, 8, and 9 dose-dependently in SKOV-3 cells, indicating that SW III-123 kills ovarian cancer cells by activating both intrinsic and extrinsic apoptotic pathways. In conclusion, sigma-2 ligand is a promising tumor-targeting drug delivery agent. SSMC will likely offer a novel class of therapeutic drugs for treating ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5690. doi:1538-7445.AM2012-5690
2097 Automated tracking of a passive intramyocardial needle with off-resonance mri: a feasibility study

Direct intramyocardial therapies aimed at treating myocardial regions affected by severe ischemia may benefit from CMR-guided interventional procedures. Although interventional MR approaches using active devices are considered to be the method of choice, potential tissue heating and altered mechanical properties are some of their limitations. Methods that have the capacity to visualize MR-compatible passive devices may overcome many of these obstacles. Recently, an off-resonance-based real-time positive contrast method (FLAPS) was used to visualize the passage of an intramyocardial needle (PIN) through the aorta and into the heart of swine [1,2]. We envision this procedure may benefit from computer assisted strategies that track the needle's location throughout the MR procedure. However, the feasibility of real-time automated tracking of a PIN has not been established.
In defence of Affirmative Action : The American case

(1983). In defence of Affirmative Action : The American case. Journal of Ethnic and Migration Studies: Vol. 10, No. 3, pp. 464-469.
Feeling-of-knowing judgments and strategy selection in spelling.

Metacognitive processes, such as monitoring one's knowledge and selecting appropriate strategies, may be important in skilled spelling. We hypothesized that skilled spellers have knowledge of which words they know how to spell and also that the accuracy with which people monitor their knowledge should be related to the spelling strategies they select. College students provided Feeling-of-Knowing ratings about the spellings of words and also spelled the same words and indicated whether they sounded out or remembered the spellings. Feeling-of-Knowing ratings were moderately correlated with Spelling Accuracy and were more strongly predictive of Spelling Accuracy when Feeling-of-Knowing ratings and spellings were done as part of the same task rather than as separate tasks. Analyses indicate that those who were better at monitoring their knowledge of spelling also chose more congruent spelling strategies. The results suggest that skilled spellers can monitor which words they know how to spell, but this ability...
Evidence for a fifth (g) region in the h-2 complex of the mouse.

Antisera (B10.129×A)F1 anti-P and (B10×A)F1 anti-B10.P contain antibodies that define, in the PVP hemagglutination test, an antigen originally described as G or H-2.7. Of the independentH-2 haplotypes, the H-2.7 antigen is present inf, j, k, p, ands. In addition, the antisera also contain a weak cytotoxic antibody, distinct from anti-H-2.7. The cytotoxic antibody reacts with antigens controlled by theK orI regions. The hemagglutinating H-2.7 antibody does not have cytotoxic activity. The genetic determinant coding for antigen H-2.7 can be mapped into the chromosomal segment between theS andD regions. The H-2.7 antigen thus serves as a marker for a new region of theH-2 complex. The locus coding for antigen H-2.7 is designatedH-2 G and the correspondingH-2 regionG. The H-2.7 antigen has a tissue distribution distinct from that of the H-2 antigens controlled by theK orD regions. So far it could be detected primarily on erythrocytes.
A VHDL Based Controller Design for Non-contact Temperature and Breathing Sensors Suitable for Crib

Continuous monitoring of vital signs has the potential of improving infant health care and reduce SIDS (sudden infant death syndrome). With the emergence of micro-sensors and wireless technology can enable change in the conventional health care systems, replacing it with wearable and non-contact based wireless health care system. In this paper, an infrared non-contact temperature sensor, and a microphone based breathing sensor are used to detect vitals sign of an infant. Interfacing different sensors and acquiring and processing data in real time is a challenging task and requires a dedicated hardware. Field programmable gate array (FPGA) based technology has become the most widely used technique for real-time application. The HDL (hardware description language) based FPGA implementation of necessary drivers and interfacing hardware are proposed in this paper. With the help of necessary simulations and experimental results, the functionality and accuracy of the proposed system are justified.
Seniority, Commitment, and Self-Governing Groups

Kenneth Shepsle and Barry Nalebuff have written a challenging and insightful essay on "The Commitment to Seniority in Self-Governing Groups." Its challenge arises from the richness of its focal concepts: seniority, commitment, and self-governing. Its insights come from clarifying these concepts while working toward a theory that has more immediate empirical implications than current theories. Shepsle and Nalebuff regard their paper as a "prolegomenon." As a preliminary statement, it will undoubtedly be useful for future research. This note attempts to provide some additional guidance by highlighting some strengths and limitations of the Shepsle-Nalebuff analysis. My premise is that a useful theory of seniority should have clear and empirically motivated concepts, explicit assumptions, and results that can be translated into testable predictions. Comments are organized accordingly.
Developmental and protein modification defects caused by mutations in the Drosophila gene l(3)c21R

A temperature-sensitive Drosophila mutation, l(3)c21RRW630 (abbreviated RW630), has been previously shown to have biochemical as well as developmental defects. To analyze further the relationship between the biochemical and developmental defects, recombinational mapping, deletion analysis, and complementation studies with other l(3)c21R alleles were performed. These experiments showed that the biochemical and developmental defects in RW630 can be attributed to a single mutation. Four non-temperature-sensitive l(3)c21R alleles were found to have biochemical defects similar to those seen in RW630 at restrictive temperature. In RW630 and in these four other l(3)c21R alleles, the severity of expression of the biochemical and the developmental defects was closely correlated. Temperature-shift studies of the expression of the RW630 maternal lethal effect on embryogenesis in females transheterozygous for RW630 and other l(3)c21R alleles yielded results which indicated that these defects must accumulate over a period of time before the maternal lethal effect can be detected. These data provide further support for the hypothesis that defects in protein modification produce developmental defects in l(3)c21R mutants.
Respiratory oxidation of pyruvate by plant mitochondria.

Abstract Cytoplasmic particles isolated from mung bean seedlings can oxidize all of the acids of the Krebs cycle. The oxidation of pyruvate is dependent upon the concomitant oxidation of a catalytic amount of one of the di- or tricarboxylic acids, and in this function the various acids are approximately equivalent. Preparational procedures for the isolation of such particles have been defined. Among the most important requirements for full activity of the isolated particles is the presence of phosphate in the grinding medium. It has been shown that the isolated particles oxidize at a rate sufficient to account for all of the respiration of the inta ct tissue.
Introduction to Color Facsimile: Hardware, Software and Standards

The design of a color facsimile machine presents a number of unique challenges. From the technical side it requires a very efficient, seamless integration of algorithms and architectures in image scanning, compression, color processing, communications and printing. From the standardization side, it requires that agreements on the color representation space, negotiation protocols and coding methods must be reached through formal international standardization process. This paper presents an introduction to the overall development of color facsimile. An overview of the recent development of the international Color Facsimile Standard is first presented. The standard enables the transmission of continuous-tone colors and gray-scale images in Group 3 (over conventional telephone lines) and Group 4 (over digital lines) facsimile services, with backwards compatibility to current black and white facsimile. The standard provides specifications on color representation and color image encoding methods as well as extensions to current facsimile protocols to enable the transmission of color images. The technical challenges in implementing the color facsimile standard on existing facsimile machines are described next. The integration of algorithms and architectures in color scanning, compression, color processing, transmission and rendering of received hardcopy facsimile in a color imaging pipeline is described. Lastly, the current status on softcopy color facsimile standardization is reported.
Optical properties of ion beam synthesized nitrogen‐rich GaN1‐xAsx

We have synthesized GaN1-xAsx alloys using implantation of As into GaN followed by rapid thermal annealing. Appearance of a new As-derived band at about 2.5 eV below the conduction band edge is confirmed by photomodulated transmission (PT) and photoluminescence (PL). Photoluminescence peaks at about 2.37 eV observed at low temperature in As and Ar implanted Mg doped GaN samples are attributed to emission associated with complexes of damage produced donors and Mg acceptors. The results demonstrate a feasibility of using ion beam synthesis to produce N-rich group III nitride based highly mismatched alloys. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Epigenetic mechanisms in mammals

DNA and histone methylation are linked and subjected to mitotic inheritance in mammals. Yet how methylation is propagated and maintained between successive cell divisions is not fully understood. A series of enzyme families that can add methylation marks to cytosine nucleobases, and lysine and arginine amino acid residues has been discovered. Apart from methyltransferases, there are also histone modification enzymes and accessory proteins, which can facilitate and/or target epigenetic marks. Several lysine and arginine demethylases have been discovered recently, and the presence of an active DNA demethylase is speculated in mammalian cells. A mammalian methyl DNA binding protein MBD2 and de novo DNA methyltransferase DNMT3A and DNMT3B are shown experimentally to possess DNA demethylase activity. Thus, complex mammalian epigenetic mechanisms appear to be dynamic yet reversible along with a well-choreographed set of events that take place during mammalian development.
Induction of Tyrosine Aminotransferase with N6, O2‐Dibutyryl Adenosine 3′‐5′‐Monophosphate in Rat‐Hepatoma Cells Grown in Culture

The dibutyryl analogue of adenosine 3′:5′ monophosphate (Bu2-Ado-3′:5′-P) stimulates tyrosine-aminotransferase synthesis in rat-hepatoma cells cultured in Dulbecco medium supplemented with excess L-tyrosine. This effect of Bu2-Ado-3′ :5′-P is not observed in cells incubated in regular Dulbecco medium. It has been shown previously that tyrosine-aminotransferase activity increases in hepatoma cells incubated in a glucose-free medium that is also supplemented with excess L-tyrosine. The increase in enzyme activity observed after administration of Bu2-Ado-3′:5′-P and after glucose removal can be prevented by cycloheximide or actinomycin-D. Bu2-Ado-3′ :5′-P in the absence of glucose does not cause an additive increase in tyrosine-amino transferase activity. The latter observation suggests that increased enzyme synthesis in each circumstance occurs via the same mechanism. Combination experiments, using Bu2-Ado-3′ :5′-P and cortisol, indicate that each of these inducers of tyrosine aminotransferase acts independently. In light of recent observations concerning β-galactosidase induction in bacteria, a mechanism of tyrosine-aminotransferase induction in these mammalian-derived cells is discussed.
Issues surrounding protection and assent in pediatric research.

PURPOSE: This article provides the physical therapist (PT) researcher with valuable information regarding the issues of assent by reviewing the history, regulations, and issues surrounding the protection of children participating in research. KEY POINTS: To conduct ethical research, knowledge about the history, regulations, and issues surrounding the protection of children in research is important. While most of the research done by PTs is non-invasive and low risk, it is still important for a researcher to be aware of the full spectrum of risk involved with research. An important topic for PTs involves the related concepts of parental permission and child assent. Those children, who are capable of understanding a research study, need to know what is involved in the study and have the choice to participate or to decline to participate. SUMMARY/CLINICAL IMPLICATIONS: PTs should be encouraged to be involved in research to advance the profession and contribute to evidence-based practice. Due to this, PTs are becoming more involved in the process of obtaining assent from a child, and therefore need to be aware of the unique aspects of this process.
Mycoplasma gallisepticum lipid associated membrane proteins up-regulate inflammatory genes in chicken tracheal epithelial cells via TLR-2 ligation through an NF-κB dependent pathway.

Mycoplasma gallisepticum-mediated respiratory inflammation in chickens is associated with accumulation of leukocytes in the tracheal submucosa. However the molecular mechanisms underpinning these changes have not been well described. We hypothesized that the initial inflammatory events are initiated upon ligation of mycoplasma lipid associated membrane proteins (LAMP) to TLRs expressed on chicken tracheal epithelial cells (TEC). To test this hypothesis, live bacteria or LAMPs isolated from a virulent (Rlow) or a non-virulent (Rhigh) strain were incubated with primary TECs or chicken tracheae ex vivo. Microarray analysis identified up-regulation of several inflammatory and chemokine genes in TECs as early as 1.5 hours post-exposure. Kinetic analysis using RT-qPCR identified the peak of expression for most genes to be at either 1.5 or 6 hours. Ex-vivo exposure also showed up-regulation of inflammatory genes in epithelial cells by 1.5 hours. Among the commonly up-regulated genes were IL-1β, IL-6, IL-8, IL-12p40, CCL-20, and NOS-2, all of which are important immune-modulators and/or chemo-attractants of leukocytes. While these inflammatory genes were up-regulated in all four treatment groups, Rlow exposed epithelial cells both in vitro and ex vivo showed the most dramatic up-regulation, inducing over 100 unique genes by 5-fold or more in TECs. Upon addition of a TLR-2 inhibitor, LAMP-mediated gene expression of IL-1β and CCL-20 was reduced by almost 5-fold while expression of IL-12p40, IL-6, IL-8 and NOS-2 mRNA was reduced by about 2–3 fold. Conversely, an NF-κB inhibitor abrogated the response entirely for all six genes. miRNA-146a, a negative regulator of TLR-2 signaling, was up-regulated in TECs in response to either Rlow or Rhigh exposure. Taken together we conclude that LAMPs isolated from both Rhigh and Rlow induced rapid, TLR-2 dependent but transient up-regulation of inflammatory genes in primary TECs through an NF-κB dependent pathway.