cssi/SciSciGPT-SciSciNet huggingface dataset:
Pulmonary Complications in Cystic Fibrosis: Past, Present, and Future: Adult Cystic Fibrosis Series

1Cystic fibrosis (CF) is an autosomal recessive genetic condition with multisystemic disease manifestations, the most prominent of which occur in the respiratory system. Despite significant developments in disease understanding and therapeutics, each contributing to improved lung function and survival in patients with CF, several pulmonary complications, including pneumothorax, massive hemoptysis, and respiratory failure, continue to occur. In this review, we briefly describe each of these complications and their management and discuss how they impact the care and disease trajectory of individuals in whom they occur. Finally, we discuss the evolving role that palliative care and CF transmembrane conductance regular modulator therapies play in the natural disease course and care of patients with CF.
Abstract 1310: Peptide delivery of siRNA in GBM

Glioblastoma Multiforme (GBM), a grade VI glioma, is an aggressive malignant tumorwith a poor prognosis. With an incidence rate of 3.19 per 100,000, GBM has a median survivalrate of 12-15 months and a five-year survival rate of less than 5%. Typical treatments involvesurgical removal, chemotherapy, and radiation; however, these treatments still result in a lowsurvival rate and can lead to potential harm to healthy cells. Therefore, a new therapeutic isneeded for GBM treatment to improve patient outcomes. RNAi, a naturally found process,utilizes siRNA to target specific mRNA for degradation to inhibit protein translation and hasshown clinical potential for targeting and silencing oncogenes. However, barriers to siRNAdelivery, such as cellular uptake, non-specificity, and lack of endosomal escape hinder clinicaltranslation of RNAi therapeutics. Peptides are a promising carrier for siRNAs and havedemonstrated the potential to overcome barriers to delivery. The purpose of this study is todesign a novel tandem peptide for siRNA delivery, evaluate ability to mediate knockdown of atarget oncogene, and compare the efficacy of the tandem peptide to the individual peptidesalone. The tandem peptide is a novel combination of a fusogenic peptide and a targetingpeptide. STAT3, the target gene, is an oncogene that plays a role in cell proliferation,differentiation, apoptosis, and angiogenesis in GBM. Initial results have confirmed basal expression of EGFR and STAT3 in all three GBM cell lines, LN18, U118, and T98G.Characterization of the fusogenic, targeting, and tandem peptides indicated formation of monodispere nanoparticles with diameters less than 150 nm when complexed with siRNA. Furthermore, gel shift assays were conducted and confirmed that the tandem peptide protectedthe siRNA from degradation in 50% FBS. MTS assays conducted in all three cell lines for eachpeptide confirmed that there was no significant cytotoxicity due to the vehicles alone. Finally, flow cytometry confirmed uptake of the tandem peptide in T98G cell line. Therefore, it ishypothesized that the tandem peptide composed of both fusogenic targeting peptide willenhance cell-specific uptake of STAT3 siRNA into glioblastoma cells for mediating endosomalescape, resulting in more effective gene silencing and associated downstream effects comparedto the fusogenic and targeting peptides alone. Future studies include immunofluorescence for uptake and endosomal escape, knockdown studies (MTS, Western Blot, and qPCR assays), and assays to examine the downstream effect of silencing STAT3, such as migration and invasion assays. Citation Format: Jessica Boulos, Angela Alexander-Bryant. Peptide delivery of siRNA in GBM [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1310.
Role of MR-guided Radiotherapy (MRgRT) in Colorectal Cancer

The current standard treatment for locally advanced or metastatic colorectal cancer often includes radiotherapy delivered under computed tomography (CT)–based image guidance. Magnetic resonance–guided radiotherapy (MRgRT) offers a substantial improvement in target and adjacent organ visualization and allows for real-time imaging throughout treatment to ensure target accuracy with each fraction. However, this technology is in its relative infancy, with many open questions regarding how to maximize the potential of this new treatment modality. We review the literature and share our institutional experience to highlight the strengths and limitations of MRgRT for treatment of colorectal cancer. MRgRT is safe and effective in both the locally advanced and metastatic settings. Dose can be safely escalated in locally advanced cases, potentially improving rates of pathologic complete response. Functional imaging offers insight into treatment response dynamics, opening the possibility for nonoperative management of select cases. Liver metastases can be treated to ablative doses with high rates of local control. MRgRT has the potential to shift the paradigm of treatment for locally advanced and metastatic colorectal cancer. Improved target accuracy and real-time gating allows for dose prescriptions beyond what has been achievable with CT-based imaging, allowing for higher rates of tumor control with no significant increase in toxicity. Future work will focus on optimal dose fractionation schemes and functional radiographic assessment of tumor response.
Interactions of Epstein-Barr Virus with Human Retroviruses

AIDS has become one of the most threatening new epidemics to our world. Fortunately, this viral infection appeared at a time when advances in molecular biology have allowed us to quickly characterize and study the human immunodeficiency virus (HIV-1), the causative agent of AIDS. Because HIV-1 causes profound immunodeficiency, preexisting persistent viral infections can recur causing new twists on old diseases. In this discussion, I wish to point out new challenges posed to the scientist studying the Epstein-Barr virus (EBV) as we learn more about infections caused by human retroviruses.
Regulation of Porins in Escherichia coli by the Osmosensing Histidine Kinase/Phosphatase EnvZ

Publisher Summary EnvZ, the osmotic sensor for Escherichia coli, belongs to the largest class of histidine kinases. In response to changes in medium osmolarity, EnvZ regulates the level of phosphorylated OmpR (OmpR-P), its cognate response-regulating transcription factor for ompF and ompC genes. EnvZ has dual-opposing enzymatic activities: OmpR-phosphorylase (kinase) and phospho-OmpR-dephosphorylase (phosphatase). The osmotic signal is proposed to regulate the ratio of the kinase to the phosphatase activity of EnvZ to modulate the level of OmpR phosphorylation. The C-terminal kinase domain of EnvZ has been dissected successfully into two independent domains: A and B. This chapter describes results that shed new light on various aspects of EnvZ function. It demonstrates that domain A is not simply a structural scaffold for the EnvZ dimer formation by forming a central four-helix bundle, it also plays an essential role in the phosphatase reaction, providing the invariant histidine residue at the active center. Domain A by itself is able to dephosphorylate OmpR-P, and phosphorylated domain A is able to transfer the phosphoryl group to OmpR. However, domain B plays an essential role in phosphorylation of the invariant histidine residue in domain A with ATP and significantly enhances domain A phosphatase activity when it is linked covalently to domain A. The chapter also discusses how the opposing enzymatic activities of EnvZ are regulated on the basis of the biochemical characterization of individual domains A and B, mutagenesis analysis of these domains, and the experiments using Tazl, a Tar.
Turning Off the Tap: Determinants of Expropriation in the Energy Sector

This paper analyzes the dependence of the decision of a government to expropriate foreign investment in the energy sector on macroeconomic factors and crude oil and natural gas prices. The contribution of the paper is two-fold. First, using data on eight countries that made recent steps to expropriate foreign investment in their respective energy sectors, we identify the factors that are significant for the decision. These factors are assumed to be invariant across countries. Second, we use our results to calculate the probability that the seven major petroleum exporters with at most partial state ownership will nationalize their respective energy sectors in the next month. The results of this paper can be used to design optimal exit strategies for companies invested in energy sectors in developing countries.
Toxicity and antitumor activity of cis-bis-cyclopentenecarboxylato-1,2-diaminocyclohexane platinum(ii) encapsulated in multilamellar vesicles

The potential of multilamellar vesicles (MLVs) as carriers of cis-bis-cyclopentenecarboxylato-1,2-diaminocyclohexane platinum(II) (CPDP), a lipophilic cisplatin derivative, was assessed. MLVs composed of dimyristoyl phosphatidylcholine (DMPC), dimyristoyl phosphatidylglycerol (DMPG), and cholesterol at different molar ratios were tested. The MLV-CPDP preparation with the highest antitumor activity against L1210 leukemia in vivo was DMPC:DMPG 7:3-CPDP. The encapsulation efficiency of this preparation was 66 +/- 4% (SD); the stability in 0.9% NaCl solution at 4 degrees C was 89% at 14 days and 93% 18 h after incubation in human AB serum at 37 degrees C. The toxicities of DMPC:DMPG 7:3-CPDP and free CPDP (suspended in hydroxypropyl cellulose) administered i.p. were similar (50% lethal dose = 75 versus 91 mg/kg; blood urea nitrogen values 96 h after the administration of the 50% lethal dose = 32.0 versus 34.4 mg/dl). The mean %T/C [(median survival time of treated mice divided by median survival time of control mice) X 100] obtained after a single i.p. injection of the optimal dose of each preparation tested was 215 (range 200 to 232) for DMPC:DMPG 7:3-CPDP, 175 (range 158 to 209) for DMPG-CPDP, 162 (range 136 to 179) for free CPDP, and 178 (range 169 to 189) for cisplatin. Using a multiple i.p. injection schedule (injections on Days 1, 5, and 9), DMPC:DMPG 7:3-CPDP was more active than free CPDP and cisplatin (%T/C: 403, 284, and 253% respectively). DMPC:DMPG 7:3-CPDP is less toxic and more active against L1210 leukemia in vivo than is cisplatin. The encapsulation of CPDP in MLVs composed of DMPC:DMPG 7:3 provides an adequate vehicle for the administration of this lipophilic compound and enhances its antitumor activity against L1210 leukemia.
The Psychology of Hindsight and After-the-Fact Review of Ineffective Assistance of Counsel

Strickland v. Washington tries to guarantee criminal defendants effective assistance of counsel by individually reviewing each defense lawyer's performance after-the-fact. Despite much terrible lawyering, courts rarely reverse convictions. Why? Behavioral psychology provides a key insight: Judges have difficulty reviewing individual lawyers' performance in hindsight. While the Supreme Court and some commentators have worried about the dangers of Monday-morning quarterbacking and 20/20 hindsight, they have overlooked the greater danger that in retrospect, convictions appear inevitable. Psychologists call this the inevitability or confirmatory bias. Strickland's vagueness and its refusal to lay down more specific guidelines for counsel exacerbate this problem by leaving plenty of room for the inevitability bias. The poor records surrounding guilty pleas further exacerbate the problem. The better solution is to move from case-by-case retrospective review to prospective efforts to improve indigent-defender systems, whether through structural-reform litigation or legislative change.
An Approach to Constrained Neural Global Optimization

This paper presents a stochastic neural approach to the problem of determining the global extremum of multivariable, non-linear objective functions subject to constraints. The approximate value of the global extremum is found by using a special transformation followed by neural least squares estimation.
Distributed multimedia: Technologies, applications, and opportunities in the digital information industry : a guide for users and providers

1. Framework. Interactivity. Media and Terminology. Text. Graphics. Images. Audio. Video. Smell, Taste, Touch. Media Sizes and Data Rates. Enhancing Television Sets, Computers, and Telephones. Enhancing Education, Work, and Entertainment. Compressing Images and Video. Compressing Audio. 2. Delivery. Affordable High Capacity. Handling Audio and Video. Network Connections. Digital Transmission. Higher Bandwidth Connection. Circuit-switch Multiplexing. Frequency-division Multiplexing. Time-division Multiplexing. Fiber Deep in the Network. 3. Servers. Manual Analog System. LAN Server System. Options for Function Splits and Processors. Hard Drives vs. CD-ROM's. Hard Drive Design Criteria. File System Design Criteria. Starlight Networks' Software. IBM's Software. Novell. Microsoft. Hewlett-Packard. IBM's Workstation Hardware and Software. Silicon Graphics. Digital Equipment Corporation. IBM's Minicomputer. IBM's Mainframe. NCube's Massively Parallel Hardware and Oracle's Video Server Software. 4. End User Devices. End Users. Types of Devices. Hardware. Performance. Software Standards. Changing Environment. Faster Processors. Faster Computer Buses. High Color and True Color Displays. Mix Computer Displays and NTSC. High Definition Television. Higher-Function Telephones. Set-Top Boxes. Game Devices. Hand-held Devices. Standard Control Interfaces. Significant Alliances. 5. Applications. Desk Top Video Conferences with Collaboration. Multimedia Store and Forward Mail. Consumer Edutainment, Infotainment, Sociotainment. Shopping and Advertising. Digital Libraries. Video-on-Demand. Educational and Health Applications. Hybrid Applications. 6. Providers. Microware Systems Corporation. Macromedia, Inc. CompuServe. Scientific Atlanta. Ameritech. AT&T Network Systems. Broadband Technologies. Institute for Academic Technology. Institute for Learning Sciences. Interactive Multimedia Association. Digital Audio-Visual Council. Viacom. Microsoft Corporation. Spectra.Net Communications. Netscape. Form An Alliance. Reorganize and Integrate Vertically. Hire Needed Skills. Found a Start-Up. 7. Trials. Economic, Marketing, and Technical Motives. Time Warner. Microsoft and TCI. Microsoft and SBC. US West. NYNEX. Bell Atlantic, Virginia. Bell Atlantic, New Jersey. IBM. GTE. Cable Modems. NYU Distance Learning. Sprint. World Wide Web. 8. Skills. Surveys. Investigations. Education. Adoption Rates. Marketing High Technology Products. References. 0201765365T04062001
Numerical Study of the Phenomenon of Turbulence Suppression in a Plane Shear Layer

The phenomenon of turbulence suppression in a free shear layer due to controlled excitation has been studied using vortex-in-cell method. When the amplitude of the sinusoidal excitation is low, the maximum suppression occurs for excitation at the maximally unstable frequency (St θ = 0.017) of the shear layer, consistent with experimental data. An interesting new result of the numerical simulation is that the above Strouhal number preference is lost at high amplitudes of excitation. Also, it is found that the level of random fluctuations superimposed on the initial sinusoidal disturbance affects the extent of suppression significantly.
Association of the Lipoprotein Receptor SCARB1 Common Missense Variant rs4238001 with Incident Coronary Heart Disease

Background Previous studies in mice and humans have implicated the lipoprotein receptor SCARB1 in association with atherosclerosis and lipid levels. In the current study, we sought to examine association of SCARB1 missense single nucleotide polymorphism (SNP) rs4238001 with incident coronary heart disease (CHD). Methods and Results Genotypes for rs4238001 were imputed for 2,319 White, 1,570 African American, and 1,292 Hispanic-American MESA participants using the 1,000 Genomes reference set. Cox proportional hazards models were used to determine association of rs4238001 with incident CHD, with adjustments for age, sex, study site, principal components of ancestry, body mass index, diabetes status, serum creatinine, lipid levels, hypertension status, education and smoking exposure. Meta-analysis across race/ethnic groups within MESA showed statistically significant association of the T allele with higher risk of CHD under a consistent and formally adjudicated definition of CHD events in this contemporary cohort study (hazard ratio [HR]=1.49, 95% CI [1.04, 2.14], P = 0.028). Analyses combining MESA with additional population-based cohorts expanded our samples in Whites (total n = 11,957 with 871 CHD events) and African Americans (total n = 5,962 with 355 CHD events) and confirmed an increased risk of CHD overall (HR of 1.19 with 95% CI [1.04, 1.37], P = 0.013), in African Americans (HR of 1.49 with 95% CI [1.07, 2.06], P = 0.019), in males (HR of 1.29 with 95% CI [1.08, 1.54], P = 4.91x10-3) and in White males (HR of 1.24 with 95% CI [1.03, 1.51], P = 0.026). Conclusion SCARB1 missense rs4238001 is statistically significantly associated with incident CHD across a large population of multiple race/ethnic groups.
Cloning of the proteinase that facilitates infection by schistosome parasites.

Abstract Four cDNA clones encoding a proteinase which facilitates skin invasion by schistosome parasites were isolated by screening a schistosome sporocyst cDNA library, using an oligonucleotide probe containing sequences complementary to predicted 5'-translated regions of its RNA. The amino acid sequence of the enzyme, as deduced from the DNA sequence of the clones, indicates that the enzyme is a serine protease which in many respects is similar to vertebrate pancreatic elastases, although regions outside of the putative active site, binding pocket, and amino-terminal cysteines differ significantly. Regulation of expression of the enzyme occurs at the level of mRNA transcription as well as posttranslationally, the latter involving the processing of a previously unidentified pre-proenzyme (zymogen) sequence. In situ hybridization of the cDNA clones to tissue sections of developing larvae indicates that the enzyme is synthesized within a discrete time frame in specialized cells of the organism.
Hertwig, Wilhelm August Oscar

1849–1922 German cell biologist who was the first to observe the fusion of male and female nuclei during fertilization. Keywords: cytology; fertilization; coelom theory; Ernst Haeckel; organicism
Response of the damaged dopamine system to GM1 and semisynthetic gangliosides: effects of dose and extent of lesion.

Abstract G M1 ganglioside, administered to young C57/BI6J mice with moderate (approx 85%) 1-methyl-4-phenyl-1,2,3,6-terahydropyridine (MPTP)-induced striatal dopamine depletions, caused a dose-dependent increase in striatal dopamine levels. This effect was maximal between 7.0 and 30.0 mg/kg and was not apparent at higher and lower doses of G M1 . G M1 ganglioside treatment had no effect on striatal dopamine levels in mice with more extensive lesions of the dopamine system (i.e. approx 93% loss of striatal dopamine). The semisynthetic ganglioside derivative LIGA 20, administered orally, also increased striatal dopamine levels in moderately lesioned animals, albeit at lower doses than G M1 . LIGA 20 administration also resulted in increased striatal dopamine levels in animals with more extensive dopamine lesions, where G M1 had no effect. These results show that both G M1 and its semisynthetic derivative LIGA 20 can partially restore striatal dopamine levels in MPTP-treated mice and that LIGA 20 is more potent and not subject to the same dose-limiting effects as G M1 .
A VME-VMX Interface to FASTBUS via the LeCroy 1821 Segment Manager

An interface between multiple LeCroy Segment Managers [1] and a VME-VMX system is described. The host I/O registers of the 1821, and control registers for DMA have been mapped into the short I/O address space of VME. Transfers from the data memory of the 1821 occur via pipelined DMA to the VMXbus. As many as sixteen Segment Managers may be controlled by a single interface.
Risk Factors Associated with HCV Among Opioid-Dependent Patients in a Multisite Study

We examined risk factors associated with hepatitis C virus (HCV) infection among opioid-dependent patients enrolled into medication-assisted therapy (buprenorphine or methadone) to determine factors affecting chronic infection. Patients (N = 1039) were randomized as part of a larger, multisite clinical trial sponsored by the National Drug Abuse Treatment Clinical Trials Network assessing liver function. HCV status was first assessed with an antibody screen; if positive, then current infection was determined with an antigen screen testing for detectable virus. Patients were classified as HCV negative, HCV positive but have cleared the virus, or as having chronic HCV. Logistic regression analysis was used to examine demographic and behavioral correlates of the three groups. Thirty-four percent of patients were classified with chronic infection and 14% had evidence of prior infection with apparent clearing of the virus. Chronic infection was associated with recent injection drug use and cocaine use. Chronic HCV infection was also associated with being older and Hispanic. Age, ethnicity, and current drug use increase the likelihood of being chronically infected with HCV. Strategies targeting high risk subgroups can aid in preventing further disease escalation.
Changing the DNA-binding specificity of a repressor

Abstract The Mnt repressor of Salmonella phage P22 recognizes a 17 base pair operator. We constructed an Mnt binding site with two symmetric operator-constitutive mutations. We then selected Mnt mutants that have lost the ability to bind the wild-type operator but acquired the ability to bind the mutant operator. Four independent mutations change the same CAC codon in the mnt gene to CCT or CCC. The corresponding amino acid change in Mnt is His6 → Pro. DNA binding assays with purified wild-type and mutant proteins confirm the change of binding specificity in vitro. Wild-type Mnt binds strongly to the wild-type operator, but binds the mutant operator with 1000-fold less affinity. The mutant Mnt binds with converse affinities to the two operators.
Effects of Electroconvulsive Therapy in Adolescents with Severe Endogenous Depression Resistant to Pharmacotherapy

Abstract Background: This open, prospective study examined the effects of electroconvulsive therapy (ECT) in 10 adolescents with primary, endogenous, psychotic depression who were resistant to antidepressant pharmacotherapy. Methods: Change in symptom severity from baseline was assessed weekly with Hamilton Depression Rating Scale (HDRS) ratings, and outcome was measured additionally at 1 month, and again at 1 year, post-ECT. Results: All but 1 patient demonstrated dramatic improvement, with statistically significant decreases in mean HDRS score detected after the first week of treatment. All responders maintained the benefits of their treatment. Conclusions: The results provide evidence of the clinical effectiveness of ECT in adolescents with phenomenological characteristics shown to be predictive of ECT response in adults.
The power of tests of predictive ability in the presence of structural breaks

This paper presents analytical, Monte Carlo, and empirical evidence on the effects of structural breaks on tests for equal forecast accuracy and encompassing. We show that out-of-sample predictive content can be hard to find because out-of-sample tests are highly dependent on the timing of the predictive ability. Moreover, predictive content is harder to find with some tests than others: in power, F-type tests of equal forecast accuracy and encompassing often dominate t-type alternatives. Based on these results and evidence from an empirical application, we conclude that structural breaks under the alternative may explain why researchers often find evidence of in-sample, but not out-of-sample, predictive content.
The increased replicative capacity of a late-stage simian immunodeficiency virus mne variant is evident in macrophage- or dendritic cell-T-cell cocultures.

Abstract Human and simian immunodeficiency virus (HIV and SIV) may co-opt antigen capture and presentation functions of antigen presenting cells (APCs) to facilitate infection of CD4 + T-cells. To address whether the replicative capacity of SIV in the host may be associated with the extent of viral replication in response to APC–T-cell interactions, we compared the replicative phenotypes of cloned early and late-stage SIVmne variants of known pathogenicity. Here, we show that the highly pathogenic late variant SIVmne027 replicates more efficiently in both macrophage- and dendritic cell (DC)-T-cell cocultures than the minimally pathogenic early virus SIVmneCl8. Contact between either macrophages or DC and T-cells increases replication of SIVmne027. Our analysis also demonstrates that mutations in pol and nef contribute to the greater replicative capacity of SIVmne027 in DC– or macrophage–T-cell cocultures. Together, these data suggest that variant viruses that evolve to replicate vigorously in response to APC–T-cell interactions may have increased replicative capacity in vivo.
A Fabry-Pérot pressure sensor fabricated on left ventricular assist device for heart failure implant

An implantable Fabry-Perot interferometer based pressure sensor is developed. The pressure sensor could be integrated directly onto the inlet shell of a left ventricular assist device (LVAD) to monitor blood pressure in real-time and provide a feedback control signal to achieve the optimal operation of LVAD. The diaphragm of the pressure sensor is made out of biocompatible polymer parylene-C.
Comparison of drug-eluting stents with bare metal stents in unselected patients with acute myocardial infarction.

Objectives: The aim of this study was to compare the procedural characteristics and outcomes of patients with acute myocardial infarction treated with drug-eluting stents (DES) vs. bare metal stents (BMS). Background: DES have been shown to reduce the incidence of restenosis and target vessel revascularization (TVR) in clinical randomized studies when compared with BMS in patients undergoing elective percutaneous intervention. Limited data are available with the use of DES in patients with acute ST-segment elevation myocardial infarction. Methods: Two hundred and sixty-one consecutive patients who presented with myocardial infarction between 7/2001 and 8/2005 were studied. The procedural characteristics, 30-day and 12-month outcomes of 131 patients treated with DES were compared with 130 patients treated with BMS. Results: At 12-months follow-up DES therapy was associated with a substantial decrease in major adverse cardiovascular events (MACE) (HR 0.33; P =0.002), TVR (HR 0.19; P =0.002), and recurrent myocardial infarction (HR 0.23; P =0.051) vs. BMS therapy. Coronary interventions utilizing DES were characterized by a marked increase in the number of stent per target vessel (DES: 1.9 ± 0.9 vs. BMS: 1.38 ± 0.6, P < 0.0001), treatment of bifurcation (DES: 21% vs. BMS: 5%, P =0.0004), and multivessel intervention (DES: 22% vs. BMS: 8%, P =0.003). Conclusion: The routine use of DES in acute myocardial infarction is associated with reduced rates of MACE at 12 months vs BMS, despite a higher rate of complex procedures in the DES treated patients. In addition to its anti-restenosis effect, the improved outcome of patients treated with DES may be linked to a more complete revascularization in association with prolonged clopidogrel therapy. © 2007 Wiley-Liss, Inc.
Immunotherapy for brain tumors: quo vadis?

‘...the last 10 years has seen an increasing number of clinical trials involving immunomodulatory cytokines, dendritic cells, and gene therapy vectors, all of which have advanced our knowledge and understanding of brain tumor immunology.’
Anterior prefrontal cortex contributes to action selection through tracking of recent reward trends

The functions of prefrontal cortex remain enigmatic, especially for its anterior sectors, putatively ranging from planning to self-initiated behavior, social cognition, task switching, and memory. A predominant current theory regarding the most anterior sector, the frontopolar cortex (FPC), is that it is involved in exploring alternative courses of action, but the detailed causal mechanisms remain unknown. Here we investigated this issue using the lesion method, together with a novel model-based analysis. Eight patients with anterior prefrontal brain lesions including the FPC performed a four-armed bandit task known from neuroimaging studies to activate the FPC. Model-based analyses of learning demonstrated a selective deficit in the ability to extrapolate the most recent trend, despite an intact general ability to learn from past rewards. Whereas both brain-damaged and healthy controls used comparisons between the two most recent choice outcomes to infer trends that influenced their decision about the next choice, the group with anterior prefrontal lesions showed a complete absence of this component and instead based their choice entirely on the cumulative reward history. Given that the FPC is thought to be the most evolutionarily recent expansion of primate prefrontal cortex, we suggest that its function may reflect uniquely human adaptations to select and update models of reward contingency in dynamic environments.
Symmetry relations in nucleon decay

Abstract Some experimental consequences of the structure of the effective hamiltonian for nucleon decay are presented. New results concern relations among inclusive decay rates, a striking test of the kinship hypothesis involving μ + polarization, and soft π theorems.
Influence of flanking sequence context on the conformational flexibility of aminofluorene-modified dG adduct in dA mismatch DNA duplexes

When positioned opposite to a dA in a DNA duplex, the prototype arylamine–DNA adduct [N-(2′-deoxyguanosin-yl)-7-fluoro-2-aminofluorene (FAF)] adopts the so-called ‘wedge’ (W) conformation, in which the carcinogen resides in the minor groove of the duplex. All 16 FAF-modified 12-mer NG*N/NAN dA mismatch duplexes (G* = FAF, N = G, A, C, T) exhibited strongly positive induced circular dichroism in the 290–360 nm range (ICD290–360 nm), which supports the W conformation. The ICD290–360 nm intensities were the greatest for duplexes with a 3′-flanking T. The AG*N duplex series showed little adduct-induced destabilization. An exception was the AG*T duplex, which displayed two well-resolved signals in the 19F NMR spectra. This was presumably due to a strong lesion-destabilizing effect of the 3′-T. The flanking T effect was substantiated further by findings with the TG*T duplex, which exhibited greater lesion flexibility and nucleotide excision repair recognition. Adduct conformational heterogeneity decreased in order of TG*T > AG*T > CG*T > AG*A > AG*G > AG*C. The dramatic flanking T effect on W-conformeric duplexes is consistent with the strong dependence of the ICD290-360 on both temperature and salt concentration and could be extended to the arylamine food mutagens that are biologically relevant in humans.
Cryogenic Current Lead Optimization Using Peltier Elements and Configurable Cooling

Current leads for high-temperature superconductor transmission lines impose substantial heat load on the cryogenic system, in particular, for large-current short-distance transmission. Minimization of the heat load is challenging both at the designed operating current and during part load operation, particularly as the current is reduced towards zero. We examine the use of Peltier elements incorporated into current leads and propose the novel concept of configurable cooling to reduce the cryogenic heat load. The use of Peltier elements reduces the cryogenic load by at least 30%, as compared to normal metal leads. The configurable cooling concept uses multiple heat exchangers along the current leads to permit reoptimization of cooling conditions during reduced current operation. The combination of Peltier elements and configurable cooling can reduce the cryogenic load by up to a factor of four during low-current operation. Transient operation of current leads, with and without Peltier elements, and during overload conditions, is presented.
The Effect of the Energy Policy and Conservation Act (EPCA) Regulation of Petroleum Product Prices, 1976-1981

Recent events have led to renewed interest in the petroleum industry. Over the years, the American government has imposed a number of regulatory regimes on this industry. One of the most interesting was the price regulation and product allocation system set in place by the Energy Policy and Conservation Act of 1975 (EPCA) which lasted from 1976 until 1981. To determine the impact of this regime, supply and demand equations are used to derive a reduced form model to test whether the other-things-equal prices of petroleum products were significantly lower or higher during the EPCA period than during the comparatively unregulated 1980s. With some exceptions, the results indicate that the EPCA regulation system either raised prices or had no effect. These results should lead to caution on the part of policy-makers. Even the immediate goal of the policy, lowering prices, did not usually occur.
Fluorescence detection of proteins released by Bacillus subtilis spores during heat shock germination

Fluorescence and absorption spectroscopy were performed on Bacillus subtilis spores which were heat treated at temperatures ranging from 20°C to 90°C. The tryptophan (trp) emission from the spore suspensions treated at temperatures greater than 60°C was shifted towards longer wavelength as compared to the spores which were heat treated at lower temperatures. These spectral changes were the result of proteins released by the spores into the suspension. Trp residues in the emitted proteins are in a more polar environment and therefore exhibit a larger Stokes shift. Fluorescence and absorption measurements show that the concentration of proteins in the supernatant was greater for spores treated at higher temperatures. Electrophoresis gel analysis showed the presence of a 47 KDa protein in the supernatant.
SU‐E‐T‐838: Inverse‐Planned Multi‐Beam Intensity‐Modulated Radiation Therapy versus Three‐Dimensional Conformal Radiotherapy for Left Breast Cancer Patients after Mastectomy

Purpose: The purpose of this study was to compare dose distribution and normal tissue sparing in the treatment of left chest wall, as well as supraclavicular nodes (SCV), and, in one case, internal mammary nodes (IMN) for patients undergoing post mastectomy radiation using three‐dimensional conformal radiotherapy (3D‐CRT) vs. multi‐beam intensity‐modulated radiotherapy(IMRT). Methods: To date, a total of five patients were randomly selected for comparison. All the planning target volumes (PTV) were contoured according to the Breast Cancer Atlas for the Radiation Therapy Planning from Radiation TherapyOncology Group (RTOG). A dose of 5040cGy was prescribed in 28 fractions to each PTV. Two plans were evaluated for each patient, one with beam split tangents and an additional supraclavicular field for 3D‐CRT, and the other one with five inverse‐planned IMRT beams. To obtain the desired skindose, bolus was used every other day. Dose comparison metrics included: PTV homogeneity index (HI) and conformity index (CI), V30 and V5, and mean and maximum doses to normal tissue structures, such as heart, left lung, right lung, contralateral chest wall, and V20 to both lungs. Results: Compared to a conventional 3D‐CRT plan, the five‐field IMRT significantly improved PTV HI and CI, and marginally reduced heart and left lung maximum doses without compromising PTV coverage, but at the same time increased contralateral chest wall and lungdose, and heart V5. Conclusions: Five‐field IMRT plan provides far superior target volume coverage and comparable heart V30 and lung V20 to a conventional plan, while increasing low dose to contralateral side. The use of five beams —instead of 9 or 11, as recommended by other studies‐ reduces the treatment time and, consequently, possible setup and internal organ motion errors. Further clinical studies are needed to determine whether IMRT improves tumor control or reduces acute or late toxicities when compared to 3D‐CRT.
Effect of ethanol on the binding of conformationally rigid and labile ligands of opioid receptors to rat brain membranes.

Abstract The effect of ethanol on the binding of conformationally rigid and labile ligands for μ and δ opioid receptors to rat brain membranes was determined. The β ligands used for the studies were [ 3 H]naltrexone and [ 3 H ] Tyr- d -Ala-Gly -N- MePhe-Gly-ol (DAGO), and δ ligands used were [ 3 H]Tyr- d -Ser-Gly-Phe-Leu-Thr and [ 3 H]Tyr- d -Ala-Gly-Phe-Leu (DADLE). The binding of all the opioid ligands was inhibited by ethanol in a concentration-dependent manner. For μ ligands the inhibition was greater for [ 3 H]DAGO binding than for the binding of [ 3 H]naltrexone. For δ ligands, the inhibition by ethanol of the binding of [ 3 H]DADLE was greater than that of [ 3 H]DSTLE. Fourier-transform infrared (FT-IR) spectroscopy was used to determine the conformation of opioid peptides. The data indicated that the conformation of peptides was altered in the presence of ethanol. The results suggest that ethanol inhibits the binding of both μ and δ opioid ligands with greater inhibition observed with conformationally labile ligands. Finally, the alteration in the conformation of the peptide ligands by ethanol, in addition to denaturation of the receptor protein, may also account for the observed inhibitory effect of ethanol on brain opioid receptors.
Performance of Oxygen Fuel Cell Cathodes catalysed with Boron Carbide

THE development of suitable inexpensive electrode catalysts is one of the major tasks confronting fuel cell technologists. The platinum group metals have received considerable attention as catalysts, despite their high cost, because of their combination of stability and high catalytic activity. It has been pointed out1, however, that only a small amount of the world demand for power could be generated by hydrogen/oxygen fuel cells using the entire world production of platinum. The situation is equally unattractive for the other platinum-group metals. Consequently, for any broad-based terrestrial application of fuel cells, it is necessary to find a cheaper and more readily available material. There have been several publications describing some anode2–6 and cathode7,8 catalysts that are cheaper than the platinum-group metals.
A detection-identification process with geometric target detection and subpixel spectral visualization

In this paper we present a new methodology for automated target detection and identification in hyperspectral imagery. The standard paradigm for target detection in hyperspectral imagery is to run a detection algorithm, typically statistical in nature, and visually inspect each high-scoring pixel to decide whether it is a true detection or a false alarm. Detection filters have constant false alarm rates (CFARs) approaching 10−5, but these can still result in a large number of false alarms given multiple images and a large number of target materials. Here we introduce a new methodology for target detection and identification in hyperspectral imagery in conjunction with a data-driven target detection algorithm that shows promise for hard targets. The result is a greatly reduced false alarm rate and a practical methodology for aiding an analyst in quantitatively evaluating detected pixels.
Alterations of neutrophil L-selectin and CD18 expression by tobacco smoke: implications for periodontal diseases

Alterations in neutrophil functions by both chronic low levels of tobacco and by acute short-term higher levels of tobacco smoke, as encountered during the act of smoking, may play a role in the pathogenesis of periodontal diseases in smokers. Among the early migration events of neutrophil function is the alteration in surface expression of L-selectin and the CD11/18 integrins. In the present study we examined the effect of in vitro smoke exposure and nicotine alone on the expression of these 2 adhesion molecules in neutrophils from smokers and non-smokers. We also determined the physiological relevance of this in vitro system by assessing the levels of nicotine exposure in this in vitro system and comparing these levels to acute and chronic levels of nicotine in saliva and gingival crevicular fluid. Peripheral neutrophils were isolated from the blood of smokers (> 1 pack/d) and non-smokers and incubated in vitro with either cigarette smoke (0-5 min), 10(-7) M F-met-leu-phe, or nicotine alone at 1.62 mg/ml to 162 ng/ml (10(-2) M-10(-6) M). The neutrophils were then incubated with fluoresceine conjugated anti-Leu8 (L-selectin), anti-CD18 (CD18 integrin), or gamma-4 (non-specific control), fixed and analyzed by flow cytometry. With cigarette smoke exposure, there was an approximate 75% shedding of L-selectin in both smokers and non-smokers with no marked difference between groups at 1-5 min of smoke exposure. Cigarette smoke exposure resulted in a 15-20% increase in CD18 expression in both smokers and non-smokers. At all time points, there was slightly greater but statistically insignificant expression of CD18 integrin in non-smokers when compared to smokers. These patterns of CD18 increases and L-selectin shedding were similar in magnitude to incubations with 10(-7) M F-met-leu-phe. Acute smoke exposure resulted in elevation of nicotine in the smoke box to 529 ng/ml at 5 min, in saliva from 109.2 ng/ml before smoking to 1821.4 ng/ml after smoking, and in gingival crevicular fluid to 5961 ng/ml after smoking. No significant alterations in L-selectin or CD18 expression were noted with in vitro nicotine from 1.62 mg/ml to 162 ng/ml.
Investment and Diversification in the American Whaling Industry

This article analyzes the connection between investment decisions and financing arrangements in the nineteenth-century American whaling industry. Managers of whaling ventures shared their risks by selling some equity claims but retained a substantial portion due to moral hazard considerations. As a result, they had little incentive to consider the covariance between their own returns, and those of others, in planning their voyages. This stifled diversity in whaling voyages and increased industry-wide risk. The analysis suggests a link between financial market development, or the extent of risk sharing in financial markets, and the range of economic activities pursued. n October 1851 news of the whaling fleet's summer season in the North Pacific reached American ports. The reports were devastating: due to the unexpectedly early incursion of ice in the Bering Straits, many of the vessels were badly damaged, and eight were lost. Conditions were so difficult that even the vessels that escaped serious harm were unable to pursue whales. In a letter home, the first mate of one New Bedford vessel described the ordeal:
The ABCs of Performing Highly Effective Think-Alouds

The purpose of this article is to provide teachers with examples of how to perform effective think-alouds. Twelve think-alouds are described. A rationale for their use in kindergarten through grade 5 is also included. In addition, this article was designed to provide teachers with lessons and activities to assist students in developing the ability to perform think-alouds independently, without teacher prompting. The last section of the article provides teachers with methods of assessing think-alouds.
Use of ultrasonographic guidance for needle localization of osteoid osteoma of the capitate.

Osteoid osteomas are benign small (typically less than 1.5 cm) osteoid-forming tumors accounting for 10–12% of all primary bone tumors. The most common sites are in the appendicular skeleton, but osteoid osteomas can occur in any bone. Classically, these tumors appear as a small sclerotic lesion with a circular lucent defect, the nidus. The nidus represents “osteoid and interconnected bone superimposed on highly vascularized connective tissue” [1, 2]. Treatment most commonly consists of medical management with nonsteroidal anti-inflammatory drugs (NSAIDs), surgical excision, and/or radiofrequency ablation. Fast scanning now made possible with multidetector computed tomography (CT) has resulted in CT-guided drilling (curettage or burr) and CT-guided percutaneous resection. More recently, there has been increased use of radiofrequency ablation of osteoid osteoma utilizing percutaneous guidance with CT [3–6]. This paper illustrates a case of an osteoid osteoma of the wrist, which was treated with surgical excision and radiofrequency ablation after needle localization under ultrasound guidance.
Effect of the "cough technique" on cryotherapy freezing temperature.

Abstract Objective To assess the impact of the cough technique on the tip temperature reached in a cryotherapy device commonly used to treat precancerous cervical lesions. Methods During February to March 2009, bench testing was conducted in Peru on 3 Wallach LL100 cryotherapy units using locally obtained carbon dioxide as the refrigerant. The temperature at the cryo tip was measured continuously with a thermocouple. Mean temperatures recorded with and without the cough technique were compared across the 3 cryotherapy devices. Results Higher mean temperatures were observed with the cough technique (– 21.7 °C [95% CI, – 23.0 to – 20.4]; – 22.0 °C [95% CI, – 24.2 to – 19.7]; – 29.4 °C [95% CI, – 30.3 to – 28.6]) compared with mean temperatures observed with the standard procedure (– 38.6 °C [95% CI, – 44.8 to – 32.4]; – 36.0 °C [95% CI, – 43.5 to – 28.5]; – 41.4 °C [95% CI, – 49.8 to – 33.0]). No test performed with the cough technique reached a temperature below – 33 °C. Conclusion Higher temperatures were observed when the cough technique was used. Caution should be exercised by practitioners who use this procedure when performing cryotherapy because the temperatures obtained may not be sufficient to destroy precancerous tissue.
Incorporating climate change and exotic species into forecasts of riparian forest distribution

We examined the impact climate change (CC) will have on the availability of climatically suitable habitat for three native and one exotic riparian species. Due to its increasing prevalence in arid regions throughout the western US, we predicted that an exotic species, Tamarix, would have the greatest increase in suitable habitat relative to native counterparts under CC. We used an ecological niche model to predict range shifts of Populus fremontii, Salix gooddingii, Salix exigua and Tamarix, from present day to 2080s, under five general circulation models and one climate change scenario (A1B). Four major findings emerged. 1) Contrary to our original hypothesis, P. fremontii is projected to have the greatest increase in suitable habitat under CC, followed closely by Tamarix. 2) Of the native species, S. gooddingii and S. exigua showed the greatest loss in predicted suitable habitat due to CC. 3) Nearly 80 percent of future P. fremontii and Salix habitat is predicted to be affected by either CC or Tamarix by the 2080s. 4) By the 2080s, 20 percent of S. gooddingii habitat is projected to be affected by both Tamarix and CC concurrently, followed by S. exigua (19 percent) and P. fremontii (13 percent). In summary, while climate change alone will negatively impact both native willow species, Tamarix is likely to affect a larger portion of all three native species' distributions. We discuss these and other results in the context of prioritizing restoration and conservation efforts to optimize future productivity and biodiversity. As we are accounting for only direct effects of CC and Tamarix on native habitat, we present a possible hierarchy of effects- from the direct to the indirect- and discuss the potential for the indirect to outweigh the direct effects. Our results highlight the need to account for simultaneous challenges in the face of CC.