cssi/SciSciGPT-SciSciNet huggingface dataset:
Decaf: moving device drivers to a modern language

Writing code to interact with external devices is inherently difficult, and the added demands of writing device drivers in C for kernel mode compounds the problem. This environment is complex and brittle, leading to increased development costs and, in many cases, unreliable code. Previous solutions to this problem ignore the cost of migrating drivers to a better programming environment and require writing new drivers from scratch or even adopting a new operating system. We present Decaf Drivers, a system for incrementally converting existing Linux kernel drivers to Java programs in user mode. With support from program-analysis tools, Decaf separates out performance-sensitive code and generates a customized kernel interface that allows the remaining code to be moved to Java. With this interface, a programmer can incrementally convert driver code in C to a Java decaf driver. The Decaf Drivers system achieves performance close to native kernel drivers and requires almost no changes to the Linux kernel. Thus, Decaf Drivers enables driver programming to advance into the era of modern programming languages without requiring a complete rewrite of operating systems or drivers. With five drivers converted to Java, we show that Decaf Drivers can (1) move the majority of a driver's code out of the kernel, (2) reduce the amount of driver code, (3) detect broken error handling at compile time with exceptions, (4) gracefully evolve as driver and kernel code and data structures change, and (5) perform within one percent of native kernel-only drivers.
Imatinib Mesylate Therapy for Patients (pts) with Polycythemia Vera (PV).

Imatinib is a potent inhibitor of tyrosine kinases, including abl, c-kit, and platelet-derived growth factor receptor (PDGFR). A role for PDGF in PV has been suspected, and direct inhibition of PV colonies with imatinib has been reported. We initiated a phase II trial of imatinib in pts with PV diagnosed by the Polycythemia Vera Study Group criteria. Pts were treated with imatinib at 400 mg daily; if no significant response after 1 month (mo) of therapy, the dose could be escalated to 800 mg daily. Hydroxyurea could be used only during the first mo of therapy, but anagrelide was allowed at any time. 9 patients have been treated (6 male, 3 female). Median age was 51 years (yrs) (range 28 to 72 yrs); median duration of PV was 8 years (range 1/4–35 years). ECOG performance status was 0 for 2 pts and 1 for 7 pts. Most common symptoms included fatigue (n=7), intractable pruritus (n=5) and headache (n=4). 4 pts had splenomegaly, 1 had hepatomegaly, and 1 had prior splenectomy. All patients were dependent on repeated phlebotomies. All pts had diploid cytogenetics except one who had 20q − (prior therapy with 32 P). FISH and PCR confirmed absence of Bcr-Abl translocation. After a median follow-up of 4 mo (range, 2 to 37 mo), 3 pts have ≥50% reduction in phlebotomy requirements. These include one pt with complete remission defined as hemoglobin
Trends in the Prevalence of Severe Obesity and Bariatric Surgery Access: A State-Level Analysis from 2011 to 2014.

Abstract Background: Understanding what proportion of the eligible population is undergoing bariatric surgery at the state level provides critical insight into characterizing bariatric surgery access. We sought to describe statewide trends in severe obesity demographics and report bariatric surgery volume in Wisconsin from 2011 to 2014. Methods: Self-reported data from the Behavioral Risk Factor Surveillance System (BRFSS) were used to calculate prevalence rates of severe obesity (class II and III) in Wisconsin. Bariatric surgery volume data were analyzed from the Wisconsin Hospital Association. A survey was sent to all American Society for Metabolic and Bariatric Surgery member bariatric surgeons in Wisconsin to assess perspectives on bariatric surgery access, insurance coverage, and referral processes. Results: The prevalence of severe obesity in Wisconsin increased by 30% from 2011 to 2014 (10.4%–13.2%; P = .035); the odds of severe obesity nearly doubled for adults age 20–39 (odds ratio [OR] 1.9, 95% ...
Exposure to intermittent hypoxia and sustained hypercapnia reduces therapeutic CPAP in participants with obstructive sleep apnea.

Our new finding is that exposure to mild intermittent hypoxia reduced the therapeutic pressure required to treat sleep apnea. These findings are consistent with previous results, which have shown t...
Sovereign Comity: Factors in Recognizing Tribal Court Criminal Convictions in State and Federal Courts

State and federal courts increasingly are being confronted with prosecutors moving the court to consider prior convictions in American Indian tribal courts during the sentencing phase, and sometimes earlier. If the conviction being introduced occurred in state or federal court, the instant court would be obligated to give full faith and credit to that conviction. But if the prior conviction occurred in a tribal court, state and federal courts are often confronted with unforeseen complexities. This paper is intended to parse through much of the political baggage associated with recognizing tribal court convictions. To be frank, the law is unsettled, leaving little guidance for state and federal judges in these cases, while at the same time granting enormous discretion to judges on the questions involved. The first part of this paper will provide a quick overview of the constitutional status of Indian tribes and tribal courts, as well providing a basic but sufficient introduction to relevant principles of federal Indian law. The second part will offer a summary of criminal jurisdiction in Indian Country and, in particular, what role tribes play – and how well they play it. The third part offers a short description of the key cases in the field, as well as relevant federal and state statutes, and state court rules. It also offers a short normative argument on the question of what state and federal court judges who are confronted with prior tribal court convictions should look for in these cases, especially where the defendants convicted in tribal court are not represented by counsel.
Optimization of dipeptidic inhibitors of cathepsin L for improved Toxoplasma gondii selectivity and CNS permeability.

Abstract The neurotropic protozoan Toxoplasma gondii is the second leading cause of death due to foodborne illness in the US, and has been designated as one of five neglected parasitic infections by the Center for Disease Control and Prevention. Currently, no treatment options exist for the chronic dormant-phase Toxoplasma infection in the central nervous system (CNS). T. gondii cathepsin L (TgCPL) has recently been implicated as a novel viable target for the treatment of chronic toxoplasmosis. In this study, we report the first body of SAR work aimed at developing potent inhibitors of TgCPL with selectivity vs the human cathepsin L. Starting from a known inhibitor of human cathepsin L, and guided by structure-based design, we were able to modulate the selectivity for Toxoplasma vs human CPL by nearly 50-fold while modifying physiochemical properties to be more favorable for metabolic stability and CNS penetrance. The overall potency of our inhibitors towards TgCPL was improved from 2 μM to as low as 110 nM and we successfully demonstrated that an optimized analog 18b is capable of crossing the BBB (0.5 brain/plasma). This work is an important first step toward development of a CNS-penetrant probe to validate TgCPL as a feasible target for the treatment of chronic toxoplasmosis.
Blood Protozoa: In Search of the Holy Grail

The earliest case description of sleeping sickness, or African trypanosomiasis, was reported by the Arab historian Ibn Khaldun (1332–1406) about Sultan Mari Jata, Emperor of Mali. He wrote: “He told me that Jata had been smitten by the sleeping illness, a disease which frequently afflicts the inhabitants of that climate… Those afflicted are virtually never awake or alert. The sickness harms the patient and continues until he perishes”. However it was only with the advent of European conquest and colonization of Africa in the nineteenth century that a series of large scale epidemics of sleeping sickness started. The worst epidemic occurred in the Congo Basin around 1889 where it was estimated that between 300,000 and 500,000 people died under the Belgian colonial authorities. This was a consequence of forced dislocation of populations and indentured labor for the purposes of construction of roads and railways, opening of new lands in tsetse infested areas for plantations of cash crops and the collection of rubber, and harsh imposition of new taxes on already vulnerable populations. New and relatively fast means of transport by railways meant too that trypanosome strains were transferred from one area to another, and the “cordon sanitaire” maintained in the past by long distances between villages and limited contact between local tribal communities had been broken.
Reduced oxygen concentration for the resuscitation of infants with congenital diaphragmatic hernia.

To evaluate whether infants with congenital diaphragmatic hernia (CDH) can be safely resuscitated with a reduced starting fraction of inspired oxygen (FiO2) of 0.5. A retrospective cohort study comparing 68 patients resuscitated with starting FiO2 0.5 to 45 historical controls resuscitated with starting FiO2 1.0. Reduced starting FiO2 had no adverse effect upon survival, duration of intubation, need for ECMO, duration of ECMO, or time to surgery. Furthermore, it produced no increase in complications, adverse neurological events, or neurodevelopmental delay. The need to subsequently increase FiO2 to 1.0 was associated with female sex, lower gestational age, liver up, lower lung volume–head circumference ratio, decreased survival, a higher incidence of ECMO, longer time to surgery, periventricular leukomalacia, and lower neurodevelopmental motor scores. Starting FiO2 0.5 may be safe for the resuscitation of CDH infants. The need to increase FiO2 to 1.0 during resuscitation is associated with worse outcomes.
Qualitative reasoning of Bayesian belief using meta-knowledge

Ordering composite hypotheses in a Bayesian network based on its associated a posteriori probabilities can be exponentially hard. This paper discusses a qualitative reasoning approach which reduces the computational complexity of deriving a partial ordering of composite hypotheses. Such a reasoning makes use of the meta-knowledge about the causal relationships among individual hypotheses to deduce qualitative conclusions about the ordering of local composite hypotheses. By doing so, we can employ "divide and conquer" strategy to derive the global ordering of the composite hypotheses from a set of local ordering in which consistencies are guaranteed. We view the contribution of this research is on the integration of qualitative reasoning with the use of local computations to find not only the most likely composite hypotheses, but also the partial ordering of the composite hypotheses.
History of liver and other splanchnic organ transplantation

In the late 1950s, transplant models were developed in dogs for all of the intra-abdominal organs (Fig. 1). The most fruitful of these efforts involved the liver (Table 1) (Starzl TE (1969a) In: Starzl TE (ed) Experience in hepatic transplantation. WB Saunders, Philadelphia). In addition to its direct clinical application, the research in liver transplantation yielded new information about the metabolic interrelations of the intra-abdominal viscera in disease and health; a more profound understanding of the mechanisms of organ alloengraftment; and the addition of new nontransplant procedures to the treatment armamentarium against gastrointestinal diseases.
Preoperative Evaluation: Physical Examination

Physical examination is an invaluable tool that assists in diagnosis and evaluation of the patient and has been used since the advent of medicine. As nephrologists and interventionists, we are well aware that hemodialysis vascular access problems represent an exceedingly important part of the management of the end-stage renal disease patient. A detailed physical examination is an excellent, noninvasive, and accurate method for initial evaluation and helps guide our interventional procedures. This chapter describes the information that can be obtained through a thorough physical examination of the dialysis vascular access.
Physics and Applications of Doping Superlattices

Semiconductor superlattices can be fabricated by priodic variation of either composition (AlxGai1-xAs — GaAs, e.g.) or doping (n-i-p-i, e.g.). During the past decade they have proven as ideal model substances for the study of the electronic properties of two-dimensional quantum systems, but also as an interesting material for new electronic and opto-electronic devices. The special interest in n-i-p-i doping superlattices originates from the “tunabiiity” of their electronic structure, a feature which is due to an “indirect band gap in real space” and which is not shown by any uniform semiconductor nor by compositional superlattices. In this lecture the basic theoretical concept of n-i-p-i doping superlattices is briefly reviewed. The emphasis is on a discussion of recent theoretical and experimental investigations of new phenomena in doping superlattices and on their implications for device applications. This includes photo response studies of GaAs n-i-p-i structures, where room temperature values of photoconductive gain in excess of 107 have been obtained. Applications for fast high-detectivity detectors, based on a combination of the unusual transport properties of n-i-p-i’s with selective n- and p-contacts will be discussed. We report on room temperature studies of tunable photo- and electroluminescence in conventional n-i-p-i structures and on temperature-dependent and time-resolved luminescence measurements on type-II hetero n-i-p-i’s In the latter case contributions from different subbands can be clearly resolved as individual lines, due to strongly reduced impurity broadening- of the subband levels. We discuss recent experimental and theoretical results on the tunable absorption coefficient of n-i-p-i’s and on potential applications for optical modulators and switches. Finally, we will discuss the non-linear optical properties conventional and type-1 hetero n-i-p-i’s which result from the unique combination of long electron-hole recombination lifetimes and of weak, but still significant absorption at photon energies far below the band gap of the host material(s) of the n-i-p-i structure. These properties again relate to interesting basic phenomena (carrier- induced band gap shrinkage, excitonic absorption, oversaturation of quantum-well absorption) as well as to device applications as purely optical logic components or optical switches.
Women and Cartography in the Progressive Era

In the twenty-first century we speak of a geospatial revolution, but over one hundred years ago another mapping revolution was in motion. Women’s lives were in motion: they were playing a greater role in public on a variety of fronts. As women became more mobile (physically, socially, politically), they used and created geographic knowledge and maps. The maps created by American women were in motion too: created, shared, distributed as they worked to transform their landscapes. Long overlooked, this women’s work represents maps and mapping that today we would term community or participatory mapping, critical cartography and public geography. These historic examples of women-generated mapping represent the adoption of cartography and geography as part of women’s work. While cartography and map use are not new, the adoption and application of this technology and form of communication in women’s work and in multiple examples in the context of their social work, is unprecedented. This study explores the implications of women’s use of this technology in creating and presenting information and knowledge and wielding it to their own ends. This pioneering and original book will be essential reading for those working in Geography, Gender Studies, Women’s Studies, Politics and History.
Contemplative faculty in the United States

Contemplative faculty are higher education professors who regularly implement contemplative approaches in their teaching to address their students’ social and emotional needs, promote creativity and nurture stable behavior. Through an analysis of contemplative faculty narratives this study explored contemplative higher education faculty perceptions on the use of contemplative pedagogy in the classroom and its impact on student mental and emotional health. After experiencing the benefits of contemplative practice for themselves, faculty wanted to pass along these practices to their students to address mental and emotional wellbeing. Faculty perceived specific benefits for their students including focus and acceptance.
Operative Times Can Predict and Are Correlated With Lengths-of-Stay in Primary Total Knee Arthroplasty: A Nationwide Database Study.

Abstract Background The specific influence of operative times on lengths-of-stay (LOS) has not been well assessed and is therefore an important topic of evaluation for multiple reasons, including potential economic implication. The purpose of this study is to (1) identify predictors of longer operative times; (2) identify predictors of longer LOS; and (3) evaluate the effects of operative times on LOS in primary total knee arthroplasty (TKA). Methods The National Surgical Quality Improvement Program database was queried for primary TKAs performed between 2008 and 2016, yielding 225,344 cases. Multivariate analysis was performed to determine the effect of operative times on LOS after adjusting for patient factors. Univariate analyses were performed with 1-way analysis of variance (ANOVA), linear regression, and independent sample t-tests where appropriate. Multivariate analysis was performed with a multiple linear regression model adjusted for patient age, sex, and body mass index (BMI). Results The mean operative time was 93 ± 35 minutes and the mean LOS was 3 ± 3 days. Young age, male sex, and obesity were predictors of longer operative times (P Conclusion This study provides unique insight by directly correlating operative times to LOS in over 200,000 TKAs. The results from this study indicate that there is a strong correlation between operative times and LOS, so that operative time had a greater association than age, sex, and BMI with postoperative TKA LOS.
Abstract WMP58: Blacks Have Higher Risk of 1-Year Recurrent Ischemic Stroke: An Analysis of White and Black Medicare Beneficiaries 1999-2013

Introduction: Blacks have a higher incidence of stroke compared with whites. Most stroke survivors in the United States are 65 years and older but few data are available on racial differences in re...
Neuronally Enriched RUFY3 Is Required for Caspase-Mediated Axon Degeneration

Summary Selective synaptic and axonal degeneration are critical aspects of both brain development and neurodegenerative disease. Inhibition of caspase signaling in neurons is a potential therapeutic strategy for neurodegenerative disease, but no neuron-specific modulators of caspase signaling have been described. Using a mass spectrometry approach, we discovered that RUFY3, a neuronally enriched protein, is essential for caspase-mediated degeneration of TRKA+ sensory axons in vitro and in vivo. Deletion of Rufy3 protects axons from degeneration, even in the presence of activated CASP3 that is competent to cleave endogenous substrates. Dephosphorylation of RUFY3 at residue S34 appears required for axon degeneration, providing a potential mechanism for neurons to locally control caspase-driven degeneration. Neuronally enriched RUFY3 thus provides an entry point for understanding non-apoptotic functions of CASP3 and a potential target to modulate caspase signaling specifically in neurons for neurodegenerative disease.
Two Approaches to Nonlinear Least Squares Adjustments

The following discussion of Newton-Raphson and Newton-Gauss applied to least squares adjustment of nonlinear conditions with parameters is abstracted from the longer paper, “Modern Trends in Adjust...
Optimizing biodegradable nanoparticle size for tissue-specific delivery

Nanoparticles (NPs) are promising vehicles for drug delivery because of their potential to target specific tissues [1]. Although it is known that NP size plays a critical role in determining their biological activity, there are few quantitative studies of the role of NP size in determining biodistribution after systemic administration. Here, we engineered fluorescent, biodegradable poly(lactic-co-glycolic acid) (PLGA) NPs in a range of sizes (120-440nm) utilizing a microfluidic platform and used these NPs to determine the effect of diameter on bulk tissue and cellular distribution after systemic administration. We demonstrate that small NPs (∼120nm) exhibit enhanced uptake in bulk lung and bone marrow, while larger NPs are sequestered in the liver and spleen. We also show that small NPs (∼120nm) access specific alveolar cell populations and hematopoietic stem and progenitor cells more readily than larger NPs. Our results suggest that size of PLGA NPs can be used to tune delivery to certain tissues and cell populations in vivo.
Postoperative management factors affect urinary retention following posterior spinal fusion for adolescent idiopathic scoliosis.

Retrospective cohort study. This study investigates postoperative urinary retention (POUR) following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) and the effects of postoperative analgesia and mobility on retention. High opioid use and decreased postoperative mobility are proposed risk factors for retention in adults. There is a paucity of literature on POUR in the adolescent population undergoing surgery for AIS. The impact of pain control and mobility on POUR in these patients is unknown. A retrospective cohort study was conducted of adolescents (11–18 years) undergoing elective PSF for AIS at a single institution (2012–2018). POUR was defined as the inability to void > 8 h after catheter removal. Possible risk factors for retention including opioid usage and ambulatory status at the time of catheter removal were assessed on univariate and binomial logistic regression analyses. One hundred and thirty-six patients were included, with 21 (15.4%) experiencing POUR. On the day of catheter removal, 24 patients had not attempted ambulation; these patients had 2.5 times higher rate of POUR than those who were walking (30% vs. 12%, p = 0.04). Patients who developed retention ambulated a mean threefold shorter distance than those without POUR (45 vs. 136 feet, p = 0.04). On binomial logistic regression, decreased ambulation distance was associated with retention (p = 0.038). While opioid use was not significant on univariate analysis, higher opioid use on the day of catheter removal predicted retention on logistic regression (p = 0.001). POUR resolved in all patients (median duration 0.5 days, range 0–12 days). The development of POUR after PSF for AIS affects one in six patients but resolves quickly. Non-ambulatory patients and patients who received large doses of opioids on the day of catheter removal were more likely to develop POUR. III.
Exploiting fluorescent zinc(ii) and copper(ii) complexes for enantiomeric excess determination of hydroxycarboxylates.

Chiral hydroxycarboxylates are useful compounds in the syntheses of natural products, pharmaceutical intermediates, and drugs. Here, we report on Zn- and Cu-containing sensors that can distinguish between enantiomers of hydroxycarboxylates through the quenching or the enhancement of fluorescence. A Zn-based sensor—[ZnRRL]2+—is used in an assay to perform analyses of enantiomeric excess (% ee) of scalemic mixtures of α-hydroxycarboxylates and various drugs including the statin drug atorvastatin. This assay enables determination of mixtures of enantiomers across the range from 0 to 100% ee.
Predictors of postoperative opioid use in NCAA Division 1 collegiate athletes

Abstract Background With the growing severity of the opioid epidemic in the United States, it is increasingly important for surgeons to understand the opioid requirements of their patients, especially in the population of collegiate athletes. The purpose of this study is to determine variables influencing the quantity of total morphine milligram equivalents (TMEs) and percent of prescribed TMEs used following surgery in Division 1 collegiate athletes. Methods A consecutive cohort of 25 Division 1 collegiate athletes from one institution undergoing knee or shoulder surgery at a single hospital for sport-related injuries between December 2016 and December 2018 were retrospectively identified. A regional prescription drug monitoring program was used to verify discharge medications. Patients were instructed to bring their unused pills to a follow-up visit 2–4 days after surgery. The amount of opioids prescribed and used was standardized using morphine conversion factors to determine milligram morphine equivalents. TMEs Used was determined by summing the amount of morphine equivalents the patients used of their discharge opioids. The Percent of TMEs Used was determined by dividing the amount of TMEs used by the amount of TMEs prescribed at discharge. Demographic variables and other regulated prescriptions were also recorded. Bivariate and multivariate analyses were used to determine variables that influence and/or predict the amount of TMEs Used and Percent of TMEs Used. Results Multivariable regression found that a history of non-analgesic controlled substance use (p = 0.027) and the amount of TMEs prescribed at discharge (p Conclusions Providers for Division I collegiate athletes should carefully consider a patient’s nonanalgesic controlled substance history, comorbidities, and prescribed opioid burden when planning a postoperative pain management course.
Analysis and Classification of Vaccine Dialogue in the Coronavirus Era

As the coronavirus tears through our global community, the world pins its hopes on the expedient availability of a safe and effective vaccine. In the U.S, however, mere mention of vaccines galvanizes a community that remains steadfastly opposed to them. This paper analyzes the vaccine dialogue on Twitter in the coronavirus era, using the data collected a week after President Trump's announcement of Operation Warp Speed. These tweets are explored in three ways. Informal opinion mining reveals both concerns and support; the anti-vaxx community is vociferous in opposing the vaccine, spreading misinformation, spinning conspiracies and whipping hysteria. Significant hesitation about the safety of the Covid-19 vaccine is also expressed in particular because of its rapid deployment. The pro-vaxx community counters this opposition by pointing to prior successes of immunizations as well as by mocking the anti-vaxx attitudes. A comparison of the social features of the anti-vaxx and pro-vaxx tweets suggests that the anti-vaxx community has gained steam on social media platforms and is better connected than the pro-vaxx community, which may lead to a penetration of discordant information through the online world. Identifying and labeling tweets that sow discordant information is one way to prevent their spread, which is facilitated by our classification framework that can distinguish between the anti-vaxx and pro-vaxx tweets with an accuracy of over 80%. Taken together, our results suggest that unless a concerted effort is made to dispel these myths and misgivings, the fringe anti-vaxx minority is likely to become an outspoken majority by dragging many skeptics into their fold, and hence, hinder herd immunity.
Sinodalità come rinnovamento ecclesiale in Papa Francesco

Il pontificato di Francesco ha portato al centro del magistero papale sulla chiesa il tema della sinodalita. L’articolo analizza i principali pronunciamenti di Francesco sul tema della sinodalita, identificando una prima fase di lancio del tema (2013-2016), un intermezzo (2016-2018), e una seconda fase (2019-2021) di maggiore cautela improntata all’enfasi sulla distinzione tra sinodalita ecclesiale e funzionalismo di tipo parlamentare.
Reusability of autoclaved 3D printed polypropylene compared to a glass filled polypropylene composite

Health care waste can be a costly expenditure for facilities as specific disposal methods must be used to prevent the spread of pathogens. If more multi-use medical devices were available, it could potentially relieve some of this burden; however, sterilization between uses is important in preventing disease transmission. 3D printing has the ability to easily create custom medical devices at a low cost, but the majority of filaments utilized cannot survive steam sterilization. Polypropylene (PP) can withstand autoclave temperatures, but is difficult to print as it warps and shrinks during printing; however, a composite PP filament reduces these effects. Commercially available PP and glass filled PP (GFPP) filaments were successfully 3D printed into 30 × 30 × 30 mm cubes with no shrinking or warping and were autoclaved. The 134 °C autoclave temperature was too high as several cubes melted after two to three rounds, but both PP and GFPP cubes displayed minimal changes in mass and volume after one, four, seven, and ten rounds of autoclaving at 121 °C. GFPP cubes autoclaved zero, four, seven, and ten times had significantly smaller average compressive stress values compared to all PP groups, but the GFPP cubes autoclaved once were only less than PP cubes autoclaved zero, seven and ten times. GFPP cubes autoclaved zero, one, four, and seven times also deformed less indicating that the embedded glass fibers provided additional strength. While a single method was found that successfully printed PP and GFPP cubes that were able to survive up to ten rounds of autoclaving, future work should include further investigation into the mechanical properties and increasing the number of autoclave rounds.
Melanoma Resistance to Photodynamic Therapy

Melanoma is a dreaded form of skin cancer caused by the malignant transformation of skin melanocytes and can be highly aggressive and has a rapidly growing incidence and elevated mortality and a poor prognosis at an advanced stage. Because melanomas are intrinsically resistant to conventional radiotherapy and chemotherapy, many alternative treatment approaches are being developed. Photodynamic therapy (PDT) has shown promising results for the treatment of different types of cancer. This therapy involves administration of a photosensitizer (PS), which on excitation after suitable irradiation generates singlet oxygen and other cytotoxic reactive oxygen species (ROS), thus, killing the cancer cells. Unfortunately, melanoma is considered to be resistant to PDT. There are many different reasons for this resistance including: (1) optical interference by melanin; (2) the anti-oxidant effect of melanin (3) sequestration of PS inside melanosomes (4) efflux of PS by multi-drug transporters and (5) errors in apoptotic pathways. Various approaches to overcome this PDT resistance of melanoma are being evaluated such as the use of agents that overcome the apoptotic defects, or hinder the efflux of PS, or use of methods to reduce the quantity or the pigmentation of the melanin. The introduction of highly active PS absorbing in the 700–800 nm near infrared (NIR) spectral region, and new advances in two-photon excitation of PS, together with PS linked to upconverting nanoparticles may overcome the optical interference of melanin. Finally, employing immunotherapy and, thus, exploiting the ability of PDT to activate the host immune system against the treated tumor, may also play a role in allowing PDT to overcome resistant melanomas.
Viral Transneuronal Tracing Technology: Defining the Synaptic Organisation of Neural Circuits

Viral transneuronal tracing is a powerful approach that has been widely used to define the cellular organisation of functionally defined systems that underlie brain function. The method exploits the ability of neurotropic viruses to infect neurons and produce infectious progeny that pass through the intimate synaptic connections among neurons to infect polysynaptic pathways. A number of important technological advances in recent years have dramatically improved the ability of this experimental approach to define the synaptology of complex neural circuits. In this chapter we provide an overview of the method as well as mechanisms that contribute to its effectiveness for circuit analysis. We focus on alpha herpesviruses and rabies virus as these pathogens have been most widely applied in transneuronal tracing studies. Key Concepts: Viral transneuronal tracing exploits the invasive properties of neurotropic viruses. Knowledge of the functional organisation of the viral genome is fundamental to an informed application of the viral transneuronal tracing method. Circuit architecture is influential in determining the progression of viral infection through a neural circuit. Isogenic recombinant viruses expressing unique reporters permit analysis of collateralisation of projections within complex neural circuits. Colocalisation of reporters of infection with neurotransmitters and peptides permits neurochemical phenotyping of neurons within labelled circuits. Keywords: alpha herpesvirus; pseudorabies; rabies; transneuronal; transsynaptic
Identifying mental tasks from spontaneous EEG: Signal representation and spatial analysis

Feedforward neural networks are trained to classify half-second segments of six-channel, EEG data into one of five classes corresponding to five mental tasks performed by one subject. Two and three-layer neural networks are trained on a 128-processor SIMD computer using 10-fold cross-validation and early stopping to limit over-fitting. Four representations of the EEG signals, based on autoregressive (AR) models and Fourier Transforms, are compared. Using the AR representation and averaging over consecutive segments, an average of 72% of the test segments are correctly classified; for some test sets 100% are correctly classified. Cluster arm, is of the resulting hidden-unit weight vectors suggests which electrodes and representation components are the most relevant to the classification problem.
The distribution and clearance of (2S,6S)‐hydroxynorketamine, an active ketamine metabolite, in Wistar rats

The distribution, clearance, and bioavailability of (2S,6S)-hydroxynorketamine has been studied in the Wistar rat. The plasma and brain tissue concentrations over time of (2S,6S)-hydroxynorketamine were determined after intravenous (20 mg/kg) and oral (20 mg/kg) administration of (2S,6S)-hydroxynorketamine (n = 3). After intravenous administration, the pharmacokinetic parameters were estimated using noncompartmental analysis and the half-life of drug elimination during the terminal phase (t1/2) was 8.0 ± 4.0 h and the apparent volume of distribution (Vd) was 7352 ± 736 mL/kg, clearance (Cl) was 704 ± 139 mL/h per kg, and the bioavailability was 46.3%. Significant concentrations of (2S,6S)-hydroxynorketamine were measured in brain tissues at 10 min after intravenous administration, ~30 μg/mL per g tissue which decreased to 6 μg/mL per g tissue at 60 min. The plasma and brain concentrations of (2S,6S)-hydroxynorketamine were also determined after the intravenous administration of (S)-ketamine, where significant plasma and brain tissue concentrations of (2S,6S)-hydroxynorketamine were observed 10 min after administration. The (S)-ketamine metabolites (S)-norketamine, (S)-dehydronorketamine, (2S,6R)-hydroxynorketamine, (2S,5S)-hydroxynorketamine and (2S,4S)-hydroxynorketamine were also detected in both plasma and brain tissue. The enantioselectivity of the conversion of (S)-ketamine and (R)-ketamine to the respective (2,6)-hydroxynorketamine metabolites was also investigated over the first 60 min after intravenous administration. (S)-Ketamine produced significantly greater plasma and brain tissue concentrations of (2S,6S)-hydroxynorketamine relative to the (2R,6R)-hydroxynorketamine observed after the administration of (R)-ketamine. However, the relative brain tissue: plasma concentrations of the enantiomeric (2,6)-hydroxynorketamine metabolites were not significantly different indicating that the penetration of the metabolite is not enantioselective.
Learning-guided automatic three dimensional synapse quantification for drosophila neurons

The subcellular distribution of synapses is fundamentally important for the assembly, function, and plasticity of the nervous system. Automated and effective quantification tools are a prerequisite to large-scale studies of the molecular mechanisms of subcellular synapse distribution. Common practices for synapse quantification in neuroscience labs remain largely manual or semi-manual. This is mainly due to computational challenges in automatic quantification of synapses, including large volume, high dimensions and staining artifacts. In the case of confocal imaging, optical limit and xy-z resolution disparity also require special considerations to achieve the necessary robustness. A novel algorithm is presented in the paper for learning-guided automatic recognition and quantification of synaptic markers in 3D confocal images. The method developed a discriminative model based on 3D feature descriptors that detected the centers of synaptic markers. It made use of adaptive thresholding and multi-channel co-localization to improve the robustness. The detected markers then guided the splitting of synapse clumps, which further improved the precision and recall of the detected synapses. Algorithms were tested on lobula plate tangential cells (LPTCs) in the brain of Drosophila melanogaster, for GABAergic synaptic markers on axon terminals as well as dendrites. The presented method was able to overcome the staining artifacts and the fuzzy boundaries of synapse clumps in 3D confocal image, and automatically quantify synaptic markers in a complex neuron such as LPTC. Comparison with some existing tools used in automatic 3D synapse quantification also proved the effectiveness of the proposed method.
Effective retrieval of audio information from annotated text using ontologies

To improve the accuracy in terms of precision and recall of an audio information retrieval system we have created a domain-specific ontology (a collection of key concepts and their interrelationships), as well as a novel, pruning algorithm. Taking into account the shortcomings of keyword-based techniques, we have opted to employ a concept-based technique utilizing this ontology. The key problem in the retrieval of audio information is to achieve high precision and high recall. Typically, in traditional approaches, high recall is achieved at the expense of low precision, and vice versa. Through the use of a domain-specific ontology appropriate concepts can be identified during metadata generation (description of audio) or query generation, thus improving precision. In case of the association of irrelevant concepts to queries or documents there is a loss of precision. On the other hand, if relevant concepts are discarded, a loss of recall will ensue. Therefore, in conjunction with the use of a domain specific ontology we have proposed a novel, automatic pruning algorithm which prunes as many irrelevant concepts as possible during any case of query generation. By associating concepts in the ontology through techniques of correlation, this algorithm presents a method for the selection of concepts in the query generation. To improve recall, controlled and correct query expansion mechanism is proposed. This guarantees that precision will not be lost. Moreover, we present a way for the query generation in which domain-specific ontology can be used to generate information selection requests in terms of database queries in SQL. In trial implementations we have demonstrated that our ontology-based model outperforms keyword-based technique (vector space model) in terms of precision and recall.
On the Quasi-regularity of Semi-Dirichlet Forms

We prove that if a right Markov process is associated with a semi-Dirichlet form, then the form is necessarily quasi-regular. As applications, we develop the theory of Revuz measures in the semi-Dirichlet context and we show that quasi-regularity is invariant with respect to time change.
Post-operative bleaching: effect on microleakage.

The effect of a carbamide peroxide bleaching gel on the microleakage of Class V resin composite restorations with two dentin bonding agents was evaluated using extracted human teeth. Class V cavity preparations were placed at the cementoenamel junction of the facial and lingual surfaces of 20 teeth for a total of 40 preparations. Half of the teeth were restored with Scotchbond 2/Silux Plus and half were restored with Prisma Universal Bond 3/AP.H. Five teeth were randomly selected from each of the two groups and were stored in water at 37 degrees C to serve as controls. The remaining teeth were exposed to a carbamide peroxide gel for three 2-hour periods per day for 9 days. The specimens were stored in distilled water at 37 degrees C except during treatment periods. All teeth were then thermally stressed for 100 cycles. Microleakage was assessed by dye penetration. The results demonstrated that the carbamide peroxide agent adversely affected the marginal seal of both restorative systems.
Purification and Properties of Protein Methylase II

Abstract An enzyme, "protein methylase II," has been purified approximately 900-fold from calf thymus cytosol. The enzyme methylates exogenously added proteins with S-adenosyl-l-methionine-methyl-14C. Among the proteins tested, a protein isolated from calf thymus serves the best as methyl acceptor. The purified enzyme is completely free of endogenous substrate protein, and is electrophoretically homogenous. Molecular weight of the enzyme has been estimated to be 35,000 by means of Sephadex G-100. The enzymatically incorporated methyl group becomes volatile upon either acid or alkaline hydrolysis of the protein, and the product is identified as methyl alcohol. Optimum pH for the reaction is 6 in citrate-phosphate buffer, and the Km values for S-adenosyl-l-methionine with the protein isolated from calf thymus and with histone are 1.05 x 10-6 m and 1.54 x 10-6 m, respectively. The enzyme does not require any cofactor, and 50% glycerol protects the enzyme from thermal denaturation.
History, International Relations, and Integrated Approaches: Thinking about Greater Interdisciplinarity

This essay starts by exploring how history can contribute to the discipline of international relations (IR). It then moves beyond this question to explore a broader question, beyond IR and history, with which this symposium is concerned: how can we enhance interdisciplinary analysis in international studies? With regard to the first question, this essay advances several themes. First, while history can serve IR in several ways, it is especially salient to the study of change in IR. Second, the study of history can help us connect the dots across time in ways that can complement IR. Stringing detailed cases together or examining the broader sweep of a longer time period may help us discern causal connections that would have been buried in more streamlined and short-term analyses. Third, history can aid in theory-building, modeling, and testing in the study of IR. Quantitative approaches can also benefit from in-depth historical studies. In assessing the value of history to IR, however, it is critical to ask what type of historians and IR scholars we are considering and to be aware of the differences among them. Fourth, while it is useful to draw on history for IR, history also has its limits and may be misused. At the core, this essay examines how history can contribute to IR, but that analysis raises a broader question: how can we integrate notions and insights from various disciplines in international studies, including history and IR? This essay advances one schema for doing so, which it calls “integrated approaches.” It demonstrates one type of integrated approach for the study of foreign policy behavior. The approach systematically draws on multiple disciplines to explain behaviors such as decisions to make treaties, go to war, or ally with other countries.
Quantum Mechanics at the Macroscopic Level

Since most participants at this conference come from sub-areas of physics different from the one in which most of the technical work associated with the subject of this talk has been done (namely superconducting devices exploiting the Josephson effect), I thought that rather than talking about the technical details it might be more interesting to review the general motivation for the work and the philosophy associated with it. An additional reason for doing so is that I believe that the sorts of effects we are looking for in the superconducting-device area may also occur in other systems, and are most likely to occur in those which show the strongly nonlinear behavior which is the subject of this conference.
A Critical Look at Our Adolescence: Notes on Turning 18 (and 75)

Within the contexts of both the American Association of Suicidology's (AAS's) history and the history of associating suicidologists, an integrative identity based on the tenets of science is urged for the AAS. Two propositions are made: first, that we must promote and adopt more discriminative, standardized terminology; second, that we must promote and implement standards of informational competency for professionals and paraprofessionals alike.
Detection of bacteremia by Difco ESP blood culture system.

In a multicenter study, the Difco ESP blood culture system (Difco Laboratories, Detroit, Mich.) was compared with the BACTEC NR660 system (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.). The ESP system monitors each blood culture bottle every 12 to 24 min to detect changes in oxygen consumption and gas production by microbes. Equal volumes of blood were inoculated into aerobic ESP-80A and BACTEC 6A, 16A, or PEDS Plus broths and anaerobic ESP-80N and BACTEC 7A or 17A broths and were incubated for up to 7 days. ESP bottles contain supplemented tryptic soy broth without antimicrobial agent-adsorbing resins. From 7,532 aerobic compliant sets, the ESP system detected 356 clinically significant positive cultures and the BACTEC NR660 system detected 329. From 6,007 anaerobic cultures, the ESP system detected 234 clinically significant positive cultures and the BACTEC NR660 system detected 198. In aerobic broths, 292 organisms were isolated from both systems and 78 organisms were isolated from the ESP system alone, whereas 54 organisms were isolated from the BACTEC NR660 system alone (P 6h earlier in ESP broths compared with BACTNEC NR660 broths were significant, as were earlier times to detection. Although the total number of organisms detected was not significantly different, the ESP system alone detected more organisms in a shorter time than did the BACTEC NR660 system alone. The continuous monitoring capability of the ESP system makes it an attractive alternative to the BACTEC NR660 system.
Meta Math!: The Quest for Omega

This book presents a personal account of the mathematics and metamathematics of the 20th century leading up to the discovery of the halting probability Omega. The emphasis is on history of ideas and philosophical implications.
Validation study of energy expenditure and intake during calorie restriction using doubly labeled water and changes in body composition.

Background Clinical trials involving calorie restriction (CR) require an assessment of adherence to a prescribed CR with the use of an objective measure of energy intake (EI).