cssi/SciSciGPT-SciSciNet huggingface dataset:
A pooled analysis of published, basket trials in cancer medicine.

Abstract Background There is widespread interest in cancer basket trials. However, to date, there has been no formal analysis of all published basket trials. Methods We performed a systematic review to identify all published basket trials in cancer medicine. We included studies that (1) did not place restriction on tumour type and (2) used a biomarker for the basis of enrolment (3) administered at least one anti-cancer agent in prospective fashion and (4) reported responses by each tumour type included. We sought information regarding the tumour histology included and the response rate in basket trials. In addition, we used national cancer statistics to identify which tumour types have been overrepresented in basket studies (i.e. more representation in trials than their incidence would suggest) and those which are under-represented. Results We identified eight articles with a combined enrolment of 1176 patients were included in our analysis, representing over 33 tumour types. Ovarian and fallopian tube cancers 221/1176 (19%), colorectal cancer 144/1176 (12%) and sarcoma 129 (11%) were the most common tumours represented, whereas renal cell cancer, seminoma, thymic carcinoma and neuroendocrine tumour and appendiceal carcinoma were the least represented with one case each. The overall response rate was 25%. Common cancers may be underrepresented compared with rarer tumour types (linear regression beta = 0.58, 95% confidence interval = −0.037–1.21) (slope 1 over-representation). Conclusions We found that, to date, over 1100 patients have been enrolled on published basket studies. Common cancers may be underrepresented compared with rarer tumours. The overall response rate was 25%. Patients enrolling on basket trials should be counselled appropriately that although these studies are highly promising, most patients did not respond. Future targets and drugs may improve on these results.
A Biodegradable Wireless Blood-Flow Sensor

A soft implant wirelessly senses arterial blood flow post-surgery before being gradually resorbed.
Abstract 3631: Development of targeted nanoformulation of talazoparib for combined chemoradiation therapy in lung cancer

Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) therapy exploits a synthetic lethality strategy in cancers with inherent damage in DNA repair or transcription pathways. Talazoparib is a potent PARPi that is currently indicated for oral inhibitor therapy in several cancer clinical trials. Oral administration of these inhibitors typically results in poor bioavailability and tumor accumulation. In contrast, nanoparticle formulation provides a safe vehicle for parenteral administration of therapeutic drugs with sustainable release reducing systemic toxicity and also protect from surveillance of immune cells, thereby increasing the bioavailability of the drugs in vivo. Moreover, targeting strategy for the nanoparticles will improve the accumulation of drugs in the tumors. Here, we developed a targeted formulation of Talazoparib (NanoTLZ) which was decorated with anti-EGFR antibody as a ligand to ameliorate the cellular uptake of NanoTLZ via EGFR-mediated endocytosis. In vitro tests showed that NanoTLZ is more effective in cell growth inhibition than free Talazoparib. When combined with radiation with different doses from 2-10Gy, NanoTLZ showed a strong radiosensitization effect as evidenced with almost no colonies formation at 6 Gy of radiation dose. The high therapeutic efficacy of combined chemoradiation therapy in Calu 6 cell line can be attributed to the higher accumulation of NanoTLZ in the cancer cells as compared to the free Talazoparib which is also marred with efflux of the drug from the cells. The slow and sustained release of Talazoparib from nanoparticle formulation inside the cells lead enhanced inhibition of DNA repair pathways. These studies provide very encouraging results to evaluate the efficacy of these nanoparticles in lung cancer animal models. Citation Format: Bijay Singh, Mostafa Abdelhalim, Stephanee Warrington, Srinivas Sridhar. Development of targeted nanoformulation of talazoparib for combined chemoradiation therapy in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3631.
Amplifying and Attenuating Inequity in Collaborative Learning: Toward an Analytical Framework

AbstractResearch on collaborative learning has focused on its potential to foster successful problem solving. Less attention, though, has been given to issues of equity. In this article, we investi...
Online Learning of Dynamical Systems: An Operator Theoretic Approach.

In this paper, we provide an algorithm for online computation of Koopman operator in real-time using streaming data. In recent years, there has been an increased interest in data-driven analysis of dynamical systems, with operator theoretic techniques being the most popular. Existing algorithms, like Dynamic Mode Decomposition (DMD) and Extended Dynamic Mode Decomposition (EDMD), use the entire data set for computation of the Koopman operator. However, many real life applications like power system analysis, biological systems, building systems etc. requires the real-time computation and updating of the Koopman operator, as new data streams in. In this paper, we propose an iterative algorithm for online computation of Koopman operator such that at each time step the Koopman operator is updated incrementally. In particular, we propose a Recursive Extended Dynamic Decomposition (rEDMD) algorithm for computation of Koopman operator from streaming data. Further, we test the algorithm in three different dynamical systems, namely, a linear system, a nonlinear system and a system governed by a Partial Differential Equation (PDE) and illustrate the computational efficiency of the iterative algorithm over the existing DMD and EDMD algorithms.
MicroRNA Expression and Regulation of Hematopoiesis in CD34+ Cells: A Bioinformatic Circuit Diagram of the Hematopoietic Differentiation Control.

MicroRNAs (miRs) are a recently realized class of epigenetic elements which block translation of mRNA to protein. MicroRNAs have been shown to control cellular metabolism, apoptosis, differentiation and development in numerous organisms including drosophila, rat, mouse, and humans. Recently, miRs have been implicated in the control of hematopoiesis. Importantly, both aberrant expression and deletion of miRs are have been associated with the development of various cancers. In a previous study, we determined the gene expression profiles of HSC-enriched, HPC-enriched, and total CD34+ cells from human PBSC, BM, and CB. One rather surprising finding from this study was that virtually all of “hematopoietic important” genes were expressed at virtually identical levels within all populations examined. One of our hypotheses to explain this phenomena was that miRs may control differentiation by controlling protein expression from these “hematopoietic” RNAs. To examine the possible role of miRs in normal hematopoiesis and their relation to the HSPC transcriptome, we used mir-miroarrays to determine the miR expression profile of primary normal human mobilized blood and bone marrow CD34+ hematopoietic stem-progenitor cells (HSPCs). We have combined this miR data with (1) our extensive mRNA expression data obtained previously for CD34+ HSPCs, CD34+/CD38−/Lin- stem cell-enriched, CD34+/CD38+/Lin+ progenitor-enriched populations, and total CD34+ HSPC (Georgantas, Cancer Research 64:4434) and (2) miR target predictions from various published algorithms. Combining these datasets into one integrated database allowed us to bioinformaticly examine the global interaction of HSPC mRNAs and miRs during hematopoiesis. The 3′UTR sequences from many of these “hematopoietic” mRNA were cloned behind a luciferase reporter. K562 cells were transfected with these luc-3′UTR constructs, confirmating that expression of many important hematopoietic proteins are controlled by miRs. Based on our bioinformatic and protein expression studies, we present a global in silico model by which microRNAs control and direct hematopoietic differentiation. Actual in vitro and in vivo studies addressing the action of specific miRs in hematopoietic differentiation are presented in separate abstracts.
Changing In-Group Boundaries: The Effect of Immigration on Race Relations in the US

How do social group boundaries evolve? Does the appearance of a new outgroup change the ingroup's perceptions of other outgroups? We introduce a conceptual framework of context-dependent categorization, in which exposure to one minority leads to recategorization of other minorities as in- or outgroups depending on perceived distances across groups. We test this framework by studying how Mexican immigration to the US affected White Americans' attitudes and behaviors towards Black Americans. We combine survey and crime data with a difference-in-differences design and an instrumental variables strategy. Consistent with the theory, Mexican immigration improves Whites' racial attitudes, increases support for pro-Black government policies and lowers anti-Black hate crimes, while simultaneously increasing prejudice against Hispanics. Results generalize beyond Hispanics and Blacks and a survey experiment provides direct evidence for recategorization. Our findings imply that changes in the size of one group can affect the entire web of inter-group relations in diverse societies.
Educational behaviors of pregnant women in the Bronx during Zika's International emerging epidemic: "First mom … and then I'd Google. And then my doctor".

Background The objective of the study was to understand how pregnant women learned about Zika infection and to identify what sources of information were likely to influence them during their pregnancy. Methods We conducted 13 semi-structed interviews in English and Spanish with women receiving prenatal care who were tested for Zika virus infection. We analyzed the qualitative data using descriptive approach. Results Pregnant women in the Bronx learned about Zika from family, television, the internet and their doctor. Informational sources played different roles. Television, specifically Spanish language networks, was often the initial source of information. Women searched the internet for additional information about Zika. Later, they engaged in further discussions with their healthcare providers. Conclusions Television played an important role in providing awareness about Zika to pregnant women in the Bronx, but that information was incomplete. The internet and healthcare providers were sources of more complete information and are likely the most influential. Efforts to educate pregnant women about emerging infectious diseases will benefit from using a variety of approaches including television messages that promote public awareness followed up by reliable information via the internet and healthcare providers.
Editorial: Let's talk about P(ee).

PRACTITIONER POINTS Phosphorus recycling and reuse are imperative, and the water industry has an important role to play in this effort. Technologies capable of removing phosphorus to ultra-low levels and subsequent recovery for phosphorus reuse are needed. Inorganic ion exchange resins and organic bioadsorbents are promising for phosphorus removal and recovery as part of the waste-to-resource paradigm.
Suicidal Ideation Among University Students During the COVID-19 Pandemic: Identifying At-risk Subgroups

Given concerns of increased suicide risk among university students during the COVID-19 pandemic, this study examined rates of lifetime and past-year suicidal ideation (SI) among university students in Fall 2020 (vs. two earlier semesters), overall and across gender, racial/ethnic background, and sexual identity. Participants included 1700 university students enrolled in a general education psychology course in Fall 2020, Fall 2014, or Fall 2013. Rates of SI were not significantly higher in Fall 2020 versus the earlier semesters and did not differ across racial/ethnic background. However, rates of SI in Fall 2020 were significantly higher among sexual minority than heterosexual students.
An approach to system optimization for X-Ray photon-counting systems using performance on a detection/localization task

We address the problem of optimizing data acquisition for photon-counting CT. We formulate a task-driven approach using a clinically relevant task of detection and localization of a lesion in a search region. The appropriate scalar measure of task performance is ALROC, the area under the LROC curve. For hardware optimization, the observer performing the task should operate on the raw (sinogram) data so that the best possible information, independent of the parameters of any particular reconstruction algorithm, is collected. To carry out the task, we use the ideal observer (IO), a numerical observer that yields the maximal ALROC amongst all observers. This differs from the usual numerical observer that operates on the reconstructed data and is designed so that its performance tracks that of a human observer. So while the optimization is carried out in the sinogram domain, the task definition is in the object domain. In this work, we mathematically specialize a previously developed IO to the case of photon-counting transmission tomography. We applied the IO to a 2D simulation of CT with the task of detecting a 3mm lung nodule in a lung region of a 512×512 phantom. The application was to optimize the number of angular acquisitions given a fixed dose. A plot of ALROC vs. angle number peaks at 42 angles. We also plotted ALROC vs. dose (at 105 angles) to characterize the increase in task performance with count level.
Friedrich Nietzsche: A Philosophical Biography

Part I. Youth: 1. Da campo 2. Pforta 3. Bonn 4. Leipzig 5. Schopenhauer Part II. The Reluctant Professor: 6. Basel 7. Richard Wagner and the birth of The Birth of Tragedy 8. War and aftermath 9. Anal philology 10. Untimely Meditations 11. Aimez vous Brahms? 12. Aufwiedersehen Bayreuth 13. Sorrento 14. Human, All-Too-Human Part III. The Nomad: 15. The wanderer and his shadow 16. Dawn 17. The Gay Science 18. The Salome affair 19. Zarathustra 20. Nietzsche's circle of women 21. Beyond Good and Evil 22. Clearing the decks 23. The Genealogy of Morals 24. 1888 25. Catastrophe 26. The rise and fall of The Will to Power 27. The end Postscript: Nietzsche's madness.
Effect of Sodium Saccharin on Urinary Bladder Epithelial Regenerative Hyperplasia following Freeze Ulceration

Abstract Sequential observations of the light and scanning electron microscopic appearances and labeling index of rat urinary bladder epithelium following freeze ulceration were performed for 8 weeks, and the effect of sodium saccharin on this process when fed as 5% of the diet, beginning either immediately or 2 weeks after ulceration, was investigated. All rats treated with freeze ulceration of the bladder developed marked nodular and papillary hyperplasia around the ulcer by the fourth day. Under scanning electron microscopy, there were uniform and pleomorphic microvilli on the hyperplastic cell surfaces for the first 14 days after the ulcer. The labeling index of the bladder epithelium ([3H]thymidine injected 1 hr prior to sacrifice) was 10 to 20% after 1 day, and it rapidly diminished to 0.5 to 1.0% by the seventh day. When rats treated with freeze ulceration were fed control diet, the incidence of the light and scanning electron microscopic lesions rapidly diminished after the 14th day, and they were present at very low incidence after 56 days. The labeling index also decreased to the normal level (0.02 to 0.06%) by the 21st day. In contrast, rats fed sodium saccharin, either immediately after ulceration or beginning after 2 weeks of control diet following ulceration, developed nodular and papillary hyperplasia and luminal surface abnormalities detectable by scanning electron microscopy, and the incidences of these abnormalities remained high for the entire 8 weeks of this experiment. The labeling index in these groups also remained elevated. The rats fed control diet without ulceration had normal bladders. However, rats fed sodium saccharin developed mild simple hyperplasia and an increased labeling index. Another experiment evaluated the effect of delaying the beginning of sodium saccharin administration until 8 weeks after ulceration. Surprisingly, the development of nodular and papillary lesions detected by light microscopy, surface abnormalities detected by scanning electron microscopy, and increased labeling index determined by autoradiography were similar to results after sodium saccharin administered immediately or beginning 2 weeks after ulceration. The results of these experiments suggest that sodium saccharin prolongs the regenerative hyperplastic changes following ulceration and maintains an increased proliferative rate in the epithelium. These changes appear to contribute to the eventual induction of bladder neoplasms in rats fed sodium saccharin following ulceration.
Mass Customization Strategies

Mass customization is a strategy that enables the practice of customer-centric marketing by providing customers with product offerings that are individually tailored to their specific needs. To successfully apply a mass customization strategy, marketers must shift from a supply-side orientation to a demand-side orientation and change product development and manufacturing processes. Keywords: mass customization; customer-centric marketing; cocreation marketing strategy
Multirate filter bank reconstruction of bandlimited signals from bunched samples

A method for reconstructing a bandlimited signal from its periodic bunched samples is presented. As in prior approaches, a multirate filter bank structure is used to reconstruct the signal; however, the technique used to design the reconstruction filter bank is different. The solution presented employs an interpolation filter to model the signal at the input of the reconstruction filter band. FIR synthesis filters are selected to reduce aliasing and distortions of the reconstructed signal. Simulation results showing the quality of reconstruction are presented.
Using Patterns in the Design of Inter-organizational Systems – An Experience Report

The modeling, design, and implementation of inter-organizational systems (IOS) is a challenging new problem. In contrast to previous systems, where components have clearly defined interfaces and serve a well-defined purpose, components of IOS exist in a distributed environment, where each component of the system may exist at a separate corporation and must conform to the interface of partner components. This creates a complicated problem for designers. In this paper, we investigate to which extent control flow, communication, and data manipulation patterns can help to ease the manual design process of IOS implemented in the Business Process Execution Language for Web services (BPEL4WS). By applying patterns of all three types in an iterative fashion we go from an abstract representation of the example process to a graphical solution with a one-to-one mapping to executable BPEL4WS code.
Self-authorship in undergraduate students in a blended-learning multicultural course

Self-authorships provided the theoretical lens for this exploration of a blended learning multicultural course. Universities must help students develop a complex array of capacities to function effectively in today‘s interconnected world. Self-authorship provides a framework to analyze student development across three domains: cognitive, intrapersonal, and interpersonal. Self-authorship development can be fostered through the use of the Learning Partnerships Model. This qualitative study used the theory of self-authorship to analyze interactions in the online discussion portion of one section of twenty-one students in a multicultural course at a rural Midwestern university. The course used dialogic principles in a blended learning environment, combining face-to-face interactions with an online platform which supported online journaling, a variety of resources including articles and videos, and an online discussion forum. Six students were interviewed to determine self-authorship development. Their interactions with classmates in the online discussion were analyzed. Some evidence of students‘ self-authorship development was found. Lack of facilitation in the online discussion appeared to have the potential to engender some resistance. A number of suggestions for course improvement could be made based on literature on dialogic principles, optimal online discussion formations and the Learning Partnerships Model.
Active and cooperative learning techniques for the computer science classroom

* Copyright © 2002 by the Consortium for Computing Sciences in Colleges. Permission to copy without fee all or part of this material is granted provided that the copies are not made or distributed for direct commercial advantage, the CCSC copyright notice and the title of the publication and its date appear, and notice is given that copying is by permission of the Consortium for Computing Sciences in Colleges. To copy otherwise, or to republish, requires a fee and/or specific permission.
Radical Cystectomy Perioperative Care Redesign

Objective To present an evidence-based review of the perioperative management of the radical cystectomy (RC) patient in the context of a care redesign initiative. Methods A comprehensive review of the key factors associated with perioperative management of the RC patient was completed. PubMed, Medline, and the Cochrane databases were queried via a computerized search. Specific topics were reviewed within the scope of the three major phases of perioperative management: preoperative, intraoperative, and postoperative. Preference was given to evidence from prospective randomized trials, meta-analyses, and systematic reviews. Results Preoperative considerations to improve care in the RC patient should include multi-disciplinary medical optimization, patient education, and formal coordination of care. Efforts to mitigate the risk of malnutrition and reduce postoperative gastrointestinal complications may include carbohydrate loading, protein nutrition supplementation, and avoiding bowel preparation. Intraoperatively, a fluid and opioid sparing protocol may reduce fluid shifts and avoid complications from paralytic ileus. Finally, enhanced recovery protocols including novel medications, early feeding, and multi-modal analgesia approaches are associated with earlier postoperative convalescence. Conclusion RC is a complex and morbid procedure that may benefit from care redesign. Evidence based quality improvement is integral to this process. We hope that this review will help guide further improvement initiatives for RC.
Determination of traces of palladium by adsorptive stripping voltammetry of the dimethylglyoxime complex

Abstract Preconcentration is achieved by adsorption of a palladium-dimethylglyoxime complex on a hanging mercury drop electrode. Optimal conditions area stirred acetate buffer solution (pH 5.15) containing 2 × 10−4 M dimethylglyoxime and an accumulation potential of —0.20 V. The height of the stripping peak in a negative-going linear scan is linearly dependent on palladium concentration and preconcentration time (over the ranges 0–16 μg l−1 and 0–300 s, respectively). For a 10-min preconcentration time, the detection limit is 20 ng l−1 (2.1 × 10−10 M). Possible interferences by other trace metals are investigated. Palladium added to seawater samples was easily quantified.
Mansart and le Brun in the Genesis of the Grande Galerie de Versailles

No artistic masterpiece of the reign of Louis XIV is more familiar than the famous Galerie des Glaces at Versailles, with its associations from the time of the grand monarque to the crowning of William I as German Emperor and the signing of the Treaty of Versailles. The original designs for it, however, have never been produced, so that no one has been able to determine whether the artistic credit for it should be assigned to Mansart, the architect of the palace, or to Charles Le Brun, first painter to the King, who painted the immense vault and is generally regarded as the artistic dictator of the period. “M. Le Brun,” says the Mercure of December, 1682, in the first description of this gallery, “en a fait tout le dessin, c'est a dire que les ornemens, le sculpture, et toutes les choses qui contribuent a l'enrichissement de la Galerie, part du genie de ce Premier Peintre de Sa Majeste.” Let us see.
Polychlorinated biphenyl-induced oxidative stress in organotypic co-cultures: experimental dopamine depletion prevents reductions in GABA.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been demonstrated to be toxic to the dopamine (DA) systems of the central nervous system. One proposed mechanism for PCB-induced DA neurotoxicity is inhibition of the vesicular monoamine transporter (VMAT); such inhibition results in increased levels of unsequestered DA and DA metabolism leading to oxidative stress. We have used an organotypic co-culture system of developing rat striatum and ventral mesencephalon (VM) to determine whether alterations in the vesicular storage of DA, resulting from PCB exposure and consequent induction of oxidative stress, leads to GABA and DA neuronal dysfunction. Twenty-four-hour exposure to an environmentally relevant mixture of PCBs reduced tissue DA and GABA concentrations, increased medium levels of DA and measures of oxidative stress in both the striatum and VM. Alterations in neurochemistry and increases in measures of oxidative stress were blocked in the presence of n-acetylcysteine (NAC). Although NAC treatment did not alter PCB-induced changes in DA neurochemistry, it did protect against reductions in GABA concentration. To determine whether alterations in the vesicular storage of DA were responsible for PCB-induced oxidative stress and consequent reductions in GABA levels, we depleted DA from the co-cultures using α-methyl-p-tyrosine (AMPT). AMPT reduced striatal and VM DA levels by 90% and 70%, respectively. PCB exposure, following DA depletion, neither increased levels of oxidative stress nor resulted in GABA depletion. These results suggest that PCB-induced alterations in the vesicular storage of DA, resulting in increased levels of unsequestered DA, leads to increased oxidative stress, depletion of tissue glutathione, and consequent reductions in tissue GABA concentrations.
Surgical treatment of primary hyperparathyroidism: An institutional perspective

Three hundred and eighty-four consecutive patients with primary hyperparathyroidism (HPT) were surgically treated at a single institution during the 2 year period 1983 through 1984. Two patients were found to have benign familial hypocalciuric hypercalcemia and a single patient had parathyroid carcinoma. In the remaining 379 patients, the cure rate was 99.5%, the operative mortality 0.3%, persistent vocal cord paralysis 0.8%, and permanent hypocalcemia 0.3%. This data supports a liberal policy regarding cervical exploration in patients with HPT and questions any policy of observation without surgical intervention.
SIRT1 deacetylase is overexpressed in human melanoma and its small molecule inhibition imparts anti-proliferative response via p53 activation

Melanoma causes more deaths than any other skin cancer, and its incidence in the US continues to rise. Current medical therapies are insufficient to control this deadly neoplasm, necessitating the development of new target-based approaches. The objective of this study was to determine the role and functional significance of the class III histone deacetylase SIRT1 in melanoma. We have found that SIRT1 is overexpressed in clinical human melanoma tissues and human melanoma cell lines (Sk-Mel-2, WM35, G361, A375, and Hs294T) compared to normal skin and normal melanocytes, respectively. In addition, treatment of melanoma cell lines A375, Hs294T, and G361 with Tenovin-1, a small molecule SIRT1 inhibitor, resulted in a significant decrease in cell growth and cell viability. Further, Tenovin-1 treatment also resulted in a marked decrease in the clonogenic survival of melanoma cells. Further experiments showed that the anti-proliferative response of Tenovin-1 was accompanied by an increase in the protein as well as activity of the tumor suppressor p53. This increase in p53 activity was substantiated by an increase in the protein level of its downstream target p21. Overall, these data suggest that small molecule inhibition of SIRT1 causes anti-proliferative effects in melanoma cells. SIRT1 appears to be acting through the activity of the tumor suppressor p53, which is not mutated in the majority of melanomas. However, future detailed studies are needed to further explore the role and mechanism of SIRT1 in melanoma development and progression and its usefulness in melanoma treatment.
Naked TSH Receptor DNA Vaccination: A TH1 T Cell Response in Which Interferon-γ Production, Rather than Antibody, Dominates the Immune Response in Mice

Two approaches have been developed to induce TSH receptor antibodies in mice with properties resembling those in Graves' disease, the Shimojo model of injecting live fibroblasts coexpressing the TSH receptor and major histocompatibility complex antigen Class II, and TSH receptor-DNA vaccination. Thyroid-stimulating antibodies appear to occur less commonly after DNA vaccination, but there has been no direct comparison of these models. We performed a three-way comparison of 1) AKR/N and 2) BALB/c mice vaccinated with TSH receptor-DNA and 3) AKR/N mice injected with fibroblasts expressing the TSH receptor and the major histocompatibility complex antigen class II of AKR/N mice. TSH receptor-DNA vaccinated mice had low or undetectable levels of TSH receptor antibodies determined by ELISA or flow cytometry. Nonspecific binding precluded comparisons with sera from Shimojo mice by these assays. TSH binding inhibition and thyroid-stimulating antibody were undetectable in TSH receptor-DNA vaccinated mice. In Shimojo mice, TSH binding inhibition was positive in approximately 60%, and thyroid-stimulating antibodies were positive in hyperthyroid animals. Unlike the negative antibody data, splenocytes from TSH receptor-vaccinated (but not Shimojo) mice proliferated and produced the Th1 cytokine interferon-gamma in response to TSH receptor antigen. In conclusion, DNA vaccination is less effective at inducing TSH receptor antibodies than the Shimojo approach, but it permits the future characterization of TSH receptor-specific T cells generated without adjuvant.
Centrally active differentiation factors in the nervous system

The adult mammalian brain is a remarkably heterogeneous structure comprised of more than 50 biochemically distinct types of neurons. This phenotypic diversity is established during development, not only as the result of genetic but also epigenetic influences. It is believed that extracellular proteins, called differentiation factors, both instruct neurons in their original choice of neurotransmitter substance and, in certain situations, revise those biochemical decisions. The first candidate differentiation factor in the brain has only recently been proposed. This muscle-derived substance has the unique ability, in culture, to initiate expression of genes associated with catecholamine transmitter synthesis in non-catecholamine neurons of the brain. Because it also amplifies expression in cultured catecholamine-producing neurons in vitro and in vivo, it may prove to be an important therapeutic agent in diseases involving catecholamine shortages.
Some Observations on the Sporogonic Cycle of Plasmodium schwetzi, P. vivax and P. ovale in Five Species of Anopheles

SYNOPSIS. The sporogonic cycles of Plasmodium schwetzi, P. vivax and P. ovale are distinctly different with regard to rate of sporozoite development and median oocyst diameter. Differences in the oocyst structure, particularly with regard to the presence of inclusions in those of P. schwetzi, were noted. These findings tend to support the continued designation of these parasites as distinct and separate species.
STATE OF THE CLIMATE IN 2004

Abstract From a global perspective, the annual average surface temperature in 2004 was the fourth highest value observed since regular instrumental records began in 1880. Global surface air temperatures in 2004 were 0.44°C (0.79°F) above the 1961–90 mean, according to both the U.S. and U.K. archives. Observations of the global annual mean temperature in 2004 from the combined lower and middle troposphere was 0.38°C (0.68°F)—the fourth warmest year in the 47-yr archive of worldwide radiosonde observations, and the ninth warmest year out of the past 26 based on satellite measurements. The average precipitation anomaly over global land areas in 2004 was 10.7 mm above average, which was ∼1% above the 1961–90 mean, and the first year since 2000 that the global mean value was wetter than average. Northern Hemisphere sea ice extent was the third lowest on record for the year, dating back to 1973. The annual snow cover extent over Northern Hemisphere land areas was 25.1 million km2, which was the 25th most extens...
CNS localization of neuronal nicotinic receptors.

Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand-gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 12 neuronal nAChR subunits have been identified (
Mid-term results after endovascular repair of the abdominal aortic aneurysm

Abstract Purpose: As a minimally invasive strategy for the treatment of patients with abdominal aortic aneurysm (AAA), endovascular repair has been embraced with enthusiasm because of the promise of achieving a durable result with a reduced risk of perioperative morbidity and mortality. Our mid-term experience with endovascular AAA repair was assessed by examining early and late clinical outcome in concurrent cohorts of patients stratified either as low-risk or as at increased-risk for intervention. Methods: From April 1994 to December 1999, endovascular AAA repair was performed in 104 patients with commercially available systems. A subset of patients considered at increased risk for intervention (n = 51) were categorized as such based on a pre-existing history of ischemic coronary artery disease (73%), with documentation of myocardial infarction (57%) or congestive heart failure (29%), or because of the presence of chronic obstructive pulmonary disease, liver disease, or malignancy. Results: The perioperative mortality rate (30-day) was 7.8% for patients at increased risk compared with 1.9% among those classified as low-risk ( P = NS). There was no difference between groups in age (72 ± 7 years vs 74 ± 7 years; mean ± SD), surgical time (221 ± 90 minutes vs 192 ± 68 minutes), blood loss (437 ± 402 mL vs 331 ± 238 mL), postoperative hospital stay (4.4 ± 2.7 days vs 4.2 ± 2.5 days), or days in the intensive care unit (1.2 ± 1.6 days vs 0.6 ± 1.3 days). Patients at increased risk of intervention had larger aneurysms than patients at low risk (58 ± 11 mm vs 52 ± 12 mm; P P = NS). Conversion rates to open operative repair were similar in increased-risk and low-risk groups at 3.9% and 5.7%, respectively. The initial endoleak rate was 21% versus 18% based on the first computed tomography performed (either at discharge or 1 month; P = NS). To date, patients at increased risk have been monitored for 14.6 ± 12.4 months, and patients at low risk have been monitored for 17.7 ± 15.0 months. Kaplan-Meier analysis for cumulative patient survival demonstrated a reduced probability of survival among those patients initially classified as at increased risk for intervention ( P Conclusion: Despite the use of an endovascular approach for aneurysm treatment, the risk of perioperative death and morbidity remains present for all patients including those who have no significant medical comorbidity. Moreover, although clinical success rates are comparable in both patient groups, 2 years after endovascular repair was performed, at least one in four patients was classified as a clinical failure. Given the continued uncertainty associated with clinical outcome and the need for close life-long surveillance, caution is dictated in advocating endovascular treatment for the patient who is otherwise considered an ideal candidate for standard open surgical repair. (J Vasc Surg 2001;33:S70-6.)
Novel Methodologic Approaches to Phase I, II, and III Trials

Among the future directions of stroke research identified by the Stroke Progress Review Group was a call for improved trial design, conduct, and outcome assessment. This demand is underscored by recent trial findings. Of the >100 clinical trials in ischemic stroke published during the first decade of the 21st century, only 5 of 31 phase III trials demonstrated efficacy on the primary outcome.1 As the number of experimental therapies undergoing clinical investigation in stroke increases, there is a rising need for more efficient statistical designs to (1) determine the optimal dose, (2) identify interventions with therapeutic potential, and (3) evaluate clinically relevant treatment effects. The correct selection of the optimal dose, via a thorough understanding of the dose–toxicity and dose–efficacy relationships, is critical for establishing the efficacy of a potential therapeutic agent.2 Traditional rule–based dose-escalation designs,3 such as the 3+3 design and its variations, have suboptimal statistical operating characteristics. The inefficiency in the 3+3 design is that it stems from the decision to escalate or de-escalate, a decision is based solely on event data from the current dose, without considering event information available from neighboring doses. An alternative design called the Continual Reassessment Method4 is an adaptive dose-finding algorithm, wherein escalation or de-escalation through the dose region is determined by continuous re-estimation of the dose–toxicity curve, and each cohort of subjects is treated at the dose currently believed to be the maximum tolerated dose. Although computationally more intensive than the 3+3 design, the Continual Reassessment Method and its variations use all available toxicity data in the estimation of the maximum tolerated dose, and thus are statistically more efficient. Ethical considerations also favor the Continual Reassessment Method, because the Continual Reassessment Method typically treats fewer patients at subtherapeutic doses. Once the appropriate dose has been determined through …
Examining the displacement practices of johns with on-line data

Abstract Situational crime prevention has proven successful in reducing crime rates, though critics argue these programs simply displace criminality into different venues. Research exploring the phenomenon of displacement found offenders change their behavior in response to law enforcement intervention, particularly in research on prostitution. Most research on displacement in the sex trade, however, focuses on the sex worker rather than their clients. This limits the amount of knowledge concerning the dynamics of prostitution, and the illegal sex trade as a whole. This study addressed this gap by examining the displacement practices of the customers of prostitutes, also called johns. Using a sample of posts from Web forums for johns in ten U.S. cities, this qualitative analysis found that johns engage in multiple forms of displacement in the real world. In addition, the Internet appears to act as a resource to identify sex workers, thereby enabling tactical displacement. Implications for law enforcement and situational crime prevention theory are also discussed.
ILLICIT DRUG USE AND DIASTOLIC FUNCTION: DATA FROM THE MIND YOUR HEART STUDY

Due to unique exposures, illicit drug use is associated with myocyte injury and cardiomyopathy. It is not known whether drug use has an independent association with diastolic dysfunction (DD). We examined the association between illicit drug use by self-reported questionnaire and quantified by drug
Some Aspects of Western Hemisphere Circulation and the Madden–Julian Oscillation

AbstractAlthough the greatest variance in convection associated with the Madden–Julian oscillation (MJO) occurs over the Indo-Pacific warm pool, the MJO is associated with substantial circulation patterns in the tropics and the extratropics of the Western Hemisphere. Reanalysis data suggest that upper-tropospheric easterly wind anomalies on the equator between 40° and 140°W precede 86% of active convective phases of MJO events greater than one standard deviation in amplitude over the Indian Ocean basin during the Northern Hemisphere winter. Composites of those MJO events that are preceded by westerly wind anomalies and those events preceded by easterly wind anomalies are compared. Results show that those events that are preceded by westerly wind anomalies fail to thrive and do not yield the amplitude in convection or the canonical atmospheric circulation response that is associated with those preceded by easterly wind. The composite of events preceded by easterly winds reveals that these winds amplify coi...
Effects of exposing DBA/2J mice to a high-frequency augmented acoustic environment on the cochlea and anteroventral cochlear nucleus.

DBA/2J (D2) mice, which exhibit very early progressive sensorineural hearing loss, were treated for 12 h nightly with an augmented acoustic environment (AAE) initiated before the onset of hearing. The AAE consisted of repetitive bursts of a 70 dB sound pressure level, half-octave noise band centered at 20 kHz (i.e. low frequencies were excluded). At 55 days of age, AAE-treated mice, compared to control mice, exhibited less elevation of auditory brainstem response thresholds for tone frequencies from 16 to 32 kHz and fewer missing outer hair cells in the high-frequency tonotopic region of the cochlea. The dorsal region of their anteroventral cochlear nucleus (most strongly stimulated by the AAE) was larger, had more surviving neurons, and larger neurons than those of untreated control mice. These and previous findings using an AAE band containing lower frequencies indicate that AAE treatment effects are frequency-related. The findings provide support for the hypothesis that the beneficial effects of AAE treatment on the cochlea are associated with increased physiological activity evoked by the AAE, and the central AAE effects result from increased AAE-evoked neural activity and a healthier cochlea providing the auditory input.
Solid-state 13C nuclear magnetic resonance investigation of poly(oxetanes): Effect of chain conformation

Abstract Carbon-13 nuclear magnetic resonance (n.m.r.) in the solid state has been applied to the study of poly(oxetane) and poly(3,3-dimethyloxetane). Two different crystalline modifications, with T 2 G 2 and T 3 G conformations, have been prepared for each of the polymers. The corresponding 13 C chemical shifts for each sample, both amorphous and crystalline, have been determined. Single resonances for the methylene carbons α to the oxygens are observed for the crystal forms having T 2 G 2 conformation. Two resonances are observed for these carbons in each of the crystals having T 3 G conformation. The equivalence of these carbons in the T 2 G 2 conformation and their inequivalence, within the same monomer unit, in the T 3 G conformation is a property of the isolated chain. It is argued that the observed n.m.r. inequivalence in the T 3 G crystalline forms has the same origin.
Chord length distributions in binary stochastic media in two and three dimensions

Simple models for transport through stochastic media usually assume that the chord lengths of materials are distributed exponentially. Theory predicts that, in a medium consisting of disks/spheres that can interpenetrate, chord lengths in the background material (between the disks/spheres) should exactly follow an exponential. In a medium with impenetrable (non-overlapping) disks/spheres, the distribution is only approximately exponential. This paper demonstrates, through direct numerical simulations, that for randomly distributed disks in 2D and spheres in 3D, with distributions of radii, chord lengths in the background material (between the disks/spheres) are accurately described by exponentials over five orders of magnitude when the material is dilute. The chord lengths inside the disks and spheres are not exponentially distributed, but those distributions can be calculated. A scaling relationship between the mean chord lengths in the two materials is presented for an infinite medium. By knowing the mean properties of the disks/spheres in a medium, this relationship allows one to accurately describe the statistical properties of the background material. The stochastic simulations are validated by this infinite medium relationship. When the fraction of space occupied by the disks or spheres becomes large, the distributions are no longer accurately described by an exponential.
Modeling Heat Generation in a Lithium Ion Battery

This paper presents a numerical study on heat generation in a lithium-ion (LiC6 /LiPF6 /Liy Mn2 O4 ) battery cell. The numerical model considered multi-physics including battery kinetics, diffusion, and thermal analysis. The heat generation rate was determined by a local heat generation model. This model enables the investigation of the effects of battery parameters on different heat generation mechanisms and the overall heat generation rate in the battery. The effects of the thickness of the battery components and the size of the electrode particles at different discharge rates were evaluated. The results revealed the relationships between these parameters. A battery with a low heat generation rate and efficient battery utilization may be achieved through parameter optimization.Copyright © 2011 by ASME and General Motors Company
Ctf19p: A Novel Kinetochore Protein in Saccharomyces cerevisiae and a Potential Link between the Kinetochore and Mitotic Spindle

A genetic synthetic dosage lethality (SDL) screen using CTF13 encoding a known kinetochore protein as the overexpressed reference gene identified two chromosome transmission fidelity (ctf) mutants, YCTF58 and YCTF26. These mutant strains carry independent alleles of a novel gene, which we have designated CTF19. In light of its potential role in kinetochore function, we have cloned and characterized the CTF19 gene in detail. CTF19 encodes a nonessential 369-amino acid protein. ctf19 mutant strains display a severe chromosome missegregation phenotype, are hypersensitive to benomyl, and accumulate at G2/M in cycling cells. CTF19 genetically interacts with kinetochore structural mutants and mitotic checkpoint mutants. In addition, ctf19 mutants show a defect in the ability of centromeres on minichromosomes to bind microtubules in an in vitro assay. In vivo cross-linking and chromatin immunoprecipitation demonstrates that Ctf19p specifically interacts with CEN DNA. Furthermore, Ctf19-HAp localizes to the nuclear face of the spindle pole body and genetically interacts with a spindle-associated protein. We propose that Ctf19p is part of a macromolecular kinetochore complex, which may function as a link between the kinetochore and the mitotic spindle.
239 THE EFFECT OF INTRAUTERINE GROWTH RETARDATION (IUGR) UPON HEPATIC AND RENAL PHOSPHOENOL PYRUVATE CARBOXY- KINASE (PEPCK) ACTIVITY IN THE NEONATAL RAT

The contribution of renal gluconeogenesis to glucose homeostasis in the newborn has been neglected despite its well-established role in fasting glucose homeostasis. We have studied the activity of the key gluconeogenic enzyme PEPCK (forward spectro-photometric reaction) in normal and IUGR rat neonates (uterine vessel ligation) fasted for 4 hours postpartum (34°C).