cssi/SciSciGPT-SciSciNet huggingface dataset:
Towards Internet-of-Things for Wearable Neurotechnology

This paper outlines the prevalent challenges for the emerging wearable neurotechnology in modern IoT systems. We underline the recent insights in neuroscience and the ability to decode the brain circuitry with high confidence. We address the imminent challenges of translating the advanced high-cost medical setup for neural activity recording to a commodity IoT system. Emphasis is placed on non-invasive wearable sensing technology and the advances in data analytic for neurosignals. In particular, we focus on human-in-the-loop IoT systems where privacy concerns of leaking private human state and energy limitations for local data processing lay significant constraints on such systems’ architecture. Along the way, we envision applications that will reach their full potential and provide the promised functionality by embedding wearable neurotechnology in their design. We end the paper by highlighting the prominent research opportunities and challenges for designing and developing the next generation of low-cost, energy-efficient, privacy-aware, and ubiquitous wearable neurotechnology. Most of these research challenges need to be addressed from a multi-disciplinary approach. Researchers from various communities need to coordinate and collaborate to successfully advance the research, development, and standardization of such neurotechnologies for the larger benefit of society.
Preweaning Health and Performance of Minnesota Dairy Calves Fed Either Pasteurized Waste Milk or a Traditional Milk Replacer Feeding Program

A great deal of interest has developed in adopting commercial pasteurization systems for feeding waste milk on commercial dairies and heifer growing operations. Some considerations in adopting this technology include economics, infectious disease control, and calf health and performance. The objective of this study was to describe preweaning morbidity, mortality and growth rates in calves fed either pasteurized waste milk or a traditional 20:20 milk replacer feeding program between birth and weaning
IL-1 receptor antagonist for prevention of severe immune effector cell-associated neurotoxicity syndrome.

7566Background: Progress in chimeric antigen receptor (CAR) T-cell therapy has included reduction in life-threatening toxicity. Rates of severe cytokine release syndrome (CRS) have declined from 50...
Mammalian Development and Human Cancer: from the Phage Group to the Genetics of Intestinal Cancer

This chapter focuses on the abiding interest in the intersection of mammalian development and human cancer. In this essay, a mouse model for intestinal cancer is discussed. To answer the question of what are the molecular and biological intersections of mammalian development and human cancer, one determines what neoplastic processes occur spontaneously in a mutant that has lost the function of a single developmental gene. In human cancer genetics, this case is approximated by families in which a mutant allele inherited in heterozygous form predisposes the individual to a particular cancer syndrome. The tumor lineage has somatically lost the remaining normal allele by one of several possible mitotic mechanisms. A full exploration of the intersection with normal mammalian development of the loss-of-function neoplasms requires analysis of embryos homozygous for the mutant allele. The chapter focuses on two genes: Apc on chromosome 18, in which the Min nonsense allele has been induced by ethylnitrosourea, and the first modifier-of-Min locus, Mom-1, on chromosome. In sections of Min-induced tumors, the expression of cellular markers for three differentiated cell types of the intestinal epithelium is detected by immunohistochemistry: the Paneth cell (lysozyme), the enteroendocrine cell (serotonin), and the enterocyte (fatty acid-binding protein). The properties of the tumor can in principle be altered by changes either in the provirus or in the source of any differential growth factors.
Construction of Thinned Gated Single-Assignment Form

Analysis of symbolic expressions benefits from a suitable program representation. We show how to build thinned gated single-assignment (TGSA) form, a value-oriented program representation which is more complete than standard SSA form, defined on all reducible programs, and better for representing symbolic expressions than program dependence graphs or original GSA form. We present practical algorithms for constructing thinned GSA form from the control dependence graph and SSA form. Extensive experiments on large Fortran programs show these methods to take linear time and space in practice. Our implementation of value numbering on TGSA form drives scalar symbolic analysis in the ParaScope programming environment.
Abstract 2507: Circulating proteolytic products of carboxypeptidase N for early detection of breast cancer

Background: Carboxypeptidase N (CPN) plays an important role in regulating vasoactive peptide hormones, growth factors, and cytokines by specifically cleaving their C-terminal basic residues. Herein we demonstrated that the circulating peptides specifically cleaved by CPN in the tumor microenvironment can indeed be stage-specific indicators of breast cancer. Methods: The activity of CPN was evaluated using an ex-vivo peptide cleavage assay, in which synthesized C3f peptide (His6-C3f_S1304-R1320-His6) is incubated in interstitial fluids of breast tumor and adjacent normal breast tissues in mice with orthotopic implantation of the human cell line MDA-MB-231. Fragment profiling, by an approach combining nanopore fractionation and mass spectrometry, revealed the nature and extent of cleavage by CPN. These results correlated with the level of CPN-catalyzed peptides in blood specimens taken from the tumor-bearing mice, healthy women and breast cancer patients. CPN expression in the same set of samples was further examined by immunohistochemistry and immunoblotting. Results: We showed that generation of C3f_R1310-L1319 specifically correlated with the CPN expression level. In both the mouse and clinical patient samples, the amount of CPN was clearly increased in tumor tissues compared to that seen in normal breast tissue, while its counterpart in blood remained constant. The amount of 6 CPN-catalyzed peptides predominantly increased in sera taken from the mice (n=8) at 2 weeks after orthotropic implantation. Six homologous peptides displayed the significantly higher expression in the patients9 plasma as early as the first pathologic stage of breast cancer. Conclusions: The amount of circulating CPN-catalyzed peptides reported here reflects the extent of this enzyme9s activity in tumors, and our results clearly indicate their strong potential as biomarkers for non-invasive and early diagnosis of breast cancer. It would certainly be naive to think that CPN-catalyzed peptides and the enzyme itself are the only biomarkers specific for breast cancer diagnosis. We do however argue that they can be used as a complementary measure for very early diagnosis of tumor growth, particularly because CPN activity within the tumor at this point is already detectable by blood sampling. Such sensitivity together with all of the features mentioned above lend well to their translation to the clinic, for breast cancer and perhaps other pathologies. Citation Format: Ye Hu. Circulating proteolytic products of carboxypeptidase N for early detection of breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2507. doi:10.1158/1538-7445.AM2014-2507
A new neural net approach to robot 3D perception and visuo-motor coordination

A novel neural network approach to robot hand-eye coordination is presented. The approach provides a true sense of visual error servoing, redundant arm configuration control for collision avoidance, and invariant visuo-motor learning under gazing control. A 3-D perception network is introduced to represent the robot internal 3-D metric space in which visual error servoing and arm configuration control are performed. The arm kinematic network performs the bidirectional association between 3-D space arm configurations and joint angles, and enforces the legitimate arm configurations. The arm kinematic net is structured by a radial-based competitive and cooperative network with hierarchical self-organizing learning. The main goal of the present work is to demonstrate that the neural net representation of the robot 3-D perception net serves as an important intermediate functional block connecting robot eyes and arms. >
Probes for Multivariant Flow Characteristics

Diagnostic methods in unsteady, multivariant flows can aim either at measuring one flow property regardless of variations in others, or at measuring each of two or more properties at the same time. This review lecture primarily addresses Eulerian detectors in a continuum, chemically inert environment undergoing a stationary random process, and assumes that the detector is simultaneously affected by two or more flow variables. An outline of the basic theory is given which examines the quasi-steady detector response and its statistical moments in terms of the statistics of the flow variable fluctuations. This theory reveals the need for reinterpretation of classic detecting techniques and sensors in regimes of current technological interest involving non-linear and high frequency phenomena. From this point of view the lecture addresses the current status of the most popular detectors and evaluates their potential in isolating the individual history of the flow velocity, density, pressure, temperature and concentration.
The Use of Ferritin-Conjugated Antibodies in Electron Microscopy

Publisher Summary This chapter discusses the blocking technique as a control for the specificity of antigen–antibody reactions in tissue. If unconjugated antibody is applied, followed by the conjugate, there are very few free antigenic sites where tagging could occur. In actual practice, however, a relatively complete block is rarely seen. There is usually a reduction in the amount of tagging, but preparations are seldom devoid of ferritin. One of the major drawbacks associated with the use of ferritin-conjugated antibodies is their large size. Ferritin is approximately 100 A in diameter, whereas the antibody is about 250 A long and 35 A wide. To reduce the dimensions of the conjugate, ferritin is coupled with an active fragment of the antibody obtained by papain digestion. The challenge that remains is to develop techniques for labeling thin sections themselves. With this accomplishment, ease, consistency, and a high degree of specificity can be reached in the study of fine structure.
Public Address and Moral Argument: Critical Studies in Ethical Tensions, Shawn J. Parry-Giles and Trevor Parry-Giles, eds.

The editors and eight other rhetorical critics have produced powerful critiques of public address with a special emphasis on the relationship between our rhetorical practices and moral issues. Thes...
A study of Solidification/Stabilization process for disposal of pentachlorophenol

Abstract Solidification/Stabilization (S/S) are emerging technologies for disposal of toxic waste. However, they have been applied mostly to inorganic toxic wastes. In the present study, we investigated the applicability of S/S technologies for disposal of a widely used toxic organic compound, pentachlorophenol (PCP), in the cementous matrix. Effect of a number of parameters (temperature, pH, sonic energy, method of mixing) on the ability of cement to hold PCP was examined. UV-VIS spectrophotometry was used to determine the leaching of PCP from cement and FT-IR was employed to study the mechanistic details. The results of the present work indicate that PCP can be almost fully retained by the cement. A very small amount of PCP that leaches from the surface of the solidified product can be reduced to a negligible amount by encapsulating it with a cement jacket.
Inhibition of human lung cyclic GMP and cyclic AMP phosphodiesterases by certain nuleosides, nucleotides, and pharmacological phosphodiesterase inhibitors

Abstract The effects of various known inhibitors on the cyclic GMP phosphodiesterase and cyclic AMP phosphodiesterase enzymatic activities found in human lung tissue were investigated. Of the five compounds studied, 1-methyl-3-isobutylxanthine was the most specific for cyclic GMP hydrolysis, while 1-ethyl-4-(isopropylidine-hydrazino-1H-pyrazolo-(3,4-b)-pyr acid, ethyl ester hydrochloride (SQ 20009) was the most potent for inhibiting cyclic AMP hydrolysis. Common non-cyclic nucleotides were tested for their inhibitory abilities only. ATP, GMP and IMP revealed significant inhibition of both phosphodiesterase activities. Certain nucleosides and cyclic nucleotides were also tested at 1 μM substrate concentrations for their ability to inhibit hydrolysis. Cyclic IMP inhibited cyclic GMP activity, but it had no effect on the cyclic AMP phosphodiesterase. The 2′-deoxy nucleosides (2'-deoxy guanosine and 2′-deoxy inosine) inhibited both enzymes; 2′-deoxy GMP inhibited mainly the cyclic GMP acitivity, while 2′-deoxy adenosine inhibited only the cyclic AMP activity. The observation that 2′-deoxy guanosine was a non-competitive inhibitor of cyclic GMP hydrolysis suggested that a site on the enzyme, distinct from the active site, might be involved in the regulation of the human lung phosphodiesterase.
The value of clofibrate in coronary heart disease

Abstract What can the physician conclude from all this confusion, and what should his practice be? First, there is no absolute indication for the use of clofibrate in patients with coronary heart disease. Second, there is no evidence that lowering lipids by the use of clofibrate helps such patients; therefore hyperlipidemia in these patients is not an indication for treatment. Third, there is no evidence that clofibrate helps patients who have had a myocardial infarction but do not have angina, whatever their serum lipid level. Fourth, one trial suggests that clofibrate may prevent sudden death in patients who have angina by some mechanism other than its effect on lipids. Fifth, there is no study of the use of clofibrate in patients over the age of 65 years. Therefore the use of clofibrate should be confined to patients with angina under the age of 65. No great claims for this drug can be made, since its efficacy may be slight once clinical coronary heart disease is established and any beneficial result remains to be confirmed. However, clofibrate is a safe drug and many will feel that patients should be given the benefit of any doubt. They will therefore use the drug until there is definite evidence that it does no good.
Designing Job Enrichment Projects

This paper describes a management strategy for a job satisfaction program utilized in a large occupational therapy department. The goal of the program is to retain satisfied, productive employees and reduce attrition of therapists and assistants. The use of job enrichment projects for occupational therapy assistants will be presented with brief descriptions of two projects.
Recognition and Classification of Seizures in Infants

Summary: Purpose: We wished to assess the reliability of the International League Against Epilepsy (ILAE) seizure classification system applied to infantile seizures and to test a proposed new classification. Methods: We first analyzed 39 seizures in 20 infants (aged 1–26 months) recorded with simultaneous closed-circuit television and EEG (CCTV/EEG). EEGs and videotapes of all seizures were independently analyzed by two epileptologists blinded to clinical histories. Videotapes of each seizure were reviewed without simultaneous EEG (phase I), and printouts of ictal EEGs were assessed without behavioral correlates (phase II). The observers classified seizures according to ILAE criteria. Interrater agreement was assessed by the kappa statistic. Results: Agreement on EEG features (phase II) was moderate (= 0.54) in identifying focal ictal onsets and substantial (= 0.79) in identifying generalized onsets. In contrast, analysis of videotapes showed substantial disagreement between observers in terms of classifying seizures as partial or generalized. Therefore, agreement between observers for partial was slight (= 0.14) and fair for generalized seizures (= 0.26). Similarly, conclusions of the observers as compared with those of a consensus panel were divergent for both partial (= 0.18) and generalized seizures (= 0.30). We therefore developed an alternative classification scheme and retested interrater agreement in a review of 50 seizures in 25 other infants. With this classification scheme, there was substantial agreement between observers (= 0.72). Conclusions: With clinical observations and interictal EEGs, seizures in infants cannot be reliably classified by current ILAE criteria. In contrast, a proposed new classification scheme based solely on semiology showed substantial reliability.
Software Piracy: Is It Related to Level of Moral Judgment?

The possible relationship between widespread unauthorized copying of microcomputer software (also known as software piracy) and level of moral judgment is examined through analysis of over 350 survey questionnaires that included the Defining Issues Test as a measure of moral development. It is hypothesized that the higher one's level of moral judgment, the less likely that one will approve of or engage in unauthorized copying. Analysis of the data indicate a high level of tolerance toward unauthorized copying and limited support for the hypothesis. The most plausible explanation for these findings is that software copying is perceived as an issue of low moral intensity. This study calls into question the software industry's strategy of concentrating exclusively on institutional compliance with copyright rules, rather than working to raise the perceived moral intensity about software piracy at the individual level. As long as the issue remains low in moral intensity, the industry cannot expect significant shifts in copying behaviors. Individuals must become more aware of and concerned about the nature and magnitude of harm to society and to the rightful copyright owners from unauthorized copying before their attitudes and behaviors come to reflect higher levels of moral judgment.
Effects of anticonvulsants on human p450c17 (17alpha-hydroxylase/17,20 lyase) and 3beta-hydroxysteroid dehydrogenase type 2.

Summary: Purpose: Women with epilepsy apparently have a higher incidence of polycystic ovary syndrome (PCOS) than do women without epilepsy. Whether the underlying disease or the antiepileptic drug (AED) treatment is responsible for this increased risk is unknown, although clinical reports implicate valproic acid (VPA) as a potential cause. The steroidogenic enzymes 3βHSDII (3β-hydroxysteroid dehydrogenase) and P450c17 (17α-hydroxylase/17,20 lyase) are essential for C19 steroid biosynthesis, which is enhanced during adrenarche and in PCOS. Methods: To determine whether the AEDs VPA, carbamazepine (CBZ), topiramate (TPM), or lamotrigine (LYG) directly affect the activities of human 3βHSDII and P450c17, we added them to yeast expressing human P450c17 or 3βHSDII and assayed enzymatic activities in the microsomal fraction. Results: Concentrations of VPA ≤10 mM had no effect on activities of P450c17; however, VPA inhibited 3βHSDII activity starting at 0.3 mM (reference serum unbound concentration, 0.035–0.1 mM) with an IC50 of 10.1 mM. CBZ, TPM, and LTG did not influence 3βHSDII or P450c17 activities at typical reference serum unbound concentrations, but did inhibit 3βHSDII and P450c17 at concentrations >10-fold higher. Conclusions: None of the tested AEDs influenced 3βHSDII or P450c17 activities at concentrations normally used in AED therapy. However, VPA started to inhibit 3βHSDII activity at concentrations 3 times above the typical reference serum unbound concentration. Because inhibition of 3βHSDII activity will shift steroidogenesis toward C19 steroid production when P450c17 activities are unchanged, very high doses of VPA may promote C19 steroid biosynthesis, thus resembling PCOS. CBZ, TPM, and LTG influenced 3βHSDII and P450c17 only at toxic concentrations.
Improving science through online commentary.

The Internet offers a timely opportunity to widen, and reduce delays in, scientific debate.
Phase II evaluation of topotecan and navelbine in patients with recurrent ovarian, fallopian tube or primary peritoneal cancer

Abstract Objective To assess the efficacy and toxicity profile in patients with recurrent ovarian or primary peritoneal cancer treated with topotecan at 2.5 mg/m 2 days 1 and 8 plus vinorelbine at 25 mg/m 2 days 1 and 8 every 3 weeks. Materials and methods Eligibility criteria included patients with recurrent primary peritoneal or epithelial ovarian cancer with either platinum-resistant or platinum-sensitive disease. Patients were required to have a performance status of ≤ 2 and normal hepatic and renal function. Response to therapy and toxicity were assessed using standard criteria. Chi square and Student's t -tests were used as appropriate. Survival was assessed with Kaplan–Meier method. Results All 40 patients enrolled were assessable for response. The median age of the patients was 58 years (range 30–82). Median treatment-free interval was 4.0 months. A total of 216 cycles of chemotherapy were administered with a median of 5.0 cycles per patient. Overall median TTP with this treatment regimen was 19 weeks (range 2–136 weeks). The response rate was 30% overall, and the response for platinum-sensitive and platinum-resistant patients was 44% (95% CI:22–69%) and 18% (95% CI:5–40%) respectively. Median progression-free survival was 3.0 months (range 1–9 months). Median overall survival was 16.4 months (range 1.5–51.7 months). Assessment of toxicity by patient showed 58% demonstrating grade 3/4 neutropenia with the vast majority being uncomplicated. No severe non-hematological toxicity was observed. Conclusion Administration of topotecan and navelbine is feasible with demonstrable activity and tolerable toxicity. This regimen may be considered especially in platinum-sensitive patients if a non-platinum based doublet is desired.
Regulation of the activity and cellular localization of the circadian clock protein FRQ

Eukaryotic circadian clocks employ autoregulatory negative feedback loops to control daily rhythms. In the filamentous fungus Neurospora, FRQ, FRH, WC-1, and WC-2 are the core components of the circadian negative feedback loop. To close the transcription-based negative feedback loop, the FRQ-FRH complex inhibits the activity of the WC complex in the nucleus by promoting the casein kinases-mediated WC phosphorylation. Despite its essential role in the nucleus, most FRQ is found in the cytoplasm. In this study, we mapped the FRQ regions that are important for its cellular localization. We show that the C-terminal part of FRQ, particularly the FRQ-FRH interaction domain, plays a major role in controlling FRQ localization. Both the mutation of the FRQ-FRH interaction domain and the down-regulation of FRH result in the nuclear enrichment of FRQ, suggesting that FRH regulates FRQ localization via a physical interaction. To study the role of FRQ phosphorylation, we examined the FRQ localization in wild-type as well as an array of FRQ kinase, FRQ phosphatase, and FRQ phosphorylation site mutants. Collectively, our results suggest that FRQ phosphorylation does not play a significant role in regulating its cellular localization. Instead, we find that phosphorylation of FRQ inhibits its transcriptional repressor activity in the circadian negative feedback loop. Such an effect is achieved by inhibiting the ability of FRQ to interact with WCC and casein kinase 1a. Our results indicate that the rhythmic FRQ phosphorylation profile observed is an important part of the negative feedback mechanism that drives robust circadian gene expression.
Crystallization behavior of polypropylene/ethylene butene copolymer blends

One polypropylene (PP) was mixed with two ethylene butene copolymers (EBM). EBM1 had 12.5 mol % of butene and was immiscible with the PP. EBM2 had 51.6 mol % of butene and was miscible with the PP. The dispersed PP in EBM1 showed fractionalized crystallization behavior with a crystallization temperature at around 45°C and a much slower isothermal crystallization rate comparing to the neat PP. The PP did not exhibit fractionalized crystallization behavior in EBM2. EBM1 did not decrease both the crystallization and melting temperatures of the continuous PP. However, EBM2 could decrease both the two temperatures. It was found that EBM2 could largely suppress the epitaxial lamellar branching of the PP. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Adenylate cyclase type 9 (AC9) polymorphism and in vivo vascular response

Background Adenylate cyclases (AC) catalyse the conversion of intracellular ATP to the second messager cyclic AMP. AC9 is the least well-characterized and most divergent of the nine AC isoforms. A common polymorphism in the AC9 gene, an Ile to Met at codon 772 due to an A to G substitution at bp 2312, resulted in reduced basal and beta-2 adrenergic receptor-stimulated AC activity in vitro. Prostaglandin (PG) E1 is a vasodilator that acts through stimulation of cAMP production. We hypothesized that the AC9 Met772 variant would result in impaired venodilation to PGE1 in vivo. Methods Vascular responses to PGE1 (2000 pg/min) infused into a phenylephrine-preconstricted dorsal hand vein were measured in 16 healthy subjects using a linear variable differential transformer. Venodilation was expressed as the percentage of reversal of the phenylephrine-induced constriction. Results Responses to PGE1 varied 13-fold among individuals (18% - 241%) but did not differ significantly in wild-type homozygotes (I/I, n= 5) and subjects carrying at least one variant Met772 allele (I/M, n= 8; M/M, n= 3) (84.8± 29.8 % versus 95.9± 68.9 %; P= 0.74). Conclusions These data suggest that the AC9 Met772 polymorphism is not associated with altered vasodilation in response to PGE1 in humans. Clinical Pharmacology & Therapeutics (2005) 77, P25–P25; doi: 10.1016/j.clpt.2004.11.097
Rethinking the Machine Metaphor Since Descartes: On the Irreducibility of Bodies, Minds, and Meanings

Michael Polanyi’s conceptions of tacit knowing and emergent being are used to correct a reductionism that developed from, or reacted against, the excesses of several Cartesian assumptions: (a) the ...
RURAL INCOME DIFFERENCES AND INSTRUMENTAL VARIABLES BEIWAL

Improving personal income in low income rural communities is of widespread interest in many areas of the United States, Canada and in other parts of the world. This paper suggests a useful method of analyzing inter-area income differences and identifying factors that are useful in developing alternative policies to raise low per capita income levels as wetl as in delineating areas for public investment. While the results of the study are of special relevance to the Omro area of the United States, the mythology and the general reacts have much wider implications.
An embedded storage framework abstracting each raw flash device as an MTD

Existing embedded flash storage systems are built based on a single MTD (Memory Technology Device) architecture no matter how many raw flash devices exist under a flash controller. The single-MTD architecture impedes exploiting device-level parallelism to further improve the performance of a storage system. In this paper, we design and implement a new embedded flash storage framework called MA (MTD-array), which abstracts each underlying raw flash device as an independent MTD device to boost performance. To verify its effectiveness, we implement a new flash file system called MA-UBIFS by incorporating UBIFS, one of the best contemporary flash file systems, into MA in Ubuntu 13.04 with 3.8.0 kernel. Simulation results from real-world applications show that MA-UBIFS outperforms UBIFS in mean response time by up to 71.6%. Further, we build an FPGA evaluation platform. Results from the hardware platform show that on average MA-UBIFS improves write and read throughput in a 2-MTD scenario by 55.2% and 84%, respectively.
Role of latent membrane protein 2 isoforms in Epstein–Barr virus latency

The oncogenic Epstein-Barr virus (EBV) infects the majority of the human population without doing harm and establishes a latent infection in the memory B-cell compartment. To accomplish this, EBV hijacks B-cell differentiation pathways and uses its own viral genes to interfere with B-cell signalling to achieve life-long persistence. EBV latent membrane protein 2A (LMP2A) provides a surrogate B-cell receptor signal essential for cell survival and is believed to have a crucial role in the maintenance of latency by blocking B-cell activation which would otherwise lead to lytic EBV infection. These two functions demand tight control of LMP2A activity and expression levels. Based on recent insights in the function of LMP2B, an isoform of LMP2A, we propose a model for how LMP2B modulates the activity of LMP2A contributing to maintenance of EBV latency.
The hematologic toxicity of interleukin-2 in patients with metastatic melanoma and renal cell carcinoma.

Background. High dose interleukin-2 (IL-2) has been found to produce durable antitumor responses in some patients, benefiting most greatly those patients with melanoma and renal cell carcinoma. In this paper, the hematologic toxicity and changes resulting from high dose IL-2 alone administered by intravenous bolus are discussed. Methods. One hundred ninety-nine consecutive patients treated with high dose IL-2 alone from January 1, 1988 to December 31, 1992 were included in this study. All patients had a diagnosis of metastatic melanoma or metastatic renal cell carcinoma and were treated at the National Cancer Institute (Bethesda, MD). Results. Anemia, requiring erythrocyte transfusions, occurred in 14% of all treatment courses, with a median of two units of erythrocytes transfused. Severe leukopenia (<1,000 leukocytes/mm 3 ) was rare (1.5% of all patients) and was not associated with any infectious complications. Severe thrombocytopenia (<30,000 platelets/ mm 3 ) occurred in 2.2% of all treatment cycles, with two patients experiencing a grade 3 hemorrhage, defined as gross blood loss, and one patient experiencing a grade 4 hemorrhage, defined as a debilitating blood loss. Defects in the coagulation pathway were common : abnormal partial thromboplastin time and prothrombin time values occurred in 64% and 25% of the treatment cycles, respectively. In addition, a mean clearance of 93% of lymphocytes from the peripheral blood was observed within 24 hours after initiating IL-2 therapy. This was followed by rebound lymphocytosis to a mean of 198% of baseline on posttreatment Day 4. There were no treatment-related deaths. Conclusions. During IL-2 therapy, adverse sequelae of anemia, thrombocytopenia, coagulopathy, and leukopenia were usually mild, transient and rarely limited therapy. A profound decrease in lymphocytes in the peripheral circulation occurred within 24 hours after initiating therapy, with a rebound occurring after stopping IL-2. No specific hematologic parameter was associated significantly with a patient's increased probability of responding to therapy. Cancer 199575 :1030-7.
Molecular dynamics simulations of imidazolium-based ionic liquid/water mixtures: Alkyl side chain length and anion effects

Abstract This paper describes molecular dynamics (MD) simulations of three ionic liquid (IL)/water mixtures at various water mole fractions: 1-butyl-3-methylimidazolium (BMIM + )/BF 4 − , 1-octyl-3-methylimidazolium (OMIM + )/BF 4 − , and OMIM + /Cl − . The goal is to elucidate the effect of alkyl side chain length and anion on the structure and dynamics of the mixtures. Replacing the BMIM + cation with OMIM + results in stronger aggregation of the cations and slower diffusion of the anions. Replacing the BF 4 − anion with Cl − alters the water distribution at low water mole fractions and slows diffusion in the mixtures. Potential experimental manifestations of the behavior in both cases are given.
Reinforcement learning algorithms as function optimizers

Any nonassociative reinforcement learning algorithm can be viewed as a method for performing function optimization through (possibly noise-corrupted) sampling of function values. A description is given of the results of simulations in which the optima of several deterministic functions studied by D.H. Ackley (Ph.D. Diss., Carnegie-Mellon Univ., 1987) were sought using variants of REINFORCE algorithms. Results obtained for certain of these algorithms compare favorably to the best results found by Ackley. >
New piezoelectric thin-shell vibration theory

In recent years, the strong demand on high-performance structures has driven the development of "smart" materials and stractures. Piezoelectric smart stri.ictures composed of passive elastic materials and active piezoelectric materials are developed recently and they seem to be very promising in a variety of engineering applications. In this paper, a new piezoelectric thin-shell vibration theory is proposed and the system electrodynamic eqtations of piezoelectric shells are formulated vising Hamilton 's principle and piezoelectricity theory. General electric and mechanical boundary conditions are also derived. The proposed piezoelectric shell theory is very generic, which can be simplified to account for many other commonly occurred geometries, such as spheres, cylinders, plates, cones, etc. Simplification of the generic theory to two plate cases (thin and thick) is demonstrated in a case study.
Education inequality in mortality: The age and gender specific mediating effects of cigarette smoking

A debate within the mortality literature centers around the impact of health behaviors on the prospects of disadvantaged groups. Meanwhile, a growing body of work illustrates the social processes that shape changes in smoking levels by socioeconomic status (SES), especially educational attainment. These literatures are merged by examining the mediating effects of cigarette smoking on education gaps in U.S. adult mortality by age and gender. Findings reveal that cigarette smoking is an important mediator of the education-mortality gap for all males and for younger females. In particular, education-mortality gaps for young men narrow considerably when cigarette smoking is accounted for, while older women experienced no reduction in the education-mortality gap with controls for smoking. These results are consistent with diffusion arguments that describe SES differences in smoking adoption by age and gender and provide strong evidence that smoking is an important differentiator of mortality risks by education.
17β-Estradiol Protects the Lung against Acute Injury: Possible Mediation by Vasoactive Intestinal Polypeptide

Beyond their classical role as a class of female sex hormones, estrogens (e.g. 17β-estradiol) exert important biological actions, both protective and undesirable. We have investigated the ability of estradiol to protect the lung in three models of acute injury induced by 1) oxidant stress due to the herbicide paraquat; 2) excitotoxicity, caused by glutamate agonist N-methyl-d-aspartate; and 3) acute alveolar anoxia. We also assessed the role of estrogen receptors (ER) ERα and ERβ and the neuropeptide vasoactive intestinal peptide (VIP) in mediating this protection. Isolated guinea pig or rat lungs were perfused in situ at constant flow and mechanically ventilated. The onset and severity of lung injury were monitored by increases in pulmonary arterial and airway pressures, wet/dry lung weight ratio, and bronchoalveolar lavage fluid protein content. Estradiol was infused into the pulmonary circulation, beginning 10 min before induction of injury and continued for 60–90 min. Lung injury was marked by signifi...
Non-conservative systems with symmetrizable stiffness matrices exhibiting limit cycles

Abstract Non-conservative dissipative systems under partial follower loading, with stiffness matrices that are symmetrizable, are reexamined with the aid of non-linear analysis. In this work, the conditions under which the above autonomous systems may experience a limit cycle response, stable (periodic attractor) or unstable (dynamic instability via flutter) in a certain region of existence of adjacent equilibria (region of divergence instability) are properly established. This region where a limit cycle response may occur is defined by an interval of values of the non-conservativeness loading parameter η with lower bound η = η0 (boundary between existence and non-existence of adjacent equilibria) and upper bound η = 0.50 (being invariant with respect to all other parameters). In this region although the set of buckling eigenvectors is complete (associated with distinct eigenvalues) there is one postbuckling equilibrium path passing through two consecutive branching points. Hence, only non-conservative systems with η > 0.50 (having all postbuckling equilibrium paths independent of each other) behave dynamically like symmetric (conservative) systems. These findings are verified with the aid of various numerical examples.
Reverse engineering legacy code for finite element field computation in magnetics

The development of code for finite elements-based field computation has been going on at a pace since the 1970s, yielding code that was not put through the formal software lifecycle. As a result, today we have legacy code running into millions of lines, implemented without planning and not using proper state-of-the-art software design tools. It is necessary to redo this code to exploit object oriented facilities and make corrections or run on the web in Java. Object oriented code's principal advantage is reusability. It is ideal for describing autonomous agents so that values inside a method are private unless otherwise so provided — that is encapsulation makes programming neat and less error-prone in unexpected situations. Recent advances in software make such reverse engineering/reengineering of this code into object oriented form possible. In this paper we reverse engineer legacy code in FORTRAN written decades ago for the computation of magnetic fields by the finite element method into the modern languages of Java and C++.
A Theoretical Study of Excited State Properties of Adenine-Thymine and Guanine-Cytosine Base Pairs

Geometries of the Watson−Crick adenine−thymine (AT) and guanine−cytosine (GC) base pairs were optimized in the ground and some selected low-lying singlet π−π* and n−π* excited states. Ground-state geometries were optimized at the Hartree−Fock level of theory without symmetry restriction. Excited states were generated by employing a configuration interaction technique involving singly excited configurations (CIS method) using the ground-state optimized geometry, and this was followed by excited-state geometry optimization under planar symmetry. The standard 6-31++G(d,p) basis set was employed in all calculations. Ground-state geometries are found to be planar; the predicted planarity was validated by the harmonic vibrational frequency calculations. Electronic excitations are found to be localized at either of the monomeric units. The existence of higher energy charge-transfer type excited states is also revealed. These states are characterized by the excitation of electrons from occupied orbitals of one mo...
Numerical modeling of the thermal behavior during the LENS® process

Laser Engineered Net-Shaping (LENS®) is an emerging manufacturing technique that ensures significant reduction of process time between initial design and final components. The fabrication of fully dense parts with appropriate properties using the LENS® process requires an in-depth understanding of the entire thermal behavior of the process. In this paper, the thermal behavior during LENS® was studied, both numerically and experimentally. Temperature distribution and gradient in the fabricated part were obtained by finite element method (FEM) simulation. The numerical results are in good agreement with the experimental observations. The numerical method may be used to optimize process parameters and predict the thermal response of LENS® fabricated components.
Combined effect of terazosin and finasteride on apoptosis, cell proliferation, and transforming growth factor-beta expression in benign prostatic hyperplasia.

Background Medical treatment of benign prostatic hyperplasia (BPH) targets relief of symptoms by causing either relaxation of the prostatic smooth muscle with α1 adrenergic blockade, or shrinkage of the gland with 5α-reductase inhibitors. We recently demonstrated that α1-blockers, such as terazosin, induce apoptosis in prostatic cells. In this study, we examined the combined effect of finasteride and terazosin on the rate of apoptosis and cellular proliferation to investigate their potential synergy at the cellular level. Methods Prostate specimens were obtained from men who were treated with either finasteride (n = 24), terazosin (n = 42), or combination therapy (n = 10) for varying time periods (1 week to 36 months) for the relief of the symptoms of BPH. The proliferative and apoptotic indices of both stromal and epithelial prostatic cell populations were determined. Antibodies against TGF-β1 and TβRII were used to examine the immunoreactivity of TGF-β1 and TβRII, respectively, in all prostate tissue sections. Results The apoptotic index in both prostate cell populations was significantly higher following the combination treatment compared to terazosin or finasteride alone. There were no significant changes in the rate of cellular proliferation with any treatment. Furthermore, there was a significant increase in TGF-β1 expression in the prostates of patients treated with terazosin or combination therapy, while there was no change in TβRII expression. Conclusions These results support the concept that induction of prostate apoptosis is a potential molecular mechanism underlying the combination effect of α1 blockade with 5α-reductase inhibitors in the effective treatment of BPH. The upregulation of TGF-β1 implies a role for this ligand as an effector of apoptosis induction in response to α1-blockade or finasteride therapy of BPH patients. Prostate 46:45–51, 2001. © 2001 Wiley-Liss, Inc.
The nature of the passive film on iron and ferrous alloys

Abstract A review is given of experiments that have contributed to a better understanding of the nature of the passive film on iron and ferrous alloys. The important questions relating to the nature of passive films on iron that are considered are: (1) the thickness —are the films two- or three-dimensional? (2) the composition —do the films contain hydrogen and cations introduced by alloying elements or inhibitors? (3) the structure —are the films crystalline spinel structures or non-crystalline glassy structures? and (4) the electronic properties —are the films insulators or semiconductors?
Aortic valve morphology is associated with outcomes following balloon valvuloplasty for congenital aortic stenosis.

Objectives Evaluate the incidence of various morphologic types of congenital AS, and the association between valve morphology and long-term outcomes, including repeat BAV, AVR, and death/transplant. Background Reports on long-term outcomes have low agreement on the influence of morphologic type. Methods We queried our institutional database and hospital billing records to identify all patients who underwent balloon aortic valvuloplasty (BAV) from 1992 through 2009. We excluded cases where morphology was not clear based on the description in the pre-BAV echocardiogram report and patients who underwent single ventricle palliation. The primary outcome of the study was the occurrence of any of the following events: repeat valvuloplasty, AVR, heart transplant, or death. Results There were 147 patients in our study cohort. The most common morphology was functionally bicuspid (n = 92, 63%), followed by functionally unicuspid (n = 20, 14%), dysplastic (n = 16, 11%), true bicuspid (n = 13, 9%), and true unicuspid (n = 6, 4%). The primary endpoint was less likely to occur in patients with functionally bicuspid valves (P < 0.01) and patients with true bicuspid valves (P = 0.03), whereas it was more likely to occur in patients with functionally unicuspid valves (P = 0.02) and patients with true unicuspid valves (P = 0.05). Multivariate Cox regression analysis demonstrated that valve type other than functionally bicuspid was associated with diminished freedom from repeat intervention, death or transplant (HR 3.3, CI 1.2 – 8.6, P = 0.02). Conclusions In our cohort, patients with functionally bicuspid aortic valves, the most common type, had improved outcomes as compared with all other morphologic types. © 2012 Wiley Periodicals, Inc.
Bias-dependant jitter of InGaAs(P) single-photon detectors

Output pulse jitter from single photon detection events in single photon sensitive detectors sets an upper limit to the useful bandwidth of a photon counting signal processing system. Unlike counting losses, single photon jitter is not improved by splitting the signal across a detector array, but rather degrades due to the introduction of additional variable propagation delays in additional wiring. We have observed that both the mean delay from photon arrival to output pulse and the delay variance (jitter) can be a strong function of detector bias conditions, as well as incident illumination conditions. We have characterized samples of both Geiger mode and negative-avalanche feedback (NAF) InGaAs(P) single photon detectors for single photon timing jitter at both 1.06 and 1.5 microns at temperatures ranging from 298K to below 200K. Using pulse-picked mode-locked laser sources, we attenuate the beam greatly to ensure that we are measuring true single photon mean delay and jitter, not a multi-photon response.
X-ray microbeam studies of brittle fractures of metals

Abstract X-ray microbeam studies of the fracture surfaces of polycrystalline iron and zinc reveal that the plastic strain associated with brittle fracture of both metals can be resolved into two parts: the pre-fracture strain and the fracture strain. Brittle fracture is therefore preceded by plastic strain. The energy associated with the fracture strain component is found to be approximately two orders of magnitude larger than the surface energy of the metal and can thus be regarded as the determining energy term for the propagation of a crack. The experimental results support the dislocation mechanism of crack nucleation in crystalline solids recently advanced by several investigators.
Computational model of interstitial transport in the spinal cord using diffusion tensor imaging.

Local drug delivery methods, including convection-enhanced delivery (CED), are being used to increase distribution in selected regions of nervous tissue. There is a need for 3D models that predict spatial drug distribution within these tissues. A methodology was developed to process magnetic resonance microscopy (MRM) and diffusion tensor imaging (DTI) scans, segment gray and white matter regions, assign tissue transport properties, and model the interstitial transport of macromolecules. Fiber tract orientation was derived from DTI data and used to assign directional dependence of hydraulic conductivity, K, and tracer diffusivity, D t , transport tensors. Porous media solutions for interstitial fluid pressure, velocity, and albumin distribution were solved using a finite volume method. To test this DTI-based methodology, a rat spinal cord transport model was developed to simulate CED into the dorsal white matter column. Predicted distribution results correspond well with small volume (∼1 μl) trends found experimentally, although albumin loss was greater at larger infusion volumes (>2 μl). Simulations were similar to those using fixed transport properties due to the bulk alignment of white matter fibers along the cord axis. These findings help to validate the DTI-based methodology which can be applied to modeling regions where fiber tract organization is more complex, e.g., the brain.