cssi/SciSciGPT-SciSciNet huggingface dataset:
On translation of antibody drug conjugates efficacy from mouse experimental tumors to the clinic: a PK/PD approach

Objectives of the present investigation were: (1) to compare three literature reported tumor growth inhibition (TGI) pharmacodynamic (PD) models and propose an optimal new model that best describes the xenograft TGI data for antibody drug conjugates (ADC), (2) to translate efficacy of the ADC Trastuzumab-emtansine (T-DM1) from mice to patients using the optimized PD model, and (3) to apply the translational strategy to predict clinically efficacious concentrations of a novel in-house anti-5T4 ADC, A1mcMMAF. First, the performance of all four of the PD models (i.e. 3 literature reported + 1 proposed) was evaluated using TGI data of T-DM1 obtained from four different xenografts. Based on the estimates of the pharmacodynamic/pharmacokinetic (PK/PD) modeling, a secondary parameter representing the efficacy index of the drug was calculated, which is termed as the tumor static concentration (TSC). TSC values derived from all four of the models were compared with each other, and with literature reported values, to assess the performance of these models. Subsequently, using the optimized PK/PD model, PD parameters obtained from different cell lines, human PK, and the proposed translational strategy, clinically efficacious doses of T-DM1 were projected. The accuracy of projected efficacious dose range for T-DM1 was verified by comparison with the clinical doses. Aforementioned strategy was then applied to A1mcMMAF for projecting its efficacious concentrations in clinic. TSC values for A1mcMMAF, obtained by fitting TGI data from 4 different xenografts with the proposed PK/PD model, were estimated to range from 0.6 to 11.5 μg mL−1. Accordingly, the clinically efficacious doses for A1mcMMAF were projected retrospectively. All in all, the improved PD model and proposed translational strategy presented here suggest that appropriate correction for the clinical exposure and employing the TSC criterion can help translate mouse TGI data to predict first in human doses of ADCs.
Re: Ethnic Differences in Estrogen Metabolism in Healthy Women

The high incidence of breast cancer observed in young African-American women (7) and the apparent aggressiveness of the disease in this ethnic group (2) might be because of biologic differences, such as genetic susceptibility to environmental factors and/or hormonal levels. We have recently shown (3) that a polymorphism in the CYP1 Al gene, which is involved in estrogen metabolism, is significantly associated with breast cancer in African-American, but not in Caucasian, women. The endogenous metabolism of estrogens is primarily oxidative and involves hydroxylation of the steroid at either C2 (2-0HE1) or C16a (16a-0HEl). While the 2-OHE1 metabolites are essentially devoid of peripheral biologic activity, 16a-0HEl is an estrogen agonist (4,5). There is evidence of an inverse association between the 2-OHEl/16a-OHEl metabolite ratio and breast cancer risk (6). We present here the basal urinary estrogen metabolite ratio (as measured by an enzyme-linked immunosorbent assay method) in 33 healthy women aged 18-73 years (7). Women taking oral contraceptives or who were pregnant or lactating were excluded. African-American women had significantly lower 2-OHEl/16a-OHEl urinary metabolite ratios than did Caucasian women (Table 1). No effect of age, weight, smoking status, or CYP1A1 genotype was observed. The observed differences in the estrogen metabolite ratio between CauTable 1. Base-line ratios of urinary estrogen metabolites (2-OHE1/16a-OHE 1) according to ethnicity*
NDE of historic structures: USS Constitution

The USS Constitution is the oldest flowing commissioned ship in the US Navy. Recently, the USDA Forest Service, Forest Products Laboratory, was involved in developing an inspection methodology for the use of Navy personnel responsible for maintaining the ship. Several NDE techniques were used to assess the condition of fasteners in the ship and the general condition of the wood comprising it. Radiography and ultrasonic techniques were used to assess the condition of the copper pins used as fasteners. Stress wave NDE techniques were used to locate areas of degradation in the wood. This paper describes the stress wave techniques employed and results obtained form their use.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
On the other hand: the stereoselectivity of drug action at ion channels.

Ion channels are pharmacological receptors with specific drug binding sites. These binding sites define specific structure–function relationships for the actions of drug classes. Interpretation of these structure–function relationships may be complex because of state-dependent drug-channel interactions. These state-dependent interactions determine affinity and access of drug to binding sites and may result in both quantitative and qualitative changes in structure–function relationships including stereoselectivity. A channel-active drug may exhibit antagonist or activator properties according to membrane potential and the stereoselectivity of interaction may also change with channel state. © 1994 Wiley-Liss, Inc.
Mercury Absorption in Aqueous Oxidants Catalyzed by Mercury(II)

The absorption of elemental Hg vapor into aqueous solution containing Hg(II) was measured in a stirred cell contactor at 25 and 55 °C. In 0.8 M HNO3, the reaction is first-order in Hg and Hg(II), respectively. The overall second-order rate constant is given by k2 = 2.90 × 109 × exp(−1765/T). In 0.8 M HNO3 with the addition of H2O2, the reaction is first-order in Hg, H2O2, and Hg(II), respectively. The overall third-order rate constant is given by k3 = 2.13 × 1023 × exp(−10110/T). The addition of Fe2+ or Fe3+ has no immediate effect on mercury removal. In 0.8 M HNO3 with the addition of K2Cr2O7, the reaction is first-order in Hg, Cr2O7, and Hg(II), respectively. The overall third-order rate constant is 4.3 × 108 M-2 s-1 at 25 °C. For mercury absorption in Hg(II) obtained by HgCl2 injection, the presence of HNO3 greatly enhanced Hg absorption. H2SO4 had a comparable positive effect while HCl had a negative effect. Succinic acid−NaOH buffer solution greatly enhanced Hg absorption in Hg(II), but NaHCO3−NaOH i...
Navigating the Road Ahead: Public Health Challenges and the Interactive Systems Framework for Dissemination and Implementation

Public health is currently faced with an array of critical challenges and disconnects. Research and evaluation have identified a number of evidence-based strategies for effecting behavior change at individual, group, organizational, and environmental levels, all of which hold promise for leading to substantial reductions in morbidity and mortality, and increased quality of life. Unfortunately, there is huge variability across the public health system in awareness of the value of using evidence to inform decision making, let alone in capacity to locate, assess, compare, select, justify, adapt, implement, and evaluate evidence-based strategies, or to participate in building the evidence base for practice-based innovations. As a result, many communities may not be benefitting from research-tested and practice-based strategies that could help them to meet their public health goals more efficiently and effectively. CDC's Interactive Systems Framework for Dissemination and Implementation (ISF), released in 2008, was designed to help close this gap between research and practice. This commentary identifies the ways in which the ISF framework is useful in addressing the research practice gap; revisits the elements of the framework that have continued to guide research and practice in fruitful ways; and highlights areas that need further development to meet current public health challenges.
Saludos Amigos: Hollywood and FDR's Good Neighbor Policy

Every student of American film history is familiar with how, after the myth-making aesthetic success of Citizen Kane (1940), Orson Welles’ second film, The Magnificent Ambersons (1942), was edited ...
The Return of Political Theology: The Scarf Affair in Comparative Constitutional Perspective in France, Germany and Turkey

The contemporary world is caught in the throes of religious and cultural conflicts which destabilize what seemed like accepted walls of separation between the state and religion, the public sphere of politics and law and the private realm of faith and belief. This article examines the destabilization of these dualisms by focusing on the constitutional and political controversies around the wearing of the “hijab,” religiously mandated clothing by Muslim women, in France, Germany and Turkey.
The isolation of high molecular weight DNA from whole organisms or large tissue masses

Abstract The isolation of high molecular weight DNA from whole organisms (or large tissue masses) is improved by the disruption of tissues by freeze-grinding and the rapid introduction of organic deproteinizers.
AMBULATORY ENDOVASCULAR SURGERY : COST ADVANTAGE AND FACTORS INFLUENCING ITS SAFE PERFORMANCE

PURPOSE To perform a retrospective analysis of chronic limb ischemia and determine whether endovascular surgery can be performed safely and cost effectively on an ambulatory basis. METHODS Among 42 patients undergoing endovascular interventions for lower limb ischemia over a 12-month period ending October 1997, 32 (18 men, mean age 68 years, range 44 to 89) were treated solely by endovascular interventions. These patients were grouped according to time inhospital: 20 (63%) patients had endovascular procedures performed on an ambulatory basis, 7 (22%) were hospitalized for > 24 hours, and 5 (16%) required an overnight stay. The angioplasty procedures, which included placement of 21 stents, were performed in the abdominal aorta (n = 1) and the common iliac (n = 9), external iliac (n =7), superficial femoral (n = 11), popliteal (n = 5), tibioperoneal (n = 7), and subclavian (n = 1) arteries. Hospital charges were compared for the 3 groups. RESULTS Other than the presence of coronary artery disease, there were no significant differences in demographics or risk factors among the 3 groups. Angioplasty was technically successful in all patients, and there were no procedural complications. Patients with tissue loss required hospitalization more frequently compared to those with claudication. Significantly more patients who were hospitalized had epidural anesthesia as opposed to local when compared to the ambulatory group, 43% versus 5%, respectively (p = 0.04). Excluding professional fees, mean total hospital cost differed significantly between the ambulatory group and the group of patients with a hospital stay > 24 hours ($8227 versus $40,383, respectively; p = 0.03) and between the 2 hospitalized groups ($9476 for overnight stay versus $40,383 for > 24-hour stay, p = 0.03). CONCLUSIONS Peripheral endovascular interventions can be performed safely on an ambulatory basis resulting in decreased hospital cost. Patients who receive epidural anesthesia, require concomitant open vascular reconstruction, present with tissue loss, or have unstable medical conditions are more likely to require hospitalization.
Some test results of an anti-Cherenkov photomultiplier tube

Abstract We report on the beam test results of a photomultiplier tube (PMT) specially designed to suppress the signal due to Cherenkov light emitted by window glass when impacted by relativistic charged particles. This signal becomes a concern when it is comparable to the true PMT signal, especially in the case of calorimeters, where the response is at the level of a few photoelectrons per GeV. This design allows for placement of these PMTs behind the calorimeter without concern for hot spots from the Cherenkov background.
Identification of the tet(B) resistance gene in Streptococcus suis.

Abstract The tetracycline resistance gene, tet(B), has been described previously in Gram negative bacteria. In this study tet(B) was detected in plasmid extracts from 17/111 (15%) Streptococcus suis isolates from diseased pigs, representing the first report of this resistance gene in Gram positive bacteria.
Nonlinear integral inequalities of the Volterra type

We are studying the integral inequalitywhere all functions appearing are defined and increasing on the right half-axis and take the value zero at zero. We are interested in determining when the inequality admits solutions u(x) which are non-vanishing in a neighbourhood of zero. It is well-known that if ψ(x) is the identity function then no such solution exists. This due to the fact that the operator defined by the integral on the right-hand side of the equation is linear and compact. So if we are interested in non-trivial solutions it is natural to require that ψ(x) > 0 at least for all non-zero points in some neighbourhood of zero. One of the typical examples is the power function ψ(x) = xα, where α < 1. This situation was explored in [2]. The functions a(x) that admit non-zero solutions were characterized by Bushell in [1]. For a general approach to the problem we refer to [2], [3] and [4].
Community Networks: Where Offline Communities Meet Online

This study explores the design and practice of the Blacksburg Electronic Village (BEV), a mature networked community. We describe findings from longitudinal survey data on the use and social impact of community computer networking. The survey data show that increased involvement with people, issues and community since going online is explained by education, extroversion and age. Using path models, we show that a person's sense of belonging and collective efficacy, group memberships, activism and social use of the Internet act as mediating variables. These findings extend evidence in support of the argument that Internet use can strengthen social contact, community engagement and attachment. Conversely, it underlines concern about the impact of computer networking on people with lower levels of education, extroversion, efficacy, and community belonging. We suggest design strategies and innovative tools for non-experts that might increase social interaction and improve usability for disadvantaged and underrepresented individuals and groups.
Rapid Virologic Response: A New Milestone in the Management of Chronic Hepatitis C

Background. Rapid virologic response (RVR), defined as an undetectable serum hepatitis C virus (HCV) RNA level at week 4 of treatment, is emerging as an important milestone in the treatment of patients who have chronic hepatitis C by use of pegylated interferon-alfa and ribavirin-the current standard of care. This assessment is being used to individualize treatment duration, which is currently recommended as 48 weeks in patients infected with HCV genotype 1 (G1) and 24 weeks in those infected with HCV G2 or G3. Methods. We collated information from studies including assessment of HCV RNA level at week 4, specifically highlighting the relationship between RVR and other predictors of treatment outcome and the manner in which RVR can be used to optimize treatment outcomes for specific patient groups. Results. The role of RVR in the treatment of patients with chronic hepatitis C varies according to viral genotype. Among patients with HCV G2/G3 infection, several studies have shown that shortening the treatment duration to 12-16 weeks is effective among those who attain RVR. In contrast, RVR may be used as an indicator for both shortened and extended treatment durations among patients with HCV G1 infection. HCV G1-infected patients with low baseline viral load who attain RVR may be effectively treated for 24 weeks, whereas patients who do not attain RVR may be candidates for an extended 72-week regimen. Conclusions. RVR is rapidly becoming a new tool for predicting treatment outcomes in patients with chronic hepatitis C and represents a key opportunity to individualize therapy according to treatment-related viral kinetics.
Selected nanotechnologies for renewable energy applications

As the world faces serious energy challenges, the development and implementation of renewable energy technologies become increasingly important. In this article, we offer a glimpse of the role nanotechnology, in particular, innovations of nanostructures and nanomaterials, is playing in the development of selected renewable energy technologies. These technologies, based on the authors' research interests, include (1) converting the energy of sunlight directly into electricity using solar cells; (2) converting solar energy into hydrogen fuel by splitting water into its constituents; (3) storing hydrogen in solid-state forms; and (4) utilizing hydrogen to generate electricity through the use of fuel cells. It is clear that nanotechnology-enabled renewable energy technologies are starting to scale up dramatically. As they become mature and cost effective in the decades to come, renewable energy could eventually replace the traditional, environmentally unfriendly, fossil fuels. Published in 2007 by John Wiley & Sons, Ltd.
Virtual reality: a training tool in the 21st century for disabled persons and medical students

Virtual Reality (VR) technology will emerge as an excellent tool for training in the 21st century. VR can be defined as a computer integrated system that supports user interaction allowing him to participate in an environment that mimics a scenario in the real world. VR environments allow individuals with disabilities to become immersed in a computer simulated environments that mimic real world scenarios to facilitate the learning of cognitive and physical skills. The use of VR when training medical students should provide hands-on experimentation and improve the reliability of their work activities. Also, VR environments will afford the opportunity to repeat a procedure at any point of the cycle and minimize risks of being in contact with bodily fluids as well as the occurrences of accidents from surgical tools. Training efforts undertaken in virtual environments should enhance the transferability of information while reducing training time, cost and errors. This paper looks at the use of VR as a training tool for individuals with disabilities as well as medical student trainees.
Luteinizing Hormone-Releasing Hormone Quantified in Tissues and Slice Explant Cultures of Postnatal Rat Hypothalami

LH-releasing hormone (LHRH) peptide from postnatal rat preoptic area (POA)/hypothalamic tissues in vivo and slice explant cultures maintained in vitro was quantitated using an enzyme-linked immunosorbant assay. Moreover, messenger RNA (mRNA) copy number was calculated in LHRH neurons maintained in culture using in situ hybridization histochemistry with autoradiographic film analysis. POA/hypothalami from postnatal day 5–6 pups averaged 1250 pg of LHRH, with approximately 28% of peptide residing within rostral tissues where most LHRH perikarya reside. Explant cultures maintained 18 days in vitro contained 30.4–92.0 pg/slice with a whole animal total of 244.8 pg. Considering cell numbers in vivo and in vitro, LHRH neurons in whole animal produce 1.0 pg of LHRH/cell, whereas those in culture average 2.0 pg/cell. Furthermore, LHRH mRNA copies/cell in organotypic culture was estimated conservatively at 1410 copies/cell, a relatively high number. This work shows that, compared with whole animal, cultures have s...
Transfer Rates: A Problematic Criterion for Measuring the Community College

Studies of transfer rates typically yield inaccurate perceptions about the role community colleges play in the attainment of baccalaureate degrees. This chapter provides a clearer picture than the one that emerges from the literature.
Cephalic vein measurement before forearm fistula creation: does use of a tourniquet to meet the venous diameter threshold increase the number of usable fistulas?

Objective. To optimize forearm radiocephalic fistula success, many programs recommend a minimal cephalic vein diameter of 0.25 cm or greater on preoperative sonographic mapping. It is not established, however, whether a vein diameter before or after application of a tourniquet should be used in determining suitability for creation of a forearm fistula. Methods. Before forearm radiocephalic fistula placement, preoperative sonographic mapping measured the cephalic vein diameter before and after application of a tourniquet. The patients fell into 2 groups: those with a pretourniquet vein diameter of 0.25 cm or greater (group 1) and those with a pretourniquet vein diameter of less than 0.25 cm that increased to 0.25 cm or greater after application of the tourniquet (group 2). The adequacy of each fistula for dialysis was determined clinically. Results. Among 73 radiocephalic fistulas with known clinical outcomes, 28 were in group 1, and 45 were in group 2, on the basis of sonography. Fistula success rates were similar in group 1 patients (11 [39%] of 28) and group 2 patients (15 [33%] of 45) (P = .624, Fisher exact test). Inclusion of group 2 patients increased the number of patients recommended for placement of forearm fistulas and increased the total number of usable forearm fistulas from 11 to 26. The overall success rate of forearm fistulas was lower in women (19% versus 50%; P = .015, Fisher exact test). Conclusions. The use of a venous tourniquet increases the number of patients eligible for forearm fistulas without decreasing the adequacy rate of these fistulas. Therefore, a tourniquet should routinely be used in patients with small cephalic veins on pretourniquet evaluation.
Regulation of ERBB2 Receptor by t-DARPP Mediates Trastuzumab Resistance in Human Esophageal Adenocarcinoma

Esophageal adenocarcinoma (EAC) is an aggressive malignancy with a poor outcome. Although targeting ERBB2 with trastuzumab has been evaluated in clinical trials, the molecular mechanisms of trastuzumab resistance remain uncharacterized in EAC. The dopamine and cyclic AMP-regulated phosphoprotein of MR 32000 (DARPP-32), also known as PPP1R1B, is located together with ERBB2 at the 17q12-q21 amplicon. We evaluated the expression of a transcript variant of DARPP-32 (t-DARPP) and ERBB2 in 141 primary tumors and investigated the role of t-DARPP in trastuzumab resistance using OE19 and OE33 EAC cell models. Overexpression of t-DARPP mRNA was detected in two-thirds of tumors with a correlation between ERBB2 and t-DARPP overexpression levels (r = 0.58, P = 0.003). Cell viability and clonogenic survival assays showed that t-DARPP increased survival by 40% in response to trastuzumab (P < 0.01). The Annexin-V staining and Western blot analysis indicated that t-DARPP effectively abrogated trastuzumab-induced apoptosis, inhibited cleavage of caspase-3, and blocked trastuzumab-induced dephosphorylation of ERBB2 and AKT proteins. The knockdown of endogenous t-DARPP reversed these effects and sensitized cells to trastuzumab (P < 0.01). The cycloheximide-based protein degradation analysis indicated that t-DARPP extended the half-life of ERBB2, explaining the increase in the basal levels of ERBB2, p-ERBB2(Y1248), and p-AKT(S473). Coimmunoprecipitation and Western blot analysis showed that t-DARPP associated with ERBB2 in a protein complex, and interfered with trastuzumab binding to the ERBB2 receptor. Using EAC-xenografted mouse model, t-DARPP enhanced tumor growth and rendered tumors unresponsive to trastuzumab. This study establishes t-DARPP as a mediator of trastuzumab resistance and underscores its potential importance in clinical trials of EAC.
Radiation detection with distributed sensor networks

Given the heightened awareness and response to threats posed to national security, it is important to evaluate, and if possible, improve current measures being taken to ensure our nation’s safety. With terrorism so prevalent in our thoughts, the possible risk of nuclear attacks remains a major concern. Portal monitors are one type of technology that may be used to combat this risk. Their purpose is to detect nuclear materials and, if found, alert first responders to such a discovery. Los Alamos National Laboratory (LANL) is currently working on an alternative to these costly portal monitors through the Distributed Sensor Network (DSN) project. In collaboration with the University of New Mexico (UNM), this project aims to develop distributed networks of heterogeneous sensors with the ability to process data in-situ in order to produce real-time decisions regarding the presence of radioactive material within the network. The focus of the work described in this paper has been the evaluation of current commercial products available for application deployments, as well as the development of a sensor network in simulation to reduce key deployment issues.
Phenotypic differences in cardiovascular regulation in inbred rat models of aerobic capacity.

Koch, Lauren Gerard, Steven L. Britton, John C. Barbato, David W. Rodenbaugh, and Stephen E. DiCarlo. Phenotypic differences in cardiovascular regulation in inbred rat models of aerobic capacity. P...
Detection of Epstein-Barr Virus in T-Cell Prolymphocytic Leukemia Cells in vitro

Background: Epstein-Barr virus (EBV) is closely associated with the development of a number of tumors. During latent infection, EBV continuously expresses a number of viral genes which are essential for cell transformation and maintenance of the malignant phenotype of EBV-related tumors. There has been no previous link between EBV and T-cell prolymphocytic leukemia (T-PLL), a distinctive form of leukemia derived from T-cells at an intermediate stage of differentiation between a cortical thymocyte and a mature peripheral blood T-cell. Objective: To determine if EBV was present in the T-PLL cells collected. Study design: T-PLL cells were isolated from the peripheral blood of a patient diagnosed with T-PLL and continuously cultured for about 1 year. The existence of EBV in these cells was detected using multiple strategies including PCR, Western blotting, immunofluorescent assay and flow cytometry analysis. Results: The EBV genome was present in these T-PLL cells by PCR analysis across multiple sites in the viral genome. In addition, these T-PLL cells expressed a number of EBV latent antigens. The EBV oncoproteins LMP1, EBNA1 and EBNA3C were expressed in the majority of the infected cells. Conclusion: This report suggests a potential link between EBV infection and T-PLL and provides new information about the potential contribution of EBV in the initiation or maintenance of T-PLL.
In situ observation of texture development in olivine, ringwoodite, magnesiowüstite and silicate perovskite at high pressure

Magnesium silicates are the dominant minerals in the earth’s mantle. Their preferred orientation is important for understanding the rheology and seismic anisotropy in the deep earth. Here we report results of radial synchrotron diffraction diamond anvil cell (DAC) experiments on San Carlos olivine, axially compressed to 50 GPa. Experiments were performed at room temperature, except for brief laser heating to induce phase transformations. High stresses and development of preferred orientation were observed in diffraction images. Quantitative texture information was obtained by analyzing the images with the Rietveld method. With increasing pressure (between 9 and 43 GPa) olivine develops a texture with [001] axes perpendicular to the compression direction that is compatible with {hk0}[001] pencil glide. Ringwoodite (between 20 and 50 GPa) develops weak preferred orientation with {011} lattice planes perpendicular to the compression direction. After the phase transformation, perovskite and magnesiowqstite display transformation textures that are then modified by continuing deformation. Magnesiowqstite has a weak h111i maximum parallel to the compression direction that changes towards h001i with increasing deformation. Perovskite, transforming from olivine, has a pronounced (100) transformation texture and with increasing deformation a {012} maximum develops. The transformation texture is probably produced by mechanical {110} twinning and nucleation in orientations that minimize elastic strain energy. The deformation texture of perovskite is due to slip. D 2004 Elsevier B.V. All rights reserved.
Demonstration of "discontinuities" in the time derivatives of body surface potentials, and their prospective role in noninvasive imaging of the ventricular surface activation map

The ill-posed nature of the inverse electrocardiography problem has necessitated use of regularization techniques as a means of rendering epicardial potential maps. Significant inaccuracies are introduced by such methods (on the order of 50% error relative to the actual map), due to imposition of the regularizing functionals. It has been previously shown that the generator of topological changes in epicardial potential maps during ventricular activation is of much lower order than the epicardial maps themselves, yet sufficiently constrains the full ventricular surface activation mapping problem so as to obviate the need for further regularization. The mathematical formalism for reconstructing this generator has previously been presented under the assumption of negligible depolarization wavefront thickness, and requires identification and processing of "step discontinuities" predicted to occur in body surface potential derivatives. Using principal component analysis and spatial averaging methods, we have examined this fundamental prediction of the formalism in the context of a nonzero depolarization wavefront thickness (leading to prediction of dominant body surface potential derivative deflections with rise times comparable to those of ventricular electrogram intrinsic deflections). Studies of the body surface potential data obtained in three normal subjects supports the predictions of the theory, thereby suggesting the possible usefulness of the approach as an alternative to traditional regularization methods. >
Biological specificities of 4,5-dehydro analogues of isoleucine and alloisoleucine.

The synthesis of 2-amino-3-methyl-4-pentynoic acid with a configuration corresponding to alloisoleucine has been reported (4), and a partial hydrogenation of this compound would afford a method of obtaining w-dehydroalloisoleucine. However, in the method of synthesis of 2-amino-3-methyl-4-pentynoic acid herein reported, a mixture of both of the diastereoisomeric forms of the acetylenic derivatives was obtained. Subsequent fractional recrystallization of the mixture separated the isomers into the two racemic forms. Partial hydrogenation of the appropriate triple bond compound produced either w-dehydroisoleucine or w-dehydroalloisoleucine, and complete hydrogenation yielded the anticipated nn-isoleucine or nn-alloisoleucine. The ethylenic analogues are more effective growth inhibitors than the acetylenic deriviatives for Escherichia coli, but for Lactobacillus arabinosus the relative inhibitory activity depends upon whether the antagonism of isoleucine or of valine is being determined. Under appropriate conditions, antagonism of both isoleucine and valine by these analogues can be demonstrated with both organisms.
Evolvable real-time C3 systems

This paper describes MITRE's Evolvable Real-Time Command, Control, and Communications (C3) systems initiative that attempts to develop an approach that would enable current real-time systems to evolve into the systems of the future. In particular, this article describes the infrastructure requirements that we have developed. We first provide an overview of the current real-time C3 systems and describe the systems of the future. Next, we describe some candidate architectures that we have examined for future systems. Then a detailed discussion of the requirements for the infrastructure are given. The main focus is on operating systems, data management systems, and communication systems requirements. The discussion is based on the candidate architectures that we have examined. The project has chosen Airborne Warning and Control System (AWACS) as an example to test out the concepts and architectures to be developed.
Endocytosis of beta 2 integrins by stimulated human neutrophils analyzed by flow cytometry.

Flow cytometry and fluorescently labeled mono- clonal antibodies were used to investigate endocytosis of human neutrophil f32 integrins following cellular activa- tion. CD18 initially present on the cell surface cycled in two phases after exposure to formyl peptide or platelet- activating factor. The first phase lasted 3 mm at 37#{176}C; af- ter a lag, CD18 was specifically internalized at approxi- mately 20%/mm. Subsequently a second phase was detec- table consisting of exponential reduction of internal fluorescence with a half-time of approximately 2 mm, representing probe reexpression. At peak endocytosis ap- proximately 40% of CD18 was internalized. All of the in- ternalized CD18 was associated with aM (CR3); no en- docytosis of aL (LFA-1) was observed. When neutrophils were stimulated with phorbol esters or calcium iono- phore, CD18 was internalized much more slowly (ti/2 = 5 mm) and probe was not reexpressed. Endocytosis of CD18 may participate in regulating neutrophil adhesive- ness, removing activated receptors, or permitting recep- tor recycling. J. Leukoc. Rio!. 53: 462-469; 1993.
Performance characteristics of common immunologic biomarkers used in clinical trials

620 Background: Standardization of cell-based immunologic monitoring is becoming increasingly important as methods for measuring cellular immunity become more complex. We assessed the ability of 2 ...
Follow-Up and Salvage Therapy for Recurrent Hepatocellular Carcinoma

Although liver transplantation has become a viable option for treatment of many patients with hepatocellular carcinoma (HCC), the limited availability of donor organs and the strict criteria for organ transplantation limit the use of transplantation for this disease. Hepatic resection remains the gold standard nontransplant treatment modality and is still the first-line treatment in many centers.
Test Results of Thiocyanate in Dairy Products in the Market

Objective To understand the thiocyanate content in dairy products in the market through the determination of thiocyanate in the samples of dairy products.Methods The thiocyanate in samples was detected by ammonium ferric sulfate spectrophotometry.Results The thiocyanate contain was detected in all the 9 samples,with the positive rate 100%.The content of thiocyanate was 5-40 mg/kg.The brands of these 9 samples accounted for 55.6% of total dairy product brands in the market,in which the milk powder brands accounted for 33.3% of total milk powder brands in the market;the infant milk powder brands accounted for 50.0% of the total;and the milk brands accounted for 40.0% of the total.Conclusion The proportion of dairy products in the market containing thiocyanate is at a high level,but the content is low.Investigation should be conducted to test the background value of thiocyanate in raw milk,so as to provide scientific theoretical basis for the supervision department.
Epidemiological Investigation on Drug Abusers in Community Methadone Maintenance Treatment Clinic in Zhenjiang City

[Objective] To understand the characteristics of methadone maintenance treatment(MMT) participants such as demography,substance abuse,the age of using the drug for the first time,sexual behavior and out-patient treatment in Zhenjiang City,so as to provide evidence for developing effective and comprehensive measures for AIDS control.[Methods]A total of 309 drug addicts who were accepted in Zhenjiang MMT clinic from March 2006 to June 2008 were conducted questionnaire survey which included the demographic characteristics,behavior of sharing injector and sexual behavior.[Results] Of the 309 drug addicts,males accounted for 71.2%(220/309) while the percentage of female was 29.8%.The average age was 33.5±6.0 years old,259 drug addicts(83.5%) had intravenous drug abuse behavior,the average number of daily drug use 1 month before treatment was 2.6±1.1 times,median of 2 times;the number of injecting drug use was 65.8±41.4 in average1 month before treatment,median of 60 times;average daily cost of drugs was 446.9±306 yuan,median of 300 yuan.54 drug addicts(17.5%) had been caught by the public security departments 3 months before treatment.210(68.2%) had non-spuse sexual behavior,while only 78(36.8%) had used condoms during their last sex behaviors.3 HIV positive cases were detected,the positive rate was 0.98%(3/309);11 cases were syphilis positive,positive rate was 3.5%(11/309);232 were hepatitis C antibody positive,the positive rate was 75.1%(232/309);12 were HSAg positive,the positive rate was 3.9%(12/309).[Conclusion]The participants of MMT clinic have high-risk of HIV transmission.It's highly necessary to implement health education of AIDS prevention and behavioral intervention while conducting methadone maintenance treatment.
BingeOn Under the Microscope: Understanding T-Mobiles Zero-Rating Implementation

The popularity of mobile devices for ubiquitous Internet access has led to exploding demand for relatively scarce cellular bandwidth. As a result, cellular operators increasingly turn to creative ways to manage their customers’ demand on capacity, using traffic shaping and transcoding and zero-rating. With zero-rating, Internet Service Providers (ISPs) do not charge users for traffic sent to/from certain services, often because those services agree to use limited bandwidth resources. Perhaps the most well-publicized of case in the U.S. is T-Mobile’s “BingeOn ” service, which zero-rates video streams from a large number of partner sites. In this paper, we address this issue by conducting a case study of T-Mobile’s zero-rating policy to understand its implications for users and content providers in terms of data quota, performance, and QoE. We focus on T-Mobile and BingeOn due to their recent controversy, but we believe that lessons learned from this exercise will readily apply to other carriers using similar technologies to implement their policies.
The Use of Prostate Specific Antigen for Prostate Cancer Screening: A Managed Care Perspective

AbstractA large nonprofit staff model Health Maintenance Organization experienced increased use of prostate specific antigen (PSA) as a screening test for prostate cancer beginning in May 1991. A critical evaluation of the evidence in support of PSA screening was done and concluded that the use of PSA to screen for prostate cancer did not meet the criteria for an effective screening program. A guideline stating that PSA was not recommended as a screening test was implemented focusing on a model of shared decision making. PSA test ordering decreased significantly when patients were fully informed about the evidence for PSA screening. If PSA screening had continued at the peak rate, the cascade of intervention initiated by screening would have resulted in significant complications and approximately $4,800,000 in increased costs.
Book Review, Nancy MacLean, Freedom is Not Enough: The Opening of the American Work­place, Cambridge: Harvard University Press, 2006. pp. 496.

In her compelling and important new book, Nancy MacLean describes a fundamental transformation of postwar American society from a “culture of exclusion” to one that values race, sex, and ethnic diversity, especially in the workplace. According to MacLean, the contours of modern American society — with its cultural commitment to diversity accompanied by some continuing economic stratification — are the joint handiwork of the heroic efforts of civil rights activists and the conservative response to those efforts. In describing the always complicated and double-sided dynamic of creating a more inclusive workplace, MacLean has produced a historiographic powerhouse. At the heart of the book is MacLean’s unearthing of the hard work of women and minority activists who took advantage of Title VII of the Civil Rights Act of 1964, engaged the administrative machinery of the Equal Employment Opportunity Commission, and revolutionized the American workplace. Because MacLean takes employment — rather than the flashier and better excavated ground of education, voting rights, or public accommodations — as her focus, she importantly reorients the history of civil rights. MacLean views employment as central to notions of citizenship, and she emphasizes the preeminence of workplace change in the larger civil rights struggle and in the broader transformation of American society.
Conclusion and Implications

In this chapter I revisit some key terms and summarize the recently arrived Karenni refugees’ transnational trajectories and their accumulating, existing, and emerging language and literacy skills as part of their refugee experiences. The chapter highlights the pedagogical and practical implications, especially for educators, service providers, practitioners, and resettlement agencies.
High-Purcell high-quantum-yield gap-plasmon spontaneous emission enhancement based on optically thin metallic substrates

We theoretically predict optically thin metallic substrates facilitates high-Purcell (> 104), high-efficiency (>50%) gap-plasmon spontaneous emission with vanishing gap size. The enhancement is almost spatially uniform and does not suffer from quenching that commonly exist in previous structures.
Audio-Visual beamforming with the Eigenmike microphone array an omni-camera and cognitive auditory features

Audio-visual beamforming involves both an acoustic sensor and an omni-camera to form a composite 3D audio-visual representation of the environment. Information from the respective modalities is combined in the process of acoustic localization taking into account high level cognitive features of the signals, namely the presence of specific sounds - speech and tones - which have characteristic signatures in specific spectral bands. We compare the results from two systems. One is a custom-built architecture based on the MH Acoustics Eigenmike microphone array and a consumer grade omni-camera (Bloggie). The other is the commercially available Visisonics Audio-Visual (AV) camera. We show that the performances of the two systems are comparable.
Ecological Networks and Neighborhood Social Organization.

Drawing on the social disorganization tradition and the social ecological perspective of Jane Jacobs, the authors hypothesize that neighborhoods composed of residents who intersect in space more frequently as a result of routine activities will exhibit higher levels of collective efficacy, intergenerational closure, and social network interaction and exchange. They develop this approach employing the concept of ecological networks—two-mode networks that indirectly link residents through spatial overlap in routine activities. Using data from the Los Angeles Family and Neighborhood Survey, they find evidence that econetwork extensity (the average proportion of households in the neighborhood to which a given household is tied through any location) and intensity (the degree to which household dyads are characterized by ties through multiple locations) are positively related to changes in social organization between 2000–2001 and 2006–2008. These findings demonstrate the relevance of econetwork characteristics...
Convergence and Regularization of Sampling Series

This chapter consists of an overview of recent results concerning the convergence and regularization of the quintessential sampling series, the cardinal sine series. Conditions, that go beyond those associated with the standard theory, are formulated that ensure reconstruction by this series. The conditions are one of two types: (i) on the coefficients or samples or (ii) on the functions or signals being reconstructed. A class of regularization methods, that in effect consist of mollifications of cardinal sine series, is discussed. One of the highlights is a result that shows how piecewise polynomial splines and certain variants can be regarded as such mollifications.
Lay Beliefs About the Accuracy and Value of Cancer Screening.

Introduction Appreciating the accuracy and value of cancer screening is essential to informed decision making about screening. This study’s objectives were to (1) examine people’s beliefs about the accuracy and value of cancer screening, and (2) determine whether sociodemographics, cancer beliefs, and shared decision making are associated with these beliefs. Methods Data from the National Cancer Institute’s Health Information National Trends Survey (cycle 4, August–November 2014) were used. Respondents were non-institutionalized adults (aged ≥18 years, n=3,677). Weighted generalized linear modeling was used to examine bivariate and multivariate associations between key covariates and beliefs about cancer screening (assessed by four-item scale and independently). Secondary analyses examined whether these beliefs were associated with self-reported cancer screening. Data were analyzed between 2016 and 2017. Results Only 5.6% (n=189) of respondents answered all four cancer screening items correctly. Men, racial/ethnic minorities, and those with lower education and higher cancer fatalism were less likely to have accurate beliefs about cancer screening. However, those who reported shared decision making for colorectal cancer screening were more likely to know that “when a test finds something abnormal, more tests are needed to know if it is cancer” and “when a test finds something abnormal, it is [not] very likely to be cancer” (adjusted risk ratio=1.13, p Conclusions Educators, researchers, and clinicians should consider opportunities (e.g., through shared decision making) to improve the accuracy of individuals’ beliefs about cancer screening.
Electron-Enhanced Atomic Layer Deposition of Boron Nitride Thin Films at Room Temperature and 100 °C

Electron-enhanced atomic layer deposition (EE-ALD) was used to deposit boron nitride (BN) thin films at room temperature and 100 °C using sequential exposures of borazine (B3N3H6) and electrons. Electron-stimulated desorption (ESD) of hydrogen surface species and the corresponding creation of reactive dangling bonds are believed to facilitate borazine adsorption and reduce the temperature required for BN film deposition. In situ ellipsometry measurements showed that the BN film thickness increased linearly versus the number of EE-ALD cycles at room temperature. Maximum growth rates of ∼3.2 A/cycle were measured at electron energies of 80–160 eV. BN film growth was self-limiting versus borazine and electron exposures, as expected for an ALD process. The calculated average hydrogen ESD cross section was σ = 4.2 × 10–17 cm2. Ex situ spectroscopic ellipsometry measurements across the ∼1 cm2 area of the BN film defined by the electron beam displayed good uniformity in thickness. Ex situ X-ray photoelectron spe...
IGF-Binding Proteins: Why Do They Exist and Why Are There So Many?

Insulin-like Growth Factors (IGFs) are key growth-promoting peptides that act as both endocrine hormones and autocrine/paracrine growth factors. In the bloodstream and in local tissues, most IGF molecules are bound by one of the members of the IGF binding protein (IGFBP) family, of which 6 distinct types exist. These proteins bind to IGF with an equal or greater affinity than the IGF1 receptor and are thus in a key position to regulate IGF signaling globally and locally. Binding to an IGFBP increases the half-life of IGF in the circulation and prevents the potential binding to the insulin receptor. In addition to these classical roles, IGFBPs have been shown to modulate IGF signaling locally under various conditions. Although members of the IGFBP family share significant sequence homology, they each have unique structural features and play distinct roles. These IGFBP genes also have different modes of regulation and distinct expression patterns. Some IGFBPs have been found to bind to their own receptors or to translocate into the interior compartments of cells where they may execute IGF-independent actions. In spite of this functional and regulatory diversity, it has been puzzling that loss-of-function studies have yielded relatively little information about the physiological functions of IGFBPs. In this review, we suggest that evolution has tended to retain an array of IGFBPs in order to facilitate fine-tuning of IGF signaling. We explore the emerging explanation that many IGFBP functions have evolved to allow the targeted adjustment of IGF signaling under stressful or irregular conditions, which would likely not be revealed in a standard laboratory setting.