cssi/SciSciGPT-SciSciNet huggingface dataset:
589 Efficacy of oncolytic vaccinia virus requires infection of suppressive immune cells in the tumor microenvironment leading to their reprogramming and deletion

Background Checkpoint blockade immunotherapy has dramatically changed cancer treatment; however, these therapies depend on the presence of a pre-existing immune infiltrate. Unfortunately, some patients have few to no infiltrating immune cells, highlighting the need for therapies that can generate antigenic stimuli. Oncolytic viruses, which infect and lyse tumor cells while leaving healthy tissue unharmed, are an attractive means to provide these signals, although the mechanisms of action of these engineered viral therapies remain incompletely understood. Virally induced immunogenic death causes an influx of tumor- and virus- specific effector CD8+ T cells. Many oncolytic viruses also decrease tumor-infiltrating suppressive immune populations, such as regulatory T cells (Treg), however the mechanism for this is unknown. Here we show that an oncolytic strain of vaccinia virus (VV) infects tumor infiltrating Tregs, in contrast to the prevailing idea that oncolytic viruses only infect tumor cells. Infection leads to viral-mediated Treg depletion that is required for tumor regression. Methods Using a mouse model of head and neck squamous cell carcinoma (MEER), a VV-resistant line was generated through serial treatment of a VV-sensitive MEER line. At varied time points post-intratumoral treatment with VV, tumor infiltrating lymphocytes (TIL) were isolated from both the VV-resistant and VV-sensitive lines and analyzed by flow cytometry. Results One day post-treatment of VV-sensitive MEER tumors, tumor isolated Tregs were infected by VV as determined by viral GFP expression. Infection was confirmed in vitro with purified Tregs. Four days post-treatment, tumor infiltrating Treg counts were reduced, and active caspase 3 staining was increased, suggesting that infection lead to Treg death. At 7 days post-treatment, the remaining Tregs in the VV-sensitive tumors acquired a fragile phenotype (IFN?+ Nrp1-). This was not observed in the VV-resistant MEER line. Fragile Tregs are less suppressive and indeed we observed an increase in pro-inflammatory cytokine production from CD8+ and Tconv (CD4+ Foxp3-) T cells in the VV-sensitive tumors compared to VV-resistant. We then engineered oncolytic VV to be susceptible to Cre mediated inactivation. Infection of various murine transgenic Cre lines confirmed the importance of non-tumoral immune infection for therapeutic efficacy, with a particular emphasis on Treg infection. Conclusions These data reveal a previously unappreciated mechanism of action of oncolytic virus immunotherapy, in which new tumor immunity accompanies the viral mediated loss and phenotypic change of regulatory populations. Importantly, as this treatment is delivered intratumorally the loss of Tregs is tumor specific, resulting in targeted Treg deletion without systemic autoimmunity.
Privacy, Practice, and Performance

Privacy law is at a crossroads. In the last two years, U.S. policymakers have introduced more than 50 proposals for comprehensive privacy legislation, most of which look roughly the same: they all combine a series of individual rights with internal compliance. The conventional wisdom in privacy scholarship explains this uniformity by looking to catalyzing precedent: the General Data Protection Regulation in Europe or the California Consumer Privacy Act. This article challenges that emerging consensus. Relying on contemporary sociological and critical studies scholarship, this article develops the concept of the social practice of privacy law and argues that recent privacy proposals in the U.S. look similar because the practices of privacy law are performative: they have socially constructed what we think privacy law is and should be. In other words, we have not only become accustomed to conceptualizing privacy law in a certain ways; we have come to see the rights-compliance model as the normal, ordinary, common sense modality of privacy law. So constructed, privacy law is flawed, with substantial negative effects for privacy, equality, and justice. Individual rights are misplaced weapons against the population-level harms of data-extractive capitalism. They also allow industry to weaponize our rights against us. Privacy law-as-compliance is even more troubling. It is internally inconsistent, protects the interests of the most powerful industry players, and elides informational capitalism’s substantive injustices. This article provides a full critical account of the latest developments in privacy law, focusing on its practices rather than law on the books alone. It details and challenges current privacy law’s focus on individual rights and internal compliance. And it explores potential new directions for privacy law based on the developing law and political economy literature, including new practices and performances that center privacy law around principles of power, equality, and democracy.
A parallel ensemble genetic algorithm for the traveling salesman problem

A parallel ensemble of Genetic Algorithms for the Traveling Salesman Problem (TSP) is proposed. Different TSP solvers perform efficiently on different instance types. However, finding the best solver for all instances is challenging. A hybrid of the Mixing Genetic Algorithm (MGA) and Edge Assembly Crossover (EAX) has been shown to perform well on hard instances. The MGA uses Generalized Partition Crossover (GPX) to find the best and worst out of 2k possible solutions, where k is a decomposition factor of two-parent tours. MGA mixes the edges without any loss of diversity in the population. The best individuals move to the top of the population. The worst individuals are filtered to the bottom of the population. Previously, MGA was applied to TSP instances with less than 4,500 vertices. In this article, various Island Model implementations of MGA are introduced to handle larger problem sizes. The island model uses two mixing policies - migration, which does not lose diversity, and replacement, which loses some population diversity. The islands are configured in two patterns - a ring and a hypercube. An ensemble running multiple versions of an hybrid of MGA and EAX algorithms yields excellent performance for problems as large as 85,900.
Classification of wheelchair pressure relief maneuvers using changes in center of pressure and weight on the seat.

BACKGROUND Pressure injuries from prolonged sitting are a significant problem for wheelchair users incurring high costs in healthcare expenditures and reducing quality-of-life. There is a need to improve pressure relief training and adherence in a variety of settings. OBJECTIVE To identify effective common wheelchair pressure relief (PR) manoeuvres based on changes to users' seated centre of pressure (CoP) and seated weight. PARTICIPANTS 20 individuals who use manual wheelchairs as their primary means of mobility. METHODS Participants performed 5 types of PR including seated push-ups, leftward, rightward, forward, and backward leans-while sitting in a wheelchair equipped with a custom instrumented seat pan support. Data were analysed using both clustering and decision tree approaches to identify types of PR. RESULTS Both clustering and decision tree approaches were able to identify and classify PR though neither could accurately distinguish between forward and backward PR. CONCLUSION Changes in the centre of pressure and the total weight on the wheelchair's seat can be used to automatically characterise type, amplitude and duration of pressure relief manoeuvres. Building such a classification and quality assessment scheme into an algorithm could enable a virtual coaching system to track users' pressure relief behaviour and make suggestions to improve adherence with clinical recommendations.IMPLICATIONS FOR REHABILITATIONMultiple bending beam load cells can be used to measure wheelchair users' seated centre of pressure independent of type of cushion used.Both cluster analysis and decision tree algorithms can classify commonly practiced pressure reliefs by measuring changes to the centre of pressure and total weight on the wheelchair's seat.The combination of force sensing for centre of pressure determination and either algorithm could serve as the basis for an application to coach wheelchair users to do effective pressure reliefs.
Low-cost 3DIC process technologies for wide-I/O memory cube

Low-cost 3DIC process approaches are investigated in terms of 3D stacking method and TSV process integration scheme. The permanent and bumpless wafer-to-wafer (PBWW) bonding technology can be applied to the DRAM wafers in the wide-I/O memory cube application. Backside TSV process with its electrical characteristics is also studied. The combination of these two process technologies can further lower the overall process cost and speed up the mass production.
Wedge-based corner model for widely separated view matching

A novel interest point detector is presented in this paper. It uses a wedge model that characterizes corners by their orientation and angular width. The detector is compared to two popular corner detectors: Harris and SUSAN. It is also shown how widely separated views can be matched by using information provided by the detector to approximate local affine transformations between corners.
Capturing, recording, and analyzing LTE signals using USRPs and LabVIEW

Long Term Evolution (LTE) systems are currently playing a major role in catering the ever increasing traffic demand. Better performance and better throughput compared to other mobile communication technologies are main objectives of LTE deployments. To provide a better quality of experience, LTE signals from real base stations should be captured and analyzed, for possibly making adjustments to network operation parameters, or for deploying new base stations. In this paper, real LTE signals from the base stations are recorded using universal software radio peripheral (USRP) devices and NI LabVIEW software. Then, these recorded LTE signals are processed and analyzed in MATLAB to identify information such as primary cell identifier (PCI) and master information block (MIB). LabVIEW and MATLAB graphical user interfaces (GUIs) are provided to make the system more user friendly.
A Region-of-Interest Approach for Detecting Progression of Glaucomatous Damage With Optical Coherence Tomography.

Importance Detecting progression of glaucomatous damage is often challenging. Objective To test the feasibility of using frequency-domain optical coherence tomography (FD-OCT) and a region-of-interest (ROI) approach to measure progressive changes in glaucomatous damage. Design, Setting, and Participants Among a group of patients in an institutional glaucoma practice who were likely to show glaucoma progression, eyes with a history of an optic disc hemorrhage (DH) confirmed by stereophotography were followed up with FD-OCT cube scans of the optic disc. All patients underwent FD-OCT scans on at least 2 occasions separated by at least 1 year (mean, 3.45 years; range, 1.42-6.39 years). Because we were not studying the effects of an optic DH, no constraint was placed on the time between the documentation of an optic DH and the first scan used in the analysis. Main Outcomes and Measures After en face images of the FD-OCT scan were aligned based on the blood vessels, circumpapillary images were derived for an annulus 100 µm in width, and the retinal nerve fiber layer (RNFL) thickness profiles were plotted for the first and last visits. The ROI width associated with the optic DH was defined as the region of the RNFL profile below the 1% CI based on healthy norms. The change in the ROI width was compared with the change in the global RNFL thickness, which was obtained by averaging the circumpapillary RNFL thickness. Results The change in the ROI width (mean [SD], 8.0° [6.4°]; 95% CI, 4.9° to 11.1°; range, −0.7° to 19.3°) was significant ( P t test) while the change in the global thickness (mean [SD], 2.40 [5.87] μm; 95% CI, −0.48 to 5.28 μm) was not significant ( P > .12, 2-tailed t test). Although 15 of the 16 ROIs increased in width between visits, only 11 showed a decrease in the global RNFL thickness. Conclusions and Relevance For detecting progression of local RNFL damage in patients with glaucoma, an OCT ROI approach appears superior to the OCT global RNFL thickness measure typically used.
Substance P primes lipoteichoic acid‐ and Pam3CysSerLys4‐mediated activation of human mast cells by up‐regulating Toll‐like receptor 2

Substance P (SP) is a neuropeptide with neuroimmunoregulatory activity that may play a role in susceptibility to infection. Human mast cells, which are important in innate immune responses, were analysed for their responses to pathogen-associated molecules via Toll-like receptors (TLRs) in the presence of SP. Human cultured mast cells (LAD2) were activated by SP and TLR ligands including lipopolysaccharide (LPS), Pam3CysSerLys4 (Pam3CSK4) and lipoteichoic acid (LTA), and mast cell leukotriene and chemokine production was assessed by enzyme-linked immunosorbent assay (ELISA) and gene expression by quantitative PCR (qPCR). Mast cell degranulation was determined using a β-hexosaminidase (β-hex) assay. SP treatment of LAD2 up-regulated mRNA for TLR2, TLR4, TLR8 and TLR9 while anti-immunoglobulin E (IgE) stimulation up-regulated expression of TLR4 only. Flow cytometry and western blot confirmed up-regulation of TLR2 and TLR8. Pretreatment of LAD2 with SP followed by stimulation with Pam3CSK4 or LTA increased production of leukotriene C4 (LTC(4) ) and interleukin (IL)-8 compared with treatment with Pam3CSK4 or LTA alone (>2-fold; P<0·01). SP alone activated 5-lipoxygenase (5-LO) nuclear translocation but also augmented Pam3CSK4 and LTA-mediated 5-LO translocation. Pam3CSK4, LPS and LTA did not induce LAD2 degranulation. SP primed LTA and Pam3CSK4-mediated activation of JNK, p38 and extracellular-signal-regulated kinase (ERK) and activated the nuclear translocation of c-Jun, nuclear factor (NF)-κB, activating transcription factor 2 (ATF-2) and cyclic-AMP-responsive element binding protein (CREB) transcription factors. Pretreatment with SP followed by LTA stimulation synergistically induced production of chemokine (C-X-C motif) ligand 8 (CXCL8)/IL-8, chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemotactic protein 1 (MCP-1), tumour necrosis factor (TNF) and IL-6 protein. SP primes TLR2-mediated activation of human mast cells by up-regulating TLR expression and potentiating signalling pathways associated with TLR. These results suggest that neuronal responses may influence innate host defence responses.
Inhibition of apoptotic Bax translocation to the mitochondria is a central function of parkin

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, affecting 1–3% of the population over 65. Mutations in the ubiquitin E3 ligase parkin are the most common cause of autosomal recessive PD. The parkin protein possesses potent cell-protective properties and has been mechanistically linked to both the regulation of apoptosis and the turnover of damaged mitochondria. Here, we explored these two functions of parkin and the relative scale of these processes in various cell types. While biochemical analyses and subcellular fractionation were sufficient to observe robust parkin-dependent mitophagy in immortalized cells, higher resolution techniques appear to be required for primary culture systems. These approaches, however, did affirm a critical role for parkin in the regulation of apoptosis in primary cultured neurons and all other cells studied. Our prior work demonstrated that parkin-dependent ubiquitination of endogenous Bax inhibits its mitochondrial translocation and can account for the anti-apoptotic effects of parkin. Having found a central role for parkin in the regulation of apoptosis, we further investigated the parkin-Bax interaction. We observed that the BH3 domain of Bax is critical for its recognition by parkin, and identified two lysines that are crucial for parkin-dependent regulation of Bax translocation. Last, a disease-linked mutation in parkin failed to influence Bax translocation to mitochondria after apoptotic stress. Taken together, our data suggest that regulation of apoptosis by the inhibition of Bax translocation is a prevalent physiological function of parkin regardless of the kind of cell stress, preventing overt cell death and supporting cell viability during mitochondrial injury and repair.
Cross-Bispectrum Computation and Variance Estimation

A method for the estimation of cross-bispectra of discrete real time series is developed. The asymptotic variance properties of the bispectrum are reviewed, and a method for the direct estimation of bispectral variance is given. The symmetry properties are described which minimize the computations necessary to obtain a complete estimate of the cross-bispectrum in the right-half-plane. A procedure is given for computing the cross-bispectrum by subdividing the domain into rectangular averaging regions which help reduce the variance of the estimates and allow easy application of the symmetry relationships to minimize the computational effort. As an example of the procedure, the cross-bispectrum of a numerically generated, exponentially distributed time series is computed and compared with theory.
Recent developments in the study of cardiovascular reactivity : contributions from psychometric theory and social psychology

Two related ongoing research programs are described. The first examines optimal measurement strategies for assessing individual differences in cardiovascular reactivity, and the second investigates the effects of the social environment as a moderator of cardiovascular responding during psychological challenge. Models and evidence from related behavioral sciences (Psychometric Theory and Social Psychology, respectively) have provided useful guidance for this work. Relevant background and current data examining the measurement and determinants of cardiovascular reactivity are reviewed, with a focus on these multidisciplinary contributions. The implications of the work for the construct of reactivity and its possible role as a marker of disease risk are discussed.
“Ghosts of Sociologies Past:” Settlement Sociology in the Progressive Era at the Chicago School of Civics and Philanthropy

This embedded case study of the Chicago School of Civics and Philanthropy (CSCP) illustrates the development of disciplinary boundaries during a transitional period of professionalization in the social sciences, particularly for the fields of sociology and social work. Drawing on archival data (e.g., reports, scholarly and autobiographical writings, and correspondence) we first document sociological contributions of the community-based school, one of many progressive projects among social settlements and social gospelers of the day. Then using the lens of an intergenerational struggle reflective of the historical social movements of the period, we analyze the circumstances surrounding the 1920 merger of the CSCP with the University of Chicago. Succeeding their early social settlement mentors, Graham Taylor of the Chicago Commons and Jane Addams and Julia Lathrop of Hull House, a second generation of social reformer proteges became a formidable force in this disciplinary differentiation. This case can be read as a micro-level illustration of a much larger macro-level political contest as professional social scientists vied for control of the definition of social science and its applied mission. The "ghosts of sociologies past" still haunt the discipline today offering important lessons for sustaining a science that joins theory with action to solve social problems.
The adaptation of coated piezoelectric devices for use in the detection of gases in aqueous solutions

Abstract A method for the determination of ammonia and hydrogen sulfide in aqueous solution is presented. This method involves the use of a gas-permeable membrane which isolates the piezoelectric crystal device from the solution yet allows the desired gases to pass. Concentrations up to 0.45 M for NH3, and 9 · 10-4 M for H2S give linear calibration curves of concentration vs. frequency change.
Real time identification of contaminants in assembly and test

The accuracy and speed of identification of organic foreign contaminants has always been a major challenge faced by every Assembly and Test factory. The current method of analyzing this failure through FTIR (Fourier Transform Infrared (spectroscopy) analysis is a tedious and difficult process. Interpretation of the FTIR result is also complicated. Alternative method using visual analysis is subjective and inaccurate. These challenges apparently impact the through put time of analysis and the accuracy of result. The best known method described on this paper involved the creation of assembly and test materials infrared spectrum library through the use of FTIR. Improvement in the Yield and accuracy of FM (foreign material) identification, analysis TPT (through put time) and effective root cause fix were achieved using this new technique.
A Comparative Study of the Development of Facial Expressions in Canids; Wolf, Coyote and Foxes

The development of facial expressions in the wolf, coyote and grey fox is described, and facial expressions of these species also compared with the red and Arctic fox. In the various species of fox, which lack the high degree of social organization of the wolf, facial expressions are clearly identified under different motivational or social situations, associated with an increase or decrease of social distance. These same expressions are seen in the coyote and in the wolf (with the exception of the jaw-gape which is not seen to the same degree in the wolf). The wolf, coyote and domesticated dog differ from the foxes in that they manifest a wider range of simultaneous combinations of various facial expressions. This may indicate an evolutionary advancement of visual signals in more social species. During ontogeny in these latter species, the more 'primitive' facial expressions common to the foxes were seen earlier than other expressions, simultaneous combinations thereof, and more complex social behavior patterns which emerged later in life. These later emerging components may be phylogenetically more recently acquired than those patterns which are common to both the foxes and other canids. These findings are correlated with the social behavior and organization of these various canids and are closely compared with other studies of the facial expressions of primates. The contribution of specific facial markings and of body movements associated with different facial expressions are considered.
A model to explain the rapid pressure decrease after air-inflation of diseased middle ears

Objectives: Air-inflation in humans and monkeys with significant negative middle ear pressure or with middle ear inflammation was shown to cause greater than ambient middle ear pressure initially, followed by a rapid rate of pressure decrease to approach the preinflation value. Study Design: A mathematical model of middle ear pressure regulation is presented and used to simulate air-inflation of the normal and diseased middle ear. Materials and Methods: The model represents the total volume of the middle ear as consisting of three subcompartments representing the airspace, effusion, and mucosa/blood. Gas exchange among those compartments was assumed to be diffusion limited, and the gas exchange between the mucosa/blood compartment and systemic blood was assumed to be perfusion limited. Disease was modeled as an increase in mucosal blood flow or, alternatively, as an increase in the volumes of the effusion and mucosa/blood compartments. Results: The predictions of the model agree better with the experimental data when the increased rate of pressure change after middle ear inflation in diseased ears is driven by an increased volume of the effusion compartment as opposed to an increased perfusion rate. The responsible mechanism is a rapid redistribution among subcompartments of the gas volume introduced into the air compartment. Conclusions: These results suggest that middle ear inflation with inert gas can be used to diagnose the presence and relative amount of middle ear effusion, and that current protocols for treating otitis media with effusion using inflation need to be modified to optimize their intended effect.
Nonlinear differential equations in reflexive Banach spaces

In this paper we shall be concerned with the existence of solutions tothe Cauchy initial value problem,(1.1) u'(t) + A(t)u(t) = 0 ; w(0) = x ,where iA(t) \ t € [0, T]} is a family of operators which map a reflexiveBanach space X to itself. Basically we require that the operator/!(•) : [0, T] x X •* X be weakly continuous and that for each * € [0, T]the operator A(t) satisfy a modified accretivity condition. In [/]Browder provides a local solution to (l.l) in case X is a complex Hilbertspace. More recently, Diaz and Weinacht [3] and Medeiros [II] discuss theuniqueness of solutions to (l.l) in Hilbert spaces; Goldstein in [6]extends their results to general Banach spaces; and Chow and Schuur [2]guarantee local existence to (l.l) in case I is a separable reflexive,Banach space. In [5] the author establishes the global existence ofsolutions to (l.l) in case A(t) = A is accretive.Received 20 August 1973.31
Incinerator production, fate and health effects of polychlorinated dioxins and furans

Abstract We review information on toxic loads produced by municipal-waste incineration and methods used to calculate health risks. Production rates of dioxins and furans are used to evaluate long-term health hazards in terms of an analytical model.
Complete heart block and fatal right ventricular failure in an infant.

### Drs David W. Sapire and Suzanne M. Lopez #### Maternal History The mother of this child was a 22-year-old primigravida in apparent good health. There was no clinical or biochemical evidence indicating use of ethanol, addictive drugs, or other possibly teratogenic substances. Fetal heart rate on ultrasonograms done early in her pregnancy was about 150 beats per minute. Near the end of her fifth month of pregnancy, she was referred to the John Sealy Hospital at the University of Texas Medical Branch (UTMB) because the fetal heart rate had decreased to 86 beats per minute. Although the atrial rate on subsequent examinations remained about 150 beats per minute, the ventricular rate ranged from 40 to 50 beats per minute. Two weeks before delivery, atrial and ventricular rates were 144 and 47 beats per minute, respectively. When the ventricular rate began to slow even further, it was decided that risk of intrauterine death was imminent, and a Caesarean section delivery was performed at approximately the 28th week of gestation. There was no significant family history relevant to the case. The mother’s serological studies for lupus erythematosus and antiphospholipid syndrome were negative. #### Infant’s Hospital Course The baby was in no major distress just after delivery, but her heart rate increased very little in response to increasing doses of isoproterenol. Within hours after birth, it was decided that an electronic pacemaker was advisable. During epicardial placement of electrodes near the left ventricular apex, the surgeon noted that the “infiltrated” right ventricular myocardium was thin and that it did not respond to electronic pacing. Over the following weeks, there were no conducted atrial beats, although there were regular P waves. Occasional single and multiple ventricular premature beats were recorded, but the heart was driven primarily by the electronic pacemaker. The main clinical problem was increasing right ventricular failure that did not respond to intensive care in the high-risk …
Ion channels and apoptosis in cancer

Humans maintain a constant cell number throughout their lifespan. This equilibrium of cell number is accomplished when cell proliferation and cell death are kept balanced, achieving a steady-state cell number. Abnormalities in cell growth or cell death can lead to an overabundance of cells known as neoplasm or tumours. While the perception of cancer is often that of an uncontrollable rate of cell growth or increased proliferation, a decrease in cell death can also lead to tumour formation. Most cells when detached from their normal tissue die. However, cancer cells evade cell death, tipping the balance to an overabundance of cell number. Therefore, overcoming this resistance to cell death is a decisive factor in the treatment of cancer. Ion channels play a critical role in cancer in regards to cell proliferation, malignant angiogenesis, migration and metastasis. Additionally, ion channels are also known to be critical components of apoptosis. In this review, we discuss the modes of cell death focusing on the ability of cancer cells to evade apoptosis. Specifically, we focus on the role ion channels play in controlling and regulating life/death decisions and how they can be used to overcome resistance to apoptosis in the treatment of cancer.
Direct Observation of NS3 Substeps at Single Base Pair Resolution

Helicases are a ubiquitous class of nucleic acid motor proteins. They utilize ATP to catalyze the opening of double-stranded nucleic acids. Previous crystallographic and single molecule fluorescence studies have implied that a single ATP molecule would be used for every base pair (bp) being opened by a helicase. However, this has not been directly observed. The hepatitis C virus encodes NS3, an RNA helicase that is essential for viral RNA replication. Previous single molecule optical tweezers studies on NS3 unwinding have revealed an 11-bp periodicity with 3.6 bp substeps on average. By building an optical tweezers instrument with high spatial resolution and low drift, we were able to monitor the discrete unwinding substeps of NS3 on RNA at single base pair resolution. We show that under conditions where ATP binding limits the motor dwell time between successive substeps, single base pair substeps are clearly visible. We present a distribution of these substep sizes and the implication of this result on mechanisms of NS3 catalyzed RNA base pair opening and strand release. The distribution of motor dwell times between substeps gave us a direct measure of the coupling ratio between ATP and base pair opening, and we propose an integrated model to rationalize all these observations.
Hepatitis C Virus: A Critical Appraisal of New Approaches to Therapy

The HCV council 2011 convened 11 leading clinicians and researchers in hepatitis C virus from academic medical centers in the United States to provide a forum for the practical and comprehensive evaluation of current data regarding best practices for integrating new direct-acting antiviral agents into existing treatment paradigms. The council investigated 10 clinical practice statements related to HCV treatment that reflect key topical areas. Faculty members reviewed and discussed the data related to each statement, and voted on the nature of the evidence and their level of support for each statement. In this new era of DAAs, a comprehensive and critical analysis of the literature is needed to equip clinicians with the knowledge necessary to design, monitor, and modify treatment regimens in order to optimize patient outcomes.
Is Glutamate-Induced Reduction in Growth Hormone-Releasing Hormone a Neuroendocrine Model of Aging in the Rat?

AbstractDecreases in serum growth hormone (GH) associated with aging may be a result of age-related degenerative changes in neurons of the hypothalamus resulting in a decrease of growth hormone-releasing hormone (GHRH). This study tests the utility of glutamate-induced hypothalamic neuronal degeneration in the rat as a neuroendocrine model of aging. Sprague-Dawley female rats received three 4-mg/g monosodium glutamate (MSG) subcutaneous injections during the first 5 days following birth. Animals were anesthetized at 60 days of age and challenged with GHRH. Blood samples were assayed for GH.Serum GH levels following GHRH challenge in the MSG-treated group rose more slowly and to a lower peak than in controls (P < 0.05). There was no difference in total GH release over the 1-hr interval following challenge. MSG-treatment of animals resulted in lower gross body (P < 0.05) and kidney (P < 0.05) weights with no difference in ovary or adrenal weights. There were also no differences In pituitary GH or total prot...
Securing VANETs: industry approaches and current research directions

Security plays a critical role in Vehicular Ad-Hoc Networks (VANETs). In the absence of secure mechanisms, malicious parties could inject bogus information, at best robbing VANETs of their safety benefits or at worst causing accidents. Unfortunately, VANETs pose unique new research challenges, preventing the use of existing network security mechanisms.Industry has proposed security mechanisms to safeguard VANET operations. In this talk, we will discuss the properties and limitations of these mechanisms and present remaining research challenges.We will then present promising proposed research mechanisms to secure VANETs beyond current industry standards, such as the application of advanced cryptographic techniques to provide anonymity, the use of trusted computing technologies such as the Trusted Computing Group's (TCG's) Trusted Platform Module (TPM), or the use of location verification. We conclude the talk with remaining open research challenges, as well as opportunities and directions for addressing these challenges.
Fluorite structural principles: disordered α-phase to ordered intermediate phases in praseodymia

Abstract Experimental observations of the structural changes effected during rapid cooling of α-phase praseodymium oxide of various compositions in their ambient oxygen pressure have been reported. These results are discussed in terms of the recently discovered structural principles for the anion-deficient, fluorite-related rare earth higher oxides. Two new polymorphs of the β-phase of praseodymia were found in the experiments, and their structures are now predicted using the new structural principles. Furthermore, the structure of one of two new π-phase polymorphs, Pr n O 2 n –2 m , that were discovered, π(1) R 16 O 30 ( n =16, m =1), RO 1.88 , is predicted. The transformation of the established β(1)-phase in the praseodymium oxides to the newly observed β(3)-phase, found in the quenching experiments, is modeled. Finally the surfaces of β(1)- and the α-phase are compared. It is observed that the superstructure of β(1) is clearly reflected in its surface structure.
Stabilization of Vitamin B12 II: α-Hydroxynitriles

Abstract The destruction of vitamin B 12 in liquid multiple vitamin products can be greatly reduced by the addition of α -hydroxynitriles or their esters. The stabilizing effect appears to be due to decomposition of the α-hydroxynitrile into hydrogen cyanide and the corresponding aldehyde. An initial stabilization of cyanocobal-amin was seen in solutions which contained α -hydroxynitriles and were exposed to ultraviolet irradiation. However, upon long exposure to ultraviolet light, cyano-cobalamin solutions containing α -hydroxynitriles eventually decomposed more than the control.
Leucine aminopeptidase (bovine lens): synthesis and kinetic properties of ortho-, meta-, and para-substituted leucyl-anilides.

Abstract The synthesis of a number of leucyl derivatives of substituted anilides and their properties as substrates and inhibitors of Zn 2+ -Mg 2+ leucine aminopeptidase (EC 3.4.11.1) at pH 8.5 and 30 °C are described. The compounds include leucyl-X where X is o -, m -, or p -aminobenzenesulfonic acid, o -, m -, or p -anisidine, and m - or p -aminobenzenesulfonyl fluoride. The latter two sulfonyl fluorides, designed to be active site-directed irreversible inhibitors, turned out to be good substrates for leucine aminopeptidase. The K m and V values of the above compounds as substrates for leucine aminopeptidase are reported. N -Leucyl- m -aminobenzenesulfonate exhibits desirable properties (solubility much greater than K m , Δϵ at 295 nm of 2000 m −1 cm −1 , and V of 300 μmol min −1 mg −1 ) as a substrate for a spectrophotometric assay of leucine aminopeptidase. With the exception of N -leucyl- p -aminobenzenesulfonate, all of the above compounds are inhibitors of the hydrolysis of leucyl- p -nitroanilide by leucine aminopeptidase with K i values approximately their K m values when they are used as substrates. Despite wide variability in steric bulk, chemical composition, and electrical charge of the substituted anilides, the K m values of the above compounds vary over a narrow range (0.5 to 4.8 m m ), which indicates that the leucyl moiety plays the predominant role in the determination of K m values. Although the K m values of m - substituents are similar to those of o - substituents, the V values for m -substituents are much greater than those for o - substituents, which suggests that o -substituents interfere with the catalytic process. N -Leucyl- p -aminobenzenesulfonate and N -alanyl- p -aminobenzenesulfonate as well as the nonsubstrate p -aminobenzenesulfonate stimulate rather than inhibit the proteolysis of leucyl- p -nitroanilide. The stimulation has no effect on V but lowers the K m for the hydrolysis of leucyl- p -nitroanilide, which is compatible with these compounds' serving as nonessential activators.
Holographic optical elements (HOEs) for true-time delays aimed at phased-array antenna applications

True time-delay beam steering in optical domain for phased-array antenna application using multiplexed substrate guided wave propagation is introduced. Limitations of practical true- time-delays are discussed. Aspects on making holographic grating couplers are considered. Finally, experimental results on the generation of 25 GHz broadband microwave signals by optical heterodyne technique and 1-to-30 massive substrate guided wave optical fanout with an uniform fanout intensity distribution are presented.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Effects of acid treatment on structure, properties and biocompatibility of carbon nanotubes

Abstract Carbon nanotubes (CNTs) are promising to be the next generation of viable tools for bioapplications. Further advances in such bioapplications may depend on improved understanding of CNTs physical and chemical properties as well as control over their biocompatibility. Herein we performed a systematic study to show how acid oxidation treatment changes CNTs physical and chemical properties and leads to improved CNTs biocompatibility. Specifically, by incubating CNTs in a strong acid mixture we created a user-defined library of CNTs samples with different characteristics as recorded using Raman energy dispersive X-ray spectroscopy, atomic force microscopy, or solubility tests. Systematically characterized CNTs were subsequently tested for their biocompatibility in relation to human epithelial cells or enzymes. Such selected examples are building pertinent relationships between CNTs biocompatibility and their intrinsic properties by showing that acid oxidation treatment lowers CNTs toxicity providing feasible platforms to be used for biomedical applications or the next generation of biosensors.
Action of the “calcium-antagonist”, prenylamine, on skeletal muscle, the myoneural junction, and the adrenal of the frog

Abstract 1. 1. Prenylamine was studied as a suggested inhibitor of stimulated Ca 2+ influx into excitable cells. 2. 2. It affects neuromuscular transmission, muscle action potentials and contraction, and the release of catecholamines from the adrenal, but the actions are not reasonably interpreted as the result of specific block of a Ca 2+ influx mechanism.
Host density and competency determine the effects of host diversity on trematode parasite infection.

Variation in host species composition can dramatically alter parasite transmission in natural communities. Whether diverse host communities dilute or amplify parasite transmission is thought to depend critically on species traits, particularly on how hosts affect each other’s densities, and their relative competency as hosts. Here we studied a community of potential hosts and/or decoys (i.e. non-competent hosts) for two trematode parasite species, Echinostoma trivolvis and Ribeiroia ondatrae, which commonly infect wildlife across North America. We manipulated the density of a focal host (green frog tadpoles, Rana clamitans), in concert with manipulating the diversity of alternative species, to simulate communities where alternative species either (1) replace the focal host species so that the total number of individuals remains constant (substitution) or (2) add to total host density (addition). For E. trivolvis, we found that total parasite transmission remained roughly equal (or perhaps decreased slightly) when alternative species replaced focal host individuals, but parasite transmission was higher when alternative species were added to a community without replacing focal host individuals. Given the alternative species were roughly equal in competency, these results are consistent with current theory. Remarkably, both total tadpole and per-capita tadpole infection intensity by E. trivolvis increased with increasing intraspecific host density. For R. ondatrae, alternative species did not function as effective decoys or hosts for parasite infective stages, and the diversity and density treatments did not produce clear changes in parasite transmission, although high tank to tank variation in R. ondatrae infection could have obscured patterns.
Human Cdc34 Employs Distinct Sites To Coordinate Attachment of Ubiquitin to a Substrate and Assembly of Polyubiquitin Chains

The Cdc34 E2 ubiquitin (Ub) conjugating enzyme catalyzes polyubiquitination of a substrate recruited by the Skp1-Cullin 1-F-box protein-ROC1 E3 Ub ligase. Using mutagenesis studies, we now show that human Cdc34 employs distinct sites to coordinate the transfer of Ub to a substrate and the assembly of polyubiquitin chains. Mutational disruption of the conserved charged stretch (residues 143 to 153) or the acidic loop residues D102 and D103 led to accumulation of monoubiquitinated IκBα while failing to yield polyubiquitin chains, due to a catalytic defect in Ub-Ub ligation. These results suggest an ability of human Cdc34 to position the attacking Ub for assembly of polyubiquitin chains. Analysis of Cdc34N85Q and Cdc34S138A revealed severe defects of these mutants in both poly- and monoubiquitination of IκBα, supporting a role for N85 in stabilizing the oxyanion and in coordinating, along with S138, the attacking lysine for catalysis. Finally, Cdc34S95D and Cdc34E108A/E112A abolished both poly- and monoubiquitination of IκBα. Unexpectedly, the catalytic defects of these mutants in di-Ub synthesis can be rescued by fusion of a glutathione S-transferase moiety at E2's N terminus. These findings support the hypothesis that human Cdc34 S95 and E108/E112 are required to position the donor Ub optimally for catalysis, in a manner that might depend on E2 dimerization.
Two-dimensional symmetric form discrimination: Fast learning, but notthat fast

Several authors have characterized a striking phenomenon of perceptual learning in visual discrimination tasks. This learning process is selective for the stimulus characteristics and location in the visual field. Since the human visual system exploits symmetry for object recognition we were interested in exploring how it learns to use preattentive symmetry cues for discriminating simple, meaningless, forms. In this study, similar to previous studies of perceptual learning, we asked whether the effects of practice acquired in the discrimination of pairs of shape with a specific orientation of the symmetry axis would transfer to the discrimination of shapes with different orientation of symmetry axis, or to shapes presented in different areas of the visual field. We found that there was no learning transfer between forms with very different axes of symmetry (90° apart). Interestingly, however, we found a transfer of learning effect to horizontally oriented symmetry axis from a condition with an axis of symmetry differing by 45°. Also it appears that some subjects took a longer time to learn than the typical “fast learning” paradigm would predict. Data showed that when observers practice discrimination of meaningless symmetric forms, consistent improvement in the performance occurs. This improvement is lasting over days, and it tends to be specific for the area of the visual field trained. We will discuss results from some of the observers whose learning was not “fast”, but who actually improved with more practice and with large time intervals (1 day) between training sessions.
PALLIATIVE RADIATION THERAPY FOR NON-SMALL CELL LUNG CANCER

Lung cancer represents the leading cancer killer of both women and men. The estimated number of deaths due to lung cancer in the United States for 1996 was 158,700 40 and continues to escalate. Given the 5-year survival of about 13%, it is apparent that a large number of patients with lung cancer require palliative treatment. The goals of palliative treatment are to improve the quality of life for patients by ameliorating symptoms and thereby improving their functional status and emotional well-being. These goals are best reached through interactive decision-making with the individual patient. Before embarking on palliative treatment it is important to establish the following: (1) define the objective of therapy; (2) determine that the symptom in question is caused by the metastatic lesion; (3) propose a therapy that has a reasonable likelihood of improving the symptom and will avoid undue toxicity; and (4) consider the patient's overall condition and wishes. Radiation therapy (RT) is an effective means of palliation of both primary intrathoracic non–small cell lung cancer (NSCLC) and metastatic NSCLC to bone and brain. This review will discuss the indications, efficacy, and techniques of palliative RT for NSCLC.
Subject loss and its implications for a high-risk population

Abstract Forty-six of 97 available families (47%) participated in an investigation of mothers and their high-risk infants who had been discharged from a neonatal intensive care unit. Twenty-three infant demographic, infant medical, maternal demographic, and maternal medical variables were analyzed to determine if differences existed between participating and nonparticipating subjects. Subjects were categorized into three groups: (1) those who completed and returned their questionnaires, (2) those who agreed to participate but did not return their questionnaires, and (3) those who were contactable by letter only. Multivariate analyses of variance yielded no significant effect for Group Status for the Infant Medical, Maternal Demographic, and Maternal Medical variables. The multivariate analysis of the infant demographic variables yielded a significant Group effect with univariate analyses indicating that the groups differed on the Transport variable. Participating mothers more frequently had infants who had been transported to our facility than did nonparticipating mothers. The findings are discussed in relation to sample representativeness and suggestions are offered for reporting subject-loss data.
Combined sequence of Markov parameters and moments in linear systems

The combined sequence of Markov parameters and moments in linear systems is discussed. This sequence is shown to be generated by a linear feedback shift register. Application to the minimal degree partial realization from a mixture of any number of Markov parameters and moments is considered. Central in this particular realization problem is the extension of a Toeplitz partial behavior matrix. This is accomplished on the basis of the algebraic theory of Iohvidov indexes for Toeplitz matrices. >