cssi/SciSciGPT-SciSciNet huggingface dataset:
An Investigation of Power Migration Policies for Many-Core Processors to Manage On-Chip Thermal Profile

Transition from single core to multicore technology has brought daunting challenge for thermal management of microprocessor chips. The issue of power dissipation in next generation chip will be far more critical as further transition from multicore to many-core processors is soon to be expected. It is very important to obtain uniform on-chip thermal profile with low peak temperature for improved performance and reliability of many-core processors. In this paper, a proactive thermal management technique called ‘power multiplexing’ is explored for many-core processors. Power multiplexing involves redistribution of locations of power dissipating cores at regular time intervals to obtain uniform thermal profile with low peak temperature. Three different migration policies namely random, cyclic and global coolest replace have been employed for power multiplexing and their efficacy in reducing the peak temperature and thermal gradient on chip is investigated. A comparative study of these policies has been performed enlisting their limits and advantages from the thermal and implementation perspective considering important relevant parameters such as migration frequency. For a given migration frequency, global coolest replace policy is found to be the most effective among the three policies considered as this policy leads to 10 °C reduction in peak temperature and 20 °C reduction in maximum spatial temperature difference on a 256 core chip. Proximity of active cores or power configuration on chip is characterized by a parameter ‘proximity index’ which emerges as an important parameter to represent the spatial power distribution on a chip. Global coolest replace policy optimizes the power map on chip taking care of not only the proximity of active cores but also the finite-size effect of chip and the 3D system of electronic package leading to almost uniform thermal profile on chip with lower average temperature.© 2011 ASME
Considerations in order picking zone configuration

In today’s competitive global economy, the focus is on faster delivery of small more frequent orders of inventory at a lower total cost. This often precludes the use of full pallet picking in warehouses so firms commonly use manual picking of cases and broken‐cases. Many firms increase the efficiency of their warehouses by using zone picking. Zone picking requires that a worker only pick those stock‐keeping units (SKUs) stored within their picking zone. In this paper we examine the configuration or shape of these picking zones by simulating a bin‐shelving warehouse to measure picker travel where SKUs are assigned storage locations either using random or volume‐based storage. The results show that the size or storage capacity of the zone, the number of items on the pick list, and the storage policy have a significant effect on picking zone configuration. In addition, we found that the absence of a back cross aisle also affected picking zone configuration. These results offer solutions to managers looking to implement improvements in distribution center operations.
The graphs of polytopes with involutory automorphisms

Steinitz’ theorem states that a graph is the graph of a 3-dimensional convex polytope if and only if it is planar and 3-connected. Grunbaum has shown that Steinitz’ proof can be modified to characterize the graphs of polytopes that are centrally symmetric or have a plane of symmetry. We show how to modify Steinitz’ proof to take care of the remaining involutory case—polytopes that are symmetric about a line.
p62/SQSTM1 prominently accumulates in renal proximal tubules in nephropathic cystinosis

Background Nephropathic cystinosis, a lysosomal storage disorder, is associated with generalized proximal tubular dysfunction and progressive renal failure. The underlying molecular and cellular mechanisms leading to renal tubular injury remain largely unknown. Abnormal induction of autophagy has been shown in cystinosis. We have studied the autophagic flux in cystinosis by evaluating autophagy-specific substrates.
Monoids and Cuspidal Group Characters

Let M be a finite monoid with unit group G. By the work of Munn and Ponizovski, the irreducible complex representations of M are classified according to which J-class (apex) they come from. Consider the irreducible representations of M with apex \(\neq G\). These representations restrict to representations of G, whose components we view as coming from J-classes below G. The remaining irreducible representations (and their characters) of G are called cuspidal. We show that an irreducible character \(\chi\) of G is cuspidal if and only if \(\chi(\sum V(e)) =0\) for all idempotents \(e \neq 1\), where \(V(e) = \{x \in G \mid exe = e\}\).
Deep geothermal brine near Salton Sea, California

A well drilled for geothermal power near Salton Sea in Imperial Valley, Calif., is 5,232 feet deep; it is the deepest well in the world (1962) in a high-temperature hot spring area. In the lower half of the hole temperatures are too high to measure with available equipment, but are at loast 270°C, and may be as much as 370°C. For comparison, maximum temperature heretofore reported at depth (1962) for hot spring areas is 295°C.
Reaction of Organoboranes with iodine

Abstract The reaction of organoboranes with iodine is an efficient method for synthesizing alkyl iodides.1–3 Unfortunately the earlier methods employed sodium methoxide as a reactant which is a potential problem when the organoborane contians reactive functional groups. We recently reported that organoboranes readily react with iodine monochloride in the presence of sodium acetate, a mild base.4,5.
Active learning with neural networks for intrusion detection

This paper presents a neural-network-based active learning procedure for computer network intrusion detection. Applying data mining and machine learning techniques to network intrusion detection often faces the problem of very large training dataset size. For example, the training dataset commonly used for the DARPA KDD-1999 offline intrusion detection project contained approximately five hundred thousand (10% sample of the original five million) observations, which were used to build intrusion detection classification models. The practical problems associated with such a large dataset include very long model training times, redundant information, and increased complexity in understanding the domain-specific data. We demonstrate that a simple active learning procedure can dramatically reduce the size of the training data, without significantly sacrificing the classification accuracy of the intrusion detection model. A case study of the DARPA KDD-1999 intrusion detection project is used in our work. The network traffic instances are classified into one of two categories - normal and attack. A comparison of the actively trained neural network model with a C4.5 decision tree indicated that the actively learned model had better generalization accuracy. In addition, the training data classification performance of the actively learned model was comparable to that of the C4.5 decision tree.
Necrotizing otitis externa occurring concurrently with epidermoid carcinoma.

Malignant external otitis (necrotizing otitis externa) is an infectious process which occurs most often in middle-aged and elderly diabetic patients and is characterized by cultures positive for Pseudomonas and granulation tissue at the junction of the bony and cartilaginous portion of the external auditory canal. Epidermoid carcinoma of the external auditory canal is also seen most often in the middle-aged and elderly population. To the best of our knowledge, no case of acute necrotizing otitis externa occurring concomitantly with epidermoid carcinoma of the external auditory canal has been documented. A case is presented and discussed here and the importance of biopsy of the external auditory canal is stressed. Theoretical considerations of the possible relationship between these two disorders are discussed. This case illustrates the need to discontinue the use of the term "malignant external otitis" and replace it with the term "necrotizing otitis externa."
Synthesis and purification of methyl-13C fluoride

A 20 mmole quantity of methyl-13C fluoride at a 13C-enrichment level of 90% was prepared by a two-step synthesis starting with methanol-13C. The overall yield was 60% of methanol used. A series of gas-chromatographic treatments using Ascarite, silica gel, and Chromosorb-102 columns yielded a highly purified methyl fluoride in which the major impurities were less than 10 parts per million of carbon dioxide and 10 parts per million of methyl chloride.
Minimal Structural Requirements for Diglyceride-Site Directed Activators of Protein Kinase C

Abstract The important regulatory enzyme protein kinase C is physiologically activated by the interaction of (S)-diglycerides with its regulatory domain. This interaction can be mimicked by the structurally diverse tumor promoters, which share, along with the diglycerides, the common structural feature of three hydrophilic atoms at the vertices of a triangle with sides of approximately 6 A. It is shown in this article that molecules with the same triangular arrangement of hydrophillic atoms but with shorter sides can also activate PKC. S-Farnesylthiotriazole (FTT) is a heterocyclic molecule previously shown to specifically activate PKC. In the work reported here, structure-activity studies in the FTT series reveal that three hydrophilic atoms are required for activation, and that the minimal activation unit is close to an equilateral triangle with sides of between 2.4 – 2.7 A. This demonstrates that there is an unanticipated flexibility at the PKC regulatory site. The intermolecular activation model based on structural analysis of the tumor promoters may represent the maximum distances allowed between the hydrophilic atoms of a PKC activator. © 1997 Elsevier Science Ltd.
Tryptophan dynamics of the FK506 binding protein: time-resolved fluorescence and simulations

The FK506-binding protein (FKBP12) is important in the immunosuppressant action of FK506 and rapamycin. We have investigated Trp side chain dynamics in FKBP12, with and without a bound immunosuppressant, by measuring the Trp time-resolved fluorescence anisotropy decay r(t). The r(t) for W59 in aqueous uncomplexed FKBP12 at 20 degrees C is well described by a single exponential with a recovered initial anisotropy, r(eff)o, of 0.192 and an overall rotational correlation time for the protein, phi p, of 4.7 ns; r(eff)o = 0.214 and phi p = 4.2 ns for the FKBP12/FK506 complex. Using an expression for the order parameter squared, namely S2 = r(eff)o/rTo, where rTo is the vitrified steady-state excitation anisotropy, we recovered an S2 of 0.75 for W59 fluorescence in uncomplexed FKBP12 and S2 approximately equal to 1 in the FKBP12/FK506 complex. Results obtained for the FKBP12/rapamycin complex are similar to those found for the FKBP12/FK506 complex. Minimum perturbation mapping simulations were performed on the free and complexed forms of FKBP12 and the results were generally in agreement with the experimental data.
Treatment of Burkitt's Lymphoma during Pregnancy

Objective:To report a case of both successful maternal treatment outcome and normal fetal outcome in a patient who was diagnosed with Burkitt's lymphoma (BL) and aggressively treated with 6 different chemotherapy agents during the second and third trimesters of pregnancy.Case Summary:A 21-year-old white woman was diagnosed with stage II BL of the head and neck at 26 weeks' gestation. She was treated with 2 cycles of systemic intensive polychemotherapy, including cyclophosphamide, vincristine, doxorubicin, cytarabine, etoposide, ifosfamide, mesna, and intrathecal cytarabine with growth factor support during the second and third trimesters. She delivered a healthy, premature boy 6 weeks after diagnosis. At a follow-up 1 year after diagnosis, the patient remained disease-free and the baby remained healthy.Discussion:The prognosis of BL depends on the stage at diagnosis, as well as treatment aggressiveness. Previous reports indicate that most patients diagnosed with BL during pregnancy received either no trea...
Cancer chemotherapy with indole-3-carbinol, bis(3′-indolyl)methane and synthetic analogs

Indole-3-carbinol (I3C) conjugates are phytochemicals expressed in brassica vegetables and have been associated with the anticancer activities of vegetable consumption. I3C and its metabolite bis(3′-indolyl)methane (DIM) induce overlapping and unique responses in multiple cancer cell lines and tumors, and these include growth inhibition, apoptosis and antiangiogenic activities. The mechanisms of these responses are complex and dependent on cell context. I3C and/or DIM activate or inactivate multiple nuclear receptors, induce endoplasmic reticulum stress, decrease mitochondrial membrane potential, and modulate multiple signaling pathways including kinases. DIM has been used as a template to synthesize a series of 1,1-bis(3′indolyl)-1-(substituted aromatic)methanes (i.e. C-DIMs) which are also cytotoxic to cancer cells and tumors. Some of the effects of C-DIMs resemble those reported for DIM analogs; however, structure–activity studies with the aromatic ring has resulted in generation of highly unique receptor agonists. For example, p-trifluoromethylphenyl, p-t-butylphenyl and p-biphenyl analogs activate peroxisome proliferator-activated receptor γ (PPARγ), and p-methoxyphenyl and p-phenyl compounds activate nerve growth factor-induced-Bα (NGFI-Bα, Nur77) orphan nuclear receptor. The effects of C-DIMs on PPARγ and Nur77 coupled with their receptor-independent activities has resulted in the development of a novel group of multi-targeted anticancer drugs with excellent potential for clinical treatment of cancer.
Lipid Raft Localization of Cell Surface E-Selectin Is Required for Ligation-Induced Activation of Phospholipase Cγ

E-selectin, an endothelial cell surface adhesion receptor for leukocytes, also acts as a signaling receptor. Upon multivalent ligation, E-selectin transduces outside-in signals into the endothelium leading to changes in intracellular Ca(2+) concentration and activation of the mitogen-activated protein kinase signaling pathway. In addition, following leukocyte engagement, E-selectin associates via its cytoplasmic domain with components of the actin cytoskeleton and undergoes alterations in phosphorylation state that result in changes in gene expression. In this study, we show that E-selectin is localized in cholesterol-rich lipid rafts at the cell surface, and that upon ligation E-selectin clusters and redistributes in the plasma membrane colocalizing with a fraction of caveolin-1-containing rafts. In addition, we demonstrate that leukocyte adhesion via E-selectin results in association with and activation of phospholipase Cgamma (PLCgamma). Moreover, we show that disruption of lipid rafts with the cholesterol-depleting drug methyl-beta-cyclodextrin disrupts the raft localization of E-selectin as well as the ligation-induced association of E-selectin with PLCgamma, and subsequent tyrosine phosphorylation of PLCgamma. In contrast, cholesterol depletion has no effect on E-selectin-dependent mitogen-activated protein kinase activation. Thus, these findings demonstrate that the presence of E-selectin in lipid rafts is necessary for its association with, and activation of, PLCgamma, and suggest that this subcellular localization of E-selectin is related to its signaling function(s) during leukocyte-endothelial interactions.
Underground Corrosion and Electrical Grounding

Underground corrosion associated with electrical grounding has caused numerous problems in operating electric systems. Much of the difficulty is due to dissimilar metal effects between buried copper and steel connected together via the grounding network. Unfortunately, these effects are widely ignored in electrical design and the requirements of electrical protection and corrosion mitigation are often seen as opposing each other. Experience has shown that both sets of requirements can be met. On electric distribution lines, the most helpful measures against corrosion include the use of galvanized steel rather than copper for grounding electrodes. Sacrificial anodes are helpful for adding additional corrosion protection where needed. Underground copper wire should be tinned or otherwise coated to avoid or minimize dissimilar metal effects. Research is in progress for determining what coatings would be best for this purpose.
Locally finite approximation of Lie groups. II

In an earlier paper [10], we constructed a ‘locally finite approximation away from a given prime p’ of the classifying space BG of a Lie group with finite component group. Such an approximation consists of a locally finite group g and a homotopy class of maps which in particular induces an isomorphism in cohomology with finite coefficients of order prime to p. The usefulness of such a construction is that it reduces various homotopy-theoretic questions concerning the space BG to the corresponding questions concerning Bπ for finite subgroups π. For example, we demonstrated in [10] how H. Miller's proof of the Sullivan conjecture concerning maps from , where π is a finite group and X is a finite-dimensional complex, can be extended to maps BG→X for G a Lie group with finite component group.
Risk for Suicidal Ideation and Attempt among a Primary Care Sample of Adolescents Engaging in Nonsuicidal Self‐Injury

One in five adolescents in the United States has engaged in nonsuicidal self-injury (NSSI), one in eight have had serious thoughts of suicide, and one in 25 have attempted suicide. Research suggests that NSSI may increase risk for suicide attempt, yet little is known about the relationship between NSSI and suicidal ideation or attempts. In a primary care setting, 1,561 youth aged 14-24 years completed a brief, comprehensive, mental health screen as part of a routine well visit to determine which factors were most likely to predict suicidal ideation and attempt among youth engaging in NSSI. RESULTS of recursive partitioning revealed that current depression and history of alcohol use best differentiated youth engaging in NSSI with low versus high risk for suicidal ideation and attempts. This simple algorithm is presented as a clinical screening tool that might aid medical providers in determining which youth would benefit from more intensive assessment and intervention. Language: en
Surveying residents of postgraduate year 2 critical care pharmacy residencies about their level of preparedness to practice

Abstract Objective As the scope of pharmacy services in the critical care setting advances, there has been a parallel evolution in critical care pharmacy residency training programs. The purpose of this study was to assess the ability of critical care pharmacy residency learning experiences to prepare trainees for provision of critical care pharmacy services. Methods This prospective, cross-sectional study of critical care pharmacy residents used a 53-item web-based questionnaire to evaluate resident satisfaction and the exposure frequency, self-perceived competency, and satisfaction rates for the provision of clinical, administrative, educational, and scholarly pharmacy services. Satisfaction and competency were rated on a scale of −10 to +10. The survey was distributed via email and reminder email to 98 critical care residency programs in May 2012. Descriptive statistics were used to categorize responses. Results A total of 45 (54.1%) respondents, representative of all 98 programs, completed the questionnaire. The majority of residents reported feeling somewhat or very satisfied with both the program and their mentorship (91% and 76%, respectively). With the exception of managing nutrition support, respondents felt competently trained to provide most clinical services and educational activities. In contrast, trainees were infrequently exposed as well as uncomfortable providing many administrative and scholarly services. Conclusion Most critical care pharmacy residents were satisfied with their overall experience and mentorship and felt competent providing routine clinical and educational functions. Programs should enhance administrative responsibilities of their residents to adequately prepare them for real-world practice. Additional scholarship may be outside the current resident requirements.
A Micro-Empirical Foundation for the Political Economy of Exchange Rate Populism

Latin American countries have experienced cycles of expansionary policies, currency appreciation, and crises. The popularity of appreciations, through their effect on consumers' purchasing power, has been an accepted assumption in the literature despite a dearth of studies on the distributional impact of exchange rate movements. This study computes the welfare effects of exchange rate movements at different points of the income distribution for Brazil and Mexico. It shows that the distributional effects of appreciations split both countries on a regional basis, instead of across income levels. In Brazil, appreciations are found to benefit less or harm more the rural areas; in Mexico, they benefit less or harm more the Northern border states.
Combination of RSS newsfeeds and forms for driving Web-based workflow

This paper proposes a novel application of the popular content syndication format RSS (really simple syndication) to improve the user experience of humans interacting with electronic workflows. We will discuss this in relation to a more general solution, formidable, for developing and deploying electronic business processes that consist of a mixture of automatic and human-facing steps
The Invisible Interface: Increasing the Power of the Environment through Calm Technology

Dr. Mark Weiser is the Chief Technologist at the Xerox Palo Alto Research Center (PARC). Weiser has no bachelor’s degree; his PhD is in Computer and Communications Sciences from the University of Michigan (1979). Weiser was assistant and associate professor and associate chair in the Computer Science Department at the University of Maryland from 1979 to 1987, when he joined Xerox PARC as member of the technical staff, then heading the Computer Science Laboratory for seven years. He has started three companies. His over 75 technical publications are on such areas as the psychology of programming, program slicing, operating systems, programming environments, garbage collection, and technological ethics. Weiser’s work since 1988 has been focused on Ubiquitous Computing, a program he initiated that envisions PC’s being replaced with invisible computers embedded in everyday objects. He believes that this will lead to an era of “calm technology”, in which technology, rather than panicking us, helps us focus on what is really important to us. Weiser is also the drummer of the rock band Severe Tire Damage, the first live band on the Internet.
First-Generation College Students: Characteristics, Experiences, and Cognitive Development.

This study sought answers to three questions: (1) Do the precollege characteristics of first-generation students differ from those of traditional students? (2) Do first-generation students' college experiences differ from those of other students? (3) What are the educational consequences of any differences on first-year gains in students' reading, math, and critical thinking abilities? Answers come from 2,685 students (825 first-generation and 1,860 traditional students) who entered 23 diverse institutions nationwide in Fall 1992 and who completed one year of study. First-generation students differ from their traditional peers in both entering characteristics and college experiences. Although traditional students make greater net gains in reading during their first year, the two groups gain to about the same degree in math and critical thinking skills. Those gains, however, appear to result from somewhat different experiences.
Comparison of function based web proxy cache replacement strategies

Most web proxy caches use simple cache replacement techniques like Least Recently Used. This technique although simple is not necessarily the most efficient. Function based cache replacement strategies are more sophisticated. They consider recency, frequency, and size attributes of web objects to make replacement decisions. In this paper we provide a comprehensive study to compare eight of the most well known function based web proxy cache replacement strategies. We use the two most important performance metrics, hit rate and byte hit rate, to evaluate these techniques. We also introduce a new performance metric; the object removal rate, which is an indication of CPU usage and disk access at the proxy server. Our study provides valuable insights for both industry and academia. They are especially important for web proxy cache system administrators.
Cell-Cell Interactions during the Migration of an Identified Commissural Growth Cone in the Embryonic Grasshopper

One of the fascicles of the posterior commissure of the embryonic grasshopper is pioneered by an individually identifiable neuron named Q1. Q1 initially grows along a longitudinal pathway established by another pioneer neuron, MP1, and then crosses to the midline, where it meets and fasciculates with the axon of the contralateral Q1. The Q1 growth cone follows the contralateral Q1 axon to the contralateral longitudinal pathway, where it then fasciculates with axons of the MP1/dMP2 fascicle. In this work, we have identified a small set of early neurons that Q1 could use as guidance cues while negotiating its way along a specific and stereotyped pathway to the midline. Furthermore, we have observed characteristic morphological changes in the Q1 growth cone that could indicate responses to changing adhesivity in the substrates it contacts. We have also quantified the pattern of dye coupling between neurons in this system. Most of the neurons to which Q1 becomes coupled retain a strong, consistent pattern of dye coupling that shows no recognizable variation at times when growth cones are making pathway decisions. However, we have found one clear instance of transient, site-specific dye coupling between the Q1 growth cone and the ipsilateral MP1 soma. The timing and pattern of dye coupling in this system suggest that dye coupling may play a role in synchronizing the initiation of axon outgrowth among a small population of neurons. Although dye coupling may not play a direct role in neuronal pathfinding, it may exert a profound indirect influence on neuronal interactions by regulating the timing of axon outgrowth.
The Search for Environmental Complexity

Contingency organization theory suggests that the match between environmental complexity and formal structure is an important determinant of organizational performance. However, there are a number of different interpretations of environmental complexity which may or may not be related. The purpose of this paper is to outline several different views of environmental complexity and empirically test the extent to which they predict the performance of 26 mechanistically structured antipoverty agencies. Statistical analysis is based on multiple linear regression. Measures for complexity include the general level of socioeconomic development, the occupational mix in the surrounding area, the uncertainty in the immediate environment of the agency, and the reliance of the agency on outside units. The performance criteria are based on an analysis of the degree of goal attainment of the sample units. Results suggest that there are considerable differences in different interpretations of environmental complexity in ...
Channel coordination and quantity discounts

This paper presents a model for analyzing the impact of joint decision policies on channel coordination in a system consisting of a supplier and a group of homogeneous buyers. The joint decision policy characterized by the unit selling price and the order quantity is coordinated through quantity discounts and franchise fees. Both the annual demand rate and the operating cost-including the purchase, ordering, and inventory holding costs-depend on the joint decision policy employed. This paper contributes by integrating work addressing quantity discounts on inventory and ordering policies and work focusing on the control mechanism provided by quantity discounts in channel coordination. It is shown that the optimal all-unit quantity discount policy is equivalent to the optimal incremental quantity discount policy in achieving channel coordination. Furthermore, it is shown that quantity discounts alone are not sufficient to guarantee joint profit maximization. The analyses of the general models are illustrated by specific analytical results obtained for a given demand function.
Early pregnancy termination with vaginal misoprostol combined with loperamide and acetaminophen prophylaxis.

Abstract The objectives of this prospective non-concurrent cohort study were to confirm the efficacy of vaginal misoprostol for early pregnancy termination and to determine whether the incidence of side effects is lower with prophylactic loperamide and acetaminophen. Two-hundred women with an intrauterine pregnancy ≤56 days gestational age seeking medical pregnancy termination in an ambulatory research clinic were enrolled in the study. One-hundred participants (group 1) ingested 4 mg of loperamide and 500 mg of acetaminophen before the vaginal placement of 800 μg of misoprostol moistened with 2 mL of saline. If abortion had not occurred, the same regimen was repeated every 24 h (maximum three doses). One-hundred participants (group 2) from the same clinic who previously underwent the same misoprostol regimen without prophylactic medication served as a control group for comparison with respect to abortion success and the incidence of side effects. The rate of successful abortion was not statistically significantly different between the two groups (group 1 93%, group 2 89%). The incidence of opiate analgesic use was significantly less in group 1 (4%) compared with group 2 (16%) (OR 0.22, 95% CI 0.06–0.73, p = 0.01). There was a significantly lower incidence of diarrhea in group 1 (23%) compared with group 2 (44%) (OR 0.38, 95% CI 0.20–0.73, p = 0.003). There was no difference in the incidence of fever/chills or the incidence of emesis between the two groups. Vaginal misoprostol is effective for termination of pregnancy ≤56 days and the incidence of diarrhea and the use of opiate analgesia is significantly reduced with prophylactic loperamide and acetaminophen.
Electrode Fabrication and Implantation in Aplysia californica for Multi-channel Neural and Muscular Recordings in Intact, Freely Behaving Animals

Recording from key nerves and muscles of Aplysia during feeding behavior allows us to study the patterns of neural control in an intact animal. Simultaneously recording from multiple nerves and muscles gives us precise information about the timing of neural activity. Previous recording methods have worked for two electrodes, but the study of additional nerves or muscles required combining and averaging the recordings of multiple animals, which made it difficult to determine fine details of timing and phasing, because of variability from response to response, and from animal to animal. Implanting four individual electrodes has a very low success rate due to the formation of adhesions that prevent animals from performing normal feeding movements. We developed a new method of electrode fabrication that reduces the bulk of the electrodes inside the animal allowing for normal feeding movements. Using a combination of glues to attach the electrodes results in a more reliable insulation of the electrode which lasts longer, making it possible to record for periods as long as a week. The fabrication technique that we describe could be extended to incorporate several additional electrodes, and would be applicable to vertebrate animals.
Neurotrophin‐3 (NT‐3) diminishes susceptibility of the oligodendroglial lineage to AMPA glutamate receptor‐mediated excitotoxicity

Prior reports demonstrated that cells of the oligodendroglial lineage are susceptible to excitotoxic necrosis mediated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid glutamate receptors (AMPA-GluR), and also showed that these cells express the high affinity neurotrophin receptors, TrkC and TrkA. We now report that: a) oligodendroglial progenitors (OP) and immature oligodendroglia are more vulnerable to AMPA-GluR-mediated excitotoxicity than are mature oligodendroglia; b) TrkC expression falls substantially during differentiation of cultured OP to mature oligodendroglia, whereas TrkA expression increases markedly; and c) neurotrophin-3, and to a lesser extent, nerve growth factor, protect the oligodendroglial lineage against AMPA-GluR-mediated excitotoxicity.
Stamp-and-stick room-temperature bonding technique for microdevices

Multilayer MEMS and microfluidic designs using diverse materials demand separate fabrication of device components followed by assembly to make the final device. Structural and moving components, labile bio-molecules, fluids and temperature-sensitive materials place special restrictions on the bonding processes that can be used for assembly of MEMS devices. We describe a room temperature "stamp and stick (SAS)" transfer bonding technique for silicon, glass and nitride surfaces using a UV curable adhesive. Alternatively, poly(dimethylsiloxane) (PDMS) can also be used as the adhesive; this is particularly useful for bonding PDMS devices. A thin layer of adhesive is first spun on a flat wafer. This adhesive layer is then selectively transferred to the device chip from the wafer using a stamping process. The device chip can then be aligned and bonded to other chips/wafers. This bonding process is conformal and works even on surfaces with uneven topography. This aspect is especially relevant to microfluidics, where good sealing can be difficult to obtain with channels on uneven surfaces. Burst pressure tests suggest that wafer bonds using the UV curable adhesive could withstand pressures of 700 kPa (7 atmospheres); those with PDMS could withstand 200 to 700 kPa (2-7 atmospheres) depending on the geometry and configuration of the device.
Granzyme B- and Fas ligand-mediated cytotoxic function induced by mitogenic CD28 stimulation of human memory CD4+ T cells.

Some human memory CD4+ T cells have cytotoxic functions best understood in the context of viral infections; however, their possible role in pathologic processes is understudied. The novel discovery that mitogenic CD28 antibodies induced proliferation and expansion of Tregs offered therapeutic promise for autoimmune disorders. However, the failed TGN1412 trial forced reassessment of this concept. As memory CD4+ T cells are known to produce toxic molecules, including granzyme B (GrzB) and FasL, we wondered whether mitogenic CD28 was able to induce these cytotoxic molecules. A commercially available mitogenic human CD28 mAb (clone ANC28.1) was used to determine whether mitogenic CD28 induces cytotoxic function from human memory CD4+ T cells. We found that stimulation of memory CD4+ T cells by ANC28.1, as well as by conventional costimulation (CD3/CD28 mAb), robustly induced enzymatically active GrzB, along with increased surface expression of FasL. These functional phenotypes were induced in association with increased expression of T cell activation markers CD69 and CD25, and elimination of target cells by ANC28.1-activated memory CD4+ T cells involved both GrzB and FasL. Additionally, ANC28.1-activated memory CD4+ T cells caused disruption of epithelial cell monolayer integrity, which was partially mediated by GrzB. These findings reveal functions of memory CD4+ T cells previously unknown to be induced by mitogenic CD28, and suggest that these pathogenic mechanisms may have been responsible for some of the widespread tissue destruction that occurred in the TGN1412 trial recipients.
O Acetylation of the Enterobacterial Common Antigen Polysaccharide Is Catalyzed by the Product of the yiaH Gene of Escherichia coli K-12

The carbohydrate component of the enterobacterial common antigen (ECA) of Escherichia coli K-12 occurs primarily as a water-soluble cyclic polysaccharide located in the periplasm (ECACYC) and as a phosphoglyceride-linked linear polysaccharide located on the cell surface (ECAPG). The polysaccharides of both forms are comprised of the amino sugars N-acetyl-d-glucosamine (GlcNAc), N-acetyl-d-mannosaminuronic acid (ManNAcA), and 4-acetamido-4,6-dideoxy-d-galactose (Fuc4NAc). These amino sugars are linked to one another to form trisaccharide repeat units with the structure →3-α-d-Fuc4NAc-(1→4)-β-d-ManNAcA-(1→4)-α-d-GlcNAc-(1→. The hydroxyl group in the 6 position of the GlcNAc residues of both ECACYC and ECAPG are nonstoichiometrically esterified with acetyl groups. Random transposon insertion mutagenesis of E. coli K-12 resulted in the generation of a mutant defective in the incorporation of O-acetyl groups into both ECACYC and ECAPG. This defect was found to be due to an insertion of the transposon into the yiaH locus, a putative gene of unknown function located at 80.26 min on the E. coli chromosomal map. Bioinformatic analyses of the predicted yiaH gene product indicate that it is an integral inner membrane protein that is a member of an acyltransferase family of enzymes found in a wide variety of organisms. The results of biochemical and genetic experiments presented here strongly support the conclusion that yiaH encodes the O-acetyltransferase responsible for the incorporation of O-acetyl groups into both ECACYC and ECAPG. Accordingly, we propose that this gene be designated wecH.
Therapeutic Effect of Caffeine Treatment Immediately Following Neonatal Hypoxic-Ischemic Injury on Spatial Memory in Male Rats

Hypoxia Ischemia (HI) refers to the disruption of blood and/or oxygen delivery to the brain. Term infants suffering perinatal complications that result in decreased blood flow and/or oxygen delivery to the brain are at risk for HI. Among a variety of developmental delays in this population, HI injured infants demonstrate subsequent memory deficits. The Rice-Vannucci rodent HI model can be used to explore behavioral deficits following early HI events, as well as possible therapeutic agents to help reduce deleterious outcomes. Caffeine is an adenosine receptor antagonist that has recently shown promising results as a therapeutic agent following HI injury. The current study sought to investigate the therapeutic benefit of caffeine following early HI injury in male rats. On post-natal day (P) 7, HI injury was induced (cauterization of the right common carotid artery, followed by two hours of 8% oxygen). Male sham animals received only a midline incision with no manipulation of the artery followed by room air exposure for two hours. Subsets of HI and sham animals then received either an intraperitoneal (i.p.) injection of caffeine (10 mg/kg), or vehicle (sterile saline) immediately following hypoxia. All animals later underwent testing on the Morris Water Maze (MWM) from P90 to P95. Results show that HI injured animals (with no caffeine treatment) displayed significant deficits on the MWM task relative to shams. These deficits were attenuated by caffeine treatment when given immediately following the induction of HI. We also found a reduction in right cortical volume (ipsilateral to injury) in HI saline animals as compared to shams, while right cortical volume in the HI caffeine treated animals was intermediate. These findings suggest that caffeine is a potential therapeutic agent that could be used in HI injured infants to reduce brain injury and preserve subsequent cognitive function.
A Brief, Multifaceted, Generic Intervention to Improve Blood Pressure Control and Reduce Disparities Had Little Effect

Background . Poor blood pressure (BP) control and racial disparities therein may be a function of clinical inertia and ineffective communication about BP care. Methods. We compared two different interventions (electronic medical record reminder for BP care (Reminder only [RO]), and clinician training on BP care-related communication skills plus the reminder (Reminder + Training, [R+T]) with usual care in three primary care clinics, examining BP outcomes among 8,866 patients, and provider-patient communication and medication adherence among a subsample of 793. Results. Clinician counseling improved most at R+T. BP improved overall; R+T had a small but significantly greater reduction in diastolic BP (DBP; -1.7 mm Hg). White patients at RO experienced greater overall improvements in BP control. Site and race disparities trends suggested that disparities decreased at R+T, either stayed the same or decreased at Control; and stayed the same or increased at RO. Conclusions. More substantial or racial/ethnically tailored interventions are needed. Ethn Dis. 2016;26(1):27-36; doi: 10.18865/ed.26.1.27
Up-regulation of oxytocin receptor expression at term is related to maternal body mass index.

Background The likelihood of cesarean is in part related to maternal body mass index (BMI). Myometrial changes may be responsible. Methods Myometrial biopsies were collected from the upper edge of the hysterotomy from women undergoing scheduled cesarean with term, singleton gestations. Oxytocin receptor and connexin-43 mRNA protein expression was quantified with real-time polymerase chain reaction and Western blot. Results Twenty subjects were recruited: 13 repeat and 7 primary cesareans. Oxytocin receptor mRNA was associated with BMI among women undergoing primary ( r = 0.75; p = 0.05) but not repeat cesarean ( p > 0.05). Controlling for gestational age, this association strengthened ( p = 0.004). Receptor protein expression showed a linear correlation with BMI in the primary cesarean group ( p = 0.002). Connexin-43 mRNA expression was not related to BMI in women undergoing primary ( r = −0.14, p = 0.76) or repeat ( r = −0.01, p = 0.86) cesarean. Conclusions Oxytocin receptor, but not connexin-43, expression is related to BMI, suggesting an alteration in oxytocin receptor expression or function related to obesity.
Imidazo[1,2-a]Pyridine-3-Carboxamides Are Active Antimicrobial Agents against Mycobacterium avium Infection In Vivo

A panel of six imidazo[1,2-a]pyridine-3-carboxamides (IAPs) were shown to have low-micromolar activity against Mycobacterium avium strains. Compound ND-10885 (compound 2) showed significant activity in the lung, spleen, and liver in a mouse M. avium infection model. A combined regimen consisting of ND-10885 (compound 2) and rifampin was additive in its anti-M. avium activity in the lung. Our data indicate that IAPs represent a new class of antibiotics that are active against M. avium and could potentially serve as an effective addition to a combined treatment regimen.
Dapsone acetylation by human liver arylamine N-acetyltransferases and interaction with antiopportunistic infection drugs

Dapsone is used in the treatment of Pneumocystis carinii pneumonia, an opportunistic infection that afflicts acquired immunodeficiency syndrome (AIDS) patients. Inhibition of N-acetyltransferase (NAT)-dependent acetylation of dapsone could increase peak plasma concentrations of dapsone and shift the biotransformation pathway to the P450-mediated formation of a toxic metabolite of dapsone, the hydroxylamine. Therefore, we have determined using human liver cytosol and bacterially expressed NATs, the NAT isoform responsible for acetylating dapsone and the potential for antiopportunistic infection drugs to inhibit this metabolic pathway. Formation of monoacetyldiaminodiphenylsulfone (MADDS) was quantitated by HPLC/UV detection at 270 nm after incubation of dapsone with 100 microM acetyl coenzyme A regenerating system and human liver cytosol. The mean +/- SD apparent KM for the formation of MADDS in three different human livers predicted to be fast acetylators based on genotyping was 98 +/- 17.6 microM, and the Vmax was 190 +/- 20 pmol/min/mg cytosol protein. Eadie-Hofstee transformation of the substrate velocity data was linear, indicating acetylation by a kinetically single enzyme. Sulfamethazine (250 microM) inhibited dapsone acetylation by 100% and 80%, respectively, at dapsone concentrations of 3 and 100 microM, in both fast- and slow-acetylating liver cytosol preparations, whereas para-amino-benzoic acid (100 microM) did not inhibit MADDS formation at either of these dapsone concentrations. Lineweaver-Burk plots of dapsone acetylation in the presence of 0, 25, and 50 microM sulfamethazine showed an increase in the apparent KM, with increase in sulfamethazine concentration with no change in the Vmax, indicating competitive inhibition of dapsone acetylation by sulfamethazine. The apparent KM of dapsone acetylation by bacterially expressed NAT1 and NAT2 enzymes was 687 and 136 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Commentary on 'Dissecting the hemagglutinin head and stalk specific IgG antibody response in healthcare workers following pandemic H1N1 vaccination'.

Commentary on ‘Dissecting the hemagglutinin head and stalk specific IgG antibody response in healthcare workers following pandemic H1N1 vaccination’
Closed-Form Solutions for Electroacoustic Wave Energy Harvesting in a Coupled Plate-Harvester System

This paper introduces an analytical framework for predicting wave energy harvested by a circular piezoelectric layer from a harmonic point source excitation. The explored acoustic system analyzes a circular piezoelectric disk attached to an infinite host domain. An harmonic point source is located away from the piezoelectric disk on the infinite host layer. The analysis approach decomposes the system into two subdomains, the piezoelectric disk and an infinite plate, which are then separately analyzed. In contrast to traditional analysis methods for such systems (a sandwich of layers with different dimensions), this technique uses internal interaction forces between the different subdomains to find a close-form solution for the vibration of propagating waves over the entire field. In addition, the voltage generated by the harvester is calculated by using coupled electromechanical equations. The analysis is validated by comparing response quantities and frequency response functions at different points on the piezoelectric circular layer and host layers to those predicted using COMSOL simulations, which document good agreement. Analysis of this system is an important stepping stone to the next goal, which is optimization of energy captured from the propagating wave by designing boundary walls (reflector) on the host layer which focus the energy of the wave onto the piezoelectric domain. This focused energy can then be transferred to the electrical power by via a piezoelectric layer through an electrical circuit.Copyright © 2016 by ASME
An Enyne Cope Rearrangement Enables Polycycloalkane Synthesis from Readily Available Starting Materials.

Cyclohexanone-derived Knoevenagel adducts (cyclohexylidenemalononitriles) and two different propargyl electrophiles serve as carbon sources for assembling diverse 6/7/5 tricycloalkanes, a common terpenoid framework. The sequence involves three unique reactions: 1) deconjugative propargylation, 2) one-pot enyne Cope rearrangement/deconjugative propargylation, and 3) an allenic Pauson-Khand reaction.