gebhart/patrepeval huggingface dataset:
A regulated approach to certificate management (2005)

Traditionally, creation and revocation of certificates are performed manually, by trusted agents, under conditions that are rarely formalized. This approach to certificate management is appropriate for many current applications, where the certification or revocation of certificates is based on non-digital credentials. But it is expensive, time consuming and error-prone for the growing class of applications where credentials are digital and may be verified automatically. It is our thesis that what is needed in this situation is a mechanism that provides for the explicit formulation of certificate management policies, and for their enforcement. In order for such an approach to be effective, the range of supported policies should not be limited to certificate management regulations alone. It is often the case that an activity cannot be fully described and understood independently of the management of the certificates it uses. Conversely, creation and revocation cannot always be specified autonomously: they may be called for as side-effects of operations unrelated to certificate management. We show how a control mechanism, called LGI, can be extended to support a wide range of certificate management policies as well as regulations for the various activities that use these certificates.
Embryonic Neural Progenitor Cells: The Effects of Species, Region, and Culture Conditions on Long-Term Proliferation and Neuronal Differentiation (2003)

One of the major obstacles to the use of neural stem/progenitor cells in neuronal replacement therapy is the limited ability of these cells to generate sufficient numbers of specific neuronal phenotypes either in the culture dish or after transplantation in animal models of neurodegenerative disease. It is not yet fully understood whether embryonic neural stem and progenitor cells show species-specific or regional identities, or if current culture paradigms select for a particular subset of stem cells/progenitors with similar proliferation and differentiation capacities. To investigate this issue, we isolated embryonic neural progenitors derived from the developing rat and mouse central nervous system for in vitro culture to assess the regional, species-specific, and temporal effects on both cell proliferation and generation of neurons. Neurosphere cultures were derived from E13-15 mouse or rat developing striatum (medial, lateral, or whole ganglionic eminence), ventral mesencephalon, and cortex. We compared basic fibroblast growth factor and epidermal growth factor for their influence on cell proliferation and neuronal differentiation under defined differentiation paradigms. Seeding density and conditioned media were also tested for their effects on maintenance of cell proliferation over protracted time periods. Results showed that embryonic neural stem/progenitor cells maintained defined patterns of proliferation and neuronal differentiation, with both declining with time in vitro. Proliferation rate was more dependent on species and region than the neurotrophins or conditions used for culture. These results suggest that the appropriate selection of embryonic neural stem cells and culture conditions may be crucial for the optimization of their neurogenic potential.
Beyond CMOS: heterogeneous integration of III–V devices, RF MEMS and other dissimilar materials/devices with Si CMOS to create intelligent microsystems (2014)

Advances in silicon technology continue to revolutionize micro-/nano-electronics. However, Si cannot do everything, and devices/components based on other materials systems are required. What is the best way to integrate these dissimilar materials and to enhance the capabilities of Si, thereby continuing the micro-/nano-electronics revolution? In this paper, I review different approaches to heterogeneously integrate dissimilar materials with Si complementary metal oxide semiconductor (CMOS) technology. In particular, I summarize results on the successful integration of III-V electronic devices (InP heterojunction bipolar transistors (HBTs) and GaN high-electron-mobility transistors (HEMTs)) with Si CMOS on a common silicon-based wafer using an integration/fabrication process similar to a SiGe BiCMOS process (BiCMOS integrates bipolar junction and CMOS transistors). Our III-V BiCMOS process has been scaled to 200 mm diameter wafers for integration with scaled CMOS and used to fabricate radio-frequency (RF) and mixed signals circuits with on-chip digital control/calibration. I also show that RF microelectromechanical systems (MEMS) can be integrated onto this platform to create tunable or reconfigurable circuits. Thus, heterogeneous integration of III-V devices, MEMS and other dissimilar materials with Si CMOS enables a new class of high-performance integrated circuits that enhance the capabilities of existing systems, enable new circuit architectures and facilitate the continued proliferation of low-cost micro-/nano-electronics for a wide range of applications.
B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406 (2009)

Antigenic stimulation through the B-cell antigen receptor (BCR) is considered to promote the expansion of chronic lymphocytic leukemia (CLL) B cells. The spleen tyrosine kinase (Syk), a key component of BCR signaling, can be blocked by R406, a small-molecule Syk inhibitor, that displayed activity in CLL patients in a first clinical trial. In this study, we investigated the effects of BCR stimulation and R406 on CLL cell survival and migration. The prosurvival effects promoted by anti-IgM stimulation and nurselike cells were abrogated by R406. BCR triggering up-regulated adhesion molecules, and increased CLL cell migration toward the chemokines CXCL12 and CXCL13. BCR activation also enhanced CLL cell migration beneath marrow stromal cells. These responses were blocked by R406, which furthermore abrogated BCR-dependent secretion of T-cell chemokines (CCL3 and CCL4) by CLL cells. Finally, R406 inhibited constitutive and BCR-induced activation of Syk, extracellular signal-regulated kinases, and AKT, and blocked BCR-induced calcium mobilization. These findings suggest that BCR activation favors CLL cell homing, retention, and survival in tissue microenvironments. R406 effectively blocks these BCR-dependent responses in CLL cells, providing an explanation for the activity of R406 in patients with CLL.
Hypoxic regulation of the 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase gene family (PFKFB‐1–4) expression in vivo (2003)

When oxygen becomes limiting, cells shift primarily to a glycolytic mode for generation of energy. A key regulator of glycolytic flux is fructose-2,6-bisphosphate (F-2,6-BP), a potent allosteric regulator of 6-phosphofructo-1-kinase (PFK-1). The levels of F-2,6-BP are maintained by a family of bifunctional enzymes, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB or PFK-2), which have both kinase and phosphatase activities. Each member of the enzyme family is characterized by their phosphatase:kinase activity ratio (K:B) and their tissue-specific expression. Previous work demonstrated that one of the PFK-2 isozyme genes, PFKFB-3, was induced by hypoxia through the hypoxia-inducible factor-1 (HIF-1) pathway. In this study we examined the basal and hypoxic expression of three members of this family in different organs of mice. Our findings indicate that all four isozymes (PFKFB-1-4) are responsive to hypoxia in vivo. However, their basal level of expression and hypoxia responsiveness varies in the different organs studied. Particularly, PFKFB-1 is highly expressed in liver, heart and skeletal muscle, with the highest response to hypoxia found in the testis. PFKFB-2 is mainly expressed in the lungs, brain and heart. However, the highest hypoxia responses are found only in liver and testis. PFKFB-3 has a variable low basal level of expression in all organs, except skeletal muscle, where it is highly expressed. Most importantly, its hypoxia responsiveness is the most ample of all three genes, being strongly induced in the lungs, liver, kidney, brain, heart and testis. Further studies showed that PFKFB-1 and PFKFB-2 were highly responsive to hypoxia mimics such as transition metals, iron chelators and inhibitors of HIF hydroxylases, suggesting that the hypoxia responsiveness of these genes is also regulated by HIF proteins. In summary, our data demonstrate that PFK-2 genes are responsive to hypoxia in vivo, indicating a physiological role in the adaptation of the organism to environmental or localized hypoxia/ischemia.
Update on acquired tetracycline resistance genes (2005)

This mini-review summarizes the changes in the field of bacterial acquired tetracycline resistance (tet) and oxytetracycline (otr) genes identified since the last major review in 2001. Thirty-eight acquired tetracycline resistant (Tc(r)) genes are known of which nine are new and include five genes coding for energy-dependent efflux proteins, two genes coding for ribosomal protection proteins, and two genes coding for tetracycline inactivating enzymes. The number of inactivating enzymes has increased from one to three, suggesting that work needs to be done to determine the role these enzymes play in bacterial resistance to tetracycline. In the same time period, 66 new genera have been identified which carry one or more of the previously described 29 Tc(r) genes. Included in the new genera is, for the first time, an obligate intracellular pathogen suggesting that this sheltered group of bacteria is capable of DNA exchange with non-obligate intracellular bacteria. The number of genera carrying ribosomal protection genes increased dramatically with the tet(M) gene now identified in 42 genera as compared with 24 and the tet(W) gene found in 17 new genera as compared to two genera in the last major review. New conjugative transposons, carrying different ribosomal protection tet genes, have been identified and an increase in the number of antibiotic resistance genes linked to tet genes has been found. Whether these new elements may help to spread the tet genes they carry to a wider bacterial host range is discussed.
Predictability of WLAN Mobility and Its Effects on Bandwidth Provisioning (2006)

Wireless local area networks (WLANs) are emerging as a popular technology for access to the Internet and enterprise networks. In the long term, the success of WLANs depends on services that support mobile network clients. Although other researchers have explored mobility prediction in hypothetical scenarios, evaluating their predictors analytically or with synthetic data, few studies have been able to evaluate their predictors with real user mobility data. As a first step towards filling this fundamental gap, we work with a large data set collected from the Dartmouth College campus-wide wireless network that hosts more than 500 access points and 6,000 users. Extending our earlier work that focuses on predicting the next-visited access point (i.e., location), in this work we explore the predictability of the time of user mobility. Indeed, our contributions are two-fold. First, we evaluate a series of predictors that reflect possible dependencies across time and space while benefiting from either individual or group mobility behaviors. Second, as a case study we examine voice applications and the use of handoff prediction for advance bandwidth reservation. Using application-specific performance metrics such as call drop and call block rates, we provide a picture of the potential gains of prediction. Our results indicate that it is difficult to predict handoff time accurately, when applied to real campus WLAN data. However, the findings of our case study also suggest that application performance can be improved significantly even with predictors that are only moderately accurate. The gains depend on the applications’ ability to use predictions and tolerate inaccurate predictions. In the case study, we combine the real mobility data with synthesized traffic data. The results show that intelligent prediction can lead to significant reductions in the rate at which active calls are dropped due to handoffs with marginal increments in the rate at which new calls are blocked.
Automatic Tachycardia Recognition (1984)

A microcomputer algorithm for tachycardia identification, suitable for use in an implanted antitachycardia pacemaker, is described. The system employs an atrial and ventricular electrogram, detects a sustained fast rate in either chamber, and awakens the main program to perform detailed analysis of the tachycardia and its immediately preceding beats. The algorithm distinguishes atrial, ventricular, and AV nodal and re-entrant tachycardia from high rates due to sinus tachycardia. For testing of the program, we used a data base of twenty-two tape-recorded and documented arrhythmias provoked during electrophysiologic studies in which atrial and ventricular bipolar electrodes were in place; twenty-one were successfully detected. These included atrial fibrillation, atrial flutter, atrial tachycardia, AV nodal re-entrant tachycardia, AV re-entrant tachycardia using an accessory pathway, and ventricular tachycardia with and without ventriculo-atrial conduction.
Intradermal needle-free powdered drug injection (2012)

This thesis presents a new method for needle-free powdered drug injection. The design, construction, and testing of a bench-top helium-powered device capable of delivering powder to controllable depths within the dermis is presented. This de-vice uses a jet of gas undergoing choked flow to entrain powder and subsequently penetrates through the skin for delivery of the powder. Different nozzle designs and orifice geometries are also explored. In vitro injection of polymer beads (1-5 pim in diameter) into porcine tissue demonstrate the device&amp;apos;s capability of drug delivery to depths of 260 to 5000 pm. The jet parameters of nozzle orifice diameter and applied pressure are shown to affect injection depth, shape, and success rate. The presented device has the potential to be implemented with stabilized formulations of vaccines to address the cold chain problem-the cost and risk of transporting temperature sensitive vaccines to developing countries.
First integrated continuously tunable AWG-based laser using electro- optical phase shifters (2005)

In this paper, we present a novel continuously tunable arrayed-waveguide grating (A WG) based laser. Electrooptical phase shifters in the array arms allow for wavelength tuning over the complete A WG free spectral range. Preliminary measurements with a single electrode show tuning over a range of 6 nm.
Acid haze air pollution and breast and colon cancer mortality in 20 Canadian cities. (1989)

Sulfur dioxide absorbs ultraviolet light in the region of the spectrum which is most active in forming vitamin D on the skin. Sulfate particles reflect light at this wavelength. High concentrations of these pollutants (acid haze) may lead to vitamin D deficiencies in exposed populations. Epidemiologic and laboratory evidence suggests that vitamin D plays a role in reducing risk of colon and breast cancer. We examined the association between sulfur dioxide and ultraviolet-light-blocking aerosols in 20 Canadian cities, and age-adjusted breast and colon cancer mortality rates in the census divisions encompassing these cities. Statistically significant positive associations were found between these two measures of air pollution and age-adjusted mortality rates for colon cancer in women (multiple r = +.74, p = 0.003), and men (multiple r = +.61, p = 0.03), and breast cancer in women (multiple r = +.69, p = 0.007). Mortality rates for all other reported cancer sites were also examined, and no statistically significant positive associations were found consistently in both sexes. The ecological nature of this study is emphasized, and the possibility that an indirect association could explain these findings is discussed.
Assay for Macrophage‐Mediated Anti‐Tumor Cytotoxicity (1994)

This unit describes a procedure for determining ability of mouse macrophages to lyse tumor cells in vitro. The Basic Protocol outlines a three-stage assay that includes: (1) culture of macrophages (freshly explanted from mice or grown from a cell line) with suspected activating reagents; (2) extensive washing of the cultured macrophages to remove residual reagents, followed by incubation with [(111)In]-labeled tumor cells to allow lysis to occur; and (3) collection of cell-free culture supernatants and measurement of cytolytic activity as a function of (111)In released from tumor cells destroyed by activated macrophages. The Support Protocol outlines a method for radiolabeling tumor cells with [(111)In]oxine.
Abnormal skeletal and cardiac muscle mitochondria induced by zidovudine (AZT) in human muscle in vitro and in an animal model. (1991)

To examine the mechanism of mitochondrial myocytotoxicity caused by long-term administration of zidovudine (AZT) in human immunodeficiency virus-positive patients, we examined the effect of AZT in vitro on human muscle in tissue culture and in vivo in rats treated with daily intraperitoneal injections of AZT at doses equivalent to the total daily dose used in acquired immunodeficiency syndrome patients. After 19 days, the AZT-treated myotubes in tissue culture exhibited abnormal mitochondria characterized by proliferation (mean +/- SD, 27.5 +/- 8 mitochondria/16 microns2 surface area, compared with 12.8 +/- 4 in the control cultures (p less than 0.001], enlarged size, abnormal cristae and electron-dense deposits in their matrix. The changes were partially reversible after AZT withdrawal. Rats treated with AZT developed weight loss, 100-fold elevation of creatine kinase, and increased serum lactate and glucose. In tissues, AZT had its highest concentration in the skeletal muscle and the heart. Skeletal and heart muscles from the treated animals, but not the controls, showed enlarged mitochondria with disorganized or absent cristae and electron-dense deposits in their matrix. Study of the mitochondrial functions assessed by evaluating stimulated oxygen consumption rate, enzymatic activities of electron transport chain and coupling state of oxidative phosphorylation (respiratory control ratio) revealed a decrease in rotenone-sensitive NADH cytochrome C reductase (complex I + III) and an uncoupling effect demonstrated by decreased respiratory control ratio. We conclude that AZT, a DNA chain terminator, is a muscle mitochondrial toxin that affects the oxidation-phosphorylation coupling and the activity of complex I and III of the mitochondrial respiratory chain.
CD45, an integral membrane protein tyrosine phosphatase. Characterization of enzyme activity. (1990)

Although CD45 resembles the low Mr protein tyrosine phosphatases (PTPases) from human placenta in its specificity for phosphotyrosyl residues and absolute dependence on sulfhydryl compounds for activity, it also exhibits a number of distinguishing features. Most notably, it displayed substrate specificity in vitro, preferentially dephosphorylating myelin basic protein, over the other substrates tested, with high specific activity. Limited trypsinization of CD45 generated active fragments of approximately 65 kDa that were apparently derived exclusively from the intracellular segment of the molecule. These retained high activity against myelin basic protein, suggesting that this is an intrinsic feature of the PTPase domains and not the result of secondary interactions between the substrate and the putative ligand binding structure. With reduced carboxamidomethylated and maleylated lysozyme as substrate, CD45 was stimulated up to 12-fold by basic compounds such as spermine; divalent metal ions were also stimulatory, most notably Zn2+, which was previously identified as a potent inhibitor of the low Mr PTPases. CD45 was phosphorylated to high stoichiometry by casein kinase-2 (up to 1.5 mol/mol) and also by glycogen synthase kinase 3 (approximately 0.3 mol/mol) and protein kinase C (approximately 0.1 mol/mol); in all cases, no alteration in enzyme activity was detected following these modifications. Autophosphorylated preparations of epidermal growth factor receptor, insulin receptor, and p56lck protein tyrosine kinases were also substrates for CD45 in vitro.
Multipath propagation simulator for V2X Communication Tests on Cars (2013)

Test and evaluation of wireless communication performance with cars can be done in many ways. One approach, for both vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) tests, is to use a multipath propagation simulator to achieve realistic signal environments for the different communication systems under test. Multipath propagation simulators have previously been shown to be useful for testing mobile handsets. Specific issues related to tests with cars are the large size of the test object and the disturbances it can cause. In this paper we experimentally study how different design parameters of the multipath propagation simulator affect the received signals. The analysis of the setup as well as the data is performed using the so-called “Design of Experiments” method.
Immunomodulatory properties of antineoplastic drugs administered in conjunction with GM-CSF-secreting cancer cell vaccines. (1998)

Cancer cells genetically modified to secrete immunoregulatory cytokines offer great promise for human cancer treatment as tumor vaccines. However, in preclinical animal studies, large established cancer burdens have appeared difficult to eradicate with such vaccines. For example, lethally-irradiated GM-CSF-secreting CT26 colon carcinoma cell vaccine therapy tends to cure only animals bearing 1 x 10(5) wild-type CT26 cells or less. For many human cancers, antineoplastic chemotherapy can often significantly reduce systemic cancer burdens. Unfortunately, for most advanced metastatic solid organ cancers, such as cancers of the breast, colon, and prostate, antineoplastic drug treatments generally fail to effect cancer cures. Treatment regimens combining genetically-modified cancer cell vaccine therapy and antineoplastic chemotherapy have the potential to increase advanced cancer cure rates if antineoplastic drugs and drug combinations that do not inhibit vaccine-induced immune responses can be identified. To assess the potential immunomodulatory properties of commonly-used antineoplastic drugs that might be used in combination with cancer vaccine treatments, we studied the effects of the drugs on antitumor immune responses manifest by animals receiving lethally-irradiated GM-CSF-secreting CT26 cell vaccines. Immunomodulatory properties of the antineoplastic drugs were evaluated i) by monitoring drug effects on the generation of tumor-specific CD8+ cytotoxic T-lymphocytes (CTLs) in response to GM-CSF-secreting CT26 vaccine administration, ii) by determining drug effects on the resistance of vaccinated animals to subsequent challenge with lethal inoculac of CT26 cells, and iii) by evaluating combination drug and vaccine treatment efficacy against established CT26 tumors. Using this approach, doxorubicin was found to possess apparent immunostimulatory activities, depending on the dose and schedule of administration, while cyclophosphamide appeared immunosuppressive. The different immunomodulatory properties of doxorubicin and cyclophosphamide may be clinically relevant: combination doxorubicin and vaccine treatment of established CT26 cancers increased cure rates over that achieved with either agent alone, while combination cyclophosphamide and vaccine treatment of animals carrying CT26 tumors was no better in curing the animals than drug treatment alone.