gebhart/patrepeval huggingface dataset:
SINR maximizing space-time filtering for asynchronous DS-CDMA (2000)

Direct sequence code division multiple access (DS-CDMA) is a core technology for wireless access that is proposed for future generation (3G) mobile and personal communication systems. The use of a base-station antenna array is strongly endorsed in these systems, because of its capabilities of filtering out the interference in the space domain. This paper considers space-time one shot single user receivers for DS-CDMA, based on a multiple input single output time invariant linear filter. The optimization of the filter response is performed jointly in the space and time domains yielding maximal signal-to-interference-plus-noise ratio. Using this framework, a space-time noise whitening matched filter (ST-NWMF) for DS-CDMA demodulation is introduced. It is shown that combined spatio-temporal filtering, taking advantage of the fact that the multiple access interference is colored in the space as well as time domains, can reduce the effects of strong interference components and improves the performance. Simpler suboptimal space-time linear receivers, consisting of a single temporal LT filter following the antenna array, are also considered. It is shown that such a filter approaches the ST-NWMF in the limit, when the M chip waveform has a flat spectrum with no excess bandwidth and N the observation interval is infinite. These schemes, optimal as well as suboptimal, for large observation intervals are suitable also for DS-CDMA systems employing long sequence spreading.
Spatiotemporal Sensing in Cognitive Radio Networks (2007)

Cognitive radio networks need to continuously monitor spectrum to detect the presence of the licensed users. In this paper, we have exploited spatial diversity in multiuser networks to improve the spectrum sensing capabilities of centralized cognitive radio (CR) networks. We develop a fixed and a variable relay sensing scheme. The fixed relay scheme employs a relay that is fixed in location to help the cognitive network base station detect the presence of the primary user. The variable relay sensing scheme employs cognitive users distributed at various locations as relays to sense data and to improve the detection capabilities. We theoretically prove that the proposed variable relay sensing scheme effectively reduces the average detection time which is also illustrated by an insightful example. Finally, we introduce a useful metric to measure the performance of fixed relay and variable relay schemes.
Mechanisms of low level light therapy (2006)

The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing tissue damage has been known for almost forty years since the invention of lasers. Originally thought to be a peculiar property of laser light (soft or cold lasers), the subject has now broadened to include photobiomodulation and photobiostimulation using non-coherent light. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial. This likely is due to two main reasons; firstly the biochemical mechanisms underlying the positive effects are incompletely understood, and secondly the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. In particular a biphasic dose response has been frequently observed where low levels of light have a much better effect than higher levels. This introductory review will cover some of the proposed cellular chromophores responsible for the effect of visible light on mammalian cells, including cytochrome c oxidase (with absorption peaks in the near infrared) and photoactive porphyrins. Mitochondria are thought to be a likely site for the initial effects of light, leading to increased ATP production, modulation of reactive oxygen species and induction of transcription factors. These effects in turn lead to increased cell proliferation and migration (particularly by fibroblasts), modulation in levels of cytokines, growth factors and inflammatory mediators, and increased tissue oxygenation. The results of these biochemical and cellular changes in animals and patients include such benefits as increased healing in chronic wounds, improvements in sports injuries and carpal tunnel syndrome, pain reduction in arthritis and neuropathies, and amelioration of damage after heart attacks, stroke, nerve injury and retinal toxicity.
Antisense RNA Downregulation of Coenzyme A Transferase Combined with Alcohol-Aldehyde Dehydrogenase Overexpression Leads to Predominantly Alcohologenic Clostridium acetobutylicum Fermentations (2003)

Plasmid pAADB1 for the overexpression of the alcohol-aldehyde dehydrogenase (aad) gene and downregulation of the coenzyme A transferase (CoAT) using antisense RNA (asRNA) against ctfB (the second CoAT gene on the polycistronic aad-ctfA-ctfB message) was used in order to increase the butanol/acetone ratio of Clostridium acetobutylicum ATCC 824 fermentations. Acetone and butanol levels were drastically reduced in 824(pCTFB1AS) (expresses only an asRNA against ctfB) compared to 824(pSOS95del) (plasmid control). Compared to strain 824(pCTFB1AS), 824(pAADB1) fermentations exhibited two profound differences. First, butanol levels were ca. 2.8-fold higher in 824(pAADB1) and restored back to plasmid control levels, thus supporting the hypothesis that asRNA downregulation of ctfB leads to degradation of the whole aad-ctfA-ctfB transcript. Second, ethanol titers in 824(pAADB1) were ca. 23-fold higher and the highest (ca. 200 mM) ever reported in C. acetobutylicum. Western blot analysis confirmed that CoAT was downregulated in 824(pAADB1) at nearly the same levels as in strain 824(pCTFB1AS). Butyrate depletion in 824(pAADB1) fermentations suggested that butyryl-CoA was limiting butanol production in 824(pAADB1). This was confirmed by exogenously adding butyric acid to 824(pAADB1) fermentations to increase the butanol/ethanol ratio. DNA microarray analysis showed that aad overexpression profoundly affects the large-scale transcriptional program of the cells. Several classes of genes were differentially expressed [strain 824(pAADB1) versus strain 824(pCTFB1AS)], including genes of the stress response, sporulation, and chemotaxis. The expression patterns of the CoAT genes (ctfA and ctfB) and aad were consistent with the overexpression of aad and asRNA downregulation of ctfB.
Roles of Thermal Instability and Proteolytic Cleavage in Regulation of Activated Thrombin-activable Fibrinolysis Inhibitor (2000)

We have used site-directed mutagenesis and a recombinant expression system for thrombin-activable fibrinolysis inhibitor (TAFI) in order to identify the thrombin cleavage site in activated TAFI (TAFIa) and to determine the relative contribution of proteolytic cleavage and thermal instability in regulation of TAFIa activity in clots. Arg-330 of TAFIa had been proposed to be the thrombin cleavage site based on studies with trypsin, but mutation of this residue to Gln did not prevent thrombin-mediated cleavage nor did mutation to Gln of the nearby Arg-320 residue. However, mutation of Arg-302 to Gln abolished thrombin-mediated cleavage of TAFIa. All TAFIa variants were susceptible to plasmin cleavage. Interestingly, all Arg to Gln substitutions decreased the thermal stability of TAFIa. The antifibrinolytic potential of the TAFI mutants in vitro correlates with the thermal stability of their respective TAFIa species, indicating that this property plays a key role in regulating the activity if TAFIa. Incubation of TAFIa under conditions that result in complete thermal inactivation of the enzyme accelerates subsequent thrombin- and plasmin-mediated cleavage of TAFIa. Moreover, the extent of cleavage of TAFIa by thrombin does not affect the rate of decay of TAFIa activity. Collectively, these studies point to a role for the thermal instability, but not for proteolytic cleavage, of TAFIa in regulation of its activity and, thus, of its antifibrinolytic potential. Finally, we propose a model for the thermal instability of TAFIa.
Polysulfated Heparinoids Selectively Inactivate Heparin‐Binding Angiogenesis Factors (1999)

Angiogenesis is a prerequisite for tumor expansion and metastasis. The angiogenic potential of the heparin-binding growth factors acidic fibroblast growth factor (FGF) and basic FGF has been demonstrated in various publications. We studied the inhibitory effects of suramin and the polysulfated heparinoids pentosan polysulfate, dextran sulfate, and fucoidan on the action of FGF. As an experimental model, we used the adrenal cancer cell line SW 13, whose anchorage-independent growth depends on the presence of FGF. The polysulfated heparinoids inhibited FGF-induced growth and binding to the receptor at an IC50 of 0.5-3 micrograms/ml. Suramin inhibited FGF at an IC50 of 100 micrograms/ml. The polysulfated heparinoids exerted no effect on IGF-1 or TGF alpha-related growth. Suramin inhibited the anchorage-independent growth induced by IGF-1 or TGF alpha only at an IC50 of 100 micrograms/ml. Our results indicate that suramin inhibits growth factors in a nonselective way. By contrast, polysulfated heparinoids exert a selective inhibitory effect on heparin binding angiogenesis factors at an IC50, which is 100 times below the IC50 of suramin. Therefore, the administration of polysulfated heparinoids might become a novel approach to tumor therapy based on blocking angiogenesis.
Triplex forming oligonucleotides: sequence-specific tools for gene targeting (2001)

Sequence-specificity is the key to effective genetic targeting. With specificity, targeted genes can be manipulated in multiple ways; without it, gene therapy agents become loose canons within cells. Triplex forming oligonucleotides (TFOs) bind in the major groove of duplex DNA with high specificity and affinity. Because of these characteristics, TFOs have been proposed as homing devices for genetic manipulation in vivo. Here we review work demonstrating the ability of TFOs and related molecules to alter gene expression and mediate genome modification in mammalian cells. Recent studies have established that TFOs can mediate targeted gene knock out in mice, laying the foundation for the potential application of these molecules in human gene therapy.
Soluble HLA class I induces NK cell apoptosis upon the engagement of killer-activating HLA class I receptors through FasL-Fas interaction (2002)

The engagement of the activating isoforms of C-type lectin inhibitory receptor (CLIR) or killer Ig-like receptor (KIR) by their natural ligands, represented by soluble HLA-I (sHLA-I) molecules, induced programmed cell death of natural killer (NK) cells. Indeed, NK cell apoptosis elicited by either putative HLA-E and HLA-F (sHLA-I non-A, -B, -C, and -G) or sHLA-I-Cw4 or -Cw3 from untransfected or -Cw4 or -Cw3 alleles transfected HLA-A(-), B(-), C(-), G(-), E(+), F(+) 721.221 lymphoblastoid cell line, respectively, was blocked by covering the corresponding activating receptor with either anti-CLIR- or anti-KIR-specific monoclonal antibodies (mAbs). After sHLA-I-activating receptor interaction, NK cells produced and released Fas ligand (FasL), which in turn led to NK cell apoptosis by interacting with Fas at the NK cell surface. Blocking anti-Fas mAb, or anti-FasL mAb, inhibited sHLA-I-mediated apoptosis via activating receptor in NK cell clones. This apoptosis was inhibited by NK cell treatment with cyclosporin A, whereas this drug had no effect on activating receptor-mediated activation of cytolysis. Conversely, concanamycin A, an inhibitor of vacuolar type H(+)-adenosine triphosphatase (H(+)-ATPase) of granules, inhibited activating receptor-induced NK cell cytolysis, suggesting that activating receptor-mediated apoptosis and cytolysis can use different intracellular pathways. Furthermore, a large amount of interferon-gamma (IFN-gamma) was detectable in culture supernatant of activating receptor(+) NK cells incubated with the appropriate sHLA-I ligand. Again, cyclosporin A, but not concanamycin A, strongly reduced activating receptor-mediated IFN-gamma production. This suggests that activating receptor-induced apoptosis of NK cells could play a role in eliminating potentially harmful NK cell clones and, at the same time, it leads to production of IFN-gamma, an antiviral cytokine able to amplify immune responses.
Humulon, a Bitter in the Hop, Inhibits Tumor Promotion by 12-O-Tetradecanoylphorbol-13-Acetate in Two-Stage Carcinogenesis in Mouse Skin (1995)

Humulon, one of the bitters in the hop, was isolated from the female flowers of Humulus lupulus. This component has inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. At 1 mg/mouse, humulon inhibited markedly the tumor-promoting effect of TPA (1 microgram/mouse) on skin tumor formation following initiation with 7,12-dimethylbenz[a]anthracene (50 micrograms/mouse). Furthermore, humulon inhibited arachidonic acid-induced inflammatory ear edema in mice.
Alteration of cross-bridge kinetics by myosin light chain phosphorylation in rabbit skeletal muscle: implications for regulation of actin-myosin interaction. (1990)

Myosin light chain phosphorylation in permeable skeletal muscle fibers increases isometric force and the rate of force production at submaximal levels of calcium activation; myosin light chain phosphorylation may underlie the increased rate and extent of force production associated with isometric twitch potentiation in intact fibers. To understand the mechanism by which myosin light chain phosphorylation manifests these effects, we have measured isometric force, isometric stiffness, rate of isometric force redevelopment after isotonic shortening, and isometric ATPase activity in permeabilized rabbit psoas muscle fibers. These measurements were made in the presence and absence of myosin light chain phosphorylation over a range of calcium concentrations that caused various levels of activation. The results were analyzed with a two-state cross-bridge cycle model as suggested by Brenner [Brenner, B. (1988) Proc. Natl. Acad. Sci. USA 85, 3265-3269]. The results indicate that myosin light chain phosphorylation exerts its effect on force generation and the isometric rate of force redevelopment in striated muscle through a single mechanism, namely, by increasing the rate constant describing the transition from non-force-generating cross-bridges to force-generating states (fapp). gapp, the reverse rate constant, is unaffected by phosphorylation as are the number of cycling cross-bridges. Since both calcium and myosin light chain phosphorylation increase fapp, the possibility is considered that modulation of fapp may represent a general mechanism for regulating force in actin-myosin systems.
The role of Iron on breast cancer stem-like cells. (2016)

Iron is a fundamental nutrient that enables the functions of vital enzymes involved in cell replication, metabolism and growth. Cancer cells contain higher systemic iron levels relative to normal cells. In breast cancer cells, human epidermal growth factor receptor 2 (HER2) is overexpressed more than 30% of normal and its poorly prognosis results in elevated the proportion of cancer stem cells (CSCs) which are the main drivers in cancer recurrence. Finding a relation between increases of iron levels, HER2 expression and CSC population may provide new tools for breast cancer therapy. In this study, therefore, iron dependency in HER2 overexpression and CSC survival is examined in breast cancer cell line, MCF7. It has shown that cells overexpressing HER2 require iron more than their vector counterparts and HER2-increased CSCs are vulnerable to iron chelation. Additionally, this sensitivity of CSCs to iron reduction is obviously indicated in various breast cancer cell lines; HCC1954, MDA-MB-435 and Hs578T. Finally, the concept is also shown in neoplastically transformed breast cancer cell line, HMLER. Altogether, this study demonstrates that iron depletion causes toxicity for CSCs.
Recombinant adeno‐associated viral (rAAV) vectors mediate efficient gene transduction in cultured neonatal and adult microglia (2015)

Microglia are a specialized population of myeloid cells that mediate CNS innate immune responses. Efforts to identify the cellular and molecular mechanisms that regulate microglia behaviors have been hampered by the lack of effective tools for manipulating gene expression. Cultured microglia are refractory to most chemical and electrical transfection methods, yielding little or no gene delivery and causing toxicity and/or inflammatory activation. Recombinant adeno-associated viral (rAAVs) vectors are non-enveloped, single-stranded DNA vectors commonly used to transduce many primary cell types and tissues. In this study, we evaluated the feasibility and efficiency of utilizing rAAV serotype 2 (rAAV2) to modulate gene expression in cultured microglia. rAAV2 yields high transduction and causes minimal toxicity or inflammatory response in both neonatal and adult microglia. To demonstrate that rAAV transduction can induce functional protein expression, we used rAAV2 expressing Cre recombinase to successfully excise a LoxP-flanked miR155 gene in cultured microglia. We further evaluated rAAV serotypes 5, 6, 8, and 9, and observed that all efficiently transduced cultured microglia to varying degrees of success and caused little or no alteration in inflammatory gene expression. These results provide strong encouragement for the application of rAAV-mediated gene expression in microglia for mechanistic and therapeutic purposes. Neonatal microglia are functionally distinct from adult microglia, although the majority of in vitro studies utilize rodent neonatal microglia cultures because of difficulties of culturing adult cells. In addition, cultured microglia are refractory to most methods for modifying gene expression. Here, we developed a novel protocol for culturing adult microglia and evaluated the feasibility and efficiency of utilizing Recombinant Adeno-Associated Virus (rAAV) to modulate gene expression in cultured microglia.
Efficacy of 2-Hydroxypropyl-β-cyclodextrin in Niemann–Pick Disease Type C Model Mice and Its Pharmacokinetic Analysis in a Patient with the Disease (2015)

Niemann-Pick type C disease (NPC), an autosomal recessive lysosomal storage disorder, is an inherited disease characterized by the accumulation of intracellular unesterified cholesterol. A solubilizing agent of lipophilic compounds, 2-hydroxypropyl-β-cyclodextrin (HPBCD), is an attractive drug candidate against NPC disease. However, establishment of the optimum dosage of HPBCD remains to be determined. In this study, we evaluated the effective dosage of HPBCD in NPC model (Npc1(-/-)) mice, and determined serum HPBCD concentrations. Subcutaneous injection of 1000-4000 mg/kg HPBCD improved the lifespan of Npc1(-/-) mice. In addition, liver injury and cholesterol sequestration were significantly prevented by 4000 mg/kg HPBCD in Npc1(-/-) mice. Serum HPBCD concentrations, when treated at the effective dosages (1000-4000 mg/kg), were approximately 1200-2500 µg/mL at 0.5 h after subcutaneous injection, and blood HPBCD concentrations were immediately eliminated in Npc1(-/-) mice. Furthermore, we examined serum HPBCD concentrations when treated at 40000 mg (approximately 2500 mg/kg) in a patient with NPC. We observed that the effective concentration in the in vivo study using Npc1(-/-) mice was similar to that in the patient. In the patient, systemic clearance and the volume of distribution of HPBCD were in accordance with the glomerular filtration rate and extracellular fluid volume, respectively. These results could provide useful information for developing the optimal dosage regimen for HPBCD therapy when administered intravenously to NPC patients.
A Highly Characterized Yeast Toolkit for Modular, Multipart Assembly (2015)

Saccharomyces cerevisiae is an increasingly attractive host for synthetic biology because of its long history in industrial fermentations. However, until recently, most synthetic biology systems have focused on bacteria. While there is a wealth of resources and literature about the biology of yeast, it can be daunting to navigate and extract the tools needed for engineering applications. Here we present a versatile engineering platform for yeast, which contains both a rapid, modular assembly method and a basic set of characterized parts. This platform provides a framework in which to create new designs, as well as data on promoters, terminators, degradation tags, and copy number to inform those designs. Additionally, we describe genome-editing tools for making modifications directly to the yeast chromosomes, which we find preferable to plasmids due to reduced variability in expression. With this toolkit, we strive to simplify the process of engineering yeast by standardizing the physical manipulations and suggesting best practices that together will enable more straightforward translation of materials and data from one group to another. Additionally, by relieving researchers of the burden of technical details, they can focus on higher-level aspects of experimental design.
Detection of Concealed Individuals Based on Their Vital Signs by Using a See-Through-Wall Imaging System With a Self-Injection-Locked Radar (2012)

This paper presents a self-injection-locked (SIL) radar with ranging and tracking capabilities to see through walls for discovering hidden people. Characterized by low complexity and high sensitivity, the proposed SIL radar merges the frequency-modulated continuous-wave and sum-difference pattern detection approaches to determine the distance and azimuth from the radar to each individual in a scene behind a wooden partition wall. An individual can be distinguished from a stationary object by using dynamic spectral subtraction to extract human motions or vital signs. Additionally, two or more individuals can be distinguished from each other by decomposing the Doppler signal into contributions of individuals in a polar domain. Consequently, a see-through-wall imaging system is constructed with the proposed SIL radar to position different individuals concealed behind a wall.
Allergens of the House Dust Mite <i>Dermatophagoides farinae</i>. II. Immunological Characterization of Four Allergenic Molecules (1989)

In a previous study, we detected four major allergens from the house dust mite extract prepared from the body of Dermatophagoides farinae, employing radioimmunoelectrophoresis. The four allergenic proteins were designated as Me1, Me2, Me3 and Me4. The most prevalent allergen was found to be Me1 and its molecular weight was determined to be 17,000 daltons. In this study, the molecular weight of the second prevalent allergen, Me2, was determined to be 27,000 daltons using the immunoblotting method. The molecular weights of the other two major allergens, Me3 and Me4, were also estimated.