gebhart/patrepeval huggingface dataset:
Abstract 1687: A BRCA2-targeting antisense oligodeoxynucleotide enhances cisplatin effectiveness by decreasing human tumor cell proliferation, metastatic frequency, and metabolic response (2014)

Abstract BRCA2 is involved in homologous recombination repair of double-stranded DNA breaks in human cells. Inactivating mutations in BRCA2 predispose to early onset cancer of the breast, ovary and other tissues. However, patients with tumors that harbor BRCA2 mutations respond better to cancer therapy. Therefore, reducing BRCA2 in cancer cells capable of homologous recombination repair may sensitize otherwise resistant tumors to DNA-damaging anti-cancer treatment. We developed a second generation antisense oligodeoxynucleotide (BR-1) that specifically targets BRCA2. BR-1 decreased BRCA2 mRNA and protein and inhibited BRCA2-mediated RAD51 repair focus formation. BR-1 potently sensitized A549 (lung), SKOV-3 (ovarian), and MDA-MB-231 (breast) cells to cisplatin as evidenced by decreased cell proliferation. However, non-cancerous HK-2 kidney cells were not sensitized to cisplatin by BR-1. In A549 cells BR-1 enhanced cisplatin or ionizing radiation-induced inhibition of in vitro colony formation. Cisplatin-resistant head and neck squamous cancer cells (HN-15a) were rendered as sensitive to cisplatin following BR-1 treatment as the parent population. In addition, BR-1 plus cisplatin treatment decreased A549 cell metastatic frequency in an in vivo chicken chorio-allantoic membrane (CAM) model by over 70% when compared with drug treatment alone. Treatment with BR-1 and cisplatin decreased cellular respiration (decreased oxygen consumption) compared to control oligonucleotide plus cisplatin treatment, suggesting that downregulation of BRCA2 in the context of platinating drug treatment alters cellular metabolism. This change in respiration occurred independently of changes in mitochondrial number. We are continuing to develop and test BR-1 with the aim of applying it in an adjuvant setting with cisplatin in human clinical trials in the future. Supported by grants from the Ontario Centres of Excellence (OCE) Citation Format: Mateusz Rytelewski, Jessica Tong, Adrian Buensuceso, Hon Leong, Peter Ferguson, Saman Maleki Vareki, Christine Di Cresce, Larissa Romanow, Trevor Shepherd, Bonnie Deroo, Ann Chambers, Mark Vincent, James Koropatnick. A BRCA2-targeting antisense oligodeoxynucleotide enhances cisplatin effectiveness by decreasing human tumor cell proliferation, metastatic frequency, and metabolic response. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1687. doi:10.1158/1538-7445.AM2014-1687
Electron Transfer Kinetics at Single-Walled Carbon Nanotube Electrodes using Scanning Electrochemical Microscopy (2010)

An important open question on the electrochemistry of single-walled carbon nanotube (SWNT) electrodes concerns the sites at which electron transfer (ET) occurs. This issue is addressed herein for the case of a simple outer sphere redox couple, (ferrocenymethyl)trimethylammonium (FcTMA+). Using relatively sparse networks (<1% surface coverage) of electrically connected SWNTs, coupled to a scanning electrochemical microscopy (SECM) substrate generation−tip collection setup, we show that high rates of mass transport can be generated to SWNTs, allowing kinetic effects to be observed in the voltammetric waveshape. By developing a numerical model that faithfully represents all aspects of the experimental geometry, highly accurate kinetic data can be obtained. Assuming that all SWNTs are active, a minimum average ET rate constant k0SWNT > 1.0 ± 0.6 cm s−1 is assigned, which is of similar size to other electrode materials and suggests that the sidewall of SWNTs has considerable ET activity.
Synthesis and antitumor activity of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine (1980)

The synthesis of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine (BW301U, 7) by a route that has general applicability to the preparation of many 6-(substituted benzyl)-5-methylpyrido[2,3-d]pyrimidines is described. The key intermediate, 2,4-diamino-7,8-dihydro-6-(2,5-dimethoxybenzyl)-5-methyl-7-oxopyrido[2,3-d]pyrimidine (4), is converted to the 7-chloro compound 5 by treatment with a 1:1 complex of N,N-dimethylformamide--thionyl chloride, and 5 is hydrogenolyzed with palladium on charcoal in the presence of potassium hydroxide to yield 7. BW301U is a potent lipid-soluble inhibitor of mammalian dihydrofolate reductase and has significant activity against the Walker 256 carcinosarcoma in rats.
Effect of tensile uniaxial stress on the electron transport properties of deeply scaled FD-SOI n-type MOSFETs (2006)

The effect of longitudinal uniaxial mechanical stress on electron mobility in high-performance fully depleted ultrathin silicon-on-insulator nFETs with a raised source/drain (RSD) architecture and channel lengths ranging from 1 μm (long channel) to 30 nm (deeply scaled) is reported. Longitudinal uniaxial stress in the channel was achieved using a stressed nitride contact liner technique. A dR/dL method was used to minimize errors in the mobility extraction due to uncertainties in external resistance and channel length. Significant mobility enhancement of 1.6-1.8 times was achieved despite the use of an RSD and strong channel doping of roughly 5×10/sup 18/ cm/sup -3/, required for short-channel effect control.
IC100: A Novel Anti-Asc Monoclonal Antibody Improves Functional Outcomes In An Animal Model Of Multiple Sclerosis (2020)

Abstract Background The inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) is involved in immune signaling by bridging the interactions between inflammasome sensors and caspase-1. Strong experimental evidence has shown that ASC -/- mice are protected from disease progression in animal models of multiple sclerosis (MS), suggesting that targeting inflammasome activation via ASC inhibition may be a promising therapeutic strategy in MS. Thus, the goal of our study is to test the efficacy of IC100, a novel humanized antibody targeting ASC, in preventing and/or suppressing disease in the experimental autoimmune encephalomyelitis (EAE) model of MS. Methods We employed the EAE model of MS where disease was induced by immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG 35-55 ). Mice were treated with vehicle or increasing doses of IC100 (10, 30 and 45 mg/kg) and clinical disease course was evaluated up to 35 days post EAE induction. Immune cell infiltration into the spinal cord and microglia responses were assessed. Results We show that IC100 treatment reduced the severity of EAE when compared to vehicle-treated controls. At a dose of 30 mg/kg, IC100 significantly reduced the number of CD4 + and CD8 + T cells and CD11b + MHCII + activated myeloid cells entering the spinal cord from the periphery, and reduced the number of total and activated microglia. Conclusions These data indicate that IC100 suppresses the immune-inflammatory response that drives EAE development and progression, thereby identifying ASC as a promising target for the treatment of MS as well as other neurological diseases with a neuroinflammatory component.
Parallel intracellular integration of nanoscale structures for delivery and expression of free and scaffolded DNA (2004)

We report on the parallel integration of nanoscale structures with the intracellular domains of viable cells to provide long-term, controlled cellular biochemical manipulation. Vertically-aligned carbon nanofibers (VACNF) are self-assembling structures that feature nanoscale diameter tips on vertical supports that can be grown to tens of microns in length. Using wafer-scale processing techniques, VACNFs may be synthesized and incorporated as functional elements of microscale devices and thus provide a bridge between molecular-scale phenomena (at nanofiber tips) and the microscale architecture of the underlying device. The vertical orientation and needlelike aspect of VACNFs facilitate their implementation as molecular-scale interfaces that potentially can be introduced, on a massively parallel basis, to the intracellular domains of viable cell matrices. To demonstrate this parallel introduction, and to observe cell response to such manipulations, VACNFs were modified with either adsorbed or covalently-linked plasmid DNA and such arrays were interfaced with cellular matrices. Following VACNF/cell interfacing, cells were found to proliferate on the nanofiber substrate and to express delivered plasmid DNA (a fluorescent reporter construct) from both desorbed and adsorbed, immobilized plasmid, as well as from plasmid that was covalently tethered to the penetrant nanofiber scaffold. Post interfacing viability of these cells was observed for relatively long durations (>22 day) by tracking expression of the introduced plasmid. Of particular interest, covalently bound plasmids appeared to remain tethered to nanofibers and were expressed in interfaced cells but were not partitioned into noninterfaced progeny. Expression from such immobilized plasmids ceased when the nanofiber was no longer retained within a cell. In addition to demonstrating parallel microinjection of macromolecules, these results provide a method for achieving a genetic modification that is noninheritable and whose extent in time can be directly and precisely controlled. This work also provides basis for application of VACNF device architectures for molecular-scale engineering within whole cells and as a platform for biosensing and clinical diagnostic applications.
Investigation of 0.8-μm InGaAsP-GaAs laser diodes with multiple quantum wells (1995)

In this paper, we studied the effects of the active region structure (one, two and three quantum wells with same total thickness) for high-power InGaAsP-GaAs separate confinement heterostructure lasers emitting at 0.8 micrometers wavelength. Experimental results for the lasers grown by low pressure metalorganic chemical vapor deposition show excellent agreement with the theoretical model. Total output power of 47 W from an uncoated 1 cm-wide laser bar was achieved in quasi-continuous wave operation.
Acoustic Mechanical Feedthroughs (2013)

Electromagnetic motors can have problems when operating in extreme environments. In addition, if one needs to do mechanical work outside a structure, electrical feedthroughs are required to transport the electric power to drive the motor. In this paper, we present designs for driving rotary and linear motors by pumping stress waves across a structure or barrier. We accomplish this by designing a piezoelectric actuator on one side of the structure and a resonance structure that is matched to the piezoelectric resonance of the actuator on the other side. Typically, piezoelectric motors can be designed with high torques and lower speeds without the need for gears. One can also use other actuation materials such as electrostrictive, or magnetostrictive materials in a benign environment and transmit the power in acoustic form as a stress wave and actuate mechanisms that are external to the benign environment. This technology removes the need to perforate a structure and allows work to be done directly on the other side of a structure without the use of electrical feedthroughs, which can weaken the structure, pipe, or vessel. Acoustic energy is pumped as a stress wave at a set frequency or range of frequencies to produce rotary or linear motion in a structure. This method of transferring useful mechanical work across solid barriers by pumping acoustic energy through a resonant structure features the ability to transfer work (rotary or linear motion) across pressure or thermal barriers, or in a sterile environment, without generating contaminants. Reflectors in the wall of barriers can be designed to enhance the efficiency of the energy/power transmission. The method features the ability to produce a bi-directional driving mechanism using higher-mode resonances. There are a variety of applications where the presence of a motor is complicated by thermal or chemical environments that would be hostile to the motor components and reduce life and, in some instances, not be feasible. A variety of designs that have been designed, fabricated and tested will be presented
A block cipher cryptosystem using wavelet transforms over finite fields (2004)

We present a new private key cryptosystem based on the finite-field wavelet. The encryption and decryption are performed by the synthesis and analysis banks of the nonlinear finite-field wavelet transform, whose filter coefficients are determined by the keys of the users. We exploit the polyphase representation of the wavelets to introduce a shared key mechanism for the wavelet cryptosystem. We propose to use wavelets that operate over GF(256) and a nonlinear device that performs a mapping on the field elements to their inverse in the field. The introduced cryptographic system can operate in either stream-cipher or block-cipher modes depending on whether the filterbanks perform linear or circular convolution. The block cipher system has a key length of 16 symbols (128 bits) and an input block size of 30 symbols (240 bits). To evaluate the efficiency of the developed two-round wavelet cryptographic scheme, we compare it with DES and AES. Our results suggest that the wavelet cryptosystem has comparable computational complexity to AES and approximately half the complexity of DES. The security is tied to the length of the wavelet basis function and to the nonlinearity within the wavelet transform. We study the security of the block-cipher wavelet cryptosystem in response to classical attacks and those specific to this algorithm, particularly those which use variations of the divide and conquer, interpolation attack, and discrete Fourier transform techniques. We show that chosen ciphertext attacks of the wavelet encryption system can reduce to the problem of solving a set of nonlinear equations over finite fields. By considering existing classical and structure-specific attacks, we conclude that the lowest complexity of any of these attacks is greater than an exhaustive key search.
Characterization of the human A1 adenosine receptor gene. Evidence for alternative splicing. (1994)

To approach transcriptional and translational regulation of adenosine receptors, we have isolated cDNA and genomic clones of the human A1 adenosine receptor (A1AR). The cDNA, when inserted into the pCMV5 expression vector and transfected into COS-7 or CHO cells, leads to the expression of a functional A1AR that displayed all the appropriate pharmacologic properties. The human A1AR gene consists of at least six exons and five introns. A single intron interrupts the coding sequence, while the remaining introns are within the 5'-untranslated region. Comparison of our cDNA with one by Libert et al. (Libert, F., Van Sande, J., Lefort, A., Czernilofsky, A., Dumont, J. E., Vasart, G., Ensinger, H. A., and Mendla, K. D. (1992) Biochem. Biophys. Res. Commun. 187, 919-926) reveals that exon 4 in the 5'-untranslated region was completely missing from their sequence. Study of mRNAs from a range of human tissues by reverse transcription-polymerase chain reaction using a variety of primers revealed clear evidence for alternative splicing. Transcripts containing exons 4, 5, and 6 were found in all tissues expressing A1AR, while a separate transcript with exons 3, 5, and 6 was seen only in selected tissues. No transcript contains both exons 3 and 4. No evidence for expression of exons 1 and 2 could be discerned. Exon 4 contains two AUG initiation codons with reasonable Kozak consensus, suggesting the possibility of translational regulation. Exon 3 contains no AUG initiation codons.
Cloning of the Gene Encoding a 22-Kilodalton Cell Surface Antigen of<i>Mycobacterium bovis</i>BCG and Analysis of Its Potential for DNA Vaccination against Tuberculosis (2000)

Using spleen cells from mice vaccinated with live Mycobacterium bovis BCG, we previously generated three monoclonal antibodies reactive against a 22-kDa protein present in mycobacterial culture filtrate (CF) (K. Huygen et al., Infect. Immun. 61:2687-2693, 1993). These monoclonal antibodies were used to screen an M. bovis BCG genomic library made in phage lambdagt11. The gene encoding a 233-amino-acid (aa) protein, including a putative 26-aa signal sequence, was isolated, and sequence analysis indicated that the protein was 98% identical with the M. tuberculosis Lppx protein and that it contained a sequence 94% identical with the M. leprae 38-mer polypeptide 13B3 recognized by T cells from killed M. leprae-immunized subjects. Flow cytometry and cell fractionation demonstrated that the 22-kDa CF protein is also highly expressed in the bacterial cell wall and membrane compartment but not in the cytosol. C57BL/6, C3H, and BALB/c mice were vaccinated with plasmid DNA encoding the 22-kDa protein and analyzed for immune response and protection against intravenous M. tuberculosis challenge. Whereas DNA vaccination induced elevated antibody responses in C57BL/6 and particularly in C3H mice, Th1-type cytokine response, as measured by interleukin-2 and gamma interferon secretion, was only modest, and no protection against intravenous M. tuberculosis challenge was observed in any of the three mouse strains tested. Therefore, the 22-kDa antigen seems to have little potential for a DNA vaccine against tuberculosis, but it may be a good candidate for a mycobacterial antigen detection test.
Noncoherent sequence detection of coded linear modulations (2002)

New noncoherent sequence detection algorithms for combined demodulation and decoding of coded amplitude/phase modulations transmitted over additive white Gaussian noise (AWGN) channels are presented. Optimal noncoherent sequence detection requires a tree search and a complexity exponentially increasing with the duration of the transmission. In order to realize simple suboptimal receivers based on the Viterbi algorithm (VA), approximate schemes are proposed, characterized by a performance which approaches that of coherent detection. In the proposed schemes the tradeoff between complexity and performance is simply controlled by a parameter referred to as implicit phase memory and the number of trellis states. These schemes represent a significant improvement over previous results.
AN IMPROVED SELF-POWERED VEHICLE DETECTION SYSTEM (1980)

A randomized prospective clinical trial was carried out to assess the usefulness of the addition of mitomycin C to radiation therapy used alone or in combination with surgery for the treatment of squamous cell carcinoma of the head and neck region. One hundred and twenty patients with biopsy proven tumor of the oral cavity, oropharynx, larynx, hypopharynx, and nasopharynx were randomly assigned to receive or not receive mitomycin C; all other aspects were similar in the two treatment groups. One hundred and seventeen patients were evaluable with a median follow-up time of greater than 5 years. Acute and chronic normal tissue radiation reactions were equivalent in the two treatment groups. Hematologic and pulmonary toxicity were observed in the drug treated patients. Actuarial disease-free survival at 5 years was 49% in the radiation therapy group and 75% in the radiation therapy plus mitomycin C group, p less than 0.07. Local recurrence-free survival was 66% in the radiation therapy group and 87% in the radiation therapy plus mitomycin C group, p less than 0.02. The findings demonstrate that mitomycin C can be administered safely as an adjunct to radiation therapy in the treatment of head and neck cancer. The drug improves local tumor control without enhancing normal tissue radiation reactions.
Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5 (2000)

Hyperphosphorylation of microtubule-associated proteins such as tau and neurofilament may underlie the cytoskeletal abnormalities and neuronal death seen in several neurodegenerative diseases including Alzheimer's disease. One potential mechanism of microtubule-associated protein hyperphosphorylation is augmented activity of protein kinases known to associate with microtubules, such as cdk5 or GSK3beta. Here we show that tau and neurofilament are hyperphosphorylated in transgenic mice that overexpress human p25, an activator of cdk5. The p25 transgenic mice display silver-positive neurons using the Bielschowsky stain. Disturbances in neuronal cytoskeletal organization are apparent at the ultrastructural level. These changes are localized predominantly to the amygdala, thalamus/hypothalamus, and cortex. The p25 transgenic mice display increased spontaneous locomotor activity and differences from control in the elevated plus-maze test. The overexpression of an activator of cdk5 in transgenic mice results in increased cdk5 activity that is sufficient to produce hyperphosphorylation of tau and neurofilament as well as cytoskeletal disruptions reminiscent of Alzheimer's disease and other neurodegenerative diseases.
Regulation of apoptosis during homeostasis and disease in the intestinal epithelium (2006)

A single epithelial layer serves as the interface between the organism and the contents of the gastrointestinal tract, underlining the importance of regulating cellular viability despite an onslaught of pathogens, toxins, waste by-products, and cytokines. A balance between cellular proliferation and apoptosis is necessary to maintain this critical barrier. Recent findings have begun to explain the mechanisms by which intestinal epithelial cells are able to survive in such an environment and how loss of normal regulatory processes may lead to inflammatory bowel disease (IBD) and predispose to inflammation-associated neoplasia. This review focuses on the regulation of physiological apoptosis in development and homeostasis and on pathological apoptosis in intestinal disease, inflammation, and neoplasia, identifying remaining questions and areas of needed investigation.
Polymeric Materials for Gas Separations (1999)

Industrial applications of polymers as gas separations membrane materials fall broadly into two categories: (1) separations using polymers that are more permeable to the smaller components in a gas mixture and (2) separations requiring polymers that are more permeable to larger components in a gas mixture. Optimum polymeric membrane materials for the first type of separations are stiff chain, glassy, moderately high free volume polymers that sieve penetrant molecules rather strictly according to penetrant size. Optimum polymers for the second type of separations are either highly flexible, rubbery polymers or certain ultrahigh free volume, glassy substituted polyacetylenes. Such polymers sieve gas molecules weakly based on size. Therefore, larger, more soluble penetrants are more permeable than smaller, less soluble ones. This overview provides an introduction to the fundamentals of gas separations with polymers, provides examples of polymers for both categories of separations and provides current theoretical and practical design rules for preparing polymeric membranes with optimum performance characteristics.