gebhart/patrepeval huggingface dataset:
Precision Alignment Packaging for Microsystems With Multiple Fluid Connections (2001)

Abstract The application of microfluidic Microsystems to solve real world problems depends on effective packaging techniques. In this paper, we report on packaging methods that allow the connection of multiple fluid lines to a microfluidic chip. Eight different fluid connections are made in a 5 mm square area (100 connections possible) using a flip chip aligner/bonder with precise alignment on the order of 10 microns between holes (1 micron precision possible). The critical fluid connections are made using 0.002 inch thick double sided adhesive tape and are shown to hold greater than 20 atm of pressure without leaking. The packaging flow manifold and assembly methods are suitable for inexpensive mass production and are compatible with existing electronics packaging technologies.
Gas‐flow assisted ion transfer for mass spectrometry (2012)

Methods and devices that use gas flows to collect ions and transfer them over long distances for mass spectrometric analysis have been developed. Gas flows derived from the ionization source itself or provided by means of additional pumping were used to generate a laminar flow inside cylindrical tube. Hydrodynamic simulations and experimental tests demonstrate that laminar flow can transfer ions over long distance. The typical angular discrimination effects encountered when sampling ions from ambient ionization sources are minimized, and the sampling of relatively large surface areas is demonstrated with desorption electrospray ionization (DESI). Ion transfer over 6 m has been achieved and its application to multiplexed chemical analysis is demonstrated on samples at locations remote from the mass spectrometer.
CRF receptor type 1 and 2 expression and anatomical distribution in the rat colon (2004)

Corticotropin-releasing factor (CRF) receptor agonists administered peripherally increase colonic propulsive motility and fecal output in experimental animals. In addition, endogenous CRF-related peptides are found in the lower gastrointestinal (GI) tissues, suggesting a local expression of CRF receptors. In the present study, we report the expression of both CRF receptor type 1 (CRF(1)) and 2 (CRF(2)) in the rat colon at the mRNA and protein levels. For the purpose of receptor protein mapping, a specific antiserum against the C-terminus of CRF(2) (2064a-CRF(2)) was generated and characterized. This antiserum in conjunction with a selective anti-CRF(1) antiserum (4467a-CRF(1)) was used in immunofluorescent staining to demonstrate the anatomical distribution of receptor protein expression. Using RT-PCR for the CRF(1) and CRF(2) genes, both receptor gene transcripts were found in RNA isolated from crude colonic samples. CRF(1) was found in the goblet and stem cells of the colonic crypts and in scattered cells of the surface epithelium and the lamina propria of the proximal colonic mucosa. In addition, double staining against neuron-specific antigens revealed CRF(1) expression in the myenteric and submucosal nervous plexus. CRF(2) expression was localized mainly in the luminal surface of the crypts and in blood vessels of the submucosal layer. These results demonstrate expression of both CRF receptor types in the rat colon and support a role for their involvement in regulating peripheral effects of CRF ligands.
Tumor Cell Kill by c-MYC Depletion: Role of MYC-Regulated Genes that Control DNA Double-Strand Break Repair (2010)

MYC regulates a myriad of genes controlling cell proliferation, metabolism, differentiation, and apoptosis. MYC also controls the expression of DNA double-strand break (DSB) repair genes and therefore may be a potential target for anticancer therapy to sensitize cancer cells to DNA damage or prevent genetic instability. In this report, we studied whether MYC binds to DSB repair gene promoters and modulates cell survival in response to DNA-damaging agents. Chromatin immunoprecipitation studies showed that MYC associates with several DSB repair gene promoters including Rad51, Rad51B, Rad51C, XRCC2, Rad50, BRCA1, BRCA2, DNA-PKcs, XRCC4, Ku70, and DNA ligase IV. Endogenous MYC protein expression was associated with increased RAD51 and KU70 protein expression of a panel of cancer cell lines of varying histopathology. Induction of MYC in G(0)-G(1) and S-G(2)-M cells resulted in upregulation of Rad51 gene expression. MYC knockdown using small interfering RNA (siRNA) led to decreased RAD51 expression but minimal effects on homologous recombination based on a flow cytometry direct repeat green fluorescent protein assay. siRNA to MYC resulted in tumor cell kill in DU145 and H1299 cell lines in a manner independent of apoptosis. However, MYC-dependent changes in DSB repair protein expression were not sufficient to sensitize cells to mitomycin C or ionizing radiation, two agents selectively toxic to DSB repair-deficient cells. Our results suggest that anti-MYC agents may target cells to prevent genetic instability but would not lead to differential radiosensitization or chemosensitization.
Anti-epileptic effects of triheptanoin in two chronic mouse epilepsy models (2009)

The ability of autonomously replicating plasmids to recombine in mammalian cells was investigated. Two deletion plasmids of the eukaryotic-prokaryotic shuttle vector pSV2neo were cotransfected into transformed monkey COS cells. Examination of the low molecular weight DNA isolated after 48 hr of incubation revealed that recombination between the plasmids had occurred. The DNA was also used to transform recA- E. coli. Yield of neoR colonies signified homologous recombination. Examination of the plasmid DNA from these colonies confirmed this view. Double-strand breaks in one or both of the input plasmids at the sites of deletion resulted in an enhancement of recombination frequency. The recombination process yielded monomeric and dimeric molecules. Examination of these molecules revealed that reciprocal recombination as well as gene conversion events were involved in the generation of plasmids bearing an intact neo gene. The COS cell system we describe is analogous to study of bacteriophage recombination and yeast random-spore analysis.
Interferon‐γ variants with deletions in the AB surface loop (1998)

The receptor-binding AB loop of recombinant human interferon-gamma (IFN-gamma) has multiple contacts with the extracellular part of the IFN-gamma receptor a chain (IFN-gammaRalpha). We explored the possible length of truncated AB loops and their conformations by molecular modelling. Deletions of two amino acids at the tip of the loop were tolerated in the model without van der Waals collisions of the AB loop with helix F. Based on these modelling results, two deletion mutants were constructed by overlap-extension PCR mutagenesis: des-(A23, D24)-IFN-gamma and des-(N25, G26)-IFN-gamma. Both mutations were tolerated by the folding pattern of recombinant human IFN-gamma, as proved by CD spectroscopy. The stability of both mutants against cosolvent-induced unfolding was equal to that of wild-type IFN-gamma. In contrast to the biophysical similarities of wild-type and mutant IFN-gamma proteins, the biological activities of both mutants dropped significantly. Antiviral activity and human leucocyte antigen (HLA)-DR induction of des-(N25, G26)-IFN-gamma was 10% that of wild-type activity. des-(A23, D24)-IFN-gamma had only 1% remaining activity. Receptor-binding experiments confirmed that both deletions had a negative influence on the affinity of recombinant human IFN-gamma to its cellular receptor. We conclude from this combined molecular modelling and mutagenesis experiments, that the reduced flexibility of the truncated AB loop abrogates the possibility of the formation of a 3(10) helix in the receptor-bound state as observed in the X-ray structure of the IFN-gammaRalpha-IFN-gamma complex.
High-spatial-resolution distributed strain measurement in optical fiber with Rayleigh scatter (1998)

A method of measuring strain over 30-cm intervals to an accuracy of10 microstrain in unaltered low-loss communications-grade single-modeoptical fiber is presented. The method uses a tunable external cavity diode laser to measure the reflected intensity of a reflector-fiber system as a function of wavelength. This measurement is performed with no strain applied to the fiber to produce a reference and then again after a strain has been induced. Cross correlation of the Rayleigh scatter spectra from a selected section of fiber in the strained and unstrained states determines the spectral shift resulting from the applied strain.
Screening for Novel Antimicrobials from Encoded Combinatorial Libraries by Using a Two-Dimensional Agar Format (1998)

A sensitive lawn-based format has been developed to screen bead-tethered combinatorial chemical libraries for antimicrobial activity. This method has been validated with beads linked to penicillin V via a photocleavable chemical linker in several analyses including a spike-and-recover experiment. The lawn-based screen sensitivity was modified to detect antibacterial compounds of modest potency, and a demonstration experiment with a naive combinatorial library of over 46,000 individual triazines was evaluated for antibacterial activity. Numerous hits were identified, and both active and inactive compounds were resynthesized and confirmed in traditional broth assays. This demonstration experiment suggests that novel antimicrobial compounds can be easily identified from very large combinatorial libraries of small, nonpeptidic compounds.
A Photonic Analog-to-Digital Converter Based on an Unbalanced Mach-Zehnder Quantizer (2007)

A Mach-Zehnder modulator (MZM) based analog to digital converter (ADC) design is described. A single high speed unbalanced modulator is utilized as a quantizer. The signal to be digitized is applied to a single electrode. The rest of the system consists of commercially available, well developed wavelength division multiplexing (WDM) components. Analysis indicates that this system could provide 6 bits of resolution at 40 giga samples per second (GS/s) with moderate optical power.
Toll‐like receptors – sentries in the B‐cell response (2009)

Toll-like receptors (TLR) play a central role in the initiation of the innate immune response to pathogens. Upon recognition of molecular motifs specific for microbial molecules TLR mediate pro-inflammatory cytokine secretion and enhance antigen presentation; in B cells they further promote expansion, class switch recombination and immunoglobulin secretion. As a result of their adjuvant properties, TLR ligands have become an integral component of antimicrobial vaccines. In spite of this, little is known of the direct effects of TLR engagement on B-lymphocyte function. The scope of this review is to outline the differences in TLR expression and reactivity in murine and human B-cell subsets and to provide an overview of the currently available literature. We will further discuss the possible roles of TLR in regulating B-cell effector functions and shaping antibody-mediated defence against microbial pathogens in vivo.
Lipid binding and membrane penetration of polymyxin B derivatives studied in a biomimetic vesicle system (2003)

Understanding membrane interactions and cell-wall permeation of Gram-negative bacteria is of great importance, owing to increasing bacterial resistance to existing drugs and therapeutic treatments. Here we use biomimetic lipid vesicles to analyse membrane association and penetration by synthetic derivatives of polymyxin B (PMB), a potent naturally occurring antibacterial cyclic peptide. The PMB analogues studied were PMB nonapeptide (PMBN), in which the hydrophobic alkyl residue was cleaved, PMBN diastereomer containing D-instead of L-amino acids within the cyclic ring (dPMBN) and PMBN where the hydrophobic alkyl chain was replaced with an Ala6 repeat (Ala6-PMBN). Peptide binding measurements, colorimetric transitions induced within the vesicles, fluorescence quenching experiments and ESR spectroscopy were applied to investigate the structural parameters underlying the different membrane-permeation profiles and biological activities of the analogues. The experiments point to the role of negatively charged lipids in membrane binding and confirm the prominence of lipopolisaccharide (LPS) in promoting membrane association and penetration by the peptides. Examination of the lipid interactions of the PMB derivatives shows that the cyclic moiety of PMB is not only implicated in lipid attachment and LPS binding, but also affects penetration into the inner bilayer core. The addition of the Ala6 peptide moiety, however, does not significantly promote peptide insertion into the hydrophobic lipid environment. The data also indicate that the extent of penetration into the lipid bilayer is not related to the overall affinity of the peptides to the membrane.
Atomic-Signal-Based Zero-Field Finding Technique for Unshielded Atomic Vector Magnetometer (2012)

We describe a novel technique that can find the zero field in Earth's magnetic field for unshielded laser-pumped atomic magnetometer using atomic signal itself. By comparing light intensity of the pumping beam through atomic vapor cell under different magnetic fields, it decides which direction to move the compensation magnetic field and whether to increase or decrease the magnitude of increments in the compensating field. A convergence criterion is proposed, which not only keeps the field around zero, but also gives the precision of the compensation. The zero field is found in less than 23 s and the field increment after converging is smaller than 0.01, 0.01, and 0.04 μT for the <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</i> , <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">y</i> , and <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">z</i> axes, respectively, limited by 50-Hz noise in the laboratory environment. This method uses only one laser beam, which facilitates its application in chip-scale devices.
Dysregulation of apoptotic signaling in cancer: Molecular mechanisms and therapeutic opportunities (2008)

Apoptosis is a tightly regulated cell suicide program that plays an essential role in the maintenance of tissue homeostasis by eliminating unnecessary or harmful cells. Defects in this native defense mechanism promote malignant transformation and frequently confer chemoresistance to transformed cells. Indeed, the evasion of apoptosis has been recognized as a hallmark of cancer. Given that multiple mechanisms function at many levels to orchestrate the regulation of apoptosis, a multitude of opportunities for apoptotic dysregulation are present within the intricate signaling network of cell. Several of the molecular mechanisms by which cancer cells are protected from apoptosis have been elucidated. These advances have facilitated the development of novel apoptosis-inducing agents that have demonstrated single-agent activity against various types of cancers cells and/or sensitized resistant cancer cells to conventional cytotoxic therapies. Herein, we will highlight several of the central modes of apoptotic dysregulation found in cancer. We will also discuss several therapeutic strategies that aim to reestablish the apoptotic response, and thereby eradicate cancer cells, including those that demonstrate resistance to traditional therapies.
Human RIF1 encodes an anti-apoptotic factor required for DNA repair (2009)

Human Rap1-interacting protein 1 (RIF1) contributes to the ataxia telangiectasia, mutated-mediated DNA damage response against the dexterous effect of DNA lesions and plays a critical role in the S-phase checkpoint. However, the molecular mechanisms by which human RIF1 conquers DNA aberrations remain largely unknown. We here showed that inhibition of RIF1 expression by small interfering RNA led to defective homologous recombination-mediated DNA double-strand break repair and sensitized cancer cells to camptothecin or staurosporine treatment. RIF1 underwent caspase-dependent cleavage upon apoptosis. We further found that RIF1 was highly expressed in human breast tumors, and its expression status was positively correlated with differentiation degrees of invasive ductal carcinoma of the breast. Our results suggest that RIF1 encodes an anti-apoptotic factor required for DNA repair and is a potential target for cancer treatment.
The Effect of Oral Feeding of Lactobacillus casei Strain Shirota on Immunoglobulin E Production in Mice (1998)

We investigated the effect of oral feeding of heat-killed Lactobacillus casei strain Shirota on immunoglobulin E (IgE) production in mice. The strain was orally administered to BALB/c mice that had been preinjected intraperitoneally with ovalbumin, and the level of IgE in serum was determined. Results indicated that the oral feeding of L. casei strain Shirota was effective in inhibiting IgE production in serum, and the IgE production in response to ovalbumin was significantly inhibited in the mice. The in vitro production of IgE by the spleen cells from mice fed L. casei strain Shirota in response to restimulation with ovalbumin was inhibited in contrast to that of spleen cells from the control group. We also examined the pattern of cytokine production by spleen cells from mice fed L. casei strain Shirota followed by restimulation with ovalbumin in vitro. In the mice fed L. casei strain Shirota, the production by the spleen cells of Th1 cell-associated cytokines, such as interferon-gamma and interleukin-2, was higher than that by the spleen cells from the control group. In contrast, the production of Th2 cell-associated cytokines, such as interleukin-4, interleukin-5, interleukin-6, and interleukin-10, by spleen cells in the group fed L. casei strain Shirota was lower than that by the cells from the control group. Furthermore, the interleukin-12 production of the spleen cells from mice fed L. casei strain Shirota was also higher than that of the control group.
Monoclonal Antibodies to Human Osteosarcoma-Associated Antigen(s)<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref> (1986)

Monoclonal antibodies (MoAbs) against human osteosarcoma cells were obtained by the production and cloning of hybrids resulting from the fusion of mouse myeloma cells P3 X 63Ag8.653 with spleen cells from partially purified, osteosarcoma-associated antigen (OSAA)-immunized BALB/c mice. OSAAs were isolated from the spent culture medium of a human osteosarcoma cell line (TE-85). Five hybrid clones were established and designated as OSA1, OSA2, OSA3, OSA4, and OSA5. OSA1 and OSA2 had similar activity. All 5 MoAbs reacted strongly with most osteosarcoma cell lines and with all osteosarcoma tissues tested but not with 10 tumor cell lines and 2 tumor tissues from other cancers. OSA3, OSA4, and OSA5 cross-reacted with a fibrosarcoma cell line, a colon cell line, and fibrosarcoma, respectively, as well as with a melanoma cell line. None of the MoAbs were reactive with activated normal human peripheral blood mononuclear cells (PBMC). Immunoprecipitation of membrane protein isolated from LM cells and TE-85 cells with the MoAbs OSA1 and OSA2 conjugated with Staphylococcus aureus yielded a molecule with molecular weight of approximately 92,000. No detectable membrane protein was precipitated when 125I-labeled membrane protein from pooled activated human PBMC and tumor cells of other histologic types were used in the immunoprecipitation.
Ketone Bodies Stimulate Chaperone-mediatedAutophagy (2005)

Chaperone-mediated autophagy (CMA) is a selective lysosomal protein degradative process that is activated in higher organisms under conditions of prolonged starvation and in cell culture by the removal of serum. Ketone bodies are comprised of three compounds (beta-hydroxybutyrate, acetoacetate, and acetone) that circulate during starvation, especially during prolonged starvation. Here we have investigated the hypothesis that ketone bodies induce CMA. We found that physiological concentrations of beta-hydroxybutyrate (BOH) induced proteolysis in cells maintained in media with serum and without serum; however, acetoacetate only induced proteolysis in cells maintained in media with serum. Lysosomes isolated from BOH-treated cells displayed an increased ability to degrade both glyceraldehyde-3-phosphate dehydrogenase and ribonuclease A, substrates for CMA. Isolated lysosomes from cells maintained in media without serum also demonstrated an increased ability to degrade glyceraldehyde-3-phosphate dehydrogenase and ribonuclease A when the reaction was supplemented with BOH. Such treatment did not affect the levels of lysosome-associated membrane protein 2a or lysosomal heat shock cognate protein of 70 kDa, two rate-limiting proteins in CMA. However, pretreatment of glyceraldehyde-3-phosphate and ribonuclease A with BOH increased their rate of degradation by isolated lysosomes. Lysosomes pretreated with BOH showed no increase in proteolysis, suggesting that BOH acts on the substrates to increase their rates of proteolysis. Using OxyBlot analysis to detect carbonyl formation on proteins, one common marker of protein oxidation, we showed that treatment of substrates with BOH increased their oxidation. Neither glycerol, another compound that increases in circulation during prolonged starvation, nor butanol or butanone, compounds closely related to BOH, had an effect on CMA. The induction of CMA by ketone bodies may provide an important physiological mechanism for the activation of CMA during prolonged starvation.
Logic Synthesis for Fault-Tolerant Quantum Computers (2013)

Efficient constructions for quantum logic are essential since quantum computation is experimentally challenging. This thesis develops quantum logic synthesis as a paradigm for reducing the resource overhead in fault-tolerant quantum computing. The model for error correction considered here is the surface code. After developing the theory behind general logic synthesis, the resource costs of magic-state distillation for the $T = \exp(i π(I-Z)/8)$ gate are quantitatively analyzed. The resource costs for a relatively new protocol distilling multi-qubit Fourier states are calculated for the first time. Four different constructions of the fault-tolerant Toffoli gate, including two which incorporate error detection, are analyzed and compared. The techniques of logic synthesis reduce the cost of fault-tolerant quantum computation by one to two orders of magnitude, depending on which benchmark is used. Using resource analysis for $T$ gates and Toffoli gates, several proposals for constructing arbitrary quantum gates are compared, including "Clifford+$T$" sequences, $V$-basis sequences, phase kickback, and programmable ancilla rotations. The application of arbitrary gates to quantum algorithms for simulating chemistry is discussed as well. Finally, the thesis examines the techniques which lead to efficient constructions of quantum logic, and these observations point to even broader applications of logic synthesis.