gebhart/patrepeval huggingface dataset:
Simultaneous targeting of linked loci in mouse embryos using base editing (2019)

A particular challenge in genome engineering has been the simultaneous introduction of mutations into linked (located on the same chromosome) loci. Although CRISPR/Cas9 has been widely used to mutate individual sites, its application in simultaneously targeting of linked loci is limited as multiple nearby double-stranded DNA breaks created by Cas9 routinely result in the deletion of sequences between the cleavage sites. Base editing is a newer form of genome editing that directly converts C∙G-to-T∙A, or A∙T-to-G∙C, base pairs without introducing double-stranded breaks, thus opening the possibility to generate linked mutations without disrupting the entire locus. Through the co-injection of two base editors and two sgRNAs into mouse zygotes, we introduced C∙G-to-T∙A transitions into two cytokine-sensing transcription factor binding sites separated by 9 kb. We determined that one enhancer activates the two flanking genes in mammary tissue during pregnancy and lactation. The ability to introduce linked mutations simultaneously in one step into the mammalian germline has implications for a wide range of applications, including the functional analysis of linked cis-elements creating disease models and correcting pathogenic mutations.
Tumor Microsatellite-Instability Status as a Predictor of Benefit from Fluorouracil-Based Adjuvant Chemotherapy for Colon Cancer (2003)

Colon cancers with high-frequency microsatellite instability have clinical and pathological features that distinguish them from microsatellite-stable tumors. We investigated the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II and stage III colon cancer.
Neurotrophic factors influence upregulation of constitutive isoform of heme oxygenase and cellular stress response in the spinal cord following trauma. An experimental study using immunohistochemistry in the rat. (2000)

The influence of brain derived neurotrophic factor (BDNF) or insulin like growth factor-1 (IGF-1) on spinal cord trauma induced carbon monoxide (CO) production and cellular stress response was examined using immunostaining of the constitutive isoform of the hemeoxygenase (HO-2) enzyme and the heat shock protein (HSP 72kD) expression in a rat model. Subjection of rats to a 5 h spinal trauma inflicted by an incision into the right dorsal horn at T10-11 segment markedly upregulated the HO-2 and HSP expression in the adjacent spinal cord segments (T9 and T12). Pretreatment with BDNF or IGF-1 significantly attenuated the trauma induced HSP expression. The upregulation of HO-2 was also considerably reduced. These results show that BDNF and IGF-1 attenuate cellular stress response and production of CO following spinal cord injury which seems to be the key factors in neurotrophins induced neuroprotection.
Phase-noise-canceled differential phase-shift-keying (PNC-DPSK) for coherent optical communication systems (1990)

A modulation scheme using a nonlinear demodulation process, phase-noise-canceled differential phase-shift keying (PNC-DPSK), is used to circumvent the effects of phase noise in a phase-shift keying (PSK) system. A theoretical description of the system is given, and results of an experimental test system are shown to be in good agreement with the predictions. In particular, it is shown that the phase-noise-induced bit error rate (BER) floor can be eliminated despite using lasers with linewidths comparable to the data rate. Furthermore, for an optimized PNC-DPSK system, the degradation at high signal-to-noise compared to heterodyne PSK with ideal sources (i.e. no phase noise) should only be approximately=3 dB.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Measuring interactions of MHC class I molecules using surface plasmon resonance (1995)

To examine the molecular interactions between major histocompatibility complex (MHC)-encoded molecules and peptides, monoclonal antibodies (mAbs), or T cell receptors, we have developed model systems employing genetically engineered soluble MHC class I molecules (MHC-I), synthetic peptides, purified mAbs, and engineered solubilizable T cell receptors. Direct binding assays based on immobilization of one of the interacting components to the dextran modified gold biosensor surface of a surface plasmon resonance (SPR) detector have been developed for each of these systems. The peptide binding site of the MHC-I molecule can be sterically mapped by evaluation of a set of peptides immobilized through the thiol group of cysteine substitutions at each peptide position. Kinetic binding studies indicate that the MHC-I/peptide interaction is characterized by a low to moderate apparent kass (approximately 5000-60000 M-1 s-1) and very small kdis (approximately 10(-4)-10(-6) s-1) consistent with the biological requirement for a long cell surface residence time to permit engagement with T cell receptors. Several mAb directed against different MHC-I epitopes were examined, and kinetic parameters of their interaction with MHC molecules were determined. These showed characteristic moderate association rate constants and moderate dissociation rate constants (kass approximately 10(4)-10(6) M-1 s-1 and kdis approximately 10(-2)-10(-4) s-1), characteristic of many antibody/protein antigen interactions. The interaction of an anti-idiotypic anti-TCR mAb with its purified cognate TCR was of moderate affinity and revealed kinetic binding similar to that of the anti-MHC mAbs. The previously determined interaction of a purified T cell receptor with its MHC-I/peptide ligand is characterized by kinetic constants more similar to those of the antibody/antigen interaction than of the MHC-I/peptide interaction, but is remarkable for rapid dissociation rates (apparent kdis approximately 10(-2) s-1). Such binding studies of reactions involving the MHC-I molecules offer insight into the mechanisms responsible for the initial specific events required for the stimulation of T cells.
Unconventional Geometric Quantum Computation (2003)

We propose a new class of unconventional geometric gates involving nonzero dynamic phases, and elucidate that geometric quantum computation can be implemented by using these gates. Comparing with the conventional geometric gate operation, in which the dynamic phase shift must be removed or avoided, the gates proposed here may be operated more simply. We illustrate in detail that unconventional nontrivial two-qubit geometric gates with built-in fault-tolerant geometric features can be implemented in real physical systems.
Microfabricated vapor cells filled with a cesium dispensing paste for miniature atomic clocks (2017)

A method for filling alkali vapor cells with cesium from a dispensing paste is proposed and its compliance with miniature atomic clock applications is evaluated. The paste is an organic-inorganic composition of cesium molybdate, zirconium-aluminum powder, and a hybrid organic-inorganic binder. It is compatible with collective deposition processes such as micro-drop dispensing, which can be done under ambient atmosphere at the wafer-level. After deposition and sealing by anodic bonding, cesium is released from the consolidated paste through local heating with a high power laser. Linear absorption signals have been observed over one year in several cells, showing a stable atomic density. For further validation of this technology for clock applications, one cell has been implemented in a coherent population trapping clock setup to monitor its frequency stability. A fractional frequency aging rate around –4.4 × 10−12 per day has been observed, which is compliant with a clock frequency instability below 1 × 10−11 at one day integration time. This filling method can drastically reduce the cost and the complexity of alkali vapor cell fabrication.
False-Negative Results in Nucleic Acid Amplification Tests—Do We Need to Routinely Use Two Genetic Targets in all Assays to Overcome Problems Caused by Sequence Variation? (2008)

Nucleic acid amplification tests (NAATs) have numerous advantages over traditional diagnostic techniques and so are now widely used by diagnostic laboratories for routine detection of infectious agents. However, there is some concern over the increasing numbers of reports of NAAT false-negative results caused by sequence variation. Highly conserved NAAT target sequences have been reported for many organisms, yet sequence-related problems continue to be observed in commercial and in-house assays targeting a broad range of microbial pathogens. In light of these ongoing problems, it may be time to consider the use of two genetic targets in NAAT methods to reduce the potential for sequence-related false-negative results.
Venture Capital Definitions and Approaches (2008)

THEOXFORD ENGLISHDICTIONARY defines venture as a 'risky undertaking' but, to me, venture capital is an investment with very high upside and varying degrees of risk, depending on the stage of investment in a company. In a world in which, for most people, money and time are scarce commodities, it is important to concentrate on situations in which the rewards are potentially very high and the risks are therefore commensurate with the rewards. The old adage 'nothing ventured, nothing gained' could perhaps be rewritten as 'nothing gained, nothing ventured' in this context.KeywordsCash FlowVenture CapitalDeductive LogicVenture Capital InvestmentVenture Capital FirmThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Synthesis, structure, and morphology of polymer–silica hybrid nanocomposites based on hydroxyethyl methacrylate (1999)

Two types of polymer–silica nanocomposites have been prepared by undergoing free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) either in the presence of HEMA-functionalized SiO2 nanoparticles (Type 1) or during the simultaneous in situ growing of the silica phase through the acid-catalyzed sol–gel polymerization of tetraethoxysilane (TEOS) (Type 2). Relationships between synthesis conditions, chemical structure, and resulting morphology have been studied. Type 1 systems exhibit a classical particle-matrix morphology, but where particles tend to form aggregates. Type 2 systems possess a finer morphology characterized by a very open mass-fractal silicate structure, which is believed to be bicontinuous with the organic phase at a molecular level. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 3172–3187, 1999
Postsynaptic Supersensitivity after 6‐Hydroxy‐dopamine Induced Degeneration of the Nigro‐striatal Dopamine System (1971)

Abstract The effect of L‐DOPA and the dopamine (DA) receptor stimulating drug apomorphine was studied in rats after unilateral degeneration of the nigrostriatal DA system by intracerebral injection of 6‐hydroxydopamine. Both apomorphine and L‐DOPA induced a strong rotational behaviour which was registered in a specially designed “rotameter”. The direction of the rotation indicated that the denervated striatum was more sensitive to DA receptor stimulating drugs than the innervated striatum. This supersensitivity probably corresponded to the decentralisation type of supersensitivity in the peripheral nervous system although it developed faster. The action of L‐DOPA was inhibited by pretreatment with the DOPA‐decarboxylase inhibitor Ro4–4602 which indicated that L‐DOPA must be converted to DA in order to stimulate the supersensitive postsynaptic cells. Pretreatment with a single dose of reserpine also induced supersentitivity to apomorphine which reached its maximum on the 3rd day and then decreased on the 4th day. Postsynaptic supersensitivity after degeneration of the nigro‐striatal DA system is probably an important reason for the effectiveness of the L‐DOPA therapy against Parkinson's disease.
Anti-inflammatory effects of glaucocalyxin B in microglia cells (2015)

Over-activated microglia is involved in various kinds of neurodegenerative process including Parkinson, Alzheimer and HIV dementia. Suppression of microglial over activation has emerged as a novel strategy for treatment of neuroinflammation-based neurodegeneration. In the current study, anti-inflammatory and neuroprotective effects of the ent-kauranoid diterpenoids, which were isolated from the aerial parts of Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara, were investigated in cultured microglia cells. Glaucocalyxin B (GLB), one of five ent-kauranoid diterpenoids, significantly decreased the generation of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in the lipopolysaccharide (LPS)-activated microglia cells. In addition, GLB inhibited activation of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) in LPS-activated microglia cells. Furthermore, GLB strongly induced the expression of heme oxygenase (HO)-1 in BV-2 microglia cells. Finally, GLB exhibited neuroprotective effect by preventing over-activated microglia induced neurotoxicity in a microglia/neuron co-culture model. Taken together, the present study demonstrated that the GLB possesses anti-nueroinflammatory activity, and might serve as a potential therapeutic agent for treating neuroinflammatory diseases.
Modules and brain mapping (2011)

This review highlights the key role of modularity and the additive factors method in functional neuroimaging. Our focus is on structure-function mappings in the human brain and how these are disclosed by brain mapping. We describe how modularity of processing (and possibly processes) was a key point of reference for establishing functional segregation as a principle of brain organization. Furthermore, modularity plays a crucial role when trying to characterize distributed brain responses in terms of functional integration or coupling among brain areas. We consider additive factors logic and how it helped to shape the design and interpretation of studies at the inception of brain mapping, with a special focus on factorial designs. We look at factorial designs in activation experiments and in the context of lesion-deficit mapping. In both cases, the presence or absence of interactions among various experimental factors has proven essential in understanding the context-sensitive nature of distributed but modular processing and discerning the nature of (potentially degenerate) structure-function relationships in cognitive neuroscience.
High expression of Y-box-binding protein 1 is associated with local recurrence and predicts poor outcome in patients with colorectal cancer. (2014)

Colorectal cancer (CRC) is one of the most common and fatal malignancies worldwide. Novel prognostic biomarkers are urgently warranted to help improve the treatment of CRC. Y-box-binding protein 1 (YB-1) has been identified as a multifunctional oncoprotein in various malignancies. Our previous study has suggested that YB-1 may promote malignant progression of CRC cells in vitro. However, its clinical and prognostic significance in CRC patients remains unclear. In this study, the expression of YB-1 was examined in 32 fresh CRC tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and in 170 paraffin-embedded CRC tissues using immunohistochemistry. The result of qRT-PCR demonstrated mRNA expression of YB-1 was increased in 26 of 32 (81.25%) of CRC patients. The statistical analysis based on immunohistochemical staining suggested that YB-1 expression was significantly correlated with tumor differentiation, tumor invasion, lymph node metastasis and Dukes' classification (all P<0.05). Furthermore, we found that patients with high YB-1 expression had a poorer prognosis and were more likely to undergo local recurrence, compared to those with low YB-1 expression. We also identified that YB-1 expression, together with lymph node metastasis and Dukes' classification were independent prognostic factors for CRC patients. In conclusion, our study for the first time demonstrated the clinical and prognostic significance of YB-1 in CRC and suggested that YB-1 is of great potential to be an attractive therapeutic target as well as prognostic biomarker for CRC patients.
Hydrodynamic Manipulation of DNA in Nanopost Arrays: Unhooking Dynamics and Size Separation (2011)

Micro- or nanofabricated obstacle arrays are widely used as model matrices to perform fast DNA separations by electrophoresis. In this report, a gallery of obstacles of radii spanning from 40 to 250 nm are used to investigate the dynamics of hydrodynamic-field-driven DNA-nanopost collisions at the single-molecule level. The data shows that DNA disengagement dynamics are reasonably well described by conventional electrophoretic models in the limit of a large spacing between obstacles and for moderate migration velocities. It is also demonstrated that the use of hydrodynamic flow fields to convey DNA molecules is associated with changes in the configurational space of hooking events, and to altered relaxation dynamics between consecutive collisions. This study defines experimental conditions for the efficient separation of DNA fragments of tens of base pairs, and provides a complete framework by which to understand the behavior of DNA in the course of hydrodynamic-driven migrations through nanopost arrays.
Structure, function, and fate of the BlaR signal transducer involved in induction of beta-lactamase in Bacillus licheniformis (1992)

The membrane-spanning protein BlaR is essential for the induction of beta-lactamase in Bacillus licheniformis. Its nature and location were confirmed by the use of an antiserum specific for its carboxy-terminal penicillin sensor, its function was studied by genetic dissection, and the structure of the penicillin sensor was derived from hydrophobic cluster analysis of the amino acid sequence by using, as a reference, the class A beta-lactamases with known three-dimensional structures. During the first 2 h after the addition of the beta-lactam inducer, full-size BlaR, bound to the plasma membrane, is produced, and then beta-lactamase is produced. By 2 h after induction, BlaR is present in various (membrane-bound and cytosolic) forms, and there is a gradual decrease in beta-lactamase production. The penicillin sensors of BlaR and the class D beta-lactamases show strong similarities in primary structures. They appear to have the same basic spatial disposition of secondary structures as that of the class A beta-lactamases, except that they lack several alpha helices and, therefore, have a partially uncovered five-stranded beta sheet and a more readily accessible active site. Alterations of BlaR affecting conserved secondary structures of the penicillin sensor and specific sites of the transducer annihilate beta-lactamase inducibility.
Gene Therapy Using Dc-Chol Liposomes (1995)

Gene therapy offers the potential to deliver genetic material inside the cells for correcting a disease phenotype. Various techniques for the transgene delivery have been developed, among which cationic liposome mediated delivery is widely acceptable. DC-Chol/DOPE cationic liposomes, synthesized in our laboratory, have several alluring features such as low toxicity, non-immunogenicity, ease of utilization and stability. These liposomes have been successfully used as a vector in clinical trials for treating melanoma and cystic fibrosis. Only a small portion of the DNA-liposome complex taken up by the cell is eventually available for gene expression in the nucleus. To overcome the problem of limited expression, we have developed a cytoplasmic expression system in which the reporter gene is placed under the control of a bacteriophage T7 promoter. To initiate the expression of the gene either purified T7 RNA polymerase or T7 autogene expression vector is transfected along with the reporter gene. Prolonged transgene expression was observed in tumor cells treated with this novel gene transfer system. In an effort to enhance the transgene expression in vivo, we discovered that injections of cisplatin into tumor-bearing mice prior to injecting the DNA-liposome complex significantly enhances the transgene expression. A sequential, combination therapy protocol is therefore proposed for cancer gene therapy.
The aetiology of Kaposi's sarcoma. (1991)

The aetiology of KS remains unknown, but recent evidence suggests that the disease is caused by the presence of an infectious agent in an immunosuppressed host. Although there are a variety of clinical presentations, the putative infectious agent is likely to be the same in all cases. The pathophysiology of the lesions, the types of immunosuppression that facilitate disease expression, the response to therapy and the distribution of disease within immunosuppressed populations provide important clues to the nature of the unidentified infectious agent.
Hot-carrier effects in thin-film fully depleted SOI MOSFET's (1994)

Previous conflicting reports concerning fully depleted SOI device hot electron reliability may result from overestimation of channel electric field (E/sub m/). Experimental results using SOI MOSFET's with body contacts indicate that E/sub m/ is just a weak function of thin-film SOI thickness (T/sub si/ and that E/sub m/ can be significantly lower than in a bulk device with drain junction depth (X/sub j/) comparable to SOI's T/sub si/. The theoretical correlation between SOI MOSFET's gate current and substrate current are experimentally confirmed. This provides a means (I/sub G/) of studying E/sub m/ in SOI device without body contacts. Thin-film SOI MOSFET's have better prospects for meeting breakdown voltage and hot-electron reliability requirements than previously thought.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Central Nervous System Damage During Cardiac Surgery Assessed by 3 Different Biochemical Markers in Cerebrospinal Fluid (1992)

Three cerebral biochemical markers, adenylate kinase (AK), neuron-specific enolase (NSE) and protein S-100, were determined in the cerebrospinal fluid (CSF) of male patients 24 h after coronary artery bypass grafting to investigate the extent of possible center nervous system (CNS) damage and relation to the type of oxygenator and the use of an arterial line filter. The patients were randomized into three groups for extracorporeal circulation (ECC); bubble oxygenator without an arterial line filter (Group I, n = 30), bubble oxygenator with a filter (Group II, n = 29) and a flat-sheet membrane oxygenator without a filter (Group III, n = 33). Pathologically high CSF levels of AK and NSE were found 24 h after ECC in respectively 93% and 95% of the patients. All protein S-100 concentrations were within the normal range. Isolated high CSF concentrations of AK, NSE and protein S-100 were observed in group I. Levels of AK and NSE were the lowest in group III, although there was no statistical difference between the groups. In conclusion, our study suggested that CNS damage caused by ECC involved neurons rather than glial cells. AK and NSE in the CSF seemed to be markers of ischaemic neuronal damage. Postoperative levels of biochemical markers in the CSF tended to be the lowest in the flat-sheet membrane oxygenator group.
Evaluation of sensor calibration in a biometric person recognition framework based on sensor fusion (2000)

Biometric person authentication is a secure and user-friendly way of identifying persons in a variety of everyday applications. In order to achieve high recognition rates, we propose an audio-visual person recognition system based on voice, lip motion and still image. The combination of these three data sources (called sensor fusion) may be performed in several ways. We present a method for sensor normalization based on statistical sensor properties. We call this procedure sensor calibration. The final decision fusion simplifies to a multiplication or addition of the normalized outputs of each sensor. This approach is evaluated on a large database of 170 people with a total of 6315 recordings.