gebhart/patrepeval huggingface dataset:
Nonenzymatic, Template-Directed Ligation of Oligoribonucleotides Is Highly Regioselective for the Formation of 3‘−5‘ Phosphodiester Bonds (1996)

We have found that nonenzymatic, template-directed ligation reactions of oligoribonucleotides display high selectivity for the formation of 3'-5' rather than 2'-5' phosphodiester bonds. Formation of the 3'-5'-linked product is favored regardless of the metal ion catalyst or the leaving group, and for several different ligation junction sequences. The degree of selectivity depends on the leaving group: the ratio of 3'-5'- to 2'-5'-linked products was 10-15:1 when the 5'-phosphate was activated as the imidazolide, and 60-80:1 when the 5'-phosphate was activated by the formation of a 5'-triphosphate. Comparison of oligonucleotide ligation reactions with previously characterized single nucleotide primer extension reactions suggests that the strong preference for 3'-5'-linkages in oligonucleotide ligation is primarily due to occurence of ligation within the context of an extended Watston-Crick duplex. The ability of RNA to correctly self-assemble by template-directed ligation is an intrinsic consequence of its chemical structure and need not be imposed by an external catalyst (i.e., an enzyme polymerase); RNA therefore provides a reasonable structural basis for a self-replicating system in a prebiological world.
Nkx3.1 and Myc crossregulate shared target genes in mouse and human prostate tumorigenesis (2012)

Cooperativity between oncogenic mutations is recognized as a fundamental feature of malignant transformation, and it may be mediated by synergistic regulation of the expression of pro- and antitumorigenic target genes. However, the mechanisms by which oncogenes and tumor suppressors coregulate downstream targets and pathways remain largely unknown. Here, we used ChIP coupled to massively parallel sequencing (ChIP-seq) and gene expression profiling in mouse prostates to identify direct targets of the tumor suppressor Nkx3.1. Further analysis indicated that a substantial fraction of Nkx3.1 target genes are also direct targets of the oncoprotein Myc. We also showed that Nkx3.1 and Myc bound to and crossregulated shared target genes in mouse and human prostate epithelial cells and that Nkx3.1 could oppose the transcriptional activity of Myc. Furthermore, loss of Nkx3.1 cooperated with concurrent overexpression of Myc to promote prostate cancer in transgenic mice. In human prostate cancer patients, dysregulation of shared NKX3.1/MYC target genes was associated with disease relapse. Our results indicate that NKX3.1 and MYC coregulate prostate tumorigenesis by converging on, and crossregulating, a common set of target genes. We propose that coregulation of target gene expression by oncogenic/tumor suppressor transcription factors may represent a general mechanism underlying the cooperativity of oncogenic mutations during tumorigenesis.
Optoelectronic conversion through 850nm band single mode Si/sub 3/N/sub 4/ photonic waveguides for Si-on-chip integration (2003)

We have directly coupled Si PIN vertical-junction diode photodetectors and Si/sub 3/N/sub 4/ photonic waveguides on the same horizontal plane of an SOI wafer using a standard Si process. For the stress-free CVD deposition of Si/sub 3/N/sub 4/, the core thickness was set at 200 nm. The single-mode is solved by simulation for the 0.7 /spl mu/m-wide waveguide at a wavelength of 850 nm. Photo-electronic conversion characteristics were examined by introducing a 650 nm and 850 nm laser beam from a rounded-end optical fiber to the on-chip waveguide. Efficient optoelectronic conversion is confirmed through an 850 nm band single mode Si/sub 3/N/sub 4/ photonic waveguide for Si-on-chip integration.
Knockdown of platinum‐induced growth differentiation factor 15 abrogates p27‐mediated tumor growth delay in the chemoresistant ovarian cancer model A2780cis (2014)

Molecular mechanisms underlying the development of resistance to platinum-based treatment in patients with ovarian cancer remain poorly understood. This is mainly due to the lack of appropriate in vivo models allowing the identification of resistance-related factors. In this study, we used human whole-genome microarrays and linear model analysis to identify potential resistance-related genes by comparing the expression profiles of the parental human ovarian cancer model A2780 and its platinum-resistant variant A2780cis before and after carboplatin treatment in vivo. Growth differentiation factor 15 (GDF15) was identified as one of five potential resistance-related genes in the A2780cis tumor model. Although A2780-bearing mice showed a strong carboplatin-induced increase of GDF15 plasma levels, the basal higher GDF15 plasma levels of A2780cis-bearing mice showed no further increase after short-term or long-term carboplatin treatment. This correlated with a decreased DNA damage response, enhanced AKT survival signaling and abrogated cell cycle arrest in the carboplatin-treated A2780cis tumors. Furthermore, knockdown of GDF15 in A2780cis cells did not alter cell proliferation but enhanced cell migration and colony size in vitro. Interestingly, in vivo knockdown of GDF15 in the A2780cis model led to a basal-enhanced tumor growth, but increased sensitivity to carboplatin treatment as compared to the control-transduced A2780cis tumors. This was associated with larger necrotic areas, a lobular tumor structure and increased p53 and p16 expression of the carboplatin-treated shGDF15-A2780cis tumors. Furthermore, shRNA-mediated GDF15 knockdown abrogated p27 expression as compared to control-transduced A2780cis tumors. In conclusion, these data show that GDF15 may contribute to carboplatin resistance by suppressing tumor growth through p27. These data show that GDF15 might serve as a novel treatment target in women with platinum-resistant ovarian cancer.
Targeting the Extracellular Domain of Fibroblast Growth Factor Receptor 3 with Human Single-Chain Fv Antibodies Inhibits Bladder Carcinoma Cell Line Proliferation (2005)

Our results suggest that these human anti-FGFR3 scFv antibodies may have potential applications as antitumoral agents in bladder cancer.
Combined use of borneol or menthol with labrasol promotes penetration of baicalin through rabbit cornea in vitro. (2015)

The permeability of most drugs through the eyes is very limited, so finding safe and effective penetration enhancers is of high importance in current ophthalmology research. In this paper, we use a new approach that integrates Chinese and Western medicine to improve the corneal permeability of baicalin, a water- and fat-insoluble target drug, in vitro. Rabbits were divided into three groups. The first group was dosed with borneol (0.05%, 0.1%). menthol (0.1%, 0.2%), or Labrasol (1%, 2%) individually, the second was dosed with a combination of Labrasol with either borneol or menthol, and the third group received a control treatment. Compared with the control treatment, borneol, menthol, or Labrasol alone clearly improved the permeability of baicalin in vitro. Furthermore, the penetrating effects were significantly increased by combining the application of Labrasol with menthol or borneol. Among the various combined penetration enhancers, 0.1% borneol with 2% Labrasol achieved the best apparent permeability, approximately 16.35 times that of the control. Additionally, the calculation of corneal hydration level and the Draize test demonstrated the safety of these penetration enhancers to the rabbit corneas in vivo. This study confirms that the combined use of borneol or menthol, compounds both derived from Chinese herbs, with Labrasol can improve the corneal permeability of water- and fat-insoluble drugs.
Electron transport through a metal-molecule-metal junction (1999)

Molecules of bisthiolterthiophene have been adsorbed on the two facing gold electrodes of a mechanically controllable break junction in order to form metal-molecule(s)-metal junctions. Current-voltage $(I\ensuremath{-}V)$ characteristics have been recorded at room temperature. Zero bias conductances were measured in the 10--100 nS range and different kinds of nonlinear $I\ensuremath{-}V$ curves with steplike features were reproducibly obtained. Switching between different kinds of $I\ensuremath{-}V$ curves could be induced by varying the distance between the two metallic electrodes. The experimental results are discussed within the framework of tunneling transport models explicitly taking into account the discrete nature of the electronic spectrum of the molecule.
Therapeutic use of monoclonal anti-CD4 antibody in rheumatoid arthritis. (1991)

Ten patients with severe rheumatoid arthritis were treated with a murine monoclonal anti-CD4 (B-F5) antibody in an open study (one with 10 mg/day, 2 with 15 mg/day, 7 with 20 mg/day) for 10 consecutive days. Tolerance was excellent. All patients improved during treatment clinically (Ritchie's index, morning stiffness, pain scale) (p = 0.005), as well as biologically C-reactive protein (p = 0.008) with an average 60% reduction of each of these variables at Day 15, and clinical benefit lasted over 6 months in some patients. No significative depletion was noted in total lymphocyte or CD3, CD4, CD8, CD20, positive cells after treatment. Evidence of murine immunization was found in only 2 patients.
Quantitative immunohistochemical analysis of transforming growth factor-α and epidermal growth factor receptor in patients with squamous cell carcinoma of the head and neck (1996)

TGF-alpha and EGFR protein expression is increased early in head and neck squamous cell carcinogenesis and can be quantitated by computerized image analysis of immunohistochemical staining. Altered distribution of TGF-alpha protein in histologically normal mucosa from SCCHN patients compared with control mucosa from patients without cancer suggests a switch from a paracrine to an autocrine pathway.
Mixed-conducting ceramic membranes for partial oxygenation of methane (1995)

The most significant cost associated with the conventional partial oxidation of methane is that of an oxygen plant. Our new technology offers a way to lower this cost, and in this paper we explore the technology that is based on dense ceramic membranes and that uses air as the oxidant for methane-conversion reactions. Mixed-conducting ceramic materials have been produced from mixed-oxide systems of the La-Sr-Fe-Co-O (SFC) type, in the form of tubes and bars. Thermodynamic stability of the tubes was studied as a function of oxygen partial pressure by high-temperature XRD. Mechanical properties were measured and found to be adequate for a reactor in the case of SFC-2: Electronic and ionic conductivities were measured; SFC-2 is unique in the sense that the ratio of ionic to electronic conductance is close to unity. Performance of the membrane tubes was good only with SFC-2. Fracture of other SFC tubes was the consequence of an oxygen gradient that introduced a volumetric lattice difference between the inner and outer walls. SFC-2 tubes provided methane conversion efficiencies of >99% in a reactor. These tubes have operated for >1000 h.
Drug Delivery System of Anti-fungal and Parasitic Agents (2002)

The antifungal agents for systemic mycoses are only a few in number. Among them amphotericin-B is still the most widely used drug, but substantial side effects including nephrotoxicity limits its clinical usefulness. Efforts to lower the toxicity are synthesis of AMPH-B analogues such as AMPH-B esters and encapsulation in lipid vesicles in the forms of liposomal AMPH-B (AmBisome), amphotericin-B lipid complex (Abelcet), amphotericin-B colloidal dispersion (Amphocil) and intralipid AMPH-B. The newer formulations are effective against wide range of fungi, may be given in higher doses and nephrotoxicity is lowered. Although all of them showed comparable efficacies, a standard formulation is yet to be determined. In Japan, studies on efficacies of lipid nanosphere-encapsulated AMPH-B are in progress. Special drug career systems and dosage forms, such as nanoparticles and liposomes hold the promise of overcoming the pharmacokinetic limitations. Nanoparticles are stable, solid colloidal particles consisting of macromolecular material and vary in size. Nanoparticles represent an interesting carrier system for the specific enrichment in macrophage containing organs like liver and spleen. Injectable nanoparticle carriers have important potential applications as in site-specific drug delivery. Modifications of liposomes in order to avoid uptake by RES, thus increase targetability has been attempted. A novel targetable liposome 34A-PEG-L modified with polyethylene glycol conjugated with MoAb, 34A specific to murine pulmonary epithelia has been evaluated in murine pulmonary aspergillosis. 34A-PEG-L-AmB showed higher tissue concentration and comparable efficacy than other AMPH-B formulations.
Neonatal White Matter Abnormalities an Important Predictor of Neurocognitive Outcome for Very Preterm Children (2012)

Findings highlight the importance of cerebral white matter connectivity for later intact cognitive functioning amongst children born very preterm. Preterm born children without cerebral white matter abnormalities on their term MRI appear to be spared many of the cognitive impairments commonly associated with preterm birth. Further follow-up will be important to assess whether this finding persists into the school years.
Five SWI/SNF gene products are components of a large multisubunit complex required for transcriptional enhancement. (1994)

The Saccharomyces cerevisiae SWI1, SWI2 (SNF2), SWI3, SNF5, and SNF6 gene products play a crucial role in the regulation of transcription. We provide here direct biochemical evidence that all five SWI/SNF polypeptides are components of a large multisubunit complex. These five polypeptides coelute from a gel-filtration column with an apparent molecular mass of approximately 2 MDa. The five SWI/SNF polypeptides do not copurify when extracts are prepared from swi- or snf- mutants. We show that SWI/SNF polypeptides also remain associated during an affinity-chromatography step followed by gel filtration. Assembly of the SWI/SNF complex is not disrupted by a mutation in the putative APT-binding site of SWI2, although this mutation eliminates SWI2 function.
Cloning and Characterization of the Gene for β-Tubulin from a Benomyl-Resistant Mutant of Neurospora crassa and Its Use as a Dominant Selectable Marker (1986)

We cloned the beta-tubulin gene of Neurospora crassa from a benomyl-resistant strain and determined its nucleotide sequence. The gene encodes a 447-residue protein which shows strong homology to other beta-tubulins. The coding region is interrupted by six introns, five of which are within the region coding for the first 54 amino acids of the protein. Intron position comparisons between the N. crassa gene and other fungal beta-tubulin genes reveal considerable positional conservation. The mutation responsible for benomyl resistance was determined; it caused a phenylalanine-to-tyrosine change at position 167. Codon usage in the beta-tubulin gene is biased, as has been observed for other abundantly expressed N. crassa genes such as am and the H3 and H4 histone genes. This bias results in pyrimidines in the third positions of 96% of the codons in codon families in which there is a choice between purines and pyrimidines in this position. Bias is also evident by the absence of 19 of the 61 sense codons. We demonstrated that benomyl resistance is due to the cloned beta-tubulin gene of strain Bml511(r)a and that this gene can be used as a dominant selectable marker in N. crassa transformation.
Multiwavelength light source with precise frequency spacing using a mode-locked semiconductor laser and an arrayed waveguide grating filter (1997)

A multiwavelength light source with precise optical frequency spacing can be created by extracting an individual mode of a semiconductor mode-locked laser using an arrayed waveguide grating filter. The outputs of the light source are locked to wavelength division multiplexing (WDM) optical frequency grids using an optical frequency standard light source. They can be successfully modulated by 5 Gb/s nonreturn-to-zero (NRZ) signals and can be transmitted through 100-km-long optical fiber.
Sensor networks: an overview (2003)

Advances in hardware and wireless network technologies have created low-cost, low-power, multifunctional miniature sensor devices. These devices make up hundreds or thousands of ad hoc tiny sensor nodes spread across a geographical area. These sensor nodes collaborate among themselves to establish a sensing network. A sensor network can provide access to information anytime, anywhere by collecting, processing, analyzing and disseminating data. Thus, the network actively participates in creating a smart environment.
Development of an Avian Leukosis-Sarcoma Virus Subgroup A Pseudotyped Lentiviral Vector (2001)

We are using avian leukosis-sarcoma virus (ALSV) vectors to generate mouse tumor models in transgenic mice expressing TVA, the receptor for subgroup A ALSV. Like other classical retroviruses, ALSV requires cell division to establish a provirus after infection of host cells. In contrast, lentiviral vectors are capable of integrating their viral DNA into the genomes of nondividing cells. With the intention of initiating tumorigenesis in resting, TVA-positive cells, we have developed a system for the preparation of a human immunodeficiency virus type 1 (HIV-1)-based lentiviral vector, pseudotyped with the envelope protein of ALSV subgroup A (EnvA). The HIV(ALSV-A) vector retains the requirement for TVA on the surface of target cells and can be produced at titers of 5 x 10(3) infectious units (IU)/ml. By inserting the central polypurine tract (cPPT) from the HIV-1 pol gene and removing the cytoplasmic tail of EnvA, the pseudotype can be produced at titers approaching 10(5) IU/ml and can be concentrated by ultracentrifugation to titers of 10(7) IU/ml. HIV(ALSV-A) also infects embryonic fibroblasts derived from transgenic mice in which TVA expression is driven by the beta-actin promoter. In addition, this lentivirus pseudotype efficiently infects these fibroblasts after cell cycle arrest, when they are resistant to infection by ALSV vectors. This system may be useful for introducing genes into somatic cells in adult TVA transgenic animals and allows evaluation of the effects of altered gene expression in differentiated cell types in vivo.
Nitric Oxide And Oxygen: Actions And Interactions In Health And Disease (2015)

Nitric oxide (NO) inhibits cell respiration reversibly and in competition with O<sub>2</sub> through the inhibition of the mitochondrial cytochrome c oxidase (Complex IV). At concentrations lower than those required to inhibit respiration, endogenous NO enhances the reduction of the electron transport chain, thus enabling cells to maintain their O<sub>2</sub> consumption. This however facilitates the release of superoxide anion, which initiates the transcriptional activation of NF-kB as an early signal of a stress response. Through free radical formation, long-term inhibition of mitochondrial respiration by NO leads to persistent inhibition of Complex I. This is dependent on the S-nitrosylation of a specific thiol in the active form of this protein. S-nitrosylation of Complex I might indicate the early stages of a pathological process. Inhibition of mitochondrial respiration by low concentrations of NO at critical O2 concentrations also leads to prevention of the stabilization of hypoxia-inducible factor-1α (HIF-1α) due to the redistribution of O<sub>2</sub> towards non-respiratory O<sub>2</sub>-dependent targets. This prevents the cell from registering a state of hypoxia at low O<sub>2</sub> concentrations. On the other hand, at higher concentrations such as those generated in certain forms of cancer, NO increases the expression of HIF-1α by an action most probably involving a free radical mechanism. It is likely that the interactions between oxygen and NO, either at the mitochondria or in the cell in general, play a role in the initiation and development of neoplastic transformation and spreading. The ways in which these interactions operate remain unclear and are likely to vary from cancer to cancer.
Fusing the carboxy-terminal peptide of the chorionic gonadotropin (CG) beta-subunit to the common alpha-subunit: retention of O-linked glycosylation and enhanced in vivo bioactivity of chimeric human CG. (1995)

The hCG beta-subunit contains a carboxy-terminal extension bearing four serine-linked oligosaccharides [carboxy-terminal peptide (CTP)], which is important for maintaining its longer half-life compared with the other glycoprotein hormones. Previously, we enhanced the in vivo half-life of FSH by fusing the CTP to the carboxy end of FSH beta coding sequence. The alpha-subunit is common to the glycoprotein family. We constructed alpha-subunit CTP chimeras, since such analogs with the appropriate O-linked glycosylation and conformation would increase the in vivo stability of the entire glycoprotein hormone family. Two chimeras were constructed using overlapping polymerase chain reaction mutagenesis: a variant with CTP at the carboxy end and another analog with the CTP at the N-terminal region of the subunit, between amino acids 3 and 4. The latter design was based on models showing that the amino-terminal region of alpha is not involved in assembly with the beta-subunit, nor is it essential for receptor binding and signal transduction. These chimeras were cotransfected with the hCG beta gene into Chinese hamster ovary cells. The chimeras were secreted and combined efficiently with the CG beta-subunit, comparable to the wild type alpha-subunit. CG dimers containing the alpha-subunit chimera with CTP at the carboxy end of the subunit had a much lower binding affinity for the hLH-hCG receptor in vitro, whereas the binding of the dimer containing the CTP at the amino-terminal end of the subunit was similar to wild type hCG. Furthermore, the in vivo activity of this analog was enhanced significantly. Moreover, regardless of the two insertion points in the alpha-subunit, the CTP sequence was O-glycosylated. These data suggest that the entire signal for O-glycosylation is primarily contained within the CTP sequence and is not dependent on the flanking regions of the recipient protein. The transfer of CTP to the alpha-subunit of hCG results in an agonist with prolonged biological action in vivo. These data further support the rationale for using the CTP as a general target to increase the potency of bioactive glycoproteins.
Elevated Levels of IFN-γ in CSF and Serum of Patients with Amyotrophic Lateral Sclerosis (2015)

These results demonstrated that IFN-γ in CSF may serve as a biomarker of ALS differentiation and progression. CSF IFN-γ was a more reliable biomarker of disease diagnosis and progression than serum IFN-γ.