gebhart/patrepeval huggingface dataset:
LTD and LTP induced by transcranial magnetic stimulation in auditory cortex (1996)

Using a system capable of relatively localized and rapidrate transcranial magnetic stimulation (rTMS), evoked trains of complex spikes were studied in rodent auditory cortex. Low rate rTMS from 1 to 10Hz produced a frequency-dependent increase in spike rate. Iterations of rTMS resulted in long-term potentiation (LTP)-like, and more durable long-term depression (LTD)-like changes in evoked spike rate. These observations generate new perspectives for studying mechanisms of learning and memory non-invasively as well as introducing some caveats for use of rTMS in humans.
Genomic structure of the human prion protein gene. (1991)

Creutzfeld-Jacob disease and Gerstmann-Sträussler syndrome are rare degenerative disorders of the nervous system which have been genetically linked to the prion protein (PrP) gene. The PrP gene encodes a host glycoprotein of unknown function and is located on the short arm of chromosome 20, a region with few known genes or anonymous markers. The complete structure of the PrP gene in man has not been determined despite considerable interest in its relationship to these unusual disorders. We have determined that the human PrP gene has the same simple genomic structure seen in the hamster gene and consists of two exons and a single intron. In contrast to the hamster PrP gene the human gene appears to have a single major transcriptional start site. The region immediately 5' of the transcriptional start site of the human PrP gene demonstrates the GC-rich features commonly seen in housekeeping genes. Curiously, the genomic clone we have isolated contains a 24-bp deletion that removes one of five octameric peptide repeats predicted to form a B-pleated sheet in this region of the PrP. We have also identified 5' of the PrP gene an RFLP which has a high degree of heterozygosity and which should serve as a useful marker for the pter-12 region of human chromosome 20.
Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase (2007)

Abuse of the dissociative anesthetic ketamine can lead to a syndrome indistinguishable from schizophrenia. In animals, repetitive exposure to this N-methyl-d-aspartate-receptor antagonist induces the dysfunction of a subset of cortical fast-spiking inhibitory interneurons, with loss of expression of parvalbumin and the gamma-aminobutyric acid-producing enzyme GAD67. We show here that exposure of mice to ketamine induced a persistent increase in brain superoxide due to activation in neurons of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Decreasing superoxide production prevented the effects of ketamine on inhibitory interneurons in the prefrontal cortex. These results suggest that NADPH oxidase may represent a novel target for the treatment of ketamine-induced psychosis.
Effects of human amniotic fluid on peripheral nerve scarring and regeneration in rats (2003)

Preliminary data show that HAF enhances peripheral nerve regeneration. The preventive effect of HAF on epineural scarring and the rich content of neurotrophic and neurite-promoting factors possibly contribute to this result.
αMSH and Cyclic AMP Elevating Agents Control Melanosome pH through a Protein Kinase A-independent Mechanism (2009)

Melanins are synthesized in melanocytes within specialized organelles called melanosomes. Numerous studies have shown that the pH of melanosome plays a key role in the regulation of melanin synthesis. However, until now, acute regulation of melanosome pH by a physiological stimulus has never been demonstrated. In the present study, we show that the activation of the cAMP pathway by alphaMSH or forskolin leads to an alkalinization of melanosomes and a concomitant regulation of vacuolar ATPases and ion transporters of the solute carrier family. The solute carrier family members include SLC45A2, which is mutated in oculocutaneous albinism type IV, SLC24A4 and SLC24A5, proteins implicated in the control of eye, hair, and skin pigmentation, and the P protein, encoded by the oculocutaneous albinism type II locus. Interestingly, H89, a pharmacological inhibitor of protein kinase A (PKA), prevents the cAMP-induced pigmentation and induces acidification of melanosomes. The drastic depigmenting effect of H89 is not due to an inhibition of tyrosinase expression. Indeed, H89 blocks the induction of melanogenesis induced by LY294002, a potent inhibitor of the PI 3-kinase pathway, without any effect on tyrosinase expression. Furthermore, PKA is not involved in the inhibition of pigmentation promoted by H89 because LY294002 induces pigmentation independently of PKA. Also, other PKA inhibitors do not affect pigmentation. Taken together, our results strengthen the support for a key role of melanosome pH in the regulation of melanin synthesis and, for the first time, demonstrate that melanosome pH is regulated by cAMP and alphaMSH. Notably, these are both mediators of the response to solar UV radiation, the main physiological stimulus of skin pigmentation.
Optically-induced growth of fiber patterns into a photopolymerizable resin (1999)

We present evidence of optically-induced growth of fiber patterns into a photopolymerizable resin. Optical growth of a single or multiple fibers is achieved by focusing an ultraviolet (UV)-laser light into the photopolymerizable resin used. The fiber growth is due to an effect in which photopolymerization of the resin upon light irradiation produces an increase of the resin refractive index, the change of which, in turn, confines the light propagation into waveguide-type fiber structures. We have also observed that two optically grown independent fibers can merge to form a single fiber under specific conditions. We have studied the dependence of this optical growth of fiber structures phenomena on all the experimental parameters, including the numerical aperture (NA) of the lens used to focus the light, the light power, and the exposure time.
YAC Transfer into Mammalian Cells by Cell Fusion (2003)

The large regions of DNA that can be cloned in yeast artificial chromosomes (YACs) are ideal for expression studies of the complex genes and gene clusters found in the mammalian genome. Such studies require that the YAC of interest be transferred into a suitable expression system, such as mammalian cells in tissue culture or transgenic animals. Recent experiments indicate that large genes cloned on YACs may be transferred intact and are often expressed at a level comparable to the endogenous genes and in a fully controlled fashion owing to the large amount of flanking DNA containing long range controlling elements (reviewed in ref. 1).
Optimization and Characterization of Flexible Polymeric Optical Waveguide Fabrication Process for Fully Embedded Board-level Optical Interconnects (2008)

Optical interconnections on printed circuit board are promising approach for use throughout the backplane and motherboard. Optical interconnect with its low propagation loss and high data-transfer density become the key driver to solve the limitation of electrical interconnections which fail to meet with increasing data rate requirement The advantages of embedded polymer waveguide as optical interconnects is the potential compatibility with current PCB or silicon manufacturing process which could facilitate a smooth technology transition from electrical to optical technologies. This paper reports on optimization of the fabrication process of 10 cm long flexible polymer waveguide layer with 45° micro-mirror on a PI film by using soft molding to achieve fully embedded board-level optoelectronic interconnects. The photo-active UV-curable fluorinated acrylate resin with low propagation loss (0.05 dB/cm @ 830 nm), WIR30-RI series (Chemoptics) was chosen as clad and core (70 ¿m × 70 ¿m) materials, respectively. The waveguide layers are sandwiched between two polyimide films which support and protect the waveguide layer. Soft molding process is developed to replicate the polymer waveguide. It is known that oxygen inhibition is the key issue when UV-curing the acrylate coating under oxygen atmosphere. Nitrogen shielding is successfully eliminating the oxygen inhibition effect and has improved the surface condition. Scanning electron microscope (SEM) was used to analyze the effectiveness of the optimization process. The 45 micro-mirror in waveguide was formed by using 90° V-shaped diamond blade. The propagation loss of fabricated waveguide is -0.3 dB/cm at 850 nm wavelength. Detailed of each process are discussed in the paper.
On augmented Schottky spaces and automorphic forms, II (1982)

This is the second half of the paper entitled “On augmented Schottky spaces and automorphic forms”. In the first half, we introduced new coordinates to the Schottky space, and defined the augmented Schottky space by using the new coordinates. Furthermore we considered relations between the augmented Schottky space and Riemann surfaces with or without nodes.
New pOp/LhG4 vectors for stringent glucocorticoid‐dependent transgene expression in Arabidopsis (2005)

To facilitate glucocorticoid-inducible transgene expression from the pOp promoter in Arabidopsis the ligand-binding domain of a rat glucocorticoid receptor (GR LBD) was fused to the amino terminus of the synthetic transcription factor LhG4 to generate LhGR-N. Fusions bearing the GR LBD at other positions in LhG4 exhibited incomplete repression or inefficient induction. LhGR-N was stringently repressed in the absence of exogenous glucocorticoid but was fully activated by addition of 2 microm dexamethasone which resulted in 1000-fold increase in GUS reporter activity. Half maximal induction was achieved with 0.2 microm dexamethasone. Reporter transcripts were detectable within 2 h of dexamethasone application and peaked 4-10 h later. Neither LhGR-N nor dexamethasone affected seedling development although ethanol retarded development when used as a solvent for dexamethasone. The efficiency of the pOp target promoter was improved 10- to 20-fold by incorporating six copies of the ideal lac operator with sufficient inter-operator spacing to allow simultaneous occupancy. Introduction of the TMV Omega sequence into the 5'UTR resulted in a further 10-fold increase in dexamethasone-inducible reporter activity and an increase in the induction factor to 10(4). Although promoters containing the TMV Omega sequence exhibited slightly increased basal expression levels in the absence of dexamethasone, stringent regulation of the cytokinin biosynthetic gene ipt was achieved with all promoters. Despite the severity of the induced ipt phenotypes, transcripts for the KNOX homoeodomain transcription factors BREVIPEDICELLUS and SHOOTMERISTEMLESS were not significantly increased within 48 h of dexamethasone application to seedlings.
Tumor Necrosis Factor and the Pathogenesis of Pichinde Virus Infection in Guinea Pigs (1995)

Pichinde virus (PIC) is a reticuloendothelial arenavirus of the New World tropics. A guinea pig passage-adapted strain of this virus (adPIC) is uniformly lethal for inbred guinea pigs, while the related, prototype strain (PIC3739) has attenuated virulence. The abilities of adPIC and PIC3739 to induce tumor necrosis factor (TNF) in vivo and in cultured macrophages were compared. Infection with adPIC, but not PIC3739, was associated with detectable serum TNF that peaked in week 2 of infection. Tumor necrosis factor was found in the spleens of adPIC- and PIC3739-infected animals in week 1 of infection; TNF alpha mRNA levels in spleens and livers of adPIC infected animals increased and remained high throughout infection, whereas PIC3739-infected organs showed down regulation of TNF alpha mRNA late in infection. Peritoneal macrophages explanted from adPIC-infected animals showed enhanced lipopolysaccharide-inducible TNF production. Altered regulation of TNF production may play a role in the pathogenesis of guinea pig arenavirus disease.
Cranial and cardiac neural crest defects in endothelin-A receptor-deficient mice (1998)

Neural crest cells arise in the dorsal aspect of the neural tube and migrate extensively to differentiate into a variety of neural and non-neural tissues. While interactions between neural crest cells and their local environments are required for the proper development of these tissues, little information is available about the molecular nature of the cell-cell interactions in cephalic neural crest development. Here we demonstrate that mice deficient for one type of endothelin receptor, ETA, mimic the human conditions collectively termed CATCH 22 or velocardiofacial syndrome, which include severe craniofacial deformities and defects in the cardiovascular outflow tract. We show that ETA receptor mRNA is expressed by the neural crest-derived ectomesenchymal cells of pharyngeal arches and cardiac outflow tissues, whereas ET-1 ligand mRNA is expressed by arch epithelium, paraxial mesoderm-derived arch core and the arch vessel endothelium. This suggests that paracrine interaction between neural crest-derived cells and both ectoderm and mesoderm is essential in forming the skeleton and connective tissue of the head. Further, we find that pharyngeal arch expression of goosecoid is absent in ETA receptor-deficient mice, placing the transcription factor as one of the possible downstream signals triggered by activation of the ETA receptor. These observations define a novel genetic pathway for inductive communication between cephalic neural crest cells and their environmental counterparts.
Controllability Analysis of Protein Glycosylation in Cho Cells (2014)

To function as intended in vivo, a majority of biopharmaceuticals require specific glycan distributions. However, achieving a precise glycan distribution during manufacturing can be challenging because glycosylation is a non-template driven cellular process, with the potential for significant uncontrolled variability in glycan distributions. As important as the glycan distribution is to the end-use performance of biopharmaceuticals, to date, no strategy exists for controlling glycosylation on-line. However, before expending the significant amount of effort and expense required to develop and implement on-line control strategies to address the problem of glycosylation heterogeneity, it is imperative to assess first the extent to which the very complex process of glycosylation is controllable, thereby establishing what is theoretically achievable prior to any experimental attempts. In this work, we present a novel methodology for assessing the output controllability of glycosylation, a prototypical example of an extremely high-dimensional and very non-linear system. We first discuss a method for obtaining the process gain matrix for glycosylation that involves performing model simulations and data analysis systematically and judiciously according to a statistical design of experiments (DOE) scheme and then employing Analysis of Variance (ANOVA) to determine the elements of process gain matrix from the resulting simulation data. We then discuss how to use the resulting high-dimensional gain matrix to assess controllability. The utility of this method is demonstrated with a practical example where we assess the controllability of various classes of glycans and of specific glycoforms that are typically found in recombinant biologics produced with Chinese Hamster Ovary (CHO) cells. In addition to providing useful insight into the extent to which on-line glycosylation control is achievable in actual manufacturing processes, the results also have important implications for genetically engineering cell lines design for enhanced glycosylation controllability.
Synthesis of Potent Cyclic Hexapeptide NK-1 Antagonists. Use of a Minilibrary in Transforming a Peptidal Somatostatin Receptor Ligand into an NK-1 Receptor Ligand via a Polyvalent Peptidomimetic (1996)

The endogenous peptides somatostatin (SRIF) and substance P comprise very different structures. Although both bind G-protein-coupled receptors, the SRIF receptors (SSTR 1-5) recognize SRIF and related peptides which retain its beta-turn such as the potent cyclic hexapeptide SRIF agonist L-363,301 (6a), but not substance P. Conversely the NK-1 receptor binds substance P but not the above ligands. In contrast, the beta-D-glucosides 1 and 2, designed to mimic the beta-turn of 6a, bind both receptors. This observation led us to attempt the conversion of 6a into the first potent, selective cyclic hexapeptide ligand for the NK-1 receptor. To this end, we combined design with a minilibrary approach. The goal was accomplished with surprising ease, leading to the NK-1 receptor antagonist 9 (IC50 2.0 +/- 0.4 nM). This demonstrates that peptidomimetics, incorporating in this case the promiscuous beta-D-glucose scaffold, can provide valuable clues about receptor similarities not revealed by their endogenous ligands. In addition, this work suggests that the use of libraries and rational design need not be mutually exclusive approaches to lead discovery.
General digital microfluidic platform manipulating dielectric and conductive droplets by dielectrophoresis and electrowetting (2009)

A general digital (droplet-based) microfluidic platform based on the study of dielectric droplet manipulation by dielectrophoresis (DEP) and the integration of DEP and electrowetting-on-dielectric (EWOD) is reported. Transporting, splitting, and merging dielectric droplets are achieved by DEP in a parallel-plate device, which expands the fluids of digital microfluidics from merely being conductive and aqueous to being non-conductive. In this work, decane, hexadecane, and silicone oil droplets were successfully transported in a 150 microm-high gap between two parallel plates by applying a DC voltage above threshold voltages. Non-volatile silicone oil droplets with viscosities of 20 and 50 cSt were studied in more detail in parallel-plate geometries with spacings of 75 microm, 150 microm, and 225 microm. The threshold voltages and the required driving voltages to achieve droplet velocities up to 4 mm/s in the different circumstances were measured. By adding a dielectric layer on the driving electrodes of the tested parallel-plate device, a general digital microfluidic platform capable of manipulating both dielectric and conductive droplets was demonstrated. DEP and EWOD, selectively generated by applying different signals on the same dielectric-covered electrodes, were used to drive silicone oil and water droplets, respectively. Concurrent transporting silicone oil and water droplets along an electrode loop, merging water and oil droplets, and transporting and separating the merged water-in-oil droplet were performed.
Sipping From a Poisoned Chalice (2003)

People have believed since antiquity that tiny doses of toxicants can be healthful. Now hormesis, a concept once discredited in scientific circles, is making a surprising comeback.
CD8+CD205+ Splenic Dendritic Cells Are Specialized to Induce Foxp3+ Regulatory T Cells (2008)

Foxp3(+)CD25(+)CD4(+) regulatory T cells (Treg) mediate immunological self-tolerance and suppress immune responses. A subset of dendritic cells (DCs) in the intestine is specialized to induce Treg in a TGF-beta- and retinoic acid-dependent manner to allow for oral tolerance. In this study we compare two major DC subsets from mouse spleen. We find that CD8(+) DEC-205/CD205(+) DCs, but not the major fraction of CD8(-) DC inhibitory receptor-2 (DCIR2)(+) DCs, induce functional Foxp3(+) Treg from Foxp3(-) precursors in the presence of low doses of Ag but without added TGF-beta. CD8(+)CD205(+) DCs preferentially express TGF-beta, and the induction of Treg by these DCs in vitro is blocked by neutralizing Ab to TGF-beta. In contrast, CD8(-)DCIR2(+) DCs better induce Foxp3(+) Treg when exogenous TGF-beta is supplied. In vivo, CD8(+)CD205(+) DCs likewise preferentially induce Treg from adoptively transferred, Ag-specific DO11.10 RAG(-/-) Foxp3(-)CD4(+) T cells, whereas the CD8(-)DCIR2(+) DCs better stimulate natural Foxp3(+) Treg. These results indicate that a subset of DCs in spleen, a systemic lymphoid organ, is specialized to differentiate peripheral Foxp3(+) Treg, in part through the endogenous formation of TGF-beta. Targeting of Ag to these DCs might be useful for inducing Ag-specific Foxp3(+) Treg for treatment of autoimmune diseases, transplant rejection, and allergy.
Effects of 5-Fluorouracil and Leucovorin in the Treatment of Pancreatic–Biliary Tract Adenocarcinomas (2000)

Adenocarcinomas of the pancreas and biliary tract are highly malignant neoplasms, which are found in the advanced stage. Chemotherapy commonly plays a palliative role in the treatment of pancreatic and biliary tract cancers. 5-Fluorouracil (5-FU) is the most widely studied single agent; the response rate of 5-FU is only 20%. Recently, some reports presented interesting results, in which 5-FU, modulated with levofolinic acid (leucovorin), was active in patients with colorectal cancer. In relation, we performed a phase II study of 5-FU, modulated with leucovorin, in patients affected by advanced pancreatic or biliary tract cancer. Fifty-one patients with nonresectable carcinomas of the pancreas or biliary tract admitted to Korea University Hospital between May 1995 and December 1998 were included in this study. Chemotherapy consisted of leucovorin 25 mg/m2/day by 2-hour intravenous infusion, followed by 5-FU 375 mg/m2/day by bolus intravenous infusion, from day I to day 5. The treatment was repeated every 3 to 4 weeks. A total of 51 eligible patients with advanced adenocarcinoma of the pancreas or biliary tract were enrolled. Of 23 enrolled patients with pancreatic adenocarcinoma, one patient showed complete remission with a survival duration of 13 months (response duration was 9 months). Three patients had partial responses (PRs) with survival times of 6, 12, and 15 months, respectively. The overall response rate was 17.4% (95% confidence interval [CI], 7.2%-36.2%). The median time of overall survival was 6 months (range: 1-15 months). Of 28 enrolled patients with biliary tract cancer, complete responses were observed in 2 patients (7.1%) with survival time of 14 and 16 months, respectively. Seven patients had PRs with a median survival of 8 months. The overall response rate was 32.1% (95% CI, 20.3%-57.5%). The median time of overall survival was 6 months (range: 1-16 months). The most prominent toxicity was mucositis. Hematologic toxicity was less severe. 5-Fluorouracil in modulation with intravenous leucovorin is well tolerated by patients with stage IV pancreatic adenocarcinoma or biliary tract cancer. Although the response rate for patients with pancreatic adenocarcinoma is not better than that achieved using 5-FU monochemotherapy, the 32.1% overall response rate achieved in patients with biliary tract cancer suggests that 5-FU modulation with leucovorin is active in biliary tract cancer.