gebhart/patrepeval huggingface dataset:
Probing Biomolecule Recognition with Electron Transfer:  Electrochemical Sensors for DNA Hybridization (1997)

Identifying infectious organisms, quantitating gene expression, and sequencing genomic DNA on chips all rely on the detection of nucleic acid hybridization. Described here is a novel assay for detection of the hybridization of products of the polymerase chain reaction using electron transfer from guanine to a transition-metal complex. The hybridization assay was modeled in solution by monitoring the cyclic voltammetry of Ru(bpy)3(2+) (bpy = 2,2'-bipyridine) in the presence of a probe strand containing only A, T, and C prior to and after hybridization to a complement that contained seven guanines, which led to high catalytic current due to the oxidation of guanine by Ru(bpy)3(3+). To allow recognition of all four bases in the target sequence, it was shown that inosine 5'-monophosphate was 3 orders of magnitude less reactive than guanosine 5'-monophosphate, suggesting that effective hybridization sensors could be realized by immobilization of probe strands in which inosine was substituted for guanosine; hybridization to guanosine-containing target strands would then provide high catalytic currents. A sensor design was tested in a model system for the detection of a synthetic 21-mer oligonucleotide patterned on the sequence of the ras oncogene, which gave an increase in charge collected of 35 +/- 5 microC after hybridization and of only 8 +/- 5 microC after exposure to noncomplementary DNA. Independent quantitation of probe and target by radiolabeling showed that the hybridized electrode contained 3.0 +/- 0.3 ng of target. New sensor electrodes were then prepared for the detection of PCR-amplified genomic DNA from herpes simplex virus type II, genomic DNA from Clostridium perfringens, and genomic RNA from human immunodeficiency virus and gave an additional charge of 35-65 microC for hybridization to complementary amplicon and of only 2-10 microC after exposure to noncomplementary DNA.
Catalyst-Controlled Wacker-Type Oxidation: Facile Access to Functionalized Aldehydes (2014)

The aldehyde-selective oxidation of alkenes bearing diverse oxygen groups in the allylic and homoallylic position was accomplished with a nitrite-modified Wacker oxidation. Readily available oxygenated alkenes were oxidized in up to 88% aldehyde yield and as high as 97% aldehyde selectivity. The aldehyde-selective oxidation enabled the rapid, enantioselective synthesis of an important pharmaceutical agent, atomoxetine. Finally, the influence of proximal functional groups on this anti-Markovnikov reaction was explored, providing important preliminary mechanistic insight.
Insect Immunity: Isolation and Structure of Cecropins B and D from Pupae of the Chinese Oak Silk Moth, Antheraea pernyi (1982)

The immune system in the Chinese oak silk moth, Antheraea pernyi, has been compared with that of the Cecropia moth which has been characterized earlier. Antibacterial activity against Escherichia coli was induced in diapausing pupae by injection of viable E. coli or Enterobacter cloacae. The activity reached a maximum on day 7-8 after which the response gradually declined. The pupae produced a set of immune proteins with P4 and P5 as major labelled components similar to that earlier found in Cecropia. The major antibacterial factor in A. pernyi was cecropin D. A procedure is described for the isolation of cecropin B and D, which is in principle similar to the one used for the isolation of the corresponding cecropins from Cecropia pupae. Amino acid sequence analyses of the A. pernyi cecropins show the D form to contain 36 amino acid residues and that both cecropins have blocked C-termini. The general structure of cecropins having a charged N-terminal region (residues 1-21) followed by a long hydrophobic stretch (residues 22-32) is well conserved. Cecropin B and D from A. pernyi differ from the corresponding proteins in Cecropia by four and three conservative amino acid replacements, respectively. The homology between the cecropins from the two insects suggests that they orginate from a single ancestral gene. The antibacterial activity was tested against nine different bacterial species. Evolutionary aspects of the cecropins are discussed.
“Tandem” duplication of 4p16.1p16.3 chromosome region associated with 4p16.3pter molecular deletion resulting in Wolf‐Hirschhorn syndrome phenotype (1999)

Chromosome imbalance affecting the short arm of chromosome 4 results in a variety of distinct clinical conditions. Most of them share a number of manifestations, such as mental retardation, microcephaly, pre- and post-natal growth retardation, anteverted and low-set ears, that can be considered as nonspecific signs, generally attributable to gene dosage impairment. On the other hand, more distinctive phenotypic traits correlate with the segmental aneuploidy. Duplications of the distal half of 4p give rise to the partial trisomy 4 syndrome, characterized by a “boxer” nose configuration and deep-set eyes. These signs are usually observed even in cases of small terminal duplications. Haploinsufficiency of 4p16.3 results in the so-called Wolf-Hirschhorn (WH) syndrome, a contiguous gene syndrome characterized by maxillary hypoplasia, large and protruding eyes, high nasal bridge, skeletal abnormalities, and midline defects. The smallest overlapping deletion described so far as a cause of this condition is only 165 kb long, suggesting that one or a few genes in this region act as “master” regulators of different developmental pathways. A “tandem” duplication of 4p16.1p16.3 was detected in association with a subtle deletion of 4p16.3pter on the same chromosome in a patient with the WH phenotype. The 3.2 Mb deletion, spanning the genomic region from the vicinity of D4S43 to the telomere, encompasses the recently delimited “WHS critical region” [Wright et al., 1997: Hum. Mol. Genet. 6:317–324]. This unusual chromosome rearrangement resulted in WH phenotype, clinical manifestations of partial 4p trisomy being mild or absent. This observation led us to speculate that the regulatory gene/genes in the critical WH region affect the expression of other genes in a dose-dependent manner. Haploinsufficiency of this region could be more deleterious than various partial trisomies. Am. J. Med. Genet. 82:371–375, 1999. © 1999 Wiley-Liss, Inc.
Concise Synthesis of (±)-Cytisine via Lithiation of N-Boc-bispidine (2005)

[reaction: see text] (+/-)-Cytisine has been synthesized in 19% overall yield via a six-step approach from commercially available materials. Key features of this new strategy are as follows: (i) initial construction of the bispidine core, (ii) lithiation-transmetalation-allylation of an N-Boc-bispidine, and (iii) a Pd/C-mediated dihydropyridone oxidation-N-debenzylation process.
Investigating the accuracy of microstereotactic‐body‐radiotherapy utilizing anatomically accurate 3D printed rodent‐morphic dosimeters (2015)

This work demonstrates the feasibility of using 3D printing technology to make anatomically accurate Presage rodent-morphic dosimeters incorporating spinal-mimicking inserts. High quality optical-CT 3D dosimetry is feasible on these dosimeters, despite the irregular surfaces and implanted inserts. The ability to measure dose distributions in anatomically accurate phantoms represents a powerful useful additional verification tool for preclinical microSBRT.
Efficacy and Safety of Ibandronate in the Treatment of Opioid-Resistant Bone Pain Associated With Metastatic Bone Disease: A Pilot Study (2004)

Nonstandard, intensive treatment with i.v. ibandronate seems to have a marked analgesic effect in patients with opioid-resistant bone pain from metastatic bone disease. Further investigation is warranted.
Bioinspired self-cleaning surfaces with superhydrophobicity, superoleophobicity, and superhydrophilicity (2012)

Self-cleaning methods currently employed are based on understanding of the functions, structures, and principles of various objects found in living nature. Three types of surfaces, including superhydrophobic, superoleophobic, and superhydrophilic, offer solutions to keep a surface clean. In this review article, an overview of self-cleaning surfaces inspired by nine biological objects is provided: lotus leaves, rice leaves, cicada wings, butterfly wings, snail shell, fish scale, shark skin, pitcher plant, and photosynthesis. These surfaces exhibit special properties such as low adhesion, low drag, anisotropic wetting, anti-reflection, directional adhesion, anti-fouling, photocatalysis, self-sterilizing, and anti-fogging. We discuss the differences between the superhydrophobic and superhydrophilic surfaces and perspectives for self-cleaning surfaces in the future.
Fundamentals of Global Positioning System Receivers (2004)

Preface. Preface to the First Edition. Chapter 1. Introduction. Chapter 2. Basic GPS Concept. Chapter 3. Satellite Constellation. Chapter 4. Earth-Centered, Earth-Fixed Coordinate System. Chapter 5. GPS C/A Code Signal Structure. Chapter 6. Receiver Hardware Considerations. Chapter 7. Acquisition of GPSb C/A Code Signals. Chapter 8. Tracking GPS Signals. Chapter 9. GPS Software Receivers. Chapter 10. Acquisition of Weak Signals. Chapter 11. Tracking Weak Signals. Chapter 12. GPS Receiver-Related Subjects. Index.
Effect of heterozygous PPARγ deficiency and TZD treatment on insulin resistance associated with age and high-fat feeding (2003)

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is the target receptor for thiazolidinedione (TZD) compounds, which are a class of insulin-sensitizing drugs used in the treatment of type 2 diabetes. Paradoxically, however, mice deficient in PPARgamma (PPARgamma(+/-)) are more insulin sensitive than their wild-type (WT) littermates, not less, as would be predicted. To determine whether PPARgamma deficiency could prevent the development of the insulin resistance associated with increasing age or high-fat (HF) feeding, insulin sensitivity was assessed in PPARgamma(+/-) and WT mice at 2, 4, and 8 mo of age and in animals fed an HF diet. Because TZDs elicit their effect through PPARgamma receptor, we also examined the effect of troglitazone (a TZD) in these mice. Glucose metabolism was assessed by hyperinsulinemic euglycemic clamp and oral glucose tolerance test. Insulin sensitivity declined with age for both groups. However, the decline in the PPARgamma(+/-) animals was substantially less than that of the WT animals, such that, by 8 mo of age, the PPARgamma(+/-) mice were markedly more insulin sensitive than the WT mice. This greater sensitivity in PPARgamma(+/-) mice was lost with TZD treatment. HF feeding led to marked adipocyte hypertrophy and peripheral tissue and hepatic insulin resistance in WT mice but also in PPARgamma(+/-) mice. Treatment of these mice with troglitazone completely prevented the adipocyte hypertrophy and normalized insulin action. In conclusion, PPARgamma deficiency partially protects against age-related insulin resistance but does not protect against HF diet-induced insulin resistance.
Three-dimensional alignment of liquid crystals in nanostructured porous thin films (2007)

Oblique evaporation of inorganic materials has long been used to induce alignment in liquid crystals, often for the purpose of controlling the pretilt angle in a liquid crystal cell. These alignment layers are relatively dense, keeping the liquid crystals above the surface of the inorganic layer. By evaporating at increasingly oblique angles (> 80&deg;), the alignment layer can be made porous, allowing liquid crystals to infiltrate the film and to align to individual nanostructures. By coupling simultaneous computer controlled substrate motion during evaporation, a process known as glancing angle deposition (GLAD), the nanostructures can be grown in a variety of useful shapes, including helices, polygonal spirals, zigzags and periodically bent S-shaped columns. Alone, these films exhibit properties such as linear and circular polarization selective Bragg reflection, and full three-dimensional photonic bandgaps. By infiltrating liquid crystals into the voids of the film, one can align liquid crystals in three dimensions, as well as tune and switch the film's optical properties. Additionally, the GLAD film can be used to template polymerizable liquid crystals for subsequent monomer infiltration. In this work, using spectroscopic ellipsometry, we examine the effects of liquid crystal infiltration on various film structures made from a variety of metal oxides, for both varying film thickness and deposition angle. Techniques for filling a porous film with a known volume of liquid crystals are also presented. Additionally, we examine the switching behaviour for these films under applied electric fields. Finally, we compare experimental and simulated results used to predict and optimize the optical properties of these hybrid films.
Spectrally efficient digital UHF mobile system (2003)

It is maintained that the cellular capacity problem can be solved by a TDM/TDMA system now used in the BETR (basic exchange telephone radio) service. 16 kb/s modified 'RELP' voice compression with 64 kb/s QPSK transmission provides four voice paths backwardly compatible with single NBFM analog circuits. All transcoding and modern functions are done by a single DSP.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
ELISA for quantification of specific IgG and IgE antibodies to ovalbumin. (1988)

Two indirect microELISA methods have been developed to determine ovalbumin (OA)-specific IgG and total OA-specific antibodies in rat's serum. Animals were immunized with OA suspended in alum s.c. and administered i.p. with Bordetella pertussis (Bp). The study was performed using serum samples taken 14 days after immunization. Anti-OA IgG, anti-OA Ig (by indirect ELISA), total IgE and total IgG (by ELISA sandwich) and also anti-OA specific IgE (by passive cutaneous anaphylaxis test) were measured. The OA concentration to coat the solid phase was 1.25 micrograms/ml. The optimal serum dilution for measuring OA-specific antibodies by the indirect ELISAs developed was between 1/640-1/1280, for both methods. Conjugate concentrations used were 1/12800 (PO-anti rat IgG) and 1/600 (PO-anti rat Ig). Considering both methods, the intra and inter-assay variability coefficients oscillate between 1.98 and 6.75%. The immunization procedure used produces a marked increase in anti-OA Ig, anti-OA IgG and specific IgE levels. The immunization does not modify total IgG levels whereas total IgE values were significantly higher. This increase can be attributed chiefly to the non-specific IgE production induced by Bp. The microELISA methods proposed in this work, are reasonable alternatives radiolabelled techniques to measure OA-specific antibodies.
Relative efficiency of tumor cell killing in vitro by two enzyme-prodrug systems delivered by identical adenovirus vectors. (1997)

Enzyme-prodrug therapy for the treatment of cancer is an experimental procedure that is under intensive investigation. However, the relative merits of the various systems for use under specific conditions are still being determined. We have compared the efficacy of cell killing by the herpesvirus thymidine kinase (HSVTK)/ganciclovir and the purine nucleoside phosphorylase (PNP)/9-(beta-M-2-deoxy-erythropentofuranosyl)6-methylpurine enzyme/prodrug systems. These were chosen because of their differential dependence on DNA replication for their mechanism of action. The HSVTK and PNP genes, expressed from the identical prostate-specific antigen promoter, were transduced into human prostate and breast cancers cells using the same human adenovirus vector. The kinetics of cell killing in the presence of the respective prodrugs was monitored using a nondestructive assay that measured total cell bioactivity. The PNP/9-(beta-D-2-deoxy-erythropentofuranosyl)6-methylpurine system was clearly superior in its ability to cause cell death in vitro. Cells were killed in about half the time and at a 5-10-fold lower input of virus relative to the HSVTK/ganciclovir system. The PNP system may offer advantages for the treatment of slow-growing tumors in which the daily proliferative rate is low or in situations in which gene delivery or expression is inefficient.
Measles Immune Suppression: Lessons from the Macaque Model (2012)

Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV) infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulent in non-human primates. By performing a comprehensive study of virological, immunological, hematological and histopathological observations made in animals euthanized at different time points after MV infection, we developed a model explaining measles immune suppression which fits with the "measles paradox". Here we show that MV preferentially infects CD45RA(-) memory T-lymphocytes and follicular B-lymphocytes, resulting in high infection levels in these populations. After the peak of viremia MV-infected lymphocytes were cleared within days, followed by immune activation and lymph node enlargement. During this period tuberculin-specific T-lymphocyte responses disappeared, whilst strong MV-specific T-lymphocyte responses emerged. Histopathological analysis of lymphoid tissues showed lymphocyte depletion in the B- and T-cell areas in the absence of apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell follicles and reappearance of proliferating cells. Our findings indicate an immune-mediated clearance of MV-infected CD45RA(-) memory T-lymphocytes and follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this depletion, explaining the short duration of measles lymphopenia yet long duration of immune suppression.
Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3 (2006)

The endothelial cell (EC)-derived tissue inhibitor of metalloproteinase-2 (TIMP-2) and pericyte-derived TIMP-3 are shown to coregulate human capillary tube stabilization following EC-pericyte interactions through a combined ability to block EC tube morphogenesis and regression in three-dimensional collagen matrices. EC-pericyte interactions strongly induce TIMP-3 expression by pericytes, whereas ECs produce TIMP-2 in EC-pericyte cocultures. Using small interfering RNA technology, the suppression of EC TIMP-2 and pericyte TIMP-3 expression leads to capillary tube regression in these cocultures in a matrix metalloproteinase-1 (MMP-1)-, MMP-10-, and ADAM-15 (a disintegrin and metalloproteinase-15)-dependent manner. Furthermore, we show that EC tube morphogenesis (lumen formation and invasion) is primarily controlled by the TIMP-2 and -3 target membrane type (MT) 1 MMP. Additional targets of these inhibitors include MT2-MMP and ADAM-15, which also regulate EC invasion. Mutagenesis experiments reveal that TIMP-3 requires its proteinase inhibitory function to induce tube stabilization. Overall, these data reveal a novel role for both TIMP-2 and -3 in the pericyte-induced stabilization of newly formed vascular networks that are predisposed to undergo regression and reveal specific molecular targets of the inhibitors regulating these events.
PIM1 kinase as a target for cancer therapy (2012)

As PIM1 possesses oncogenic functions and is overexpressed in various kinds of cancer diseases, its inhibition provides a new option in cancer therapy. Based on the ability of highly selective organometallic PIM1 inhibitors, promising in vivo applicability is expected.
IFN‐γ activation of mesenchymal stem cells for treatment and prevention of graft versus host disease (2008)

Graft versus host disease (GVHD), mediated by donor T cells, is a significant source of morbidity and mortality following allogeneic stem cell transplantation. Mesenchymal stem cells (MSC) can successfully treat ongoing graft versus host disease, presumably due to their ability to suppress donor T cell proliferation. Little is known about the potential of MSC to prevent GVHD. Here we show that bone marrow-isolated MSC can suppress the development of GVHD if given after donor T cell recognition of antigen. IFN-gamma was required to initiate MSC efficacy. Recipients of IFN-gamma(-/-) T cells did not respond to MSC treatment and succumbed to GVHD. MSC, pre-treated with IFN-gamma, became immediately active and could suppress GVHD more efficiently than a fivefold-greater number of MSC that were not activated. When given at the time of bone marrow transplantation, activated MSC could prevent GVHD mortality (100% survival, p=0.006). MSC activation was dependent on the magnitude of IFN-gamma exposure, with increased IFN-gamma exposure leading to increased MSC suppression of GVHD. Activated MSC present a new strategy for preventing GVHD using fewer MSC.
Development and Optimization of Herpes Simplex Virus Vectors for Multiple Long-Term Gene Delivery to the Peripheral Nervous System (2000)

Herpes simplex virus (HSV) has often been suggested as a suitable vector for gene delivery to the peripheral nervous system as it naturally infects sensory nerve terminals before retrograde transport to the cell body in the spinal ganglia where latency is established. HSV vectors might therefore be particularly appropriate for the study and treatment of chronic pain following vector administration by relatively noninvasive peripheral routes. However parameters allowing safe and efficient gene delivery to spinal ganglia following peripheral vector inoculation, or the long-term expression of delivered genes, have not been comprehensively studied. We have identified combinations of deletions from the HSV genome which allow highly efficient gene delivery to spinal dorsal root ganglia (DRGs) following either footpad or sciatic nerve injection. These vectors have ICP34.5 deleted and have inactivating mutations in vmw65. We also report that peripheral replication is probably necessary for the efficient establishment of latency in vivo, as fully replication-incompetent HSV vectors allow efficient gene expression in DRGs only after peripheral inoculation at a high virus dose. Very low transduction efficiencies are otherwise achieved. In parallel, promoters have been developed that allow the long-term expression of individual or pairs of genes in DRGs by using elements from the latently active region of the virus to confer a long-term activity onto a number of promoters which otherwise function only in the short term. This work further defines elements and mechanisms within the latently active region that are necessary for long-term gene expression and for the first time allows multiple inserted genes to be expressed from HSV vectors during latency.