gebhart/patrepeval huggingface dataset:
Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery (2021)

Hitching a ride with a retroelement Retroviruses and retroelements have inserted their genetic code into mammalian genomes throughout evolution. Although many of these integrated virus-like sequences pose a threat to genomic integrity, some have been retooled by mammalian cells to perform essential roles in development. Segel et al . found that one of these retroviral-like proteins, PEG10, directly binds to and secretes its own mRNA in extracellular virus–like capsids. These virus-like particles were then pseudotyped with fusogens to deliver functional mRNA cargos to mammalian cells. This potentially provides an endogenous vector for RNA-based gene therapy. —DJ
Ruthenium Bipyridine-Containing Polymers and Block Copolymers via Ring-Opening Metathesis Polymerization (2004)

We present the direct and efficient synthesis of homopolymers and block copolymers bearing a dense arrangement of ruthenium(II) tris(bipyridine) complexes as pendant groups via ring-opening metathesis polymerization. UV/vis absorbance and luminescence studies as well as cyclic voltammetry show that the properties of the monomer are retained in the homopolymers and block copolymers. Our studies suggest that the polymers can be described as an array of independent chromophores, whose properties remain essentially unchanged upon linking to the polymer backbone. The Ru-containing block copolymers can self-assemble in selective solvents to generate large compound micellar aggregates, which retain their luminescence upon micellization.
A pilot phase II Study of digoxin in patients with recurrent prostate cancer as evident by a rising PSA. (2014)

Digoxin was well tolerated and showed a prolongation of PSDAT in 38% of the patients. However, there was no significant difference comparing that of similar patients on placebo from historical data. Digoxin at the dose used in this study may have limited benefit for patients with biochemically relapsed prostate cancer.
High voltage (450 V) GaN Schottky rectifiers (1999)

We fabricated high standoff voltage (450 V) Schottky rectifiers on hydride vapor phase epitaxy grown GaN on sapphire substrate. Several Schottky device geometries were investigated, including lateral geometry with rectangular and circular contacts, mesa devices, and Schottky metal field plate overlapping a SiO2 layer. The best devices were characterized by an ON-state voltage of 4.2 V at a current density of 100 A/cm2 and a saturation current density of 10−5 A/cm2 at a reverse bias of 100 V. From the measured breakdown voltage we estimated the critical field for electric breakdown in GaN to be (2.2±0.7)×106 V/cm. This value for the critical field is a lower limit since most of the devices exhibited abrupt and premature breakdown associated with corner and edge effects.
Mechanisms of Action of Non-Steroidal Anti-Inflammatory Drugs for the Prevention of Alzheimers Disease (2010)

Alzheimer's disease (AD) is accompanied by an activation of the innate immune system, and many epidemiological studies have shown reduced risk for dementia or AD associated with chronic consumption of non-steroidal anti-inflammatory drugs (NSAIDs). These observations led to animal model studies to test the hypothesis that NSAIDs can be disease-modifying for some aspects of AD pathogenesis. NSAIDs cannot only suppress inflammatory targets, which could contribute to neuroprotection, they also slow amyloid deposition by mechanisms that remain unclear. Several large clinical trials with NSAID therapies with AD subjects have failed, and cyclooxygenase-2 does not appear to be a useful target for disease modifying therapy. However, there may be apolipoprotein E E4 pharmacogenomic effects and a real but delayed positive signal in a large primary prevention trial with naproxen. This encourages researchers to re-address possible mechanisms for a stage-dependent NSAID efficacy, the subject of this review.
Co1−xS–Graphene Hybrid: A High‐Performance Metal Chalcogenide Electrocatalyst for Oxygen Reduction (2011)

A hybrid electrocatalyst for the oxygen reduction reaction (ORR), consisting of Co1−xS nanoparticles directly nucleated and grown on sheets of reduced graphene oxide (RGO; see SEM image), was prepared by a mild solution-phase reaction followed by an annealing step. The Co1−xS–RGO hybrid has the highest catalytic performance of all cobalt chalcogenide based ORR catalysts, as revealed inter alia by measurements with a rotating-disk electrode (see picture; RHE = reversible hydrogen electrode). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
A general integrated process for synthesizing olefin oxides (2004)

Metal oxide solid reactants are shown to react with vicinal alkyl dibromides to selectively form olefin oxides and fully regenerable metal bromides.
Spontaneous remission in hypoplastic acute leukemia. (1988)

A recurrent spontaneous complete remission of acute hypoplastic leukemia was observed. The remission occurred after a severe infection which was treated with antibiotics. Reports of spontaneous remission of acute leukemia in adults have become increasingly rare, and the remissions themselves are short-lived. Such spontaneous complete remissions are almost always associated with bacterial infections and blood transfusions. Previous cases are summarized, and the pathophysiologic factors are discussed.
Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B‐cell non‐Hodgkin lymphoma (2004)

GDP is an active regimen in B-cell NHL and can be administered with acceptable toxicity to outpatients. A Phase III trial comparing GDP with standard cisplatin-based chemotherapy is now ongoing through the National Cancer Institute of Canada Clinical Trials Group.
유지혈액투석 환자들의 영양상태에 대한 Subjective Global Assessment의 유용성 (2001)

Protein and energy malnutrition are common in dialysis patients. Nutritional assessment is of great importance because undernutrition has been shown to be associated with increased morbidity and mortality in both hemodialysis and peritoneal dialysis. To validate subjective global assessment(SGA) in dialysis patients we compared subjective global assessment with objective measurements(anthropometry, bioelectrical impedance, biochemical measurements) in 54 chronic hemodialysis patients. We divided patients into three groups(SGA1, SGA2, SGA3) according to modified subjective global assessment performed by an observer. Body weight, %IBW, BMI, TSF, MAC, nPCR were different significantly among three groups. SGA was related objective rneasurements such as body weight, %IBW, BMI, %Fat, TSF, MAC, nPCR(p$lt;0.001). Multiple regression analysis showed that the relationship of SGA(as a dependent variable) with objective measurement(covariate) was stronger(multiple r=0.789, R²=60%) than the relationship found with uniariate analysis. In other words, since no single objective method can be considered a gold standard of nutritional assessment, our data show that subjective global assessment is a clinically adequate rnethod for assessing nutritional status in maintenance hemodialysis patients.
Comparative Analysis of the Conformations of Symmetrically and Asymmetrically Deca- and Undecasubstituted Porphyrins Bearing Meso-Alkyl or -Aryl Groups (1997)

Conformational analysis of highly substituted porphyrins has potential implications for modeling the behavior of macrocycles in tetrapyrrole-containing protein complexes and during catalytic reactions. In order to study the influence of different substituent patterns on the conformation of the porphyrin macrocycle, a series of metal free and nickel(II) decasubstituted porphyrins bearing aryl or ethyl groups at opposite meso positions and alkyl groups at the pyrrole positions have been synthesized and characterized by X-ray crystallography. Crystal structures of the free-base porphyrins with 5,15-diaryl substituents showed negligible out-of-plane distortion but a large amount of in-plane distortion along the 5,15-axis accompanied by large bond angle changes similar to those previously seen for related porphyrins with 5,15-dialkyl substituents. Nickel(II) complexes of the 5,15-diaryl-substituted porphyrins show planar or modestly nonplanar conformations, suggesting that these complexes are not intrinsically nonplanar, whereas a complex with 5,15-diethyl substituents has a very ruffled conformation similar to those observed for related complexes with other metals. The nickel(II) complexes are also elongated along the 5,15-axis in a qualitatively similar but less dramatic fashion than are the free-base porphyrins. Spectrosopic studies ((1)H NMR, optical, and resonance Raman spectroscopy) suggest that conformations similar to those determined by X-ray crystallography are present in solution for the 5,15-dialkyl- and 5,15-diaryl-substituted porphyrins. Several asymmetric nickel(II) and metal-free deca- and undecasubstituted porphyrins containing both aryl and alkyl meso-substituents were also investigated. Metal-free 5,15-disubstituted porphyrins with one aryl and one alkyl group showed considerably elongated porphyrin cores, whereas nickel(II) complexes of porphyrins with 5,10- or 5,10,15-substitution patterns showed very nonplanar structures consisting mainly of ruffle and saddle type distortions.
Automated DNA sequencing: ultrasensitive detection of fluorescent bands during electrophoresis (1987)

A simple system has been designed enabling ultrasensitive on-line detection of fluorescently labelled macromolecules, e.g. nucleic acids, proteins and peptides during electrophoretic separations in gels. An important application is the automated DNA sequence determination without radioactivity. Drying of gels, film exposure and handling are not necessary. A sulphydryl containing M13 sequencing primer has been synthesised and end-labelled in a reaction with fluorescein iodoacetamide. This is then used in the dideoxy reactions. In particular no moving parts or complicated software are required for data collection and analysis. Compared to our first automated device detection sensitivity has been improved by a factor of thirty to about 3 X 10(-18) mol per band. The resolution has increased to about 400 bases in 5 hours, with the possibility to read up to about 500 bases when they are properly labelled. Gels shorter than 20 cm may be used for resolution of about 300 bases. The single gel system may be upgraded for simultaneous running and reading of six or ten sequencing samples.
Advances in antiviral agents for hepatitis B virus. (2001)

Hepatitis B virus (HBV) is the third most common disease after venereal diseases and chickenpox. HBV currently infects 2 billion people in the world, of which 350 million are chronic carriers. At least 1 million chronically infected individuals die each year due to HBV-related diseases, especially cirrhosis and liver cancer. The greatest concern about the diffusion of this virus is in endemic regions in central and southern Africa, South-East Asia and South America, where neonatal exposure results in high mortality rates. Anti-HBV therapy has made important progresses in the last decade, with two approved drugs and a number of other potent agents in the pharmaceutical industry pipeline. Nevertheless, resistance and viral rebound are still major issues in devising a winning strategy, and there is a continuous need of developing new active compounds, as well as therapeutic protocols based on combination therapy and a prophylactic approach. This review will summarize the latest advances in anti-HBV therapy, with particular regard to the latest clinical data on the most significant anti-HBV agents. Issues such as viral resistance and combination therapy will be highlighted.
Backbone Modification of Nucleic Acids: Synthesis, Structure and Therapeutic Applications (2001)

Nucleic acids have been extensively modified by replacing the phosphodiester group or the whole sugar phosphodiester with alternative anionic, neutral and cationic structures. Several of these modified oligonucleotides exhibit improved properties including enhanced recognition and binding to RNA, duplex DNA and proteins. This has resulted in the development of new and more potent antisense and antigene agents, as well as aptamers. Furthermore, backbone modified oligonucleotides have also been used in the development of several alternative strategies, which rely on altogether different mechanisms of action and show significant promise for therapeutic intervention. In this review the latest advances in the synthesis and evaluation of the most promising backbone modified oligos will be discussed, with a view to their future as novel pharmaceuticals.
Restoration of connexin26 protein level in the cochlea completely rescues hearing in a mouse model of human connexin30-linked deafness (2007)

Mutations in genes coding for connexin26 (Cx26) and/or Cx30 are linked to approximately half of all cases of human autosomal nonsyndromic prelingual deafness. Cx26 and Cx30 are the two major Cx isoforms found in the cochlea, and they coassemble to form hybrid (heteromeric and heterotypic) gap junctions (GJs). This molecular arrangement implies that homomeric GJs would remain in the cochlea if one of the coassembly partners were mutated resulting in null expression. We generated mice in which extra copies of the Cx26 gene were transgenically expressed from a modified bacterial artificial chromosome in a Cx30-/- background. In the absence of the Cx30 gene, Cx26 expressed from extra alleles completely restored hearing sensitivity and prevented hair cell death in deaf Cx30-/- mice. The results indicated that hybrid GJs consisting of Cx26 and Cx30 were not essential for normal hearing in mice and suggested that up-regulation of Cx26 or slowing down its protein degradation might be a therapeutic strategy to prevent and treat deafness caused by Cx30 mutations.
NEP: a novel receptor-like tyrosine kinase expressed in proliferating neuroepithelia. (1993)

We have isolated a murine cDNA, nep, which encodes a novel receptor-like protein tyrosine kinase. The kinase region of NEP protein bears 50% amino acid sequence identity to the neurotrophin receptors (TRKs). While the intracytoplasmic portion of NEP also contains a short kinase insert region and C-terminal tail reminiscent of the TRK proteins, the putative extracellular domain of NEP is unrelated to any known proteins. The nep gene is strongly expressed within proliferating neuroepithelia of mouse embryos, commencing at the early somite stage (embryonic day 8.0) and persisting in the proliferative ventricular zones of the brain and spinal cord, suggesting that one function of NEP kinase is to signal proliferation of neuroepithelial cells in response to an as yet unknown ligand. The nep gene is also expressed in embryonic sensory ganglia, striated muscle and epidermis, as well as in several adult tissues, including the ventricle linings and glia subpopulations in the brain.
Nested Patch PCR enables highly multiplexed mutation discovery in candidate genes (2008)

Medical resequencing of candidate genes in individual patient samples is becoming increasingly important in the clinic and in clinical research. Medical resequencing requires the amplification and sequencing of many candidate genes in many patient samples. Here we introduce Nested Patch PCR, a novel method for highly multiplexed PCR that is very specific, can sensitively detect SNPs and mutations, and is easy to implement. This is the first method that couples multiplex PCR with sample-specific DNA barcodes and next-generation sequencing to enable highly multiplex mutation discovery in candidate genes for multiple samples in parallel. In our pilot study, we amplified exons from colon cancer and matched normal human genomic DNA. From each sample, we successfully amplified 96% (90 of 94) targeted exons from across the genome, totaling 21.6 kbp of sequence. Ninety percent of all sequencing reads were from targeted exons, demonstrating that Nested Patch PCR is highly specific. We found that the abundance of reads per exon was reproducible across samples. We reliably detected germline SNPs and discovered a colon tumor specific nonsense mutation in APC, a gene causally implicated in colorectal cancer. With Nested Patch PCR, candidate gene mutation discovery across multiple individual patient samples can now utilize the power of second-generation sequencing.
Electrosynthetic control of CNT conductivity & morphology: Scale-up of the transformation of the greenhouse gas CO2 into carbon nanotubes by molten carbonate electrolysis (2016)

Transformation of carbon dioxide into carbon nanotubes, CNTs, by electrolysis in molten carbonates provides a low cost route to extract and store this greenhouse gas. CNTs are more stable, compact and valuable than fuels or other CO2 conversion products, providing an incentive to remove CO2 for climate mitigation. Previously, solid core carbon nanofibers, CNFs were formed with C-13 isotope CO2, whereas hollow core fibers - carbon nanotubes, CNTs, were formed with natural isotope CO2 splitting in molten lithium carbonate. Here we demonstrate the extraordinary range of specific morphologies and conductivities of CNTs that can be achieved through control of the electrolysis conditions in a one pot-synthesis, and scale-up of this process by which the greenhouse gas CO2 is transformed into carbon nanotubes by molten carbonate electrolysis. Addition of Li2BO3, boron dopes and greatly enhances CNT conductivity formed at the galvanized steel cathode. Addition of CaCO3 to the Li2CO3 electrolyte, decreases oxide solubility in the region of CNT growth, producing straight thin-walled CNTs.
Archaic structure of the gene encoding transcription factor USF. (1994)

The upstream stimulatory factor (USF) is a helix-loop-helix transcription factor that interacts with specific sites on the DNA that are also recognized by the MYC oncoproteins. We isolated genomic clones to the murine 44-kDa form of USF (USF2 gene). This unique gene spans 13 kilobases of DNA and is composed of 10 exons. The gene seems to have maintained its archaic structure, since many of the exons encode discrete functional domains of the transcription factor originally identified by protein sequence comparisons. A particularly striking HpaII tiny fragment island, extending over nearly 2,000 base pairs, surrounds the USF2 translation initiation site. This region, which includes the USF2 promoter and the first four exons, is characterized by an overall GC content greater than 74%. Analysis by S1 mapping and transient transfection assays revealed that the USF2 transcripts originate from an initiator element located within a highly GC-rich region that is surrounded by two long polyadenylate stretches and functions as a bidirectional promoter. Different forms of USF2 messages result from the presence or absence of the fourth exon in the processed USF2 mRNA. Alternative splicing correlates with the lack of a consensus lariat branch point in the third intron. Transient cotransfection assays revealed that the presence or absence of the amino acid sequences encoded by exon 4 affects considerably the transcription activation properties of the USF2 protein.
Genetic Alterations in Prostate Cancer (1994)

A number of genetic changes have been documented in prostate cancer, ranging from allelic loss to point mutations and changes in DNA methylation patterns (summarized in Fig. 1). To date, the most consistent changes are those of allelic loss events, with the majority of tumors examined showing loss of alleles from at least one chromosomal arm. The short arm of chromosome 8, followed by the long arm of chromosome 16, appear to be the most frequent regions of loss, suggesting the presence of novel tumor suppressor genes. Deletions of one copy of the Rb and p53 genes are less frequent, as are mutations of the p53 gene, and accumulating evidence suggests the presence of an additional tumor suppressor gene on chromosome 17p, which is frequently inactivated in prostate cancer. Alterations in the E-cadherin/alpha-catenin-mediated cell-cell adhesion mechanism appear to be present in almost half of all prostate cancers and may be critical to the acquisition of metastatic potential of aggressive prostate cancers. Finally, altered DNA methylation patterns have been found in the majority of prostate cancers examined, suggesting widespread alterations in methylation-modulated gene expression. The presence of multiple changes in these tumors is consistent with the multistep nature of the transformation process. Finally, efforts to identify prostate cancer susceptibility loci are under way and may elucidate critical early events in prostatic carcinogenesis.
Uptake of non-transferrin-bound iron by both reductive and nonreductive processes is modulated by intracellular iron. (1994)

Non-transferrin-bound iron (NTBI) uptake occurs in a variety of cells by a saturable, specific and temperature-sensitive process. Our previous studies indicated that NTBI uptake by cardiac myocytes and Hep G2 cells was reversibly up-regulated by iron deposition. In the present work we have characterized this up-regulation and examined its mechanism by comparing the uptake of oxidized (Fe3+) and ascorbate-reduced (Fe2+) forms of iron. Iron loading markedly enhanced the uptake of iron both in the presence and absence of ascorbate, but the increment was greater when ascorbate was absent. This up-regulation is partially inhibited by actinomycin D and cycloheximide, indicating a requirement for protein synthesis. Uptake by the iron-loaded cells was less sensitive to thiol-alkylating agents and competing metal ions, but was more sensitive to proteolysis. Iron loading causes an increase in both Km and Vmax for uptake of both Fe2+ and Fe3+, although the values differ, suggesting distinct rate-limiting steps for uptake of Fe2+ and Fe3+. Consistent with this idea, uptake of the two ions showed differential sensitivity to thiol reagents, competing metal ions and monensin. The Fe(2+)-specific chelators bathophenanthroline disulfonate and ferrozine markedly inhibited iron uptake whether ascorbate was present or not, indicating that Fe3+ uptake is dependent on reduction to the ferrous state. This requirement for reduction was independent of the iron status of the cells, demonstrating that the process of up-regulation is not due to the appearance of a new mechanism for translocation of Fe3+ without reduction. Taken together, the evidence favors a model of NTBI transport where an obligate and rate-determining reduction of Fe3+ occurs prior to or during uptake, followed by translocation through an Fe2+ carrier. The distinct translocation mechanisms of uptake in the presence and absence of ascorbate suggest that exogenous Fe2+ does not access the carrier available to the nascent ferrous ion derived from the reductase and is consistent with close coupling between the reduction and the translocation processes. In iron-loaded cells with increased rates of NTBI transport, a similar mechanism prevails.