gebhart/patrepeval huggingface dataset:
Chimeric Antigen Receptor T Cells Shape Myeloid Cell Function within the Tumor Microenvironment through IFN-γ and GM-CSF (2012)

The infiltration of suppressive myeloid cells into the tumor microenvironment restrains anti-tumor immunity. However, cytokines may alter the function of myeloid lineage cells to support tumor rejection, regulating the balance between pro- and anti-tumor immunity. In this study, it is shown that effector cytokines secreted by adoptively transferred T cells expressing a chimeric Ag receptor (CAR) shape the function of myeloid cells to promote endogenous immunity and tumor destruction. Mice bearing the ovarian ID8 tumor were treated with T cells transduced with a chimeric NKG2D receptor. GM-CSF secreted by the adoptively transferred T cells recruited peripheral F4/80(lo)Ly-6C(+) myeloid cells to the tumor microenvironment in a CCR2-dependent fashion. T cell IFN-γ and GM-CSF activated local, tumor-associated macrophages, decreased expression of regulatory factors, increased IL-12p40 production, and augmented Ag processing and presentation by host macrophages to Ag-specific T cells. In addition, T cell-derived IFN-γ, but not GM-CSF, induced the production of NO by F4/80(hi) macrophages and enhanced their lysis of tumor cells. The ability of CAR T cell therapy to eliminate tumor was moderately impaired when inducible NO synthase was inhibited and greatly impaired in the absence of peritoneal macrophages after depletion with clodronate encapsulated liposomes. This study demonstrates that the activation of host macrophages by CAR T cell-derived cytokines transformed the tumor microenvironment from immunosuppressive to immunostimulatory and contributed to inhibition of ovarian tumor growth.
Effects of particle size and pelleting on growth performance, nutrient digestibility, and stomach morphology in finishing pigs2 (1995)

The effects of particle size and pelleting on growth performance, carcass characteristics, nutrient digestibility, and stomach morphology were determined using 160 finishing pigs. The pigs were fed a corn-soybean meal-based diet with the corn milled to particle sizes of 1,000, 800, 600, or 400 microns. The diets were fed in meal or pellet form. Pelleting the diets resulted in 5% greater ADG (P < .01) and 7% greater grain/feed (P < .001). Also, pelleting increased digestibilities of DM, N, and GE by 5 to 8% (P < .001). Reducing particle size increased electrical energy required for milling and decreased milling production rates, especially as particle size was decreased from 600 to 400 microns. Reducing particle size of the corn from 1,000 to 400 microns increased gain/feed by 8% (linear effect, P < .001) and digestibility of GE by 7% (quadratic effect, P < .03). Improved nutrient digestibility and lower ADFI resulted in 26% less daily excretion of DM and 27% less daily excretion of N in the feces as particle size was reduced from 1,000 to 400 microns (linear effects, P < .001). Stomach lesions and keratinization increased with reduced particle size (P < .003) and keratinization increased with pelleting (P < .02), although they were unrelated to growth performance (i.e., gain/feed actually improved as lesion scores increased). Considering milling energy, growth performance, stomach morphology, nutrient digestibility, and nutrient excretion, a particle size of 600 microns, or slightly less, is an acceptable compromise for corn in both meal and pelleted diets for finishing pigs.
Aminoacyl-tRNA synthetases: Versatile players in the changing theater of translation (2002)

Aminoacyl-tRNA synthetases attach amino acids to the 3' termini of cognate tRNAs to establish the specificity of protein synthesis. A recent Asilomar conference (California, January 13-18, 2002) discussed new research into the structure-function relationship of these crucial enzymes, as well as a multitude of novel functions, including participation in amino acid biosynthesis, cell cycle control, RNA splicing, and export of tRNAs from nucleus to cytoplasm in eukaryotic cells. Together with the discovery of their role in the cellular synthesis of proteins to incorporate selenocysteine and pyrrolysine, these diverse functions of aminoacyl-tRNA synthetases underscore the flexibility and adaptability of these ancient enzymes and stimulate the development of new concepts and methods for expanding the genetic code.
Rapid SNP Allele Frequency Determination in Genomic DNA Pools by Pyrosequencing TM (2002)

Individual genotyping of single nucleotide polymorphisms (SNPs) remains expensive, especially for linkage disequilibrium mapping strategies involving high-throughput SNP genotyping. On one hand, current methods may suit scientific and laboratory needs in regard to accuracy, reproducibility/robustness, and large-scale application. On the other hand, a cheaper and less time-consuming alternative to individual genotyping is the use of SNP allelefrequencies determined in DNA pools. We have developed an accurate and reproducible protocol for allele frequency determination using Pyrosequencing technology in large genomic DNA pools (374 individuals). The measured correlation (R2) in large DNA pools was 0.980. In the context of disease-associated SNPs studies, we compared the allele frequencies between the disease (e.g., type 2 diabetes and obesity) and control groups detected by either individual genotyping or Pyrosequencing of DNA pools. In large pools, the variation between the two methods was 1.5 +/- 0.9%. It may be concluded that the allele frequency determination protocol could reliably detect over 4% differences between populations. The method is economical in regard to amounts of DNA, PCR, and primer extension reagents required. Furthermore, it allows the rapid determination of allelefrequency differences in case/control groups for association studies and susceptibility gene discovery in complex diseases.
Effects of recombinant human interleukin-11 (Neumega rhIL-11 growth factor) on megakaryocytopoiesis in human bone marrow. (1996)

We examined the effects of recombinant human interleukin 11 (rhIL-11) on in vivo human hematopoiesis. Twelve women with advanced breast cancer and no evidence of bone marrow (BM) involvement were treated with 10, 25, 50, or 75 micrograms/kg/day of rhIL-11 administered subcutaneously for 14 consecutive days. Examination of bone marrow trephine biopsies obtained before and after rhIL-11 treatment revealed unchanged BM cellularity at all doses, and a statistically significant increase in megakaryocyte (MK) frequencies (from 0.5 +/- 0.1% to 1.0 +/- 0.3%) following administration of the two highest doses (p < 0.001). The BM biopsies also showed an increased proportion of immature myeloid and erythroid precursors following 14 days of treatment in all cases. The mean proportion of marrow cells stained with PC10, a monoclonal antibody (mAb) that recognizes the proliferating cell nuclear antigen (PCNA), increased from 16.3 +/- 5.7% to 45.8 +/- 17.1% (p < 0.001) following the two highest treatment doses. Most of the PC10+ cells were promyelocytes and proerythroblasts. In this same group, the proportion of PC10+ MKs increased from 28.3 +/- 11.5% to 56.8 +/- 24.3% (p < 0.01) after treatment, while megakaryocyte ploidy analysis revealed a greater number of higher ploidy (64N) megakaryocytes following rhIL-11 treatment (p < 0.012). Numbers of BM and peripheral blood (PB) CD34+, CD34+DR+, and CD34+DR- cells did not change following rhIL-11 treatment. Following rhIL-11 therapy at the highest dose studied, a 3- and 10-fold increase in the number of committed BM MK progenitor cells (CFU-MK) was observed in two of three patients, while no change was seen in the number of the other BM or PB progenitor cells examined. rhIL-11 administration was also associated with an increase in BM reticulin content (fibrosis grade 1-2) in 7 patients. These results indicate that the administration of rhIL-11 to patients with normal hematopoiesis stimulates MK endoreduplication, PCNA expression, and, at high doses, increases MK and CFU-MK progenitor cell numbers. In addition, rhIL-11 was able to stimulate precursor cells of different marrow lineages without affecting the number of assayable progenitor cells.
Ultrathin Nanogenerators as Self‐Powered/Active Skin Sensors for Tracking Eye Ball Motion (2013)

Ultrathin piezoelectric nanogenerator (NG) with a total thickness of ≈16 μm is fabricated as an active or self‐powered sensor for monitoring local deformation on a human skin. The NG was based on an anodic aluminum oxide (AAO) as an insulating layer grown on a thin Al foil by anodization, on which a thin film made of aligned ZnO nanowire compacted arrays is grown by solution chemistry. The performance of the NG is characterized with the assistance of the finite element method (FEM) simulation. The extremely thin NG is attached on the surface of an eyelid, and its output voltage/current characterizes the motion of the eye ball underneath. Since there is no external power needed for the operation of the NG, this self‐powered or active sensor can be effective in monitoring sleeping behavior, brain activities, and spirit status of a person as well as any biological associated skin deformation.
A hammerhead ribozyme inhibits the proliferation of an RNA coliphage SP in Escherichia coli (1994)

Ribozymes are potentially powerful tools for the suppression of intracellular gene expression. However, the few reports that exist of their activities in bacteria have described mixed success. Chuat and Galibert (Chuat, J.-C., and Galibert, F. (1989) Biochem. Biophys. Res. Commun. 162, 1025-1029) failed to detect any trans-activities of hammerhead ribozymes in Escherichia coli, while Sioud and Drlica (Sioud, M., and Drlica, K. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 7303-7307) reported complete inhibition of expression of the gene for a nonbacterial protein, HIV-1 integrase, by trans-acting hammerhead ribozymes in E. coli. It is of interest to determine whether ribozymes can really be used in natural bacterial systems (Altman, S. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 10898-10900). We now report that a ribozyme designed to cleave the A2 gene of RNA coliphage SP, when transcribed from a plasmid in E. coli caused failure of the proliferation of progeny phage. Inactive ribozymes with altered catalytic sequences did not affect phage growth. These results indicate that it is mainly the catalytic activity of the ribozyme and not its function as an antisense molecule that is responsible for suppressing the proliferation of the RNA phage. Moreover, an analysis based on numbers of plaque-forming units and the function of the A2 protein indicated that antisense RNA may successfully compete with ribosomes in targeting mRNA while ribozymes in this study may not compete with ribosomes in naturally occurring bacterial transcription/translation-coupled systems.
Advances in the development of siRNA-based therapeutics for cancer. (2008)

Short interfering (si)RNA represents a promising novel therapeutic modality for the treatment of cancer. However, delivering siRNA to tumors via clinically relevant means is a major technical hurdle that has impeded the successful development of siRNA-based cancer therapeutics. Significant progress has been made in recent years for the delivery of siRNA to tumors, and several promising siRNA delivery platforms have begun to emerge. These platforms include liposomes, in which siRNA is encapsulated in a lipid vesicle; polyplexes, in which a cationic carrier is used to bind siRNA to form siRNA-containing nanoparticles; liposome-polycation-DNA (LPD) complexes, in which an siRNA-containing polyplex is encapsulated in a lipid vesicle; and siRNA conjugates, in which siRNA is coupled to a targeting moiety that carries the siRNA into target cells via receptor-mediated endocytosis. An unbiased, independent evaluation of various tumor-delivery approaches will be a critical starting point in identifying the most promising delivery platforms for the development of siRNA-based cancer therapeutics.
Silver-Catalyzed Late-Stage Fluorination (2010)

Carbon-fluorine bond formation by transition metal catalysis is difficult, and only a few methods for the synthesis of aryl fluorides have been developed. All reported transition-metal-catalyzed fluorination reactions for the synthesis of functionalized arenes are based on palladium. Here we present silver catalysis for carbon-fluorine bond formation. Our report is the first example of the use of the transition metal silver to form carbon-heteroatom bonds by cross-coupling catalysis. The functional group tolerance and substrate scope presented here have not been demonstrated for any other fluorination reaction to date.
Singing Voice Separation: A Study on Training Data (2019)

In the recent years, singing voice separation systems showed increased performance due to the use of supervised training. The design of training datasets is known as a crucial factor in the performance of such systems. We investigate on how the characteristics of the training dataset impacts the separation performances of state-of-the-art singing voice separation algorithms. We show that the separation quality and diversity are two important and complementary assets of a good training dataset. We also provide insights on possible transforms to perform data augmentation for this task.
Nuclear mechanisms of estrogen action. Effects of estradiol and anti-estrogens on estrogen receptors and nuclear receptor processing. (1978)

This study attempted to show directly how antiestrogens (tamoxifen and nafoxidine) affect the estrogen receptor (ER) in MCF-7 human breast cancer cells. The mechanisms of estrogen action through the unfilled ERs in both cytoplasm (Rc) and nuclei (Rn) of this cell line were contrasted with the effects of estradiol (E) and antiestrogens on receptor binding nuclear processing reactions and progesterone receptor (PgR) synthesis. Within 5 minutes E bound Rc and translocated it to the nucleus; E also bound Rn directly. Beginning 30 minutes after E and continuing for 3-5 hours a progressive depletion of about 70% of filled nuclear receptors (RnE) occurred without reappearance of unfilled receptor. From that point on the RnE levels stabilized a step coincident with PgR induction. The antiestrogens also bound Rc and Rn as demonstrated by in vitro competition studies and by exchange rates of tritiated E for ER complexed to antiestrogens in whole cells. However the nuclear antiestrogen receptor complexes were aberrantly processed; 3-5 hours after tamoxifen only 30% of nuclear-bound receptors were lost before nuclear receptor levels stabilized whereas nafoxidine-bound nuclear receptors were not processed at all. In spite of the only partial ER processing after tamoxifen PgR was induced as long as lower steady-state ER levels were maintained. When tamoxifen was removed total cell ERs returned to control levels as Rc were restored. Simultaneously PgR falls. Rc binding and translocation alone however are not sufficient for PgR induction since if nuclear processing fails PgR induction is prevented (as is the case with nafoxidine). These data suggest that nuclear processing steps may be integral to the function of estrogenic compounds as inducers of PgR.
Mutations in the holocarboxylase synthetase geneHLCS (2005)

Holocarboxylase synthetase (HLCS) deficiency is an autosomal recessive disorder. HLCS is an enzyme that catalyzes biotin incorporation into carboxylases and histones. Since the first report of the cDNA sequence, 30 mutations in the HLCS gene have been reported. Mutations occur throughout the entire coding region except exons 6 and 10. The types of mutations are one single amino acid deletion, five single nucleotide insertions/deletions, 22 missense mutations, and two nonsense mutations. The only intronic mutation identified thus far is c.1519+5G>A (also designated IVS10+5G>A), which causes a splice error. Several lines of evidence suggest that c.1519+5G>A is a founder mutation in Scandinavian patients. Prevalence of this mutation is about 10 times higher in the Faroe Islands than in the rest of the world. The mutations p.L237P and c.780delG are predominant only in Japanese patients. These are probably founder mutations in this population. Mutations p.R508W and p.V550M are identified in several ethic groups and accompanied with various haplotypes, suggesting that these are recurrent mutations. There is a good relationship between clinical biotin responsiveness and the residual activity of HLCS. A combination of a null mutation and a point mutation that shows less than a few percent of the normal activity results in neonatal onset. Patients who have mutant HLCS with higher residual activity develop symptom after the neonatal period and show a good clinical response to biotin therapy.
The Drosophila Insulin Receptor Contains a Novel Carboxyl-terminal Extension Likely to Play an Important Role in Signal Transduction (1995)

The nucleic acid and deduced amino acid sequence of the Drosophila insulin receptor homologue (dir) has been determined. The coding sequence of dir is contained within 10 exons spanning less than 8 kilobase pairs of genomic DNA. The deduced amino acid sequence of the dir encodes a protein of 2148 amino acids, larger than the human insulin receptor due to amino- and carboxyl-terminal extensions. The overall level of amino acid identity between the DIR and human insulin and insulin-like growth factor-I receptors is 32.5 and 33.3%, respectively. Higher levels of identity are found in exon 2 (45 and 43%, respectively) and in the beta subunit (50 and 48%, respectively), and the positions of most cysteine residues in the alpha subunit cysteine-rich domain are conserved. A novel, 400-amino acid, carboxyl-terminal extension contains 9 tyrosine residues, four of which are present in YXXM or YXXL motifs, suggesting that they function as binding sites for SH2 domain-containing signaling proteins. The presence of multiple putative SH2 domain binding sites in the DIR represents a significant difference from its mammalian homologues and suggests that, unlike the human insulin and insulin-like growth factor-I receptors, the DIR forms stable complexes with signaling molecules as part of its signal transduction mechanism.
The human immunoglobulin x locus. Characterization of the duplicated O regions (1991)

Two large regions of the human immunoglobulin kappa locus, the so-called O regions, have been characterized on cosmid and phage lambda clones. The two regions are very similar but not identical duplicates belonging to the C kappa proximal (p) and the distal (d) copies of the kappa locus. The Op and Od regions comprise contigs of 90 and 120 kb, respectively, and contain 20 V kappa genes and pseudogenes which have been sequenced. Three pairs of V kappa genes were found to be practically identical in the duplicates while allotypic differences, at least for two of the genes, are considerable. The similarities between the duplicate genes may be related to the fact that the two copies of the kappa locus are arranged in a palindrome-like fashion with the 5' sides of the O regions pointing towards each other (C kappa J kappa B Lp Ap Op-Od Ad Ld). This may have contributed to equalizing the sequences. Beyond Op and Od no further V kappa genes were found within about 80 kb. Instead, repetitive DNA sequences have been localized there, the structures of which suggest that they may have been involved in the evolution of the V kappa gene-containing regions. The V kappa pseudogene containing W regions, that had been transposed in evolution from the short to the long arm of chromosome 2 by a pericentric inversion, may have been derived from the O regions according to structural homologies between defined sections of the O and W regions.
Bragg grating-based laser sensors systems with interferometric interrogation and wavelength division multiplexing (1995)

We describe the use of fiber Bragg grating based lasers as sensors. An interferometric detection technique is presented for interrogating laser wavelength shifts due to measurand induced laser cavity strain with high resolution from both single-mode and multimode lasers. The principle of integrating multiple sensors to form an array is demonstrated using a wavelength division multiplexing approach.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus Entry That Act by Three Distinct Mechanisms (2013)

Severe acute respiratory syndrome (SARS) is an infectious and highly contagious disease that is caused by SARS coronavirus (SARS-CoV) and for which there are currently no approved treatments. We report the discovery and characterization of small-molecule inhibitors of SARS-CoV replication that block viral entry by three different mechanisms. The compounds were discovered by screening a chemical library of compounds for blocking of entry of HIV-1 pseudotyped with SARS-CoV surface glycoprotein S (SARS-S) but not that of HIV-1 pseudotyped with vesicular stomatitis virus surface glycoprotein G (VSV-G). Studies on their mechanisms of action revealed that the compounds act by three distinct mechanisms: (i) SSAA09E2 {N-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1,2-oxazole-5-carboxamide} acts through a novel mechanism of action, by blocking early interactions of SARS-S with the receptor for SARS-CoV, angiotensin converting enzyme 2 (ACE2); (ii) SSAA09E1 {[(Z)-1-thiophen-2-ylethylideneamino]thiourea} acts later, by blocking cathepsin L, a host protease required for processing of SARS-S during viral entry; and (iii) SSAA09E3 [N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)benzamide] also acts later and does not affect interactions of SARS-S with ACE2 or the enzymatic functions of cathepsin L but prevents fusion of the viral membrane with the host cellular membrane. Our work demonstrates that there are at least three independent strategies for blocking SARS-CoV entry, validates these mechanisms of inhibition, and introduces promising leads for the development of SARS therapeutics.
Intense PET Signal in the Degenerative Necrosis Superimposed on Chronic Pancreatitis (2005)

Although fluorine-18 deoxyglucose-positron emission tomography (FDG-PET) is a sensitive diagnostic modality in detecting malignant tumors, differential diagnosis of malignant tumors from inflammatory lesion is challenging. We experienced a case of acute degenerative necrosis superimposed on chronic pancreatitis, which was difficult to distinguish from pancreatic cancer. The patient was a 66-year-old man with a complaint of upper abdominal pain. Abdominal computed tomography revealed low-density masses in the head and body of the pancreas. FDG-PET revealed intense accumulations at the head and body of the pancreas (mean standard uptake value for the head and body pancreatic tumors was 4.1 and 6.7, respectively) corresponding to the 2 tumors detected by computed tomography. Because of a possible malignant pancreatic tumor, the patient underwent pylorus-preserving pancreatoduodenectomy. Histologic examination of the resected specimen revealed a characteristic of chronic pancreatitis in a nontumorous area. Two tumors detected by FDG-PET consisted of degenerative necrosis surrounded by granulation tissue. The amount of granulation tissue was correlated to the levels of standard uptake value. No malignant tumors were observed. This case suggests a limitation of FDG-PET in distinguishing malignant neoplastic lesions in the pancreas, especially from acute degenerative changes in chronic pancreatitis. Repetitive PET examination is recommended for the accurate diagnosis.
Detection and monitoring of serum p53 antibodies in patients with colorectal cancer. (1997)

Testing for serum p53 antibodies constitutes a useful technique for assessing alterations in p53 and may help physicians to follow up patients with colorectal cancer.