gebhart/patrepeval huggingface dataset:
A Biosynthetic Approach for the Incorporation of Unnatural Amino Acids into Proteins (2003)

Unnatural amino acids can be incorporated into proteins or peptides by a variety of existing methods. Peptide synthesis (1–5) and semisynthetic methods (6–10) have been used to substitute novel amino acids into small proteins (<10 kDa) and peptides (11). Solvent accessible, reactive amino acid side chains have also been modified by chemical means (12–18). Modified amino acids have been uniformly incorporated into peptides and proteins with functional analogs of aminoacyl transfer RNAs (tRNAs) (19–21). Furthermore, several unnatural amino acids have been incorporated into dipeptides through the use of chemically misacylated tRNAs (22,23). However, these methods all suffer either from nonselective introduction of the novel amino acid or from size restrictions on the protein of interest.
Novel Mechanism Associated With an Inherited Cardiac Arrhythmia (1999)

Our results from both the Xenopus oocyte and HEK293 cell expression systems and green fluorescent protein tagging and Western blot analyses support the conclusion that the G601S mutant is a hypomorphic mutation, resulting in a reduced current amplitude. Thus, it represents a novel mechanism underlying LQT2.
Study of Precursors Responsible for Off-Flavor Formation during Storage of Potato Flakes (2006)

Off-flavors frequently appear during the storage of potato flakes. Volatile profile analysis performed by solid-phase microextraction-gas chromatography-mass spectrometry revealed that hexanal is the main compound that appears during the storage period. Hexanal may be a degradation product of linoleic acid formed through linoleic acid hydroperoxide cleavage. Profiles of hexanal precursors were determined from potato flakes at different storage time points. Linoleic acid-derived oxylipins are predominant in potato flakes. The free oxylipins identified, in descending order, are as follows: hexanal, hydroxy polyunsaturated fatty (PUFAs), oxo PUFAs, divinyl ether PUFAs, and hydroperoxy PUFAs. However, the main oxylipins detected were esterified: esterified hydroxy, hydroperoxy, and oxo PUFAs. Oxylipins reveal different evolutions during the storage period. Chiral high-performance liquid chromatography analysis of the precursors of hexanal and other oxylipins revealed a racemic composition that supports the nonenzymatic formation of hexanal and most of the other oxylipins identified.
Prevention of Programmed Cell Death in Caenorhabditis elegans by Human bcl-2 (1992)

Programmed cell death is a physiological process that eliminates unwanted cells. The bcl-2 gene regulates programmed cell death in mammalian cells, but the way it functions is not known. Expression of the human bcl-2 gene in the nematode Caenorhabditis elegans reduced the number of programmed cell deaths, suggesting that the mechanism of programmed cell death controlled by bcl-2 in humans is the same as that in nematodes.
Increased Phosphorylation of Histone H1 in Mouse Fibroblasts Transformed with Oncogenes or Constitutively Active Mitogen-activated Protein Kinase Kinase (1995)

We compared the nucleosomal organization, histone H1 subtypes, and histone H1 phosphorylated isoforms of ras-transformed and parental 10T1/2 mouse fibroblasts. In agreement with previous studies, we found that ras-transformed mouse fibroblasts have a less condensed chromatin structure than normal fibroblasts. ras-transformed and parental 10T1/2 cells had similar amounts of H1 subtypes, proteins that have a key role in the compaction of chromatin. However, labeling studies with 32P and Western blot experiments with an antiphosphorylated H1 antibody show that interphase ras-transformed cells have higher levels of phosphorylated H1 isoforms than parental cells. G1/S phase-arrested ras-transformed cells had higher amounts of phosphorylated H1 than G1/S phase-arrested parental cells. Mouse fibroblasts transformed with fes, mos, raf, myc, or constitutively active mitogen-activated protein (MAP) kinase kinase had increased levels of phosphorylated H1. These observations suggest that increased phosphorylation of H1 is one of the consequences of the persistent activation of the mitogen-activated protein kinase signal transduction pathway. Indirect immunofluorescent studies show that phosphorylated H1b is localized in centers of RNA splicing in the nucleus, suggesting that this modified H1 subtype is complexed to transcriptionally active chromatin.
A Knowledge-Guided Approach to Line NURBS Curve Intersection (2013)

Computer-Aided Design and Applications is an international journal on the applications of CAD and CAM. It publishes papers in the general domain of CAD plus in emerging fields like bio-CAD, nano-CAD, soft-CAD, garment-CAD, PLM, PDM, CAD data mining, CAD and the internet, CAD education, genetic algorithms and CAD engines. The journal is aimed at all developers and users of CAD technology to ptovide CAD solutions for various stages of design and manufacturing. The journal publishes all about Computer-Aided Design and Computer-Aided technologies.
<title>Template matching using fast normalized cross correlation</title> (2001)

In this paper, we present an algorithm for fast calculation of the normalized cross correlation and its application to the problem of template matching. Given a template t, whose position is to be determined in an image f, the basic idea of the algorithm is to represent the template, for which the normalized cross correlation is calculated, as a sum of rectangular basis functions. Then the correlation is calculated for each basis function instead of the whole template. The result of the correlation of the template t and the image f is obtained as the weighted sum of the correlation functions of the basis functions. Depending on the approximation, the algorithm can by far outperform Fourier-transform based implementations of the normalized cross correlation algorithm and it is especially suited to problems, where many different templates are to be found in the same image f.
[Clinical effect of arbekacin on MRSA infections after gastrointestinal surgery]. (1994)

From January 1991 to July 1993, 58 patients with MRSA infections in our clinic at Wakayama Medical College and six affiliated hospitals were administered with arbekacin (ABK). The clinical results were as follows: 1. The clinical efficacy rates of ABK were 84% in pneumonia, 100% in both wound infections and hepatobiliary tract infections, and 85% in total. The bacteriological efficacy rate was 83%. 2. Regarding the administration route, the clinical efficacy rates were 60-79% by the intravenous treatment and inhalation therapy. Especially by the local administration with ABK, MRSA was eradicated in all cases. 3. The sufficient efficacy was obtained by the treatment of ABK alone (89%) and by the combined treatment with ABK (82%) and another antibiotics. From these results, it is concluded that ABK is useful for the treatment of MRSA infections after gastrointestinal surgery.
Dietary protein restriction and the progression of chronic renal insufficiency: a review of the literature (1996)

It is well known that dietary protein restriction can delay the appearance of uraemic symptoms and give symptomatic relief in patients with chronic renal failure. During the last decade, several investigators have argued that protein restriction instituted at an early phase in renal disease may influence the rate of progression of renal failure favourably. Animal experiments have given strong evidence that, in the case of nephron loss, high dietary protein promotes further loss of renal function. Many studies have been conducted to investigate the possible favourable effect of a protein-restricted diet in patients with renal disease. However, the scientific proof that long-term protein restriction delays the progression of chronic renal insufficiency in man is still missing.
Lysis of human keratinocytes by allogeneic HLA class I-specific cytotoxic T cells. Keratinocyte ICAM-1 (CD54) and T cell LFA-1 (CD11a/CD18) mediate enhanced lysis of IFN-gamma-treated keratinocytes (1991)

Exposure of human KC to IFN-gamma increases their susceptibility to lysis by CTL. The mechanism of this enhanced lysis was investigated by analyzing interactions of IFN-gamma-treated and nontreated cultured KC with allogeneic class I-specific CTL clones. rIFN-gamma treatment augmented KC lysis in a time- and dose-dependent manner. Increased lysis of IFN-KC was detected after only 2 h of IFN-gamma treatment and was maximal by 12 h. Enhanced lysis of IFN-KC was Ag-specific, inasmuch as nonantigenic IFN-KC were not lysed either directly or as bystanders during the lysis of antigenic KC. Parallel immunofluorescence and cytotoxicity assays of KC treated with IFN-gamma for various intervals revealed a direct correlation between the degree of increased KC lysis and levels of cell surface ICAM-1 (CD54), but not of specific alloantigen or beta 2-microglobulin. Lysis of nontreated KC was blocked by mAb against class I or CD3, but not by mAb against ICAM-1 or LFA-1. In contrast, lysis of IFN-KC was partially inhibited by anti-ICAM-1 or anti-LFA-1 mAb, but resisted inhibition by anti-class I mAb except in the presence of anti-ICAM-1. These results indicate that both ICAM-1/LFA-1 and Ag/CD3-TcR interactions are important for Ag-specific lysis of IFN-KC, whereas lysis of nontreated KC depends on Ag/CD3-TcR but not ICAM-1/LFA-1 interactions. Equivalent inhibition of IFN-KC lysis by mAb against ICAM-1 or LFA-1 suggests that ICAM-1 is the only LFA-1 ligand involved in enhanced IFN-KC lysis. Furthermore, enhanced CTL lysis of KC after short-term IFN-gamma treatment can be explained solely on the basis of ICAM-1 induction, because all of the increase in specific lysis associated with IFN-gamma treatment could be blocked by mAb that block ICAM-1/LFA-1 interactions.
Recent Developments in Catalytic Asymmetric Strecker-Type Reactions (2001)

150 years after its discovery, a truly efficient three-component asymmetric version of the Strecker reaction has finally been accomplished; there has also been significant progress in recent years in two-component Strecker-type systems: Enantiopure amino acids can now be obtained from enantioselective catalysis of the Strecker reaction with different cyanide sources and aldimines (see scheme).
Paneth cells of the human small intestine express an antimicrobial peptide gene (1992)

Mucosal surfaces of several organ systems are important interfaces for host defense against microbes. Recent evidence suggests that antimicrobial peptides contribute to the defense of these surfaces. Defensins are one family of antimicrobial peptide, but their known distribution in humans has been limited to four members found in cells of myeloid origin. We sought to determine if the human defensin family was more complex. We found that the family of human defensins is diverse and is not restricted to expression in leukocytes. Southern blot and genomic clone analyses reveal that numerous defensin-related sequences are present in the human genome. A gene for a new human defensin family member was characterized. This gene, designated human defensin-5, is highly expressed in Paneth cells of the small intestine. This is the first example of an antimicrobial peptide gene expressed in an epithelial cell in humans. The data support the hypotheses that epithelial defensins equip the human small bowel with a previously unrecognized defensive capability which would augment other antimicrobial defenses.
Abundance of Cyclo (His-Pro)-Like Immunoreactivity in the Brain of TRH-Deficient Mice (1999)

Cyclo(His-Pro) or CHP was initially discovered as a metabolite of thyrotropin-releasing hormone (TRH) resulting from the action of the enzyme Pyroglutamyl aminopeptidase. Physiologic and pharmacologic studies that followed this initial discovery provided indirect evidence that all CHP may not be derived from TRH. However, the recent availability of a TRH-deficient mouse has made it possible to reinvestigate whether CHP is derived from TRH. In the present study, we examined distribution of CHP and TRH in TRH-deficient mice. Northern blot analysis confirmed the absence of preproTRH mRNA in both the hypothalamus and the cortex of TRH-deficient mice. Brains from the wild-type and TRH-deficient mice were dissected into 7 regions, and TRH and CHP concentrations were determined by specific radioimmunoassay (RIA) in each region. Whereas TRH was identified in all regions of the wild-type brain, with the highest concentration in the hypothalamus, no detectable TRH was observed in any region in the TRH-deficient mice. While CHP-like immunoreactivity (CHP-LI) was present in all regions in the wild-type brain, its concentration was reduced by approximately 50% in the hypothalamus and cerebral cortex of TRH-deficient mice, with no change in other brain regions. Furthermore, the CHP-LI present in the brain of TRH-deficient mice was immunologically and chromatographically identical to synthetic CHP. These findings strongly suggest that a portion of the CHP in the brain is derived from sources other than TRH.
Extensive DNA methylation spanning the Rb promoter in retinoblastoma tumors. (1997)

The retinoblastoma gene (Rb) is one of the best characterized tumor suppressor genes, and its inactivation is associated with a number of cancers. Previous studies have shown, by restriction enzyme analysis, that the promoter region of the Rb gene is methylated in a significant proportion of primary retinoblastoma tumors. We now report the first detailed methylation sequence analysis of the CpG island spanning the retinoblastoma promoter from hypermethylated retinoblastoma tumors. Our results show methylation is not confined to a specific CpG site, as detected by restriction enzyme studies, but extends to essentially all 27 CpG dinucleotides spanning the retinoblastoma CpG island, including the core promoter. The methylation pattern from each tumor DNA sample is different, ranging from densely to sparsely methylated profiles. Single CpG sites, in particular the E2F transcription factor binding site, as well as blocks of CpGs, were undermethylated in some tumor samples. Possible interference of methylation could be due to the binding of sequence-specific protein factors at these sites in the tumor cells. This study highlights that the dynamics of DNA methylation in cancer cells are clearly different from normal cells and gives an insight into the mechanism of abnormal methylation of CpG islands in cancer cells.
Transcriptional regulation of the CRLR gene in human microvascular endothelial cells by hypoxia (2003)

Adrenomedullin is a 52 amino acid peptide that shows a remarkable range of effects on the vasculature that include inter alia, vasodilatation, regulation of permeability, inhibition of endothelial cell apoptosis, and promotion of angiogenesis. Recently the G-protein coupled receptor (GPCR) calcitonin receptor-like receptor (CRLR), and receptor activity modifying proteins (RAMPs) have become recognized as integral components of the adrenomedullin signaling system. However, mechanisms of regulation of CRLR expression are still largely unknown. This is in part due to lack of information on the gene promoter. In this study we have determined the transcriptional start of human CRLR cDNA by 5'-RACE and cloned the proximal 5'-flanking region of the gene by PCR. The 2318 bp genomic fragment contains the basal promoter of human CRLR, including potential TATA-boxes and several GC boxes. Regulatory elements binding known transcription factors, such as Sp-1, Pit-1, glucocorticoid receptor, and hypoxia-inducible factor-1 alpha (HIF-1alpha) were also identified. When cloned into reporter gene vectors, the genomic fragment showed significant promoter activity, indicating that the 5'-flanking region isolated by PCR contains the gene promoter of human CRLR. Of significance is that the cloned promoter fragments were activated by hypoxia when transfected in primary microvascular endothelial cells. Site-directed mutagenesis of the consensus hypoxia-response element (HRE) in the 5'-flanking region abolished such a response. We also demonstrated by semi-quantitative RT-PCR that transcription of the gene is activated by hypoxia in microvascular endothelial cells. In contrast, expression of RAMPs 1, 2, and 3 was unaffected by low oxygen tension. We conclude that simultaneous transcriptional up-regulation of CRLR and its ligand adrenomedullin in endothelial cells could lead to a potent survival loop and therefore might play a significant role in vascular responses to hypoxia and ischemia.
Substitution of cysteine for selenocysteine in type I iodothyronine deiodinase reduces the catalytic efficiency of the protein but enhances its translation (1992)

Type I iodothyronine 5' deiodinase (5'DI) contains selenocysteine, encoded by a UGA codon, and this amino acid is essential for maximum catalytic efficiency in this enzyme. We recently showed that translation of UGA as selenocysteine in this protein requires a specific sequence of about 250 nucleotides in the 3' untranslated region of the messenger RNA. Translation of a 5'DI cysteine mutant does not require the 3' untranslated region. To examine both the efficiency of UGA codon recognition and the relative catalytic efficiency of selenocysteine vs. cysteine in 5'DI, we used bromoacetyl 125I-T3 labeling to quantitate transiently expressed selenocysteine (wild type) and cysteine containing type I iodothyronine deiodinases in transfected COS-7 and JEG-3 cell lines. Kinetic analyses of the same cell sonicates were performed to determine the apparent maximum velocity and Michaelis-Menten constant values for reverse T3 5' deiodination. COS-7 cells express the cysteine mutant protein at about 20-fold and JEG-3 cells about 400-fold higher levels than the selenoenzyme. However, in both cell types, the apparent catalytic constant values were at least 100-fold higher for the wild-type enzyme, compared with the cysteine mutant. These results indicate that cell lines differ markedly in their capacity to translate UGA-containing messenger RNAs. The much higher catalytic constant values for the selenium-containing enzyme illustrate the biochemical advantage of this element as compared with sulfur in the catalysis of iodothyronine deiodination.
PMN accumulation in aqueous humor and iris-ciliary body during intraocular inflammation. (1984)

The accumulation of polymorphonuclear leukocytes (PMNs) was determined in the aqueous humor and iris-ciliary body following an intravitreal injection of endotoxin in the albino rabbit. PMN accumulation in the iris-ciliary body was quantified by measuring myeloperoxidase (MPO) activity in homogenates of this tissue. Leukocyte appearance in the aqueous humor was determined by counting the number of PMNs in diluted aspirates of aqueous humor and also by measuring MPO activity in the same aspirates. Twenty-four hours following an intravitreal injection of endotoxin, there was marked vasodilatation in the iris, breakdown of the blood-aqueous barrier, and infiltration of PMNs into the aqueous humor. There was, however, no correlation between MPO activity in the iris-ciliary body and the number of PMNs or the MPO activity in the aqueous humor. Furthermore, the number of PMNs in the aqueous humor did not increase with increasing amounts of intravitreally injected endotoxin, whereas MPO activity in the iris-ciliary body increased in a dose-dependent manner. The results of this study suggest that quantification of leukocytes in the aqueous humor does not represent a meaningful index of intraocular inflammation.
ChemInform Abstract: ORGANOSULFUR CHEMISTRY. 3. NMR SPECTRA OF CARBANIONS DERIVED FROM 1,3‐DITHIANES AS RELATED TO THE HIGH STEREOSELECTIVITY IN THEIR REACTIONS WITH ELECTROPHILES (1978)

Abstract Das aus dem Dithian (I) hervorgehende Carbanion (II) bildet in Gegenwart von HCI‐DCI in THF zu mehr als 99% das teilweise deuterierte Derivat (III) mit axialer Phenylgruppe.
The Effect of Hypoxic Depression on Genioglossal Muscle Activity in Healthy Subjects and Obstructive Sleep Apnea Patients (1993)

We investigated whether selective depression of the genioglossus muscle (GG) activity could be associated with hypoxic ventilatory depression, which is developed in the late phase of the biphasic ventilatory response during sustained hypoxia. Eleven control subjects and 10 patients with obstructive sleep apnea syndrome (OSAS) were examined by an isocapnic sustained hypoxia test for 20 minutes. Ventilatory parameters and electromyographic (EMG) activities were recorded from GG (EMGGG) and diaphragm (EMGDIA). Hypoxic depression in minute ventilation (V1) and EMGDIA occurred when compared between the peak value and the value at late period in both groups. On the contrary, depression in EMGGG was not observed in controls (86% of the peak value), whereas EMGGG was strikingly depressed in OSAS (39% of the peak value). We conclude that sustained hypoxia reduces the activity of GG in OSAS, but not in control subjects. These data suggest that the lack of a compensatory response of GG to sustained hypoxia is possibly responsible for the pathogenesis of OSA.
Combination of paclitaxel and carboplatin as second‐line therapy for patients with metastatic melanoma (2005)

Abstract BACKGROUND Patients with metastatic melanoma (MM) have very few therapy options. Based on reports of responses to paclitaxel and carboplatin (PC), 31 patients with MM were treated with PC. METHODS Data regarding patients treated with PC were abstracted from medical records. Clinical outcomes as determined by the treating oncologist were used for this analysis. Response determination was retrospectively confirmed using Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS Thirty‐one patients with MM were treated with PC. Patients had a median of 2 previous therapies, with the majority (29; 94%) having failed prior temozolomide (TMZ) or dacarbazine (DTIC) therapy. The most commonly used regimen was weekly paclitaxel (at a dose of 100 mg/m 2 ) and carboplatin (area under the curve 2) administered on Days 1, 8, and 15 of a 28‐day cycle. An objective partial response was noted in 8 patients (26%) with an additional 6 patients (19%) having stable disease; therefore, a clinical benefit was noted in 45% of those patients treated. The median time to disease progression for the entire group was 3 months (range, 0–7 mos), with a median overall survival of 7.8 months (range, 1–14 mos). The clinical benefit derived by the 14 patients, which lasted for a median of 5.7 months (range, 2.5–7.3 mos), was considered to be clinically significant. At the time of last follow‐up, eight patients continued to receive PC therapy. CONCLUSIONS The PC combination appears to have definite and clinically meaningful activity when used as second‐line therapy after TMZ or DTIC. Further evaluation of this regimen, alone or as a ‘backbone’ for other agents, needs to be considered. Cancer 2006. © 2005 American Cancer Society.
Optimizing anti-CD3 affinity for effective T cell targeting against tumor cells (2002)

Bispecific antibodies binding to the TCR/CD3 complex and to a tumor-associated surface molecule can be used to target cytotoxic T lymphocytes against tumor cells. We reasoned that high-affinity binding to CD3 may reduce the efficiency of T cell stimulation and target the bispecific reagent to T cells rather than to tumor cells in vivo. We therefore mutated a bispecific single-chain antibody (BscAb) directed to human CD3 and EpCAM to generate variants that bind to CD3 with higher or lower affinity. When compared to the wild-type molecule, a mutant with increased binding to CD3 showed lower capacity to target T cells against an EpCAM+ tumour. In contrast, mutants with decreased binding to CD3, in spite of rapid dissociation, efficiently triggered T cell activation and cytotoxicity, especially when present on tumor cells at low copy number. These results are consistent with the TCR serial triggering model and suggest that BscAb with extremely low affinity for the TCR-CD3 complex could be exploited therapeutically because of their preferential localization to tumor cells.