gebhart/patrepeval huggingface dataset:
Chimeric peptides: a new approach to enhancing the immunogenicity of peptides with low MHC class I affinity: application in antiviral vaccination (1997)

Abstract Recruitment of the CTL repertoire specific for subdominant epitopes that have a low MHC class I-binding affinity could be the way to achieve an efficient protective immunity against spontaneous tumors and viruses with high mutation rate. However, we have reported recently that subdominant peptides of influenza A Puerto Rico/8/34 (flu PR8) nucleoprotein (NP) with low Db affinity are only partially able to protect mice against lethal influenza infection. This seems to be due to their inability to recruit the specific CTL repertoire, and suggests that subdominant peptides could be used for vaccination only if they become highly immunogenic. In this work, we describe an approach that allows enhancement of the immunogenicity of every low affinity peptide presented by the Db molecule. It consists in producing chimeric peptides composed by amino acids from a high Db affinity peptide (NP366) in positions that interact with the MHC, and amino acids from low Db affinity nonimmunogenic influenza NP-derived peptides (NP17, NP97, NP330, and NP469) in positions that are exposed to the TCR. All chimeric peptides tested exhibited a high Db affinity and efficiently recruited the CTL repertoire specific for the corresponding low Db affinity peptide. Furthermore, vaccination with chimeric peptides that corresponded to subdominant NP17 and NP97 peptides induced a very potent anti-flu PR8 protective immunity.
Translational control of ornithine aminotransferase. Modulation by initiation factor eIF-4E. (1991)

Ornithine aminotransferase (OAT) is a mitochondrial enzyme expressed at high levels in liver, kidney, and retina. To characterize OAT regulation in retinal lines, we have been studying OAT synthesis in retinoblastomas RB355 and Y79. Our previous data (Fagan, R.J., Sheffield, W.P., and Rozen, R. (1989) J. Biol. Chem. 264, 20513-20517) indicated similar OAT mRNA levels in the two strains with 3-fold greater immunoreactive OAT protein and enzyme activity in Y79. To examine the regulatory mechanisms in these cell lines, we performed nuclear runoff experiments and characterized polysome-associated OAT mRNAs. The nuclear runoff data did not reveal any differences in transcription between the two strains. However, OAT mRNA of the RB355 strain was present in the lighter polysome fractions as compared with Y79. Treatment with cycloheximide, which slows the rate of elongation, indicated that initiation was decreased in RB355. Eukaryotic initiation factor eIF-4E mRNA and protein were reduced in RB355, suggesting that eIF-4E might be rate-limiting for OAT translation. Overexpression of a wild-type eIF-4E in RB355 shifted the OAT mRNA into denser fractions of the gradient and increased the amount of OAT protein to the level observed in Y79; overexpression of a mutant eIF-4E had no such effect. We previously identified an alternatively spliced OAT mRNA (containing exon 2) in these cells. This mRNA appeared in the lightest fractions of the gradient in both strains and was not affected by eIF-4E overexpression.
Differences between collagen hydroxylases and 2-oxoglutarate dehydrogenase in their inhibition by structural analogues of 2-oxoglutarate (1985)

Inhibition of lysyl hydroxylase and prolyl 3-hydroxylase was studied with 23 selected aromatic and aliphatic structural analogues of 2-oxoglutarate and the results were compared with those previously reported for prolyl 4-hydroxylase. All the compounds inhibited the hydroxylases competitively with respect to 2-oxoglutarate and noncompetitively with respect to Fe2+ and the peptide substrate. The inhibition patterns for the three collagen hydroxylases were basically similar, but certain differences in detail emerged. One systematic difference was that lysyl hydroxylase had a higher Ki for almost all the compounds than had the two prolyl hydroxylases. Another interesting difference was that pyridine-2,4-dicarboxylate was the most potent inhibitor of lysyl hydroxylase and prolyl 3-hydroxylase, with Ki values of 50 microM and 3 microM respectively, whereas pyridine-2,5-dicarboxylate was the most potent inhibitor of prolyl 4-hydroxylase. These and other data suggest that the three collagen hydroxylases have similar but not identical 2-oxoglutarate-binding sites. Pyridine-2,4-dicarboxylate and pyridine-2,5-dicarboxylate and their corresponding benzene derivatives were also found to inhibit 2-oxoglutarate dehydrogenase, but with this enzyme, unlike the collagen hydroxylases, no distinct difference in the Ki values was found between the corresponding pyridine and benzene derivatives. This demonstrates the importance of the metal ion for the binding of various compounds at the 2-oxoglutarate-binding site of the collagen hydroxylases. 2-Oxoadipate was shown to replace 2-oxoglutarate in the lysyl hydroxylase and 2-oxoglutarate dehydrogenase reactions, as has previously been reported for prolyl 4-hydroxylase, whereas no other 2-oxo acid tested had any co-substrate activity. The 2-oxoglutarate-binding site of these enzymes is thus flexible to a certain degree, as it can accommodate molecules of different shapes and volumes. On the basis of the present data pyridine-2,5-dicarboxylate seems to be a quite specific inhibitor of prolyl 4-hydroxylase, the Ki for 2-oxoglutarate dehydrogenase being about 4000-fold higher.
Current management of follicular lymphoma (1996)

Follicular lymphoma is the most common histological subtype of so-called indolent lymphomas. Despite the high rate of initial response to treatment, these low-grade B-cell non-Hodgkin's lymphomas follow a fluctuating (indolent) clinical course of regression and progression with an overall median survival of 8 to 10 years. Localized disease may be cured by radiotherapy, although in the majority of patients, the disease is already disseminated at the time of presentation. Current therapies include the use of single agents, such as the established drugs chlorambucil or cyclophosphamide, or the newer purine analogues, such as fludarabine. Combination chemotherapy, including the recently developed regimens based on fludarabine, is often advocated in those with more advanced disease or at subsequent recurrences. High-dose myeloablative therapy with autologous support has become a consideration for most patients whom are eligible or suitable for such treatment. Allogeneic transplantation may also be beneficial to a select group. The management of patients with this group of illnesses, however, may be heavily influenced in the future by the emerging immunologically oriented therapies, ie, monoclonal antibodies and idiotype vaccination.
Light trapping in thin-film silicon solar cells with submicron surface texture (2009)

The influence of nano textured front contacts on the optical wave propagation within microcrystalline thin-film silicon solar cell was investigated. Periodic triangular gratings were integrated in solar cells and the influence of the profile dimensions on the quantum efficiency and the short circuit current was studied. A Finite Difference Time Domain approach was used to rigorously solve the Maxwell's equations in two dimensions. By studying the influence of the period and height of the triangular profile, the design of the structures were optimized to achieve higher short circuit currents and quantum efficiencies. Enhancement of the short circuit current in the blue part of the spectrum is achieved for small triangular periods (P<200 nm), whereas the short circuit current in the red and infrared part of the spectrum is increased for triangular periods (P = 900nm) comparable to the optical wavelength. The influence of the surface texture on the solar cell performance will be discussed.
Control of flower development in Arabidopsis thaliana by APETALA1 and interacting genes (1993)

ABSTRACT Mutations in the APETALA1 gene disturb two phases of flower development, flower meristem specification and floral organ specification. These effects become manifest as a partial conversion of flowers into inflorescence shoots and a disruption of sepal and petal development. We describe the changes in an allelic series of nine apetala1 mutants and show that the two functions of APETALA1 are separable. We have also studied the interaction between APETALA1 and other floral genes by examining the phenotypes of multiply mutant plants and by in situ hybridization using probes for several floral control genes. The results suggest that the products of APETALA1 and another gene, LEAFY, are required to ensure that primordia arising on the flanks of the inflorescence apex adopt a floral fate, as opposed to becoming an inflorescence shoot. APETALA1 and LEAFY have distinct as well as overlapping functions and they appear to reinforce each other’s action. CAU - LIFLOWER is a newly discovered gene which positively regulates both APETALA1 and LEAFY expression. All functions of CAULIFLOWER are redundant with those of APETALA1. APETALA2 also has an early function in reinforcing the action of APETALA1 and LEAFY, especially if the activity of either is compromised by mutation. After the identity of a flower primordium is specified, APETALA1 interacts with APETALA2 in controlling the development of the outer two whorls of floral organs.
Two Views of Present Trends in the Teaching of Internal Medicine (1970)

Special Articles1 September 1970Two Views of Present Trends in the Teaching of Internal MedicineTINSLEY R. HARRISON, M.D.TINSLEY R. HARRISON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-73-3-475 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn one of his many fantasy tales of science fiction H. G. Wells, who out-Verned even Jules Verne in terms of imagination, wrote of the "time machine." With it one could move backward into the past or forward into the future. Let us imagine that such an apparatus has moved Cassandra some 3,000 years into our own era. She encounters Pollyanna. They meet in a large auditorium, and their audience consists entirely of full-time clinical teachers. They discuss modern education in internal medicine in the United States.POLLYANNA: One of the great things is that our full-time faculties are bigger... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Birmingham, Alabama▸The American College of Physicians Distinguished Teacher Award Lecture, presented April 15, 1970, at the 51st Annual Session of the American College of Physicians, Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byVALUING THE PATIENTS VIEWS: A PROBLEM FOR PUBLIC POLICY 1 September 1970Volume 73, Issue 3Page: 475-478KeywordsForecasting Issue Published: 1 September 1970 PDF downloadLoading ...
Multimodal Imaging Based on Digital Holography (2017)

Digital holography provides a method of the 3-D recording and numerical reconstruction by a simple optical system and a computer. Quantitative measurement and numerical refocusing are major characteristics. So far, many physical parameters such as amplitude, phase, polarization, fluorescence, and spectra can be obtained independently. Recently, multimodal imaging that can obtain simultaneously two or more physical parameters by combining digital holographic microscope and other optical microscopes such as a fluorescence optical microscope and a Raman scattering microscope has emerged. In this review, physical parametric imaging techniques based on digital holography are presented and then these techniques are enhanced to develop multimodal imaging based on digital holography.
Reading and writing of photochemical holes using GaAlAs-diode lasers (1983)

A current-tuned GaAlAs-diode laser is utilized both to burn and to detect narrow photochemical holes in the inhomogeneously broadened 833-nm zero-phonon line of the R' color center in LiF. Applications for reading and writing data into frequency-domain optical memories based on photochemical hole burning are discussed.
Programmed Death-Ligand 1 Immunohistochemistry Testing: A Review of Analytical Assays and Clinical Implementation in Non–Small-Cell Lung Cancer (2017)

Purpose Three programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for treatment of non-small-cell lung cancer (NSCLC). Treatment with pembrolizumab in NSCLC requires PD-L1 immunohistochemistry (IHC) testing. Nivolumab and atezolizumab are approved without PD-L1 testing, though US Food and Drug Administration-cleared complementary PD-L1 tests are available for both. PD-L1 IHC assays used to assess PD-L1 expression in patients treated with programmed death-1/PD-L1 inhibitors in clinical trials include PD-L1 IHC 28-8 pharmDx (28-8), PD-L1 IHC 22C3 pharmDx (22C3), Ventana PD-L1 SP142 (SP142), and Ventana PD-L1 SP263 (SP263). Differences in antibodies and IHC platforms have raised questions about comparability among these assays and their diagnostic use. This review provides practical information to help physicians and pathologists understand analytical features and comparability of various PD-L1 IHC assays and their diagnostic use. Methods We reviewed and summarized published or otherwise reported studies (January 2016 to January 2017) on clinical trial and laboratory-developed PD-L1 IHC assays (LDAs). Studies assessing the effect of diagnostic methods on PD-L1 expression levels were analyzed to address practical issues related to tissue samples used for testing. Results High concordance and interobserver reproducibility were observed with the 28-8, 22C3, and SP263 clinical trial assays for PD-L1 expression on tumor cell membranes, whereas lower PD-L1 expression was detected with SP142. Immune-cell PD-L1 expression was variable and interobserver concordance was poor. Inter- and intratumoral heterogeneity had variable effects on PD-L1 expression. Concordance among LDAs was variable. Conclusion High concordance among 28-8, 22C3, and SP263 when assessing PD-L1 expression on tumor cell membranes suggests possible interchangeability of their clinical use for NSCLC but not for assessment of PD-L1 expression on immune cells. Development of LDAs requires stringent standardization before their recommendation for routine clinical use.
MR thermometry‐based feedback control of laser interstitial thermal therapy at 980 nm (2004)

The computer-controlled thermal therapy system was effective at regulating heating, eliminating carbonization and vaporization, and protecting fiberoptic applicators. MRTI estimation of thermal dose accurately predicted achieved thermal necrosis.
Specificity of the SH2 Domains of SHP-1 in the Interaction with the Immunoreceptor Tyrosine-Based Inhibitory Motif-Bearing Receptor gp49B (1999)

Inhibitory receptors on hemopoietic cells critically regulate cellular function. Despite their expression on a variety of cell types, these inhibitory receptors signal through a common mechanism involving tyrosine phosphorylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM), which engages Src homology 2 (SH2) domain-containing cytoplasmic tyrosine or inositol phosphatases. In this study, we have investigated the proximal signal-transduction pathway of an ITIM-bearing receptor, gp49B, a member of a newly described family of murine NK and mast cell receptors. We demonstrate that the tyrosine residues within the ITIMs are phosphorylated and serve for the association and activation of the cytoplasmic tyrosine phosphatase SHP-1. Furthermore, we demonstrate a physiologic association between gp49B and SHP-1 by coimmunoprecipitation studies from NK cells. To address the mechanism of binding between gp49B and SHP-1, binding studies involving glutathione S-transferase SHP-1 mutants were performed. Utilizing the tandem SH2 domains of SHP-1, we show that either SH2 domain can interact with phosphorylated gp49B. Full-length SHP-1, with an inactivated amino SH2 domain, also retained gp49B binding. However, binding to gp49B was disrupted by inactivation of the carboxyl SH2 domain of full-length SHP-1, suggesting that in the presence of the phosphatase domain, the carboxyl SH2 domain is required for the recruitment of phosphorylated gp49B. Thus, gp49B signaling involves SHP-1, and this association is dependent on tyrosine phosphorylation of the gp49B ITIMs, and an intact SHP-1 carboxyl SH2 domain.
An Experimental and Computational Analysis on the Differential Role of the Positional Isomers of Symmetric Bis-2-(pyridyl)-1H-benzimidazoles as DNA Binding Agents (2007)

Three symmetrical positional isomers of bis-2-(n-pyridyl)-1H-benzimidazoles (n=2, 3, 4) were synthesized and DNA binding studies were performed with these isomeric derivatives. Like bisbenzimidazole compound Hoechst 33258, these molecules also demonstrate AT-specific DNA binding. The binding affinities of 3-pyridine (m-pyben) and 4-pyridine (p-pyben) derivatized bisbenzimidazoles to double-stranded DNA were significantly higher compared to 2-pyridine derivatized benzimidazole o-pyben. This has been established by combined experimental results of isothermal fluorescence titration, circular dichroism, and thermal denaturation of DNA. To rationalize the origin of their differential binding characteristics with double-stranded DNA, computational structural analyses of the uncomplexed ligands were performed using ab initio/Density Functional Theory. The molecular conformations of the symmetric head-to-head bisbenzimidazoles have been computed. The existence of intramolecular hydrogen bonding was established in o-pyben, which confers a conformational rigidity to the molecule about the bond connecting the pyridine and benzimidazole units. This might cause reduction in its binding affinity to double-stranded DNA compared to its para and meta counterparts. Additionally, the predicted stable conformations for p-, m-, and o-pyben at the B3LYP/6-31G* and RHF/6-31G* levels were further supported by experimental pKa determination. The results provide important information on the molecular recognition process of such symmetric head to head bisbenzimidazoles toward duplex DNA.
Expression of a Cloned Human Interleukin-2 cDNA Is Enhanced by the Substitution of a Heterologous mRNA Leader Region (1988)

A cloned interleukin-2 (IL-2) cDNA was poorly expressed in transfected eukaryotic cells. This low expression was only partly relieved by removal of the homopolymer tail present in the 5' leader region of the encoded IL-2 mRNA. However, replacement of the natural IL-2 mRNA 5' noncoding region with a leader element derived from the efficiently translated rat preproinsulin II mRNA resulted in an mRNA molecule that was utilized effectively by the transfected cell. The enhanced expression of this chimeric IL-2 mRNA did not appear to be due to changes in the sequence near the translation initiation codon. These results suggest that the leader elements of efficiently translated mRNAs may be able to confer a higher translational efficiency on heterologous protein coding regions when present in cis.
Hypoxia-induced up-regulation of angiogenin in human malignant melanoma. (1999)

Angiogenesis is essential for tumor progression and metastasis, however, the angiogenesis regulators that are biologically relevant for human melanoma are still unknown. In this study, we analyzed the expression of the potent angiogenic factor angiogenin (ANG) in human melanoma in vitro and in vivo. Four different human melanoma cell lines and two normal melanocytes were kept either under normoxic or hypoxic conditions. After 24 h of hypoxic culture conditions, ANG was up-regulated in the melanoma cell lines but not in normal melanocytes. Induction levels correlated with the metastatic potential of the cell lines. These data were confirmed by Northern blot analysis. In contrast, induction of vascular endothelial growth factor by hypoxia was equally strong in the examined highly aggressive melanoma cell lines and in one nonaggressive cell line. Other angiogenic factors tested as well as the melanoma growth stimulatory activity (Gro-alpha) showed no up-regulation. Thus, in the present study, hypoxia-induced up-regulation in melanoma cells was only observed for ANG and vascular endothelial growth factor. Immunohistochemical studies showed that 8 of 10 melanomas and all 15 metastases were positive for ANG, particularly in the vicinity of small vessels, whereas all benign nevi were negative. Reverse transcription-PCR detected only weak ANG mRNA in nevi but strong signals in primary melanomas and metastases. In conclusion, we demonstrate for the first time enhanced expression of ANG in highly metastatic cell lines as well as in melanomas and metastases in vivo, suggesting that ANG expression is associated with the metastatic potential.
Immunologic abnormalities in chronic fatigue syndrome (1990)

The chronic fatigue syndrome (CFS), formerly known as chronic Epstein-Barr virus syndrome, is a clinical state of some complexity and uncertain etiology. In order to characterize in a comprehensive manner the status of laboratory markers associated with cellular immune function in patients with this syndrome, 30 patients with clinically defined CFS were studied. All of the subjects were found to have multiple abnormalities in these markers. The most consistent immunological abnormality detected among these patients, when compared with normal controls, was low natural killer (NK) cell cytotoxicity. The number of NK cells, as defined by reactivity with monoclonal antibody NKH.1 (CD56), was elevated, but the killing of K562 tumor cells per CD56 cell was significantly diminished. Lymphoproliferative responses after stimulation with phytohemagglutinin and pokeweed mitogen were decreased in most patients when compared with those in normal controls, as was the production of gamma interferon following mitogen stimulation. Lymphocyte phenotypic marker analysis of peripheral blood lymphocytes showed that there were significant differences between patients with CFS and controls. There was an increase in the percentage of suppressor-cytotoxic T lymphocytes, CD8, and a proportionally larger increase in the number of CD8 cells expressing the class II activation marker. Most patients had an elevated number of CD2 cells which expressed the activation marker CDw26. The numbers of CD4 cells and the helper subset of CD4+CD29+ cells in patients with CFS were not different from those in controls. There was, however, a significant decrease in the suppressor inducer subset of CD4+ CD45RA+ cells. The number of B cells, CD20 and CD21, were elevated, as were the numbers of a subset of B cells which coexpressed CD20 and CD5. The patterns of immune marker abnormalities observed was compatible with a chronic viral reactivation syndrome.
Suppression of Efficiency Roll-Off Characteristics in Thermally Activated Delayed Fluorescence Based Organic Light-Emitting Diodes Using Randomly Oriented Host Molecules (2013)

The efficiency roll-off characteristics in highly efficient thermally activated delayed fluorescence (TADF) based organic light-emitting diodes (OLEDs) were effectively suppressed by controlling the molecular orientation of a 4,4′-bis(N-carbazolyl)-1,1′-biphenyl (CBP) host matrix. The hole mobility in the light emitting layer was found to govern the magnitude of this suppression. Three-dimensional finite-difference time-domain calculations and photoluminescence quantum yield measurements revealed that the optical characteristics of the fabricated devices and photophysical properties of the TADF emitter did not affect efficiency roll-off. CBP molecules adopted random orientations when films were fabricated at high temperature (350 K), resulting in low hole mobility, and shifting the recombination zone away from the interface of the emitting layer with the electron transporting layer. When CBP was randomly orientated, efficiency roll-off was suppressed by 30% at a current density of 100 mA cm–2. This result indicates that control of the molecular orientation of the host can allow us to indirectly tune the carrier balance in OLEDs.