gebhart/patrepeval huggingface dataset:
Optimized linker sequences for the expression of monomeric and dimeric bispecific single-chain diabodies (2001)

Bispecific single-chain diabodies (scDb) consist of the variable heavy and light chain domains of two antibodies connected by three linkers. The structure of an scDb in the V(H)-V(L) orientation is V(H)A-linkerA-V(L)B-linkerM-V(H)B-linkerB-V(L)A, with linkers A and B routinely chosen to be 5-6 residues and linker M 15-20 residues. Here, we applied display of scDb on filamentous phage to analyse the composition of optimal linker sequences. The three linkers were randomized in length and sequence using degenerated triplets coding for only six hydrophilic or aliphatic amino acids (Thr, Ser, Asp, Asn, Gly, Ala). Antigen-binding clones were then isolated by one to two rounds of selection on the two different antigens recognized by the bispecific scDb. Using an scDb directed against carcinoembryonic antigen (CEA) and beta-galactosidase (Gal), we found that monomeric scDb had a preferred length of 15 or more amino acid residues for the middle linker M and of 3-6 residues for the linkers A and B. No obvious bias towards a preferred linker sequence was observed. Reduction of the middle linker below 13 residues led to the formation of dimeric scDb, which most likely results from interchain pairing between all the V(H) and V(L) domains. Dimeric scDb were also formed by fragments possessing a long linker M and linkers A and B of 0 or 1 residue. We assume that these dimeric scDb are formed by intrachain pairing of the central variable domains and interchain pairing of the flanking variable domains. Thus, the latter molecules represent a novel format of bispecific and tetravalent molecules. The described strategy allows for the isolation of both optimized and minimal linker sequences for the assembly of monomeric or dimeric single-chain diabodies.
Micromechanical Detection of Proteins Using Aptamer-Based Receptor Molecules (2004)

We report label-free protein detection using a microfabricated cantilever-based sensor that is functionalized with DNA aptamers to act as receptor molecules. The sensor utilizes two adjacent cantilevers that constitute a sensor/reference pair and allows direct detection of the differential bending between the two cantilevers. One cantilever is functionalized with aptamers selected for Taq DNA polymerase while the other is blocked with single-stranded DNA. We have found that the polymerase-aptamer binding induces a change in surface stress, which causes a differential cantilever bending that ranges from 3 to 32 nm depending on the ligand concentration. Protein recognition on the sensor surface is specific and has a concentration dependence that is similar to that in solution.
HYDROGEN IN SEMICONDUCTORS (2006)

▪ Abstract Hydrogen strongly affects the properties of electronic materials. Interstitial monatomic hydrogen is always electrically active and usually counteracts the prevailing conductivity of the semiconductor. In some materials, however, hydrogen acts as a source of doping. We describe the mechanisms that govern interactions between hydrogen and semiconductors, including monatomic hydrogen, hydrogen molecules, and hydrogen-related complexes. We also discuss the behavior of hydrogen on the surface and its role in the growth process. The fundamental principles are illustrated with practical examples, many of them for the technologically relevant case of gallium nitride.
Monolithically integrated isolators based on nanowire-grid polarizers (2005)

We developed a free-space monolithically integrated semi-isolator based on a new type of wire-grid polarizer, nanowire-grid polarizer. The nanowire-grid polarizer, which has an active structure with a total thickness of about 1 μm, was fabricated directly onto a Faraday magnetooptic rotator by nanofabrication processes. Full free-space isolators based on the integrated semi-isolators were assembled which achieved very low insertion loss (/spl sim/0.2 dB) and high isolation (/spl sim/35 dB). The integrated semi-isolator enables fabrication of the full isolator more efficient and, furthermore, it allows a smaller footprint which is crucial for applications requiring a compact footprint.
Improved Pattern Transfer in Soft Lithography Using Composite Stamps (2002)

Composite stamps composed of two layersa stiff layer supported by a flexible layerextend the capabilities of soft lithography to the generation of 50−100-nm features. The preparation of these stamps was adapted from a procedure originally developed by Schmid et al. (Macromolecules 2000, 33, 3042) for microcontact printing. This paper demonstrates how pattern transfer using other soft lithographic techniquesmicromolding in capillaries, microtransfer molding, and phase-shifting lithographycan be improved using two-layer stamps relative to stamps made of Sylgard 184 poly(dimethylsiloxane).
Additive viability-loss following hsp70/hsc70 double interference and Hsp90 inhibition in two breast cancer cell lines (2007)

Hsp70 is an anti-apoptotic protein over-expressed in breast, lung, rectum, endometrial and bladder cancers. In this study, we investigated the impact of Hsp70 protein expression, and its close family member, Hsc70, on breast cancer cell viability and on the activity of the Hsp90/Hsp70 chaperone complex, a complex whose activity is important for the survival of cancer cells and tumours. The simultaneous blockade of Hsp70, Hsc70 and Hsp90 was most efficient in reducing breast cancer cell viability, as compared to their respective separate blockades. However, while the Hsp90 inhibition alone correlates with lost cell viability and reduced Hsp90/Hsp70 chaperone complex activity, the single or mixed reduction in Hsp70 and Hsc70 expression displayed no ability to reduce the activity of the Hsp90/Hsp70 chaperone complex. The results suggest that targeting both the Hsp70 family, as well as the Hsp90 protein will have an additive negative effect on cancer cell survival, even though their pathways of action are separate.
Genetic Changes in Sporadic Keratocystic Odontogenic Tumors (Odontogenic Keratocysts) (2007)

Little is known about the genetic background of keratocystic odontogenic tumors (KCOT, odontogenic keratocysts). Our aim was to characterize genomic aberrations in sporadic KCOT using cDNA-expression arrays and array-comparative genomic hybridization. For cDNA-expression arrays, 10 KCOT specimens and 20 fetal tooth germs were studied. Quantitative real-time reverse-transcription/polymerase chain-reaction and immunohistochemical studies were also undertaken. Several genes were over-expressed in 12q13, including cytokeratin 6B (KRT6B) ( approximately 10-fold), epidermal growth factor receptor ERBB3 (approximately 4.7-fold), and glioma-associated oncogene homologue 1 (GLI1) (approximately 5- to 12-fold). One amplicon (approximately 0.7 Mega base pairs [Mbp]), covering several genes involved in the regulation of cell growth, was found in 12q13.2. Deletions were found in 3q13.1, 5p14.3, and 7q31.3, including the cell-adhesion-related gene cadherin 18 (CDH18) and leukocyte cell adhesion molecule (ALCAM, MEMD). Over-expressed and amplified genes in 12q13, also reported in several other tumors and cell lines, may contribute to the persistent growth characteristics of KCOT.
The significance of p53 autoantibodies in the serum of patients with breast cancer. (1996)

Serum p53 autoantibodies were studied in 82 patients with Stage 1 or 2 breast cancer using an ELISA assay. Tissue expression of p53 in these patients was also examined. High levels of serum p53 autoantibodies were detected in 48% (39/82) patients, while 23% (19/82) were tissue positive. Patients with high serum p53 autoantibodies levels were not significantly different to those with low levels with respect to, tissue p53, tumour grade, size, stage or oestrogen receptor status. Tissue immunoreactivity for p53 was significantly associated with tumour grade and negative oestrogen receptor status. Patients in both groups were followed for a median of over five years but the presence of p53 autoantibodies in serum was not prognostic with respect to disease free interval or survival. In this study detection of p53 autoantibodies in serum does not correlate with any of the usual tumour related prognostic factors, nor does it correlate with clinical outcome.
Monocyte intracellular cytokine production during human endotoxaemia with or without a secondin vitroLPS challenge: effect of RWJ-67657, a p38 MAP-kinase inhibitor, on LPS-hyporesponsiveness (2002)

In the present study, we investigated the effect of RWJ-67657, a p38 MAP kinase inhibitor, upon in vivo LPS-induced monocyte cytokine production and upon monocyte LPS-hyporesponsiveness. Thirty minutes before a single injection of LPS (4 ng/kg BW), healthy male volunteers received a single oral dose of RWJ-67657 at increasing dosages (0-1400 mg). Blood samples (pre-medication, 3, 6 and 24 h after LPS) were immediately incubated with LPS (reflecting LPS-hyporesponsiveness) or without LPS (reflecting in vivo monocyte stimulation) for 4 h at 37 degrees C. Following red blood cells lysis and white blood cell permeabilization, cells were labelled with alpha-CD14-FITC and alpha-IL-1beta, alpha-IL-12 or alpha-TNFalpha (PE-labelled), fixed, and analysed using flow cytometry. In vivo LPS injection resulted in an increased percentage of circulating monocytes producing IL-1beta, TNFalpha and IL-12 only at 3 h after the LPS injection. This was dose-dependently inhibited by RWJ-67657 treatment. LPS-hyporesponsiveness to in vitro LPS treatment was most prominent at 3 and 6 h after the in vivo LPS injection; compared with pre-medication monocytes, at these intervals a reduced percentage of monocytes produced IL-1beta, TNFalpha or IL-12 after the in vitro LPS stimulus. At t = 6 h, this LPS-hyporesponsiveness could dose-dependently be inhibited by RWJ-67657 treatment of the volunteers. We therefore conclude that p38 MAP kinase inhibition with RWJ-67657 inhibited monocyte production of cytokines following in vivo LPS injection. Treatment with RWJ-67657 also reversed the LPS-hyporesponsiveness. Whether this result can be extended to the clinical situation remains to be elucidated. Patients with sepsis or an otherwise high risk for multi-organ failure are potential study groups.
Ad hoc OLAP: expression and evaluation (1999)

Users frequently formulate complex data analysis queries in order to identify interesting trends, make unusual patterns stand out, or verify hypotheses. Being able to express these data mining queries concisely is of major importance not only from the user's, but also from the system's point of view. Recent research in OLAP has focused on datacubes and their applications; however expression and processing of ad hoc decision support queries has been given very little attention. We present an appropriate framework for these queries and introduce a syntactic construct to support it. This SQL extension allows most OLAP queries, such as pivoting, complex intra- and inter-group comparisons, trends and hierarchical comparisons, to be expressed in a compact, intuitive and simple manner. This succinct representation of a complex OLAP query translates immediately to a novel, simple and efficient evaluation algorithm. We show how to optimize, analyze and parallelize this algorithm and discuss issues such as multiple query analysis and scaling. We present several experimental results of real life queries that show orders of magnitude of performance improvement. We argue that this tight coupling between representation and algorithm is essential to efficient processing of ad hoc OLAP queries.
Superior tumor protection induced by a cellular vaccine carrying a tumor-specific T helper epitope by genetic exchange of the class II-associated invariant chain peptide. (2000)

Efficient loading of MHC class II molecules with a T helper epitope of choice can be achieved through genetic exchange of the MHC class II-associated invariant chain peptide (CLIP) sequence with a sequence encoding the helper peptide. We have now used this method to engineer a cellular vaccine that continuously expresses a tumor-specific helper epitope in a defined costimulatory context. We provide evidence (a) that this cellular vaccine induces peptide-specific helper T cells in vivo that are functional in protecting mice from challenge with a highly aggressive tumor, (b) that this vaccine can directly prime tumor-specific helper T cells in vivo, and (c) that this cellular vaccine is superior compared with similar cells loaded with synthetic T helper peptide in inducing tumor protection. In conclusion, cellular vaccines for activation of antigen-specific helper T cells can be greatly improved by the introduction of invariant chain constructs containing a T helper epitope by class II-associated invariant chain peptide exchange.
Novel application of Phi29 DNA polymerase: RNA detection and analysis in vitro and in situ by target RNA-primed RCA (2009)

We present a novel Phi29 DNA polymerase application in RCA-based target RNA detection and analysis. The 3'-->5' RNase activity of Phi29 DNA polymerase converts target RNA into a primer and the polymerase uses this newly generated primer for RCA initiation. Therefore, using target RNA-primed RCA, padlock probes may be targeted to inner RNA sequences and their peculiarities can be analyzed directly. We demonstrate that the exoribonucleolytic activity of Phi29 DNA polymerase can be successfully applied in vitro and in situ. These findings expand the potential for detection and analysis of RNA sequences distanced from 3'-end.
High-Resolution Imaging and Spectroscopy at High Pressure: A Novel Liquid Cell for the Transmission Electron Microscope (2015)

We demonstrate quantitative core-loss electron energy-loss spectroscopy of iron oxide nanoparticles and imaging resolution of Ag nanoparticles in liquid down to 0.24 nm, in both transmission and scanning transmission modes, in a novel, monolithic liquid cell developed for the transmission electron microscope (TEM). At typical SiN membrane thicknesses of 50 nm the liquid-layer thickness has a maximum change of only 30 nm for the entire TEM viewing area of 200×200 µm.
Cellular immunity and immunotherapy of brain tumors (2004)

Factors influencing the host immune response to central nervous system (CNS) tumors are not yet well understood. This review will outline what is known about anti-tumor immune responses against CNS tumors and describe how advances in our knowledge of basic immunology may be applied to brain tumor immunotherapy. We will first focus on cellular immune system interactions involved in peripheral anti-tumor immune responses. Then, we will discuss characteristics of tumors arising within the confines of the CNS that distinguish them from peripheral neoplasms, emphasizing immune defects that seem to limit or curtail specific anti-tumor immunity against brain tumors. Finally, the current state of immune-based treatment paradigms and future directions will be discussed, paying particular attention to adoptive cellular immunotherapy and tumor vaccine approaches for the treatment of malignant gliomas.
Chirality index, molecular overlay and biological activity of diastereoisomeric mosquito repellents (2005)

Abstract Both 1‐methylisopropyl 2‐(2‐hydroxyethyl)piperidine‐1‐carboxylate, (Picaridin ® ) and cyclohex‐3‐enyl 2‐methylpiperidin‐1‐yl ketone (AI3‐37220; 220) have two asymmetric centers, and the four diastereoisomers of each compound are known to have differing degrees of mosquito‐repellent activity according to quantitative behavioral assays conducted at the United States Department of Agriculture. Computational chemistry was used to identify the structural and configurational basis for repellent activity. Molecular overlay of the optimized geometries of the lowest energy conformers of the diastereoisomers was investigated to elucidate the role of chiral centers in 220 and Picaridin. It was found that the presence of a chiral carbon alpha to the nitrogen with the S configuration in the piperidine ring is essential to the three‐dimensional arrangement of the atoms of the pharmacophore for effective repellent activity. Copyright © 2005 Society of Chemical Industry
AMINOACYL tRNA SYNTHETASES: GENERAL SCHEME OF STRUCTURE-FUNCTION RELATIONSHIPS IN THE POLYPEPTIDES AND RECOGNITION OF TRANSFER RNAS (1987)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Following G‐quartet formation by UV‐spectroscopy (1998)

Oligodeoxynucleotides which include stretches of guanines form a well-known tetrameric structure. We show that the recording of reversible absorbance changes at 295 nm allows to precisely monitor intramolecular guanine (G)-quartet formation and dissociation. Accurate Tm and thermodynamic values could be easily extracted from the data, whereas classical recordings at 260 nm led to a much larger uncertainty and in extreme cases, to completely inaccurate measurements. This inverted denaturation profile was observed for all G-quartet-forming oligonucleotides studied so far. This technique is very useful in all cases where intramolecular or intermolecular quadruplex formation is suspected.
P53 deficiency produces fewer regenerating spermatogenic tubules after irradiation (1996)

The survival of clonogenic spermatogonia was assessed by scoring regenerating tubules at 35 days after irradiation, in the p53 null, heterozygote and wild-type mouse. Survival levels in the p53 null mouse after doses between 6 and 16 Gy were reduced by a factor of 3-4 compared with the levels in the heterozygote or wild-type mouse, which responded similarly. However the radiosensitivity of the cells was similar in all three types of mice, and was characterised by a D0 = 1.7 Gy. A two-dose experimental protocol was used to show that the reduced level of survival in the null mouse at day 35 after irradiation was compatible with the interpretation that there were fewer functional radioresistant clonogenic spermatogonia in the testis of the unirradiated null mouse by about a factor of 3 compared with that in the testis of the wild-type. The lower cell number was similar to the number deduced in other mice (BDF1), where the cells were much more resistant (D0 = 3.2 +/- 0.2 Gy). It is concluded that the lack of p53 causes a reduced level of tubule regeneration at 35 days after irradiation. This is probably not due to cellular radiosensitization, but possibly to a change in the stem cell cycle phase distribution resulting in a smaller proportion of resistant stem cells, which are assayed after high doses.
Low temperature thermal oxidation sharpening of microcast tips (1992)

The authors report the fabrication of sharp tips by casting a tip material into a sharpened silicon mold whose original shape was modified by the growth of a nonuniform, low temperature, thermal oxide. The addition of the oxide layer is the only significant difference between this process and processes currently being used by the majority of commercial producers of atomic force microscope force sensing cantilevers. While commercially available molded tips typically have radii of curvature of approximately 500 Å and aspect ratios of 0.5 or less, tips made in the modified molds have radii of curvature as low as 110 Å and aspect ratios of 0.95. This technique is useful when sharpness, uniformity, and low cost are required.
Estimation non biaisée de décalages subpixelaires sur des images SPOT (2001)

L'estimation non biaisee, avec une precision inferieure au pixel, du decalage entre deux images SPOT est un enjeu majeur pour certaines applications; une des principales difficultes etant due a la faible dimension des imagettes pour lesquelles le decalage peut etre considere constant. Des problemes de biais ont ete mis en evidence et l'objectif de ce travail est d'etudier les origines potentielles du biais constate, tant du point de vue du modele d'observation que de celui des methodes utilisees, puis de proposer une methode d'estimation non biaisee du decalage.
Augmented Ultrasonic Data for Machine Learning (2021)

Abstract Flaw detection in non-destructive testing, especially for complex signals like ultrasonic data, has thus far relied heavily on the expertise and judgement of trained human inspectors. While automated systems have been used for a long time, these have mostly been limited to using simple decision automation, such as signal amplitude threshold. The recent advances in various machine learning algorithms have solved many similarly difficult classification problems, that have previously been considered intractable. For non-destructive testing, encouraging results have already been reported in the open literature, but the use of machine learning is still very limited in NDT applications in the field. Key issue hindering their use, is the limited availability of representative flawed data-sets to be used for training. In the present paper, we develop modern, deep convolutional network to detect flaws from phased-array ultrasonic data. We make extensive use of data augmentation to enhance the initially limited raw data and to aid learning. The data augmentation utilizes virtual flaws—a technique, that has successfully been used in training human inspectors and is soon to be used in nuclear inspection qualification. The results from the machine learning classifier are compared to human performance. We show, that using sophisticated data augmentation, modern deep learning networks can be trained to achieve human-level performance.
Experimental myasthenia gravis in congenic mice. Sequence mapping and H‐2 restriction of T helper epitopes on the α subunits of Torpedo californica and murine acetylcholine receptors (1991)

Immunization of mice with nicotinic acetylcholine receptor from Torpedo electric organ (TAChR) causes a disease similar to human myasthenia gravis (experimental autoimmune myasthenia gravis, EAMG). Susceptibility to EAMG correlates with the H-2 haplotype. In this study we used overlapping synthetic peptide corresponding to the complete sequences of the alpha subunits from TAChR and murine muscle AChR (MAChR) to map T helper epitopes in congenic murine strains of different H-2 haplotype. C57BL/6 and BALB/B mice (highly susceptible to EAMG) and BALB/c and CB17 mice (less susceptible to EAMG), immunized with TAChR, developed similar anti-TAChR antibody titers and L3T4+ (T helper) cell sensitization. Different sequence segments of the TAChR alpha subunit were recognized by L3T4+ cells from strains of H-2b and H-2d haplotype. The sequence segments recognized by the H-2d strains have the highest predicted propensity to form amphipatic alpha helices, while those recognized by the H-2b strains do not. We investigated whether in EAMG T helper cells cross-react with autologous AChR sequences, and a true break of the tolerance occurs. Overlapping synthetic peptides, corresponding to the complete sequence of MAChR alpha subunit, were used to test L3T4+ cell from mice immunized with TAChR. L3T4+ cell strains did not cross-react with any murine peptide sequence, while L3T4+ cells from H-2d mice were strongly stimulated by the peptide sequence Ma alpha 304-322, which is very similar to the homologous Torpedo peptide.