gebhart/patrepeval huggingface dataset:
Multidentate Terephthalamidate and Hydroxypyridonate Ligands: Towards New Orally Active Chelators (2011)

The limitations of current therapies for the treatment of iron overload or radioisotope contamination have stimulated efforts to develop new orally bioavailable iron and actinide chelators. Siderophore-inspired tetradentate, hexadentate and octadentate terephthalamidate and hydroxypyridonate ligands were evaluated in vivo as selective and efficacious iron or actinide chelating agents, with several metal loading and ligand assessment procedures, using (59)Fe, (238)Pu, and (241)Am as radioactive tracers. The compounds presented in this study were compared to commercially available therapeutic sequestering agents [deferoxamine (DFO) for iron and diethylenetriaminepentaacetic acid (DPTA) for actinides] and are unrivaled in terms of affinity, selectivity and decorporation efficacy, which attests to the fact that high metal affinity may overcome the low bioavailability properties commonly associated to multidenticity.
Crystal-state structures of Boc-Pro-Leu-Gly-NH2, hemihydrate and two lactam-restricted analogues (1989)

A crystal-state structural analysis of Boc-Pro-Leu-Gly-NH2(2a) hemihydrate and two conformationally restricted analogues that incorporate a γ- or δ-lactam modification at the –Leu-Gly– sequence, (3) and (4) respectively, has been performed by X-ray diffraction. In all three compounds the conformation of the tertiary amide group of the Nα-protecting urethane moiety is cis and the prolyl residue is semi-extended. The basic conformational feature of the published structure of H-Pro-Leu-Gly-NH2(1), the ten-membered ring type-II β-bend structure at the C-terminus, is preserved in the Nα-t-butyloxycarbonyl derivative (2a). However, the γ- and δ-lactam modifications induce drastic changes in the backbone torsion angles of the –Leu-Gly– sequence, eventually promoting the onset of extended conformations.
Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients (2008)

X-linked SCID (SCID-X1) is amenable to correction by gene therapy using conventional gammaretroviral vectors. Here, we describe the occurrence of clonal T cell acute lymphoblastic leukemia (T-ALL) promoted by insertional mutagenesis in a completed gene therapy trial of 10 SCID-X1 patients. Integration of the vector in an antisense orientation 35 kb upstream of the protooncogene LIM domain only 2 (LMO2) caused overexpression of LMO2 in the leukemic clone. However, leukemogenesis was likely precipitated by the acquisition of other genetic abnormalities unrelated to vector insertion, including a gain-of-function mutation in NOTCH1, deletion of the tumor suppressor gene locus cyclin-dependent kinase 2A (CDKN2A), and translocation of the TCR-beta region to the STIL-TAL1 locus. These findings highlight a general toxicity of endogenous gammaretroviral enhancer elements and also identify a combinatorial process during leukemic evolution that will be important for risk stratification and for future protocol design.
Modifizierte Tetrahelicen‐Systeme, III. Zweifach ortho‐verbrückte Triphenylamin‐Derivate (1980)

Abstract Die durch die Gerüsttypen A und B (s. Tab. 2) repräsentierbaren heterocyclischen ( 2a, b sowie 19, 3b – f und 9a – c ) und auch carbocyclischen Naphth[3,2,1‐ de ]anthracen‐Derivate ( 21 – 23 ) sind im stereochemischen Grundzustand helical verdrillt, racemisieren jedoch so rasch, daß ihre freien Racemisierungsenthalpien (Δ G ≠ ⩽ 21 (88) kcal(kJ)/mol) mit Standard‐DNMR‐Methoden bestimmt werden konnten. Nur Abkömmlinge des Verbindungstyps 3 mit relativ großer Brücke Y ( 3a , Y = C(CH 3 ) 2 ; 3g ′, Y = S) weisen höhere Racemisierungsbarrieren auf (Δ G 160 ≠ = 24 (100.4) bzw. 28.4 (119) kcal(kJ)/mol), zu deren Ermittlung klassische Äquilibrierungsmethoden herangezogen werden mußten. Mit den so erhaltenen Ergebnissen wurde die Arbeitshypothese bestätigt, nach der bei Verbindungen vom Typ A bzw. B sowohl Vergrößerung der Brücken Y und/oder X als auch – bei konstanter Peripherie – Verkleinerung des Zentrums Z zum Anwachsen der nichtbindenden Wechselwirkungen im planaren Übergangszustand und damit auch zum Anwachsen der Racemisierungsbarriere führen sollte. Weiterhin wurde anhand zahlreicher Substitutionsprodukte des Verbindungstyps 1 gezeigt, daß hier häufig zufällige Koinzidenzen der 1 H‐NMR‐Signale diastereotoper, aber auch konstitutoper Gruppen auftreten.
Event Stream Processing with Out-of-Order Data Arrival (2007)

Complex event processing has become increasingly important in modern applications, ranging from supply chain management for RFID tracking to real-time intrusion detection. The goal is to extract patterns from such event streams in order to make informed decisions in real-time. However, networking latencies and even machine failure may cause events to arrive out-of-order at the event stream processing engine. In this work, we address the problem of processing event pattern queries specified over event streams that may contain out-of-order data. First, we analyze the problems state-of-the-art event stream processing technology would experience when faced with out-of-order data arrival. We then propose a new solution of physical implementation strategies for the core stream algebra operators such as sequence scan and pattern construction, including stack- based data structures and associated purge algorithms. Optimizations for sequence scan and construction as well as state purging to minimize CPU cost and memory consumption are also introduced. Lastly, we conduct an experimental study demonstrating the effectiveness of our approach.
Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease.Clinical evaluation with special reference to childhood leukemia (1967)

Daunomycin is a new antibiotic in the anthracycline group obtained from Streptomyces peucetius. It consists of a pigmented aglycone (daunomycinone) in glycoside linkage with an amino sugar (daunosamine). Differences in the biological effects of daunomycin, which reacts with DNA, and actinomycin D which complexes with DNA in a different manner to inhibit RNA production, are discussed. The toxic effects of daunomycin are a severe local reaction if the drug extravasates, bone marrow depression resulting in leucopenia, anemia, thrombocytopenia and bleeding, fever, oral ulcers and alopecia. In patients receiving maintenance doses of daunomycin the development of tachypnea, tachycardia pulmonary insufficiency, heart failure and hypotension possibly is associated with daunomycin but the evidence is unclear. Sixty per cent of children with leukemia obtained brief complete or partial hematological remissions from a single course of daunomycin. The remission could be prolonged by maintenance therapy. Daunomycin is temporarily effective in some cases of neuroblastoma, reticulum cell sarcoma and rhabdomyosarcoma.
Conformational inactivation induces immunogenicity of the receptor-binding pocket of a bacterial adhesin (2013)

Inhibiting antibodies targeting receptor-binding pockets in proteins is a major focus in the development of vaccines and in antibody-based therapeutic strategies. Here, by using a common mannose-specific fimbrial adhesin of Escherichia coli, FimH, we demonstrate that locking the adhesin in a low-binding conformation induces the production of binding pocket-specific, adhesion-inhibiting antibodies. A di-sulfide bridge was introduced into the conformationally dynamic FimH lectin domain, away from the mannose-binding pocket but rendering it defective with regard to mannose binding. Unlike the native, functionally active lectin domain, the functionally defective domain was potent in inducing inhibitory monoclonal antibodies that blocked FimH-mediated bacterial adhesion to epithelial cells and urinary bladder infection in mice. Inhibition of adhesion involved direct competition between the antibodies and mannose for the binding pocket. Binding pocket-specific inhibitory antibodies also were abundant in polyclonal immune serum raised against the functionally defective lectin domain. The monoclonal antibodies elicited against the binding-defective protein bound to the high-affinity conformation of the adhesin more avidly than to the low-affinity form. However, both soluble mannose and blood plasma more strongly inhibited antibody recognition of the high-affinity FimH conformation than the low-affinity form. We propose that in the functionally active conformation the binding-pocket epitopes are shielded from targeted antibody development by ligand masking and that strong immunogenicity of the binding pocket is unblocked when the adhesive domain is in the nonbinding conformation.
Automatic web page classification in a dynamic and hierarchical way (2003)

Automatic classification of web pages is an effective way to deal with the difficulty of retrieving information from the Internet. Although there are many automatic classification algorithms and systems that have been proposed, most of them ignore the conflict between the fixed number of categories and the growing number of web pages going into the system. They also require searching through all existing categories to make any classification. We propose a dynamic and hierarchical classification system that is capable of adding new categories as required, organizing the web pages into a tree structure, and classifying web pages by searching through only one path of the tree structure. Our test results show that our proposed single-path search technique reduces the search complexity and increases the accuracy by 6% comparing to related algorithms. Our dynamic-category expansion technique also achieves satisfying results on adding new categories into our system as required.
Structure and Biology of a Carcinoma-associated Mucin, MUC1 (1991)

Although mucins have been studied at the biochemical and biophysical level for some time, attempts to define their structures in detail were only partially successful because of their size and complexity. The advent of monoclonal antibodies reactive with these molecules introduced a new approach to structural studies by defining antigenic epitopes, by allowing purification of the mucin molecules by affinity chromatography, and by providing a means to clone genes coding for the core proteins. By their profile of reactivity with the normal and cancer-associated mucin in a particular tissue, the antibodies also defined a difference in the mucin derived from the two sources. It is now clear that this difference lies in the carbohydrate side chains, as the core proteins are identical. Because the mucins are tumor-associated antigens and the cancer mucins can express epitopes that are relatively tumor specific, this family of molecules is now being intensively studied. There is also considerable interest in elucidating the normal function of the mucin and in determining whether, through an altered structure, this function is subverted in malignancy. In the next few years we should expect that the structure of other mucins will be defined in the same detail as the product of the MUC1 gene. We should also expect to see the continued application of mucin-reactive antibodies in the clinic and the investigation of mucins as agents for immunotherapy of some cancers. As to the function(s) of these molecules, perhaps we will learn enough in the future to make a critical reappraisal of the name.
Oligomeric state of the ZIKV E protein defines protective immune responses (2019)

The current leading Zika vaccine candidates in clinical testing are based on live or killed virus platforms, which have safety issues, especially in pregnant women. Zika subunit vaccines, however, have shown poor performance in preclinical studies, most likely because the antigens tested do not display critical quaternary structure epitopes present on Zika E protein homodimers that cover the surface of the virus. Here, we produce stable recombinant E protein homodimers that are recognized by strongly neutralizing Zika specific monoclonal antibodies. In mice, the dimeric antigen stimulate strongly neutralizing antibodies that target epitopes that are similar to epitopes recognized by human antibodies following natural Zika virus infection. The monomer antigen stimulates low levels of E-domain III targeting neutralizing antibodies. In a Zika challenge model, only E dimer antigen stimulates protective antibodies, not the monomer. These results highlight the importance of mimicking the highly structured flavivirus surface when designing subunit vaccines.
A hierarchy of polynomial time lattice basis reduction algorithms (1987)

We present a hierarchy of polynomial time lattice basis reduction algorithms that stretch from Lenstra, Lenstra, Lovász reduction to Korkine–Zolotareff reduction. Let λ(L) be the length of a shortest nonzero element of a lattice L. We present an algorithm which for k∈N finds a nonzero lattice vector b so that |b|2⩽(6k2)nkλ(L)2. This algorithm uses O(n2(kk+o(k))+n2)log B) arithmetic operations on O(n log B)-bit integers. This holds provided that the given basis vectors b1,…,bn∈Zn are integral and have the length bound B. This algorithm successively applies Korkine–Zolotareff reduction to blocks of length k of the lattice basis. We also improve Kannan's algorithm for Korkine-Zolotareff reduction.
The Human Y Chromosome: A 43-Interval Map Based on Naturally Occurring Deletions (1992)

A deletion map of the human Y chromosome was constructed by testing 96 individuals with partial Y chromosomes for the presence or absence of many DNA loci. The individuals studied included XX males, XY females, and persons in whom chromosome banding had revealed translocated, deleted, isodicentric, or ring Y chromosomes. Most of the 132 Y chromosomal loci mapped were sequence-tagged sites, detected by means of the polymerase chain reaction. These studies resolved the euchromatic region (short arm, centromere, and proximal long arm) of the Y chromosome into 43 ordered intervals, all defined by naturally occurring chromosomal breakpoints and averaging less than 800 kilobases in length. This deletion map should be useful in identifying Y chromosomal genes, in exploring the origin of chromosomal disorders, and in tracing the evolution of the Y chromosome.
Quantum-Dot/Aptamer-Based Ultrasensitive Multi-Analyte Electrochemical Biosensor (2006)

The coupling of aptamers with the coding and amplification features of inorganic nanocrystals is shown for the first time to offer a highly sensitive and selective simultaneous bioelectronic detection of several protein targets. This is accomplished in a single-step displacement assay in connection to a self-assembled monolayer of several thiolated aptamers conjugated to proteins carrying different inorganic nanocrystals. Electrochemical stripping detection of the nondisplaced nanocrystal tracers results in a remarkably low (attomole) detection limit, that is, significantly lower than those of existing aptamer biosensors. The new device offers great promise for measuring a large panel of disease markers present at ultralow levels during early stages of the disease progress.
Expansion of mouse embryonic stem cells on microcarriers (2006)

Embryonic stem (ES) cells have been shown to differentiate in vitro into a wide variety of cell types having significant potential for tissue regeneration. Therefore, the operational conditions for the ex vivo expansion and differentiation should be optimized for large-scale cultures. The expansion of mouse ES cells has been evaluated in static culture. However, in this system, culture parameters are difficult to monitor and scaling-up becomes time consuming. The use of stirred bioreactors facilitates the expansion of cells under controlled conditions but, for anchorage-dependent cells, a proper support is necessary. Cytodex-3, a microporous microcarrier made up of a dextran matrix with a collagen layer at the surface, was tested for its ability to support the expansion of the mouse S25 ES cell line in spinner flasks. The effect of inocula and microcarrier concentration on cell growth and metabolism were analyzed. Typically, after seeding, the cells exhibited a growth curve consisting of a short death or lag phase followed by an exponential phase leading to the maximum cell density of 2.5-3.9 x 10(6) cells/mL. Improved expansion was achieved using an inoculum of 5 x 10(4) cells/mL and a microcarrier concentration of 0.5 mg/mL. Medium replacement allowed the supply of the nutrients and the removal of waste products inhibiting cell growth, leading to the maintenance of the cultures in steady state for several days. These conditions favored the preservation of the S25 cells pluripotent state, as assessed by quantitative real-time PCR and immunostaining analysis.
A Core Cross-Linked Polymeric Micellar Platium(IV) Prodrug with Enhanced Anticancer Efficiency (2013)

A core cross-linked polymeric micellar cisplatin(IV) conjugate prodrug is prepared by attaching the cisplatin(IV) to mPEG-b-PLL biodegradable copolymers to form micellar nanoparticles that can disintegrate to release the active anticancer agent cisplatin(II) in a mild reducing environment. Moreover, in vitro studies show that this cisplatin(IV) conjugate prodrug displays enhanced cytotoxicity against HepG2 cancer cells compared with cisplatin(II). Further studies demonstrate that the high cellular uptake and platinum-DNA adduct of this cisplatin(IV) conjugate prodrug can induce more cancer-cell apoptosis than cisplatin(II), which is responsible for its enhanced anticancer activity.
Probing protein structure by amino acid‐specific covalent labeling and mass spectrometry (2008)

For many years, amino acid-specific covalent labeling has been a valuable tool to study protein structure and protein interactions, especially for systems that are difficult to study by other means. These covalent labeling methods typically map protein structure and interactions by measuring the differential reactivity of amino acid side chains. The reactivity of amino acids in proteins generally depends on the accessibility of the side chain to the reagent, the inherent reactivity of the label and the reactivity of the amino acid side chain. Peptide mass mapping with ESI- or MALDI-MS and peptide sequencing with tandem MS are typically employed to identify modification sites to provide site-specific structural information. In this review, we describe the reagents that are most commonly used in these residue-specific modification reactions, details about the proper use of these covalent labeling reagents, and information about the specific biochemical problems that have been addressed with covalent labeling strategies.
Increased MIBG uptake after transfer of the human norepinephrine transporter gene in rat hepatoma. (2003)

Transduction of the hNET gene enables Morris hepatoma cells to accumulate norepinephrine and MIBG. However, the retention of MIBG is brief; therefore, the absorbed dose of radiation in vivo is not expected to be therapeutically effective.
Effects of pH and polysaccharides on peptide binding to class II major histocompatibility complex molecules. (1991)

The binding of immunogenic peptides to class II major histocompatibility molecules was examined at various pH values. We studied binding of peptides containing residues 52-61 from hen egg lysozyme (HEL) to I-Ak on fixed peritoneal macrophages or to solubilized affinity-purified I-Ak. Optimum binding occurred at pH 5.5-6.0 with accelerated kinetics relative to pH 7.4; equilibrium binding was also higher at pH 5.5-6.0 than at 7.4. Similar enhancement at pH 5-6 was observed for the binding of hemoglobin-(64-76) to I-Ek and of ribonuclease-(41-61) to I-Ak. In contrast, the binding of HEL-(34-45) to I-Ak was minimally enhanced at acid pH. Dissociation of cell-associated or purified peptide-I-Ak complexes was minimal between pH 5.5 and 7.4, with increased dissociation only at or below pH 4.0 [HEL-(46-61)] or pH 5.0 [HEL-(34-45)]. Thus, optimum peptide binding occurs at pH values similar to the endosomal environment, where the complexes appear to be formed during antigen processing. In addition, we examined the effect of a number of polysaccharides on the binding of peptide to I-Ak. None of these competed with the HEL peptide 125I-labeled YE52-61 for binding to I-Ak. [3H]Dextran also failed to bind purified I-Ak. Polysaccharides do not appear to bind to class II major histocompatibility complex molecules, which explains the T-cell independence of polysaccharide antigens.
A 60-GHz fully-integrated Doherty power amplifier based on 0.13-&#x03BC;m CMOS process (2008)

A sixty-gigahertz (60-GHz) Doherty power amplifier (PA) has been designed and implemented on 0.13 mum RF-CMOS for use in an integrated 60-GHz transceiver. The fully-integrated design implements the main and auxiliary amplifiers, matching networks, and input and output transmission line networks on-chip. The prototype operating from a 1.6-V supply exhibits an output referred P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1dB</sub> of 7.0 dB, a P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SAT</sub> of +7.8 dBm, with peak power gain of 13.5 dB, a 3-dB bandwidth of 6.7 GHz, and 3.0 % PAE. The die area is 1.8 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . This amplifier achieves the highest reported figure of merit for power amplifiers of any published millimeter-wave PA on CMOS.
Sensitive Detection of Abnormal Aortic Architecture in Marfan Syndrome With High-Frequency Ultrasonic Tissue Characterization (1995)

These data show that high-frequency ultrasonic tissue characterization sensitively detects changes in vessel wall composition and organization that occur in the aorta of patients with Marfan syndrome. Aortic segments from these patients manifested a significant decrease in integrated backscatter compared with normal aorta (approximately 8 dB, or greater than a 6-fold decrease in scattering). A 15-fold reduction in the ultrasonic anisotropy of Marfan tissue was observed, which suggests a marked disorganization of the 3D architecture of these aortas. These data support the hypothesis that high-frequency ultrasonic tissue characterization may be useful for identifying abnormalities of vessel wall composition, architecture, and material properties.
Statistical Heterospectroscopy, an Approach to the Integrated Analysis of NMR and UPLC-MS Data Sets:  Application in Metabonomic Toxicology Studies (2005)

Statistical heterospectroscopy (SHY) is a new statistical paradigm for the coanalysis of multispectroscopic data sets acquired on multiple samples. This method operates through the analysis of the intrinsic covariance between signal intensities in the same and related molecules measured by different techniques across cohorts of samples. The potential of SHY is illustrated using both 600-MHz 1H NMR and UPLC-TOFMS data obtained from control rat urine samples (n = 54) and from a corresponding hydrazine-treated group (n = 58). We show that direct cross-correlation of spectral parameters, viz. chemical shifts from NMR and m/z data from MS, is readily achievable for a variety of metabolites, which leads to improved efficiency of molecular biomarker identification. In addition to structure, higher level biological information can be obtained on metabolic pathway activity and connectivities by examination of different levels of the NMR to MS correlation and anticorrelation matrixes. The SHY approach is of general applicability to complex mixture analysis, if two or more independent spectroscopic data sets are available for any sample cohort. Biological applications of SHY as demonstrated here show promise as a new systems biology tool for biomarker recovery.
New vaccine development (2002)

Vaccines are hailed as one of the most important public health achievements of the 20th century. 3]