gebhart/patrepeval huggingface dataset:
The yin yang of bacterial polysaccharides: lessons learned from B. fragilis PSA (2011)

Over the past several years, there have been remarkable advances in our understanding of how commensal organisms shape host immunity. Although the full cast of immunogenic bacteria and their immunomodulatory molecules remains to be elucidated, lessons learned from the interactions between bacterial zwitterionic polysaccharides (ZPSs) and the host immune system represent an integral step toward better understanding how the intestinal microbiota effect immunologic changes. Somewhat paradoxically, ZPSs, which are found in numerous commensal organisms, are able to elicit both proinflammatory and immunoregulatory responses; both these outcomes involve fine-tuning the balance between T-helper 17 cells and interleukin-10-producing regulatory T cells. In this review, we discuss the immunomodulatory effects of the archetypal ZPS, Bacteroides fragilis PSA. In addition, we highlight some of the opportunities and challenges in applying these lessons in clinical settings.
Lack of association between an interleukin-1 receptor antagonist gene polymorphism and ulcerative colitis. (1997)

No association of a polymorphism in the interleukin-1 receptor antagonist gene with ulcerative colitis could be identified in this southern German population. The findings of an earlier study reporting an increased frequency of allele 2, particularly in patients with pancolitis, could not be confirmed.
2K: A Dynamic, Component-Based Operating System for Rapidly Changing Environments (1998)

Modern, distributed computing systems need to cope continuously with changes. We identify two kinds of changes: low frequency infrastructural changes, such as software upgrade; and frequent changes in the execution environment, such asnetwork bandwidth, memory availability. This paper proposes 2K, a component-based operating system architecture for rapidly changing environments. In 2K, adaptation is driven by architectural awareness: the system software includes models of its own structure, state, and behavior. Change in the dynamic structure of the system triggers adaptation. To implement adaptation, 2K incorporates a re ective middleware layer that admits dynamic customization through the dynamic loading of components and modi cation of object mechanisms such as method dispatch. The architecture also addresses adaptation in response to software and hardware evolution through code distribution, implemented using the active networking model. Prototype implementations of 2K ideas had provided encouraging results. We also present an application study, identify problems that arose while implementing the application on a traditional system, and analyze how 2K features would alleviate those problems.
A rapid FISH technique for quantitative microscopy. (1994)

Results of quantitative microscopy for fluorescence in situ hybridization (FISH) signals with repetitive DNA probes (pUC 1.77 and D15Z1) are reported. A nonenzymatic hybridization technique was applied using fluorescein-12-dUTP labeled DNA probes and a buffer system not containing any formamide or equivalent chemical denaturing agents. Following thermal denaturation, the renaturation time was reduced to less than 30 min. The number of wash steps was reduced to one. For the pUC 1.77 probe, the major binding sites (chromosome 1) were distinguished from the minor binding sites by means of fluorescence intensity and spot size. The intensity variation of the two brightest FISH spots (major binding sites) in the same metaphase was 19% for 15 min renaturation time and 16% for 30 min renaturation time. For the D15Z1 probe, generally four bright spots were visible and tentatively assigned according to chromosome length and centromere position (chromosomes 15 and 9). The intensity variation of each two homologues in the same metaphase spread showed a coefficient of variation of 47% (15 min) and 22% (30 min) for chromosome 15, and 19% (15 min) and 15% (30 min) for chromosome 9. The results indicate that the applied technique can considerably accelerate the FISH procedure and is suited for quantitative microscopy.
Return-oriented rootkits: bypassing kernel code integrity protection mechanisms (2009)

Protecting the kernel of an operating system against attacks, especially injection of malicious code, is an important factor for implementing secure operating systems. Several kernel integrity protection mechanism were proposed recently that all have a particular shortcoming: They cannot protect against attacks in which the attacker re-uses existing code within the kernel to perform malicious computations. In this paper, we present the design and implementation of a system that fully automates the process of constructing instruction sequences that can be used by an attacker for malicious computations. We evaluate the system on different commodity operating systems and show the portability and universality of our approach. Finally, we describe the implementation of a practical attack that can bypass existing kernel integrity protection mechanisms. 1
Cytogenetic findings in a prospective series of patients with DiGeorge anomaly. (1988)

High-resolution cytogenetics analysis of peripheral blood lymphocytes was done prospectively on 27 of 28 patients with features of DiGeorge anomaly. Twenty-two patients (81%) had normal chromosome studies with no detectable deletion in chromosome 22. Five patients (18%) had demonstrable chromosome abnormalities. Three patients had monosomy 22q11, one due to a 4q;22q translocation, one due to a 20q;22q translocation, and one due to an interstitial deletion of 22q11. One patient had monosomy 10p13, and one patient had monosomy 18q21.33, although the latter had subsequent resolution of T-cell defects. These findings are consistent with the heterogeneity of DiGeorge anomaly but confirm the association with monosomy 22q11 in some cases. However, monosomy 10p13 may also lead to this phenotype. Because of these associated chromosome findings, cytogenetic analyses should be done on patients with suspected DiGeorge anomaly. This is particularly important since many of the abnormalities involving chromosome 22 are translocations that can be familial with a higher recurrence risk. Since only one subtle, interstitial deletion of chromosome 22 was observed, it is not clear whether high-resolution cytogenetic analysis is cost beneficial for all such patients.
Localized Hypersensitivity and Late Coronary Thrombosis Secondary to a Sirolimus-Eluting Stent (2004)

The known pharmacokinetic elution profile of Cypher stents and the presence of polymer fragments surrounded by giant cells and eosinophils suggest that a reaction to the polymer may have caused late stent thrombosis. Careful long-term follow-up of patients with vessel enlargement after Cypher stent placement is recommended.
PFGE and YAC analysis of the Arabidopsis genome (1990)

Procedures for the preparation, analysis, and cloning of large DNA molecules from Arabidopsis thaliana are described. Root callus protoplasts are used to prepare large DNA molecules in agarose plugs or in liquid. Large DNA preparations can be used both for restriction enzyme analysis of the Arabidopsis genome and for molecular cloning of large segments of DNA into yeast using artificial chromosome vectors. Size selection of ligation products from pulsed-field gels has allowed for the cloning of YACs with an average insert size of 0.25 Mbp; yeast artificial chromosomes range in size from 0.07 to 0.7 Mbp. PFGE and blot hybridization analyses of Arabidopsis DNA-containing yeast artificial chromosomes demonstrated that both unique and highly repeated DNA sequences are represented. The roles of PFGE and yeast artificial chromosome cloning methods for physical mapping of the Arabidopsis genome are discussed.
A Drosophila gene encoding a protein resembling the human beta-amyloid protein precursor. (1989)

We have isolated genomic and cDNA clones for a Drosophila gene resembling the human beta-amyloid precursor protein (APP). This gene produces a nervous system-enriched 6.5-kilobase transcript. Sequencing of cDNAs derived from the 6.5-kilobase transcript predicts an 886-amino acid polypeptide. This polypeptide contains a putative transmembrane domain and exhibits strong sequence similarity to cytoplasmic and extracellular regions of the human beta-amyloid precursor protein. There is a high probability that this Drosophila gene corresponds to the essential Drosophila locus vnd, a gene required for embryonic nervous system development.
The role of endosome destabilizing activity in the gene transfer process mediated by cationic lipids (1997)

We used a 32P-labeled pCMV-CAT plasmid DNA to estimate the DNA uptake efficiency and unlabeled pCMV-CAT plasmid DNA to quantify the CAT activity after transfection of COS cells using each of the three following cationic compounds: [1] vectamidine (3-tetradecylamino-N-tert-butyl-N'-tetradecylpropionamidine, and previously described as diC14-amidine [1]), [2] lipofectin (a 1:1 mixture of N-(1-2,3-dioleyloxypropyl)-N,N,N-triethylammonium (DOTMA) and dioleylphosphatidylethanolamine (DOPE)), and [3] DMRIE-C (a 1:1 mixture of N-[1-(2,3-dimyristyloxy)propyl]-N,N-dimethyl-N-(2-hydroxyethyl) ammonium bromide (DMRIE) and cholesterol). Surprisingly, a high CAT activity was observed with vectamidine although the DNA uptake efficiency was lower as compared to lipofectin and DMRIE-C. Transmission electron microscopy (TEM) revealed endocytosis as the major pathway of DNA-cationic lipid complex entry into COS cells for the three cationic lipids. However, the endosomal membrane in contact with complexes containing vectamidine or DMRIE-C often exhibited a disrupted morphology. This disruption of endosomes was much less frequently observed with the DNA-lipofectin complexes. This comparison of the three compounds demonstrate that efficient transfection mediated by cationic lipids is not only correlated to their percentage of uptake but also to their ability to destabilize and escape from endosomes.
Potent neutralization of SARS-CoV-2 in vitro and in an animal model by a human monoclonal antibody (2020)

Effective therapies are urgently needed for the SARS-CoV-2/COVID19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from eight large phage-displayed Fab, scFv and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. One high affinity mAb, IgG1 ab1, specifically neutralized live SARS-CoV-2 with exceptional potency as measured by two different assays. It competed with human angiotensin-converting enzyme 2 (hACE2) for binding to RBD suggesting a competitive mechanism of virus neutralization. IgG1 ab1 protected transgenic mice expressing hACE2 from high-titer intranasal SARS-CoV-2 challenge (105 plaque forming units). Another antibody, VH ab5 did not compete with hACE2 and ab1, and did not neutralize SARS-CoV-2 although its affinity was comparable to that of ab1. The ab1 sequence has relatively low number of somatic mutations indicating that ab1-like antibodies could be quickly elicited during natural SARS-CoV-2 infection or by RBD-based vaccines. IgG1 ab1 does not have developability liabilities, and thus has potential for therapy and prophylaxis of SARS-CoV-2 infections. The rapid identification (within 6 days) of potent mAbs shows the value of large antibody libraries for response to public health threats from emerging microbes.
The zinc fingers of human poly(ADP-ribose) polymerase are differentially required for the recognition of DNA breaks and nicks and the consequent enzyme activation. Other structures recognize intact DNA. (1990)

The recognition of double-stranded DNA breaks and single-stranded nicks by human poly(ADP-ribose) polymerase and the consequent enzymic activation were examined using derivatives of the enzyme expressed in Escherichia coli. The N-terminal 162 residues encompass two zinc fingers. Deletion or mutation of the first finger results in a loss of activation by DNA with either single-stranded or double-stranded damage. Destruction of the second finger reduces activation by double-stranded DNA breaks only slightly, but eliminates activation by single-stranded DNA nicks. These data suggest that activation by single-stranded DNA nicks requires two zinc fingers, but activation by double-stranded DNA breaks requires only the finger closer to the N terminus. Variant proteins that lack both zinc fingers are enzymically inactive but still exhibit weak DNA binding, which is independent of DNA damage. Thus, other regions are also capable of binding intact DNA, but the recognition of a strand nick or break which occasions the synthesis of poly(ADP-ribose) specifically requires the zinc fingers.
Misfolded proteins activate Factor XII in humans, leading to kallikrein formation without initiating coagulation (2008)

When blood is exposed to negatively charged surface materials such as glass, an enzymatic cascade known as the contact system becomes activated. This cascade is initiated by autoactivation of Factor XII and leads to both coagulation (via Factor XI) and an inflammatory response (via the kallikrein-kinin system). However, while Factor XII is important for coagulation in vitro, it is not important for physiological hemostasis, so the physiological role of the contact system remains elusive. Using patient blood samples and isolated proteins, we identified a novel class of Factor XII activators. Factor XII was activated by misfolded protein aggregates that formed by denaturation or by surface adsorption, which specifically led to the activation of the kallikrein-kinin system without inducing coagulation. Consistent with this, we found that Factor XII, but not Factor XI, was activated and kallikrein was formed in blood from patients with systemic amyloidosis, a disease marked by the accumulation and deposition of misfolded plasma proteins. These results show that the kallikrein-kinin system can be activated by Factor XII, in a process separate from the coagulation cascade, and point to a protective role for Factor XII following activation by misfolded protein aggregates.
Biochemical and Structural Analysis of the Binding Determinants of a Vascular Endothelial Growth Factor Receptor Peptidic Antagonist (2010)

Cyclic peptide antagonist c[YYDEGLEE]-NH(2), which disrupts the interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), represents a promising tool in the fight against cancer and age-related macular degeneration. Furthermore, coupled to a cyclen derivative, this ligand could be used as a medicinal imaging agent. Nevertheless, before generating such molecular probes, some preliminary studies need to be undertaken in order to define the more suitable positions for introduction of the cyclen macrocycle. Through an Ala-scan study on this peptide, we identified its binding motif, and an NMR study highlights its binding sites on the VEGFR-1D2 Ig-like domain. Guided by the structural relationship results deduced from the effect of the peptides on endothelial cells, new peptides were synthesized and grafted on beads. Used in a pull-down assay, these new peptides trap the VEGFRs, thus confirming that the identified amino acid positions are suitable for further derivatization.
Highly Efficient Photochemical 2‘-Deoxyribonolactone Formation at the Diagonal Loop of a 5-Iodouracil-Containing Antiparallel G-Quartet (2004)

To explore the structure-dependent hydrogen abstraction in antiparallel and parallel G-quartet DNA structures, the photochemical reactivity of 5-iodouracil ((I)U)-containing human telomeric DNA 22-mers was investigated under the 302 nm UV irradiation conditions. We discovered that only antiparallel ODN 4, in which the second T residue in the diagonal loop of the antiparallel G-quartet is substituted with (I)U, was rapidly consumed as compared with parallel ODN 4 and the other (I)U-containing 22-mers under the irradiation conditions. Product analysis of the photolyzate of antiparallel ODN 4 indicated that a 2'-deoxyribonolactone residue was effectively produced at the 5' side of the (I)U residue in the diagonal loop. Photochemical 2'-deoxyribonolactone formation was also found in the (I)U-containing diagonal loop of antiparallel G-quartets d(GGGGTTT(I)UGGGG)(2) and d(GGGGTT(I)UTGGGG)(2), whereas the reaction did not occur at other DNA structures, including the single-stranded form, the loop region of the hairpin, and linear four-stranded G-quartets. The results clearly indicate that this type of 2'-deoxyribonolactone formation efficiently occurrs only in the diagonal loop of the antiparallel G-quartet. Furthermore, we found that 2'-deoxyribonolactone was formed at the (I)U-containing G-rich sequence of the IgG switch regions and the 5' termini of the Rb gene, suggesting the formation of an antiparallel G-quartet with a diagonal loop in these sequences. These results suggest that the present photochemical method can be used as a specific probe for the antiparallel G-quartet with the diagonal loop.
Association of Acetaminophen Hepatotoxicity With Fasting and Ethanol Use (1994)

Acetaminophen hepatotoxicity after a dose of 4 to 10 g/d was associated with fasting and less commonly with alcohol use. Patients who developed hepatoxicity after taking acetaminophen doses of greater than 10 g/d for therapeutic purposes were alcohol users. Acetaminophen hepatotoxicity after an overdose appears to be enhanced by fasting in addition to alcohol ingestion.
A 1V 5mA multimode IEEE 802.15.6/bluetooth low-energy WBAN transceiver for biotelemetry applications (2012)

In recent years there has been significant interest and growth in low-power wireless technologies beyond traditional consumer use cases into medical applications [1]. Previously a bastion for application specific wireless propriety protocols, the WBAN community has worked together to develop a communication standard IEEE802.15.6 optimised for low power devices in and around the human body offering the levels of QoS required for personal medical data. Additionally, the consumer electronic industry has migrated existing standardised wireless protocols such as Bluetooth to meet the demanding low energy yet robust needs of WBAN. This paper presents a transceiver chip for both IEEE802.15.6 Narrow-Band (NB) PHY draft [2] and Bluetooth Low Energy (LE) 4.0 standards as well as proprietary protocols. Multi-mode operation offers the best solution in terms of flexibility and interoperability between devices and networks, and the appropriate protocol can be chosen to optimise power consumption in numerous applications scenarios where data throughput varies dramatically; such as streaming multi-lead ECG or episodic temperature measurements. The chip operates in the 2.36GHz MBANs spectrum, specifically allocated for medical devices, and the worldwide 2.4GHz ISM band. A TX for the 780/868/915/950MHz licence-free bands in China, EU, North America and Japan respectively, is also included. The chip is architected and designed for 5mW peak active power dissipation for compatibility with 1V button cells, hence enabling small-form factor non-intrusive body worn applications.
Indazole-Based Covalent Inhibitors To Target Drug-Resistant Epidermal Growth Factor Receptor (2017)

The specific targeting of oncogenic mutant epidermal growth factor receptor (EGFR) is a breakthrough in targeted cancer therapy and marks a drastic change in the treatment of non-small cell lung cancer (NSCLC). The recurrent emergence of resistance to these targeted drugs requires the development of novel chemical entities that efficiently inhibit drug-resistant EGFR. Herein, we report the optimization process for a hit compound that has emerged from a phenotypic screen resulting in indazole-based compounds. These inhibitors are conformationally less flexible, target gatekeeper mutated drug-resistant EGFR-L858R/T790M, and covalently alkylate Cys797. Western blot analysis, as well as characterization of the binding kinetics and kinase selectivity profiling, substantiates our approach of targeting drug-resistant EGFR-L858R/T790M with inhibitors incorporating the indazole as hinge binder.
FUNCTIONAL OXIDE NANOBELTS: Materials, Properties and Potential Applications in Nanosystems and Biotechnology (2004)

Nanobelt is a quasi-one-dimensional structurally controlled nanomaterial that has well-defined chemical composition, crystallographic structure, and surfaces (e.g., growth direction, top/bottom surface, and side surfaces). This article reviews the nanobelt family of functional oxides, including ZnO, SnO2, In2O3, Ga2O3, CdO, and PbO2 and the relevant hierarchical and complex nanorods and nanowires that have been synthesized by a solid-vapor process. The nanobelts are single crystalline and dislocation free, and their surfaces are atomically flat. The oxides are semiconductors that have been used for fabrication of nanosize functional devices of key importance for nanosystems and biotechnology, such as field-effect transistors, gas sensors, nanoresonators, and nanocantilevers. The structurally controlled ZnO nanobelts that exhibit piezoelectric properties are also reviewed. By controlling growth kinetics, we show the success of growing nanobelt-based novel structures whose surfaces are dominated by the polarized +-(0001) facets. Owing to the positive and negative ionic charges on the zinc- and oxygen-terminated +-(0001) surfaces, respectively, a spontaneous polarization is induced across the nanobelt thickness. As a result, helical nanostructures and nanorings are formed by rolling up single-crystal nanobelts; this phenomenon is a consequence of minimizing the total energy contributed by spontaneous polarization and elasticity. The polar surface-dominated ZnO nanobelts are likely to be an ideal system for understanding piezoelectricity and polarization-induced ferroelectricity at nano-scale and they could have applications as one-dimensional nano-scale sensors, transducers, and resonators.
Cross-resistance analysis of human immunodeficiency virus type 1 variants individually selected for resistance to five different protease inhibitors (1995)

Human immunodeficiency virus type 1 (HIV-1) protease inhibitor-resistant variants, isolated on passage of HIV-1HXB2 in MT-4 cells with five different protease inhibitors, have been examined for cross-resistance to five inhibitors. The protease inhibitors studied were Ro 31-8959, A-77003, XM323, L-735,524, and VX-478. Resistant variants with two to four mutations within their protease sequence and 9- to 40-fold-decreased susceptibility were selected for all five inhibitors within six to eight passes in cell culture. Passage of a zidovudine-resistant mutant in Ro 31-8959 generated a dual reverse transcriptase- and protease-resistant virus. Variants were cloned directly into a modified pHXB2-D infectious clone for cross-resistance analysis. Although the resistant variants selected possessed different combinations of protease mutations for each inhibitor, many showed cross-resistance to the other inhibitors, and one showed cross-resistance to all five inhibitors. Interestingly, some mutants showed increased susceptibility to some inhibitors. Further HIV passage studies in the combined presence of two protease inhibitors demonstrated that in vitro it was possible to delay significantly selection of mutations producing resistance to one or both inhibitors. These studies indicate that there may be some rationale for combining different protease inhibitors as well as protease and reverse transcriptase inhibitors in HIV combination therapy.