gebhart/patrepeval huggingface dataset:
Protein kinase C binding partners (2000)

Members of the protein kinase C family respond to second messengers and are involved in controlling a broad array of cellular functions. The overlapping specificity and promiscuity of these proteins has promoted the view that specific binding proteins constrain individual family members to create the appropriate specificity of action. It is speculated that such protein kinase C-regulator protein interactions affect substrate availability as well as exposure to allosteric activator(s) and that consequent interactions specify cellular location and impose integration with other signaling systems. These predicted features have been realized in the identification of many protein kinase C interacting proteins and examples of these are discussed.
Discovery of M-808 as a Highly Potent, Covalent, Small-Molecule Inhibitor of the Menin–MLL Interaction with Strong In Vivo Antitumor Activity (2020)

Targeting the menin-MLL protein-protein interaction is a new therapeutic strategy for the treatment of acute leukemia carrying MLL fusion (MLL leukemia). We describe herein the structure-based optimization of a class of covalent menin inhibitors, which led to the discovery of M-808 (<b>16</b>) as a highly potent and efficacious covalent menin inhibitor. M-808 effectively inhibits leukemia cell growth at low nanomolar concentrations and is capable of achieving partial tumor regression in an MV4;11 xenograft tumor model in mice at a well-tolerated dose schedule. Determination of the co-crystal structure of M-808 in complex with menin provides a structural basis for their high-affinity, covalent interactions. M-808 represents a promising, covalent menin inhibitor for further optimization and evaluation toward developing a new therapy for the treatment of MLL leukemia.
CRISP: Coarse-Grained Reconfigurable Image Stream Processor for Digital Still Cameras and Camcorders (2008)

To design the hardware for image signal processing pipelines in digital still cameras (DSCs) and video camcoders, it is a dilemma for conventional solutions, such as application-specific integrated circuits (ASICs) and digital signal processors (DSPs), to achieve high processing capability at low cost while maintaining high flexibility for various algorithms. With the observation of the characteristics of image signal-processing pipelines, including the different requirements for different operation modes and the algorithmic similarity of image-processing tasks, a new coarse-grained reconfigurable image stream processor (CRISP) is proposed in this paper. The design idea is to devote low-cost hardware for the requirements in the preview mode and add some hardware resources for higher flexibility and processing capability in the picture-taking mode. With the coarse-grained reconfigurable stage processing elements designed for image signal-processing tasks and the reconfigurable interconnection unit with unified communication protocol, CRISP can be reconfigured as an efficient dedicated hardware in the preview mode, and it can act like a flexible DSP for the picture-taking mode with different contexts. Implementation result shows that the core (die) size is 5 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> (7.72 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ) with TSMC 0.18-mum process, and the power consumption is 218 mW at 1.8 V. At the working frequency of 115 MHz, the processor is capable of processing 11 M-pixel still images at 10 fps for DSCs or 1920 times 1080 video frames at 55 fps for camcorders. CRISP can execute image pipelines 83 times faster than the state-of-the-art DSP with only about one-tenth die size.
ChemInform Abstract: Oligonucleotides Attached to Intercalators, Photoreactive and Cleavage Agents (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Binding of PTEN to Specific PDZ Domains Contributes to PTEN Protein Stability and Phosphorylation by Microtubule-associated Serine/Threonine Kinases (2005)

The tumor suppressor phosphatase PTEN is a key regulator of cell growth and apoptosis that interacts with PDZ domains from regulatory proteins, including MAGI-1/2/3, hDlg, and MAST205. Here we identified novel PTEN-binding PDZ domains within the MAST205-related proteins, syntrophin-associated serine/threonine kinase and MAST3, characterized the regions of PTEN involved in its interaction with distinctive PDZ domains, and analyzed the functional consequences on PTEN of PDZ domain binding. Using a panel of PTEN mutations, as well as PTEN chimeras containing distinct domains of the related protein TPTE, we found that the PTP and C2 domains of PTEN do not affect PDZ domain binding and that the C-terminal tail of PTEN (residues 350-403) provides selectivity to recognize specific PDZ domains from MAGI-2, hDlg, and MAST205. Binding of PTEN to the PDZ-2 domain from MAGI-2 increased PTEN protein stability. Furthermore, binding of PTEN to the PDZ domains from microtubule-associated serine/threonine kinases facilitated PTEN phosphorylation at its C terminus by these kinases. Our results suggest an important role for the C-terminal region of PTEN in the selective association with scaffolding and/or regulatory molecules and provide evidence that PDZ domain binding stabilizes PTEN and targets this tumor suppressor for phosphorylation by microtubule-associated serine/threonine kinases.
Cleavage and conformational changes of tau protein follow phosphorylation during Alzheimer’s disease (2008)

Phosphorylation, cleavage and conformational changes in tau protein all play pivotal roles during Alzheimer's disease (AD). In an effort to determine the chronological sequence of these changes, in this study, using confocal microscopy, we compared phosphorylation at several sites (Ser(199/202/396/404/422)-Thr(205) and the second repeat domain), cleavage of tau (D(421)) and the canonical conformational Alz-50 epitope. While all of these posttranslational modifications are found in neurofibrillary tangles (NFTs) at all stages of the disease, we found significantly higher numbers of phospho-tau positive NFTs when compared with cleaved tau (P = 0.006 in Braak III; P = 0.002 in Braak IV; P = 0.012 in Braak V) or compared with the Alz-50 epitope (P < 0.05). Consistent with these findings, in a double transgenic mice model (Tet/GSK-3beta/VLW) overexpressing the enzyme glycogen synthase kinase-3beta (GSK-3beta) and tau with a triple FTDP-17 mutation (VLW) with AD-like neurodegeneration, phosphorylation at sites Ser(199/202)-Thr(205) was greater than truncated tau. Taken together, these data strongly support the notion that the conformational changes and truncation of tau occur after the phosphorylation of tau. We propose two probable pathways for the pathological processing of tau protein during AD, either phosphorylation and cleavage of tau followed by the Alz-50 conformational change or phosphorylation followed by the conformational change and cleavage as the last step.
Smart Technical Textiles Based on Fiber Optic Sensors (2013)

Smart technical textiles are by definition textiles that can interact with their environment.
They can sense and react to environmental conditions and external stimuli from mechanical, thermal, chemical or other sources. Such textiles are multifunctional or even “intelligent” which is fulfilled by a number of sensors incorporated in the textiles. The embedded sensors are sensitive to various parameters such as temperature, strain, chemical, biological and other substances.
Liquid phase condensation in cell physiology and disease (2017)

Phase transitions are ubiquitous in nonliving matter, and recent discoveries have shown that they also play a key role within living cells. Intracellular liquid-liquid phase separation is thought to drive the formation of condensed liquid-like droplets of protein, RNA, and other biomolecules, which form in the absence of a delimiting membrane. Recent studies have elucidated many aspects of the molecular interactions underlying the formation of these remarkable and ubiquitous droplets and the way in which such interactions dictate their material properties, composition, and phase behavior. Here, we review these exciting developments and highlight key remaining challenges, particularly the ability of liquid condensates to both facilitate and respond to biological function and how their metastability may underlie devastating protein aggregation diseases.
3-Amino-2(1H)-quinolones by Cyclizaion of N-Acylated Anthranilic Acid Derivatives (1997)

Reaction of secondary amines with the N-(iodoacety1)authranilic acid derivatives, 2-(iodoacetylamino)acetophenone and 2-(iodoacety1amino)benzophenone yields 3-amino-2(lf+quinolones in two steps.Analogously heterocondensed 5-amino-6(7H)-pyrazolo[5,4-b]py~idones were prepared.Hydroxyquinolines were subjected to CUOH exchange to give chloroquinolines, which are conveuient for consecutive reactions.4-Hydroxy-and 4-amino-2(1H)-quinolones are known as AMPA-and NMDA-receptor antagonists and are considered for the treatment of neurogenerative diseases.labWe described the synthesis of 2(1H)-quinolones and heterocondensed 2(lf+pyTidones accomplished by Thorpe-Ziegler cyclization 2.3 and at this we were able to show that various patterns of substitution are
How a single amino acid change may alter the immunological information of a peptide (2011)

What types of amino acid substitutions are functionally tolerated in an epitope? This question is of importance because the immunogenicity, pathogenicity, and therapeutic potential of a peptide can be determined by a single amino acid change. As an example, a single amino acid change in the encephalitogenic myelin oligodendrocyte glycoprotein WYRSPFSRVV peptide confers the capacity to ameliorate and reverse experimental autoimmune encephalomyelitis. Currently, no rule is available to predict/explain the functional outcomes of amino acid changes. To address this issue, we examined the role of single amino acid changes in immune responses by applying proteomic similarity analyses to available data. We found that the loss or gain of immunological information in a peptide epitope following an amino acid substitution often is related to a gain or loss in the proteomic similarity. Rare, but significant epitopic sequences become immunologically insignificant when an amino acid change makes them common, repeated sequences. This study confirms that low similarity to the host proteome is a major factor in modulating the immune epitope repertoire.
Electronic structures and enhanced optical properties of blue phosphorene/transition metal dichalcogenides van der Waals heterostructures (2016)

As a fast emerging topic, van der Waals (vdW) heterostructures have been proposed to modify two-dimensional layered materials with desired properties, thus greatly extending the applications of these materials. In this work, the stacking characteristics, electronic structures, band edge alignments, charge density distributions and optical properties of blue phosphorene/transition metal dichalcogenides (BlueP/TMDs) vdW heterostructures were systematically studied based on vdW corrected density functional theory. Interestingly, the valence band maximum and conduction band minimum are located in different parts of BlueP/MoSe2, BlueP/WS2 and BlueP/WSe2 heterostructures. The MoSe2, WS2 or WSe2 layer can be used as the electron donor and the BlueP layer can be used as the electron acceptor. We further found that the optical properties under visible-light irradiation of BlueP/TMDs vdW heterostructures are significantly improved. In particular, the predicted upper limit energy conversion efficiencies of BlueP/MoS2 and BlueP/MoSe2 heterostructures reach as large as 1.16% and 0.98%, respectively, suggesting their potential applications in efficient thin-film solar cells and optoelectronic devices.
Electric-field assisted assembly and alignment of metallic nanowires (2000)

This letter describes an electric-field assisted assembly technique used to position individual nanowires suspended in a dielectric medium between two electrodes defined lithographically on a SiO2 substrate. During the assembly process, the forces that induce alignment are a result of nanowire polarization in the applied alternating electric field. This alignment approach has facilitated rapid electrical characterization of 350- and 70-nm-diameter Au nanowires, which had room-temperature resistivities of approximately 2.9 and 4.5×10−6 Ω cm.
Respiratory and circulatory activities in carotid body-resected humans (1992)

The respiratory and circulatory activities of patients who underwent carotid body resection (CBR) more than two decades ago were reviewed. No significant ventilatory response to continuous hypoxia was observed. However, in response to stimulation of peripheral chemoreceptors, transient hyperventilation occurred before hypoxemic blood arrived at the central nervous system (single-breath test), which indicated the presence of weak peripheral chemosensitivity. Because of this slight residual peripheral chemosensitivity, which was found shortly after the operation and apparently remained more or less unchanged for greater than 20 years, peripheral chemoreceptor activity, which has been reported in other animal species, does not seem to have returned. Delayed hypoxic hyperventilation reported in dogs and cats with CBR was not observed. Hypoxia significantly depressed the ventilatory response to CO2, but the delayed ventilatory depression with time that has been demonstrated in normal subjects did not occur. In our circulatory studies, hypoxia augmented the heart rate and slightly depressed the stroke volume and total peripheral resistance in the systemic circulation but induced no appreciable changes in arterial blood pressure or cardiac output. We used these results to partition the relative contributions to the overall circulatory response of carotid body stimulation, pulmonary inflation, and other modifying influences. From these calculations, it was inferred that the carotid body reflex plays a dominant role in vascular activities whereas the pulmonary inflation reflex dominates in cardiac activities in humans.
Standardization of Quantitative Imaging: The Time Is Right, and 18F-FDG PET/CT Is a Good Place to Start (2011)

Enhanced techniques have made quantitative medical imaging increasingly important to clinical research ( [1][1], [2][2]). Performance expectations, and particularly the rigor with which performance is statistically characterized, are high in the research context. Even though individual factors may
Inhibition of DKK1 Activity Is Associated with Increased Osteoblast Numbers and Bone Formation, Reduced Osteoclast Activity and Inhibition of Tumor Growth in the SCID-rab Model for Primary Myeloma. (2005)

Abstract We have previously demonstrated that myeloma (MM) cells produce the Wnt signaling antagonist, Dickkopf-1 (DKK1), and that DKK1 inhibits differentiation of osteoblasts (Tian et al. NEJM 2003). This is thought to result in an uncoupling process that may lead to induction of lytic bone disease in MM and possibly promote tumor growth. The aim of this study was to investigate the role of DKK1 in our established SCID-rab model for primary MM. Growth of primary MM in this system is restricted to the implanted bone and associated with typical disease manifestations including increased osteoclast activity, reduced osteoblast numbers and induction of osteolytic bone disease (Yata &amp; Yaccoby, Leukemia 2004). In this study, SCID-rab mice were engrafted with MM cells expressing DKK1 (assessed by global gene expression profiling) from 8 patients. The level of DKK1 expression was correlated with numbers of MRI and x-ray focal lesions in these patients. Following establishment of MM growth, as monitored by weekly measurement of human monoclonal immunoglobulins (hIg) in mouse sera and radiographically, mice were injected subcutaneously into the surrounding area of the implanted bone with neutralizing antibody (AB, R&amp;D) against DKK1 (polyclonal AB: n=4, 50 μg/injection/2 days; monoclonal AB: n=4, 100 μg/injection/day) or control IgG AB, for 4–6 weeks. Whereas bone mineral density (BMD) in control mice was reduced by 7.1%±4.6% from pre-treatment levels, BMD in mice treated with anti-DKK1 was increased by 5.6%±6.7% from pre-treatment levels (p&amp;lt;0.03). The bone anabolic effect of DKK1 AB was also visualized on x-rays and was detected in mice transplanted with cells from patients with low and high degree of bone disease. Histological examination revealed that myelomatous bones of DKK1 AB-treated mice had increased numbers of osteocalcin-expressing osteoblasts (45±5 vs. 16±2 per mm bone in control mice, p&amp;lt;0.02) and reduced number of multinucleated TRAP-expressing multinucleated osteoclasts (5±3 vs. 13±2 per mm bone in control mice, p&amp;lt;0.004). These results support recent reports demonstrating the critical involvement of Wnt signaling in osteoblasts in regulation of osteoclastogenesis as well (Glass et al., Dev. Cell 2005). Whereas in control mice myeloma burden increased in all experiments, anti-DKK1 treatment was associated with reduced tumor growth from pre-treatment levels in 4 of 8 experiments. Overall, myeloma tumor burden increased by 325%±122% and 165%±53% from pre-treatment levels in control and DKK1 AB-treated mice, respectively (p&amp;lt;0.03). Furthermore, bone marrow areas with locally high numbers of differentiated osteoblasts were depleted of myeloma cells in DKK1 AB-treated hosts. We conclude that DKK1 is a key player in myeloma bone disease and that blocking DKK1 activity in myelomatous bones reduces osteolytic bone resorption, increases bone formation and helps control myeloma progression.
Colliding beam fusion reactor space propulsion system (2000)

We describe a space propulsion system based on the Colliding Beam Fusion Reactor (CBFR). The CBFR is a high-beta, field-reversed, magnetic configuration with ion energies in the range of hundreds of keV. Repetitively-pulsed ion beams sustain the plasma distribution and provide current drive. The confinement physics is based on the Vlasov-Maxwell equation, including a Fokker Planck collision operator and all sources and sinks for energy and particle flow. The mean azimuthal velocities and temperatures of the fuel ion species are equal and the plasma current is unneutralized by the electrons. The resulting distribution functions are thermal in a moving frame of reference. The ion gyro-orbit radius is comparable to the dimensions of the confinement system, hence classical transport of the particles and energy is expected and the device is scaleable. We have analyzed the design over a range of 106−109 Watts of output power (0.15–150 Newtons thrust) with a specific impulse of, Isp∼106 sec. A 50 MW propulsion system might involve the following parameters: 4-meters diameter×10-meters length, magnetic field ∼7 Tesla, ion beam current ∼10 A, and fuels of either D-He3,P-B11,P-Li6,D-Li6, etc.
Transcranial Magnetic Resonance Imaging– Guided Focused Ultrasound Surgery of Brain Tumors (2010)

Although significant hurdles remain, these findings are a major step forward in producing a completely noninvasive alternative to surgical resection for brain disorders.
Significant association between the tau gene A0/A0 genotype and Parkinson's disease (2000)

A significant association between the tau gene A0/A0 genotype and progressive supranuclear palsy has been reported recently. To determine if the presence of a tau polymorphism could constitute a risk factor for the development of sporadic and familial Parkinson's disease, a dinucleotide repeat marker at intron 11 was genotyped in 152 patients with PD, 52 patients with Alzheimer's disease, and 150 healthy controls. We detected a significant difference in A0 allelic frequency in the Parkinson's disease group (79.27%) compared with the control group (71%) and the Alzheimer's disease group (73.07%). Individuals homozygous for the A0 allele were also detected significantly more frequently in the Parkinson's disease group (63.8%) compared with the control group (52.66%) and the Alzheimer's disease group (48.07%). These results suggest a possible involvement of the tau gene in the pathogenesis of some cases of Parkinson's disease.
Evaluation of Potent Odorants in Dill Seed and Dill Herb (Anethum graveolens L.) by Aroma Extract Dilution Analysis (1991)

ABSTRACT The volatile components of dill seed and herb were analyzed by gas chromatography‐olfactometry which revealed the odorants having highest odor‐activity value (ratio of concentration to odor threshold). (+)‐(4S)‐Carvone was the predominent odorant of dill seed. (+)‐(3R,4S,8S)‐3,9‐Epoxy‐1‐p‐menthene, methyl 2‐methylbutanoate, (+)‐(4S)‐α‐phellandrene and myristicin were the most important odorants of dill herb. Calculation of odor‐activity values on the basis of quantitative and odor threshold data confirmed results of the aroma extract dilution analysis.
Development and Application of a Broadly Sensitive Dried-Blood-Spot-Based Genotyping Assay for Global Surveillance of HIV-1 Drug Resistance (2010)

As antiretroviral therapy (ART) is scaled up in resource-limited countries, surveillance for HIV drug resistance (DR) is vital to ensure sustained effectiveness of first-line ART. We have developed and applied a broadly sensitive dried-blood-spot (DBS)-based genotyping assay for surveillance of HIV-1 DR in international settings. In 2005 and 2006, 171 DBS samples were collected under field conditions from newly diagnosed HIV-1-infected individuals from Malawi (n = 58), Tanzania (n = 60), and China (n =53). In addition, 30 DBS and 40 plasma specimens collected from ART patients in China and Cameroon, respectively, were also tested. Of the 171 DBS analyzed at the protease and RT regions, 149 (87.1%) could be genotyped, including 49 (81.7%) from Tanzania, 47 (88.7%) from China, and 53 (91.4%) from Malawi. Among the 70 ART patient samples analyzed, 100% (30/30) of the Chinese DBS and 90% (36/40) of the Cameroonian plasma specimens were genotyped, including 8 samples with a viral load of <400 copies/ml. The results of phylogenetic analyses indicated that the subtype, circulating recombinant form (CRF), and unique recombinant form (URF) distribution was as follows: 73 strains were subtype C (34%), 37 were subtype B (17.2%), 24 each were CRF01_AE or CRF02_AG (11.2% each), 22 were subtype A1 (10.2%), and 9 were unclassifiable (UC) (4.2%). The remaining samples were minor strains comprised of 6 that were CRF07_BC (2.8%), 5 that were CRF10_CD (2.3%), 3 each that were URF_A1C and CRF08_BC (1.4%), 2 each that were G, URF_BC, and URF_D/UC (0.9%), and 1 each that were subtype F1, subtype F2, and URF_A1D (0.5%). Our results indicate that this broadly sensitive genotyping assay can be used to genotype DBS collected from areas with diverse HIV-1 group M subtypes and CRFs. Thus, the assay is likely to become a useful screening tool in the global resistance surveillance and monitoring of HIV-1 where multiple subtypes and CRFs are found.
RANDOMIZED TRIAL EVALUATING SHORT-TERM EFFECTS OF INTRAVITREAL RANIBIZUMAB OR TRIAMCINOLONE ACETONIDE ON MACULAR EDEMA AFTER FOCAL/GRID LASER FOR DIABETIC MACULAR EDEMA IN EYES ALSO RECEIVING PANRETINAL PHOTOCOAGULATION (2011)

The addition of 1 intravitreal triamcinolone injection or 2 intravitreal ranibizumab injections in eyes receiving focal/grid laser for diabetic macular edema and panretinal photocoagulation is associated with better visual acuity and decreased macular edema by 14 weeks. Whether continued long-term intravitreal treatment is beneficial cannot be determined from this study.