gebhart/patrepeval huggingface dataset:
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers (2018)

Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.
Dynamic Supernodes in Sparse Cholesky Update/Downdate and Triangular Solves (2009)

The supernodal method for sparse Cholesky factorization represents the factor L as a set of supernodes, each consisting of a contiguous set of columns of L with identical nonzero pattern. A conventional supernode is stored as a dense submatrix. While this is suitable for sparse Cholesky factorization where the nonzero pattern of L does not change, it is not suitable for methods that modify a sparse Cholesky factorization after a low-rank change to A (an update/downdate, Ā = A ± WW T ). Supernodes merge and split apart during an update/downdate. Dynamic supernodes are introduced which allow a sparse Cholesky update/downdate to obtain performance competitive with conventional supernodal methods. A dynamic supernodal solver is shown to exceed the performance of the conventional (BLAS-based) supernodal method for solving triangular systems. These methods are incorporated into CHOLMOD, a sparse Cholesky factorization and update/downdate package which forms the basis of x = A\b MATLAB when A is sparse and symmetric positive definite.
Deoxyribonucleoside Cyclic N-Acylphosphoramidites as a New Class of Monomers for the Stereocontrolled Synthesis of Oligothymidylyl- and Oligodeoxycytidylyl- Phosphorothioates (2000)

A simple and straightforward synthesis of the pyrimidine 2‘-deoxyribonucleoside cyclic N-acylphosphoramidites RP-1 and SP-1 is described. Specifically, (±)-2-amino-1-phenylethanol 2 was chemoselectively N-acylated to 4 by treatment with ethyl fluoroacetate 3 followed by reaction with hexaethylphosphorus triamide to afford the cyclic N-acylphosphoramidite 5 as a mixture of diastereomeric rotamers (5a and 5b). Condensation of N4-benzoyl-5‘-O-(4,4‘-dimethoxytrityl)-2‘-deoxycytidine 8 with 5 in the presence of 1H-tetrazole gave, after silica gel chromatography, pure RP-1 and SP-1. 31P NMR studies indicated that when RP-1 or SP-1 is reacted with 3‘-O-acetylthymidine and N,N,N‘,N‘-tetramethylguanidine in CD3CN, the dinucleoside phosphotriester SP-9 or RP-9 is formed in near quantitative yield with total P-stereospecificity (δP 144.2 or 143.9 ppm, respectively). Sulfurization of SP-9 or RP-9 generated the P-stereodefined dinucleoside phosphorothioate RP-11 or SP-11 (δP 71.0 or 71.2 ppm, respectively). The 2‘-deoxycytidine cyclic N-acylphosphoramidite derivatives RP-1 and SP-1 were subsequently applied to the solid-phase synthesis of [RP,RP]- and [SP,SP]-trideoxycytidilyl diphosphorothioate d(CPSCPSC), and [RP,SP,RP]-tetradeoxycytidilyl triphosphorothioate d(CPSCPSCPSC). Following deprotection, reversed-phase (RP) HPLC analysis of these oligonucleotide analogues showed a single peak for each oligomer. By comparison, RP-HPLC analysis of purified P-diastereomeric d(CPSCPSC) and d(CPSCPSCPSC) prepared from standard 2-cyanoethyl deoxyribonucleoside phosphoramidites exhibited 4 and 8 peaks, respectively, each peak corresponding to a specific P-diastereomer (see Figure 3A). The thymidine cyclic N-acylphosphoramidite derivatives RP-14 and SP-14 were also prepared, purified, and used successfully in the solid-phase synthesis of [RP]11-d[(TPS)11T]. Thus, the application of deoxyribonucleoside cyclic N-acyl phosphoramidites to P-stereocontrolled synthesis of oligodeoxyribonucleoside phosphorothioates may offer a compelling alternative to the methods currently used for such syntheses.
Low Loss and Highly Birefringent Hollow-Core Photonic Crystal Fiber (2006)

A hollow-core photonic crystal fiber design is proposed which enables both low-loss and polarization-maintained signal propagation. The design relies on an arrangement of antiresonant features positioned on the glass ring that surrounds the air core.
Two‐Dimensional Nanoarchitectures for Lithium Storage (2012)

Two dimensional nanoarchitectures are of great interest in lithium storage for energy-storage devices, in particular lithium-ion batteries, due to its shortened paths for fast lithium ion diffusion and large exposed surface offering more lithium-insertion channels. Their competitive lithium-storage features provide huge potentials to develop next-generation high-performance lithium-ion batteries. This review is devoted to the recent progress in the fabrication of innovative 2D structures with various synthetic strategies and their applications for lithium storage in lithium-ion batteries. These 2D architectures are categorized into six styles, i.e., nanoporous nanosheets, ultrathin nanosheets, flower-like structures assembled by nanosheets, sandwich-like nanosheets, corrugated nanosheets, and nanosheets with specific facets. Based on the lithium-storage manner, we further summerized their electrochemical performance for lithium storage with four classified themes including surface Li storage, zero or low-strain Li storage, volume-variation Li storage and synergic-effect Li storage. Finally, the outlook and perspective on 2D lithium-storage materials is concisely provided.
Adverse Mortality Effect of Central Sympathetic Inhibition with Sustained-Release Moxonidine in Patients with Heart Failure (MOXCON) (2003)

Early termination of the trial limited conclusions regarding the long-term effects of central sympathetic inhibition. Nonetheless, the excess early mortality and morbidity suggest the likelihood of an adverse effect of moxonidine SR and raise concerns regarding the efficacy of generalized sympathetic inhibition in heart failure.
Origin of electric dipoles formed at high-k/SiO2 interface (2009)

A model for the physical origin of the dipole formed at high-k/SiO2 interface is proposed. In our model, an areal density difference of oxygen atoms at high-k/SiO2 interface is considered as an intrinsic origin of the dipole formation. The oxygen movement from higher-oxygen-density side to a lower-oxygen-density one will determine the direction of interface dipole. The bonding energy relaxation at the interface explains why the oxygen density difference is the driving force of the oxygen movement. Our model enables the prediction of the dipole directions for candidate gate dielectrics, including those so far not reported.
One application of SOI memory cell-memory array (2002)

A way of designing a flash memory array is illustrated. We explain the general principles of operation of a SOI flash memory cell which uses the standard way to write information and a novel method to erase information. Performances obtained by this analysis are applied to a simple memory array. An example of a layout design of 16/spl times/16 memory chip is included.
Treatment of Plasma Cell Dyscrasias With Thalidomide and Its Derivatives (2003)

Many studies have confirmed the activity of thalidomide in MM, as well as an improved response with dexamethasone. Newer thalidomide derivatives with reduced toxicity (neuropathy, teratogenicity) are also promising. Thalidomide with dexamethasone may now represent the treatment of choice for previously untreated patients. Further studies with these and other novel agents early in the course of myeloma may improve complete remission rates and frequency of long-term control.
Solid State Chemistry and its Applications (1984)

Solid State Chemistry and its Applications, 2nd Edition: Student Edition is an extensive update and sequel to the bestselling textbook Basic Solid State Chemistry, the classic text for undergraduate teaching in solid state chemistry worldwide. Solid state chemistry lies at the heart of many significant scientific advances from recent decades, including the discovery of high-temperature superconductors, new forms of carbon and countless other developments in the synthesis, characterisation and applications of inorganic materials. Looking forward, solid state chemistry will be crucial for the
Interleukin (IL)-15Rα–deficient Natural Killer Cells Survive in Normal but Not IL-15Rα–deficient Mice (2003)

Natural killer (NK) cells protect hosts against viral pathogens and transformed cells. IL-15 is thought to play a critical role in NK cell development, but its role in the regulation of peripheral NK cells is less well defined. We now find that adoptive transfer of normal NK cells into mice lacking the high affinity interleukin (IL)-15 receptor, IL-15Ralpha, surprisingly results in the abrupt loss of these cells. Moreover, IL-15Ralpha-deficient NK cells can differentiate successfully in radiation bone marrow chimera bearing normal cells. Finally, adoptively transferred IL-15Ralpha-deficient NK cells survive in normal but not IL-15Ralpha-deficient mice. These findings demonstrate that NK cell-independent IL-15Ralpha expression is critical for maintaining peripheral NK cells, while IL-15Ralpha expression on NK cells is not required for this function.
Template‐based protein structure modeling using TASSERVMT (2011)

Template-based protein structure modeling is commonly used for protein structure prediction. Based on the observation that multiple template-based methods often perform better than single template-based methods, we further explore the use of a variable number of multiple templates for a given target in the latest variant of TASSER, TASSER(VMT) . We first develop an algorithm that improves the target-template alignment for a given template. The improved alignment, called the SP(3) alternative alignment, is generated by a parametric alignment method coupled with short TASSER refinement on models selected using knowledge-based scores. The refined top model is then structurally aligned to the template to produce the SP(3) alternative alignment. Templates identified using SP(3) threading are combined with the SP(3) alternative and HHEARCH alignments to provide target alignments to each template. These template models are then grouped into sets containing a variable number of template/alignment combinations. For each set, we run short TASSER simulations to build full-length models. Then, the models from all sets of templates are pooled, and the top 20-50 models selected using FTCOM ranking method. These models are then subjected to a single longer TASSER refinement run for final prediction. We benchmarked our method by comparison with our previously developed approach, pro-sp(3) -TASSER, on a set with 874 easy and 318 hard targets. The average GDT-TS score improvements for the first model are 3.5 and 4.3% for easy and hard targets, respectively. When tested on the 112 CASP9 targets, our method improves the average GDT-TS scores as compared to pro-sp3-TASSER by 8.2 and 9.3% for the 80 easy and 32 hard targets, respectively. It also shows slightly better results than the top ranked CASP9 Zhang-Server, QUARK and HHpredA methods. The program is available for download at http://cssb.biology.gatech.edu/.
Amino acids Lys-Asp-Asp-Lys-Pro-Val402 in the Ca(2+)-ATPase of cardiac sarcoplasmic reticulum are critical for functional association with phospholamban. (1994)

Phospholamban interacts with SERCA2 (sarco/endoplasmic reticulum calcium ATPase isoform 2) but not SERCA3. The use of chimeric SERCA2/SERCA3 molecules has revealed that amino acids 336-412 in the phosphorylation domain of SERCA2 are essential for functional association with phospholamban (Toyofuku, T., Kurzydlowski, K., Tada, M., and MacLennan, D. H. (1993) J. Biol. Chem. 268, 2809-2815). When mutations were made in SERCA2 between amino acids 336 and 412 and the mutants were coexpressed with phospholamban, only mutation of amino acids Lys397 to Val402 affected phospholamban association with the Ca(2+)-ATPase. A chimeric Ca(2+)-ATPase, CH2, was created in which the phosphorylation domain of SERCA2 was replaced with that of SERCA3, disrupting functional interaction with phospholamban. The SERCA3 sequence QGEQLV402 was then mutated to the corresponding SERCA2 sequence, KDD-KPV402, and to the sequence KGEKPV402, resulting in restoration of functional interaction with phospholamban. Mutation to KGNKPV402 or to QGEQPV402 did not restore functional interaction with phospholamban. These results demonstrate that amino acids Lys397-Val402 comprise the interaction site with phospholamban in SERCA2, and probably also in SERCA1, and that the appropriate balance of charged and hydrophobic residues is an important feature of the interaction.
Pseudothionin‐St1, a potato peptide active against potato pathogens (1994)

A 5-kDa polypeptide, pseudothionin Solanum tuberosum 1 (Pth-St1), which was active against Clavibacter michiganensis subspecies sepedonicus, a bacterial pathogen of potatoes, has been purified from the buffer-insoluble fraction of potato tubers by salt extraction and HPCL. Pth-St1 was also active against other potato pathogens tested (Pseudomonas solanacearum and Fusarium solani). The N-terminal amino acid sequence of this peptide was identical (except for a N/H substitution at position 2) to that deduced from a previously reported cDNA sequence (EMBL accession number X-13180), which had been misclassified as a Browman-Birk protease inhibitor. Pth-St1 did not inhibit either trypsin or insect alpha-amylase activities, and, in contrast with true thionins, did not affect cell-free protein synthesis or beta-glucuronidase activity. Northern-blot and tissue-print analyses showed that steady-state mRNA levels were highest in flowers (especially in petals), followed by tubers (especially in the epidermal cell layers and in leaf primordia), stems and leaves. Infection of leaves with a bacterial pathogen suspended in 10 mM MgCl2 switched off the gene, whereas mock inoculation with 10 mM MgCl2 alone induced higher mRNA levels.
Multiple antibiotic susceptibility associated with inactivation of the prc gene (1992)

A Tn5 insertion which led to increased susceptibility to multiple drugs, including tetracycline, chloramphenicol, nalidixic acid, erythromycin, spectinomycin, norfloxacin, and novobiocin, was identified in Escherichia coli. Cloning and sequence studies showed that the insertion was in the previously identified prc gene at min 40.4. The prc product is known to function as a protease linked to processing of penicillin-binding protein 3 and lambda repressor and when absent to allow some leakage of periplasmic constituents. Complementation studies with the prc gene on plasmids showed complete recovery of parental levels of susceptibility to all drugs except chloramphenicol, with which only partial reversion to wild-type levels was observed.
Sortase A localizes to distinct foci on the Streptococcus pyogenes membrane (2008)

Cell wall peptidoglycan-anchored surface proteins are essential virulence factors in many gram-positive bacteria. The attachment of these proteins to the peptidoglycan is achieved through a transpeptidation reaction, whereby sortase cleaves a conserved C-terminal LPXTG motif and covalently attaches the protein to the peptidoglycan precursor lipid II. It is unclear how the sorting reaction is regulated spatially and what part sortase localization plays in determining the distribution of surface proteins. This is mainly the result of inadequate immunofluorescence techniques required to resolve these issues in certain bacterial pathogens. Here we describe the utilization of the phage lysin PlyC to permeabilize the cell wall of Streptococcus pyogenes to antibodies, thereby allowing the localization of sortase A using deconvolution immunofluorescence microscopy. We find that sortase localizes within distinct membranal foci, the majority of which are associated with the division septum and colocalize with areas of active M protein anchoring. Sortase distribution to the new septum begins at a very early stage, culminates during septation, and decays after division is completed. This implies that the sorting reaction is a dynamic, highly regulated process, intimately associated with cell division. The ability to study cytoplasmic and membrane antigens using deconvolution immunofluorescence microscopy will facilitate further study of cellular processes in S. pyogenes.
Prevention of experimental autoimmune encephalomyelitis in Lewis rats by a novel fungal source of γ-linolenic acid (1995)

The effects of oral administration of linoleic- and gamma-linolenic-acid-rich oils on the clinical and histopathological manifestations of experimental autoimmune encephalomyelitis (EAE) were investigated in Lewis rats 7 d post-inoculation. gamma-Linolenic-acid-rich fungal (Mucor javanicus) oil at 500 mg/kg body weight abrogated clinical and histological signs of EAE although at doses of 200 and 1000 mg/kg body weight it was only effective in delaying the onset of clinical disease. Linoleic-acid-rich safflower-seed (Carthamus tinctorius) oil at 500, 750 and 1000 mg/kg body weight decreased the severity of clinical EAE disease in a dose-dependent manner. The effects in healthy animals of orally administered gamma-linolenic-acid-rich fungal oil (500 mg/kg body weight) and linoleic-acid-rich safflower-seed oil (1000 mg/kg body weight) on splenic lymphocyte proliferative responses to the T-cell mitogen concanavalin-A (Con A), membrane fatty acid composition and lymphocyte sub-sets were also studied. Both treatments enhanced the T-cell proliferative response to Con A. There was no significant effect on the proportion of splenic CD8+ or CD4+ lymphocytes. Compositional studies on splenic phosphoglyceride fatty acids of oil-treated animals suggest the above responses were associated with increases in spleen dihomo-gamma-linolenic and arachidonic acids.
Persistent Crimean-Congo hemorrhagic fever virus infection in the testes and within granulomas of non-human primates with latent tuberculosis (2019)

Crimean-Congo hemorrhagic fever (CCHF) is the most medically important tick-borne viral disease of humans and tuberculosis is the leading cause of death worldwide by a bacterial pathogen. These two diseases overlap geographically, however, concurrent infection of CCHF virus (CCHFV) with mycobacterial infection has not been assessed nor has the ability of virus to persist and cause long-term sequela in a primate model. In this study, we compared the disease progression of two diverse strains of CCHFV in the recently described cynomolgus macaque model. All animals demonstrated signs of clinical illness, viremia, significant changes in clinical chemistry and hematology values, and serum cytokine profiles consistent with CCHF in humans. The European and Asian CCHFV strains caused very similar disease profiles in monkeys, which demonstrates that medical countermeasures can be evaluated in this animal model against multiple CCHFV strains. We identified evidence of CCHFV persistence in the testes of three male monkeys that survived infection. Furthermore, the histopathology unexpectedly revealed that six additional animals had evidence of a latent mycobacterial infection with granulomatous lesions. Interestingly, CCHFV persisted within the granulomas of two animals. This study is the first to demonstrate the persistence of CCHFV in the testes and within the granulomas of non-human primates with concurrent latent tuberculosis. Our results have important public health implications in overlapping endemic regions for these emerging pathogens.
How do helix–helix interactions help determine the folds of membrane proteins? Perspectives from the study of homo‐oligomeric helical bundles (2003)

The final, structure-determining step in the folding of membrane proteins involves the coalescence of preformed transmembrane helices to form the native tertiary structure. Here, we review recent studies on small peptide and protein systems that are providing quantitative data on the interactions that drive this process. Gel electrophoresis, analytical ultracentrifugation, and fluorescence resonance energy transfer (FRET) are useful methods for examining the assembly of homo-oligomeric transmembrane helical proteins. These methods have been used to study the assembly of the M2 proton channel from influenza A virus, glycophorin, phospholamban, and several designed membrane proteins-all of which have a single transmembrane helix that is sufficient for association into a transmembrane helical bundle. These systems are being studied to determine the relative thermodynamic contributions of van der Waals interactions, conformational entropy, and polar interactions in the stabilization of membrane proteins. Although the database of thermodynamic information is not yet large, a few generalities are beginning to emerge concerning the energetic differences between membrane and water-soluble proteins: the packing of apolar side chains in the interior of helical membrane proteins plays a smaller, but nevertheless significant, role in stabilizing their structure. Polar, hydrogen-bonded interactions occur less frequently, but, nevertheless, they often provide a strong driving force for folding helix-helix pairs in membrane proteins. These studies are laying the groundwork for the design of sequence motifs that dictate the association of membrane helices.
Electrotransformation of Clostridium acetobutylicum ATCC 824 using high-voltage radio frequency modulated square pulses (2000)

Molecular biological improvement of industrial solventogenic clostridia could be enhanced by a higher efficiency of electrotransformation. In this research, we used a new approach to determine the frequency spontaneously generated by Clostridium acetobutylicum ATCC 824 cells during the application of a square high-voltage pulse. Once the frequency of 100 kHz was determined we transformed clostridial cells with pSOS84 plasmid DNA using radio-frequency modulated high-voltage square pulses (electric field strength 12 kVcm-1; pulse duration 22.5 ms; frequency of pulse modulation 100 kHz) to reach an efficiency exceeding 106 transformants microg-1 of plasmid DNA. We propose a possible role for cellular membrane structures in affecting the transformation yield.
Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor‐independent mechanism (2005)

We evaluated the ability of cannabidiol (CBD) to impair the migration of tumor cells stimulated by conditioned medium. CBD caused concentration-dependent inhibition of the migration of U87 glioma cells, quantified in a Boyden chamber. Since these cells express both cannabinoid CB1 and CB2 receptors in the membrane, we also evaluated their engagement in the antimigratory effect of CBD. The inhibition of cell was not antagonized either by the selective cannabinoid receptor antagonists SR141716 (CB1) and SR144528 (CB2) or by pretreatment with pertussis toxin, indicating no involvement of classical cannabinoid receptors and/or receptors coupled to Gi/o proteins. These results reinforce the evidence of antitumoral properties of CBD, demonstrating its ability to limit tumor invasion, although the mechanism of its pharmacological effects remains to be clarified.