gebhart/patrepeval huggingface dataset:
Crystal structure of human carbonic anhydrase II complexed with ananti-convulsant sugar sulphamate (2002)

The fructose-based sugar sulphamate RWJ-37497, a potent analogue of the widely used anti-epileptic drug topiramate, possesses anti-convulsant and carbonic anhydrase-inhibitory activities. We have studied the binding interactions of RWJ-37497 in the active site of human carbonic anhydrase II by X-ray crystallography. The atomic positions of the enzyme inhibitor complex were refined at a resolution of 2.1 Å (1 Å = 0.1 nm) to the final crystallographic R and Rfree values of 0.18 and 0.23, respectively. The inhibitor co-ordinates to the active-site zinc ion through its oxygen atom and the ionized nitrogen atom of the sulphamate group by replacing the metal-bound water molecules, although the sulphamoyl oxygen atom provides a rather lengthyco-ordination. The 4,5-cyclic sulphate group is positioned in a hydrophobic pocket of the active site, making contacts with the residues Phe-131, Leu-198, Pro-201 and Pro-202. Since the ligand was found to be intact, concerns about RWJ-37947 irreversibly alkylating the enzyme through its 4,5-cyclic sulphate group were dispelled.
Multiphoton Lithography of Nanocrystalline Platinum and Palladium for Site-Specific Catalysis in 3D Microenvironments (2012)

Integration of catalytic nanostructured platinum and palladium within 3D microscale structures or fluidic environments is important for systems ranging from micropumps to microfluidic chemical reactors and energy converters. We report a straightforward procedure to fabricate microscale patterns of nanocrystalline platinum and palladium using multiphoton lithography. These materials display excellent catalytic, electrical, and electrochemical properties, and we demonstrate high-resolution integration of catalysts within 3D defined microenvironments to generate directed autonomous particle and fluid transport.
Intracavity etalon for both optical comb frequency stabilization and super mode noise suppression of harmonically modelocked semiconductor ring laser (2005)

Using an intracavity Pound-Drever-Hall technique, simultaneous optical frequency comb stabilization within &plusmn;3 MHz range and supermode phase noise suppression were demonstrated for a 10 GHz harmonically modelocked semiconductor ring laser resulting in timing jitter of 63.5 fs integrated from 10 Hz to 10 MHz.
Lanthanide-based peptide biosensor to monitor CDK4/cyclin D kinase activity (2017)

We describe a lanthanide biosensor that responds to CDK4 kinase activity in melanoma cell extracts through a significant and dose dependent increase in luminescence, thanks to sensitization of a DOTA[Tb<sup>3+</sup>] complex incorporated into a CDK4 substrate peptide by a unique tryptophan residue in an adjacent phosphoaminoacid binding moiety.
Integrin adhesion profile of human melanoma cells with different metastatic capacities (1993)

Department of Pathology, University Hospital, Nijmegen Department of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
β-Cell Autoantibodies, Human Leukocyte Antigen II Alleles, and Type 1 Diabetes in Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy* (2000)

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by lack of functional products of the autoimmune regulator gene located on chromosome 21q22.3. The patients are at high risk of developing insulin-dependent (type 1) diabetes, but the positive predictive value of GAD65 or islet cell antibodies for type 1 diabetes is only 27%. Autoantibodies against the IA-2 tyrosine phosphatase-like protein (IA-2 ab) or insulin (IAA) have been suggested to be better markers for active ss-cell destruction. We studied these antibodies in sera from 60 Finnish patients with APECED, 12 of whom subsequently developed type 1 diabetes. Four (36%) of the 11 patients for whom we had prediabetic samples had IA-2 ab, and 4 (36%) had IAA. None of the 48 nondiabetics had IAA, and only 2 (4%) had IA-2 ab. Both had the antibodies for years without diabetes. Thus, IA-2 ab or IAA have a low sensitivity (36%), but high specificity (96% or 100%), with a positive predictive value of 67% for type 1 diabetes in patients with APECED. Data for human leukocyte antigen haplotypes were available for 59 of the patients, including 11 diabetics, and for 8 additional nondiabetic Finnish patients. No association between type 1 diabetes and high risk genotypes was seen. None of the 11 patients with type 1 diabetes, but 15 of the 56 (27%; P: < 0.05) nondiabetic patients and 24 of 93 (26%; P: < 0.05) of the control subjects had the DQB1*0602 allele, which is considered protective for type 1 diabetes. This is remarkable, as previously no positive or negative associations have been reported for any disease components of APECED with human leukocyte II antigens.
Integrated gut/liver microphysiological systems elucidates inflammatory inter‐tissue crosstalk (2017)

A capability for analyzing complex cellular communication among tissues is important in drug discovery and development, and in vitro technologies for doing so are required for human applications. A prominent instance is communication between the gut and the liver, whereby perturbations of one tissue can influence behavior of the other. Here, we present a study on human gut-liver tissue interactions under normal and inflammatory contexts, via an integrative multi-organ platform comprising human liver (hepatocytes and Kupffer cells), and intestinal (enterocytes, goblet cells, and dendritic cells) models. Our results demonstrated long-term (>2 weeks) maintenance of intestinal (e.g., barrier integrity) and hepatic (e.g., albumin) functions in baseline interaction. Gene expression data comparing liver in interaction with gut, versus isolation, revealed modulation of bile acid metabolism. Intestinal FGF19 secretion and associated inhibition of hepatic CYP7A1 expression provided evidence of physiologically relevant gut-liver crosstalk. Moreover, significant non-linear modulation of cytokine responses was observed under inflammatory gut-liver interaction; for example, production of CXCR3 ligands (CXCL9,10,11) was synergistically enhanced. RNA-seq analysis revealed significant upregulation of IFNα/β/γ signaling during inflammatory gut-liver crosstalk, with these pathways implicated in the synergistic CXCR3 chemokine production. Exacerbated inflammatory response in gut-liver interaction also negatively affected tissue-specific functions (e.g., liver metabolism). These findings illustrate how an integrated multi-tissue platform can generate insights useful for understanding complex pathophysiological processes such as inflammatory organ crosstalk. Biotechnol. Bioeng. 2017;114: 2648-2659. © 2017 Wiley Periodicals, Inc.
Supplementary Figure 4 from Immunotargeting of Antigen xCT Attenuates Stem-like Cell Behavior and Metastatic Progression in Breast Cancer (2023)

&lt;p&gt;Soft agar colony formation assay of cells transfected with xCT&lt;/p&gt;
[A case of tuberous sclerosis associated with a pineal region tumor]. (1987)

The authors report a rare case of tuberous sclerosis associated with pineal region mixed glioma. A 38-year-old woman with tuberous sclerosis, who had a past history of left nephrectomy and tumorectomy of the right kidney for bilateral renal angiomyolipomas, was admitted because of headache and ataxic gait. CT scan and cerebral angiography suggested a pineal region tumor. Suboccipital craniectomy and partial removal of the tumor was performed via infratentorial supracerebellar approach. Microscopic examination revealed mixed oligodendroglioma and astrocytoma. It is well known that tuberous sclerosis is occasionally associated with brain tumors. However, with few exceptions, these have been subependymal giant cell astrocytomas in the lateral ventricles. They seem to originate from subependymal nodules of hamartomatous nature. As far as we are aware, association of pineal region tumor with tuberous sclerosis as in this case has not been reported.
Faculty Opinions recommendation of Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. (2008)

BRAF(V600E) is the most frequent oncogenic protein kinase mutation known. Furthermore, inhibitors targeting "active" protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer. Therefore, we pursued the development of specific kinase inhibitors targeting B-Raf, and the V600E allele in particular. By using a structure-guided discovery approach, a potent and selective inhibitor of active B-Raf has been discovered. PLX4720, a 7-azaindole derivative that inhibits B-Raf(V600E) with an IC(50) of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-Raf(V600E) kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-Raf(V600E)-bearing tumor cell lines but not in cells lacking oncogenic B-Raf. In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-Raf(V600E)-positive cells. In B-Raf(V600E)-dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity. The work described here represents the entire discovery process, from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-Raf(V600E)-driven tumors. PMID: 18287029 Funding information This work was supported by: NCI NIH HHS, United States Grant ID: R01 CA047159 NCI NIH HHS, United States Grant ID: CA 880999 NIAMS NIH HHS, United States Grant ID: AR 051886 NCI NIH HHS, United States Grant ID: T32 CA 09171 NCI NIH HHS, United States Grant ID: T32 CA009171 NIAMS NIH HHS, United States Grant ID: AR 051448 NCI NIH HHS, United States Grant ID: CA 47159 NIAMS NIH HHS, United States Grant ID: R01 AR051448 NIAMS NIH HHS, United States Grant ID: R01 AR051886 NIAMS NIH HHS, United States Grant ID: P50 AR0504086 More Less keyboard_arrow_down
Cell-based cytotoxicity assays for engineered nanomaterials safety screening: exposure of adipose derived stromal cells to titanium dioxide nanoparticles (2017)

We demonstrated that cytotoxicity assays based on specialized cell functions exhibit greater sensitivity and reveal damage induced by ENMs that was not otherwise detected by traditional ROS, LDH, and proliferation assays. For proper toxicological assessment of ENMs standard ROS, LDH, and proliferation assays should be combined with assays that investigate cellular functions relevant to the specific cell type.
Meniscal substitutes – human experience (1999)

A number of clinical series have described the effect of meniscus allograft replacement in humans. The general indication has been disabling pain following loss of a meniscus in a skeletally mature individual. Overall, healing of the graft to the capsule occurs in up to 80% of all transplants. Revascularization and cell repopulation is found in all grafts but is highly variable. The risk for graft failure seems to be greater with irradiated grafts and in patients with grade III or IV osteoarthritic changes. In most series, patients experienced a decrease in pain and an increase in activity level postoperatively. In many series, concominant surgery (cruciate ligament reconstruction or osteotomy) had been performed. Meniscus replacement with frozen or cryopreserved allografts seems to give the most promising short-term results in patients with post-meniscectomy pain. Controlled, randomized prospective studies are needed to confirm a long-term benefit and better define transplantation indications. Viable meniscus allografts seem to survive transplantation, as donor cells were found in the graft after 2 years. Clinically, pain was reduced and activity increased following transplantation, but after 4 years some of these gains were lost. There was no correlation between postoperative findings on MRI and clinical outcome. Meniscal replacement with a quadriceps tendon autograft in humans resulted in pain reduction, but at second-look arthroscopy, only 2 of 9 tendon autografts looked like a meniscus. Six were in position but still looked like tendons. Total medial meniscus replacement by quadriceps tendon autrograft is still an experimental procedure. There is no proof at present that meniscal substitutes (meniscus allografts or tendon autografts) in humans can protect the hyaline cartilage of the knee from the degeneration, following loss of a meniscus. There is some evidence in animal experiments that under circumstances not yet exactly known, a meniscus substitute can have a protective effect on articular cartilage. Three factors have been identified that prevent proper meniscal function: poor fixation of the meniscal horns, no contact of the graft with the articulating surfaces under load and incorrect positioning of the horns. Meniscal allograft transplantation sensitizes humoral and cell mediated immune systems. Bone plugs attached to meniscal allograft tissue may increase cell surface antigenicity. Deep freezing and especially freeze drying of meniscal tissue decreases host immunogenicity. Cryopreservation maintains the content of donor HLA encoded antigens and is likely more sensitizing to the host. The clinical importance of immune responses to meniscal allografts is not known, but it has not been shown to result in graft failure or rejection. Prospective studies are needed.
Surface-relief hologram reproduction (1992)

One of the factors determining the diffraction efficiency of the grating of a surface-relief hologram is the refractive index of the material. The refractive index of the photopoly­mer constituting a reproduced grating is smaller than that of the photoresist constituting the master grating. To reproduce the grating with a high diffraction efficiency, we studied how to optimize the grating shape. We found that a grating 0.5 μm wide required a master grating 0.9 μm wide to get the highest diffraction efficiency and that the reproduced grating had to be at least 1 μm deep. We fabricated a master and stamp and replicated gratings with a diffraction efficiency of 78 ±5%.
The impact of boundary scan on board test (1989)

Three categories of approaches to board test in manufacturing today are discussed: as a sorting process; as a repair driver: and as a process monitor. The costs associated with each are briefly examined. Elements in the overall testing and manufacturing process that can sabotage the success of a board-test operation are described. They are inaccuracies, misdiagnosis, test-repair looping, and handling-induced failures. Some industry trends that can threaten a manufacturer's ability to control the board-manufacturing process, namely, ASICs, surface-mount technology/tape automated bonding, miniaturized components, and node counts, are considered. The ability of boundary scan to enhance fault diagnosis, reduce test-repair looping, and enable standardized testing and the reuse of tests is discussed. Future trends in boundary-scan testing are indicated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Stable photoinduced charge separation in heptacene (2007)

Heptacene, generated in inert gas matrices by photobisdecarbonylation of a bridged alpha-diketone precursor, undergoes ionization into radical anion and radical cation upon UV irradiation.
Interposer-to-interposer electrical and silicon photonic interconnection platform using silicon bridge (2014)

Developing solutions that provide high-bandwidth and low-energy communication has been at the forefront of interconnect and packaging research [1]. Within a module, the challenge has been addressed by using novel 2.5D (silicon interposer) and 3D stacking for short and high-density electrical interconnections and silicon photonics based interconnects. However, wafer-level batch fabricated solutions for high-bandwidth and low-energy interconnection between modules remain largely missing. Fig. 1 illustrates three approaches for package-to-package communication: through the motherboard, Flex connection [2], and using optical fibers. Electrical connectivity through the motherboard is both bandwidth limited and energy consuming. The use of Flex connection provides lower loss channels, however it requires a serial assembly process, which may limit its scalability. Methods involving optical fibers suffer the same limitation and are limited to relatively large interconnect pitches.
Renaturation of RecombinantTreponema pallidumRare Outer Membrane Protein 1 into a Trimeric, Hydrophobic, and Porin-Active Conformation (1999)

We have previously observed that while native Treponema pallidum rare outer membrane protein 1 (Tromp1) is hydrophobic and has porin activity, recombinant forms of Tromp1 do not possess these properties. In this study we show that these properties are determined by conformation and can be replicated by proper renaturation of recombinant Tromp1. Native Tromp1, but not the 47-kDa lipoprotein, extracted from whole organisms by using Triton X-114, was found to lose hydrophobicity after treatment in 8 M urea, indicating that Tromp1's hydrophobicity is conformation dependent. Native Tromp1 was purified from 0.1% Triton X-100 extracts of whole organisms by fast-performance liquid chromatography (FPLC) and shown to have porin activity in planar lipid bilayers. Cross-linking studies of purified native Tromp1 with an 11 A cross-linking agent showed oligomeric forms consistent with dimers and trimers. For renaturation studies of recombinant Tromp1 (rTromp1), a 31,109-Da signal-less construct was expressed in Escherichia coli and purified by FPLC. FPLC-purified rTromp1 was denatured in 8 M urea and then renatured in the presence of 0.5% Zwittergent 3,14 during dialysis to remove the urea. Renatured rTromp1 was passed through a Sephacryl S-300 gel exclusion column previously calibrated with known molecular weight standards. While all nonrenatured rTromp1 eluted from the column at approximately the position of the carbonic anhydrase protein standard (29 kDa), all renatured rTromp1 eluted at the position of the phosphorylase b protein standard (97 kDa), suggesting a trimeric conformation. Trimerization was confirmed by using an 11 A cross-linking agent which showed both dimers and trimers similar to that of native Tromp1. Triton X-114 phase separations showed that all of renatured rTromp1, but none of nonrenatured rTromp1, phase separated exclusively into the hydrophobic detergent phase, similar to native Tromp1. Circular dichroism of nonrenatured and renatured rTromp1 showed a marked loss in alpha-helical secondary structure of renatured rTromp1 compared to the nonrenatured form. Finally, renatured rTromp1, but not the nonrenatured form, showed porin activity in planar liquid bilayers. These results demonstrate that proper folding of rTromp1 results in a trimeric, hydrophobic, and porin-active conformation similar to that of the native protein.
Linear versus Dendritic Molecular Binders for Hydrogel Network Formation with Clay Nanosheets: Studies with ABA Triblock Copolyethers Carrying Guanidinium Ion Pendants (2013)

ABA-triblock copolyethers 1a-1c as linear polymeric binders, in combination with clay nanosheets (CNSs), afford high-water-content moldable supramolecular hydrogels with excellent mechanical properties by constructing a well-developed crosslinked network in water. The linear binders carry in their terminal A blocks guanidinium ion (Gu(+)) pendants for adhesion to the CNS surface, while their central B block comprises poly(ethylene oxide) (PEO) that serves as a flexible linker for adhered CNSs. Although previously reported dendritic binder 2 requires multistep synthesis and purification, the linear binders can be obtained in sizable quantities from readily available starting materials by controlled polymerization. Together with dendritic reference 2, the modular nature of compounds 1a-1c with different numbers of Gu(+) pendants and PEO linker lengths allowed for investigating how their structural parameters affect the gel network formation and hydrogel properties. The newly obtained hydrogels are mechanically as tough as that with 2, although the hydrogelation takes place more slowly. Irrespective of which binder is used, the supramolecular gel network has a shape memory feature upon drying followed by rewetting, and the gelling water can be freely replaced with ionic liquids and organic fluids, affording novel clay-reinforced iono- and organogels, respectively.
Development of a CCR5-tropic HIV-1 fusion inhibition assay amenable to high-throughput screening for topical microbicides (2006)

Background The development of safe and effective topical microbicides to limit the continuing AIDS pandemic is a high priority. The current NIAID microbicide testing algorithm includes both CCR5 (R5)-tropic and CXCR4 (X4)-tropic attachment inhibition assays, and an X4-tropic fusion inhibition assay. To complete this testing algorithm, an R5-tropic fusion inhibition assay was developed. The rationale for this development was that mucosal HIV-1 infection is primarily mediated through the R5 receptor and an R5-tropic entry inhibitor should be included in combination microbicide prophylaxis.
Cell-intrinsic adenosine A2A receptor signaling is required for T cell homeostasis and control of tumor growth (47.1) (2012)

Abstract Adenosine generated as a result of normal metabolic activity is elevated in response to tissue stress, damage, or hypoxia. By stimulating adenosine A2A receptors (A2ARs) adenosine links metabolic activity to regulation of normal physiological functions such as sleep, blood flow, and inflammation. Although stimulation of A2ARs on activated T cells and APCs acutely suppresses inflammation and immune killing of tumor cells, global A2AR deletion has variable effects on the growth rate of syngeneic tumors, suggesting that A2AR signaling has opposing effects on immune function. Here we show that A2ARs are required for homeostatic maintenance of naïve T cells. In global A2AR-deficient mice naïve T cells undergo apoptosis, which drastically lower their number in blood and in peripheral lymph nodes. Lymphoid deletion of A2ARs, adoptive co-transfer and mixed bone-marrow reconstitution experiments showed that cell intrinsic A2AR signaling is required for T cell homeostasis. A2AR signaling is also required for interleukin 7 to optimally facilitate T cell survival ex vivo. In mice injected with syngeneic melanoma cells, lymphoid-specific A2AR deletion decreases T cell numbers in the periphery and in the tumor, reduces the proportion of tumor infiltrating T cells with an activated/memory phenotype, and markedly accelerates tumor growth. The results indicate that homeostatic adenosine production and A2AR signaling are required in naïve T cell maintenance and immune defense against tumors.
ChemInform Abstract: Total Synthesis of (+)‐Zaragozic Acid C. (1998)

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.