gebhart/patrepeval huggingface dataset:
Genetic Engineering in Combination with Semi‐Synthesis Leads to a New Route for Gram‐Scale Production of the Immunosuppressive Natural Product Brasilicardin A (2021)

Abstract Brasilicardin A ( 1 ) consists of an unusual anti / syn / anti ‐perhydrophenanthrene skeleton with a carbohydrate side chain and an amino acid moiety. It exhibits potent immunosuppressive activity, yet its mode of action differs from standard drugs that are currently in use. Further pre‐clinical evaluation of this promising, biologically active natural product is hampered by restricted access to the ready material, as its synthesis requires both a low‐yielding fermentation process using a pathogenic organism and an elaborate, multi‐step total synthesis. Our semi‐synthetic approach included a) the heterologous expression of the brasilicardin A gene cluster in different non‐pathogenic bacterial strains producing brasilicardin A aglycone ( 5 ) in excellent yield and b) the chemical transformation of the aglycone 5 into the trifluoroacetic acid salt of brasilicardin A ( 1 a ) via a short and straightforward five‐steps synthetic route. Additionally, we report the first preclinical data for brasilicardin A.
Cobalt-Catalyzed Dimerization of α-Olefins to Give Linear α-Olefin Products (2005)

[Cp*P(OMe)3CoCH2CH3]+ [BarF]-, generated by the addition of HBArF to Cp*P(OMe)3Co(ethene), catalyzes the oligomerization of 1-hexene to give dimers and trimers. When a deficit of the acid is used, linear alpha-olefin dimers are produced at the expense of trimeric products: e.g., 1-butene, 1-hexene, and 1-octene give 1-octene, 1-dodecene, and 1-hexadecene, respectively.
AtMBD9: a protein with a methyl‐CpG‐binding domain regulates flowering time and shoot branching in Arabidopsis (2006)

The functional characterization of mammalian proteins containing a methyl-CpG-binding domain (MBD) has revealed that MBD proteins can decipher the epigenetic information encoded by DNA methylation, and integrate DNA methylation, modification of chromatin structure and repression of gene expression. The Arabidopsis genome has 13 putative genes encoding MBD proteins, and no specific biological function has been defined for any AtMBD genes. In this study, we identified three T-DNA insertion mutant alleles at the AtMBD9 locus, and found that all of them exhibited obvious developmental abnormalities. First, the atmbd9 mutants flowered significantly earlier than wild-type plants. The expression of FLOWERING LOCUS C (FLC), a major repressor of Arabidopsis flowering, was markedly attenuated by the AtMBD9 mutations. This FLC transcription reduction was associated with a significant decrease in the acetylation level in histone H3 and H4 of FLC chromatin in the atmbd9 mutants. Secondly, the atmbd9 mutants produced more shoot branches by increasing the outgrowth of axillary buds when compared with wild-type plants. The two known major factors controlling the outgrowth of axillary buds in Arabidopsis, auxin and the more axillary growth (MAX) pathway, were found not to be involved in producing this enhanced shoot branching phenotype in atmbd9 mutants, indicating that AtMBD9 may regulate a novel pathway to control shoot branching. This pathway is not related to FLC expression as over-expression of FLC in atmbd9-2 restored its flowering time to one similar to that of the wild type, but did not alter the shoot branching phenotype.
Digital adaptive optics and imaging through deep turbulence (2013)

In this paper we study the performance of an atmospheric imaging technique we referred to as digital adaptive optics. The technique consists in two major steps: (1) an optical sensor provides simultaneous measurements of the optical field wavefront phase and intensity distributions (complex field) in the system pupil, and (2) a digital processing approach is used to synthesize a compensated image from the complex field measurement. A numerical analysis of the system performance is provided for an anisoplanatic imaging scenario.
Preventative effect of repeated nasal applications of capsaicin in cluster headache (1994)

Preliminary studies have shown that repeated nasal applications of capsaicin prevented the occurrence of cluster headache attacks. The present study was designed to verify the difference in efficacy of treatment with nasal capsaicin, depending on the side of application. Fifty-two patients affected by episodic form were divided into 2 groups, one receiving the treatment on the same side where the attacks occurred (ipsilateral side), the other on the controlateral side. Eighteen patients with a chronic form alternately received both ipsilateral and controlateral treatments. Seventy percent of the episodic patients, treated on the ipsilateral side, showed a marked amelioration whereas no improvement was noted in the patients treated on the contralateral side. The efficacy of ipsilateral treatment was emphasized by the results obtained in chronic patients. However, in these patients, the maximum period of amelioration lasted no more than 40 days. The difference between the effects of the 2 treatments (contralateral and ipsilateral) was statistically significant in both episodic and chronic sufferers. The efficacy of repeated nasal applications of capsaicin in cluster headache is congruent with previous reports on the therapeutic effect of capsaicin in other pain syndromes (post-herpetic neuralgia, diabetic neuropathy, trigeminal neuralgia) and supports the use of the drug to produce a selective analgesia.
Effects of TAK-480, a Novel Tachykinin NK2^|^ndash;Receptor Antagonist, on Visceral Hypersensitivity in Rabbits and Ricinoleic Acid^|^ndash;Induced Defecation in Guinea Pigs (2012)

TAK-480, 4-(difluoromethoxy)-N-((1R,2S)-2-(((3aR,4R,9bR)-4-(methoxymethyl)-2, 3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl)carbonyl)cyclohexyl)benzamide, is a novel tachykinin NK(2)-receptor antagonist. In this study, we investigated its antagonistic activity and efficacy in animal models of visceral hypersensitivity and stimulated bowel function which have been implicated to underlie the symptoms in irritable bowel syndrome (IBS). TAK-480 showed potent binding affinity for human NK(2) receptors with a marked species difference and a 10,000-fold selectivity versus NK(1) and NK(3) receptors. TAK-480 dose-dependently antagonized colonic contractions induced by administration of the NK(2) receptor-selective agonist beta-Ala(8)-NKA(4-10) (βA-NKA) in anesthetized rabbits. In a rabbit model of intracolonic zymosan-induced visceral hypersensitivity, TAK-480 markedly inhibited the visceromotor response to colorectal distension, in contrast to the moderate inhibition by the serotonin 5-HT(3)-receptor antagonist alosetron. In addition, TAK-480 suppressed ricinoleic acid-induced defecation without affecting spontaneous defecation in guinea pigs, whereas alosetron suppressed both. Furthermore, TAK-480 inhibited smooth muscle contractions produced by natural tachykinins (substance P, neurokinin A, and neurokinin B) as well as βA-NKA in an isolated human colon. In conclusion, the novel NK(2)-receptor antagonist TAK-480 improved visceral hypersensitivity and accelerated defecation without causing constipation in experimental animals. Furthermore, the potent functional blockade of NK(2) receptors in human colon might suggest the potential effectiveness of TAK-480 in IBS patients.
Solid-State NMR Rationalizes the Bone-Adhesive Properties of Serine- and Phosphoserine-Bearing Calcium Phosphate Cements by Unveiling Their Organic/Inorganic Interface (2020)

From a multitude of homonuclear and heteronuclear correlation magic-angle-spinning (MAS) NMR experiments, we present thorough structural and phase-quantification analyses of calcium phosphate cements (CPCs) that incorporate either l-serine (Ser) or O-phospho-l-serine (Pser), thereby rendering the cements strongly bone-adhesive and suitable for biomedical implants with capacity to glue both soft and hard tissues together. In the absence of organic additives, the CPCs comprise disordered hydroxyapatite (HA), which forms from the reaction of α-Ca3(PO4)2 with water. However, the presence of even a few mol % of Pser/Ser drastically changes the cement reactions: the HA formation is quenched, while MAS NMR experiments reveal intimate contacts between the Pser/Ser molecules and amorphous calcium phosphate (ACP) that incorporate HPO42– groups: these organic/inorganic species form a homogeneous amorphous ACP/Pser or ACP/Ser cement component. The amount of ACP/Pser in the cement is shown to correlate qualitatively with its shear strength, also rationalizing why Pser-bearing CPCs exhibit stronger adhesive properties than their Ser-based counterparts, for which the ACP/Ser content does not increase concomitantly with that of Ser (as for the Pser-based CPCs). The Pser-bearing CPCs feature the strongest shear strength for 23–72 mol % Pser, whereas the decline of the adhesive properties for the Pser-richest CPCs (>72 mol %) stems from unreacted Pser and formation of its Ca salt, as well as several minor Ca phosphate phases involving HPO42– and H2PO4– groups. By combining information from various one- and two-dimensional MAS NMR experiments with 1H, 13C, and 31P as structural probes, we examined the inorganic/organic contacts of the ACP/Pser and ACP/Ser phases, and monitored the alterations of the cement reactions for variable amounts of the organic additives.
ST Codes with Partial Channel Knowledge: Statistical CSI (2006)

This chapter contains sections titled: Partial CSI Models ST Spreading Combining OSTBC With Beamforming Numerical Examples Adaptive Modulation for Rate Improvement Optimizing Average Capacity Closing Comments
Entwicklung von Anti-CD30-Radioimmunkonstrukten zur Behandlung des Hodgkin-Lymphoms – Studien an Zellkulturen und Tieren (2010)

Objectives: Comparison of the binding affinity to a CD30-positive Hodgkin lymphoma (HL) cell line and biodistribution in HL bearing mice of new anti-CD30 radioimmunoconjugates (RICs) of varying structure and labelling nuclides. Methods: The antibodies Ki-4 and 5F11 were radioiodinated by the chloramine T method or labelled with 111In via p-NCS-Benzyl-DOTA. In addition, the Ki-4-dimer was investigated in the iodinated form. The RICs were analyzed for retained immunoreactivity by immunochromatography. In-vitro binding studies were performed on CD30-positive L540 cell lines. For in-vivo biodistribution studies, SCID mice bearing human HL xenografts were injected with the various radioimmunoconjugates. After 24 h, activities in the organs and tumour were measured for all 5 RICs. Tumour-free animals were studied in the same way with 131I- Ki-4 24 h p. i. The three RICs with the highest tumour/background ratios 24 h p.i. (131I-Ki-4, 131I–5F11, 111In-bz-DOTA-Ki-4) were analysed further at 48 h and 72 h. Results: All the RICs were successfully labelled with high specific activities (28–47 TBq/mmol) and sufficient radiochemical yields (>80%). Scatchard plot analysis proved high tumour affinity (KD = 20–220 nmol/l). In-vivo tumour accumulation in % of injected dose per g tissue (%ID/g) lay between 2.6 (131I-5F11) and 12.3 % ID/g (131I-Ki-4) with permanently high background in blood. Tumour/blood-ratios of all RICs were below one at all time points. Conclusions: In-vitro tumour cell affinities of all RICs were promising. However, in-vivo biokinetics tested in the mouse model did not meet expectations. This highlights the importance of developing and testing further new anti-CD30 conjugates.
Micron-scale lens array having diffracting structures (2023)

A novel micron-scale lens, a microlens, is engineered to concentrate light efficiently onto an area of interest, such as a small, light-sensitive detector element in an integrated electronic device. Existing microlens designs imitate the form of large-scale lenses and are less effective at small sizes. The microlenses described herein have been designed to accommodate diffraction effects, which dominate the behavior of light at small length scales. Thus a new class of light-concentrating optical elements with much higher relative performance has been created. Furthermore, the new designs are much easier to fabricate than previous designs.
Perkin 1 Abstracts: Natural Product Synthesis (1999)

Perkin 1 Abstracts: Natural Product Synthesis aims to highlight syntheses that have been recently published. It includes brief descriptions of biological activity and key steps. A more comprehensive list of Natural Product syntheses and isolation can be found in Natural Product Updates
Preparation of ordered and crosslinked films from liquid crystalline p‐vinylphenoxy‐based monomers (1995)

Abstract The synthesis of the following monofunctional and bifunctional liquid crystalline p ‐vinylphenoxy‐based monomers is described: 4‐methoxyphenyl 4‐[11‐(4‐vinylphenoxy)‐undecyloxy]benzoate ( 1 ), 4‐cyanophenyl 4‐[11‐(4‐vinylphenoxy)undecyloxy]benzoate ( 2 ) and 3‐(4‐vinylphenoxy)propyl 4‐{4‐[11‐(4‐vinylphenoxy)undecyloxy]benzoyloxy}benzoate ( 3 ). Both free radical and cationic polymerization of the monofunctional monomers 1 and 2 yielded side‐chain liquid crystalline polymers exhibiting smectic A mesomorphism. The polymers exhibited high molar masses ( M n = 40000 – 100000 g/mol) and relatively narrow molar mass distributions ( M w / M n between 1.5 and 3). Ordered thin films were prepared by in‐situ photopolymerization of monomers 1 , 2 and 3 oriented in their nematic mesophases. Thin films of a thermally stabilized ordered side‐chain liquid crystalline polymer were prepared by copolymerization of the monofunctional monomer 1 and the bifunctional monomer 3 , the latter present in low concentration. The films regained orientation when cooled down from temperatures above the isotropization point (137°C) as evidenced by polarized FT‐Raman measurements.
β-Catenin/CBP inhibition alters epidermal growth factor receptor fucosylation status in oral squamous cell carcinoma (2020)

Epidermal growth factor receptor (EGFR) is a major driver of head and neck cancer, a devastating malignancy with a major sub-site in the oral cavity manifesting as oral squamous cell carcinoma (OSCC). EGFR is a glycoprotein receptor tyrosine kinase (RTK) whose activity is upregulated in >80 % OSCC. Current anti-EGFR therapy relies on the use of cetuximab, a monoclonal antibody against EGFR, although it has had only a limited response in patients. Here, we uncover a novel mechanism regulating EGFR activity, identifying a role of the nuclear branch of the Wnt/β-catenin signaling pathway, the β-catenin/CBP axis, in control of EGFR posttranslational modification with <i>N</i>-glycans. Genomic and structural analyses reveal that β-catenin/CBP signaling represses fucosylation on the antennae of <i>N</i>-linked glycans on EGFR. By employing nUPLC-MS/MS, we determined that malignant human OSCC cells harbor EGFR with a paucity of <i>N</i>-glycan antennary fucosylation, while indolent cells display higher levels of fucosylation at sites N420 and N579. Additionally, treatment with either ICG-001 or E7386, which are both small molecule inhibitors of β-catenin/CBP signaling, leads to increased transcriptional expression of fucosyltransferases FUT2 and FUT3, with a concomitant increase in EGFR <i>N</i>-glycan antennary fucosylation. In order to discover which fucosylated glycan epitopes are involved in the observed effect, we performed in-depth characterization of multiply-fucosylated <i>N</i>-glycans via glycopeptide tandem mass spectrometry of the EGFR tryptic glycopeptides. Data are available via ProteomeXchange with identifier PXD017060. We propose that β-catenin/CBP signaling promotes EGFR oncogenic activity in OSCC by inhibiting its <i>N</i>-glycan antennary fucosylation through transcriptional repression of FUT2 and FUT3.
Pyro: a spatial-temporal big-data storage system (2015)

With the rapid growth of mobile devices and applica-tions, geo-tagged data has become a major workload for big data storage systems. In order to achieve scalability, existing solutions build an additional index layer above general purpose distributed data stores. Fulfilling the se-mantic level need, this approach, however, leaves a lot to be desired for execution efficiency, especially when users query for moving objects within a high resolution geometric area, which we call geometry queries. Such geometry queries translate to a much larger set of range scans, forcing the backend to handle orders of mag-nitude more requests. Moreover, spatial-temporal ap-plications naturally create dynamic workload hotspots1, which pushes beyond the design scope of existing solu-tions. This paper presents Pyro, a spatial-temporal big-data storage system tailored for high resolution geometry queries and dynamic hotspots. Pyro understands geome-tries internally, which allows range scans of a geometry query to be aggregately optimized. Moreover, Pyro em-ploys a novel replica placement policy in the DFS layer that allows Pyro to split a region without losing data locality benefits. Our evaluations use NYC taxi trace data and an 80-server cluster. Results show that Pyro reduces the response time by 60X on 1km×1km rectan-gle geometries compared to the state-of-the-art solutions. Pyro further achieves 10X throughput improvement on 100m×100m rectangle geometries2. 1
High performance computing environment for multidimensional image analysis (2007)

Our parallel solution dramatically improves the performance of image processing, feature extraction and 3D reconstruction tasks. This increased throughput permits biologists to conduct unprecedented large scale experiments with massive datasets.
Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1 (2017)

Human intoxication with the seafood poison ciguatoxin, a dinoflagellate polyether that activates voltage-gated sodium channels (Na<sub>V</sub>), causes ciguatera, a disease characterised by gastrointestinal and neurological disturbances. We assessed the activity of the most potent congener, Pacific ciguatoxin-1 (P-CTX-1), on Na<sub>V</sub>1.1-1.9 using imaging and electrophysiological approaches. Although P-CTX-1 is essentially a non-selective Na<sub>V</sub> toxin and shifted the voltage-dependence of activation to more hyperpolarising potentials at all Na<sub>V</sub> subtypes, an increase in the inactivation time constant was observed only at Na<sub>V</sub>1.8, while the slope factor of the conductance-voltage curves was significantly increased for Na<sub>V</sub>1.7 and peak current was significantly increased for Na<sub>V</sub>1.6. Accordingly, P-CTX-1-induced visceral and cutaneous pain behaviours were significantly decreased after pharmacological inhibition of Na<sub>V</sub>1.8 and the tetrodotoxin-sensitive isoforms Na<sub>V</sub>1.7 and Na<sub>V</sub>1.6, respectively. The contribution of these isoforms to excitability of peripheral C- and A-fibre sensory neurons, confirmed using murine skin and visceral single-fibre recordings, reflects the expression pattern of Na<sub>V</sub> isoforms in peripheral sensory neurons and their contribution to membrane depolarisation, action potential initiation and propagation.
Photoactive Porous Silicon Nanopowder (2013)

Bulk processing of porous silicon nanoparticles (nSi) of 50-300 nm size and surface area of 25-230 m(2)/g has been developed using a combustion synthesis method. nSi exhibits consistent photoresponse to AM 1.5 simulated solar excitation. In confirmation of photoactivity, the films of nSi exhibit prompt bleaching following femtosecond laser pulse excitation resulting from the photoinduced charge separation. Photocurrent generation observed upon AM 1.5 excitation of these films in a photoelectrochemical cell shows strong dependence on the thickness of the intrinsic silica shell that encompasses the nanoparticles and hinders interparticle electron transfer.
Arthroscopic Management of Dysplastic Hip Morphologies (2015)

Objectives: Previous reports regarding arthroscopic management of dysplastic hip morphologies have conflicting results. Arthroscopy alone in the setting of dysplastic morphologies is controversial. Methods: We retrospectively reviewed 88 hips (77 patients, 71% female, mean age 33.9 years) with radiographic findings consistent with hip dysplasia and a mean 26.0 months follow-up (range 12-80 months) after hip arthroscopy. Procedures performed included 67 labral repairs (76%), 20 selective labral debridements (23%), 72 capsular repair /plications (82%), and management of associated cam-type morphology in 63 hips (72%). All radiographs were evaluated for parameters consistent with dysplasia including the LCE, Neck Shaft angle, Tonnis angle, Extrusion index, femoral head lateralization, and break in Shenton's line. Preoperative and post-operative function were evaluated prospectively using the Modified Harris Hip Score (MHHS), SF-12 scoring, and pain on a visual analog score (VAS). Patient demographics, procedures performed, and radiographic parameters were evaluated with regards to functional outcomes. In addition, the results of the dysplastic cohort were compared to an aged matched cohort of 231 hips (215 patients, 52% female, mean age 32 years) performed during the study period with a mean follow-up 22.7 months (12-60 months) that underwent arthroscopic FAI correction without the diagnosis of dysplasia. Results: The mean LCE was 20.8 degrees (range, 8.7 - 24.5), and mean Tonnis angle was 11.0 (range, 0 - 22.2 degrees). The dysplastic cohort had a mean latest MHHS of 81.3 (range, 34-100) and mean 15.6 point (range, -28 - 60) improvement in MHHS compared to 88.4 points and 24.4 points, respectively, in the FAI cohort (p&lt;0.01). The dysplastic cohort had 60.9% good to excellent results and 32.2% failures, compared to 81.2% good/excellent results and 10.5% failures for the FAI cohort (p&lt;0.01). Decreased head neck offset (cam-type morphology) trended towards being predictive of better scores in the dysplastic cohort (p=0.079). In addition, dysplastic hips that underwent capsular plications and labral repairs had greater good / excellent results and lower failure rates (p&lt;0.05). Grade 4 chondral defects were predictive of lower scores (p=0.02). There were no statistically significant differences for functional outcomes regarding gender or age for either cohort (p&gt;0.05). There were no iatrogenic subluxations / dislocations in either group. Conclusion: Although functional scores were improved post-arthroscopy in hips with mild to borderline dysplastic morphologies, Good/Excellent results were inferior and Failure rates were higher compared to an FAI cohort. These results were independent of gender. Associated cam-type FAI, and labral repair / capsular plications were predictive of better clinical outcomes in the dysplastic cohort. Outcomes after pelvic osteotomy in this borderline population are required to determine the optimal treatment.
Measuring atmospheric methane and water vapour using near-infrared diode lasers (1994)

Single-frequency near-infrared diode lasers are used to measure atmospheric methane and water vapor. Using high-frequency wavelength modulation methods, sensitive instrumentation with fast time response are designed. Communications lasers operating near 1310 nm probe weak overtone transitions of both molecules; lasers with custom wavelengths at present lack sophisticated packaging, but can achieve much higher sensitivity. We describe two field-tested instruments: an automated, airborne hygrometer with a sensitivity of 8 ppm (by volume) with a one second averaging time, and a fast response methane sensor with a sensitivity of 65 ppb. Improvements to these instruments are outlined, and the effects of laser nonlinearities are noted.