gebhart/patrepeval huggingface dataset:
Type 2 Diabetes Mellitus in Children (2002)

Breastfeeding reduces the risk of type 2 diabetes among Native Canadian children and should be promoted as a potential intervention to control the disease.
Synthesis of some benzopyranocyclopentapyridine and pyranoacridine derivatives (1983)

Abstract Aminocoumarins react with ethyl cyclopentanone‐and ethyl cyclohexanone‐2‐carboxylates to afford intermediates which on thermal cyclisation yield the title compounds.
Inverse problem for two-dimensional fractal sets using the wavelet transform and the moment method (1992)

Fractal geometry has provided statistical and deterministic models for classes of signals and images that represent many natural phenomena and objects. Iterated function systems (IFS) theory provides a convenient way to describe and classify deterministic fractals in the form of a recursive definition. As a result, it is conceivable to develop image representation schemes based on the IFS parameters that correspond to a given fractal image. The authors propose the use of the wavelet transform and of the moment method for the solution of the inverse problem of recovering IFS parameters from fractal images. The redundancy of a fractal with respect to scale variation is mirrored by its wavelet decomposition, thus providing a method to estimate the scaling parameters for a class of IFSs modeling the image. Displacement parameters and probabilities are then found using the moment method. Experimental results verifying the approach are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Acetylcholinesterase and butyrylcholinesterase as possible markers of low-grade systemic inflammation. (2007)

Plasma levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and lipid peroxides are high whereas those of endothelial nitric oxide are low in insulin resistance, obesity, type 2 diabetes mellitus, hypertension, hyperlipidemias, metabolic syndrome X, and Alzheimer's disease suggesting that these diseases are characterized by low-grade systemic inflammation. Recent studies showed that the plasma and tissue activities of enzymes butyrylcholinesterase and acetylcholinesterase are elevated in patients with Alzheimer's disease, and diabetes mellitus, hypertension, insulin resistance, and hyperlipidemia. As a result of this increase in the activities of enzymes acetylcholinesterase and butyrylcholinesterase, the plasma and tissue levels of acetylcholine (ACh) will be low. The "cholinergic anti-inflammatory pathway" mediated by acetylcholine acts by inhibiting the production of tumor necrosis factor, interleukin-1, macrophage migration inhibitory factor, and high mobility group box-1 and suppresses the activation of nuclear factor-kappa B expression. ACh is a neurotransmitter and regulates the levels and activities of serotonin, dopamine and other neuropeptides and thus, modulates both immune response and neurotransmission. Hence, both acetylcholinesterase and butyrylcholinesterase by inactivating acetylcholine may enhance inflammation. This suggests that increased plasma and tissue activities of acetylcholinesterase and butyrylcholinesterase seen in various clinical conditions could serve as a marker of low-grade systemic inflammation.
The Neurotrophic Receptor TrkB in Anoikis Resistance and Metastasis: A Perspective (2005)

Resistance to anoikis ("detachment-induced apoptosis") has been suggested to be a prerequisite for cancer cells to metastasize. In a functional screen for suppressors of anoikis, we identified the neurotrophic receptor TrkB. Upon s.c. inoculation in mice, TrkB-expressing cells formed highly invasive and metastatic tumors. Here, we discuss our findings within the context of the proposed role of TrkB in human malignancies and address the question of its feasibility as a target for cancer therapy.
Long-Chain Organofunctional Silanes: Synthesis and Surface Derivatization (2011)

A series of organofunctional long-chain alkylfunctional silanes have been synthesized for the purpose of derivatization of micro- and nanoparticles and generation of molecular monolayers and films on the substrates. 11-bromoundecylsilane and 1, 10-disiladecane are evaluated to interact with a variety of clean hydrogenated metal and metalloid including titanium, silicon and silicon dioxide. The surface of those treated substrates has been analyzed by X-ray photoelectron spectroscopy (XPS) and reflection-absorption infrared spectroscopy (RAIRS). Our preliminary results indicate that self-assembled monolayer has been well formed on titanium metal and silicon wafer, minimally on silicon-dioxide. The discussion of experimental results is also provided.
Pentostatin in the treatment of advanced hairy cell leukemia. (1989)

2'-Deoxycoformycin (pentostatin [dCF]), a potent inhibitor of adenosine deaminase (ADA), was administered in a biweekly low-dose (2 to 4 mg/m2) intravenous (IV) schedule to patients with advanced hairy cell leukemia. Twenty-three patients were treated, including 12 patients previously treated by splenectomy and five patients treated with interferon. Twenty-one of 23 patients had objective responses, including 20 who achieved a complete remission (CR). Responses occurred rapidly, with an average time to CR of 5.4 months. Treatment was not continued once CR was achieved, and 15 of 20 patients remain in remission with an average duration of 12.6 months. CRs were achieved in both patients previously treated with interferon (three of five) and patients with marked splenomegaly (three of three). Relapses, when seen, have occurred in the bone marrow alone and the one patient who required retreatment was reinduced into CR. Toxicity has been mild and reversible, with nausea and vomiting, conjunctivitis, and skin rash as the main complications of treatment. dCF is the most effective single agent in the treatment of hairy cell leukemia, inducing a high percentage of CRs in all subgroups. Two multiinstitutional trials are now underway to compare its effectiveness v alpha interferon.
Floating the Nonfloatables in China's Stock Market: Theory and Design (2005)

This study explains the conflict of interest between the majority stockholders, who have nonfloatable shares, and the minority stockholders, who have floatable shares in China's stock market. The growth of the Chinese financial markets is seriously constrained given the market segmentation of the two classes of stocks. This study provides a dynamic valuation model that motivates controlling stockholders to convert their nonfloatable shares to floatable shares and illustrates how a security design is able to float these shares. Issues on how to improve future corporate governance in China are also discussed.
Skyhawk: An Artificial Neural Network-based discriminator for reviewing clinically significant genomic variants (2018)

Abstract Motivation Many rare diseases and cancers are fundamentally diseases of the genome. In the past several years, genome sequencing has become one of the most important tools in clinical practice for rare disease diagnosis and targeted cancer therapy. However, variant interpretation remains the bottleneck as is not yet automated and may take a specialist several hours of work per patient. On average, one-fifth of this time is spent on visually confirming the authenticity of the candidate variants. Results We developed Skyhawk, an artificial neural network-based discriminator that mimics the process of expert review on clinically significant genomics variants. Skyhawk runs in less than one minute to review ten thousand variants, and about 30 minutes to review all variants in a typical whole-genome sequencing sample. Among the false positive singletons identified by GATK HaplotypeCaller, UnifiedGenotyper and 16GT in the HG005 GIAB sample, 79.7% were rejected by Skyhawk. Worked on the Variants with Unknown Significance (VUS), Skyhawk marked most of the false positive variants for manual review and most of the true positive variants no need for review. Availability Skyhawk is easy to use and freely available at https://github.com/aquaskyline/Skyhawk
Design of a new class of superpotent cyclic .alpha.-melanotropins based on quenched dynamic simulations (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDesign of a new class of superpotent cyclic .alpha.-melanotropins based on quenched dynamic simulationsFahad Al-Obeidi, Mac E. Hadley, B. Montgomery Pettitt, and Victor J. HrubyCite this: J. Am. Chem. Soc. 1989, 111, 9, 3413–3416Publication Date (Print):April 1, 1989Publication History Published online1 May 2002Published inissue 1 April 1989https://pubs.acs.org/doi/10.1021/ja00191a044https://doi.org/10.1021/ja00191a044research-articleACS PublicationsRequest reuse permissionsArticle Views360Altmetric-Citations164LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
O1–06–06: Improved memory capacity of amyloid precursor protein transgenic mice through passive administration of a monoclonal antibody inducing a conformational shift of amyloid–beta (2006)

Alzheimer's disease is characterized by the deposition of insoluble plaques of amyloid–β peptide in the brain of patients. A conformational change occurs in the amyloid–β peptide upon aggregation of soluble monomers into insoluble fibers with the transition of α–helixes or random coil conformation into β–sheets. The objective of this study was to use AC Immune's supramolecular technology to generate conformational sensitive antibodies targeting specifically the β–sheets of amyloidβ1–42. AC Immune's monoclonal antibody ACI–01–Ab7 was generated following immunization of mice with pegylated amyloidβ1–16peptide integrated into liposomes containing Lipid A. The functionality of the antibody was characterized in vitro by several different methods and the in vivo efficacy of the antibody was evaluated in amyloid precursor protein (APP) transgenic mice. The ACI–01–Ab7 binds amyloidβ1–42monomers with an affinity of 3x10–7 and to amyloidβ1–42 fibers with an even higher affinity of 4x10–8, as demonstrated by surface plasmon resonance. Using density gradient ultracentrifugation, we were able to establish the functional capacity of ACI–01–Ab7 monoclonal antibody to inhibit the aggregation of amyloidβ1–42 into amyloid fibers. Moreover, preformed amyloid fibrils disaggregate in the presence of ACI–01–Ab7. To investigate by which mechanism ACI–01–Ab7 inhibits the aggregation of amyloid fibers and disaggregate preformed fibers in vitro, we used Electron Microscopy and Solid state NMR spectroscopy. ACI–01–Ab7 binds to some, but not to all branches of amyloid fibers, suggesting specificity for a given secondary structure of amyloidβ1–42fibers. NMR studies directly demonstrated the induction of amyloidβ–peptide transition from β–sheets into random coil by our monoclonal antibody. Finally, in vivo administration of ACI–01–Ab7 into APP transgenic mice decreased the level of soluble amyloidβ1–40in the brain and significantly increased the cognitive memory capacity of these mice. The present results indicate that our monoclonal antibody ACI–01–Ab7 solubilizes amyloid fibers both in vitro and in vivo by inducing a conformation shift of amyloid–β from β–sheets to random coil. ACI–01–Ab7 therefore represents a promising approach for β–amyloid immune therapy of early and late stages of Alzheimer's Disease.
Fas ligation induces apoptosis of CD40-activated human B lymphocytes. (1995)

Since CD40/CD40 ligand (CD40Lig) interactions are essential in vivo for the generation of germinal center B cells that express Fas (Apo-1/CD95), we explored whether CD40 engagement may modulate Fas expression and function on human B lymphocytes. Resting tonsil B cells, isolated by density gradient centrifugation, express either absent or low levels of Fas. They could be induced to promptly express Fas after ligation of their CD40, however, using either a recombinant human CD40Lig or a cross-linked anti-CD40 mAb. In contrast, engagement of the B cell antigen receptor by immobilized anti-kappa and -lambda antibodies did not turn on Fas expression. Addition of anti-Fas mAb CH11 inhibited the later phases of CD40-induced B cell growth as a result of apoptotic cell death. Furthermore, Fas ligation inhibited proliferation and Ig secretion of CD40-activated B cells in response to recombinant cytokines such as interleukin (IL)-2, IL-4, and IL-10, as well as a cytokine-rich supernatant of phytohemagglutinin-activated T cells, indicating that none of those B cell tropic factors were able to prevent the Fas-induced death. Taken together, the present results show that engagement of CD40 antigen on B cells induces Fas expression and sensitizes them to Fas-mediated apoptosis. The delayed functional response to Fas ligation after CD40 activation may represent a way to limit the size of a specific B cell clone that is generated during T-B cell interactions.
Recent advances in focal therapy of prostate and kidney cancer (2010)

The concept of focal therapy in oncologic surgery refers to maximizing healthy tissue preservation while maintaining excellent cancer control outcomes. Herein, we address the recent advantages in the field of focal therapy for both kidney and prostate cancer, focusing on technological achievements and future perspectives.
Triterpenoids CDDO-Methyl Ester or CDDO-Ethyl Amide and Rexinoids LG100268 or NRX194204 for Prevention and Treatment of Lung Cancer in Mice (2009)

We tested members of two noncytotoxic classes of drugs, synthetic oleanane triterpenoids and rexinoids, both as individual agents and in combination, for the prevention and treatment of carcinogenesis in a highly relevant animal model of lung cancer. Lung adenocarcinomas were induced in A/J mice by injection of the carcinogen vinyl carbamate. Mice were fed drugs in diet, beginning 1 week after the carcinogen challenge for prevention or 8 weeks later for treatment. The number, size, and severity of tumors in the lungs were then evaluated. In the prevention studies, the triterpenoids CDDO-ethyl amide and CDDO-methyl ester reduced the average tumor burden (ATB) in the lungs 86% to 92%, respectively, compared with the controls, and the rexinoid LG100268 (268) reduced ATB by 50%. The combination of CDDO-ethyl amide and 268 reduced ATB by 93%. We show for the first time that these drugs also were highly effective for treatment of experimental lung cancer, and all triterpenoid and rexinoid combinations reduced ATB 85% to 87% compared with the control group. The triterpenoids also potently inhibited proliferation of VC1 mouse lung carcinoma cells and directly interacted with key regulatory proteins in these cells. In contrast, the rexinoids had little antiproliferative activity in VC1 cells but were potent inhibitors of the toll-like receptor pathway in macrophage-like cells. Triterpenoids and rexinoids are multifunctional, well-tolerated drugs that target different signaling pathways and are thus highly effective for prevention and treatment of experimental lung cancer.
Influenza Virus M2 Protein Slows Traffic along the Secretory Pathway (1998)

M2, an acid-activated ion channel, is an influenza A virus membrane protein required for efficient nucleocapsid release after viral fusion with the endosomal membrane. Recombinant M2 slows protein traffic through the Golgi complex (Sakaguchi, T., Leser, G. P)., and Lamb, R. A. (1996) J. Cell Biol. 133, 733-47). Despite its critical role in viral infection, little is known about the subcellular distribution of M2 or its fate following delivery to the plasma membrane (PM). We measured the kinetics of M2 transport in HeLa cells, and found that active M2 reached the PM considerably more slowly than inactive M2. In addition, M2 delayed intra-Golgi transport and cell surface delivery of influenza hemagglutinin (HA). We hypothesized that the effects of M2 on transport through non-acidified compartments are due to inefficient retrieval from the trans-Golgi of machinery required for intra-Golgi transport. In support of this, acutely activated M2 had no effect on intra-Golgi transport of HA, but still slowed HA delivery to the PM. Thus, M2 has an indirect effect on early transport steps, but a direct effect on late steps in PM delivery. These findings may help explain the conflicting and unexplained effects on protein traffic observed with other perturbants of intraorganelle pH such as weak bases and inhibitors of V-type ATPases.
Throughput of a wireless cell using superposition based multiple-access with non-ideal interference cancellation (2010)

In current wireless standards like 3GPP LTE or IEEE 802.16 / WiMAX multiple access is based on orthogonal signalling using single-carrier frequency-division multiple access (SC-FDMA) or orthogonal frequency-division multiple access (OFDMA). Links between a base station and different terminals use mutually orthogonal radio resources. This paper studies potential gains in average cell throughput by using multiple-access based on non-orthogonal superposition on top of orthogonal multiple access taking into account different channel gains for different users and interference-cancellation errors. The study is done for a system with a single antenna both at the base station and the terminals. Multiple terminals share a single time-frequency resource and their signals are separated by successive interference cancellation or other kinds of joint detection. This could be called multi-user SISO (MU-SISO), because multiple users can be scheduled on a single time-frequency resource in a SISO system. Frequency flat non-fading channels with a pathloss according to a common model are assumed. Especially in the case where throughput with orthogonal multiple-access is limited by low cell-edge SNR significant throughput gains of more than 80 % can be expected. The method can be extended to multiple-antennas and used on top of space-division multiple access (SDMA).
EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). (2015)

Mutations in the epidermal growth factor receptor (EGFR) gene are commonly observed in non-small-cell lung cancer (NSCLC), particularly in tumors of adenocarcinoma (ADC) histology (NSCLC/ADC). Robust data exist regarding the prevalence of EGFR mutations in Western and Asian patients with NSCLC/ADC, yet there is a lack of data for patients of other ethnicities. This review collated available data with the aim of creating a complete, global picture of EGFR mutation frequency in patients with NSCLC/ADC by ethnicity. Worldwide literature reporting EGFR mutation frequency in patients with NSCLC/ADC was reviewed, to create a map of the world populated with EGFR mutation frequency by country (a 'global EGFR mutMap'). A total of 151 worldwide studies (n=33162 patients with NSCLC/ADC, of which 9749 patients had EGFR mutation-positive NSCLC/ADC) were included. There was substantial variation in EGFR mutation frequency between studies, even when grouped by geographic region or individual country. As expected, the Asia-Pacific NSCLC/ADC subgroup had the highest EGFR mutation frequency (47% [5958/12819; 87 studies; range 20%-76%]) and the lowest EGFR mutation frequency occurred in the Oceania NSCLC/ADC subgroup (12% [69/570; 4 studies; range 7%-36%]); however, comparisons between regions were limited due to the varying sizes of the patient populations studied. In all regional (geographic) subgroups where data were available, EGFR mutation frequency in NSCLC/ADC was higher in women compared with men, and in never-compared with ever-smokers. This review provides the foundation for a global map of EGFR mutation frequency in patients with NSCLC/ADC. The substantial lack of data from several large geographic regions of the world, notably Africa, the Middle East, Central Asia, and Central and South America, highlights a potential lack of routine mutation testing and the need for further investigations in these regions.
The Number and Location of Glycans on Influenza Hemagglutinin Determine Folding and Association with Calnexin and Calreticulin (1997)

Calnexin and calreticulin are homologous molecular chaperones that promote proper folding, oligomeric assembly, and quality control of newly synthesized glycoproteins in the endoplasmic reticulum (ER). Both are lectins that bind to substrate glycoproteins that have monoglucosylated N-linked oligosaccharides. Their binding to newly translated influenza virus hemagglutinin (HA), and various mutants thereof, was analyzed in microsomes after in vitro translation and expression in live CHO cells. A large fraction of the HA molecules was found to occur in ternary HA- calnexin-calreticulin complexes. In contrast to calnexin, calreticulin was found to bind primarily to early folding intermediates. Analysis of HA mutants with different numbers and locations of N-linked glycans showed that although the two chaperones share the same carbohydrate specificity, they display distinct binding properties; calreticulin binding depends on the oligosaccharides in the more rapidly folding top/hinge domain of HA whereas calnexin is less discriminating. Calnexin's binding was reduced if the HA was expressed as a soluble anchor-free protein rather than membrane bound. When the co- and posttranslational folding and trimerization of glycosylation mutants was analyzed, it was observed that removal of stem domain glycans caused accelerated folding whereas removal of the top domain glycans (especially the oligosaccharide attached to Asn81) inhibited folding. In summary, the data established that individual N-linked glycans in HA have distinct roles in calnexin/calreticulin binding and in co- and posttranslational folding.