gebhart/patrepeval huggingface dataset:
TG101348: A Dual-Acting JAK2/FLT3 Small Molecule Kinase Inhibitor for the Treatment of AML. (2007)

Abstract A number of genetic mutations have been identified in the development of acute myeloid leukemia (AML), including mutations in the proto-oncogene N-RAS, p53, c-Kit and the FMS-like receptor tyrosine kinase 3 (FLT3). FLT3 plays an important role in the formation of early stem/progenitor cells during hematopoietic development. FLT3 is mutated in ∼30% of AMLs, with internal tandem duplications (ITD) in the juxtamembrane region being the most common (FLT3-ITD). This results in constitutive activation of FLT3 kinase activity and patients harboring such mutations do not respond well to conventional treatments and demonstrate poor clinical prognosis. There is growing evidence that the JAK/STAT pathway may also contribute to the etiology of AML. For instance, the JAK2 V617F point mutation driving various chronic myeloproliferative disorders (MPDs) has recently been detected in de novo AMLs and STAT3/5 phosphorylation is commonly elevated in AML patients. We have developed TG101348, a selective JAK2/FLT3 small molecule inhibitor which has the potential to treat both MPDs and AML. In in vitro based assays, TG101348 was capable of inhibiting the proliferation of human AML cell lines representing a variety of mutations. In AML cell lines carrying mutations in N-RAS such as KG-1, HL-60, and THP-1, EC50s ranged from ∼300 nM-1000 nM. In TF-1a AML cells, which harbor a mutation in p53, TG101348 demonstrated an EC50 of 493 nM. Most interestingly, for these cell lines, FLT3/VEGFR2 specific small molecule inhibitors such SU5416 were significantly less effective, demonstrating EC50s that were generally &gt;10-fold higher. TG101348 was most potent against the FLT3-ITD positive cells lines, MV411 (EC50=57 nM) and MOLM13 (EC50=69 nM). In MV411 cells, TG101348 functionally inhibited FLT3 autophosphorylation, and phosphorylation of downstream intermediates including STAT5, ERK, and AKT. In a human MV411 xenograft models, oral administration (120mg/kg, BID) of TG101348 resulted in complete regression of the subcutaneously implanted MV411 tumors. Taken together, these data suggest that the dual-acting JAK2/FLT3 kinase inhibitor TG101348 may have a therapeutic advantage in that it has the capacity to block multiple pathways critical for dysregulated cell proliferation and survival in AML.
A comparative study of vector fitting and orthonormal vector fitting techniques for EMC applications (2006)

Broadband rational approximations of multi- port systems are of great importance for accurate transient analysis of electrical systems. To this aim, fitting techniques have been found extremely useful in providing rational models for sampled data in the frequency domain. This paper presents a comparative study of two fitting methods, namely the standard Vector fitting (VF) and the orthonor- mal vector fitting (OVF) techniques. The latter is found to be better conditioned, reduces the numerical sensitivity to the choice of starting poles and limits the the number of iterations and, thus, the global cpu-time to obtain the rational approximation.
Essential protein interactions within the replisome regulate DNA replication (2011)

Comment on: Zhang H, et al. Proc Natl Acad Sci USA 2011; 108:9372-7.
Molecular characterization of Der p 10: a diagnostic marker for broad sensitization in house dust mite allergy (2011)

Der p 10 may be a diagnostic marker for HDM-allergic patients with additional sensitization to allergens other than Der p 1 and Der p 2. Such patients may require attention when allergen-specific immunotherapy is considered.
Isolation, Structural Characterization, and Chromosomal Mapping of the Mouse Vascular Adhesion Protein-1 Gene and Promoter, (1998)

Vascular adhesion protein-1 (VAP-1) is an endothelial cell adhesion molecule which mediates lymphocyte binding to endothelial cells. The cloning of a mouse VAP-1 (mVAP-1) cDNA revealed that mVAP-1 is a novel 110/220 kDa transmembrane molecule with significant identity to copper-containing amine oxidases. In this work the nucleotide sequence and primary structure of the mVAP-1 gene was determined and the promoter region was structurally characterized. The isolated approximately 14.4-kb mVAP-1 gene consists of 4 exons and 3 introns. Primer extension analysis and 5' rapid amplification of cDNA ends revealed multiple transcription initiation sites in different tissues suggesting that the mVAP-1 transcription is differently regulated in different tissues. Analysis of the sequence immediately upstream of the detected transcription initiation sites showed no canonical TATA or CCAAT elements, but putative regulatory elements were found close to the detected transcription start sites. The cloning of the mVAP-1 gene reveals the first insight into the genomic organization of murine amine oxidases and will, by targeted disruption of the gene, allow us to understand better the importance of VAP-1 in leukocyte trafficking and monoamine oxidase activity for the function of the immune system.
Inverse Design of a Polarization-Independent Dirac-Cone Zero-Index Metamaterial (2016)

We apply a novel computational method to systematically design Dirac cones in photonic crystals. In particular, we demonstrate an unprecedented Dirac-cone zero-index metamaterial (DC-ZIM) that exhibits zero-index for any polarization of light.
Natural and synthetic DNA elements with the CArG motif differ in expression and protein-binding properties. (1991)

DNA elements with the CC(A/T)6GG, or CArG, motif occur in promoters that are under different regulatory controls. CArG elements from the skeletal actin, c-fos, and myogenin genes were tested for their abilities to confer tissue-specific expression on reporter genes when the individual elements were situated immediately upstream from a TATA element. The c-fos CArG element, also referred to as the serum response element (SRE), conferred basal, constitutive expression on the test promoter. The CArG motif from the myogenin gene was inactive. The skeletal actin CArG motif functioned as a muscle regulatory element (MRE) in that basal expression was detected only in muscle cultures. Muscle-specific expression from the 28-bp MRE and the 2.3-kb skeletal actin promoter was trans repressed by the Fos and Jun proteins. The expression and factor-binding properties of a series of synthetic CArG elements were analyzed. Muscle-specific expression was conferred by perfect 28-bp palindromes on the left and right halves of the skeletal actin MRE. Chimeric elements of the skeletal actin MRE and the c-fos SRE differed in their expression properties. Muscle-specific expression was observed when the left half of the MRE was fused to the right half of the SRE. Constitutive expression was conferred by a chimera with the right half of the MRE fused to the left half of the SRE and by chimeras which exchanged the central CC(A/T)6GG sequences. At least three distinct proteins specifically bound to these CArG elements. The natural and synthetic CArG elements differed in their affinities for these proteins; however, muscle-specific expression could not be attributed to differences in the binding of a single protein. Furthermore, the MRE did not bind MyoD or the myogenin-E12 heterodimer, indicating that muscle-specific expression from this element does not involve a direct interaction with these helix-loop-helix proteins. These data demonstrate that the conserved CArG motifs form the core of a family of functionally different DNA regulatory elements that may contribute to the tissue-specific expression properties of their cognate promoters.
UNEXPECTED REACTION OF TRIS(TRIMETHYLSILYL)PHOSPHITE WITH A HINDERED NITRONE (1994)

Abstract Reaction of 5,5-dimethyl-2,4-diphenylpyrroline N-oxide with tris(trimethylsilyl)phosphite gave 2,2-dimethyl-3,5-trans-diphenylpyrrolidinium orthophosphite, as the only product, in 90% yield. The absolute structure of the title compound was established by X-ray crystallography. C18H24NO3P crystallizes in the triclinic space group P1 − with a = 8.806(4), b = 10.331(1), c = 11.375(5) Å, α = 65.55(6). β = 88.21(4), γ = 67.80(6), V = 866.5(4) Å3, Z = 2, dcal = 1.28, λ Mo Kα = 0.71069 Å. μ = 1.666 cm−1, F(000) = 356, T = 293 K. The compound presents a trans C-3,C-5 diphenylpyrrolidine structure with a dihedral angle = 91.66° between the two phenyl rings. Key Words: Nitrone deoxygenation2-phenylpyrroline-N-oxideimine reduction bis(trimethylsilyl)-phosphite
ChemInform Abstract: Total Synthesis of (‐)‐Cylindrocyclophanes A and F Exploiting the Reversible Nature of the Olefin Cross Metathesis Reaction. (2001)

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.
3,5-Bis(trifluoromethyl)pyrazoles:  A Novel Class of NFAT Transcription Factor Regulator (2000)

A series of bis(trifluoromethyl)pyrazoles (BTPs) has been found to be a novel inhibitor of cytokine production. Identified initially as inhibitors of IL-2 synthesis, the BTPs have been optimized in this regard and even inhibit IL-2 production with a 10-fold enhancement over cyclosporine in an ex vivo assay. Additionally, the BTPs show inhibition of IL-4, IL-5, IL-8, and eotaxin production. Unlike the IL-2 inhibitors, cyclosporine and FK506, the BTPs do not directly inhibit the dephosphorylation of NFAT by calcineurin.
Impaired Hepatocyte Glucose Transport Protein (GLUT2) Internalization in Chronic Pancreatitis (2001)

Chronic pancreatitis (CP) is associated with impaired glucose tolerance and with reduced hepatic sensitivity to insulin. We have previously shown that in normal and sham-operated rats, insulin suppresses hepatic glucose production, and this suppression is associated with a decrease in the hepatocyte plasma membrane-bound quantity of the facilitative glucose transport protein GLUT2. The insulin-mediated reduction in membrane-bound GLUT2 is impaired in CP, and may play a role in the glucose intolerance associated with CP. To determine whether GLUT2 is actively internalized and whether this mechanism is disordered in CP, livers from fed and fasting rats in whom CP had been induced 2-3 months earlier by pancreatic duct oleic acid infusion, and in sham-operated (sham) rats, were fractionated to yield endosome (E)- and plasma membrane (PM)-enriched fractions. Forty-five minutes after duodenal intubation alone (fasting) or intubation plus duodenal feeding, livers were removed, homogenized and ultracentrifuged, and microsomal pellets were separated by sucrose density gradient ultracentrifugation. GLUT2 content of fractions was determined by Western blotting and scanning densitometry. The E:PM ratio of GLUT2 increased from 0.68 +/- 0.11 (mean +/- SEM) in fasting sham livers (n = 8) to 1.04 +/- 0.09 in fed sham livers (n = 8; p < 0.05). However, there was no change in the E:PM ratio of GLUT2 in CP livers after duodenal feeding (0.90 +/- 0.12 vs. 0.86 +/- 0.10; n = 8,8; p = NS). To test our findings using confocal laser scanning microscopy, liver specimens from fed and fasting CP and sham rats were minced, fixed in 4% paraformaldehyde, sectioned, and stained with rabbit antirat GLUT2 antibody followed by rhodamine-labeled secondary antibody. GLUT2 was quantified by mean pixel intensity in an 8 x 16-pixel area of PM and a 16 x 16-pixel area of cytosol (CYT) in each of 30 random cells/field (400x) in each of three rats per group. As in the fractionation study, duodenal feeding increased the CYT:PM ratio of GLUT2 from 0.75 +/- 0.01 in fasting sham liver to 0.86 +/- 0.01 in fed sham liver (p < 0.0001), while the CYT:PM ratio in CP remained unchanged. We conclude that feeding induces a shift in GLUT2 from the plasma membrane to the endosomal pool. The feeding-induced internalization of GLUT2 is absent in livers from rats with CP and may play a role in the glucose intolerance associated with CP.
A platform with connections in many directions – further remarkable facets to the multifaceted methylbiquinoxen dication (2016)

The N,N'-dimethyl-3,3'-biquinoxalinium "methylbiquinoxen" dicationic platform is revealed to have even more fascinating possibilities than we originally thought in terms of its chemical versatility. In addition to its rich redox chemistry and coordination abilities, we have now unveiled an unexpected Lewis acid/base chemistry linked with a tuneable switching of its luminescence properties. This, amongst other things, allows for the facile fluorescent covalent labelling of hydroxyl-terminated materials. This platform provides intriguing chemical prospects realised in molecular systems such as porphyrins as well as an easy alternative functionalisation methodology to that provided by click-chemistry.
Implementation of Practical Super-Resolution Near-Field Structure System Using Commercial Drive (2006)

The implementation of a practical super-resolution near-field structure (Super-RENS) system using an existing commercial drive is achieved. Using ZnO-type Super-RENS discs as storage media, the commercial drive can perform mark position recording at a mark size of 220 nm and correctly retrieve the recorded signal.
Selective molecular assembly patterning at the nanoscale: a novel platform for producing protein patterns by electron-beam lithography on SiO2/indium tin oxide-coated glass substrates (2005)

The creation of geometrically well-defined submicron structures on insulating substrates by e-beam lithography is hampered by surface charging. This problem becomes crucial when trying to create nanosized protein patterns by selective molecular assembly patterning (SMAP) on transparent glass substrates. In this paper we demonstrate that the use of thin films of conductive indium tin oxide resolves the issue of surface charging during e-beam writing while being compatible with the standard SMAP protocol for surface modification. Â© 2005 IOP Publishing Ltd.
NMR of a synthetic peptide spanning the triphosphate binding site of adenosine 5'-triphosphate in actin (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNMR of a synthetic peptide spanning the triphosphate binding site of adenosine 5'-triphosphate in actinJulian A. Barden and Bruce E. KempCite this: Biochemistry 1987, 26, 5, 1471–1478Publication Date (Print):March 1, 1987Publication History Published online1 May 2002Published inissue 1 March 1987https://pubs.acs.org/doi/10.1021/bi00379a039https://doi.org/10.1021/bi00379a039research-articleACS PublicationsRequest reuse permissionsArticle Views23Altmetric-Citations7LEARN 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
A global approach to path planning for redundant manipulators (2002)

An approach to the path planning of redundant manipulators is presented. The path planning problem is posed as a finite-time nonlinear control problem which can be solved by a Newton-Raphson type algorithm. This technique is capable of handling various goal task definitions, as well as incorporating both joint and task space constraints. The algorithm shows promising results in planning joint path sequences and Cartesian tip tracking and goal endpoint specifications. In contrast to local approaches, this algorithm is less prone to problems such as singularities and local minima. Applications to planar 3-R and 4-R arms, cooperating 3-R arms and a spatial nine-degrees-of-freedom arm are included.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A breakthrough in understanding the molecular basis of coral heat tolerance (2020)

Respiratory virus infections in humans are a significant global health concern, causing a wide range of diseases with substantial morbidity and mortality worldwide. This underscores the urgent need for effective interventions to reduce the ...Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are ...
Lysosomal lipid peroxidation regulates tumor immunity (2023)

Lysosomal inhibition elicited by palmitoyl-protein thioesterase 1 (PPT1) inhibitors such as DC661 can produce cell death, but the mechanism for this is not completely understood. Programmed cell death pathways (autophagy, apoptosis, necroptosis, ferroptosis, and pyroptosis) were not required to achieve the cytotoxic effect of DC661. Inhibition of cathepsins, or iron or calcium chelation, did not rescue DC661-induced cytotoxicity. PPT1 inhibition induced lysosomal lipid peroxidation (LLP), which led to lysosomal membrane permeabilization and cell death that could be reversed by the antioxidant N-acetylcysteine (NAC) but not by other lipid peroxidation antioxidants. The lysosomal cysteine transporter MFSD12 was required for intralysosomal transport of NAC and rescue of LLP. PPT1 inhibition produced cell-intrinsic immunogenicity with surface expression of calreticulin that could only be reversed with NAC. DC661-treated cells primed naive T cells and enhanced T cell-mediated toxicity. Mice vaccinated with DC661-treated cells engendered adaptive immunity and tumor rejection in "immune hot" tumors but not in "immune cold" tumors. These findings demonstrate that LLP drives lysosomal cell death, a unique immunogenic form of cell death, pointing the way to rational combinations of immunotherapy and lysosomal inhibition that can be tested in clinical trials.
Assessment of Patient Factors, Surgeons, and Surgeon Teams in Immediate Implant-Based Breast Reconstruction Outcomes (2015)

Risk, III.
In vitro Biological Characteristics of Human Cord Blood-derived Megakaryocytes (2004)

The methods used in this study are specific for differentiation of Mk from CB CD34+ cell, which can partially mature and produce functional platelets in vitro. This approach for human Mk differentiation could be further optimised and may be adapted on larger scales for clinical purposes.
198 A Team-based Approach to an Integrated Model of Diabetes Care (2022)

OBJECTIVES/GOALS: Diabetes is related to risk for heart disease, stroke, high blood pressure, and COVID-19. It is exacerbated by built/social environment issues, e.g., food insecurity, access to healthy foods and health care, and other poverty-related factors. Our goal is to assess the efficacy of an integrated care model for patients with poorly controlled diabetes. METHODS/STUDY POPULATION: We utilize an integrated, team-based approach to diabetes treatment. In a traditional care model, too little focus is on social determinants and their impacts on health and well-being. Our project involves enrollment of patients with diabetes in an intervention whereby their medical care is integrated with intensive diabetes education and provision of social and other health services, including diet and nutrition, exercise, provision of foods and nutritional supplements, and other support services as needed to achieve optimal health and to reduce morbidity and unnecessary hospitalization and emergency room visits. Subjects are underserved patients treated through our non-profit community clinic partners. We track metrics including individual outcomes, organizational outcomes, and collective impact. RESULTS/ANTICIPATED RESULTS: We anticipate that patients enrolled in this study will demonstrate significant improvements in diabetes control and management. Clinical improvements will include better glycemic control, improved hypertension and dyslipidemia management, reduced complications, and increased preventive measures including foot, eye and oral health exams and monitoring of microalbuminuria. Overall, we anticipate decreased frequency of hospitalizations and readmissions as well as decreased frequency of emergency care visits for treatment of diabetes-related issues. We expect patients to experience enhanced self-efficacy, increased physical activity, and improved quality of life. Their outcomes will be compared to controls receiving the standard medical regimen, matched on age, race, gender, and time of onset. DISCUSSION/SIGNIFICANCE: These activities will improve understanding of factors influencing diabetes outcomes at individual and upstream levels. It will inform food distribution and models of care for improved patient outcomes, including social determinants of health and will establish new protocols for community-based provision of health care to our most vulnerable.
高血圧と心血管合併症に対するテーラーメイド医療(5. 高血圧の分子機序とテーラーメイド医療)(<特集>第68回日本循環器学会学術集会) (2004)

テーラーメイド医療は,試行錯誤をできるだけ減らし,最低限の副作用と最大限の効果を生み出す治療法を予測することを目標にした概念であるといえるが,高血圧の分野においてはまだ確立されたものはない.表1こ示すように,Laragh博士が唱えたレニン活性値をもとにした薬剤選択は,テーラーメイド医療の走りであったかもしれない.現在のエビデンスとガイドラインを主体にした治療法においては,個人の病態をリスクや合併症によって層別化したうえで治療指針を決めるようにしており,ある程度テーラーメイド医療に近づいたといえる.しかしながら実際には,血圧値や副作用の有無に基づいて試行錯誤的に治療法を選択する機会が多い.ヒトゲノム解析が終わり,テーラーメイド医療に必須の個人情報を遺伝子レベルで網羅的に解析することが可能になりつつあり,医療全般においては,最近の遺伝薬理学の進歩や各種疾患の遺伝子解析によってテーラーメイド医療が一部実用化されつつある.高血圧やその合併症に関しても候補遺伝子解析に加えてミレニアムプロジェクトをはじめ網羅的な遺伝子解析が進められており,テーラーメイド医療に向けてデータが蓄積されている.本稿では,高血圧のテーラーメイド医療の現状と将来について,高血圧関連遺伝子解析,遺伝薬理学の観点からそれぞれ概説する.
Several aspects concerning cold welding of cogged parts (2005)

The paper describes the process that envisages joining of an aluminium part with a harder cogged copper part by using pressing cold welding. The principle consists in the deformation of the more plastic part – namely the aluminium one. The maximum mechanical strength is obtained at the deformation rates superior to 20%, value obviously much lower that the one characterising the usual cold welding (minimum 70%). While the tensile strength of the joint is low (around 10% of the tensile strength of the parent metal), the shearing strength is much relevant. Through an appropriate thermal treatment, the value of the tensile strengths can be doubled, due to the diffusion processes. The analysis of the contact electrical resistance shows very important conclusions for the practical applications of this method.
Continuous Learning for Large-scale Personalized Domain Classification (2019)

Han Li, Jihwan Lee, Sidharth Mudgal, Ruhi Sarikaya, Young-Bum Kim. Proceedings of the 2019 Conference of the North American Chapter of the Association for Computational Linguistics: Human Language Technologies, Volume 1 (Long and Short Papers). 2019.
Supplementary Figure 1 from CD4<sup>+</sup> T-Cell Help in the Tumor Milieu Is Required for Recruitment and Cytolytic Function of CD8<sup>+</sup> T Lymphocytes (2023)

Supplementary Figure 1 from CD4&lt;sup&gt;+&lt;/sup&gt; T-Cell Help in the Tumor Milieu Is Required for Recruitment and Cytolytic Function of CD8&lt;sup&gt;+&lt;/sup&gt; T Lymphocytes
Proteoglycan 4 reduces friction more than other synovial fluid components for both cartilage-cartilage and cartilage-metal articulation (2021)

The present study demonstrates the importance of selecting the appropriate lubrication solution to evaluate implant materials with biotribology tests. Because PRG4 is a key component for reducing friction between cartilage and an opposing surface, developing coatings which bind PRG4 is recommended for cartilage resurfacing implants.