gebhart/patrepeval huggingface dataset:
Design of a linker for trivalent thrombin inhibitors: Interaction of the main chain of the linker with thrombin (1993)

N alpha-Acetyl[D-Phe45,Arg47]hirudin45-65 (P53) is a bivalent thrombin inhibitor (Ki = 5.6 nM) that consists of an active site inhibitor segment, [N alpha-acetyl-(dF)PRP]; a fibrinogen recognition exo site inhibitor segment, hirudin55-65 (DFEEIPEEYLQ-OH); and a linker, hirudin49-54 (QSHNDG), connecting these inhibitor segments (DiMaio et al., 1990). The structure-function relationships of the linker were studied using a combination of various omega-amino acids, which modified the length of the linker as well as the number and the locations of peptide bonds. Linkers with 14-18 atoms (counting only the atoms contributing to the length of the linker) showed a competitive inhibition with Ki = 1.7-3.4 nM. The potency of the inhibitors with 12-13-atom linkers was sensitive to the chemical structure of the linker. The high-potency inhibitors showed a competitive inhibition, while the low-potency inhibitors showed a hyperbolic inhibition. Among them, an inhibitor with a 13-atom linker showed the highest potency (Ki = 0.51 nM, an 11-fold improvement from that of P53 above), indicating that this is an optimal linker length. Since linkers with 6-10 atoms failed to bridge the active site and exo site inhibitor segments, a minimum of 11 atoms was required to bridge them, even though the potency of the inhibitor with an 11-atom linker was weak (Ki = 26 nM). Molecular dynamics simulation of the inhibitors with 13-atom linkers suggested that some linkers serve as a functional domain with the amide bond of the linker interacting with thrombin through hydrogen bonds.(ABSTRACT TRUNCATED AT 250 WORDS)
Transdermal Contraception (2001)

This review summarizes the clinical studies involving the once-weekly Ortho Evra/Evra contraceptive patch. The patch delivers norelgestromin (NGMN), 150 microg, and ethinyl estradiol (EE), 20 microg, daily to the systemic circulation. The contraceptive patch provided ovulation suppression and cycle control similar to that of oral norgestimate 250 microg/EE 35 microg, significantly decreased mean maximum follicular diameter following a 3-day intentional delayed dosing phase when compared with oral levonorgestrel (LNG) 50/75/125 microg/EE 30/40/30 micorg and oral LNG 100 microg/EE 20 microg, and was as effective as oral LNG 50/75/125 microg/EE 30/40/30 microg and oral desogestrel 150 microg/EE 20 microg in altering cervical mucus composition (i.e., creating a scanty, viscous consistency). The contraceptive patch provided efficacy, cycle control, and safety comparable to that seen with oral LNG 50/75/125 microg/EE 30/40/30 microg, but women were able to correctly follow the weekly dosing regimen significantly more often than the daily oral contraceptive dosing regimen. Less than 2% of patches were replaced because of complete detachment in these trials. The patch was not associated with phototoxicity or photoallergy. The contraceptive patch, the only noninvasive, weekly birth control method that a woman can self-administer, will be a valuable addition to current contraceptive options.
Fuzzy-based Methods for Privacy-Preserving Data Mining (2011)

As more and more organizations are collecting and sharing data about their customers, there is a growing concern about violation of customer privacy. While some of the sharing is for the benefit of general public such as to understand disease behavior in medical research, individuals are concerned about violation of their privacy. The middle ground is found through privacy-preserving data mapping. Here, sensitive attributes of data are mapped to another domain so that original values are not revealed and yet the original associations are retained. In this paper, we compare a set of fuzzy-based mapping techniques in terms of their privacy-preserving property and their ability to retain the same relationship with other fields. In particular, our contribution is on four fronts: (i) modification of the fuzzy function definition, (ii) introducing seven ways to combine the different functional values for a data item into a single value, (iii) using several similarity metrics to compare the original data with the mapped data, (iv) measuring the effect of mapping on derived association rule. The paper presents preliminary results in this direction and proposes future work in this area.
Anti-Human Cytomegalovirus Activity of Chemical Constituents from Kumazasa Hot Water Extract (2010)

現在我々は，代替医療薬を中心に抗 HCMV 薬の探索を行っており，防腐作用（抗菌作用）を含む種々の生理活性をもつクマザサに着目し，その熱水抽出液に抗 HCMV 作用があることを明らかにしてきた．今回，クマザサ熱水抽出液の成分の一部が分離・精製・同定され，その中の 1 つである tricin がウイルス粒子産生に最も高い抑制効果を示すことがわかった．また，その抑制効果は，クマザサ抽出液同様のウイルス感染後の処理だけでなく，感染前処理した場合にも見られることがわかった．さらにリアルタイム RT-PCR 法および，ウエスタンブロット法による解析の結果，tricin がウイルスの複製・増殖に重要な major immediate early (IE) 遺伝子の発現を抑制することがわかり，tricin が現在使用されている GCV とは異なる作用機序により抗 HCMV 効果をもつことが示され，新たな治療薬としての可能性が示唆された．
Attempt to Prevent Erythroblastosis Foetalis by Use of Cortisone During Pregnancy (1952)

Since the discovery by Landsteiner and Wiener (1940) of the rhesus factor great advances have been made in the understanding of erythroblastosis foetalis, and it is now firmly established that the condition results from the development in the pregnant woman of immune antibodies capable of crossing fhe placental barrier and causing excessive red-cell destruction in the foetus. This recent knowledge has led to several attempts to inhibit the development of such antibodies. Thus Wiener and Sonn (1946) gave injections of typhoid and pertussis vaccines during pregnancy in the hope that the administration of a strong antigen might interfere with the development of antibodies in response to the weaker (Rh) antigen. Kariher (1947), acting upon reports that ethylene disulphonate was alleged to be of value in allergic conditions, administered this substance in minute amounts to pregnant women who had pre viously given birth to infants with haemolytic disease. His results suggested that such treatment may have some effect in lowering the antibody titre in the maternal serum. Carter (1947, 1949) claimed to have isolated from human Rh-positive red cells a fraction containing an Rh hapten, and reported that injections of this frac tion into Rh-sensitized pregnant women resulted in a fall in titre of the circulating Rh antibodies. Other workers, notably Howe and Rustigian (1950), and Spurling et al. (1950), have failed to produce results comparable to those of Carter. So far no widely accepted therapeutic procedure has resulted from these attempts to inhibit Rh antibodies. At the present time the effects of cortisone and A.C.T.H. upon immunity reactions are incompletely understood. The available reports indicate a species difference: cf. guinea-pig (Dews and Code, 1951), rabbit (Germuth and Ottinger, 1950), and man (Mirick, 1951). In man A.C.T.H. and cortisone apparently do not inhibit the development of antibodies (Havens et al., 1951) but are able to prevent hypersensitivity reactions (Long and Favour, 1950). It seems that in man the adrenal agents prevent either the union of antigen and antibody or the tissue injury which results from such union.
Active Multi-View Object Recognition and Change Detection (2015)

In many systems, especially in robotic systems, active reasoning and decision making is essential for a successful deployment. The goal of active reasoning is to choose subsequent actions with the highest utility to maximally
Cytotoxicity ofin vitroproduced podophyllotoxin frompodophyllum hexandrumon human cancer cell line (2003)

Podophyllotoxin was produced by cell culture of Podophyllum hexandrum under in vitro culture conditions. A maximum of 4.26 mg/L of podophyllotoxin was produced when P. hexandrum was cultivated in 3 L stirred tank bioreactor. The compound extracted from the cell culture was applied to the human breast cancer cell line (MCF-7) and 1 nM podophyllotoxin was able to inhibit the growth of the cancer cells by 50%. The most profound inhibitory effect of podophyllotoxin was observed when it was applied in the beginning of cell growth.
Image restoration: Total variation, wavelet frames, and beyond (2012)

The variational techniques (e.g. the total variation based method) are well established and effective for image restoration, as well as many other applications, while the wavelet frame based approach is relatively new and came from a different school. This paper is designed to establish a connection between these two major approaches for image restoration. The main result of this paper shows that when spline wavelet frames of are used, a special model of a wavelet frame method, called the analysis based approach, can be viewed as a discrete approximation at a given resolution to variational methods. A convergence analysis as image resolution increases is given in terms of objective functionals and their approximate minimizers. This analysis goes beyond the establishment of the connections between these two approaches, since it leads to new understandings for both approaches. First, it provides geometric interpretations to the wavelet frame based approach as well as its solutions. On the other hand, for any given variational model, wavelet frame based approaches provide various and flexible discretizations which immediately lead to fast numerical algorithms for both wavelet frame based approaches and the corresponding variational model. Furthermore, the built-in multiresolution structure of wavelet frames can be utilized to adaptively choose proper differential operators in different regions of a given image according to the order of the singularity of the underlying solutions. This is important when multiple orders of differential operators are used in various models that generalize the total variation based method. These observations will enable us to design new methods according to the problems at hand, hence, lead to wider applications of both the variational and wavelet frame based approaches. Links of wavelet frame based approaches to some more general variational methods developed recently will also be discussed.
Safety, Immunogenicity, and Effectiveness of Defective Viral Particles Arising in Mast Cells Against Influenza in Mice (2020)

Mast cells play pivotal roles in the pathogenesis of influenza A virus (IAV) infections. Defective viral particles (DPs) often arise during IAV replication, which can interfere with the replication of infectious viruses and stimulate the antiviral response of host cells. Therefore, DPs are expected to have immune-protective functions in clinic. However, the potent immunogenicity and effectiveness of DPs arising in mast cells during IAV replication have not been reported. In the present study, we showed that DPs generated in the human mastocytoma cell line HMC-1 following H1N1 infection were safe to mice after vaccination. Compared with lung adenocarcinoma cells, A549, DPs generated in infected mast cells had much better immunostimulatory activity, enhancing both humoral and cellular immunity of hosts. Notably, they could significantly increase the expression of immune-associated cytokines, especially the IFN-γ. Due to the robust immunogenicity, thus DPs generated in infected mast cells could stimulate the robust protective immune reaction effectively to fight against lethal IAV re-challenge after vaccination, which result in the high survival, decreased lung injury as well as inhibition of viral replication and inflammatory response in lungs. This study is the first to illustrate and explore the safety, immunogenicity, and effectiveness of DPs arising in mast cells against influenza as favorable potential vaccination. The results provide insight into the advances of new prophylactic strategies to fight inﬂuenza by focusing on DPs generated in mast cells.
Abstract P4-15-02: The PI3K inhibitor GDC-0032 enhances the efficacy of standard of care therapeutics in PI3K alpha mutant breast cancer models (2013)

Abstract The phosphoinositide 3-kinases (PI3Ks) are lipid kinases that activate the PI3K signaling pathway and play an essential role in regulating breast tumor cell growth, migration, and survival. Activating and transforming mutations in the PIK3CA gene (PI3K alpha) are commonly found in HER2+ breast cancer and ER+ breast cancer. GDC-0032 is a selective, orally bioavailable inhibitor with a Ki of 0.29 nM for PI3K alpha with 30 fold less inhibition of PI3K beta. In addition, GDC-0032 has increased single agent activity against PI3K alpha mutant and HER2 amplified cancer models in vitro and in vivo. The aim of our study was to evaluate the efficacy of GDC-0032 in breast cancer models in combination with standard of care therapeutics including taxanes, endocrine therapies, and HER2 targeted therapies. We evaluated cell viability for a range of dose concentrations of GDC-0032, as single agent and in combinations, in eleven breast cancer cell lines that harbor mutations in PI3K alpha (K111N, E545K, H1047R) and/or over-expressed HER2. GDC-0032 was combined with taxanes (paclitaxel and docetaxel), endocrine therapies (fulvestrant and tamoxifen) or anti-HER2 agents (trastuzumab, pertuzumab or ado-trastuzumab-emtansine) and synergy quantified using the Chou and Talalay method of Combination Index (C.I.). The combination of GDC-0032 with taxanes, endocrine therapies or anti-HER2 therapies were synergistic in the breast cancer cell lines tested based on C.I. values of less than 1.0. The combination of GDC-0032 with docetaxel in vitro resulted in decreased viability as a result of increased cell death. The in vitro results translated in vivo as GDC-0032 enhanced the anti-tumor activity of docetaxel and paclitaxel in MCF7 (E545K) xenografts that resulted in increased tumor regressions when GDC-0032 was dosed daily or intermittently on the same schedule as the taxane. In addition, the combination of GDC-0032 and fulvestrant or tamoxifen resulted in greater efficacy in the MCF7 xenograft model when compared to either agent alone. Enhanced efficacy was also observed when GDC-0032 was combined with trastuzumab or ado-trastuzumab-emtansine in the HER2+ BT474M1 (K111N) xenograft model. Moreover, the triple combinations of GDC-0032/trastuzumab/pertuzumab or GDC-0032/trastuzumab/docetaxel resulted in durable tumor regressions that were sustained in the HER2+ KPL-4 (H1047R) and BT474M1 xenograft models, respectively. All drug combinations with GDC-0032 were well tolerated in vivo based on minimal changes in body weight. Collectively, our preclinical data demonstrate that GDC-0032 enhances the efficacy of standard of care therapeutics in PI3K alpha mutant breast cancer models and provides a strong rationale for further evaluation in patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-15-02.
Containerless Crystallization of Semiconductors (2012)

This chapter contains sections titled: Introduction Status of Research on Facetted Dendrite Growth Twin-Related Lateral Growth and Twin-free Continuous Growth Containerless Crystallization of Si [33] Summery and Conclusion Appendix 12.A: LKT Model Wilson–Frenkel Model References
Deep learning based fence segmentation and removal from an image using a\n video sequence (2016)

Conventional approaches to image de-fencing use multiple adjacent frames for\nsegmentation of fences in the reference image and are limited to restoring\nimages of static scenes only. In this paper, we propose a de-fencing algorithm\nfor images of dynamic scenes using an occlusion-aware optical flow method. We\ndivide the problem of image de-fencing into the tasks of automated fence\nsegmentation from a single image, motion estimation under known occlusions and\nfusion of data from multiple frames of a captured video of the scene.\nSpecifically, we use a pre-trained convolutional neural network to segment\nfence pixels from a single image. The knowledge of spatial locations of fences\nis used to subsequently estimate optical flow in the occluded frames of the\nvideo for the final data fusion step. We cast the fence removal problem in an\noptimization framework by modeling the formation of the degraded observations.\nThe inverse problem is solved using fast iterative shrinkage thresholding\nalgorithm (FISTA). Experimental results show the effectiveness of proposed\nalgorithm.\n
Collector-Emitter Voltage Based One-Step Commutation for Direct Three-Level Matrix Converter (2018)

This paper investigates the improvements regarding the output current distortion, voltage rise and common mode voltage stress, when applying a collector-emitter voltage based commutation process to a direct three-level matrix converter (DTMC) drive. To analyse this, a new pulse pattern that addresses the voltage stress at the converter output terminals is derived from the derived from the known direct matrix converter (DMC) modulation. Based on this a 2/3/4-step input voltage based commutation, a 1/2-step load-current based commutation and the proposed I-step u CE -based commutation strategy are compared. Their advantages and disadvantages are discussed regarding experimental results.
Figure S3 from RTK-Dependent Inducible Degradation of Mutant PI3Kα Drives GDC-0077 (Inavolisib) Efficacy (2023)

&lt;p&gt;Taselisib and GDC-0077 induce mutant p110a and not WT p110a degradation&lt;/p&gt;
Diagnostic utility of array‐based comparative genomic hybridization in a clinical setting (2007)

Array-based comparative genomic hybridization is a recently introduced technique for the detection of submicroscopic genomic imbalances (deletions or duplications) across the entire genome. To assess the potential utility of a widely available array-based comparative genomic hybridization platform that targets specific, clinically relevant, loci across the genome for cytogenetic diagnosis in a clinical setting, we reviewed the medical records of all 373 patients at Children's Hospital Boston who had normal chromosomal analysis and were tested with this targeted array-based comparative genomic hybridization over a 1-year period from November 1, 2004 to October 31, 2005. These patients were tested because of a suspicion of chromosomal abnormalities based on their clinical presentation. Thirty-six patients (9.7%) had abnormal array-based comparative genomic hybridization results. Twenty patients (5.4%) had potentially pathogenetic genomic imbalances and 16 patients (4.3%) had copy number variations that are not believed to be pathogenetic. Thirteen of 234 patients (5.6%) with mental retardation/global developmental delay, 10/114 patients (8.8%) with facial dysmorphism, 5/58 patients (8.6%) with multiple congenital anomalies, and 4/35 patients (11.4%) with both facial dysmorphism and multiple congenital anomalies had potentially pathogenetic genomic imbalances. Targeted array-based comparative genomic hybridization is a clinically available test that is useful in the evaluation of patients suspected of having chromosomal disorders. However, it is best used as an adjunct to chromosomal analysis when a clear genetic diagnosis is unavailable.
Signalling approaches to inhibition of cellular proliferation (2005)

There has been considerable progress in elucidating the mechanisms by which extracellular signals are transduced via cell surface receptors to trigger changes in gene expression determining the growth and differentiated state of the cell. Efforts to understand and target the mechanisms that underlie the development of abnormal proliferative diseases including vascular injury and cancer are under intense study [1,2]. We have targeted several strategies to inhibit cellular proliferation including blockade of platelet derived growth factor (PDGF) mediated mitogenic signalling and secondly with a downstream target by interfering with ras protein function via the enzyme ras farnesyl transferase (FTase) [1,2]. Strategies to develop potent cellular acting peptide inhibitors of the association of the C-terminal SH2 domain of the p85 subunit of phosphatidyl 3-kinase (PI, kinase) with the PDGF -receptor from the phosphorylated pentapeptide Tyr(PO3H2)751-Val-Pro-Met-Leu (IC50) = 0.67 pM) have led to potent tetraand tripeptide inhibitors. In the second signalling strategy, development of potent peptidomimetic inhibitors of the enzyme FTase are presented. Truncated triand dipeptides and peptidomimetics with cellular activity derived from the pentapeptide lead PD 083 176 (Cbz-His-Tyr(OBn)-Ser(OBn)-TrpDAla-NH2) (IC50)=17 nM) have been discovered.
The key statements of the Maastricht VI consensus (2022)

An analysis of the most important changes and provisions of the Maastricht VI consensus published in August 2022 is presented. 41 experts from 29 countries took part in the creation of the consensus. Recommendations have been developed in five areas: (1) indications for treatment and clinical associations of Helicobacter pylori (H. pylori) infection, (2) diagnosis, (3) treatment, (4) prevention of gastric cancer, (5) H. pylori and gastric microbiota -intestinal tract (GIT), taking into account the level of evidence and the strength of recommendations. Emphasis is placed on molecular testing, which is becoming an increasingly accessible research method in the world to identify both H. pylori itself and its sensitivity to antibiotics. The growing resistance of H. pylori strains to previously effective antibacterial agents requires a treatment strategy that implies the ability to determine the sensitivity of H. pylori to antibacterial agents both in the population and in a particular individual. The use of modern diagnostic tests expands the possibilities of individualization of therapy, since it allows determining not only the presence of H. pylori in the gastric mucosa, but also the sensitivity of the infection to antibacterial drugs. Along with individual approaches to treatment, the most effective empirical therapy regimens are given in case of impossibility to determine individual resistance to antibiotics. New data on the effectiveness and results of the use of primary and secondary preventive strategies for gastric cancer are presented. Given the important role of the entire microbiome of the gastrointestinal tract in the functioning of the body, the question of the interaction of H. pylori with other microorganisms is discussed. The critical issues of the near future are related to the global prevention of gastric cancer; the need to control antibiotic resistance, and the development of new methods of therapy and prevention of Helicobacter pylori infection.
Experimental realization of two-dimensional artificial skyrmion crystals at room temperature (2014)

We report the creation of an artificial skyrmion crystal, which is configurable reliably at room temperature. The samples are fabricated by embedding lithography-patterned arrays of micron-sized Co disks onto Co/Pt multilayer films that have perpendicular magnetic anisotropy. Kerr microscopy and magnetic force microscopy reveal that the disks are in the vortex state with controllable circulation. Via comparison of measured hysteresis loops and calculated ones, we find that the sample can be configured into either a skyrmion or a non-skyrmion state. The reproducible and stable skyrmion crystal at room temperature opens the door to direct exploration of their unique topological properties, which has deservedly caused a flurry of theoretical activity.
[Hereditary pancreatitis. Two new kindreds ]. (1982)

An acute pancreatitis was observed in 2 children belonging to two unrelated families in which a total of 8 kindreds also had pancreatitis. Evolution was so severe that it demanded parenteral feeding and partial pancreatectomy with Wirsung-intestinal shunting. The authors stress: the rarity of this condition (which has a dominant autosomal transmission), the lack of specificity, the severity in which pseudocysts predominate, the further occurrence of both diabetes and external pancreatic deficiency and finally, the risk of pancreatic carcinoma.