gebhart/patrepeval huggingface dataset:
Comprehensive genomic profiling and individual therapeutic planning in high-risk/refractory pediatric solid tumors: A single-center real-world study. (2023)

10035 Background: Despite major improvements in the survival of pediatric cancer patients that were achieved through the intensification of chemotherapy and the perfection of supportive care in the past decades, treatment outcomes for high-risk, relapsed, and refractory solid cancers remain unsatisfactory. Accelerating the progress of pediatric oncology requires both therapeutic advances and attention to reducing the long-term cytotoxic treatment-related side effects. This could be achieved by targeting specific molecular changes that drive pediatric malignancies. Methods: From September 2016 to August 2020, a total of 192 patients with pediatric high-risk solid tumors successfully underwent comprehensive genomic profiling. Since more than thirty patients had two or more biopsies from recurrent relapses, the total number of samples examined was 295. In the cohort, there were 78 cases of central nervous system tumors, 68 sarcomas, 14 neuroblastomas, 10 lymphomas, and 22 tumors of other histology. Whole-exome sequencing was performed in all patients, fusion gene analysis in 96% of patients, whole-transcriptome profiling in 84% of patients, and CNV analysis in 63% of patients. Results: The diagnostic yield of therapeutically actionable findings was 40%, with single-nucleotide variants and small insertions/deletions being the most common actionable alteration types. In 23% of patients, a clinically relevant gene fusion was identified. The majority of the identified fusions were of diagnostic significance, and 18% of those were therapeutically targetable gene fusions involving BRAF, RAF1, ALK, FGFR1, or NTRK2. Four patients were eligible for immunotherapy based on high tumor mutational burden ( &gt; 10 mut/Mb). Lymphomas and CNS tumors showed the highest rate of patients with therapeutically actionable findings (60% and 56%, respectively), followed by neuroblastomas (36%), sarcomas (25%), and other solid tumors (23%). All results and individual treatment plans were discussed and approved at multidisciplinary molecular tumor boards. Conclusions: Precision medicine in pediatric oncology has rapidly developed over the last decade and resulted in new therapeutic options based on molecular biomarkers and increased our understanding of the complexity of pediatric malignancies. Supported by the Ministry of Health of the Czech Republic, grant nr. NU20-03-00240 and the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU.
In Humanized Sickle Cell Mice, Imatinib Protects Against Sickle Cell–Related Injury (2023)

Drug repurposing is a valuable strategy for rare diseases. Sickle cell disease (SCD) is a rare hereditary hemolytic anemia accompanied by acute and chronic painful episodes, most often in the context of vaso-occlusive crisis (VOC). Although progress in the knowledge of pathophysiology of SCD have allowed the development of new therapeutic options, a large fraction of patients still exhibits unmet therapeutic needs, with persistence of VOCs and chronic disease progression. Here, we show that imatinib, an oral tyrosine kinase inhibitor developed for the treatment of chronic myelogenous leukemia, acts as multimodal therapy targeting signal transduction pathways involved in the pathogenesis of both anemia and inflammatory vasculopathy of humanized murine model for SCD. In addition, imatinib inhibits the platelet-derived growth factor-B-dependent pathway, interfering with the profibrotic response to hypoxia/reperfusion injury, used to mimic acute VOCs. Our data indicate that imatinib might be considered as possible new therapeutic tool for chronic treatment of SCD.
Peptidoglycan Structure Analysis of Lactococcus lactis Reveals the Presence of an l , d -Carboxypeptidase Involved in Peptidoglycan Maturation (2006)

Detailed structural analysis of Lactococcus lactis peptidoglycan was achieved by identification of its constituent muropeptides separated by reverse phase high-performance liquid chromatography. Modification of the classical elution buffer allowed direct and sensitive analysis of the purified muropeptides by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The structures of 45 muropeptides were assigned for L. lactis strain MG1363. Analysis of the muropeptide composition of an MG1363 dacB mutant showed that the dacB-encoded protein has l,d-carboxypeptidase activity and is involved in peptidoglycan maturation.
Development of laboratory tests to predict the lubricity properties of diesel fuels and their application to the development of highly refined diesel fuels (1995)

Abstract In the last few years there has been an increasing requirement for the provision of environmentally benign diesel fuels. However, the introduction of such fuels into service has been associated with high levels of field failure of rotary distribution fuel pumps due to wear. This is because the refining processes necessary to produce ecologically acceptable fuels result in greatly reduced levels of sulphur compounds, aromatics, and polar material, many of which are potential lubricity agents. This paper describes the development of bench test methods to evaluate diesel fuel lubricity and thus enable the identification of appropriate ‘solutions’. It has been found that the key to obtaining good correlation between field experience and bench tests is (1) to reproduce the thermal conditions present in operating pump contacts and (2) to ensure that the same mechanisms of wear operate in the bench test as in the pump environment. The physical and chemical processes involved in the lubrication of fuel pumps and the influence of temperature on these processes are outlined. As a result of the work described in this paper, effective additive solutions have been discovered for controlling the failure of diesel fuel pumps in the field and a provisional ISO (ISO/TC 22 / SC 7 M595: ‘Diesel engines ‐ diesel fuel ‐ performance requirement and test method for assessing fuel lubricity’) and CEC test method for assessing diesel fuel lubricity has also been developed.
DEVELOPMENT AND INVESTIGATION OF TIMOLOL MALEATE AND LATANOPROST COMBINATION LIPOSOMES FOR THE TREATMENT OF GLAUCOMA (2015)

In this study liposomes were developed and evaluated for timolol maleate (TM) and latanoprost (LP) by lipid film hydration technique for the treatment of glaucoma. A 3 2 factorial design was utilized to study the effect of the molar ratio of 1, 2 -Dipalmitoyl-sn-glycero-3-phosphocholine (DPCC) (X1) and cholesterol (X2) on vesicle size, drug entrapment efficiency and in-vitro release study. Fourier transform infrared spectroscopy (FT-IR) studies were performed to investigate and predict any physiological interactions between components in the formulation. The liposomal vesicles were found to be uniform in size and shape. The drug entrapment efficiency values for the seven batches showed a variation from a minimum of 56.65 1.39 % to maximum of 70.24 1.14 %. This clearly indicates that the drug entrapment value is strongly dependent on the variables selected. The Zeta potential, average particle size and poly dispersibility index was found to be -17.3 mV, 240 nm and 0.114 respectively. Most of the formulations were found to have a linear release and the formulations were found to provide approximately 72 % -55 % of drug release for TM and LP respectively within a period of 6 h. Kinetic study reveals that release mechanism depends on swelling, diffusion and relaxation. Best formulation (F2) was found to be sterile and stable and free from microorganisms and passes the isotonicity test. Reduction in intra ocular pressure (IOP) was greater in liposomes as compared to the marketed product of alone and combination medication. A latanoprost-timolol maleate fixed combination, has the advantage of a more convenient delivery system as well as providing a simple summing effect of the two constituents.
Boltzmann Machine Topology Learning for Distributed Sensor Networks Using Loopy Belief Propagation Inference (2008)

Distributed sensor networks, as opposed to centralized networks, offer several advantages in terms of versatility and increased safety, which make their use particularly relevant for applications of security surveillance. A challenge of such systems is how to build autonomously a global description of the sensed environment without supervision of a central processing unit and with minimal configuration effort. We present an approach to ubiquitous computing, based on a semantic representation of the world view in terms of correlation of local information learned at the local level. There, a statistical description of the sensed activity is provided. Correlations of events among nodes are learned using a Boltzmann machine approach and used in order to establish neighborhood correspondences. Moreover, the communication between nodes is used to enrich the local description of the sensed environment by approximating the a-posterior distributions by marginal distributions computed with the loopy belief propagation algorithm. We present results of simulations emulating a security surveillance environment in which the sensors are cameras and activity is learned by processing video data.
데이터 공학 : 의료 정보 추출을 위한 TF-IDF 기반의 연관규칙 분석 시스템 (2016)

u-Health에 대한 관심과 IT 기술의 발전에 따라 의료 정보를 적극적으로 활용하고자 하는 요구가 커지고 있으며, 이에 대해 텍스트 형태의 의료 정보 데이터에 연관규칙 기법을 적용하여 질병과 증상과의 관계를 추론하는 시스템에 대한 연구들이 이루어지고 있다. 그러나 일반적인 연관규칙 기법을 의료 정보 데이터에 그대로 적용할 경우, 이전에는 새로운 연관규칙들보다 일반적이며 의미없는 연관규칙들이 많이 생성되는 문제가 발생한다. 또한 필터링으로 인해 빈번하게 함께 발생하지는 않지만 의학적으로 의미있는 항목들의 연관 규칙을 발견할 수 없다는 한계점을 가지게 된다. 본 논문에서는 의료데이터 특성을 고려하여 빈번한 항목과 빈번하지 않지만 의학적으로 의미 있는 항목들을 대상으로 연관규칙을 구성하여 의료 전문가의 의사 결정에 도움을 주기 위한 시스템을 제안한다. 제안 시스템은 의료 기록 데이터에서 용어들을 TF-IDF기반으로 가중치를 부여하고 기존 FP-Growth 알고리즘을 확장하여 TF-IDF 가중치를 고려한 빈번하게 발생하거나 빈번하지 않지만 의미 있는 연관규칙을 구성한다. 특정 질의 데이터가 입력되면 해당 데이터에 나타난 연관 규칙들의 유사도를 의학분야 온톨로지를 이용하여 평가하여 해당 데이터의 내용과 관련된 후보 질병들을 추론한다. 추론된 후보 질병명은 의료 전문가에게 의사 결정의 참고 자료로 제공된다. 실제 임상 진료 및 처방 기록 데이터에 대해 제안 시스템을 적용해 본 결과, 본 제안 시스템을 통해 도출한 연관 규칙이 기존 FP-Growth 알고리즘을 적용했을 때 보다 더 구체적인 질병과 증상과의 관계들을 포함함을 확인할 수 있었다. 또한 본 제안 시스템은 자유형식의 의료 및 병리데이터를 마이닝하고 후보 질병들을 가중치 기반으로 보여주므로, 의료 기록 정보로부터 질병 관련 새로운 정보를 획득하고 의료진의 의사 결정에 도움을주는 시스템으로 활용될 수 있다.
Another locally connected Hausdorff continuum not connected by ordered continua (1972)

An example is given of a locally connected Hausdorff continuum which is not connected by ordered continua.
Quartz-controlled complementary multivibrator (1976)

The operation and performance of a new quartz multivibrator is presented. The multivibrator is based on a freerunning circuit using a complementary regenerative switch. Owing to the use of this complementary switch, the multivibrator has high regeneration, low output impedance and no integration effect. As a result, it has small transition times (40ns) and a possibility of high loading (100Ω). Owing to the use of the quartz crystal, the multivibrator frequency is very stable at changes of supply voltage and load impedance. The circuit temperature stability is mostly dependent on that of the quartz crystal. The multivibrator can be adjusted for the generation of symmetrical or asymmetrical waveforms.
Isolation of Melanin Biosynthesis Inhibitory Compounds from the Phellodendri Cortex (2007)

− By screening inhibitory activities on the melanin polymer biosynthesis in B-16 mouse melanoma cell lines, MeOH extract of Phellodendri Cortex was found to have inhibitory effect on melanin polymer biosynthesis. Twelve compounds were isolated from the MeOH extract of P. Cortex. They were identified as obacunone (1), limonin (2), β-sitosterol (3), bis(2-methylheptyl)phthalate (4), cycloeucalenol (5), berberine (6), palmatine (7), jatrorrhizine (8), syringin (9), umbelliferone (10), rutaecarpine (11) and scopoletin (12) by comparison of their physical and spectral data with those of authentic samples. Among the isolated compounds, berberine (6) and palmatine (7) showed potent inhibitory effect on the melanin polymer biosynthesis in cultured B-16 mouse melanoma cell lines, with Inhibition rate of 96% and 90%, respectively. As a positive control, arbutin exhibited an inhibition rate of 56%.
Identification of a G2-like porcine rotavirus bearing a novel VP4 type, P[32] (2010)

A porcine group A rotavirus (GARV) strain, 61/07/Ire, was isolated from a 4-5 week asymptomatic piglet, during an epidemiological survey of porcine herds in Southern Ireland, in 2007. The nucleotide (nt) and amino acid (aa) sequence of the full-length VP4 protein of the PoRV strain 61/07/Ire was determined. Based on the entire VP4 open reading frame (nt), strain 61/07/Ire displayed ≤76.5% identity to representatives of the established 31 P-types, a value far lower than the percentage identity cutoff value (80%) established by the Rotavirus Classification Working Group (RCWG) to define a novel P genotype. Strain 61/07/Ire revealed low aa identity, ranging from 57.1% to 83.6%, to the cognate sequences of representatives of the various P genotypes. The aa identity was lower in the VP8* trypsin-cleavage fragment of the VP4, which encompasses the VP4 hypervariable region, ranging from 36.9% to 75.3%. Sequence analyses of the VP7, VP6, and NSP4 genes revealed that the GARV strain 61/07/Ire possessed a G2-like VP7, an E9 NSP4 genotype and an I5 VP6 genotype. Altogether, these results indicate that the GARV strain 61/07/Ire should be considered as a prototype of a new VP4 genotype, P[32], and provide further evidence for the vast heterogeneity of group A rotaviruses.
A general data fusion architecture (2003)

Data fusion is an important component of applications for systems that use correlated data from multiple sources to determine the state ofa system. As the state of the system being monitored and available resources change, the general data fusion famework should change dynamically based on the current environment and available resources in the system. To achieve this goal, we have proposed a general Data Fusion Architecture (DFA) based on the Unfled Modeling Language (UML) and using a taxonomy based on the definitions of raw data and variables or tasks. The DFA can be reconfigured according to the measured environment and availability of the sensing units or data sources, providing a graceful degradation in the view of the environment as resources change. We have shown that we can apply the DFA to dflerent domains and applications. including a test bed health monitoring application.
Protective effects of dexrazoxane against acute ischaemia/reperfusion injury of rat hearts (2012)

Dexrazoxane (DEX), an inhibitor of topoisomerase II and intracellular iron chelator, is believed to reduce the formation of reactive oxygen species (ROS) and protects the heart from the toxicity of anthracycline antineoplastics. As ROS also play a role in the pathogenesis of cardiac ischaemia/reperfusion (I/R) injury, the aim was to find out whether DEX can improve cardiac ischaemic tolerance. DEX in a dose of 50, 150, or 450 mg·(kg body mass)(-1) was administered intravenously to rats 60 min before ischaemia. Myocardial infarct size and ventricular arrhythmias were assessed in anaesthetized open-chest animals subjected to 20 min coronary artery occlusion and 3 h reperfusion. Arrhythmias induced by I/R were also assessed in isolated perfused hearts. Only the highest dose of DEX significantly reduced infarct size from 53.9% ± 4.7% of the area at risk in controls to 37.5% ± 4.3% without affecting the myocardial markers of oxidative stress. On the other hand, the significant protective effect against reperfusion arrhythmias occurred only in perfused hearts with the dose of DEX of 150 mg·kg(-1), which also tended to limit the incidence of ischaemic arrhythmias. It is concluded that DEX in a narrow dose range can suppress arrhythmias in isolated hearts subjected to I/R, while a higher dose is needed to limit myocardial infarct size in open-chest rats.
Diamond, A Potentially New Optical Coating Material (1988)

The ability to synthesize diamond films at low pressures offers the possibility of superior optical coatings for severe environments. This is because of diamond's great hardness, high thermal conductivity, and chemical inertness. However, several problems must be overcome before practical diamond optical coatings can be made. They include difficulties in film nucleation, high substrate temperatures, and large film surface roughness leading to high optical scatter.
DETERMINATION OF THE FREEZING EFFECT ON UNCONFINED COMPRESSION STRENGTH AND PERMEABILITY OF SATURATED GRANULAR SOILS (2015)

Artificial ground freezing usage gradually rises in civil engineering applications as a soil supporting system. However, many unknown fundamental parameters have been still waiting discovery, especially for granular soil. Granular soil can not carry its own weight during unconfined conditions. If water turns to ice that locates in the soil pores, it proceeds as a cementitious material. First step of design phenomena is to identify the material properties in geotechnical engineering. Within this scope, unconfined compression tests (UCC) and permeability tests are performed on frozen granular soils subjected to 1, 3 and 7 day-freezing periods to observe time effect. Experimental procedure are applied totally on 12 sand and gravel type of specimens with saturated cases after freezing application in the CDF/CIF freezing thawing machine. Stress - strain behaviors, ultimate load capacities and permeability of specimens are determined. This method will be used while taking undisturbed granular soil samples from the construction site.
Influencia da glucana na adesão entre crisotila e solidos (2004)

Estudos previos de adesao de Saccharomyces sp. e crisotila mostraram enovelamento nao usual das celulas pelas fibrilas de crisotila. O mecanismo proposto para este fenomeno baseou-se nas interacoes de van der Waals entre as fibrilas e os polissacarideos da parede celular, interacoes estas dependentes do tamanho e da geometria das fibrilas e das celulas. Entretanto, esta interacao nao esta totalmente entendida. Neste trabalho, estudou-se quantitativamente o efeito do polissacarideo glucana, o principal componente da parede celular, na interacao de solidos com crisotila. De isotermas de adesao de glucana carboximetilada em crisotila obteve-se G max 7mg/g nas tres temperaturas estudadas; 2, 25 e 50 °C. Nao foi possivel determinar G max de glucana aderida em particulas de silica com dimensoes proximas as da levedura; analise por TGA mostrou que a silica pre-tratada com glucana contem menos agua fisissorvida. Isotermas de adesao apresentaram G max 0,4g/g para adesao da silica e crisotila, aumentando para G max > 1,0g/g quando a silica foi pre-tratada com glucana. O mesmo tipo de enovelamento das fibrilas foi verificado por SEM para ambas adesoes. A massa aderida nao variou com a temperatura (0,25 ou 50 °C) ou com a forca ionica (de 5 x 10 a 1 x 10 mol/L com KCl). Isotermas de adesao de crisotila pre-tratada com glucana e silica mostraram G max muito proximo do controle. A massa de montmorilonita, agalmatolitos ou caulim aderida em crisotila nao foi influenciada pelo pre-tratamento das argilas com glucana. A forca de adesao, no entanto, e maior para agalmotolito e silica quando pre-tratados. Apos 16 minutos de ultrassonicacao a 25KHz, a porcentagem de silica dessorvida foi de 9% para silica-glucana/crisotila e 18% para silica/crisotila; a quantidade de agalmatolito dessorvida foi de 10% para agalmatolito-glucana/crisotila e de 21% para agalmatolito/crisotila. Calculos das energias interfaciais a partir de medidas de ângulos de contato mostram que a energia livre de interacao entre silica e crisotila e menor que entre silica e glucana e entre crisotila e glucana, sendo as interacoes acido-base as principais responsaveis pela interacao de glucana com crisotila e com silica. 
Abstr
Disruption of Zika virus xrRNA1-dependent sfRNA1 production results in tissue-specific attenuated viral replication (2020)

Abstract Zika virus (ZIKV), like other flaviviruses, produces several species of sub-genomic RNAs (sfRNAs) during infection, corresponding to noncoding RNA fragments of different lengths derived from the viral 3’ untranslated region (UTR). Over the course of infection, these sfRNAs accumulate in the cell as a result of incomplete viral genome degradation of the 3’UTR by host 5’ to 3’ exoribonuclease (Xrn1). The halting of Xrn1 in the 3’UTR is due to two RNA pseudoknot structures in the 3’UTR termed exoribonuclease-resistant RNA1 and 2 (xrRNA1&amp;2). Studies with related flaviviruses have shown that sfRNAs are important for pathogenicity and inhibiting both mosquito and mammalian host defense mechanisms. However, these investigations have not included ZIKV and there is very limited data addressing how sfRNAs impact infection in a whole animal model or specific tissues. In this study, we rescued a sfRNA1-deficient ZIKV (X1) by targeted mutation in the xrRNA1 3’ UTR structure. We found that virus which lacks the production of the largest ZIKV sfRNA species, sfRNA1. Using the X1 virus to infect adult IFNAR1 -/- mice, we found that while the lack of sfRNA1 does not alter ZIKV replication in the spleen, there is a significant reduction of ZIKV genome replication in the brain and placenta compared to WT ZIKV infection. Despite thee attenuated phenotype of the X1 ZIKV, mice develop a robust neutralizing antibody response. We conclude that targeted disruption of xrRNA1 results in tissue-specific attenuation while still supporting robust neutralizing antibody responses. Future studies will need to investigate the tissue-specific mechanisms by which ZIKV sfRNAs influence infection and may utilize targeted xrRNA mutations to develop novel attenuated flavivirus vaccine approaches.
Supplementary Data from Molecular Subtypes of Breast Cancers Detected in Mammography Screening and Outside of Screening (2023)

Supplementary Data from Molecular Subtypes of Breast Cancers Detected in Mammography Screening and Outside of Screening
Differential Expression of Beta Transforming Growth Factors (TGFβ1, TGFβ2, and TGFβ3) and their Receptors (Type I and Type II) in Peri-Implantation Porcine Conceptuses1 (1996)

Beta transforming growth factors (TGF beta 1, TGF beta 2, and TGF beta 3) and type I and II TGF beta receptors were immunohistochemically localized in peri-implantation porcine conceptuses (embryos and associated membranes) collected on Day 10 through Day 14 of gestation. Our results indicate specific immunolocalization of TGF beta isoforms and their receptors in conceptuses during these gestational days. In parietal endoderm, TGF beta 1 immunoreactions were weak to undetectable, TGF beta 2 immunoreactions were intense, and TGF beta 3 immunoreactions were intermediate in intensity to TGF beta 2 and TGF beta 1. In contrast to immunoreactions in endoderm, TGF beta 1 and TGF beta 3 immunostaining in trophectoderm (Tr) was intense. Differences in TGF beta 2 immunostaining of Tr were observed from Days 10 to 14 of gestation. A drastic decrease in cytoplasmic immunostaining of ectoderm and mesoderm was detected from Days 12 to 14 for all TGF beta isoforms and type II receptor; however, type I receptor immunoreactions were consistently detected between Days 10 and 14. Concurrent expression of both type I and type II receptors in the peri-implantation conceptuses suggests that porcine conceptuses are capable of binding and responding to TGF beta s during this period. Differential expression of the three TGF beta isoforms suggests different roles for TGF beta s 1, 2, and 3 in conceptus development. Our results suggest possible roles for TGF beta s in early growth and differentiation of the embryo, differentiation of the Tr, and implantation.