gebhart/patrepeval huggingface dataset:
The mutation status of the epidermal growth factor receptor (EGFR) as a selection criterion for therapy with EGFR tyrosine kinase inhibitors (TKI’s) in non-small cell lung cancer (NSCLC) (2006)

10073 Background: Somatic mutations in the EGFR gene have been shown to be closely associated with a favorable response to small-molecule TKI’s, while K-ras mutations seem to be associated with primary resistance. We present an exploratory study confirming the importance of mutation status for response on anti EGFR therapy. Methods: Mutations in the EGFR TK domain were looked for in tumor material extracted from two series of patients with advanced NSCLC. In the first series, mutations were determined in patients with an objective response or clearly progressive under gefitinib therapy. In the second series, EGFR mutations were determined prospectively in an enriched population (two of three characteristics: female gender, non-smoking status, bronchoalveolar -or adenocarcinoma pathology). The presence of a mutation was the criterion for treatment with TKI’s. Response assessment was done according to RECIST. K-Ras mutations were determined retrospectively. Results: In the retrospective series, 15 biopsies were analyzed, belonging to 3 complete responders and 12 non-responders (gefitinib). All three responders harbored an EGFR mutation, none had a K-ras mutation. None of the non-responders had an EGFR mutation. Three of them had a K-ras mutation. In the prospective (enriched) series, 13 out of 41 patients (tumors) possessed an EGFR mutation. Eleven of them swiftly responded on erlotinib or gefitinib, 1 had stable disease, 1 stopped treatment due to severe toxicity. K-ras mutations were not found in this set. In a single EGFR mutation positive patient survival has extended over 40 months since start of therapy. Conclusions: Our findings corroborate other groups’ conclusions that EGFR mutations are a powerful indicator of response to TKI’s and that K-ras mutations are associated with resistance. [Table: see text]
A Microscopic Surface-Enhanced Raman Study of a Single Adsorbate-Covered Colloidal Silver Aggregate (1996)

Surface-enhanced Raman scattering (SERS) spectra have been successfully recorded from individual, selected clusters of colloidal silver particles on which phthalazine, dopamine, or 2,2‘-bipyridine was adsorbed. The method involved the controlled deposition of silver colloid aggregates onto a Pyrex microscope cover slide and the selection of an individual cluster by the optical microscope of a micro-Raman spectrometer followed by Raman measurement. SERS spectra of clusters of various size were recorded. With phthalazine, good quality SERS spectra were obtained with 476.2- and 530.9-nm laser excitation. Poor spectra were obtained with 568.2- and 590-nm excitation, probably due to the photofragmentation of the cluster. The wavelength at which photofragmentation occurred was cluster size and structure dependent. Smaller clusters tended to fragment at shorter wavelengths. A micropreparative technique was developed for preparing single adsorbate-covered silver colloid aggregates. Using this technique in conjunction with Raman microscopy, good quality SERS spectra were obtained from 5 pmol of phthalazine and dopamine. SERS spectra of 2,2‘-bipyridine deposited out of a dichloromethane solution also were obtained, illustrating the possibility of using this single-cluster technique for recording SERS spectra of water-insoluble adsorbates or of adsorbates dissolved in nonaqueous solvents.
A Novel Catalytic Function of Synthetic IgG‐Binding Domain (Z Domain) from Staphylococcal Protein A: Light Emission with Coelenterazine (2013)

The synthetic IgG-binding domain (Z domain) of staphylococcal protein A catalyzes the oxidation of coelenterazine to emit light like a coelenterazine-utilizing luciferase. The Z domain derivatives (ZZ-gCys, Z-gCys and Z-domain) were purified and the luminescence properties were characterized by comparing with coelenterazine-utilizing luciferases, including Renilla luciferase, Gaussia luciferase and the catalytic 19 kDa protein of Oplophorus luciferase. Three Z domain derivatives showed luminescence activity with coelenterazine and the order of the initial maximum intensity of luminescence was ZZ-gCys (100%) > Z-gCys (36.8%) > Z-domain (1.1%) > bovine serum albumin (BSA; 0.9%) > staphylococcal protein A (0.1%) and the background value of coelenterazine (0.1%) in our conditions. The luminescence properties of ZZ-gCys showed the similarity to that of Gaussia luciferase, including the luminescence pattern, the emission spectrum, the stimulation by halogen ions and nonionic detergents and the substrate specificity for coelenterazine analogues. In contrast, the luminescence properties of Z-gCys were close to the catalytic 19 kDa protein of Oplophorus luciferase. The catalytic region of the Z domain for the luminescence reaction might be different from the IgG-binding region of the Z domain.
ChemInform Abstract: Solid State Polycondensation Within Cyclodextrin Channels Leading to Watersoluble Polyamide Rotaxanes (1998)

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.
A look at aerosol formation using data mining techniques (2005)

Abstract. Atmospheric aerosol particle formation is frequently observed throughout the atmosphere, but despite various attempts of explanation, the processes behind it remain unclear. In this study data mining techniques were used to find the key parameters needed for atmospheric aerosol particle formation to occur. A dataset of 8 years of 80 variables collected at the boreal forest station (SMEAR II) in Southern Finland was used, incorporating variables such as radiation, humidity, SO2, ozone and present aerosol surface area. This data was analyzed using clustering and classification methods. The aim of this approach was to gain new parameters independent of any subjective interpretation. This resulted in two key parameters, relative humidity and preexisting aerosol particle surface (condensation sink), capable in explaining 88% of the nucleation events. The inclusion of any further parameters did not improve the results notably. Using these two variables it was possible to derive a nucleation probability function. Interestingly, the two most important variables are related to mechanisms that prevent the nucleation from starting and particles from growing, while parameters related to initiation of particle formation seemed to be less important. Nucleation occurs only with low relative humidity and condensation sink values. One possible explanation for the effect of high water content is that it prevents biogenic hydrocarbon ozonolysis reactions from producing sufficient amounts of low volatility compounds, which might be able to nucleate. Unfortunately the most important biogenic hydrocarbon compound emissions were not available for this study. Another effect of water vapour may be due to its linkage to cloudiness which may prevent the formation of nucleating and/or condensing vapours. A high number of preexisting particles will act as a sink for condensable vapours that otherwise would have been able to form sufficient supersaturation and initiate the nucleation process.
PATTERNS OF EXPRESSION OF KERATIN 19 AS DETECTED WITH MONOCLONAL ANTIBODIES IN HUMAN BREAST TISSUES AND TUMOURS (1985)

The monoclonal antibodies BA16 and BA17 directed to different epitopes on human keratin 19 have been tested for their reaction with normal breast and with benign and malignant breast lesions and associated tissue. In Western blots of gel-separated extracts of fibroadenomas, malignant tumours or normal mammary epithelial cells, the antibodies reacted with only one component of 40 kd molecular weight. Immunoperoxidase staining of sections of normal breast tissues showed all basal cells and a few luminal cells to be unstained by the antibodies. The distribution of the unstained (keratin 19-) luminal cells in the mammary tree is consistent with that of cells with the proliferative potential to give rise to the growth of terminal ductal lobular units (TDLU) seen at pregnancy. A total of 42 benign and 141 malignant lesions were stained with the antibodies, and a clear difference in staining pattern was seen between the benign and malignant tumours. All but 3 of the benign lesions showed a heterogeneous staining pattern with 5-50% unstained cells. In contrast, the cancer cells in 106/116 invasive primary tumours and in all 21 metastatic lesions examined showed a homogeneously positive reaction with antibodies BA16 and BA17: the malignant cells in 4 cases of Paget's disease also showed homogeneously positive staining with the antibody. In the malignant tumours, the observed homogeneity in expression of keratin 19 was confined to the malignant cells; tumour-associated normal tissue and benign proliferative lesions contained keratin 19-cells. Seven pure in situ tumours were examined and 5 showed the homogeneous pattern of staining characteristic of invasive tumours while 2 contained a high number of keratin 19-cells. A general model is presented to explain the presence of keratin 19-cells in benign proliferation and the dominance of keratin 19-cells in invasive carcinoma.
Immunization with Interleukin-2 Transfected Melanoma Cells. A Phase I–II Study in Patients with Metastatic Melanoma. University Hospital Leiden (1993)

The safety, tolerance and clinical effects of immunization with irradiated, allogeneic melanoma cells that express high levels of HLA-A1 and -A2 and secrete IL-2 after transfection with the Interleukin-2 gene, will be assessed in HLA-A1 or HLA-A2 positive melanoma patients with metastatic disease. As a pilot, the first 5-10 patients, if no immediate regression of tumor lesions are observed, will in addition to immunization with these allogeneic tumor cells receive recombinant IL-2 in relatively low doses during three consecutive weeks on an outpatient basis. If no clinical remissions are induced in these first 5-10 patients, subsequent 5-10 patients will receive the same dose of melanoma cells without additional rIL-2. Thereafter the dose of injected melanoma cells will be increased in every following 5-10 patients, but all subsequent patients will receive only IL-2 producing, allogeneic tumor cells, without the addition of rIL-2.
Mouse and human ornithine decarboxylase genes. Methylation polymorphism and amplification (1987)

With the use of the isoschizomeric restriction endonucleases HpaII and MspI, we found that mouse tumour ornithine decarboxylase (ODC; EC 4.1.1.17) genes are extensively methylated. ODC genes in L1210 mouse leukaemia cells were apparently more methylated than in Ehrlich ascites carcinoma, as revealed by the use of HpaII endonuclease, yet the digestion of genomic DNA isolated from these two murine tumour cell lines with MspI, which cleaves at a CCGG sequence, also with internally methylated cytosine, resulted in an apparently identical restriction pattern. It is possible that the amplification of ODC genes in Ehrlich ascites-carcinoma cells in response to 2-difluoromethylornithine (DFMO) was associated with hypomethylation, or that less-methylated genes were amplified. A human myeloma (Sultan) cell line only revealed three separate hybridization signals when cleaved with HpaII. One of these signals was amplified under the pressure of DFMO. When cleaved with MspI, these three HpaII fragments disappeared and were replaced by a double signal of 2.3-2.4 kilobase-pairs (kbp) in size. The amplified ODC sequences in the Sultan myeloma cell line apparently originated from chromosome 2, as indicated by a unique hybridization signal in a 5.8 kbp HindIII fragment specific for the human ODC locus on chromosome 2. A comparison of different human cells, the Sultan myeloma, a lymphocytic B-cell leukaemia (Ball), normal mononuclear leucocytes and leucocytes obtained from leukaemia patients, revealed interesting differences in the methylation of ODC genes. The use of two restriction endonucleases (HpaII and CfoI), the cleavage site for both of which contains a CG sequence and which only cleave when cytosine is unmethylated, indicated that ODC genes in the lymphocytic leukaemia cells were much less methylated than those in the normal leucocytes or in the Sultan cells.
Preliminary Identification of Central Auditory Processing Screening Tests for Individuals with Multiple Sclerosis (2012)

Research suggests that individuals with multiple sclerosis (MS) may be susceptible to deficits in central auditory processing (CAP). Audiologists need to be able to select appropriate tests to screen for such deficits in this patient population. The purpose of this report is to identify promising CAP tests for screening patients with MS. A comprehensive behavioral CAP test battery was administered to 26 subjects with MS and 27 subjects without MS. Out of six potential tests, selected based on the CAP deficits reported in the scientific literature, results suggest that the Staggered Spondaic Word test and the SCAN-A, followed by the Masking Level Difference test, are the most promising screening tests in this patient population. The Frequency Patterns Test, the Dichotic Digits Test, and the Gaps-in-Noise Test, on the other hand, were less promising. It should be noted, however, that this is a preliminary analysis, and that no clinical recommendations can be made until the reference standards are established in a much larger sample population.
Sparse basis pursuit for compliance minimization in the vanishing volume ratio limit (2020)

Abstract We consider a non‐smooth convex variational problem appearing as a formal limit of compliance minimization in the vanishing volume ratio limit. The problem has a classical basis pursuit form, and several successful algorithms have been utilized to solve problems of this class in other application contexts. We discuss the well‐posedness and regularity of solutions to these problems, possible solution algorithms, and their discretizations as relevant in this mechanical engineering context. We then test the algorithms on a few benchmark problems with available analytical solutions. We find that whereas many algorithms are successful in estimating the optimal objective value to the problem to a high accuracy, the same cannot be said about finding the optimal solutions themselves. In particular, in some examples the algorithms struggle to properly identify the areas where the solutions should vanish entirely. We also discuss an example where the found optimal solutions are not sparse even though sparse(r) solutions exist.
The LKB1 Tumor Suppressor as a Biomarker in Mouse and Human Tissues (2020)

Germline mutations in the LKB1 gene (also known as STK11) cause the Peutz-Jeghers Syndrome, and somatic loss of LKB1 has emerged as causal event in a wide range of human malignancies, including melanoma, lung cancer, and cervical cancer. The LKB1 protein is a serine-threonine kinase that phosphorylates AMP-activated protein kinase (AMPK) and other downstream targets. Conditional knockout studies in mouse models have consistently shown that LKB1 loss promotes a highly-metastatic phenotype in diverse tissues, and human studies have demonstrated a strong association between LKB1 inactivation and tumor recurrence. Furthermore, LKB1 deficiency confers sensitivity to distinct classes of anticancer drugs. The ability to reliably identify LKB1-deficient tumors is thus likely to have important prognostic and predictive implications. Previous research studies have employed polyclonal antibodies with limited success, and there is no widely-employed immunohistochemical assay for LKB1. Here we report an assay based on a rabbit monoclonal antibody that can reliably detect endogenous LKB1 protein (and its absence) in mouse and human formalin-fixed, paraffin-embedded tissues. LKB1 protein levels determined through this assay correlated strongly with AMPK phosphorylation both in mouse and human tumors, and with mRNA levels in human tumors. Our studies fully validate this immunohistochemical assay for LKB1 in paraffin-embedded formalin tissue sections. This assay should be broadly useful for research studies employing mouse models and also for the development of human tissue-based assays for LKB1 in diverse clinical settings.
Errors in Flash-Memory-Based Solid-State Drives: Analysis, Mitigation, and Recovery (2017)

NAND flash memory is ubiquitous in everyday life today because its capacity has continuously increased and cost has continuously decreased over decades. This positive growth is a result of two key trends: (1) effective process technology scaling; and (2) multi-level (e.g., MLC, TLC) cell data coding. Unfortunately, the reliability of raw data stored in flash memory has also continued to become more difficult to ensure, because these two trends lead to (1) fewer electrons in the flash memory cell floating gate to represent the data; and (2) larger cell-to-cell interference and disturbance effects. Without mitigation, worsening reliability can reduce the lifetime of NAND flash memory. As a result, flash memory controllers in solid-state drives (SSDs) have become much more sophisticated: they incorporate many effective techniques to ensure the correct interpretation of noisy data stored in flash memory cells. In this chapter, we review recent advances in SSD error characterization, mitigation, and data recovery techniques for reliability and lifetime improvement. We provide rigorous experimental data from state-of-the-art MLC and TLC NAND flash devices on various types of flash memory errors, to motivate the need for such techniques. Based on the understanding developed by the experimental characterization, we describe several mitigation and recovery techniques, including (1) cell-tocell interference mitigation; (2) optimal multi-level cell sensing; (3) error correction using state-of-the-art algorithms and methods; and (4) data recovery when error correction fails. We quantify the reliability improvement provided by each of these techniques. Looking forward, we briefly discuss how flash memory and these techniques could evolve into the future.
Synergistic Impact of Solvent and Polymer Additives on the Film Formation of Small Molecule Blend Films for Bulk Heterojunction Solar Cells (2015)

The addition of polystyrene (PS), a typical insulator, is empirically shown to increase the power conversion efficiencies (PCEs) of a solution‐deposited bulk heterojunction (BHJ) molecular blend film used in solar cell fabrication: p‐DTS(FBTTh 2 ) 2 /PC 71 BM. The performance is further improved by small quantities of diiodooctane (DIO), an established solvent additive. In this study, how the addition of PS and DIO affects the film formation of this bulk heterojunction blend film are probed via in situ monitoring of absorbance, thickness, and crystallinity. PS and DIO additives are shown to promote donor crystallite formation on different time scales and through different mechanisms. PS‐containing films retain chlorobenzene solvent, extending evaporation time and promoting phase separation earlier in the casting process. This extended time is insufficient to attain the morphology for optimal PCE results before the film sets. Here is where the presence of DIO comes into play: its low vapor pressure further extends the time scale of film evolution and allows for crystalline rearrangement of the donor phase long after casting, ultimately leading to the best BHJ organization.
Lipoprotein lipase controls fatty acid entry into adipose tissue, but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase (1997)

Lipoprotein lipase (LPL) is the rate-limiting enzyme for the import of triglyceride-derived fatty acids by muscle, for utilization, and adipose tissue (AT), for storage. Relative ratios of LPL expression in these two tissues have therefore been suggested to determine body mass composition as well as play a role in the initiation and/or development of obesity. To test this, LPL knockout mice were mated to transgenics expressing LPL under the control of a muscle-specific promoter (MCK) to generate induced mutants with either relative (L2-MCK) or absolute AT LPL deficiency (L0-MCK). L0-MCK mice had normal weight gain and body mass composition. However, AT chemical composition indicated that LPL deficiency was compensated for by large increases in endogenous AT fatty acid synthesis. Histological analysis confirmed that such up-regulation of de novo fatty acid synthesis in L0-MCK mice could produce normal amounts of AT as early as 20 h after birth. To assess the role of AT LPL during times of profound weight gain, L0-MCK and L2-MCK genotypes were compared on the obese ob/ob background. ob/ob mice rendered deficient in AT LPL (L0-MCK-ob/ob) also demonstrated increased endogenous fatty acid synthesis but had diminished weight and fat mass. These findings reveal marked alterations in AT metabolism that occur during LPL deficiency and provide strong evidence for a role of AT LPL in one type of genetic obesity.
Influence of propene pressure on the isotacticity of polypropene produced with typical C1‐symmetric metallocene and Ziegler‐Natta catalysts (1997)

Abstract Polymerization of propene was conducted at 40°C under reduced pressure (0.35 – 1.0 atm) using the C 1 ‐Symmetric threo ‐ i Pr(3‐ t BuCp)(3‐ t BuInd)ZrCl 2 /MAO and TiCl 4 /MgCl 2 /Al( i Bu) 3 catalyst systems and the effect of propene pressure on the microstructure of the resulting isotactic polypropene was investigated. In the case of C 1 ‐symmetric metallocene, the [ mmmm ]‐pentad fraction decreased moderately with decreasing propene pressure, but the magnitude of decrease was much smaller than those reported by Busico et al. using typical C 2 ‐symmetric metallocenes. Whereas, the [ mmmm ]‐pentad fraction of isotactic polypropene obtained with the conventional Ziegler‐Natta catalyst did not change so much in the pressure range. Thus, epimerization of the growing polymer chain was found to be drastically dependent upon the catalyst system.
Dynactin-dependent cortical dynein and spherical spindle shape correlate temporally with meiotic spindle rotation in Caenorhabditis elegans (2015)

Oocyte meiotic spindles orient with one pole juxtaposed to the cortex to facilitate extrusion of chromosomes into polar bodies. In Caenorhabditis elegans, these acentriolar spindles initially orient parallel to the cortex and then rotate to the perpendicular orientation. To understand the mechanism of spindle rotation, we characterized events that correlated temporally with rotation, including shortening of the spindle in the pole-to pole axis, which resulted in a nearly spherical spindle at rotation. By analyzing large spindles of polyploid C. elegans and a related nematode species, we found that spindle rotation initiated at a defined spherical shape rather than at a defined spindle length. In addition, dynein accumulated on the cortex just before rotation, and microtubules grew from the spindle with plus ends outward during rotation. Dynactin depletion prevented accumulation of dynein on the cortex and prevented spindle rotation independently of effects on spindle shape. These results support a cortical pulling model in which spindle shape might facilitate rotation because a sphere can rotate without deforming the adjacent elastic cytoplasm. We also present evidence that activation of spindle rotation is promoted by dephosphorylation of the basic domain of p150 dynactin.
ChemInform Abstract: ADDITION OF DIMETHYLKETENE TO 6‐HETEROSUBSTITUTED FULVENES. SYNTHESIS OF (.+‐.)‐FILIFOLONE (1985)

Abstract Aus Isobutyrylchlorid und NEt 3 nach Methode A) erzeugtes Dimethylketen reagiert in situ mit dem Dimethylaminofulven (I) zu dem Isobutyrylfulven (II) und mit dem Ethoxyfulven (III) zu einem trennbaren Gemisch der Z‐ bzw. E‐kon‐ figurierten Bicycloheptenone (IV) bzw. (W. Das Z‐Isomer (IV) liefert mit weiterem Dimethylketen das Tricyclononandion(VI).