gebhart/patrepeval huggingface dataset:
Abstract 3062: A comparative analysis of phosphothioated DNA and peptide nucleic acid molecular beacons targeting specific K-ras mutation (2011)

Abstract Introduction: Early detection of gastrointestinal malignancies may improve disease-related outcome. In vivo, real time imaging using hybridization of fluorescently-labeled complementary transcripts to intracellular RNA sequences may facilitate early detection of malignant and pre-malignant lesions Methods: Using K-ras oncogene as a model target, and adapting the molecular beacon technology, we performed an hybridization kinetics and hybridization specificity comparison of two types of molecular beacons (MBs) based on either phosphothioated DNA (PS-DNA-MB) or peptide nucleic acid (PNA-TO-MB, where thiazole orange [TO] was used as the fluorescent molecule) both in vitro and in a variety of cell lines. In order to determine the sequence-specificity of MB's at a single base resolution, a codon 12 K-ras oncogene mutation (GGT→GAT) was used as target in different cell lines. Both PS-DNA and PNA-TO MB's were designed to target this specific K-ras point mutation. We studied the hybridization of the two MBs to wild-type K-ras (HT-29 colon cancer cell line) and two cell lines, one harboring this K-ras point mutation (PANC-1) and SW-480 harboring a different (GGT→GTT) mutation. Results: Hybridization kinetics of PNA-TO-MB to target DNA or RNA was faster compared to PS-DNA-MB highlighting the advantage of such probes to be developed into diagnostic kits for the early detection of cancer. However, in solution, using synthetic DNA oligomers as targets, PS-DNA-MB demonstrated higher specificity to its complementary target (3-to 4.6-fold increase in fluorescence in comparison to DNA with a single mismatch) compared to the PNA-TO-MB (only 1.3- to 2.2-fold increase). Yet, incubation of PNA-TO-MB with total RNA (isolated from these cell lines) and with fixed cells, resulted in a significantly higher fluorescent signal (p &amp;lt; 0.001) detected for target (fully complement, PANC-1) compared to single mismatch mRNA transcript in HT29 and SW-480. In contrast, the PS-DNA-MB showed poor discrimination in total RNA and no fluorescent signal with all cell lines after 5 minutes incubation. Conclusions: Based on the fast hybridization kinetics and based on the single mismatch discrimination found for PNA-TO-MB in fixed cells and with total RNA, it is speculated that such PNA-TO-MB's are promising candidates for the early detection of cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3062. doi:10.1158/1538-7445.AM2011-3062
Fractures and dislocations of the lower cervical spine: surgical treatment. A review of 83 cases. (2005)

The authors examine 83 consecutive cases of fracture and dislocation of the lower cervical spine submitted to surgery over a period of 5 years. Sixty-five patients were monitored with minimum 5-months follow-up, 5 died, 13 could not be traced. Lesions were classified based on the method proposed by Argenson3 with the purpose of identifying guidelines for surgical treatment. Thus, different methods are proposed based on the type of lesion and on any neurologic deficit. Intersomatic fusion with anterior approach is the method of choice in most lesions. The exception to this is monoarticular dislocations that cannot be reduced, so that reduction by posterior approach associated with discectomy and anterior fusion are recommended. Circumferential fusion is proposed for traumatic spondylolistheses, complete dislocations with unsatisfactory anterior reduction, in lesions in flexion-extension and rotation associated with complete spinal cord injury, in order to favor functional rehabilitation free from ortheses. The need to review many cases of traumatic lesions of the lower cervical spine (LCS) collected over a relatively short period of time derives from the need to identify guidelines that will help the surgeon in his or her choice of the type of surgery to perform on the patient with emergency injury. The basic premise, as for other sites of traumatic injury, resides in an efficient classification (corresponding to the anatomic injury and of immediate and intuitive application) to which options for treatment may be related. In particular, an evaluation of the type of approach (anterior, posterior, combined) and of the sequence of surgical stages is essential to obtaining effective results with an acceptable complication rate. Finally, treatment must be definitive, and in cases of severe spinal cord injury it must allow for rapid rehabilitation and freedom from the use of ortheses.
Dilithium Tributylcuprate (2001)

[61288-01-5] C12H27CuLi2 (MW 248.77) InChI = 1S/3C4H9.Cu.2Li/c3*1-3-4-2;;;/h3*1,3-4H2,2H3;;;/q;;;-2;2*+1 InChIKey = ZNKNIWXRXVSSFM-UHFFFAOYSA-N (organometallic butylating agent for ketones,1 enol ethers,2 and organomercurials3) Physical Data: in ether, 1H NMR spectra have shown4 that Li2CuBu3 is not an actual species, but a more complex mixture that can be more accurately represented as a BuLi to BuCu ratio. In pentane, however, Li2CuBu3 exists in equilibrium with BuLi and LiCuBu2 (see Dilithium Trimethylcuprate). Solubility: sol ether, THF, and pentane to −80 °C. Preparative Method: n‐Butyllithium (3.3 mmol) is added to Copper(I) Iodide (1.0 mmol) in ether at −40 °C. Handling, Storage, and Precautions: Li2CuBu3 should be used as soon as possible following preparation. Use in a fume hood.
Anthrax tumor toxin (LeTx) selectively kills B-RAF mutant melanomas (2005)

7533 The efficacy of anthrax tumor toxin (LeTx) was tested on a panel of 18 human melanoma cell lines using a 3H-Leucine incorporation inhibition assay. 11/18 cell lines were sensitive to LeTx (IC50 < 350 pM, percent cell kill > 75%), while the remaining 7/18 were not sensitive to LeTx (IC50 > 750 pM, Percent cell kill < 60%). 10/11 sensitive melanoma cell lines carried the V599E BRAF. Only 1/7 resistant cell line was BRAF mutation positive (p < 0.0001). 6/7 resistant cell lines carried the Q61R or Q61K N-Ras mutation. Next, LeTx effects on 3H-Thymidine incorporation were measured. In 11/11 sensitive cell lines, the IC50 for 3H-thymidine incorporation was lower than that of 3H-Leucine incorporation indicating that the majority of surviving cells at maximal concentration were in cell cycle arrest. 4/7 cell lines that were not sensitive to LeTx by 3H-Leucine incorporation had low IC50 values in the 3H-Thymidine incorporation inhibition assay (IC50 < 275 pM) and a significantly lower percentage of 3H-thymidine uptake at maximum concentration suggesting significant tumor cell growth arrest rather than tumor cell death. Anthrax toxin receptor (ATR) levels, measured by saturation assay with 125I-PA, varied between 3562 and 32440 receptors/cell with resistant cell lines having the same levels of ATR expression as sensitive cell lines and no correlation of ATR receptor levels with IC50 for LeTx sensitive cell lines. Total and phosphorylated levels of MEK1/2 and ERK1/2 in the cell lines were quantified by western blots and densitometry. LeTx killing correlated with MEK1/2 activation levels. 9/11 sensitive melanoma cell lines and 2/7 resistant melanoma cell lines had a P-MEK1/2 to MEK1/2 ratio > 0.3 (p < 0.001). P-ERK1/2 to ERK1/2 levels did not correlate with melanoma cell line sensitivity to LeTx. The small molecular weight MEK1/2 inhibitor U0126 was tested for effects on the cell lines. 6/6 LeTx resistant cells were resistant to U0126; 5/9 LeTx sensitive cells were sensitive to U0126. In summary, melanoma cell line LeTx sensitivity correlated with B-Raf mutation, P-MEK1/2 levels, and U0126 sensitivity, but not ATR or P-ERK1/2. In future clinical trials of LeTx in metastatic melanoma, these results may provide molecular targets to identify responders. No significant financial relationships to disclose.
Contamination Control in Nursing With Filtration (2004)

Filters often are viewed as screens with openings smaller than the particles intended to be removed by a process technically known as direct interception. However, filter manufacturing embraces far more advanced technological approaches, with an evolution toward selective removal of cells or soluble constituents from complex physiologic solutions. An appreciation of filtration development makes it easy to understand how differently manufactured filters with the same claims may not perform identically. This article focuses on the filtration of intravenous solutions and point-of-use hospital water.
QoI-Based Data Upload Control for Mobility-Aware Cloud Services (2015)

Mobility-aware cloud services such as fleet management systems need to understand the positions of mobile devices accurately in a real-time manner. Generally speaking, positioning accuracy and data traffic load are in a trade-off relation. Highly accurate real-time positioning requires frequent location data upload and hence results in heavy data traffic load. Although not all data are equally important, data of low importance often consumes a lot of network resources. This paper presents a data upload control method that the dynamically assesses quality of information (QoI) of measured data at mobile devices. The proposed method balances high accuracy with low traffic loads to achieve efficient vehicle position management. We evaluated the performance of the proposed method using both artificial and actual GPS data and confirmed that it successfully controlled the accuracy and network traffic load according to application requirements.
Petrographic Examination of Bell Canyon Tests (BCT) 1-FF Field Grouts over a Three-Year Period. (1983)

ABSTRACT (Continued)in other reports.Cracking of specimens was observed; this was believed to be due largely to moisture and temperature changes in the laboratory.The two plugs were similar in composition with the Plug 1 grout having more tetracalcium aluminate monosulfate-12-hydrate (C4ASH12) and more garnethydrogarnet solid solution series material (hydrogarnet) by X-ray diffraction (XRD) than Plug 2. Tetracalcium aluminate dichloride-10-hydrate (C3A(CaCl2)H10 was present in both samples in varying amounts at different ages.The amount of c 3 A(CaC1 2 )H 10 in the samples was probably controlled by the proximity of the surface examined by XRD to the brine the samples were stored in.The Plug 2 grout contained more ettringite and calcium hydroxide; Plug 1 grout contained more detectable calcium silicate hydrate (C-S-H).The grout to host anhydrite rock bond appeared to be tight with no visible cracking in simulated borehole (SBH) samples that were examined immediately after fracturing .A white precipitate was found on samples of both events during storage and is believed to be a combination of some chemical reaction between the groundwater and grout as well as precipitate from the brine.It had no detectable detrimental effects.The infiltration of the brine during placement of the grout in satellite Holes 3 and 4 weakened the grout and retarded some of the grout so that it did not harden.The XRD examinations of both Plug 1 and Plug 2 grouts point out that chloride and carbonate ions from the brine are causing some alteration to the original phases at and near the contact of grout and brine.After 3 years of storage, this alteration has penetrated the grout to a depth of about 1 or 1.5 in.with the severity of alteration becoming less with increasing distance from contact surfaces.The grout from the two placements at ages up to 3 years showed no significant overall deterioration or alteration from the original grout.The Plug 1 and Plug 2 samples will continue to be examined by XRD and SEM at 1-year intervals for an indefinite time.
Bone graft substitutes (2005)

The current gold standard of bone grafts is the autograft since it possesses all the characteristics necessary for new bone growth, namely osteoconductivity, osteogenicity and osteoinductivity. However, the autograft has its limitations, including donor-site morbidity and supply limitations, hindering this as an option for bone repair. An extensive list of currently available alternatives to bone grafts is provided, along with a classification scheme that divides these bone graft substitutes into five groups depending on the primary material composition: allograft, cell, factor, ceramic and polymer. Of the bone graft substitutes listed, several are discussed in detail. Beyond the current state of the art, attention is paid to what lies ahead in the field of bone graft substitutes. Biodegradable composite structures and various new architectures are discussed, as are newly developed polymeric materials, with tissue engineering providing the platform for future directions within this discipline.
Kopplungseffizienz und Membranruhepotential von Astrozyten unter CXCL-8 (2009)

Hintergrund: CXCL-8 (IL-8) spielt als Chemoattraktant immunkompetenter Zellen im Rahmen inflammatorischer Prozesse, wie sie in Entzündungsherden von Multiple Sklerose (MS) Patienten zu finden sind, eine entscheidende. In Vorarbeiten konnten wir einen reduzierenden Effekt von MS-Liquores (MS-CSF) auf das Membranruhepotential (MRP) und die Gap Junction basierte Kopplung (GJK) VON Astrozyten zeigen. Zudem konnten wir einen signifikant erhöhten Spiegel von IL-8 in MS-CSF nachweisen.
Underground-coal-gasification technical summary (1983)

There are three basic reasons for the recent emergence of underground coal gasification (UCG) as a leading synfuels candidate: (1) favorable projected economics, (2) ability to use coal seams that are unattractive for mining, and (3) modest environmental impact. The objective of this paper is to list major underground coal gasification results and conclusions, particularly field-oriented results. The twenty field tests and ten years' experience have demonstrated technical feasibility and allow us to make several generalizations concerning underground coal gasification. For example, burns tend to be bowl-shaped after roof collapse, since ash and slag (and high water content in coal) impede downward burning. Burns appear to be symmetrical in plan view, but not in elevation view. Injection and linking at the bottom of the seam can improve performance. Heat losses begin, and heating value of the product gas declines, when the burn reaches the roof and the roof rock begins to collapse. In general, heating value and chemistry appear to be insensitive to operational parameters but are sensitive to process-well geometry and overburden.
Increasing p53 protein sensitizes non-small cell lung cancer to paclitaxel and cisplatin in vitro. (2010)

Increasing intracellular p53 protein concentrations can augment the effect of CDDP and PAX in NSCLC, despite the baseline level of p53 protein expression.
Abstract ES10-2: Mining noncoding mutations for drivers of development in ER alpha-positive breast cancer (2019)

Abstract Large-scale analysis of whole genome sequencing of breast tumors has identified thousands of genetic alterations, such as single-nucleotide variants (SNVs), outside of gene coding sequences. Delineating the functional impact of these noncoding SNVs is challenging, limiting their inclusion in precision genomics medicine pipelines. Pan-cancer attempts to detect evidence for positive selection within individual CREs identified promoters of a limited number of genes such as TERT. By considering the enrichment of noncoding mutations in cistromes as opposed to individual CREs, we identify the enrichment of noncoding SNVs in cistromes of breast cancer driver transcription factors, including FOXA1. This parallels enrichment of breast cancer genetic predispositions over these transcription factor cistromes. Furthermore, somatic SNVs accumulate in the regulatory plexus of some of these driver transcription factors providing evidence for a multi-targeted approach to disrupt their activity in breast cancer. In conclusion, our results support a functional impact of somatic SNVs converging on the cistrome of driver transcription factors in breast cancer. Altogether, we show how to interrogate noncoding SNVs to delineate the oncogenic determinants of breast cancer to be considered for therapeutic intervention. Citation Format: Lupien M. Mining noncoding mutations for drivers of development in ER alpha-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES10-2.
Integration of the Cytogenetic and Genetic Linkage Maps of Brassica oleracea (2002)

We have assigned all nine linkage groups of a Brassica oleracea genetic map to each of the nine chromosomes of the karyotype derived from mitotic metaphase spreads of the B. oleracea var. alboglabra line A12DHd using FISH. The majority of probes were BACs, with A12DHd DNA inserts, which give clear, reliable FISH signals. We have added nine markers to the existing integrated linkage map, distributed over six linkage groups. BACs were definitively assigned to linkage map positions through development of locus-specific PCR assays. Integration of the cytogenetic and genetic linkage maps was achieved with 22 probes representing 19 loci. Four chromosomes (2, 4, 7, and 9) are in the same orientation as their respective linkage groups (O4, O7, O8, and O6) whereas four chromosomes (1, 3, 5, and 8) and linkage groups (O3, O9, O2, and O1) are in the opposite orientation. The remaining chromosome (6) is probably in the opposite orientation. The cytogenetic map is an important resource for locating probes with unknown genetic map positions and is also being used to analyze the relationships between genetic and cytogenetic maps.
Evaluation of a Paradigm Shift From Intravenous Antibiotics to Oral Step-Down Therapy for the Treatment of Infective Endocarditis (2020)

This review found ample data demonstrating the therapeutic effectiveness of oral step-down vs intravenous-only antibiotic therapy for IE, and no contrary data were identified. The use of highly orally bioavailable antibiotics as step-down therapy for IE, after clearing bacteremia and achieving clinical stability with intravenous regimens, should be incorporated into clinical practice.
Amgen unveils its KRas covalent inhibitor AMG 510 (2019)

Drugmaker Amgen revealed the structure of AMG 510—the first covalent inhibitor of a mutant form of the cancer-target KRas to make it into human clinical trials. The molecule was disclosed at the American Chemical Society national meeting in Orlando, Florida, last week. KRas proteins relay signals for cells to grow and divide or to mature and take on specialized functions. They do this by converting guanosine triphosphate to guanosine diphosphate. Mutants of the proteins are common in many cancers. Because of their critical functions, they’ve been eyed as cancer targets for years, but the spherical protein’s landscape is as featureless as a billiard ball when in its active state, making it tough for drugmakers to find a place to slip in a compound that might muck up the protein’s inner workings. “There’s almost nowhere that a drug can stick to on that protein,” said Amgen scientist Victor Cee, who presented
Synthesis, reactions, and X-ray structures of the functionalized isocyanide complexes [Fe2{µ-CNC(O)SR}(µ-CO)(CO)2(cp)2](cp =η-C5H5, R = Me or Et) and of their carbyne and carbene derivatives (1990)

The cyanate ion NCO– inserts into the C–S bond of [Fe2(µ-CSR)(µ-CO)(CO)2(cp)2]+(cp =η-C5H5, R = Me or Et), to give the isocyanide-bridged complexes [Fe2{µ-CNC(O)SR}(µ-CO)(CO)2-(cp)2](1). These derivatives exist in solution as a mixture of cis and trans isomers with the strong electron-withdrawing CNC(O)SR group bridging in both forms. The X-ray crystal structure of complex (1b; R = Et)[monoclinic, a= 9.418(3), b= 14.827(3), c= 12.793(4)Å, β= 97.28(3)°, Z= 4, space group P21/n] reveals the CO groups in cis position relative to the Fe–Fe bond. The nitrogen atom in (1) is alkylated or protonated to generate the cationic aminocarbyne complexes [Fe2{µ-CN(R′)C(O)SR}(µ-CO)(CO)2(cp)2]+(2; R′= Me, Et, or H) which do not display cis–trans isomerization at room temperature. In accord with their carbyne nature, the µ-C atom in complexes (2) adds H– or CN–(X) to form the carbene derivatives [Fe2{µ-C(X)N(R′)C(O)SR}(µ-CO)-(CO)2(cp)2](3) which are not fluxional. The X-ray structure of (3a; X = CN, R′= R = Me)[orthorhombic, a= 9.238(3), b= 8.142(1), c= 24.712(2)Å, Z= 4, space group P212121] shows that the molecule retains the cis geometry of the parent species (1) and (2), with the bulkier µ-carbon substituent N(Me)C(O)SMe on the less-hindered carbonyl face of the complex.
Manipulation of microbiota reveals altered callosal myelination and white matter plasticity in a model of Huntington disease (2019)

Structural and molecular myelination deficits represent early pathological features of Huntington disease (HD). Recent evidence from germ-free (GF) animals suggests a role for microbiota-gut-brain bidirectional communication in the regulation of myelination. In this study, we aimed to investigate the impact of microbiota on myelin plasticity and oligodendroglial population dynamics in the mixed-sex BACHD mouse model of HD. Ultrastructural analysis of myelin in the corpus callosum revealed alterations of myelin thickness in BACHD GF compared to specific-pathogen free (SPF) mice, whereas no differences were observed between wild-type (WT) groups. In contrast, myelin compaction was altered in all groups when compared to WT SPF animals. Levels of myelin-related proteins were generally reduced, and the number of mature oligodendrocytes was decreased in the prefrontal cortex under GF compared to SPF conditions, regardless of genotype. Minor differences in commensal bacteria at the family and genera levels were found in the gut microbiota of BACHD and WT animals housed in standard living conditions. Our findings indicate complex effects of a germ-free status on myelin-related characteristics, and highlight the adaptive properties of myelination as a result of environmental manipulation.
Erweiterte EKG-Ableitungen – Schritt für Schritt (2020)

Den STEMI ohne ST-Streckenhebungen im Standard-12-Kanal-EKG erkennen, die Diagnose der rechtsventrikulären Beteiligung beim inferioren STEMI stellen, eine Hilfestellung zur besseren Darstellung atrialer Aktivität bei Tachykardien kennen – all das ermöglichen die hier vorgestellten erweiterten EKG-Ableitungen. Diese werden Sie in die Lage versetzen, therapieentscheidende Diagnosen für Ihre Patienten stellen zu können.
Primary neuroprotection (2010)

There are 7 FDA-approved therapies for relapsing forms of multiple sclerosis (MS), and over a dozen more in various stages of development. Some of these therapies are highly effective, reducing new gadolinium-enhancing lesions on brain MRI by 90% or more compared to placebo. Along with reduced active inflammation, a concomitant slowing in progressive disability and brain atrophy has been reported with most approved therapies and many currently in development. But the slowing of disability accrual and atrophy should not be surprising with these therapies: prevention of acute injury leads to preservation of tissue, i.e., secondary neuroprotection.

This bright hope for overtly inflammatory forms of MS contrasts with ongoing challenges in purely progressive forms of MS, which include primary progressive MS (PPMS) and secondary progressive MS (SPMS) without relapses. Many therapies with efficacy in relapsing MS, including interferon-β, glatiramer acetate, mitoxantrone, and rituximab, have produced disappointing results in clinical trials of purely progressive MS. Primary neuroprotection has proven to be a harder nut to crack than antiinflammation. Robust therapies to slow neurodegeneration are likewise lacking in Alzheimer, Parkinson, and other neurodegenerative diseases.

One of the challenges in developing neuroprotective therapies for progressive MS is a twofold predicament: What biologic pathway should be targeted, and what imaging metric …