gebhart/patrepeval huggingface dataset:
[Endothelins: possibly a new pharmacological approach in cardiovascular diseases, kidney diseases and oncological disorders]. (1997)

Only 10 years ago, the vasoconstricting peptide endothelin was discovered; it is produced by endothelial cells. Different isoforms and receptors of endothelin have been identified. The effects of endothelin-I, the most important isoform, are mainly vasoconstriction and proliferation of cells. In the last few years endothelin receptor antagonists have become available, which can delineate the clinical importance of the endothelin system. Possible indications for endothelin receptor blockers are renal disease (acute and chronic renal failure) and cardiovascular disease (heart failure; restenosis after percutaneous transluminal coronary angioplasty (PTCA); pulmonary hypertension; systemic hypertension). There is also a possible role for endothelin receptor blockers in oncology (prostatic carcinoma). Currently clinical trials are being carried out to determine the efficacy of these compounds for the above-mentioned indications.
Specificity of Escherichia coli endoribonuclease RNase E: in vivo and in vitro analysis of mutants in a bacteriophage T4 mRNA processing site. (1992)

Endoribonuclease RNase E has an important role in the processing and degradation of bacteriophage T4 and Escherichia coli mRNAs. We have undertaken a mutational analysis of the -71 RNase E processing site of T4 gene 32. A series of mutations were introduced into a synthetic T4 sequence cloned on a plasmid, and their effects on processing were analyzed in vivo. The same mutations were transferred into T4 by homologous recombination. In both the plasmid and the phage contexts the processing of the transcripts was similarly affected by the mutations. Partially purified RNase E has also been used to ascertain the effect of these mutations on RNase E processing in vitro. The hierarchy of the efficiency of processing of the various mutant transcripts was the same in vivo and in vitro. These results and an analysis of all of the known putative RNase E sites suggest a consensus sequence RAUUW (R = A or G; W = A or U) at the cleavage site. Modifications of the stem-loop structure downstream of the -71 site indicate that a secondary structure is required for RNase E processing. Processing by RNase E was apparently inhibited by sequences that sequester the site in secondary structure.
Development of Methodologies for the Strategic Modification of Purim Ribonwxeoside System (1989)

Abstract Development and application of new methodologies for the synthesis of novel functional l zed analogues of nebularine, inosine, and adenosine of antiviral Interest are described.
Negative Regulation of Soluble Flt-1 and Soluble Endoglin Release by Heme Oxygenase-1 (2007)

The present study demonstrates that the HO-1/CO pathway inhibits sFlt-1 and sEng release, providing compelling evidence for a protective role of HO-1 in pregnancy, and identifies HO-1 as a novel target for the treatment of preeclampsia.
Involvement of the high-affinity receptor for IgG (Fc gamma RI; CD64) in enhanced tumor cell cytotoxicity of neutrophils during granulocyte colony-stimulating factor therapy (1993)

Abstract Three different classes of Fc receptors for IgG (Fc gamma R) are currently distinguished in humans, of which polymorphonuclear phagocytes (PMN) normally express both low-affinity receptor classes-- Fc gamma RII (CD32) and Fc gamma RIII (CD16). During therapy with granulocyte colony-stimulating factor (G-CSF), neutrophils from patients with various malignancies and different hematologic disorders were found to additionally express high levels of the receptor with high affinity for IgG (Fc gamma RI; CD64). For these patients, the relative fluorescence intensity (rFI) for Fc gamma RI was 5.3 (range, 1.7 to 10.3; n = 19), compared with 1.0 (range, 1.0 to 1.1; n = 8) for healthy donors. The expression of Fc gamma RI during G-CSF therapy could be confirmed by using a panel of six CD64-specific antibodies, and by showing mRNA for Fc gamma RI. So far, three genes for Fc gamma RI have been identified, encoding four distinct transcription products. By reverse transcriptase-polymerase chain reaction technology, transcripts for both membrane-associated isoforms (hFc gamma RIa and hFc gamma RIb2) could be detected. The functional activity of Fc gamma RI on PMN during G-CSF therapy was shown by measuring binding of monomeric human IgG and antibody-dependent cellular cytotoxicity (ADCC). Thus, Fc gamma RI-positive neutrophils displayed enhanced ADCC activity to glioma (A1207), squamous cell (A431), and ovarian (SK-ov3) carcinoma cell lines. The involvement of Fc gamma RI in this increased cytotoxic activity was shown by blocking Fc gamma receptors with monoclonal antibodies, and by using F(ab')2 x F(ab')2-bispecific antibodies with specificities against tumor-related antigens and Fc gamma RI, resulting in solely Fc gamma RI-mediated cytotoxicity. Therapeutically, this additional Fc receptor on PMN may increase the efficacy of experimental antibody therapy.
Isolation and structural identification of nine avilamycins. (1986)

Avilamycin is an antibiotic complex produced by cultures of the organism Streptomyces viridochromogenes, strain NRRL 2860. These compounds belong to the orthosomycin family of antibiotics. Structural composition of the major avilamycins and several minor avilamycins are known. Nine additional minor avilamycins, designated F through N, have been isolated via semi-preparative silica gel or reverse-phase high performance liquid chromatography with final purification using a reverse-phase column loading solvent switching technique. 1H NMR and mass spectroscopy, negative ion fast atom bombardment (neg FAB) and electron impact, were used to structurally identify the avilamycins. All of the compounds were microbiologically active and similar in structure to other known avilamycins.
Modeling of blood flow in arterial trees (2010)

Advances in computational methods and medical imaging techniques have enabled accurate simulations of subject-specific blood flows at the level of individual blood cell and in complex arterial networks. While in the past, we were limited to simulations with one arterial bifurcation, the current state-of-the-art is simulations of arterial networks consisting of hundreds of arteries. In this paper, we review the advances in methods for vascular flow simulations in large arterial trees. We discuss alternative approaches and validity of various assumptions often made to simplify the modeling. To highlight the similarities and discrepancies of data computed with different models, computationally intensive three-dimensional (3D) and inexpensive one-dimensional (1D) flow simulations in very large arterial networks are employed. Finally, we discuss the possibilities, challenges, and limitations of the computational methods for predicting outcomes of therapeutic interventions for individual patients.
Determining the Optimal Inhibitory Frequency for Cancerous Cells Using Tumor Treating Fields (TTFields) (2017)

Tumor Treating Fields (TTFields) are an effective treatment modality delivered via the continuous, noninvasive application of low-intensity (1-3 V/cm), alternating electric fields in the frequency range of several hundred kHz. The study of TTFields in tissue culture is carried out using the TTFields in vitro application system, which allows for the application of electric fields of varying frequencies and intensities to ceramic Petri dishes with a high dielectric constant (Ɛ > 5,000). Cancerous cell lines plated on coverslips at the bottom of the ceramic Petri dishes are subjected to TTFields delivered in two orthogonal directions at various frequencies to facilitate treatment outcome tests, such as cell counts and clonogenic assays. The results presented in this report demonstrate that the optimal frequency of the TTFields with respect to both cell counts and clonogenic assays is 200 kHz for both ovarian and glioma cells.
Single-stranded DNA library preparation from highly degraded DNA usingT4DNA ligase (2017)

DNA library preparation for high-throughput sequencing of genomic DNA usually involves ligation of adapters to double-stranded DNA fragments. However, for highly degraded DNA, especially ancient DNA, library preparation has been found to be more efficient if each of the two DNA strands are converted into library molecules separately. We present a new method for single-stranded library preparation, ssDNA2.0, which is based on single-stranded DNA ligation with T4 DNA ligase utilizing a splinter oligonucleotide with a stretch of random bases hybridized to a 3΄ biotinylated donor oligonucleotide. A thorough evaluation of this ligation scheme shows that single-stranded DNA can be ligated to adapter oligonucleotides in higher concentration than with CircLigase (an RNA ligase that was previously chosen for end-to-end ligation in single-stranded library preparation) and that biases in ligation can be minimized when choosing splinters with 7 or 8 random nucleotides. We show that ssDNA2.0 tolerates higher quantities of input DNA than CircLigase-based library preparation, is less costly and better compatible with automation. We also provide an in-depth comparison of library preparation methods on degraded DNA from various sources. Most strikingly, we find that single-stranded library preparation increases library yields from tissues stored in formalin for many years by several orders of magnitude.
Novel Selective and Potent EGFR Inhibitor that Overcomes T790M-Mediated Resistance in Non-Small Cell Lung Cancer (2016)

Treating patients suffering from EGFR mutant non-small cell lung cancer (NSCLC) with first-generation EGFR tyrosine kinase inhibitors (EGFR TKI) provides excellent response rates. However, approximately 60% of all patients ultimately develop drug resistance due to a second T790M EGFR TKI mutation. In this study, we report the novel molecule <i>N</i>-(3-((5-chloro-2-(4-((1-morpholino)methyl)phenylamino)-4-pyrimidinyl)amino)phenyl)acrylamide (DY3002) to preferentially inhibit the EGFR T790M mutant (EGFR<sup>T790M</sup>) (IC<sub>50</sub> = 0.71 nM) over wild-type EGFR (IC<sub>50</sub> = 448.7 nM) in kinase assays. Compared to rociletinib (SI = 21.4) and osimertinib (SI = 40.9), it significantly increased selectivity (SI = 632.0) against EGFR<sup>T790M</sup> over wild-type EGFR. Furthermore, in cell-based tests, DY3002, with an IC<sub>50</sub> value of 0.037 μM, exhibited enhanced inhibitory potency against H1975 cells. Moreover, AO/EB and DAPI staining assays as well as flow cytometer analyses indicated that DY3002 possesses superior biological properties compared to alternatives. In addition, a rat oral glucose tolerance test revealed that treatment with high drug doses (50 mg/kg) of DY3002 did not result in hyperglycemia, suggesting a reduction of side effects in NSCLC patients will be achievable relative to established EGFR inhibitors. In summary, our findings indicate DY3002 as a promising preclinical candidate for effective treatment of patients with EGFR<sup>T790M</sup>-mutated NSCLC.
Diabetic Peripheral Neuropathies: A Morphometric Overview (2010)

Diabetes is now considered one of the main threats to human health in the 21st century and many researchers are dedicated to investigate the physiopathology of the disease, with further insights on the managements of its major complications. Since understanding the pathophysiology of the major complications of diabetes and their underlying processes is mandatory, experimental models of the disease may be useful as they allow the recognition of the early mechanisms involved in the long-term complications of diabetes. Peripheral nerve involvement is highly frequent in diabetes mellitus and it has been documented that one third of diabetic patients have peripheral neuropathy. The true prevalence is not known and reports vary from 10% to 90% in diabetic patients, depending on the criteria and methods used to define neuropathy. In this review, the most common experimental models of diabetes are presented and the pathological findings on major peripheral nerves are discussed. Also, the insights brought by morphometry to the diabetic neuropathy research are highlighted.
Compilation of mRNA Polyadenylation Signals in Arabidopsis Revealed a New Signal Element and Potential Secondary Structures (2005)

Using a novel program, SignalSleuth, and a database containing authenticated polyadenylation [poly(A)] sites, we analyzed the composition of mRNA poly(A) signals in Arabidopsis (Arabidopsis thaliana), and reevaluated previously described cis-elements within the 3'-untranslated (UTR) regions, including near upstream elements and far upstream elements. As predicted, there are absences of high-consensus signal patterns. The AAUAAA signal topped the near upstream elements patterns and was found within the predicted location to only approximately 10% of 3'-UTRs. More importantly, we identified a new set, named cleavage elements, of poly(A) signals flanking both sides of the cleavage site. These cis-elements were not previously revealed by conventional mutagenesis and are contemplated as a cluster of signals for cleavage site recognition. Moreover, a single-nucleotide profile scan on the 3'-UTR regions unveiled a distinct arrangement of alternate stretches of U and A nucleotides, which led to a prediction of the formation of secondary structures. Using an RNA secondary structure prediction program, mFold, we identified three main types of secondary structures on the sequences analyzed. Surprisingly, these observed secondary structures were all interrupted in previously constructed mutations in these regions. These results will enable us to revise the current model of plant poly(A) signals and to develop tools to predict 3'-ends for gene annotation.
Protection of the Small Intestinal Clonogenic Stem Cells from Radiation‐Induced Damage by Pretreatment with Interleukin 11 also Increases Murine Survival Time (1996)

The effect of administering recombinant human interleukin 11 in conjunction with cytotoxic insults to the gastrointestinal tract has been studied using the crypt microcolony assay for stem cell function and whole-animal survival time studies. The cytotoxic regimens include single doses of gamma rays; single doses of 5-fluorouracil (5-FU) and multiple doses of 5-FU spaced 6 h apart. Interleukin 11 (IL-11) (100 micrograms/kg) delivered over a period of time prior to cytotoxic exposure afforded protection to the clonogenic cells in the crypts as seen with the microcolony assay and prolonged the animal survival time following radiation exposure. Continuing this dose of IL-11 after cytotoxic exposure afforded little additional protection. Three doses of 5-FU 6 h apart generated crypt survival curves similar to those obtained after a single dose of gamma rays. IL-11 given prior to two doses of 5-FU effectively abolished the cytotoxic effect of the second dose of 5-FU; i.e., 2.5-3.0 times more crypts survived if IL-11 was administered when the higher 5-FU doses are considered. IL-11 given before a dose of 12 Gy of gamma rays prolonged the survival time of animals by three to four days. This confirms earlier studies demonstrating that protecting clonogenic cells in the crypt survival assay can result in beneficial effects on whole-animal survival times.
Chernobyl experience: biological indicators of exposure to ionizing radiation. (1995)

Using the Chernobyl accident as an example, an attempt is made to consider the possibility of using the biological markers of exposure and effects of exposure to ionizing radiation in relation to biology dosimetry, and to predict early and late nonstochastic and stochastic radiation consequences. The biological dosimetry was based on the three markers: chromosome aberrations of peripheral blood lymphocytes, dynamics of blood cell (lymphocytes, neutrophils) counts and electron spin resonance (ESR) of tooth enamel. The first two methods can be applied in a short period of time (days or weeks) after exposure and only after high doses (> 0.5-1 Gy) of acute total body irradiation (TBI). The ESR tooth enamel method possesses dosimetric value at all conditions of uniform gamma TBI (acute, prolonged, chronic and high as well as low level of doses) and at any time after exposure. The low limit of sensitivity of the ESR test is about 0.1 Gy. The use of biological markers of effects of radiation exposure as early diagnostic signs was limited to clinical significant disorders of hemopoietic, immune systems and skin in conditions of acute high-dose irradiation. In cases of acute or prolonged irradiation in low doses, many changes on the cellular as well as organism level were discovered. However, there were not enough data on radiation specificity or dose dependence of these changes. Hence they cannot be considered as the indicators of clinically significant early and late nonstochastic effects. The role of biological markers of stochastic effects in clinical practice is discussed herein.
Bit-rate selection in wireless networks (2005)

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.
Comparing total cost of care for Medicare FFS patients with pancreatic cancer by chemotherapy regimen. (2020)

e19394 Background: To analyze total cost of care for patients with pancreatic cancer by common therapeutic regimens. Methods: Cancer episodes were identified using a methodology similar to the Medicare Oncology Care Model (OCM) in the 2014-2016 100% Medicare Limited Data Set (LDS) claims files. Index dates for chemotherapy claims could not occur within 6 months of another chemotherapy claim for all Medicare FFS beneficiaries. Cancer episodes were defined as the 6-month period following an index date. Each episode was assigned a cancer type based on the plurality of cancer ICD 9/10 diagnosis codes that occurred on chemotherapy claims in the episode. Episode costs were calculated from claims paid amounts. DME and other Part B spending was estimated using episodes from the 5% Medicare LDS files using the same methodology. We analyzed total episode costs for five pancreatic cancer treatment regimens: gemcitabine plus nab-paclitaxel (gem-nab), FOLFIRINOX, liposomal irinotecan, FOLFOX, and FOLFIRI. Results: We identified 110,618 cancer episodes in 2016, of which 4,018 were pancreatic cancer. Pancreatic cancer patients in these episodes were treated with gem-nab (45% of episodes), FOLFIRINOX (14%), FOLFOX (8%), FOLFIRI (6%), and liposomal irinotecan (4%). The main drivers of episode costs among regimens were Part B chemotherapy, other Part B drugs, and inpatient services. Episode costs were $41,749, $42,086, $35,601, $36,169, and $45,851 for patients receiving gem-nab, FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan, respectively. Part B chemotherapy costs were $13,065 (gem-nab), $3,095 (FOLFIRINOX), $4,853 (FOLFOX), $3,204 (FOLFIRI), and $18,474 (liposomal irinotecan); other Part B drug costs were $7,343 (gem-nab), $17,013 (FOLFIRINOX), $11,131 (FOLFOX), $15,377 (FOLFIRI), and $10,479 (liposomal irinotecan); and inpatient service costs were $9,044 (gem-nab), $9,069 (FOLFIRINOX), $7,701 (FOLFOX), $5,838 (FOLFIRI), and $5,108 (liposomal irinotecan). Conclusions: Total episode costs for pancreatic cancer care ranged from $35,601 (FOLFOX) to $45,851 (liposomal irinotecan), but the cost components varied by regimen. Episodes with liposomal irinotecan had the largest Part B chemotherapy costs but the lowest inpatient service costs. Episodes with FOLFIRINOX and gem-nab had similar inpatient service costs, which were higher than episodes with liposomal irinotecan, FOLFOX, or FOLFIRI. Episodes with FOLFIRINOX and FOLFIRI had higher other Part B drug costs than episodes with FOLFOX, liposomal irinotecan, or gem-nab.
Applications of Infrared and Raman Microspectroscopy of Cells and Tissue in Medical Diagnostics: Present Status and Future Promises (2012)

This paper summarizes the progress achieved over the past fifteen years in applying vibrational (Raman and IR) spectroscopy to problems of medical diagnostics and cellular biology. During this time, a number of research groups have verified the enormous information content of vibrational spectra; in fact, genomic, proteomic, and metabolomic information can be deduced by decoding the observed vibrational spectra. This decoding process is aided enormously by the availability of high‐power computer workstations and advanced algorithms for data analysis. Furthermore, commercial instrumentation for the fast collection of both Raman and infrared microspectral data has rendered practical the collection of images based solely on spectral data. The progress in the field has been manifested by a steady increase in the number and quality of publications submitted by established and new research groups in vibrational biological and biomedical arenas.
PLZT laser beam modulator (1992)

Abstract Laser beam modulator on transparent electrooptic PLZT ceramics are developed for the use in teaching process in schools and universities. Characteristics of the modulator and its electronic control unit are given.
An interleukin‐1β‐converting enzyme‐like protease is a common mediator of apoptosis in thymocytes (1995)

Apoptosis was induced in thymocytes using diverse stimuli in order to identify events within a common apoptotic pathway. Benzyloxycarbonyl-valinyl-alaninyl-aspartyl fluoromethyl ketone (Z-VAD.FMK), an interleukin-1 beta-converting enzyme (ICE)-like protease inhibitor, inhibited apoptosis assessed by flow cytometry, proteolysis of poly (ADP)-ribose polymerase of DNA to both large kilobase pair fragments (30-50 and 200-300 kbp) and to nucleosomal fragments. Z-VAD.FMK also blocked all the classical ultrastructural features of apoptosis including chromatin condensation to one pole of the nucleus, nucleolar disintegration and cytoplasmic vacuolation. These results suggest the involvement of an ICE-like protease as a common mediator of apoptosis in thymocytes.
Invariant Vα14+ NKT Cells Participate in the Early Response to Enteric Listeria monocytogenes Infection (2005)

Invariant Valpha14(+) NKT cells are a specialized CD1-reactive T cell subset implicated in innate and adaptive immunity. We assessed whether Valpha14(+) NKT cells participated in the immune response against enteric Listeria monocytogenes infection in vivo. Using CD1d tetramers loaded with the synthetic lipid alpha-galactosylceramide (CD1d/alphaGC), we found that splenic and hepatic Valpha14(+) NKT cells in C57BL/6 mice were early producers of IFN-gamma (but not IL-4) after L. monocytogenes infection. Adoptive transfer of Valpha14(+) NKT cells derived from TCRalpha degrees Valpha14-Jalpha18 transgenic (TCRalpha degrees Valpha14Tg) mice into alymphoid Rag(null) gamma(c)(null) mice demonstrated that Valpha14(+) NKT cells were capable of providing early protection against enteric L. monocytogenes infection with systemic production of IFN-gamma and reduction of the bacterial burden in the liver and spleen. Rechallenge experiments demonstrated that previously immunized wild-type and Jalpha18null mice, but not TCRalpha(null) or TCRalpha(null) Valpha14Tg mice, were able to mount adaptive responses to L. monocytogenes. These data demonstrate that Valpha14(+) NKT cells are able to participate in the early response against enteric L. monocytogenes through amplification of IFN-gamma production, but are not essential for, nor capable of, mediating memory responses required to sterilize the host.
Malondialdehyde in Exhaled Breath Condensate as a Marker of Oxidative Stress in Different Pulmonary Diseases (2011)

EBC-MDA is increased in subjects with chronic airway disorders, particularly in COPD, and it is related to FEV(1) reduction.