gebhart/patrepeval huggingface dataset:
The amino‐acid sequence of the 2S sulphur‐rich proteins from seeds of Brazil nut (Bertholletia excelsa H.B.K.) (1986)

Storage proteins of the albumin solubility fraction from seeds of Bertholletia excelsa H.B.K. were separated by reversed-phase high-performance liquid chromatography and their primary structures were determined by gas-phase sequencing on intact polypeptides and on the overlapping tryptic and thermolysin peptides. The 2S storage proteins consist of two subunits linked by disulphide bridges. The large subunit (8.5 kDa) is expressed in at least six different isoforms while the small subunit (3.6 kDa) consists of only one form. These proteins are extremely rich in glutamine, glutamic acid, arginine and the sulphur-containing amino acids cysteine and methionine. One of the variants even contains a sequence of six methionine residues in a row. Comparison with known sequences of 2S proteins of other dicotyledonous plants shows limited but distinct sequence homology. In particular, the positions of the cysteine residues relative to each other appear to be completely conserved, suggesting that tertiary structure constraints imposed by disulphide bridges dominate sequence conservation. It has been proposed that the two subunits of a related protein (the Brassica napus storage protein) is cleaved from a precursor polypeptide [Crouch, M. L., Tenbarge, K. M., Simon, A. E. & Ferl, R. (1983) J. Mol. Appl. Genet. 2,273-283]. The amino acid sequence homology of the Brazil nut protein with the former suggests that a similar protein processing event could occur.
EasyClone: method for iterative chromosomal integration of multiple genes Saccharomyces cerevisiae (2013)

Development of strains for efficient production of chemicals and pharmaceuticals requires multiple rounds of genetic engineering. In this study, we describe construction and characterization of EasyClone vector set for baker's yeast Saccharomyces cerevisiae, which enables simultaneous expression of multiple genes with an option of recycling selection markers. The vectors combine the advantage of efficient uracil excision reaction-based cloning and Cre-LoxP-mediated marker recycling system. The episomal and integrative vector sets were tested by inserting genes encoding cyan, yellow, and red fluorescent proteins into separate vectors and analyzing for co-expression of proteins by flow cytometry. Cells expressing genes encoding for the three fluorescent proteins from three integrations exhibited a much higher level of simultaneous expression than cells producing fluorescent proteins encoded on episomal plasmids, where correspondingly 95% and 6% of the cells were within a fluorescence interval of Log10 mean ± 15% for all three colors. We demonstrate that selective markers can be simultaneously removed using Cre-mediated recombination and all the integrated heterologous genes remain in the chromosome and show unchanged expression levels. Hence, this system is suitable for metabolic engineering in yeast where multiple rounds of gene introduction and marker recycling can be carried out.
Genomic Analysis of Clostridium botulinum Group II by Pulsed-Field Gel Electrophoresis (1998)

Pulsed-field gel electrophoresis (PFGE) was optimized for genomic analyses of Clostridium botulinum (non-proteolytic) group II. DNA degradation problems caused by extracellular DNases were overcome by fixation of cells with formaldehyde prior to isolation. A rapid (4-h) in situ DNA isolation method was also assessed and gave indistinguishable results. Genomic DNA from 21 strains of various geographical and temporal origins was digested with 15 rare-cutting restriction enzymes. Of these, ApaI, MluI, NruI, SmaI, and XhoI gave the most revealing PFGE patterns, enabling strain differentiation. Twenty strains yielded PFGE patterns containing 13 pulsotypes. From summation of MluI, SmaI, and XhoI restriction fragments, the genome size of C. botulinum group II was estimated to be 3.6 to 4.1 Mb (mean +/- standard deviation = 3,890 +/- 170 kb). The results substantiate that after problems due to DNases are overcome, PFGE analysis will be a reproducible and highly discriminating epidemiological method for studying C. botulinum group II at the molecular level.
Formation of Decagonal Quasicrystal in the Al-Pd-Mn System and Its Structure (1991)

Formation of a decagonal quasicrystal in Al 70 Pd 30- x Mn x alloys ( x =8-20) and its structure were examined by X-ray powder diffraction, electron diffraction and high-resolution electron microscopy. The decagonal quasicrystal is formed as a coexisting phase with an icosahedral phase in the composition range of x =10-15, and as a single phase at a composition of x about 20. The structure of the decagonal phase is a mixture of decagonal quasicrystalline regions with some linear phason strain and microcrystalline regions. We propose that the structure of Al-Pd-Mn decagonal quasicrystal may be interpreted as a tiling formed by atom cluster linkages, which are different to those reported in Al-Ni-Co and Al-Cu-Co decagonal quasicrystals.
A Homologue of the Aspergillus velvet Gene Regulates both Cephalosporin C Biosynthesis and Hyphal Fragmentation in Acremonium chrysogenum (2007)

The Aspergillus nidulans velvet (veA) gene encodes a global regulator of gene expression controlling sexual development as well as secondary metabolism. We have identified the veA homologue AcveA from Acremonium chrysogenum, the major producer of the beta-lactam antibiotic cephalosporin C. Two different disruption strains as well as the corresponding complements were generated as a prelude to detailed functional analysis. Northern hybridization and quantitative real-time PCR clearly indicate that the nucleus-localized AcVEA polypeptide controls the transcriptional expression of six cephalosporin C biosynthesis genes. The most drastic reduction in expression is seen for cefEF, encoding the deacetoxycephalosporine/deacetylcephalosporine synthetase. After 120 h of growth, the cefEF transcript level is below 15% in both disruption strains compared to the wild type. These transcriptional expression data are consistent with results from a comparative and time-dependent high-performance liquid chromatography analysis of cephalosporin C production. Compared to the recipient, both disruption strains have a cephalosporin C titer that is reduced by 80%. In addition to its role in cephalosporin C biosynthesis, AcveA is involved in the developmentally dependent hyphal fragmentation. In both disruption strains, hyphal fragmentation is already observed after 48 h of growth, whereas in the recipient strain, arthrospores are not even detected before 96 h of growth. Finally, the two mutant strains show hyperbranching of hyphal tips on osmotically nonstabilized media. Our findings will be significant for biotechnical processes that require a defined stage of cellular differentiation for optimal production of secondary metabolites.
TRPV1 Signaling: Mechanistic Understanding and Therapeutic Potential (2011)

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel gated by noxious heat, vanilloids and extracellular protons. TRPV1 is acting as an important signal integrator in sensory nociceptors under physiological and pathological conditions including inflammation and neuropathy. Because of its integrative signaling properties in response to inflammatory stimuli, TRPV1 agonists and antagonists are predicted to inhibit the sensation of ongoing or burning pain that is reported by patients suffering from chronic pain, therefore offering an unprecedented advantage in selectively inhibiting painful signaling from where it is initiated. In this article, we firstly summarize recent advances in the understanding of the role of TRPV1 in pain signaling, including a overview of clinical pharmacological trials using TRPV1 agonists and antagonists. Finally, we also present an update on the mechanistic understanding and controlling of hyperthermia caused by TRPU1 antagonists, and provide perspective for future study.
A Statewide Plan to Address the Unmet Psychosocial Needs of People with Cancer (1993)

Cancer patients continue to experience unmet psychosocial needs despite the presence of supportive services in inpatient and community settings. This article describes the model of a statewide, standardized, continuing education program for health professionals who care for cancer patients that was presented in 19 different locations in southeastern Pennsylvania. The authors use a structure-prccess-outcome format to present the development, implementation, and evaluation of the program As a result of the program, participants felt more comfortable about addressing psychosocial issues in oncology. This led to positive behavioral changes at the work site regarding the way patients with unmet psychosocial needs were identified, treated, and referred.
Rapid fluorometric assay of LDL receptor activity by DiI-labeled LDL. (1993)

DiI-LDL (3,3'-dioctadecylindocarbocyanine-low density lipoprotein) has been extensively used in morphological and microscopic studies of receptor-mediated metabolism of LDL in many cell lines. To date the use of this fluorescent probe in a quantitative assay of LDL receptor activity has not been widely used in studies with multiple samples due to the lack of a practical method for quantitatively recovering cell-associated DiI. Therefore, detection by 125I-labeled LDL has remained the method of choice for assaying LDL receptor activity rapidly and reliably. In this paper, we describe a rapid, simple, and nonradioactive assay of LDL receptor activity using DiI-LDL. The increased sensitivity of this method was achieved by modifications to the labeling procedure of LDL and to the extraction of DiI from cells for subsequent fluorescence determination. These modifications did not affect the affinity of DiI-LDL toward HepG2 cells, and the assay was easily adapted to a rapid screen for LDL receptor modulators in this cell model.
Polymers for Drug Delivery Systems (2010)

Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery.
Efficiency of nano-electrospray ionization (2005)

The efficiency of nano-electrospray ionization, defined as the flux of ions reaching the detector of a triple-quadrupole mass spectrometer divided by the flux of analyte ions leaving the needle, has been measured in a series of controlled experiments with dodecyltrimethyl ammonium (DDTMA) bromide, myoglobin, Glu- [1]-fibrinopeptide, and gramicidin S. By varying the flow rate from each needle, the optimum efficiency was determined. In general, the efficiency increased as the flow rate decreased. For DDTMA, efficiencies of up to 12% were measured, although efficiencies of approximately 1% were more common. Ion current measurements indicated efficient transfer of ions from the needle through to the detector. Significant needle-to-needle variations in efficiency were encountered and attributed to variations in ion-generation efficiency.
RFID restaurant POS system (2011)

In order to reduce the labor cost, improve the service quality, and achieve energy saving and carbon reduction for restaurants, this paper integrated a RFID, server and graphical man-machine interface to develop an ordering system for restaurants. The system can improve the service efficiency, lower the operating cost, and reduce environmental burden.
A new crystalline form of 30 S ribosomal subunits from Thermus thermophilus (1988)

A new crystalline form of 30 S ribosomal subunits from an extremely thermophilic bacterium Thermus thermophilus has been obtained. Positively stained ultrathin sections of the crystals have been analysed by electron microscopy. The crystals show X‐ray diffraction to about 12 Å resolution in a synchroton beam at 0°C.
The circadian profile of epilepsy improves seizure forecasting (2017)

It is now established that epilepsy is characterized by periodic dynamics that increase seizure likelihood at certain times of day, and which are highly patient-specific. However, these dynamics are not typically incorporated into seizure prediction algorithms due to the difficulty of estimating patient-specific rhythms from relatively short-term or unreliable data sources. This work outlines a novel framework to develop and assess seizure forecasts, and demonstrates that the predictive power of forecasting models is improved by circadian information. The analyses used long-term, continuous electrocorticography from nine subjects, recorded for an average of 320 days each. We used a large amount of out-of-sample data (a total of 900 days for algorithm training, and 2879 days for testing), enabling the most extensive post hoc investigation into seizure forecasting. We compared the results of an electrocorticography-based logistic regression model, a circadian probability, and a combined electrocorticography and circadian model. For all subjects, clinically relevant seizure prediction results were significant, and the addition of circadian information (combined model) maximized performance across a range of outcome measures. These results represent a proof-of-concept for implementing a circadian forecasting framework, and provide insight into new approaches for improving seizure prediction algorithms. The circadian framework adds very little computational complexity to existing prediction algorithms, and can be implemented using current-generation implant devices, or even non-invasively via surface electrodes using a wearable application. The ability to improve seizure prediction algorithms through straightforward, patient-specific modifications provides promise for increased quality of life and improved safety for patients with epilepsy.
Detection of the QRS complex, P wave and T wave in electrocardiogram (2000)

Electrocardiogram (ECG) provides useful information of the condition of the heart. Most automatic ECG diagnosis techniques require an accurate detection of the QRS complexes. In this project, two QRS detection methods are studied. The first method, the “So and Chan” method (H.H. So and K.L. Chan, 1997), is based on the maximum slope detection with the QRS onset selected when two successive values of the slope exceed the threshold. The second method is developed by J. Pan and W.J. Tompkins (1985). American Heart Association (AHA) ECG data files are used to test these two QRS detection methods. Our results show that the “So and Chan” method performs better than the “Pan and Tompkins” method. Further development continues on the “So and Chan” method. Based on the information of the identified QRS complexes, the P waves and the T waves are also be detected. ECG classification is then carried out using the autocorrelation. The classification algorithm is trained to recognize four types of beat.
Time-to-treatment discontinuation (TTD) and real-world progression-free survival (rwPFS) as endpoints for comparative efficacy analysis between entrectinib trial and crizotinib real-world ROS1 fusion-positive (ROS1+) NSCLC patients. (2019)

9070 Background: Entrectinib is an oral tyrosine kinase inhibitor for ROS1+ NSCLC. Three phase 1/2 single-arm studies showed entrectinib efficacy in this population (Doebele WCLC 2018). Due to the rarity of ROS1+ pts generating direct comparative evidence in prospective randomized trials is difficult. We identified a retrospective real-world cohort of ROS1+ NSCLC pts from electronic health records (EHR), to compare crizotinib, the current standard of care, to entrectinib as reported in clinical trials. Methods: Crizotinib-treated pts with advanced ROS1+ NSCLC diagnosed 1 Jan 2011 to 30 Jun 2018, were identified with technology-enabled abstraction in the Flatiron Health EHR-derived database ( &gt; 2.1 million cancer pts from US oncology practice). Entrectinib trial inclusion/exclusion criteria were applied to match the crizotinib cohort as closely as possible. Primary endpoint: TTD, adapted from Gong (ASCO 2018); rwPFS (physician/scan report) and OS were secondary outcomes. Time-to-event analyses used Kaplan-Meier survival curves and Cox proportional hazard models on propensity score weighted populations; age, gender, race/ethnicity, smoking status, brain metastasis and previous lines of therapy were prognostic factors. Results: We analyzed 53 entrectinib and 69 crizotinib ROS1+ NSCLC pts. Median weighted TTD: entrectinib, 14.6 mo (95% CI: 8.3–23.8); crizotinib, 8.8 mo (95% CI: 8.2–9.9). When rwPFS from crizotinib was compared to trial PFS, entrectinib had longer PFS vs crizotinib (weighted HR: 0.44; 95% CI: 0.27–0.74). Median OS with entrectinib was not reached (median follow-up: 15.5 mo); weighted median OS with crizotinib was 18.5 mo (95% CI: 15.1–19.9). Findings were consistent across multiple sensitivity analyses. Conclusions: Entrectinib was associated with longer TTD and PFS in ROS1+ NSCLC pts vs a matched real-world crizotinib population. Control populations derived from real-world cohorts can supplement evidence from clinical trials in settings where new standards of care are needed, but where only limited data are available and randomization is not feasible.
Mining control flow graph as API call-grams to detect portable executable malware (2012)

Present day malware shows stealthy and dynamic capability and avails administrative rights to control the victim computers. Malware writers depend on evasion techniques like code obfuscation, packing, compression, encryption or polymorphism to avoid detection by Anti-Virus (AV) scanners as AV primarily use syntactic signature to detect a known malware. Our approach is based on semantic aspect of PE exectable that analyses API Call-grams to detect unknown malicious code. As in--exact source code is analysed, the machine is not infected by the executable. Moreover, static analysis covers all the paths of code which is not possible with dynamic behavioural methods as latter does not gurantee the execution of sample being analysed. Modern malicious samples also detect controlled virtual and emulated environments and stop the functioning. Semantic invariant approach is important as signature of known samples are changed by code obfuscation tools. Static analysis is performed by generating an API Call graph from control flow of an executable, then mining the Call graph as API Call-gram to detect malicious files.
Susceptibility of exogenous surfactant to phospholipase Α2 degradation (1996)

The inhibition of surfactant biophysical activity in vivo is potentially mediated by many factors, including serum proteins, particularly enzymatic proteins such as phospholipases. In the present study, we investigated the susceptibility of the phosphatidylcholine component of two exogenous surfactants, Exosurf and Survanta, to secretory-type phospholipase A2 (PLA2) deacylation in vitro. Lyophilized Exosurf and Survanta preparations were incubated at 37 degrees C for 120 min in the presence of bovine pancreatic PLA2, and the production of lysophosphatidylcholine was determined as a measure of the magnitude of phosphatidylcholine deacylation. The phosphatidylcholine component of Survanta was readily deacylated by PLA2, whereas the dipalmitoylphosphatidycholine (DPPC) component of Exosurf was resistant over the entire duration of the assay. To further evaluate this observed resistance the individual and combined effects of tyloxapol and hexadecanol, components of Exosurf, upon PLA2 deacylation of Survanta and DPPC were investigated. In both Survanta and DPPC preparations, PLA2-mediated deacylation was significantly inhibited in the presence of tyloxapol. We conclude that the presence of tyloxapol in the Exosurf preparation inhibits secretory type PLA2 mediated DPPC deacylation. This unique feature of Exosurf may be of clinical significance when this preparation is utilized in the treatment of surfactant-deficient infants.
Prevention of Radiation-Induced Oral Cavity Mucositis by Plasmid/Liposome Delivery of the Human Manganese Superoxide Dismutase (SOD2) Transgene (2003)

Oral cavity mucositis is a major toxicity of radiation therapy for head and neck cancer. In the present mouse model studies, we evaluated intraoral administration of SOD2-PL complexes 24 h before single-fraction 30-Gy irradiation for the prevention of oral cavity mucositis. Expression of the human SOD2 transgene in the oral cavity of C3H/HeNsd mice was demonstrated by nested reverse transcriptase polymerase chain reaction (RT-PCR). Mice treated intraorally with bacterial beta-galactosidase gene-plasmid/liposome (LacZ-PL) or hemagglutinin (HA)-manganese superoxide dismutase-plasmid/liposome (HA-SOD2-PL) demonstrated LacZ or HA-SOD2 expression, respectively, 24 h after injection. In a second strain of mouse, SOD2-PL-treated female athymic nude mice demonstrated significantly decreased ulceration at day 5 after 30 Gy, compared to LacZ-PL-injected, irradiated mice or irradiated controls. No further reduction in radiation-induced ulceration was detected in mice treated with both SOD2-PL and 10 mg/kg of amifostine (WR-2721) 30 min before 30 Gy compared to SOD2-PL alone. No significant protection of orthotopically transplanted murine squamous cell carcinoma (SCC-VII) tumors was detected in mice that received SOD2-PL treatment before 18 Gy. Thus overexpression of human SOD2 in the oral cavity mucosa can prevent radiation-induced mucositis with no detectable compromise in the therapeutic response of orthotopically transplanted tumors.
Interferon-gamma is an inducer of plasminogen activator inhibitor type 1 in human orbital fibroblasts (1992)

Expression of plasminogen activator inhibitor type 1 (PAI-1), an important determinant of the pericellular proteolytic environment, was assessed in cultured human orbital and dermal fibroblasts. Bidimensional electrophoretic separation of total cellular [35S]methionine-labeled proteins revealed multiple isoforms of the 50-kDa PAI-1 protein (isoelectric point range 5.6-6.3) expressed in dermal strains but not in orbital cultures. The addition of human recombinant interferon-gamma (100 U/ml) to the media for 48 h resulted in a marked induction of PAI-1 in the orbital cultures (greater than 50-fold above baseline), whereas the expression in dermal cultures was either attenuated or induced modestly (5-fold). The identity of the 50-kDa PAI-1 was verified by immunoprecipitation of secreted proteins. Indirect immunofluorescence localized PAI-1 to aggregates at the ventral undersurface of the monolayer. Interferon-gamma induced several other proteins in cultured cells. The observation that untreated orbital fibroblasts do not express detectable cell-associated PAI-1 suggests that the pericellular proteolytic environment of these cells is regulated ordinarily by other factors. The economy of the extracellular matrix of orbital connective tissue may be particularly susceptible to the influence of inflammatory cytokines such as interferon-gamma.