gebhart/patrepeval huggingface dataset:
High-yield cleavage of tryptophanyl peptide bonds by o-iodosobenzoic acid (1979)

A new procedure to cleave tryptophanyl peptide bonds in high yield is reported. The method involves treatment of the S-alkylated protein with o-iodosobenzoic acid. The procedure is highly selective for tryptophan and does not modify tyrosine or histidine, but may convert methionine to its sulfoxide derivative. The yields in the cleavage are 70--100%. Tryptophanyl bonds to alanine, glycine, serine, threonine, glutamine, arginine, and S-(pyridylethyl)cysteine are split in nearly quantitative yield, while those preceding isoleucine or valine are split in approximately 70% yield in the proteins examined in this work. The chemical mechanism for tryptophanyl bond cleavage has not been defined, but it is likely that oxidation of the indole ring occurs during the reaction with o-iodosobenzoic acid. Some problems with the quality of commercial preparations of the reagent are discussed.
A framework for the behaviour of unsaturated expansive clays (1992)

The paper presents a framework for describing the mechanical behaviour of unsaturated expansive clays. It is an extension of an existing formulation developed for unsaturated soils of low activity. The extended framework is based on the distinction within the material of a microstructural level where the basic swelling of the active minerals takes place and a macrostructural level responsible for major structural rearrangements. By adopting simple assumptions concerning the coupling between the two levels, it is possible to reproduce major features of the behaviour of unsaturated expansive clays. Some selected qualitative comparisons between model predictions and experimental results reported in the literature are presented. Despite the simplified hypotheses made, a very encouraging agreement is obtained. Key words : capillarity, clay, model, unsaturation, suction, expansive soils.
Strategy for Controlling Preferential Amplification and Avoiding False Negatives in PCR Typing (1996)

The use of the PCR method for routine testing has increased dramatically during recent years. Most assays involve co-amplification either of an internal control, of several alleles at a given locus or of a variety of bands produced by low-stringency primer annealing. In such multiplex reactions, certain products will often amplify preferentially. Amplimers that are more sensitive can be outcompeted under suboptimal PCR conditions, leading to assignment of false negatives. Optimization of PCR parameters such as temperature steps, relative concentrations of primers and their annealing temperature do not alone ensure against false negatives when caused by stable double-stranded DNA (dsDNA) regions in the amplified sequence. A two-step strategy to solve this problem is presented in this paper: (i) titration of the PCR with NaCl as a model inhibitor to establish the critical range within which false negatives occur; (ii) titration of the PCR with a dsDNA-destabilizing additive under false-negative-inducing conditions until the relative amplification efficiencies of co-amplified fragments are adjusted. Betaine is introduced as a novel and efficient cosolute. These measures to achieve reliable PCR typing of a difficult target should be useful for many qualitative and quantitative multiplex PCR applications.
Application of Continuous Flow for DIBAL-H Reduction and n-BuLi Mediated Coupling Reaction in the Synthesis of Eribulin Mesylate (2015)

Here we examined the use of continuous flow conditions for the final assembly of eribulin mesylate aimed to avoid cryogenic condition. The diisobutylaluminum hydride reduction of ester 2 to aldehyde 3 and n-butyllithium-mediated coupling of aldehyde 3 and sulfone fragment 4 to produce sulfone-diol 5 were investigated. Under optimized continuous flow conditions, both reactions could be run at temperatures higher than those used under batch conditions. For the diisobutylaluminum hydride reduction of ester 2 to aldehyde 3, under optimized continuous flow conditions at −50 °C, aldehyde 3 was afforded with better HPLC area ratio than it was under batch conditions at −70 °C. Furthermore, continuous operation for 87 min afforded the same quality of 3 as was produced with a short-time operation (yield, 96.5%). For the n-butyllithium-mediated coupling of 3 and 4, under optimized continuous flow conditions at 10 °C, 5 was afforded with a better conversion rate than it was under batch conditions at −70 °C.
Mechanisms that regulate the cell cycle status of very primitive hematopoietic cells in long-term human marrow cultures. II. Analysis of positive and negative regulators produced by stromal cells within the adherent layer (1991)

Numerous factors that can influence the proliferation and differentiation in vitro of cells at various stages of hematopoiesis have been identified, but the mechanisms used by stromal cells to regulate the cycling status of the most primitive human hematopoietic cells are still poorly understood. Previous studies of long-term cultures (LTC) of human marrow have suggested that cytokine-induced variations in stromal cell production of one or more stimulators and inhibitors of hematopoiesis may be important. To identify the specific regulators involved, we performed Northern analyses on RNA extracted from human marrow LTC adherent layers, or stromal cell types derived from or related to those present in the adherent layer. These analyses showed marked increases in interleukin-1 beta (IL-1 beta), IL-6, and granulocyte colony-stimulating factor (G-CSF) mRNA levels within 8 hours after treatments that lead to the activation within 2 days of primitive hematopoietic progenitors in such cultures. Increases in granulocyte-macrophage (GM)-CSF and M-CSF mRNA were also sometimes seen. Bioassays using cell lines responsive to G-CSF, GM-CSF, and IL-6 showed significant elevation in growth factor levels 24 hours after IL- 1 beta stimulation. Neither IL-3 nor IL-4 mRNA was detectable at any time. In contrast, transforming growth factor-beta (TGF-beta) mRNA and nanogram levels of TGF-beta bioactivity in the medium were detected at all times in established LTC, and these levels were not consistently altered by any of the manipulations that stimulated hematopoietic growth factor production and primitive progenitor cycling. We also found that addition of anti-TGF-beta antibody could prolong or reactivate primitive progenitor proliferation when added to previously stimulated or quiescent cultures, respectively. Together, these results indicate a dominant negative regulatory role of endogenously produced TGF-beta in unperturbed LTC, with activation of primitive hematopoietic cells being achieved by mechanisms that stimulate stromal cells to produce G-CSF, GM-CSF, and IL-6. Given the similarities between the LTC system and the marrow microenvironment, it seems likely that the control of human stem cell activation in vivo may involve similar variations in the production of these factors by stromal cells.
Resistance to methotrexate in SKOV-3 cell lines after chronic exposure to carbamazepine is associated with a decreased expression of folate receptor (2000)

The detrimental effect of chronic administration of carbamazepine (CBZ) on serum and erythrocyte folates of patients has been extensively analyzed. However, at present, no data have been reported on the effect of CBZ on the intracellular content and activity of antimetabolite cytotoxic agents that can be used together with CBZ in the treatment of cancer patients. To investigate this issue, we chronically exposed in vitro the human ovarian cancer cell line SKOV-3 (grown under physiological folate concentrations) to CBZ, thus selecting SKOV-CBZ clones (SKOV-CBZ-50-2, SKOV-CBZ-50-5 and SKOV-CBZ-100-2) able to grow in the continuous presence of the antiepileptic drug. All of the SKOV-CBZ clones were more resistant to methotrexate (MTX) than the parental cells. MTX resistance index, as determined by the ratio between MTX concentrations inhibiting cell growth by 50% (MTX IC(50)) in SKOV-CBZ clones and in the parental cells, ranged between 3- and 5-fold. This resistance was related to a reduced intracellular content of MTX. No alteration activity of the cellular enzymes directly involved in MTX cytotoxicity (dihydrofolate reductase, thymidylate synthase [TS] and folylpolyglutamate synthetase) was observed. SKOV-CBZ clones were cross-resistant to the TS inhibitors tomudex and CB3717, but not to the TS inhibitor 5-fluoro-deoxy uridine and other antineoplastic drugs (cisplatin, doxorubicin, vincristine and taxol), whose cellular uptake is derived from transmembrane transport mechanisms different from folate receptor alpha (FRalpha) or reduced folate carrier (RFC). FRalpha mRNA and protein levels were significantly lower in SKOV-CBZ clones than in the parental cells. The reduced level of FRalpha in SKOV-CBZ clones was associated with a decreased binding capacity of folic acid. No variation of mRNA RFC expression in the SKOV-CBZ clones as compared to the parental cells was observed. Thus, after chronic exposure to CBZ, SKOV-CBZ clones develop resistance towards MTX due to defective MTX uptake.
Secretive Bacterial Pathogens and the Secretory Pathway (2012)

Eukaryotic cells possess two extensive endomembrane systems, each consisting of several sub-compartments connected by vesicular trafficking. One of these systems, the endocytic pathway, serves incoming traffic, and the other system, the secretory pathway (SP), is responsible for surface-bound traffic of intracellularly formed vesicles. Compartments derived of either system can be colonized by intracellular pathogens. In this review, we discuss the interactions between the SP and prominent intracellular bacterial pathogens of the genera Legionella, Brucella, Chlamydia and Salmonella. We emphasize secreted bacterial effector proteins, which directly manipulate host components of this pathway.
EMFET: E-mail Features Extraction Tool (2017)

EMFET is an open source and flexible tool that can be used to extract a large number of features from any email corpus with emails saved in EML format. The extracted features can be categorized into three main groups: header features, payload (body) features, and attachment features. The purpose of the tool is to help practitioners and researchers to build datasets that can be used for training machine learning models for spam detection. So far, 140 features can be extracted using EMFET. EMFET is extensible and easy to use. The source code of EMFET is publicly available at GitHub (https://github.com/WadeaHijjawi/EmailFeaturesExtraction)
Direct Left Atrial Pressure Monitoring in Ambulatory Heart Failure Patients (2007)

Ambulatory monitoring of direct LAP with a new implantable device was well tolerated, feasible, and accurate at a short-term follow-up. Further follow-up and investigation are warranted to evaluate the clinical utility of LAP monitoring in patients with heart failure.
Intermedia: the concept and the construction of a seamless information environment (1988)

A description is given of Intermedia, a tool designed to support both teaching and research in a university environment. This multiapplication hypermedia system provides linking capabilities integrated into a desktop user environment. Hypermedia is simply an extension of hypertext that incorporates other media in addition to text. To promote consistency, the applications were built with an object-oriented framework. A sample Intermedia session is presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Androgen Receptor Coactivators Lysine-Specific Histone Demethylase 1 and Four and a Half LIM Domain Protein 2 Predict Risk of Prostate Cancer Recurrence (2006)

Prostate cancer biology varies from locally confined tumors with low risk for relapse to tumors with high risk for progression even after radical prostatectomy. Currently, there are no reliable biomarkers to predict tumor relapse and poor clinical outcome. In this study, we correlated expression patterns of the androgen receptor (AR) coactivators lysine-specific histone demethylase 1 (LSD1) and four and a half LIM-domain protein 2 (FHL2), AR, Gleason score, Gleason grade, and p53 expression in clinically organ confined prostate cancers with relapse after radical prostatectomy. Our data reveal that high levels of LSD1, nuclear expression of the FHL2 coactivator, high Gleason score and grade, and very strong staining of nuclear p53 correlate significantly with relapse during follow-up. No correlation exists with relapse and the expression of AR and cytoplasmic expression of FHL2. To confirm these data, we did quantitative reverse transcription-PCR and Western blot analyses in a subset of tumor specimens. Consistently, both LSD1 mRNA and protein levels were significantly up-regulated in high-risk tumors. We previously identified LSD1 and FHL2 as nuclear cofactors interacting specifically with the AR in prostate cells and showed that both stimulate androgen-dependent gene transcription. Our present study suggests that LSD1 and nuclear FHL2 may serve as novel biomarkers predictive for prostate cancer with aggressive biology and point to a role of LSD1 and FHL2 in constitutive activation of AR-mediated growth signals.
Statistical correlations for analysis and prediction of turbine engine component life usage (2001)

Even though engine monitoring systems including life usage monitoring for individual life limited components have been introduced for many existing and nearly all new military engines, there is a number of reasons to apply statistical methods to the life usage of engine components. For new or modernized engines a prediction of the expected component life under the planned usage is required. Statistical prediction methods are also applied to estimate the consequences of intended changes of the engine use caused by new mission types or if existing engines are used to power new or modified aircraft. For new engine types only a small amount of information on future use is available, consisting of performance requirements and design missions. A suggestion is made for a generalized robust definition of the TAG (Total Accumulated Cycles) usage parameter. A comparison of life usage figures at critical rotor areas calculated with thermal transient algorithms with the corresponding TACs and with flight times illustrates the shortcomings of flight time based usage counting. The correlation of life usage with flight time is nevertheless useful for planning purposes, if one is aware of the strong dependence of scatter bands on the time scale. A comparison of Monte Carlo simulation results of life usage with data from a fleet-wide on-board monitoring system shows, that it is indeed possible to predict the overall behavior of an engine fleet using the distributions of life usage figures derived from suitable samples of flight recordings. In spite of improved computer tools for thermal and mechanical design and analysis, a considerable uncertainty remains in the prediction, which areas of a rotor structure will eventually become life-limiting after many years of field usage. It is shown, how correlations with monitoring results from other, non life limiting areas or with other parameters describing the severity of engine usage can be used to retain at least a part of the benefits of individual monitoring, when a new life limiting area is detected only after the engine has been in service for some years.
Bid Induces the Oligomerization and Insertion of Bax into the Outer Mitochondrial Membrane (2000)

In many types of apoptosis, the proapoptotic protein Bax undergoes a change in conformation at the level of the mitochondria. This event always precedes the release of mitochondrial cytochrome c, which, in the cytosol, activates caspases through binding to Apaf-1. The mechanisms by which Bax triggers cytochrome c release are unknown. Here we show that following binding to the BH3-domain-only proapoptotic protein Bid, Bax oligomerizes and then integrates in the outer mitochondrial membrane, where it triggers cytochrome c release. Bax mitochondrial membrane insertion triggered by Bid may represent a key step in pathways leading to apoptosis.
Fastpass (2014)

An ideal datacenter network should provide several properties, including low median and tail latency, high utilization (throughput), fair allocation of network resources between users or applications, deadline-aware scheduling, and congestion (loss) avoidance. Current datacenter networks inherit the principles that went into the design of the Internet, where packet transmission and path selection decisions are distributed among the endpoints and routers. Instead, we propose that each sender should delegate control---to a centralized arbiter---of when each packet should be transmitted and what path it should follow.
Childhood hypophosphatasia: to treat or not to treat (2018)

Asfotase alfa (Strensiq™), is a first-in-class bone-targeted recombinant tissue nonspecific alkaline phosphatase which has shown significant improvements in morbidity and mortality in patients with perinatal and infantile hypophosphatasia. Subsequent research has also shown improvements in morbidity for patients with childhood hypophosphatasia as measured by improvement in rickets, growth, strength, mobility, and quality of life. This enzyme replacement therapy has generally been well-tolerated, with most adverse reactions being mild-to-moderate in nature. The author shares their approach to decisions on commencement of ERT based from experience of managing approximately fifteen patients across the age spectrum. This approach focuses on assessing the severity of five key manifestations of childhood HPP: decreased mobility, pain, rickets, deficits of growth, and fractures.
Enhancement of Immunotoxin Efficacy by Acid-cleavable Cross-linking Agents Utilizing Diphtheria Toxin and Toxin Mutants (1989)

We have utilized a new class of acid-cleavable protein cross-linking reagents in the construction of antibody-diphtheria toxin conjugates (Srinivaschar, K., and Neville, D. M., Jr. (1989) Biochemistry 28, 2501-2509). The potency of anti-CD5 conjugates assayed by inhibition of protein synthesis on CD5 bearing cells (Jurkat) is correlated with cross-linker hydrolytic rates. The maximum increase in potency of the cleavable conjugates over non-cleavable conventional conjugates is 50-fold and is specific for the CD5 uptake route as judged by competition with excess anti-CD5. The potency of conjugates made from diphtheria toxin and the anti-high molecular weight melanoma-associated antigen (HMW-MAA) is enhanced 3-10-fold by a cleavable cross-linker. However the potency of transferrin or anti-CD3 diphtheria toxin conjugates is only minimally enhanced (2-3-fold). Mutant diphtheria toxins, CRM103 and CRM9, previously shown to express less than 1/100 of the wild type in binding affinity were substituted into these conjugates as probes for possible intracellular toxin receptor interactions. Both mutants were equally as toxic to Jurkat target cells exhibiting 1/700 the wild-type potency. CRM9 non-cleavable conjugates were equally as potent as wild-type conjugates for transferrin and anti-CD3-mediated uptake but not for anti-CD5-mediated uptake where toxicity was reduced 60-fold over the wild-type analog. The cleavable cross-linker enhanced the toxicity of anti-CD5-CRM103 and anti-CD5-CRM9 conjugates, but potency was only 1/10 that of the analogous wild-type cleavable conjugate. These data are consistent with a model in which potentiation of toxicity of the anti-CD5 and anti-high molecular weight melanoma-associated antigen conjugates by the cleavable cross-linker occurs from an enhanced intracellular toxin-toxin receptor interaction that ultimately results in increased toxin translocation to the cytosol compartment. In contrast, these data indicate that the anti-CD3 and transferrin uptake systems do not require this interaction in agreement with previous work (Johnson, V.G., Wilson, D., Greenfield, L., and Youle, R. J. (1988) J. Biol. Chem. 263, 1295-1300).
Towards mechanisms for detection and prevention of data exfiltration by insiders (2011)

Data represent an extremely important asset for any organization. Confidential data such as military secrets or intellectual property must never be disclosed outside the organization. Therefore, one of the most severe threats in the case of cyber-insider attacks is the loss of confidential data due to exfiltration. A malicious insider who has the proper credentials to access the organization databases may, over time, send data outside the organization network through a variety of channels, such as email, crafted HTTP requests that encapsulate data, etc. Existing security tools for detection of cyber-attacks focus on protecting the boundary between the organization and the outside world. Numerous network-level intrusion detection systems (IDS) exist, which monitor the traffic pattern and attempt to infer anomalous behavior. While such tools may be effective in protecting against external attacks, they are less suitable when the data exfiltration is performed by an insider who has the proper credentials and authorization to access resources within the organization. In this paper, we argue that DBMS-layer detection and prevention systems are the best alternative to defend against data exfiltration because: (1) DBMS access is performed through a standard, unique language (SQL) with well-understood semantics; (2) monitoring the potential disclosure of confidential data is more effective if done as close as possible to the data source; and (3) the DBMS layer already has in place a thorough mechanism for enforcing access control based on subject credentials. By analyzing the pattern of interaction between subjects and the DBMS, it is possible to detect anomalous activity that is indicative of early signs of exfiltration. In the paper, we outline a taxonomy of cyber-insider dimensions of activities that are indicative of data exfiltration, and we discuss a high-level architecture and mechanisms for early detection of exfiltration by insiders. We also outline a virtualization-based mechanism that prevents insiders from exfiltrating data, even in the case when they manage to gain control over the network. The protection mechanism relies on explicit authorization of data transfers that cross the organizational boundary.
非洲的社会科学与知识生产：克劳德·阿克的贡献 (2011)

克劳德·阿克是非洲政治哲学的先驱之一，对非洲民主与发展的政治经济学研究作出了突出的贡献。阿克推动了非洲后殖民主义理论的辩论，并对后殖民主义提出了质疑；他对西方社会科学进行了批判，大力提倡非洲知识生产的“内生性”需要，并倡导通过内生化知识生产的完美策略使南方国家的社会科学去殖民化。阿克的著作深受马克思主义知识传统的影响，被贴上“马克思主义的原创品牌”的标签，但又改写了这一传统，对理解当代非洲政治经济与社会历史有重要的意义。
The Arabidopsis deetiolated2 Mutant Is Blocked Early in Brassinosteroid Biosynthesis (1997)

Shozo Fujioka, Jianming Li, Yong-Hwa Choi, Hideharu Seto, Suguru Takatsuto, Takahiro Noguchi, Tsuyoshi Watanabe, Hiroki Kuriyama, Takao Yokota, Joanne Chory, Akira Sakurai, The Arabidopsis deetiolated2 Mutant Is Blocked Early in Brassinosteroid Biosynthesis, The Plant Cell, Vol. 9, No. 11 (Nov., 1997), pp. 1951-1962
TEACHERS' TOPICS The Chemically Elegant Proton Pump Inhibitors (2006)

Medicinal chemistry instruction at Creighton University is designed to provide an in-depth scientifically grounded and clinically relevant learning experience for pharmacy students. Each topic covered in the 2-semester required course sequence is selected based on the general utility of the compounds in question and/or the therapeutic importance of the drugs in treating life-threatening diseases. All lessons provided to campus- and Web-based students by the author are in the form of a descriptive and conversational narrative and course requirements are in place to assure that students read the lesson prior to the class period in which it is discussed. Learning tools and aids are provided to help students more readily discern the most critical aspects of each lesson, to practice required critical thinking and structure analysis skills, and to self-assess competency in meeting specific learning objectives. This manuscript illustrates this approach by sharing a lesson on the chemistry and clinically relevant structure-activity relationships of proton pump inhibitors.