gebhart/patrepeval huggingface dataset:
Image Analysis Detects Lineage-Specific Morphologic Markers in Leukemic Blast Cells (1996)

This report outlines the morphologic classification of acute myeloid (AML: French-American-British FAB classification: M1) and lymphoid (ALL) leukemia by automatic image analysis and the correlation to immunologic and cytochemical classification. The investigation was carried out on Romanowsky-Giemsa stained bone marrow (n = 15) and blood smears (n = 10) from 25 patients with primary acute leukemia. The cases had been classified as of myeloid or lymphoid origin by three hematologic centers using immunochemistry or cytochemistry, but the specimens were submitted to the authors' laboratory without the diagnosis. The nuclear and cytoplasmic pattern of the blast cells were analyzed by a high resolution image analysis system and the measured and calculated cell features were sorted by means of a classifier program (CART). The image analysis classification was then compared with the immunophenotypical and cytochemical classification. Blood blast cells showed nuclear features that were significantly correlated to a myeloid or lymphoid immunophenotype. In contrast, bone marrow blast cells displayed overlapping and therefore nondiscriminating nuclear features. However, by generating a learning data set using the immunophenotypes the classifier program found specific cytoplasmic features that eventually permitted a differentiation into myeloid or lymphoid subtypes. In summary, the authors suggest that high resolution image analysis of leukemic blast cells detect nuclear and cytoplasmic features that are associated with the immunophenotype and therefore with the lineage determination of the cell. With this new objective and reproducible approach of morphologic cell analysis, it might not only be possible to classify blast cells with minimal cellular differentiation, but furthermore to discover prognostic features because the remarkable difference in classification quality between blood and bone marrow blast cells reported in this study, might be of biologic relevance and requires further investigation.
A strategy for the generation of conditional mutations by protein destabilization. (1992)

Conditional mutations such as temperature-sensitive (ts) mutations are important for the analysis of protein function but are often difficult, or impossible, to obtain. Here we present a simple method for generating conditional mutations based on the use of a protein-destabilizing genetic element in combination with systems allowing the induction and repression of gene expression. This genetic cassette can be fused to other protein-coding sequences, and once transcription is turned off and synthesis of the gene product ceases, the preexisting protein is rapidly degraded. We have applied this method to the analysis of the yeast ARD1 gene product, a subunit of an N-terminal acetyltransferase, and show that a complete loss of ARD1 product can be achieved in less than one generation. Despite the rapid loss of ARD1 protein, there is a prolonged delay in the expression of the ard1 mutant phenotype, suggesting that the acetylated substrates of ARD1 are metabolically stable and/or exert a long-lasting effect on processes such as the repression of the silent mating type cassettes.
Solvent variation inverts substrate specificity of an enzyme (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolvent variation inverts substrate specificity of an enzymeCharles R. Wescott and Alexander M. KlibanovCite this: J. Am. Chem. Soc. 1993, 115, 5, 1629–1631Publication Date (Print):March 1, 1993Publication History Published online1 May 2002Published inissue 1 March 1993https://pubs.acs.org/doi/10.1021/ja00058a002https://doi.org/10.1021/ja00058a002research-articleACS PublicationsRequest reuse permissionsArticle Views515Altmetric-Citations134LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
[The rule of antibody structure. The primary structure of a monoclonal IgG1 immunoglobulin (myeloma protein Nie). III. The chymotryptic peptides of the H-chain, alignment of the tryptic peptides and discussion of the complete structure]. (1976)

In this final paper the complete primary structure of the H-chain of immunoglobulin Nie (IgG1, Gm1+, 17+) is established by overlapping tryptic fragments with chymotryptic peptides. The preceding papers dealt with the purification of the protein, the characterization of the light and heavy chains, the purification and characterization of the cyanogen bromide cleavage products, the location of the disulfide bonds, the isolation of the tryptic peptides and their sequence determination. The gamma1-chain Nie comprises 448 amino acid residues. When the protein is compared with other H-chains, the switch from the variable to the constant part occurs at position 119/120. Based on the amino acid sequence of the variable part, protein Nie belongs to subgroup III of the H-chains. It was the first protein of this subgroup to be sequenced. In the meantime several other proteins are known which have been assigned to the same subgroup on the basis of linked amino acid exchanges in comparison to members of other subgroups. This confirms the evolutionary origin of antibody variability and hence the genetically fixed antibody specific. Furthermore protein Nie is the first completely determined chain with the genetic factors Gm1+, 17+. These factors are inherited codominantly and are localized on the constant part of the gamma1-chain. By comparison with protein Eu, which is Gml-, 4+ and therefore an allele of Nie, these serologically defined factors are correlated with Eu. Besides the amino acid exchanges caused by the Gm-factors we elucidated a series of differences to the constant part of the protein Eu. These differences include 6 amide postions and the sequence from residues 387 to 391. Using the structure of IgG1 Nie as an example some rules for the evolution of immunoglobulin sequences have been described. In particular the "elongation-rule" and the "Disulfide-rule" are discussed. While chain-elongation of the H-chains can simply be explained by repeated gene duplications of a basic unit containing ca 110 amino acids, the location of disulfide bonds is determined partly by gene duplication, which implies multiplication of evolutionary "old" cystein residues and partly by the relatively recent acquisition of "new" cystein in appropriate sites. Most evident is the origin of the "hindge-region" by partial gene duplication on the C-terminal residues of the first homology region.
Phosphorothioate Oligodeoxynucleotide Analogues (1989)

Phosphorothioates contain a sulphur-for-oxygen substitution at phosphorus (Figure 5.1). In relation to the need for the development of chimeric oligo analogues for the antisense approach, the substitution of one sulphur atom for one oxygen atom is perhaps the most conservative chemical substitution that can be made at the phosphate moiety.
Tumor-Killer Made; How Does It Work? (1996)

Two groups have synthesized a bacterial compound known as Epothilone A, which kills cultured tumor cells in a manner similar to taxol, thwarting their ability to divide. The achievement will let chemists alter the compound's structure and possibly improve its properties.
Long-range cooperative binding effects in a T cell receptor variable domain (2006)

Although cellular processes depend on protein-protein interactions, our understanding of molecular recognition between proteins remains far from comprehensive. Protein-protein interfaces are structural and energetic mosaics in which a subset of interfacial residues, called hot spots, contributes disproportionately to the affinity of the complex. These hot-spot residues can be further clustered into hot regions. It has been proposed that binding energetics between residues within a hot region are cooperative, whereas those between hot regions are strictly additive. If this idea held true for all protein-protein interactions, then energetically significant long-range conformational effects would be unlikely to occur. In the present study, we show cooperative binding energetics between distinct hot regions that are separated by >20 A. Using combinatorial mutagenesis and surface plasmon resonance binding analysis to dissect additivity and cooperativity in a complex formed between a variable domain of a T cell receptor and a bacterial superantigen, we find that combinations of mutations from each of two hot regions exhibited significant cooperative energetics. Their connecting sequence is composed primarily of a single beta-strand of the T cell receptor variable Ig domain, which has been observed to undergo a strand-switching event and does not form an integral part of the stabilizing core of this Ig domain. We propose that these cooperative effects are propagated through a dynamic structural network. Cooperativity between hot regions has significant implications for the prediction and inhibition of protein-protein interactions.
Yersinia YopE is targeted for type III secretion by N‐terminal, not mRNA, signals (2001)

Pathogenic Yersinia species inject virulence proteins, known as Yops, into the cytosol of eukaryotic cells. The injection of Yops is mediated via a type III secretion system. Previous studies have suggested that YopE is targeted for secretion by two signals. One is mediated by its cognate chaperone YerA, whereas the other consists of either the 5' end of yopE mRNA or the N-terminus of YopE. In order to characterize the YopE N-terminal/5' mRNA secretion signal, the first 11 codons of yopE were systematically mutagenized. Frameshift mutations, which completely alter the amino acid sequence of residues 2-11 but leave the mRNA sequence essentially intact, drastically reduce the secretion of YopE in a yerA mutant. In contrast, a mutation that alters the yopE mRNA sequence, while leaving the amino acid sequence of YopE unchanged, does not impair the secretion of YopE. Therefore, the N-terminus of YopE, and not the 5' end of yopE mRNA, serves as a targeting signal for type III secretion. In addition, the chaperone YerA can target YopE for type III secretion in the absence of a functional N-terminal signal. Mutational analysis of the YopE N-terminus revealed that a synthetic amphipathic sequence of eight residues is sufficient to serve as a targeting signal. YopE is also secreted rapidly upon a shift to secretion-permissive conditions. This 'rapid secretion' of YopE does not require de novo protein synthesis and is dependent upon YerA. Furthermore, this burst of YopE secretion can induce a cytotoxic response in infected HeLa cells.
An algorithm for anomaly-based botnet detection (2006)

We present an anomaly-based algorithm for detecting IRC-based botnet meshes. The algorithm combines an IRC mesh detection component with a TCP scan detection heuristic called the TCP work weight. The IRC component produces two tuples, one for determining the IRC mesh based on IP channel names, and a sub-tuple which collects statistics (including the TCP work weight) on individual IRC hosts in channels. We sort the channels by the number of scanners producing a sorted list of potential botnets. This algorithm has been deployed in PSU’s DMZ for over a year and has proven effective in reducing the number of botnet clients. 1
Children of divorce. (1989)

This report analyzes trends for the period 1950-1984 in the number and proportion of children whose parents divorced. Data is drawn from the National Vital Statistics System. Some highlights from the report follow. 1) More than 1 million couples divorce in the US each year. In 1984 54% of divorcing couples had at least 1 child under age 18. 2)The number of children whose parents divorced more than tripled between 1950 and 1984. 3) Couples in which 1 or both spouses had been married before had fewer children at divorce than couples who had not been married before; the more times men and women had been married the fewer children they had. 4) Divorcing couples with children were an average of 6 years younger at marriage and 3 years younger at divorce than couples who had not been married before. Among couples in which neither spouse had been married before couples with children were 2 years younger at marriage and 1 year younger at divorce than childless couples. 5) Black couples were equally likely to have children and had nearly equal family sizes at divorce. 6) In general men and women with a college education were more likely to be childless at divorce than men and women with less education. 7) The wife was more likely to be the one to file for the divorce when the couple had children than when they did not. Among couples with children the wife was the petitioner in 66% of the divorces; among childless couples the wife was the petitioner in 57% of the divorces. 8) Divorcing couples in the South were least likely to have children and divorcing couples in the Midwest and West were likely to have them; these differences were small however and the majority of couples in each region had at least 1 child.
Monitoring the electrical response of photoinduced organic oxidation on TiO 2 surfaces (2001)

12 Gaseous photo-induced oxidations of a variety of organic compounds by titanium dioxide (TiO<SUB>2</SUB>) have been studied extensively in the literature. The response of the organic to photochemical reactions with TiO<SUB>2</SUB> and the extent of organic oxidation are typically measured by monitoring the initial concentration of organic and the oxidation by- products using gas chromatography. In this study, TiO<SUB>2</SUB> sensors are produced by coating and drying films of Degussa P25 TiO<SUB>2</SUB> onto Al<SUB>2</SUB>O<SUB>3</SUB> substrates. Tests are conducted at ambient temperatures in a controlled atmospheric cell. Electrical responses from the TiO<SUB>2</SUB> sensors are monitored as the sensors are exposed to a variety of organic compounds in the presence of ultraviolet light. Unique voltammetric `signatures' are obtained from the sensors as they react with specific gaseous organics. These signatures can be used to distinguish and identify gaseous constituents.
A Novel Mutation in the D3 Domain of von Willebrand Factor Markedly Decreases Its Ability to Bind Factor VIII and Affects Its Multimerization (1998)

In type 2N von Willebrand disease (vWD), von Willebrand factor (vWF) is characterized by normal multimeric pattern, normal platelet-dependent function, but a markedly decreased affinity for factor VIII (FVIII). In this report, we describe the case of a vWD patient who has an abnormal vWF multimers distribution associated with a markedly decreased vWF ability to bind FVIII. Sequencing analysis of patient's vWF gene showed, at heterozygous state, a G-->A transition resulting in the substitution of Asn for Asp at position 116 of the mature vWF subunit and a C-->T transition, changing the codon for Arg 896 into a stop codon. His sister who has a subnormal vWF level, but a normal FVIII/vWF interaction, was found to be heterozygous for the Arg896ter mutation only. Recombinant vWF (rvWF) containing the candidate (Asn116) missense mutation was expressed in COS-7 cells. The expression level of Asn116rvWF was significantly decreased compared with wild-type rvWF. The multimeric pattern of Asn116rvWF was greatly impaired as shown by the decrease in high molecular weight forms. The FVIII binding ability of Asn116rvWF was dramatically decreased. These data show that the Asp116Asn substitution is the cause of both the defective FVIII/vWF interaction and the impaired multimeric pattern observed in the patient's vWF. The monoclonal antibody 31H3 against D' domain of vWF (epitope aa 66-76) that partially inhibits the FVIII binding and recognizes only nonreduced vWF, showed a decreased ability to bind Asn116rvWF when used as capture-antibody in enzyme-linked immunosorbent assay (ELISA). This result suggests that a potential conformation change in the D' domain is induced by the Asp116Asn substitution, which is localized in the D3 domain.
The effect of different graft tensioning in anterior cruciate ligament reconstruction: A prospective randomized study (1998)

A prospective study was performed to establish the influence on stability of tensioning the graft after anterior cruciate ligament reconstruction with a bone-patellar tendon-bone graft. There were 38 consecutive patients randomly divided into two groups; in the first group (19 patients) the graft was tensioned at 20 N, and in the second group the tension was 40 N. Evaluation included Lysholm scores, instrumented Lachman tests, IKDC level, and lateral radiographs to measure the tibia position versus the femur. One year after surgery we did not find any significant difference between the two groups. We conclude that the importance of graft tensioning has yet to be established in the clinical situation. Based on our results, graft tension of 20 N seems to be sufficient, without the risk of overconstraining the knee joint.
Template-Free Directional Growth of Single-Walled Carbon Nanotubes on a- and r-Plane Sapphire (2005)

We report high-throughput growth of highly aligned single-walled carbon nanotube arrays on a-plane and r-plane sapphire substrates. This is achieved using chemical vapor deposition with ferritin as the catalyst. The nanotubes are aligned normal to the [0001] direction for growth on the a-plane sapphire. They are typically tens of micrometers long, with a narrow diameter distribution of 1.34 +/- 0.30 nm. In contrast, no orientation was achieved for growth on the c-plane and m-plane sapphire, or when Fe films, instead of ferritin, were used as the catalyst. Such orientation control is likely related to the interaction between carbon nanotubes and the sapphire substrate, which is supported by the observation that when a second layer of nanotubes was grown, they followed the gas flow direction. These aligned nanotube arrays may enable the construction of integrable and scalable nanotube devices and systems.
Clinical pharmacokinetics/pharmacodynamics (PK/PD) of ivosidenib in patients with IDH1-mutant advanced hematologic malignancies from a phase 1 study. (2018)

2581 Background: Mutant isocitrate dehydrogenase 1 (mIDH1) produces the oncometabolite D-2-hydroxyglutarate (2-HG). Ivosidenib (IVO) is a selective mIDH1 inhibitor under evaluation in patients with mIDH1 hematologic malignancies. This translational analysis explored the PK profile of IVO, the relationship between IVO exposure and 2-HG suppression, and the impact of intrinsic/extrinsic patient factors on IVO exposure from the phase 1 monotherapy study (NCT02074839). Methods: IVO was administered orally once (QD) or twice (BID) daily in continuous 28-day cycles. As of May 12, 2017, 258 patients had received IVO at doses ranging from 100 mg BID to 1200 mg QD in dose escalation (n = 78) and at 500 mg QD (n = 180) in dose expansion. IVO levels were assessed in plasma and 2-HG levels in plasma/bone marrow using LC-MS/MS methods. Results: After single and multiple doses, IVO was readily absorbed (median Tmax 3 h). After peaking, IVO concentrations declined in a bi-exponential manner, with a mean terminal half-life of 72–138 h after a single dose. Dose-exposure nonlinearity of IVO from 300 to 1200 mg QD suggests doubling of the dose would result in a ~30% increase in AUC. Steady state (SS) was reached within 14 days. Moderate accumulation was observed after 500 mg QD, with mean AUC and Cmax accumulation ratios of 1.9- and 1.46-fold. IVO clearance was not altered by intrinsic patient factors. Concomitant administration of weak CYP3A4 inhibitors/inducers did not affect IVO clearance, though moderate/strong CYP3A4 inhibitors decreased IVO clearance and increased IVO SS exposure (AUC0-24hr by ~56%; Cmax by ~47%). Plasma 2-HG reduction reached a plateau within 14 days of dosing after multiple doses of 500 mg QD, and was reduced by ≥90% over the range of IVO SS AUC in patients with newly diagnosed and relapsed/refractory AML, regardless of IDH1-R132 mutation type. Conclusions: IVO demonstrated a long half-life suitable for QD dosing, moderate accumulation, and robust 2-HG inhibition in patients with mIDH1 myeloid malignancies. Intrinsic/extrinsic patient factors, including concomitant moderate/strong CYP3A4 inhibitors, did not significantly alter IVO exposure. Clinical trial information: NCT02074839.
Original Article: Low Regulatory Volume Decrease Rate in Platelets from Ischemic Patients: A Possible Role for Hepoxilin A3in Thrombogenicity (1995)

Hepoxilin-A(3) (Hx-A(3)) is produced by platelets in response to shear-stress. It has an antithrombotic effect on platelets. A low Hx-A(3) level may contribute to the high thrombogenic state that exists in patients with acute coronary syndromes. Since we have previously demonstrated that the regulatory volume decrease (RVD) of human platelets exposed to hypotonic solutions is controlled by Hx-A(3) it is possible that the RVD rate reflects Hx-A(3) activity. In this study, the RVD rate of platelets taken from a healthy control group (n=21) was compared to that of patients with chronic ischemic heart disease (n=23), acute ischemic heart disease (n = 24) and acute myocardial infarction (MI, n = 29). The RVD rate of the control group was significantly higher than the other three groups (P < 0.001). The addition of 100 nM of Hx-A, to the platelets of eight patients with MI increased their RVD rate to that of the controls. Patients with diabetes mellitus or hypertension have the lowest RVD rates. Medications such as aspirin, heparin, and streptokinase did not affect the Hx-A(3) activity of platelets obtained from patients with ischemic heart disease. The results of the present study indicate that patients with acute ischemia may have a low level of platelet Hx-A(3) activity. This possible low level of Hx-A, activity may be associated with a failure to develop an antithrombotic reaction to the shear-stress forces generated during acute ischemia.
A cytoplasmic protein, NfrC, is required for bacteriophage N4 adsorption (1993)

At least four genes are required for irreversible adsorption of bacteriophage N4. nfrA and nfrB have been characterized previously and encode an outer membrane protein and inner membrane protein, respectively. The nfrC gene product is characterized in detail in this study. We have mapped the nfrD locus to min 52 on the Escherichia coli linkage map. Maxicell analysis of nfrC and a null allele (nfrC2) cloned into a high-copy-number plasmid shows its gene product to be 42 kDa in size. We determined the nfrC nucleotide sequence which predicts a gene product of 42 kDa. Western blots (immunoblots) of Escherichia coli proteins after cellular fractionation show NfrC to be a cytoplasmic protein which is required for irreversible bacteriophage N4 adsorption, an event occurring at the cell surface.