gebhart/patrepeval huggingface dataset:
CD20+ B Cells: The Other Tumor-Infiltrating Lymphocytes (2010)

Tumor-infiltrating CD8(+) T cells are strongly associated with patient survival in a wide variety of human cancers. Less is known about tumor-infiltrating CD20(+) B cells, which often colocalize with T cells, sometimes forming organized lymphoid structures. In autoimmunity and organ transplantation, T cells and B cells collaborate to generate potent, unrelenting immune responses that can result in extensive tissue damage and organ rejection. In these settings, B cells enhance T cell responses by producing Abs, stimulatory cytokines, and chemokines, serving as local APCs, and organizing the formation of tertiary lymphoid structures that sustain long-term immunity. Thus, B cells are an important component of immunological circuits associated with persistent, rampant tissue destruction. Engagement of tumor-reactive B cells may be an important condition for generating potent, long-term T cell responses against cancer.
Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions (2016)

Recombinant human IgG antibodies (hIgGs) completely devoid of binding to Fcγ receptors (FcγRs) and complement protein C1q, and thus with abolished immune effector functions, are of use for various therapeutic applications in order to reduce FcγR activation and Fc-mediated toxicity. Fc engineering approaches described to date only partially achieve this goal or employ a large number of mutations, which may increase the risk of anti-drug antibody generation. We describe here two new, engineered hIgG Fc domains, hIgG1-P329G LALA and hIgG4-P329G SPLE, with completely abolished FcγR and C1q interactions, containing a limited number of mutations and with unaffected FcRn interactions and Fc stability. Both 'effector-silent' Fc variants are based on a novel Fc mutation, P329G that disrupts the formation of a proline sandwich motif with the FcγRs. As this motif is present in the interface of all IgG Fc/FcγR complexes, its disruption can be applied to all human and most of the other mammalian IgG subclasses in order to create effector silent IgG molecules.
Gadolinium texaphyrin–methotrexate conjugates. Towards improved cancer chemotherapeutic agents (2005)

Conjugates between methotrexate (MTX, Matrex, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-l-glutamic acid), an antifolate cancer chemotherapeutic to which resistance is often observed, and motexafin gadolinium (MGd), an experimental agent demonstrating selective tumor localization, are described. These systems were prepared in order to test whether linking these two species would produce agents with enhanced activity relative to MTX alone. Both ester- and amide-linked conjugates were synthesized starting from MGd and MTX. The ester conjugate showed greater in vitro anti-proliferative activity against the A549 lung carcinoma cell line at short incubation times than did MTX alone. Neither the amide conjugate, nor MGd, showed any observable activity under these in vitro conditions. These results are rationalized in terms of enhanced cellular uptake of both the ester and amide conjugates that is coupled with an effective rate of release (e.g., inherent or enzyme-mediated hydrolysis) in the case of the ester-linked conjugate, but not the corresponding amide system.
Reliability defect detection and screening during processing-theory and implementation (1992)

The authors derive a model that relates electrical in-process measurements to reliability defect occurrence. The model begins with an understanding of reliability defect physics and statistics and then uses elements of semiconductor manufacture yield modeling. An experiment, using intensive microscopic inspections, that was used to verify this model is described. The type and nature of yield and reliability defect monitors and the use of in-process electrical measurements of these monitors for reliability defect detection are described. The implementation of 'maverick' screens for a highly defective product is outlined, and the improvement in reliability that these screens provide is estimated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Akt2 Negatively Regulates Assembly of the POSH-MLK-JNK Signaling Complex (2003)

We demonstrate that POSH, a scaffold for the JNK signaling pathway, binds to Akt2. A POSH mutant that is unable to bind Akt2 (POSH W489A) exhibits enhanced-binding to MLK3, and this increase in binding is accompanied by increased activation of the JNK signaling pathway. In addition, we show that the association of MLK3 with POSH is increased upon inhibition of the endogenous phosphatidylinositol 3-kinase/Akt signaling pathway. Thus, the assembly of an active JNK signaling complex by POSH is negatively regulated by Akt2. Further, the level of Akt-phosphorylated MLK3 is reduced in cells expressing the Akt2 binding domain of POSH, which acts as a dominant interfering protein. Taken together, our results support a model in which Akt2 binds to a POSH-MLK-MKK-JNK complex and phosphorylates MLK3; phosphorylation of MLK3 by Akt2 results in the disassembly of the JNK complex bound to POSH and down-regulation of the JNK signaling pathway.
Automatic generation of domain models for call centers from noisy transcriptions (2006)

Call centers handle customer queries from various domains such as computer sales and support, mobile phones, car rental, etc. Each such domain generally has a domain model which is essential to handle customer complaints. These models contain common problem categories, typical customer issues and their solutions, greeting styles. Currently these models are manually created over time. Towards this, we propose an unsupervised technique to generate domain models automatically from call transcriptions. We use a state of the art Automatic Speech Recognition system to transcribe the calls between agents and customers, which still results in high word error rates (40%) and show that even from these noisy transcriptions of calls we can automatically build a domain model. The domain model is comprised of primarily a topic taxonomy where every node is characterized by topic(s), typical Questions-Answers (Q&As), typical actions and call statistics. We show how such a domain model can be used for topic identification of unseen calls. We also propose applications for aiding agents while handling calls and for agent monitoring based on the domain model.
Predictability of creatinine clearance estimates in critically ill patients (1993)

The utilization of the Cockcroft-Gault equation as used clinically (the lower of ideal or total body weight and the higher of actual serum creatinine or corrected serum creatinine concentration to 1 mg/dL [85 mumol/L]) results in more accurate predictions of glomerular filtration rate in the medical, critically ill patient than urine creatinine clearance measures. If creatinine clearance measures are used, the 30-min collection provided results not different from those results obtained with 24-hr urinary collections.
Dynamic range improvement in Fourier transform infrared spectrometry (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDynamic range improvement in Fourier transform infrared spectrometryTomas. HirschfeldCite this: Anal. Chem. 1978, 50, 8, 1225–1226Publication Date (Print):July 1, 1978Publication History Published online1 May 2002Published inissue 1 July 1978https://pubs.acs.org/doi/10.1021/ac50030a056https://doi.org/10.1021/ac50030a056research-articleACS PublicationsRequest reuse permissionsArticle Views67Altmetric-Citations3LEARN 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
Genetic analysis of bovine papillomavirus type 1 trans-acting replication factors (1985)

The establishment of bovine papillomavirus type 1 in somatic mammalian cells is mediated by extrachromosomal replication and stable maintenance of the viral genome as a multicopy nuclear plasmid. Previous studies indicated the requirement of viral gene expression for bovine papillomavirus type 1 replication and plasmid maintenance (M. Lusky and M. R. Botchan, Cell 36:391-401, 1984; Turek et al., Proc. Natl. Acad. Sci. U.S.A. 79:7914-7918, 1982). To define the viral genes which are necessary for this process, we constructed a series of specific mutations within the viral genome and assayed the resulting mutants for their ability to replicate extrachromosomally in mouse C127 cells. We report here that the bovine papillomavirus type 1 trans-acting replication factors were encoded by at least two distinct viral genes since the mutants fell into two complementation groups, rep and cop. Mutants (rep-) affecting the E1 open reading frame (ORF) failed to replicate bovine papillomavirus type 1 DNA extrachromosomally and would integrate into chromosomal DNA. We suggest that this gene product is one of the factors required to specifically preclude the integration event. Mutants (cop-) affecting the E7 ORF were maintained in the extrachromosomal state; however, the copy number of the mutant genomes was reduced 100-fold compared with that of wild-type DNA. Analysis of single-cell subclones showed that each cell contained the mutant genomes at a copy number of one to two, indicating that the cop- phenotype did not reflect a simple segregation defect. We propose that the gene defined by mutations in the E7 ORF played a crucial role in stably maintaining the copy number of the viral plasmid at high levels. Genomes with mutations in the cop and rep complementation groups, when cotransfected, rescued the wild-type phenotype, extrachromosomal replication with a high, stable copy number for both types of plasmids. Therefore, the gene products acted in trans, and the mutations were recessive to the wild-type functions. One specific rep- mutant showed a 30-fold-increased transformation efficiency when compared with that of the wild-type genome. In addition, morphological transformation mediated by the cop- mutants appeared to be unstable. These results imply that either or both of the replication functions played some role in regulating the expression of the viral transforming functions.
Investigations by mass isotopomer analysis of the formation of D‐2‐hydroxyglutarate by cultured lymphoblasts from two patients with D‐2‐hydroxyglutaric aciduria (2003)

D-2-Hydroxyglutaric aciduria is an inborn error of metabolism first described in 1980. To date, more than 40 patients have been diagnosed with this disease. To identify the metabolic precursor of D-2-hydroxyglutarate (D-2-HG), cultured human lymphoblasts from two patients with D-2-HG aciduria were grown in culture medium supplemented with [U-(13)C(6)]glucose or [(2)H(5)]glutamate. Mass isotopomer distribution measurements of D-2-HG, 2-ketoglutarate (2-KG) and citrate were performed by gas chromatography-mass spectrometry. The mass isotopomer distributions in D-2-HG, 2-KG and citrate, following [U-(13)C(6)]glucose and [(2)H(5)]glutamate incubations, revealed that 2-KG interconverts rapidly to D-2-HG and that D-2-HG is formed within the mitochondria.
Allosteric Hammerhead Ribozyme TRAPs (2002)

A new mode of allosteric regulation of nucleic acid enzymes is described and shown to operate effectively with hammerhead ribozymes. In the "TRAP" design (for targeted ribozyme-attenuated probe), a 3' terminal "attenuator" anneals to conserved bases in the catalytic core to form the "off" state of the ribozyme. Binding of RNA or DNA to an antisense sequence linking the ribozyme and attenuator frees the core to fold into an active conformation, even though the antisense sequence itself does not interfere with the ribozyme. TRAP hammerheads based on the previously characterized HH8 ribozyme were shown to be activated more than 250-fold upon addition of the sense strand. RNA oligonucleotides were more effective activators than DNA oligos, consistent with the known relative helix stabilities (RNA-RNA > RNA-DNA). Oligonucleotides that directly paired with the attenuator gave up to 1760-fold activation. The magnitude of the activation was greater when the oligo was added prior to folding than if it was added during the cleavage reaction. The TRAP design requires no prior knowledge of (deoxy)ribozyme structure beyond identification of the essential core. Thus, this approach should be readily generalizable to other systems for biomedicine, sensor technology, and additional applications.
White cell depletion of single‐donor platelet preparations by a new adsorption filter (1991)

A newly developed adsorption filter has been evaluated for the removal of white cells (WBCs) from platelet concentrates. It consists of surface-modified polyester fibers and can be used at the patient's bedside. WBC mean removal rate was 98.8 +/- 0.9 percent, and platelet recovery was 99.0 +/- 0.7 percent. The aggregation curves (ADP, collagen) and hypotonic shock response of platelets were not influenced by the filtration, and the plasma electrolyte and lactate dehydrogenase concentrations were unaffected. Transmission and scanning electron micrographs showed no difference in platelet ultrastructure before and after filtration. Determination of posttransfusion platelet recovery did not reveal any significant difference from that of nonfiltered platelets. The tested filter seems to be a suitable device for WBC depletion of single-donor platelet concentrates at the bedside.
KAP: a dual specificity phosphatase that interactswith cyclin-dependent kinases. (1994)

The cyclin-dependent kinases are key cell cycle regulators whose activation is required for passage from one cell cycle phase to the next. In mammalian cells, CDK2 has been implicated in control of the G1 and S phases. We have used a two-hybrid protein interaction screen to identify cDNAs encoding proteins that can interact with CDK2. Among those identified was a protein (KAP), which contained the HCXX-XXGR motif characteristic of protein tyrosine phosphatases. KAP showed phosphatase activity toward substrates containing either phosphotyrosine or phosphoserine residues. Since KAP is not significantly similar to known phosphatases beyond the catalytic core motif, it represents an additional class of dual specificity phosphatase. KAP interacted with cdc2 and CDK2 in yeast. In mammalian cells, KAP also associated with cdc2 and CDK2 but showed a preference for cdc2. The ability of KAP to bind multiple cyclin-dependent kinases suggests that it may play a role in cell cycle regulation.
SURVEY OF INDEPENDENT COMPONENT ANALYSIS (1999)

A common problem encountered in such disciplines as statistics, data analysis, signal processing, and neural network research, is finding a suitable representation of multivariate data. For computational and conceptual simplicity, such a representation is often sought as a linear transformation of the original data. Well-known linear transformation methods include, for example, principal component analysis, factor analysis, and projection pursuit. A recently developed linear transformation method is independent component analysis (ICA), in which the desired representation is the one that minimizes the statistical dependence of the components of the representation. Such a representation seems to capture the essential structure of the data in many applications. In this paper, we survey the existing theory and methods for ICA.
Using multiple devices simultaneously for display and control (2000)

The Pebbles research project (http://www.cs.cmu.edu/spl sim/pebbles) has been studying the use of hand-held personal digital assistants (PDAs) along with other kinds of hand-held computers, at the same time as other computing devices. A key focus of our research is that the hand-held computers are used both as output devices and as input devices to control the activities on the other computers. Our previous articles have described parts of the project in detail. The article presents four scenarios that illustrate some of the capabilities we are already investigating.
In Vitro Fermentation Profiles, Gas Production Rates, and Microbiota Modulation as Affected by Certain Fructans, Galactooligosaccharides, and Polydextrose (2009)

It is of interest to benefit from the positive intestinal health outcomes of prebiotic consumption but with minimal gas production. This study examined gas production potential, fermentation profile, and microbial modulation properties of several types of oligosaccharides. Substrates studied included short-chain, medium-chain, and long-chain fructooligosaccharides, oligofructose-enriched inulin, galactooligosaccharide, and polydextrose. Each substrate was fermented in vitro using human fecal inoculum, and fermentation characteristics were quantified at 0, 4, 8, and 12 h. Gas and short-chain fatty acid (SCFA) production data showed that short-chain oligosaccharides were more rapidly fermented and produced more SCFA and gas than substrates with greater degrees of polymerization. Lactobacilli increased similarly among substrates. Short-chain oligosaccharides fermentation resulted in the greatest increase in bifidobacteria concentrations. Mixing short- and long-chain oligosaccharides attenuated short-chain oligosaccharide fermentation rate and extent. This study provides new information on the fermentation characteristics of some oligosaccharides used in human nutrition.
Blind source separation using Renyi's mutual information (2001)

A blind source separation algorithm is proposed that is based on minimizing Renyi's mutual information by means of nonparametric probability density function (PDF) estimation. The two-stage process consists of spatial whitening and a series of Givens rotations and produces a cost function consisting only of marginal entropies. This formulation avoids the problems of PDF inaccuracy due to truncation of series expansion and the estimation of joint PDFs in high-dimensional spaces given the typical paucity of data. Simulations illustrate the superior efficiency, in terms of data length, of the proposed method compared to fast independent component analysis (FastICA), Comon's (1994) minimum mutual information, and Bell and Sejnowski's (1995) Infomax.
Missense Variations in the Fibulin 5 Gene and Age-Related Macular Degeneration (2004)

Missense mutations in the fibulin 5 gene were found in 1.7 percent of patients with AMD. Many variations in other fibulin genes were also found in these patients, and the evolutionary conservation of the affected residues suggests that several of these variations may also be involved in AMD.
Change of the sequence specificity of daunorubicin-stimulated topoisomerase II DNA cleavage by epimerization of the amino group of the sugar moiety. (1995)

Antitumor drugs stimulate topoisomerase II-mediated DNA cleavage in a DNA sequence-specific manner. The drug sequence specificity is often very similar among antitumor agents of the same chemical class. In this work, we demonstrate, however, that 3'-epidaunorubicin has a markedly different sequence specificity as compared with the parent drugs daunorubicin and doxorubicin. The analogue stimulates distinct cleavage intensity patterns in agarose and sequencing gels with two different DNA substrates, although its cleaving activity was lower than that of daunorubicin. A statistical analysis of 44 sites specifically stimulated by the analogue showed that a major difference between the analogue and parent drugs was at position -2, where a guanine is highly preferred by the analogue, whereas parent drugs prefer a thymine and exclude instead a guanine. Interestingly, an analogue with no substituents at the 3'-C of the sugar was able to stimulate DNA cleavage at sites stimulated by parent drugs as well as at those stimulated by 3'-epidaunorubicin. In contrast, the presence of a 2'-OH or a 3'-epi-OH in the sugar moiety and the removal of the OH at 9-C of the A ring did not alter the drug site selectivity, in agreement with several other modifications studied previously. DNA binding affinities of studied agents were not related to drug sequence specificity. The data demonstrate a critical role of the 3' position for optimal anthracycline interactions in the ternary complex. The findings, for the first time, establish a clear relationship between a specific drug substituent and base sequence selectivity and indicate putative DNA- and enzyme-interacting domains of the anthracycline molecule.
Grafting of a calcium-binding loop of thermolysin to Bacillus subtilis neutral protease (1991)

The surface loop which in the Bacillus subtilis neutral protease (NP) extends from amino acid residue 188 to residue 194 was replaced, by site-directed mutagenesis, with the 10-residue segment which in the homologous polypeptide chain of thermolysin (TLN) binds calcium-4 [Matthews, B. W., Weaver, L. H., & Kester, W. R. (1974) J. Biol. Chem. 249, 8030-8044]. The mutant NP was isolated to homogeneity, and its structural, functional, calcium-binding, and stability properties were investigated. Proteolytic fragmentation with Staphylococcus aureus V8 protease of mutant NP was used to isolate and analyze the protein fragment encompassing the site of mutation, unambiguously establishing the effective insertion of the new 10-residue segment. Atomic absorption measurements allowed us to demonstrate that mutant NP binds three calcium ions instead of the two ions bound to wild-type NP, showing that indeed the chain segment grafted from TLN to NP maintains its calcium-binding properties. The mutant NP showed kinetic parameters essentially similar to those of the wild-type NP with Z-Phe-Leu-Ala-OH as substrate. The enzyme inactivation of mutant vs wild-type NP was studied as a function of free [Ca2+]. It was found that mutant NP was much less stable than the wild-type NP when enzyme solutions were dialyzed at neutral pH in the presence of [Ca2+] below 10(-3) M. On the other hand, the kinetic thermal stability to irreversible inactivation of mutant NP, when measured in the presence of 0.1 M CaCl2, was found to be increased about 2-fold over that of the wild-type NP. Thus, modulation of enzyme stability by free [Ca2+] in mutant NP correlates with similar findings previously reported for thermolysin. Overall, the results obtained indicate that protein engineering experiments can be used to prepare hybrid proteins on the basis of sequence and function analysis of homologous protein molecules and show the feasibility of engineering metal ion binding sites into proteins.
DNA Damage, Aging, and Cancer (2009)

This review gives an account of how the cell repairs DNA damage and presents evidence that DNA damage contributes to aging and cancer, with the outcome dependent on the type and number of lesions in DNA. Examples of accelerated aging syndromes associated with defects in DNA repair mechanisms are contrasted with cancers.