gebhart/patrepeval huggingface dataset:
The CD70/CD27 Pathway Is Critical for Stimulation of an Effective Cytotoxic T Cell Response against B Cell Precursor Acute Lymphoblastic Leukemia (2009)

For effective immunotherapy, maintaining the frequency and cytotoxic potential of effector cells is critical. In this context costimulation via the CD70/CD27 pathway has been proven essential. CD70 has been reported to be expressed to varying degrees on malignant B cells. However, in B cell precursor acute lymphoblastic leukemia, the most common childhood malignancy, the role of CD70 in stimulation of antileukemic T cell responses has so far not been delineated. Herein we demonstrate that in B cell precursor acute lymphoblastic leukemia expression of CD70 is low but can be induced upon blast activation via CD40. Both CD70 and CD80/CD86 up-regulated on CD40-stimulated blasts contribute to primary stimulation of T cell proliferation and cytokine production in an additive manner. These two signals also cooperate in the prevention of T cell anergy. In contrast to blockade of CD70 during the effector phase, inhibition of CD70-mediated costimulation during generation of antileukemic T cells prevents effector cell proliferation and reduces their cytotoxic capacity. Modulation of the CD70/CD27 pathway may thus represent a novel therapeutic approach for augmenting magnitude and quality of the antileukemic response in B cell precursor acute lymphoblastic leukemia.
Analysis of Peptide and Protein Samples Containing Surfactants by MALDI-MS (1997)

Protein samples containing ionic surfactants such as sodium dodecyl sulfate (SDS) can be analyzed by matrix-assisted laser desorption/ionization mass spectrometry, contrary to what is currently accepted. SDS at varying concentrations was added to four polypeptide samples. As expected, a decrease in the signal was observed for increasing concentrations of SDS up to 0.1% (w/v), at which no signal was observed for three of the analytes. However, a recovery of the signals of all the analytes was observed at concentrations of SDS above 0.3%, with useful spectra at concentrations as high as 10%. The SDS concentration at which signal recovery starts is always the same, regardless of the type and the concentration of the analyte. Another two surfactants 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and octylphenolpoly(ethylene glycol ether)10 (Triton X-100) were also tested. The trend for signal variation with CHAPS addition is similar to that for SDS addition, but for Triton X-100, the signal always diminishes with increasing surfactant concentration. For protein samples containing surfactants with anionic groups, addition of more surfactant allows the acquisition of useful mass spectrometric data.
The effects of dNTP pool imbalances on frameshift fidelity during DNA replication. (1992)

The use of unequal concentrations of the four deoxynucleoside triphosphates (dNTPs) in DNA polymerization reactions alters base substitution error rates in a predictable way. Less is known about the effects of substrate imbalances on base addition and deletion error rates. Thus, we examined pool bias effects on frameshift fidelity during DNA synthesis catalyzed by replicative DNA polymerases. Imbalanced pools altered the frameshift fidelity of the human immunodeficiency virus type-1 reverse transcriptase. Both mutagenic and antimutagenic effects were observed for minus-one, plus-one, and minus-two nucleotide errors, in a highly sequence-specific manner. Most of this specificity can be rationalized by either of two models. One involves frameshifts initiated by pool bias-induced nucleotide misinsertion, and the other involves pool bias-initiated template-primer slippage. Several examples of complex mutations were also recovered more than once in small mutant collections. These contained closely spaced single-base substitution and minus-one base frameshift changes. The two changes occurred at a frequency much higher than predicted if they were generated independently. This suggests that when the polymerase makes one mistake, the probability that it will make a second mistake within the next few incorporations increases significantly. Perturbation of dNTP pools also affected the frameshift fidelity of the replicative yeast DNA polymerase alpha. In reactions containing a low concentration of one dNTP, the error rate increased for one-nucleotide deletions at homopolymeric template nucleotides complementary to the dNTP whose concentration was low. We extended this approach to determine the frameshift fidelity of simian virus 40 origin-dependent semiconservative replication of double-stranded DNA in extracts of human cells. In reactions performed with an equal concentration of all four dNTPs, replication was highly accurate for minus-one-nucleotide errors. However, when the concentration of one dNTP was decreased, the replication error rate increased at complementary, homopolymeric template positions. This response provides an approach for describing frameshift accuracy during replication of the leading and lagging strands.
Novel truncating mutations in PKP1 and DSP cause similar skin phenotypes in two Brazilian families (2009)

Inherited mutations in components of desmosomes result in a spectrum of syndromes characterized by variable abnormalities in the skin and its appendages, including blisters and erosions, palmoplantar hyperkeratosis, woolly hair or hypotrichosis and, in some cases, extracutaneous features such as cardiomyopathy. We investigated the molecular basis of two Brazilian patients presenting with clinical features consistent with ectodermal dysplasia-skin fragility syndrome. In patient 1 we identified a homozygous nonsense mutation, p.R672X, in the PKP1 gene (encoding plakophilin 1). This particular mutation has not been reported previously but is similar to the molecular pathology underlying other cases of this syndrome. In patient 2 we found compound heterozygosity for two frameshift mutations, c.2516del4 and c.3971del4, in the DSP gene (encoding desmoplakin). Although there was considerable clinical overlap in the skin and hair abnormalities in these two cases, patient 2 also had early-onset cardiomyopathy. The mutation c.3971del4 occurs in the longer desmoplakin-I isoform (which is the major cardiac transcript) but not in the more ubiquitous desmoplakin-II. In contrast, PKP1 is not expressed in the heart, which accounts for the lack of cardiomyopathy in patient 1. Collectively, these cases represent the first desmosomal genodermatoses to be reported from Brazil and add to genotype-phenotype correlation in this group of inherited disorders. Loss-of-function mutations in the DSP gene can result in a phenotype similar to ectodermal dysplasia-skin fragility syndrome resulting from PKP1 mutations but only DSP pathology is associated with cardiac disease.
Measurement of technology mediated communication style: the communication preferences inventory (CPI) (2002)

This paper describes the development of a new inventory for measuring communication preferences (the CPI). It begins with a discussion of the need for such an inventory, along with a description of earlier work on use of unified communications technology that motivated its development. The current 62-item of the CPI is presented, along with the associated factor structure based on a sample of 110 respondents. The relationship of the CPI to the big five personality factors is discussed, and a study is reported that assesses the ability of CPI items to predict email and newsgroup behaviour.
On the impact of hardware impairments on massive MIMO (2014)

Massive multi-user (MU) multiple-input multiple-output (MIMO) systems are one possible key technology for next generation wireless communication systems. Claims have been made that massive MU-MIMO will increase both the radiated energy efficiency as well as the sum-rate capacity by orders of magnitude, because of the high transmit directivity. However, due to the very large number of transceivers needed at each base-station (BS), a successful implementation of massive MU-MIMO will be contingent on of the availability of very cheap, compact and power-efficient radio and digital-processing hardware. This may in turn impair the quality of the modulated radio frequency (RF) signal due to an increased amount of power-amplifier distortion, phase-noise, and quantization noise. In this paper, we examine the effects of hardware impairments on a massive MU-MIMO single-cell system by means of theory and simulation. The simulations are performed using simplified, well-established statistical hardware impairment models as well as more sophisticated and realistic models based upon measurements and electromagnetic antenna array simulations.
A Fresh Look at the Rotten Kid Theorem--and Other Household Mysteries (1989)

Gary Becker's "rotten kid theorem" asserts that if all family members receive gifts of money income from a benevolent household member, then even if the household head does not precommit to an incentive plan for family members, it will be in the interest of selfish family members to maximize total family income. The author shows by examples that the rotten kid theorem is not true without assuming transferable utility. He finds a simple condition on utility functions that is necessary and sufficient for there to be the kind of transferable utility needed for a rotten kid theorem. While restrictive, these conditions still allow one to apply the strong conclusions of the rotten kid theorem in an interesting class of examples. Copyright 1989 by University of Chicago Press.
Quantitative mass imaging of single biological macromolecules (2018)

The cellular processes underpinning life are orchestrated by proteins and their interactions. The associated structural and dynamic heterogeneity, despite being key to function, poses a fundamental challenge to existing analytical and structural methodologies. We used interferometric scattering microscopy to quantify the mass of single biomolecules in solution with 2% sequence mass accuracy, up to 19-kilodalton resolution, and 1-kilodalton precision. We resolved oligomeric distributions at high dynamic range, detected small-molecule binding, and mass-imaged proteins with associated lipids and sugars. These capabilities enabled us to characterize the molecular dynamics of processes as diverse as glycoprotein cross-linking, amyloidogenic protein aggregation, and actin polymerization. Interferometric scattering mass spectrometry allows spatiotemporally resolved measurement of a broad range of biomolecular interactions, one molecule at a time.
Structure–Activity Relationship for FDA Approved Drugs As Inhibitors of the Human Sodium Taurocholate Cotransporting Polypeptide (NTCP) (2013)

The hepatic bile acid uptake transporter sodium taurocholate cotransporting polypeptide (NTCP) is less well characterized than its ileal paralog, the apical sodium dependent bile acid transporter (ASBT), in terms of drug inhibition requirements. The objectives of this study were (a) to identify FDA approved drugs that inhibit human NTCP, (b) to develop pharmacophore and Bayesian computational models for NTCP inhibition, and (c) to compare NTCP and ASBT transport inhibition requirements. A series of NTCP inhibition studies were performed using FDA approved drugs, in concert with iterative computational model development. Screening studies identified 27 drugs as novel NTCP inhibitors, including irbesartan (Ki = 11.9 μM) and ezetimibe (Ki = 25.0 μM). The common feature pharmacophore indicated that two hydrophobes and one hydrogen bond acceptor were important for inhibition of NTCP. From 72 drugs screened in vitro, a total of 31 drugs inhibited NTCP, while 51 drugs (i.e., more than half) inhibited ASBT. Hence, while there was inhibitor overlap, ASBT unexpectedly was more permissive to drug inhibition than was NTCP, and this may be related to NTCP possessing fewer pharmacophore features. Findings reflected that a combination of computational and in vitro approaches enriched the understanding of these poorly characterized transporters and yielded additional chemical probes for possible drug-transporter interaction determinations.
Damping-limited modulation bandwidths up to 40 GHz in undoped short-cavity In/sub 0.35/Ga/sub 0.65/As-GaAs multiple-quantum-well lasers (1996)

We demonstrate record direct modulation bandwidths from MBE-grown In/sub 0.35/Ga/sub 0.65/As-GaAs multiple-quantum-well lasers with undoped active regions and with the upper and lower cladding layers grown at different growth temperatures. Short-cavity ridge waveguide lasers achieve CW direct modulation bandwidths up to 40 GHz for 6×130 μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> devices at a bias current of 155 mA, which is the damping limit for this structure. We further demonstrate large-signal digital modulation up to 20 Gb/s (limited by the measurement setup) and linewidth enhancement factors of 1.4 at the lasing wavelength at threshold of /spl sim/1.1 μm for these devices.
A Comparative Study of 200 Fine Needle Aspiration Biopsies Performed by Clinicians and Cytopathologists (2006)

Fine needle aspiration (FNA) biopsy is a useful tool in the diagnosis and management of suspicious masses. Most FNA biopsies of palpable masses can be performed without radioguidance by either clinicians or cytopathologists; however, it is unclear if there is a difference in the diagnostic yield of the procedure based on who performs the FNA. We reviewed the FNA biopsy results of 200 patients presenting with head and neck masses to a tertiary care center from 2003 to 2004. One hundred FNA biopsies were performed by clinicians and 100 performed by cytopathologists. Seventy-one underwent subsequent surgical biopsy or definitive surgery. Results of the FNA biopsies performed by the clinicians and the cytopathologists were compared based on the percentages of FNAs that were diagnostic, suspicious/suggestive, and nondiagnostic. Additionally, the pathology results of the 71 surgical biopsies or resections were compared with the preoperative FNA results. Of the 100 FNA biopsies performed by cytopathologists, 83% were diagnostic, 10% were suspicious/suggestive, and 7% were nondiagnostic. Of the 100 FNA biopsies performed by clinicians, 24% were diagnostic, 43% were suspicious/suggestive, and 33% were nondiagnostic. Cytopathologists achieved significantly better results (P<.0001, two-tailed t-test). Of the 71 cases with surgical follow up (50 by cytopathologists and 21 by clinicians), 94% of cases performed by cytopathologists and 67% of those performed by clinicians show agreement with final surgical pathology results. Overall, the FNAs performed by cytopathologists show significantly better diagnostic accuracy (P=.0002134, two-tailed t-test). FNA provides valuable information in the workup of suspicious head and neck masses. Cytopathologists may achieve significantly better results.
Cellular expression of lymphocyte function associated antigens and the intercellular adhesion molecule-1 in normal tissue. (1990)

A detailed immunohistological analysis of normal tissues for the distribution of lymphocyte function-associated antigens (LFA) and the intercellular adhesion molecule-1 (ICAM-1) showed several hitherto unrecognised patterns of LFA-3 and ICAM-1 expression. The widespread, but not ubiquitous, distribution of LFA-3 contrasted with the more restricted distribution of ICAM-1. Among epithelial cells, all tissues which were ICAM-1 positive were also LFA-3 positive with the single exception that thymic cortical epithelium, in contrast to previous reports, expressed only ICAM-1. It was striking that LFA-3 molecules were absent in some tissues which are considered to be sites of immunological privilege (such as brain and testis), suggesting an additional mechanism by which these microenvironments maintain immunological autonomy. Furthermore, the unexpected finding that LFA-3 is strongly expressed on intercalated discs of cardiac muscle may possibly be related to a non-immune function, or indicate a structurally similar epitope expressed by an unrelated molecule within this tissue.
Novel Mutations in gB and gH Circumvent the Requirement for Known gD Receptors in Herpes Simplex Virus 1 Entry and Cell-to-Cell Spread (2012)

Both entry and cell-to-cell spread of herpes simplex virus (HSV) involve a cascade of cooperative interactions among the essential glycoproteins D, B, and H/L (gD, gB, and gH/gL, respectively) initiated by the binding of gD to a cognate HSV entry receptor. We previously reported that a variant (D285N/A549T) of glycoprotein B (gB:NT) enabled primary virus entry into cells that were devoid of typical HSV entry receptors. Here, we compared the activities of the gB:NT variant with those of a newly selected variant of glycoprotein H (gH:KV) and a frequently coselected gB variant (gB:S668N). In combination, gH:KV and gB:S668N enabled primary virus entry into cells that lacked established HSV entry receptors as efficiently as did gB:NT, but separately, each variant enabled only limited entry. Remarkably, gH:KV uniquely facilitated secondary virus spread between cells that lacked canonical entry receptors. Transient expression of the four essential entry glycoproteins revealed that gH:KV, but not gB:NT, induced fusion between cells lacking the standard receptors. Because the involvement of gD remained essential for virus spread and cell fusion, we propose that gH:KV mimics a transition state of gH that responds efficiently to weak signals from gD to reach the active state. Computational modeling of the structures of wild-type gH and gH:KV revealed relatively subtle differences that may have accounted for our experimental findings. Our study shows that (i) the dependence of HSV-1 entry and spread on specific gD receptors can be reduced by sequence changes in the downstream effectors gB and gH, and (ii) the relative roles of gB and gH are different in entry and spread.
Cholesteric Liquid Crystal Flakes — A New Form of Domain (1998)

Abstract Cholesteric liquid crystal polysiloxane oligomers can be prepared in the Grandjean texture and fractured into smaller pieces called flakes. These flakes function as discrete domains whose degree of orientation can be evaluated by means of Fergason's Equation and turbidity. Further, these flakes can be embedded in a carrier providing a mixed system analogous to polymer-dispersed or gel systems. These embedded flakes have applications as color coatings and polarizing paints and inks without the limitations of elevated temperature or applied voltage.
Assembly of complete, functionally active herpes simplex virus DNA replication compartments and recruitment of associated viral and cellular proteins in transient cotransfection assays (1997)

Early during the herpes simplex virus (HSV) lytic cycle or in the presence of DNA synthesis inhibitors, core viral replication machinery proteins accumulate in intranuclear speckled punctate prereplicative foci, some of which colocalize with numerous sites of host cellular DNA synthesis initiation known as replisomes. At later times, in the absence of inhibitors, several globular or large irregularly shaped replication compartments are formed; these compartments also contain progeny viral DNA and incorporate the IE175(ICP4) transcription factor together with several cellular proteins involved in DNA replication and repair. In this study, we demonstrate that several forms of both prereplication foci and active viral replication compartments that display an appearance similar to that of the compartments in HSV-infected cells can be successfully assembled in transient assays in DNA-transfected cells receiving genes encoding all seven essential HSV replication fork proteins together with oriS target plasmid DNA. Furthermore, bromodeoxyuridine (BrdU)-pulse-labeled DNA synthesis initiation sites colocalized with the HSV single-stranded DNA-binding protein (SSB) in these replication compartments, implying that active viral DNA replication may be occurring. The assembly of complete HSV replication compartments and incorporation of BrdU were both abolished by treatment with phosphonoacetic acid (PAA) and by omission of any one of the seven viral replication proteins, UL5, UL8, UL9, UL42, UL52, SSB, and Pol, that are essential for viral DNA replication. Consistent with the fact that both HSV IE175 and IE63(ICP27) localize within replication compartments in HSV-infected cells, the assembled HSV replication compartments were also able to recruit both of these essential regulatory proteins. Blocking viral DNA synthesis with PAA, but not omission of oriS, prevented the association of IE175 with prereplication structures. The assembled HSV replication compartments also redistributed cotransfected cellular p53 into the viral replication compartments. However, the other two HSV immediate-early nuclear proteins IE110(ICP0) and IE68(ICP22) did not enter the replication compartments in either infected or transfected cells.
Granulocyte-Macrophage Colony-Stimulating Factor Gene-Modified Autologous Tumor Vaccines in Non-Small-Cell Lung Cancer (2004)

To evaluate the feasibility, safety, and efficacy of vaccination with autologous tumor cells genetically modified with an adenoviral vector (Ad-GM) to secrete human granulocyte-macrophage colony-stimulating factor (GM-CSF), we conducted a phase I/II multicenter trial in patients with early and advanced stage non-small-cell lung cancer (NSCLC). Vaccines were generated from autologous tumor harvests. Intradermal injections were given every 2 weeks for a total of three to six vaccinations. Tumors were harvested from 83 patients, 20 with early-stage NSCLC and 63 with advanced- stage NSCLC; vaccines were successfully manufactured for 67 patients, and 43 patients were vaccinated. The most common toxicity was a local injection-site reaction (93%). Three of 33 advanced-stage patients, two with bronchioloalveolar carcinoma, had durable complete tumor responses (lasting 6, 18, and >or=22 months). Longer survival was observed in patients receiving vaccines secreting GM-CSF at more than 40 ng/24 h per 10(6) cells (median survival = 17 months, 95% confidence interval [CI] = 6 to 23 months) than in patients receiving vaccines secreting less GM-CSF (median survival = 7 months, 95% CI = 4 to 10 months) (P =.028), suggesting a vaccine dose-related survival advantage.
Thrombospondin-1 Is the Key Activator of TGF-β1 in Human Mesangial Cells Exposed to High Glucose (2001)

Elevated levels of transforming growth factor-beta1 (TGF-beta1) are synthesized by human mesangial cells that are cultured in medium that contains high concentrations of glucose and mediate increased synthesis of fibronectin (FN), plasminogen activator inhibitor-1 (PAI-1), and changes in the expression of other genes. TGF-beta1 is synthesized as a latent complex. Previous work indicated that high-glucose conditions also upregulate expression of thrombospondin-1 (TSP-1), a potential activator of latent TGF-beta1. With the use of the synthetic peptide GGWSHW, an inhibitor of the TSP-1 activation mechanism, endogenous TSP-1 is shown to be responsible for converting high levels of latent TGF-beta1 to bioactive growth factor over 3 wk of exposure of mesangial cells to 30 mM D-glucose. Peptide inhibition of TGF-beta1 activation by TSP-1 in high-glucose conditions completely suppressed increases in FN and PAI-1 expression. Treating mesangial cells maintained in high glucose with a TSP-1 antisense oligonucleotide reduced TSP-1 expression to levels found in 4 mM D-glucose cultures, prevented TGF-beta1 activation, and normalized expression of FN.