gebhart/patrepeval huggingface dataset:
DNA-Targeted 1,2,4-Benzotriazine 1,4-Dioxides:  Potent Analogues of the Hypoxia-Selective Cytotoxin Tirapazamine (2003)

Tirapazamine (TPZ, 1,2,4-benzotriazin-3-amine 1,4-dioxide) is a bioreductive hypoxia-selective cytotoxin, currently in phase II/III clinical trials in combination with radiotherapy and with cisplatin-based chemotherapy. We have prepared a series of 1,2,4-benzotriazine 1,4-dioxide (BTO) analogues of TPZ where a DNA-targeting chromophore is attached at the 3-position via a flexible linker. DNA binding affinity was modified through variation of the chromophore or the pK(a) of the linker chain. The association constants (K(DNA)) for calf thymus DNA ranged from 1 x 10(2) to 5.6 x 10(5) M(-1) (ionic strength of 0.01 M). DNA binding affinity was dependent on the presence of a positive charge, either in the linker chain or in the chromophore, and (for a series of 4-acridine carboxamide chromophore analogues) correlated strongly with linker chain pK(a). The efficacy of these BTOs in killing aerobic and hypoxic mouse SCCVII tumor cells in vitro was determined by clonogenic survival. Cytotoxicity was measured as the concentration required to reduce plating efficiency to 10% of controls (C(10)), and the hypoxic cytotoxicity ratio (HCR) for each BTO was calculated as C(10)(aerobic)/C(10)(hypoxic). BTOs bearing a positive charge showed increased hypoxic cytotoxicity (1.5-56-fold) compared to TPZ and mostly modest HCRs (8-51), but some excellent (>167 and 400) values. There was a strong correlation between K(DNA) and hypoxic cytotoxicity but no correlation between K(DNA) and HCR. Cytotoxicity in HT-29 human colon carcinoma cells, determined using IC(50) assays, showed similar relationships with a correlation between K(DNA) and hypoxic cytotoxicity but no correlation between K(DNA) and HCR. In this cell line, a higher proportion of compounds (7 of 11) had HCRs greater than or equal to that of TPZ. The data confirm that DNA targeting is a useful concept for increasing potency while maintaining hypoxic selectivity and provide a direction for the further development of DNA-targeted analogues of TPZ.
The Effect of Placenta Extract on Proliferation and Differentiation of Human Chondrocytes (2006)

Purpose: The isolated human chondrocytes for cartilage reconstruction and transplantation presents a major problem as these cells would change biologically in vitro. For more effective applications of these cells in the clinical field, it is necessary to get a large amount of cells in a short period without affecting their function and phenotype.Methods: This study reports the effects of placenta extract on chondrocytes in vitro. We initiated this study on the basis of the hypothesis that placenta extract can influence both the proliferation of chondrocytes and their biologic functions(for example, to express cell specific gene or to produce their own extracellular matrix). Chondrocytes in monolayer culture with or without placenta extract were collected and analyzed by MTT assay, ECM assay, and RT-PCR.Results: Placenta extract stimulated the proliferation of chondrocytes in monolayer culture. The phenotype of chondrocytes was well maintained during the expansion in monolayers. Chondrocytes expanded in the presence of placenta extract produced ECM, glycosaminoglycan, abundantly. Compared to chondrocyte expanded in culture medium only, chondrocytes expanded with placenta extract demonstrated higher COL2A1 expression that was biochemically comparable to primary chondrocytes. This study provides an evidence that placenta extract is helpful to expand chondrocytes during tissue cultivation, to maintain their differentiated phenotype and to promote their function. Conclusion: These results suggest that placenta extract during cultivation play an important role in controlling cell behaviors. Furthermore, these results provide a biologic basis for cartilage tissue engineering.
The new war correspondents (2013)

In this paper we examine the information sharing practices of people living in cities amid armed conflict. We describe the volume and frequency of microblogging activity on Twitter from four cities afflicted by the Mexican Drug War, showing how citizens use social media to alert one another and to comment on the violence that plagues their communities. We then investigate the emergence of civic media "curators," individuals who act as "war correspondents" by aggregating and disseminating information to large numbers of people on social media. We conclude by outlining the implications of our observations for the design of civic media systems in wartime.
Allowing Safe Contact in Robotic Goal-Reaching: Planning and Tracking in Operational and Null Spaces (2023)

In recent years, impressive results have been achieved in robotic manipulation. While many efforts focus on generating collision-free reference signals, few allow safe contact between the robot bodies and the environment. However, in human's daily manipulation, contact between arms and obstacles is prevalent and even necessary. This paper investigates the benefit of allowing safe contact during robotic manipulation and advocates generating and tracking compliance reference signals in both operational and null spaces. In addition, to optimize the collision-allowed trajectories, we present a hybrid solver that integrates sampling- and gradient-based approaches. We evaluate the proposed method on a goal-reaching task in five simulated and real-world environments with different collisional conditions. We show that allowing safe contact improves goal-reaching efficiency and provides feasible solutions in highly collisional scenarios where collision-free constraints cannot be enforced. Moreover, we demonstrate that planning in null space, in addition to operational space, improves trajectory safety. Further information is available at https://rolandzhu.github.io/ContactReach/.
The changing landscape of system-on-a-chip design (2003)

The 1940s are remembered in electronic history for the invention of the transistor, and the 1950s for the invention of the integrated circuit. As the millennium comes to a close, another major development in the world of electronic design has come to the forefront: the ability to integrate an entire "system" onto a single computer chip. System-on-a-chip (SOC) designs have been in existence for only a few years; however, in that span of time, the definition of the "system" designed and manufactured on a chip has significantly changed and expanded as did the technology, skills, tools and methodologies required to produce it. This paper examines the changing characteristics of SOC design, from the mid 1990s when there was a limited number of processor-based in-house designs, to the present-day definition which includes multiple processors, peripherals, communication subsystems, bus hierarchies, analog components, and radio frequency (RF). The increasing levels of SOC integration are illustrated by a family of set-top box designs.
Investigations on microRNAs in human chronic lymphocytic leukemia and control of cancer-associated molecular pathways (2008)

A variety of studies on microRNAs in human chronic lymphocytic leukemia (CLL) opened the way to the assessment of the importance of this large class of genes in human cancer. The first example of involvement of miRNAs in a human neoplasm was provided by the discovery of mir-15a and mir-16-1 locus within the minimal region of deletion at chromosome 13q14 in human CLL. The proof that a large number of miRNAs are deregulated in malignant cells was initially given by genome-wide expression studies of miRNAs in CLL. The finding of a prognostic miRNA signature was discovered in human CLL. One of the first molecular links with cancer molecular pathways came by the discovery of the regulation of the BCL2 oncogene operated by miR-15a/miR-16-1, which is aberrant in CLL cells. Finally, the potential cancer predisposing role of miRNAs was suggested by the discovery of mir-15a/mir-16-1 germ-line mutations in families associated with an increased risk of CLL. Together with the CLL studies, many additional investigations increased the importance of the field as they proved that numerous miRNAs are deregulated in human cancers and may act either as oncogenes or tumor suppressor genes. Aberrant miRNA expression has been linked to cell cycle progression, loss of differentiation, increased survival, invasion and metastasis. The discovery that miRNAs interact with oncogenes and tumor suppressor genes established multiple links with molecular pathways implicated in malignant transformation. These findings hold the promise that miRNAs could become important diagnostic and therapeutic tools.
The Promise of Nanoneuromedicine (2014)

While biomaterials, sensors, nanoparticles, and nanospheres
Embryonic stem cell tumor model reveals role of vascular endothelial receptor tyrosine phosphatase in regulating Tie2 pathway in tumor angiogenesis (2009)

Inhibiting angiogenesis has become an effective approach for treating cancer and other diseases. However, our understanding of signaling pathways in tumor angiogenesis has been limited by the embryonic lethality of many gene knockouts. To overcome this limitation, we used the plasticity of embryonic stem (ES) cells to develop a unique approach to study tumor angiogenesis. Murine ES cells can be readily manipulated genetically; in addition, ES cells implanted subcutaneously in mice develop into tumors that contain a variety of cell types (teratomas). We show that ES cells differentiate into bona fide endothelial cells within the teratoma, and that these ES-derived endothelial cells form part of the functional tumor vasculature. Using this powerful and flexible system, the Angiopoietin/Tie2 system is shown to have a key role in the regulation of tumor vessel size. Endothelial differentiation in the ES teratoma model allows gene-targeting methods to be used in the study of tumor angiogenesis.
The OmpA vaccine protects mice against lethal, extreme drug resistant- Acinetobacter baumannii infection (106.20) (2011)

Abstract Extreme drug resistant (XDR) Acinetobacter baumannii is a rapidly emerging pathogen causing infections with unacceptably high mortality rates due to inadequate available treatment. Prevention of such infections is a critical unmet medical need. Because diabetes is a clinical risk factor for A. baumannii infections, a diabetes ketoacidosis (DKA) mouse model of such infections was established to support a rational vaccine discovery program. Specific humoral immune responses to A. baumannii cell membrane proteins occurred during tail-vein infection with multiple clinical isolates in DKA mice. Western blots with paired pre-immune and immune sera identified outer membrane protein A (OmpA) as the immunodominant antigen. Vaccination of DKA mice with recombinant OmpA (rOmpA) with aluminum hydroxide adjuvant markedly improved survival, reduced tissue bacterial burden, and promoted inflammatory cytokine production in infected tissues. rOmpA is a promising vaccine candidate to prevent A. baumannii infections.
Sialylation of the Gram-Negative Bacterial Cell Surface (2014)

Sialic acids (NeuAc) and its derivatives are found on cell membranes and in body fluids in all mammals and many higher-order animals, as well as pathogenic microorganisms. Based on an understanding of the biosynthesis of sialic acid and the evolving elucidation of the genomes of multiple microbes, researchers have described at least four mechanisms of microbial surface sialylation. These include de novo synthesis, donor scavenging, trans-sialylation and precursor scavenging. To understand the role of sialic acids in pathogenesis, it is important to examine their role in eukaryotic systems. Sialic acid-dependent receptors play an important role in adhesion to mammalian cells. Two examples of the receptors, the selectin and sialoadhesin families, are discussed in this chapter. There is a correlation between sialic acid levels and the development of cancer. A tumor cell has an increased amount of sialylation and sialyltransferase activity. The biological effects of sialylation, which mediate antiphagocytosis, anticomplement activity, and protection against bactericidal killing, have the potential to act with sialic acid binding immunoglobulinlike lectins (siglecs) on the surface of hematopoietic and immune system cells. Many bacteria produce neuraminidases, which can modify the sialylation of microbial and human tissues. Bacterial biofilms and their role in pathogenicity have generated considerable interest because of their role in antimicrobial resistance and pathogenesis. Recent studies demonstrating the potential for cooperative behavior between bacteria suggest that in complex communities, the disadvantages of surface sialylation may be obviated by neuraminidase production by a neighboring microbial partner.
Co-Delivery of CPT-11 and Panobinostat with Anti-GD2 Antibody Conjugated Immunoliposomes for Targeted Combination Chemotherapy (2020)

The consistent expression of disialoganglioside GD2 in neuroblastoma tumor cells and its restricted expression in normal tissues open the possibility to use it for molecularly targeted neuroblastoma therapy. On the other hand, immunoliposomes combining antibody-mediated tumor recognition with liposomal delivery of chemotherapeutics have been proved to enhance therapeutic efficacy in brain tumors. Therefore, we develop immunoliposomes (ImmuLipCP) conjugated with anti-GD2 antibody, for targeted co-delivery of CPT-11 and panobinostat in this study. U87MG human glioma cell line and its drug resistant variant (U87DR), which were confirmed to be associated with low and high expression of cell surface GD2, were employed to compare the targeting efficacy. From in vitro cytotoxicity assay, CPT-11 showed synergism drug interaction with panobinostat to support co-delivery of both drugs with ImmuLipCP for targeted synergistic combination chemotherapy. The molecular targeting mechanism was elucidated from intracellular uptake efficacy by confocal microscopy and flow cytometry analysis, where 6-fold increase in liposome and 1.8-fold increase in drug uptake efficiency was found using targeted liposomes. This enhanced intracellular trafficking for drug delivery endows ImmuLipCP with pronounced cytotoxicity toward U87DR cells in vitro, with 1.6-fold increase of apoptosis rate. Using xenograft nude mice model with subcutaneously implanted U87DR cells, we observe similar biodistribution profile but 5.1 times higher accumulation rate of ImmuLip from in vivo imaging system (IVIS) observation of Cy5.5-labelled liposomes. Taking advantage of this highly efficient GD-2 targeting, ImmuLipCP was demonstrated to be an effective cancer treatment modality to significantly enhance the anti-cancer therapeutic efficacy in U87DR tumors, shown from the significant reduced tumor size in and prolonged survival time of experiment animals as well as diminished expression of cell proliferation and enhanced expression of apoptosis marker proteins in tumor section.
Fluorescence microscopy imaging of cells with a plasmonic dish integrally molded (2016)

Abstract A plastic dish with a wavelength-scale periodic structure at a bottom panel was integrally molded and coated with thin metal films. The integrally molded dish called plasmonic dish was applied to bioimaging under a fluorescence microscope. On the plasmonic substrate, the enhanced electric field based on a grating-coupled surface plasmon resonance (GC-SPR) can provide an enhanced fluorescence. In this study, two kinds of cells, human embryonic kidney (HEK) cells and neuronal cells, were observed in our plasmonic dish. Fluorescence images of HEK cells were above 10 times brighter than those obtained on a conventional glass-bottomed dish. Neuronal cells were successfully cultured for 10 d on the plasmonic dish integrally molded, and in fluorescence images with transmitted light, a higher contrast was obtained than in epifluorescence images. The plasmonic dish integrally molded, as well as that fabricated by the UV nanoimprint method, was also found to be useful for sensitive bioimaging.
Mathematical model for time-resolved and frequency-domain fluorescence spectroscopy in biological tissues (1994)

In general it is not possible to write an analytic expression for the fluorescence signal generated by a fluorophore distributed in a scattering medium such as tissue. However, by assuming that the scattering properties of the tissue are the same at the excitation and emission wavelengths, we have derived a simple relation between the fluorescence and the scatter signals. Along with diffusion theory, this was used to write expressions for the fluorescence signal detected at the tissue surface in both the time and the frequency domains. Experiments using the fluorophore aluminum chlorosulfonated phthalocyanine in tissue-simulating materials confirmed the accuracy of the model. Applications to in vivo spectroscopy are discussed.
Photoperiod alters phase difference between activity onset in vivo and mPer2::luc peak in vitro (2008)

Photoperiod is a significant modulator of behavior and physiology for many organisms. In rodents changes in photoperiod are associated with changes in circadian period and photic resetting of circadian pacemakers. Utilizing rhythms of in vivo behavior and in vitro mPer2::luc expression, we investigated whether different entrainment photoperiods [light:dark (L:D) 16:8 and L:D 8:16] alter the period or phase relationships between these rhythms and the entraining light cycle in Per2::luc C57BL/6J mice. We also tested whether mPer2::luc rhythms differs in anterior and posterior suprachiasmatic nucleus (SCN) slices. Our results demonstrate that photoperiod significantly changes the timing of the mPer2::luc peak relative to the time of light offset and the activity onset in vivo. In both L:D 8:16 and L:D 16:8 the mPer2::luc peak maintained a more stable phase relationship to activity offset, while altering the phase relationship to activity onset. After the initial cycle in culture, the period, phase, and peaks per cycle were not significantly different for anterior vs. posterior SCN slices taken from animals within one photoperiod. After short-photoperiod treatment, anterior SCN slices showed increased-amplitude Per2::luc waveforms and posterior SCN slices showed shorter-duration peak width. Finally, the SCN tissue in vitro did not demonstrate differences in period attributable to photoperiod pretreatment, indicating that period aftereffects observed in behavioral rhythms after long- and short-day photoperiods are not sustained in Per2::luc rhythms in vitro. The change in phase relationship to activity onset suggests that Per2::luc rhythms in the SCN may track activity offset rather than activity onset. The reduced amplitude rhythms following long-photoperiod treatment may represent a loss of coupling of component oscillators.
Self‐assembled alkylsilane monolayers for the preparation of stable and efficient coatings in capillary electrophoresis (1994)

Abstract The approach of forming self‐assembled monolayers on the surface of fused silica capillaries has been evaluated for capillary electrophoresis of proteins. Two polymer matrices (polymerized acrylamide or methacryloyl‐Tris) were successfully grafted on the self‐assembled monolayers, as evidenced by electroosmotic flow measurements and efficient separations of model proteins.
Structural similarities between the aspartate receptor of bacterial chemotaxis and the trp repressor of E. coli Implications for transmembrane signaling (1992)

A high resolution structure of the N-terminal ligand-binding domain of the aspartate receptor which mediates aspartate chemotaxis in Salmonella typhimurium has recently been reported. A least-squares superposition of the alpha-amino nitrogen, alpha-carbon, beta-carbon, and alpha-carboxylate carbon of the aspartate bound to the aspartate receptor onto the equivalent atoms in the tryptophan bound to the trp repressor provides evidence for similarity between key parts of the active sites that bind to the alpha-amino and alpha-carboxylates of the respective ligands. Because the N-terminal domain of the aspartate receptor and the trp repressor also share other structural similarities, we hypothesize that the similarity between the aspartate receptor and the trp repressor derives from a similarity in ligand-induced conformational changes at the active sites of these proteins. This hypothesis also implies that an important signaling event in the aspartate receptor occurs through tertiary conformational changes within a single subunit.
Assessment of potential doubling time (Tpot), argyrophilic nucleolar organizer regions (AgNOR), and proliferating cell nuclear antigen (PCNA) as predictors of therapy response in canine non-Hodgkin's lymphoma. (1996)

The predictive potential of several proliferation indices for therapeutic outcome was investigated in 55 dogs with spontaneously occurring non-Hodgkin's lymphoma (NHL). Indices included potential doubling time (Tpot), argyrophilic nucleolar organizer region (AgNOR) frequency, and proliferating cell nuclear antigen labeling index (PCNA-LI). All tumors were of intermediate- or high-grade histology as assessed by the Working Formulation, and all dogs presented with disease of advanced clinical stage. All tumors were treated with an identical chemotherapeutic protocol. Tpot determination by a bromodeoxyuridine (BrdU) delayed-biopsy technique was readily applied in the dog. AgNOR frequency and PCNA-LI were easily obtained from archival, formalin-fixed, paraffin-embedded canine tissues. When accounting for all other prognostic variables by employing multivariate analysis, Tpot (p=0.017), and AgNOR frequency (p=0.021), but not PCNA-LI, were predictive of first remission duration. AgNOR frequency (p=0.033) was also predictive of survival time, and the predictive potential of Tpot approached significance (p=0.076). We conclude that Tpot and AgNOR frequency can be used as predictors of outcome in dogs with NHL, and spontaneous NHL in the dog may have significant potential as a model for further characterization of the association between tumor cell kinetics and chemoresponsiveness.
Soluble E-Selectin Is an Inverse and Independent Predictor of Left Ventricular Wall Thickness in End-Stage Renal Disease Patients (2009)

This study demonstrates that soluble E-selectin is inversely associated with the muscular component of the left ventricle, thereby suggesting that the lack of such a reparative factor may be associated with cardiac remodeling in ESRD patients.
Immunotherapy for Cutaneous T-Cell Lymphoma (2012)

The cutaneous T-cell lymphomas have been shown to be associated with dysregulation of effector T-cell activity, making them an attractive target for immune activating therapies. Interferons and extracorporeal photopheresis-based therapeutic approaches have been shown to induce clinical responses of significant duration in selected patients. Similarly, activity has been demonstrated with cytokine-based therapies, including interleukin-2, interleukin-12, and the toll-like receptor agonists. Retinoids and histone deacetylase inhibitors, widely used therapies in early stage CTCL, have been shown to modulate immune effector mechanisms. For most patients with CTCL, the goals of therapy are to exploit immunotherapeutic approaches for as long as possible and to keep immune function intact.