gebhart/patrepeval huggingface dataset:
Learning a Neural Solver for Multiple Object Tracking (2020)

Graphs offer a natural way to formulate Multiple Object Tracking (MOT) within the tracking-by-detection paradigm. However, they also introduce a major challenge for learning methods, as defining a model that can operate on such structured domain is not trivial. As a consequence, most learning-based work has been devoted to learning better features for MOT and then using these with well-established optimization frameworks. In this work, we exploit the classical network flow formulation of MOT to define a fully differentiable framework based on Message Passing Networks (MPNs). By operating directly on the graph domain, our method can reason globally over an entire set of detections and predict final solutions. Hence, we show that learning in MOT does not need to be restricted to feature extraction, but it can also be applied to the data association step. We show a significant improvement in both MOTA and IDF1 on three publicly available benchmarks. Our code is available at https://bit.ly/motsolv.
Identification of promiscuous HPV16-derived T helper cell epitopes for therapeutic HPV vaccine design (2014)

Cervical carcinoma and several other human papillomavirus (HPV)-induced malignancies are a global public health problem, thus novel treatment modalities are urgently needed. Immunotherapy is an attractive option for treatment of HPV infection and HPV-mediated premalignant and malignant lesions. However, previous approaches--focusing on the induction of cytotoxic CD8+ T cells (CTLs)--have as yet not yielded clinical successes. Since CD4+ T cells have been shown to be crucial for the induction and maintenance of CTL responses, and more recently to be also important for direct anti-tumor immunity, human leukocyte antigen (HLA) class II-restricted epitopes are intensively investigated to improve the efficacy of peptide-based HPV immunotherapy. We here present an approach to identify promiscuous HPV16-derived CD4+ T helper epitopes, which are capable of inducing T cell immunity in a large proportion of the population. To this end, we combined HLA class II epitope prediction servers with in vitro immunological evaluation to identify HPV16 E2-, E5-, E6-, and E7-derived CD4+ T cell epitopes. Candidate selected HPV16-derived epitopes were found to be restricted by up to nine HLA-DR molecules. Furthermore, they were found to induce frequent and robust HPV16 peptide-specific Th1 responses in healthy donors, as monitored by interferon (IFN)-γ ELISPOT and cytokine secretion assays. Moreover, these selected peptides also induced specific IFN-γ T cell responses in blood from HPV16+ CIN2/3 and cervical carcinoma patients. We thus conclude that the identified T helper epitopes are valuable candidates for the development of a comprehensive therapeutic HPV vaccine.
Purified Horseshoe Crab Factor G (1995)

Horseshoe crab hemocyte lysate responds to (1-->3)-beta-D-glucans, initiating an enzymatic cascade, which culuminates in clot formation. We have purified to homogeneity the serine protease zymogen factor G, which is directly activated by (1-->3)-beta-D-glucans and which initiates the hemolymph clotting cascade. Factor G is a heterodimeric protein composed of two noncovalently associated subunits alpha (72 kDa) and beta (37 kDa). In the presence of (1-->3)-beta-D-glucans such as curdlan and paramylon, factor G is autocatalytically activated to an active serine protease named factor G. This activation is accompanied by limited proteolysis of both subunits: the 72-kDa subunit alpha is cleaved to 55-kDa and 17-kDa fragments, and the 37-kDa subunit beta is shortened to 34 kDa. Longer incubations with (1-->3)-beta-D-glucans result in cleavage of the 55-kDa fragment to 46 kDa and the 34-kDa fragment to 32 kDa, with concomitant loss of amidase activity. Reconstitution experiments using purified proteins participating in the hemolymph clotting cascade demonstrate that factor G is capable of activating proclotting enzyme directly, resulting in the conversion of coagulogen to coagulin gel. Thus, purified factor G is shown to be the primary initiator of the (1-->3)-beta-D-glucan-sensitive coagulation pathway in the horseshoe crab hemocyte lysate.
Detection of an elevated HER2 expression in MCF-7 breast cancer cells overexpressing estrogen receptor β1 (2008)

The estrogen receptor (ER) expression and HER2 amplification are important factors in determining the prognosis and therapy of breast cancer. Interactions between the two signaling pathways for example resulted in ERalpha-dependent regulation of HER2 expression in breast cancer cells. In this study, we investigated to what extent ERbeta is able to affect the HER2 expression. For this purpose, we analyzed HER2 levels in ERbeta1-overexpressing clones of the breast cancer cell lines MCF-7 and SK-BR-3 and of the ovarian cancer cell lines SK-OV-3 and OVCAR-3 by both RT-PCR and Western blot analysis. Treatment with ligand 17-beta estradiol diminished the HER2 expression in MCF-7 wild-type cells, an effect partially inhibited by treatment with 4-OH tamoxifen. MCF-7 breast cancer cells stably overexpressing ERbeta1 exhibited elevated >5-fold HER2 mRNA levels and elevated >3-fold HER2 protein levels even in the absence of estradiol. In contrast, ERbeta1 overexpression did not affect HER2 protein levels in the ERalpha-positive OVCAR-3 ovarian cancer cells and in the HER2 overexpressing, hormone-independent SK-BR-3 and SK-OV-3 cells. By demonstrating the elevated HER2 expression in a hormone-dependent breast cancer cell line overexpressing ERbeta1, our data suggest the presence of cross-talk between the two receptors. This is one of the molecular mechanisms underlying the significant ERbeta/HER2 co-expression observed in recent clinical studies.
Cement Line Staining in Undecalcified Thin Sections of Cortical Bone (1990)

A technique for demonstrating cement lines in thin, undecalcified transverse sections of cortical bone has been developed. Cortical bone samples are processed and embedded undecalcified in methyl methacrylate plastic. After sectioning at 3-5 microns, cross-sections are transferred to a glass slide and flattened for 10 min. Sections of cortical bone are stained for 20 sec free-floating in a fresh solution of 1% toluidine blue dissolved in 0.1% formic acid. The section is dehydrated in t-butyl alcohol, cleared in xylene, and mounted with Eukitt's medium. Reversal lines appear as thin, scalloped, dark blue lines against a light blue matrix, whereas bone formation arrest lines are thicker with a smooth contour. With this technique cellular detail, osteoid differentiation, and fluorochrome labels are retained. Results demonstrate the applicability of a one-step staining method for cement lines which will facilitate the assessment of bone remodeling activity in thin sections of undecalcified cortical bone.
Attachment of fibroblasts on smooth and microgrooved polystyrene (1999)

In this study rat dermal fibroblasts (RDFs) were cultured on smooth or microgrooved (1-20 microm wide, 0.5-5.4 microm deep) substrates. Polystyrene microgrooved substrates were produced by solvent casting on molds that had been produced by photolithographic techniques. We investigated the attachment of RDFs with various analytical techniques. Light microscopy and image analysis showed that RDFs were oriented on most microgrooves. The rate of orientation effectively was increased by an increase of groove depth. An analysis of confluent layers of RDF showed that at confluency microgrooves were able to support greater numbers of cells. However, the largest numbers of cells were not found on the narrowest and deepest microgrooves even though such microgrooves have the largest total surface and induce the strongest alignment. Interference reflection microscopy (IRM) showed that the RDFs form focal adhesions where the cell membrane is only 10 nm from the substrate. IRM also showed that RDFs follow the contours of shallow and wide microgrooves but bridge the grooves on deeper and narrower ones. This could explain why such grooves are not able to increase the numerical cell adhesion to a greater degree. The absence of contact between cells and the bottom of the grooves is a very important factor in establishing contact guidance.
HPV-16 E7 protein bypasses keratinocyte growth inhibition by serum and calcium (1998)

The E6 and E7 genes of HPV-16 or HPV-18 both are necessary for effective immortalization of primary human genital keratinocytes. To analyse the individual role of E6 and E7 genes in dysregulating cell growth, we cloned the HPV-16 E6, E7 and E6/E7 genes into retroviruses. Primary human keratinocytes (PHK) were then infected with these retroviruses and selected in differentiation-inducing medium (high calcium and serum). The E6/E7 retroviruses were the most effective at inducing differentiation-resistant colonies. Intermediate numbers of colonies were induced by E6 and low numbers by E7. Interestingly, only cultures infected with E7 and E6/E7 retroviruses showed a significant proportion of cells progressing into the S phase, consistent with our earlier studies showing that E7 is required for the efficient immortalization of genital keratinocytes. Accompanying this entry into S phase, the E7 or E6/E7 transduced cells expressed high levels of cyclins A, B and E, but lower levels of cyclin D. In addition, cdc-2, cdk-2 and cdk-4 were also increased. No significant differences were detected in the expression of c-myc and c-fos between the vector and any of the transduced cells. Keratinocytes infected with the E7 retrovirus exhibited decreased levels of Rb protein and increased levels of p53, whereas cells infected with E6-expressing retroviruses displayed normal levels of Rb protein and decreased levels of p53. Finally, E7 induced a three-fold increase in bcl-2 expression. Our results indicate that the HPV-16 E7 gene alone is sufficient to bypass keratinoctye growth arrest induced by serum and calcium exposure and that the discordant expression of several cell regulatory proteins accompanies this unregulated proliferation.
Thermal Techniques for the Recovery of Heavy Oil and Bitumen (2005)

Abstract Over 90% of the world's heavy oil and bitumen (oil sands) are deposited in Canada and Venezuela. Alberta holds the world's largest reserves of bitumen and the reserves are of the same order of magnitude as reserves of conventional oil in Saudi Arabia. Up to 80% of estimated reserves could be recovered by in-situ thermal operation. As the resources available for conventional crude in Canada continue to decline, further development of heavy oil and oil sands in-situ recovery technologies is critical to meeting Canada's present and future energy requirements. Sophisticated technologies have been required to economically develop Canada's complex and varying oil fields. Various existing in-situ technologies such as hot water injection, steam flooding, cyclic steaming and combustion processes have been successfully applied in Venezuela and California. Most recently, advances made in directional drilling and measuring while drilling (MWD) technologies have facilitated development of new in-situ production technologies such as the steam assisted gravity drainage (SAGD), expanding solvent-SAGD (ES-SAGD) and solvent vapor extraction (VAPEX) that have significantly improved well-bore reservoir contact, sweep efficiencies, produced oil rates and reduced production costs. This paper provides an overview of existing and new thermal in-situ technologies and current projects. Potential of new technologies are assessed and compared to various existing in-situ thermal processes. Critical issues affecting production performance are discussed.
Gene Expression Profiling of the Effect of High-Dose Intravenous Ig in Patients with Kawasaki Disease (2005)

Kawasaki disease (KD) is an acute vasculitis of infants and young children, preferentially affecting the coronary arteries. Intravenous infusion of high dose Ig (IVIG) effectively reduces systemic inflammation and prevents coronary artery lesions in KD. To investigate the mechanisms underlying the therapeutic effects of IVIG, we examined gene expression profiles of PBMC and purified monocytes obtained from acute patients before and after IVIG therapy. The results suggest that IVIG suppresses activated monocytes and macrophages by altering various functional aspects of the genes of KD patients. Among the 18 commonly decreased transcripts in both PBMC and purified monocytes, we selected six genes, FCGR1A, FCGR3A, CCR2, ADM, S100A9, and S100A12, and confirmed the microarray results by real-time RT-PCR. Moreover, the expressions of FcgammaRI and FcgammaRIII on monocytes were reduced after IVIG. Plasma S100A8/A9 heterocomplex, but not S100A9, levels were elevated in patients with acute KD compared with those in febrile controls. Furthermore, S100A8/A9 was rapidly down-regulated in response to IVIG therapy. Persistent elevation of S100A8/A9 after IVIG was found in patients who later developed coronary aneurysms. These results indicate that the effects of IVIG in KD may be mediated by suppression of an array of immune activation genes in monocytes, including those activating FcgammaRs and the S100A8/A9 heterocomplex.
Isolation and transcriptome analyses of human erythroid progenitors: BFU-E and CFU-E (2014)

Burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) cells are erythroid progenitors traditionally defined by colony assays. We developed a flow cytometry-based strategy for isolating human BFU-E and CFU-E cells based on the changes in expression of cell surface markers during in vitro erythroid cell culture. BFU-E and CFU-E are characterized by CD45(+)GPA(-)IL-3R(-)CD34(+)CD36(-)CD71(low) and CD45(+)GPA(-)IL-3R(-)CD34(-)CD36(+)CD71(high) phenotypes, respectively. Colony assays validated phenotypic assignment giving rise to BFU-E and CFU-E colonies, both at a purity of ∼90%. The BFU-E colony forming ability of CD45(+)GPA(-)IL-3R(-)CD34(+)CD36(-)CD71(low) cells required stem cell factor and erythropoietin, while the CFU-E colony forming ability of CD45(+)GPA(-)IL-3R(-)CD34(-)CD36(+)CD71(high) cells required only erythropoietin. Bioinformatic analysis of the RNA-sequencing data revealed unique transcriptomes at each differentiation stage. The sorting strategy was validated in uncultured primary cells isolated from bone marrow, cord blood, and peripheral blood, indicating that marker expression is not an artifact of in vitro cell culture, but represents an in vivo characteristic of erythroid progenitor populations. The ability to isolate highly pure human BFU-E and CFU-E progenitors will enable detailed cellular and molecular characterization of these distinct progenitor populations and define their contribution to disordered erythropoiesis in inherited and acquired hematologic disease. Our data provides an important resource for future studies of human erythropoiesis.
Collaborative Recommendations (2004)

Loss of lean body mass in patients with HIV, commonly referred to as wasting, remains a significant threat to outcome in the era of highly active antiretroviral therapy. It does not require advanced immune deficiency to progress. It is appropriate to reevaluate guidelines for diagnosis and treatment of wasting in the context of the increasing detail with which the risks and causes of HIV wasting are being understood. A wide range of therapies can be effective in preventing weight loss, but the pharmacologic options for restoring body cell mass, a key measure of HIV wasting, are far more limited. A collaborative meeting of clinicians and researchers with an interest in HIV wasting was held to evaluate published guidelines in the context of current clinical data.
Complement-Mediated Ischemia-Reperfusion Injury (2009)

Ischemia-reperfusion (I/R) injury provides a substantial limitation to further improvements in the development of therapeutic strategies for ischemia-related diseases. Studies in animal I/R models, including intestinal, hindlimb, kidney, and myocardial I/R models, have established a key role of the complement system in mediation of I/R injury using complement inhibitors and knock-out animal models. As complement activation has been shown to be an early event in I/R injury, inhibiting its activation or its components may offer tissue protection after reperfusion. However, clinical study results using complement inhibitors have largely been disappointing. Therefore, identification of a more specific pathogenic target for therapeutic intervention seems to be warranted. For this purpose more detailed knowledge of the responsible pathway of complement activation in I/R injury is required. Recent evidence from in vitro and in vivo models suggests involvement of both the classic and the lectin pathways in I/R injury via exposition of neo-epitopes in ischemic membranes. However, most of these findings have been obtained in knock-out murine models and have for a large part remained unconfirmed in the human setting. The observation that the relative role of each pathway seems to differ among organs complicates matters further. Whether a defective complement system protects from I/R injury in humans remains largely unknown. Most importantly, involvement of mannose-binding lectin as the main initiator of the lectin pathway has not been demonstrated at tissue level in human I/R injury to date. Thus, conclusions drawn from animal I/R studies should be extrapolated to the human setting with caution.
Cancer Immunotherapy Comes of Age (2011)

Cancer immunotherapy comprises a variety of treatment approaches, incorporating the tremendous specificity of the adaptive immune system (T cells and antibodies) as well as the diverse and potent cytotoxic weaponry of both adaptive and innate immunity. Immunotherapy strategies include antitumor monoclonal antibodies, cancer vaccines, adoptive transfer of ex vivo activated T and natural killer cells, and administration of antibodies or recombinant proteins that either costimulate immune cells or block immune inhibitory pathways (so-called immune checkpoints). Although clear clinical efficacy has been demonstrated with antitumor antibodies since the late 1990s, other immunotherapies had not been shown to be effective until recently, when a spate of successes established the broad potential of this therapeutic modality. These successes are based on fundamental scientific advances demonstrating the toleragenic nature of cancer and the pivotal role of the tumor immune microenvironment in suppressing antitumor immunity. New therapies based on a sophisticated knowledge of immune-suppressive cells, soluble factors, and signaling pathways are designed to break tolerance and reactivate antitumor immunity to induce potent, long-lasting responses. Preclinical models indicate the importance of a complex integrated immune response in eliminating established tumors and validate the exploration of combinatorial treatment regimens, which are anticipated to be far more effective than monotherapies. Unlike conventional cancer therapies, most immunotherapies are active and dynamic, capable of inducing immune memory to propagate a successful rebalancing of the equilibrium between tumor and host.
Desorption Electrospray Ionization Mass Spectrometry for High-Throughput Analysis of Pharmaceutical Samples in the Ambient Environment (2005)

Desorption electrospray ionization (DESI) allows mass spectrometry to be used for on-line high-throughput monitoring of pharmaceutical samples in the ambient environment, without prior sample preparation. Positive and negative ion DESI are used to characterize the active ingredients in pharmaceutical samples formulated as tablets, ointments, and liquids. Compounds of a wide variety of chemical types are detected in these complex matrices. The effects on analytical performance of operating parameters, including the electrospray high voltage, heated capillary temperature, solvent infusion rate, and solvent composition, are evaluated and optimized. In addition to experiments in which a simple solvent is sprayed onto the solid analyte samples, reactive desorption is performed by adding reagents to the solvent spray to generate particularly stable or characteristic ions with the analytes of interest. A variable-speed moving belt was built for high-throughput sampling and used to provide rapid qualitative and semiquantitative information on drug constituents in tablets. Sampling rates as high as 3 samples/s are achieved in the ambient environment. Relative standard deviations of the relative ion abundances for major components in the mass spectra are in the range of 2-8%. Impurities and components present at levels as low as approximately 0.1% are identified and carryover effects are minimized in high-throughput on-line analysis of pharmaceutical samples.
Augmentation of glutathione in the fluid lining the epithelium of the lower respiratory tract by directly administering glutathione aerosol. (1990)

Glutathione (GSH), a cysteine-containing tripeptide, functions as an antioxidant, provides cells with cysteine, and is required for optimal function of the immune system. Because the epithelial-lining fluid (ELF) of the lower respiratory tract normally contains high GSH levels and lung ELF GSH deficiency states can exist, we evaluated the feasibility of augmenting lung ELF GSH levels by (i) administering GSH to sheep i.v. and by direct aerosolization and then (ii) measuring the GSH levels in lung ELF, lung lymph, venous plasma, and urine. When GSH (600 mg) was administered i.v. (n = 11), GSH levels in venous plasma, lung lymph, and ELF rose, but only transiently, suggesting the i.v. route would not deliver adequate GSH to the alveolar epithelial surface. For directly administering GSH to the lung by the aerosol route, in vitro studies were first conducted to show that greater than 50% of a GSH solution could be converted to droplets less than 3 microns in aerodynamic diameter without oxidizing the GSH. To target functional GSH to the lower respiratory tract, an aerosolized solution of GSH (600 mg) was administered to sheep (n = 12). Significantly, the GSH level in ELF increased 7-fold at 30 min (preaerosol, 45.7 +/- 10 microM; 30-min postaerosol, 337 +/- 64 microM; P less than 0.001). The ELF GSH levels remained above baseline at 1 hr (P less than 0.01), returning toward baseline over a 2-hr period. In contrast, GSH levels in lung lymph, venous plasma, and urine were not significantly increased during the period--i.e., aerosol therapy selectively augmented the GSH levels only at the lung epithelial surface. Thus, functional GSH can be delivered by aerosol to directly augment the ELF GSH levels of the lower respiratory tract. Such an approach may prove useful in treating a variety of lung disorders.