gebhart/patrepeval huggingface dataset:
Transcriptional signature with differential expression of BCL6 target genes accurately identifies BCL6-dependent diffuse large B cell lymphomas (2007)

Diffuse large B cell lymphomas (DLBCLs) often express BCL6, a transcriptional repressor required for the formation of normal germinal centers. In a subset of DLBCLs, BCL6 is deregulated by chromosomal translocations or aberrant somatic hypermutation; in other tumors, BCL6 expression may simply reflect germinal center lineage. DLBCLs dependent on BCL6-regulated pathways should exhibit differential regulation of BCL6 target genes. Genomic array ChIP-on-chip was used to identify the cohort of direct BCL6 target genes. This set of genes was enriched in modulators of transcription, chromatin structure, protein ubiquitylation, cell cycle, and DNA damage responses. In primary DLBCLs classified on the basis of gene expression profiles, these BCL6 target genes were clearly differentially regulated in "BCR" tumors, a subset of DLBCLs with increased BCL6 expression and more frequent BCL6 translocations. In a panel of DLBCL cell lines analyzed by expression arrays and classified according to their gene expression profiles, only BCR tumors were highly sensitive to the BCL6 peptide inhibitor, BPI. These studies identify a discrete subset of DLBCLs that are reliant on BCL6 signaling and uniquely sensitive to BCL6 inhibitors. More broadly, these data show how genome-wide identification of direct target genes can identify tumors dependent on oncogenic transcription factors and amenable to targeted therapeutics.
Some observations on Amphibia at and near Las Vegas, New Mexico (1941)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.
Binder stability and powder/binder interaction in three dimensional printing (1995)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 1995.
Regulation of HLA Class II Expression and its Role in Autoimmune Disease (2007)

Excessive HLA class II expression is found on the target tissues of the majority of human autoimmune diseases, together with activated (interleukin 2 receptor-expressing) T lymphocytes, suggesting that the target tissues act as antigen-presenting cells for infiltrating autoreactive cells, which in turn produce molecules that maintain class II expression. This vicious cycle has been shown to operate in Graves' thyroiditis, because interferon-gamma (IFN-gamma) induces class II expression on thyrocytes, and thyrocytes expressing class II antigens present their autoantigens to T cells cloned from thyroid tissue of Graves' disease patients. These results led us to consider whether the same mechanisms operate in other autoimmune diseases. In investigations into class II induction in other cell types we found that IFN-gamma is not the only regulator of HLA class II expression and that synergy exists among mediators regulating class II differentially on different cell types. This concept makes it possible to envisage selective diminution of class II antigens on target tissues without loss of class II on antigen-presenting cells. The study of mediators regulating class II expression on cells in vitro led us to ask whether the appropriate regulator molecules are important in disease states. To investigate this question we have developed the use of cDNA probes to analyse the expression of lymphokines, other cytokines, and receptors in small local biopsy samples of tissue from patients with autoimmune diseases. Results obtained so far indicate that mRNAs for many lymphokines are present in synovial fluid cell samples from patients with rheumatoid arthritis.
Hemophilia A Mutations within the Factor VIII A2-A3 Subunit Interface Destabilize Factor VIIIa and Cause One-stage/ Two-stage Activity Discrepancy (2002)

Thrombin-activated factor VIII (FVIIIa) is a heterotrimer with the A2 subunit in a weak ionic interaction with the A1 and A3-C1-C2 subunits. Dissociation of the A2 subunit correlates with inactivation of FVIIIa. A homology model (Blood 89:2413, 1997) of the triplicated A domains of factor VIII (FVIII) predicts a pseudo-threefold axis at the tightly packed hydrophobic core with several interdomain interactions. These lie at the interface of A1-A2, A2-A3 and A1-A3. We have previously demonstrated that hemophilia A mutations (R531H, A284E, S289L) within the predicted A1-A2 and A1-A3 interface disrupt potential intersubunit hydrogen bonds and have the molecular phenotype of increased rate of inactivation of FVIIIa due to increased rate of A2 subunit dissociation. Patients with these mutations exhibit a clinical phenotype where the FVIII activity by one-stage(1-st) assay is at least two-fold higher than by two-stage(2-st) assay. We have now also explored mutations within the predicted A2-A3 interface (N694I, R698W and R698L) that also have the phenotype of 1-st/2-st activity discrepancy. These mutations exhibit the same molecular mechanism of increased instability of FVIIIa as those mutations described along the A1-A2 and A1-A3 interfaces. This suggests that the entire tightly packed hydrophobic core within the predicted pseudo-threefold axis contributes to stabilization of FVIIIa.
Simultaneous coherent anti-Stokes Raman scattering and two-dimensional laser Rayleigh thermometry in a contained technical swirl combustor (1995)

The simultaneous application of vibrational coherent anti-Stokes Raman scattering (CARS) and the two-dimensional (2D) UV laser Rayleigh technique is reported for the investigation of a highly turbulent swirl frame inside a contained technical combustor. The CARS technique has been used to determine accurate temperature values at one point within the 2D Rayleigh-probed combustion field. These values were necessary to normalize the Rayleigh data to overcome influences of absorption effects along the detection path of the Rayleigh-scattered light through the exhaust gas volume and by the sealing window of the combustion chamber. At several different downstream positions, 500 simultaneous measurements with the point and with the 2D technique were performed to cover the whole combustion field. These data can be used for both the evaluation of 2D temperature structures in single frames and for the calculation of temperature probability density functions from the Rayleigh data at one single camera pixel over 500 frames. With this information, characterization of a highly turbulent flame is possible.
Thalidomide metabolites in mice and patients with multiple myeloma. (2003)

This research examines the profile of metabolites of thalidomide that are formed in refractory multiple myeloma patients undergoing thalidomide therapy in comparison with those that are detected in healthy mice.Urine or plasma samples from patients during thalidomide therapy (100-400 mg daily), or from mice treated i.p. (100 mg/kg) or p.o. with thalidomide (50 mg/kg) were analyzed using liquid chromatography-mass spectrometry. Metabolites in each of the peaks observed in the UV- and mass spectrometry-detected high-performance liquid chromatography traces were identified by comparison of retention times and spectra with those of authentic standards.Plasma and urine samples from mice 4 h after treatment with thalidomide contained eight major metabolites formed by hydroxylation and/or hydrolysis of thalidomide. In contrast, urine samples from seven multiple myeloma patients at steady state levels of thalidomide therapy showed the presence of only three hydrolysis breakdown products and no hydroxylated metabolites.Our results show that thalidomide metabolite profiles in multiple myeloma patients differ considerably from those in mice. The lack of measurable hydroxylated metabolites in urine and in 1 case plasma of these patients suggests that such metabolites are not responsible for the therapeutic effects of thalidomide in multiple myeloma. We suggest that thalidomide may act directly, down-regulating growth factors essential for multiple myeloma growth.
Efficient substitutes for subdivision surfaces (2009)

Subdivision surfaces provide a compact representation for smooth surfaces that facilitate modeling and animation. They have widespread application in the movie industry, and there's a natural desire to use them also in real-time applications. This course presents theoretical results, implementations, applications, and future research directions. Topics include an introduction to subdivision surfaces, an overview of the surface-evaluation algorithms that are suitable for real-time rendering, implementation of those algorithms on current and next-generation GPUs, and other practical considerations. The course concludes with a section on practical application of these theoretical schemes and GPU implementations to Valve's source game engine and ILM's film production.
LAG3’s Enigmatic Mechanism of Action (2021)

LAG3 is an important immune checkpoint with relevance in cancer, infectious disease and autoimmunity. However, despite LAG3's role in immune exhaustion and the great potential of LAG3 inhibition as treatment, much remains unknown about its biology, particularly its mechanism of action. This review describes the knowns, unknowns and controversies surrounding LAG3. This includes examination of how LAG3 is regulated transcriptionally and post-translationally by endocytosis and proteolytic cleavage. We also discuss the interactions of LAG3 with its ligands and the purpose thereof. Finally, we review LAG3's mechanism of action, including the roles of LAG3 intracellular motifs and the lack of a role for CD4 competition. Overall, understanding the biology of LAG3 can provide greater insight on LAG3 function, which may broaden the appreciation for LAG3's role in disease and potentially aid in the development of targeted therapies.
Decreased levels of soluble amyloid β‐protein precursor are associated with Alzheimer's disease in concordant and discordant monozygous twin pairs (1994)

Abstract We conducted immunochemical measurements of soluble amyloid β‐protein precursor (βPP) in cerebrospinal fluid (CSF) from three monozygous twin pairs. Two of the twin pairs are discordant for Alzheimer's disease and one pair showed concordance for Alzheimer's disease, which was confirmed neuropathologically. All affected individuals displayed substantially lower levels of soluble βPP in CSF compared with the unaffected individuals. There were no differences in total protein levels in CSF samples from the affected twins compared with those of the unaffected twins. These studies suggest that decreased soluble βPP in CSF may reflect neuropathological processes in Alzheimer's disease involving βPP.
Biochemical properties of the human guanylate binding protein 5 and a tumor‐speciﬁc truncated splice variant (2010)

The human guanylate binding protein 5 (hGBP5) belongs to the family of interferon-gamma-inducible large GTPases, which are well known for their high induction by pro-inflammatory cytokines. The cellular role of this protein family is unclear at this point, but there are indications for antiviral and antibacterial activity of hGBP1. hGBP5 exists in three splice variants, forming two different proteins, of which the tumor-specific one is C-terminally truncated by 97 amino acids, and therefore lacks the CaaX motif for geranylgeranylation. Here we present biochemical data on the splice variants of hGBP5. We show that, unlike hGBP1, hGBP5a/b and hGBP5ta do not bind GMP or produce any GMP during hydrolysis despite the fact the residues involved in GMP production from hGBP1 are conserved in hGBP5. Hydrolysis of GTP is concentration-dependent and shows weak self-activation. Thermodynamic studies showed strongly negative entropic changes during nucleotide binding, which re fl ect structural ordering in the protein during nucleotide binding. These structural changes were also observed during changes in the oligomerization state. We observed only a minor in fluence of the C-terminal truncation on hydrolysis, nucleotide binding and oligomerization of hGBP5. Based on these similarities we speculate that the missing C-terminal part, which also carries the geranylgeranylation motif, is the reason for the dysregulation of hGBP5's function in lymphoma cells.
A 30-ps jitter, 3.6-μs locking, 3.3-volt digital PLL for CMOS gate arrays (2002)

A 3.3-V digital phase-locked loop (DPLL) with a 30-ps jitter resolution and 3.6-/spl mu/s locking time has been developed to support a 0.65-/spl mu/m CMOS gate array. The innovative DPLL features dual-mode automatic control logic for coarse and fine locking, and autorecovery circuitry to compensate for locking failure due to substantial system clock drift, and a nominal 200-/spl mu/W power dissipation. Multiple DPLLs can be utilized in each gate array to support system clocks of above 100 MHz. Low-power operation is accomplished with no DC-current-consuming circuitry, in order to better serve portable applications. Multiple high-resolution DPLL instances are allowed on virtually any spot of the die, and support either 3.3-V or 5-V operation. System reliability is enhanced by the implementation of the autorecovery circuitry which monitors the high-resolution DPLL for faults caused by poor system and environmental control.
Link adaptation strategy for IEEE 802.11 WLAN via received signal strength measurement (2004)

IEEE 802.11 wireless local area network (WLAN) physical layers (PHYs) support multiple transmission rates. The PHY rate to be used for a particular frame transmission is solely determined by the transmitting station. The transmitting rate should be chosen in an adaptive manner since the wireless channel condition varies over time due to such factors as station mobility, time-varying interference, and location-dependent errors. In this paper, we present a novel link adaptation algorithm, which aims to improve the system throughput by adapting the transmission rate to the current link condition. Our algorithm is simply based on the received signal strength measured from the received frames, and hence it does not require any changes in the current IEEE 802.11 WLAN medium access control (MAC) protocol. Based on the simulation and its comparison with a numerical analysis, it is shown that the proposed algorithm closely approximates the ideal case with the perfect knowledge about the channel and receiver conditions.
Theory of structured cogitation in speech recognition (1999)

This paper describes a task oriented, mixed initiative dialog manager. To perform a task according to a user's request, the dialog manager needs many pieces of information. It may have to query the user for missing information, clarify ambiguous information, inherit information from context, and con rm information before performing critical tasks. We describe a form-based framework for freeow dialog management that deals with these issues. Here, a form corresponds to a speci c task in the domain. To allow users to address any task any time, the dialog manager determines the best form that corresponds to the user's intention on every turn. Our dialog manager associates a score to each form as a measure of matching between the form and the user's input. Then the best scoring form corresponds to user's intention.
Protective Effect of Clusterin from Oxidative Stress–Induced Apoptosis in Human Retinal Pigment Epithelial Cells (2010)

Purpose.: Oxidative stress to retinal pigment epithelial (RPE) cells is thought to play a critical role in the pathogenesis of age-related macular degeneration (AMD). This study was conducted to investigate whether clusterin protects human RPE cells from ROS-induced apoptosis through a PI3K/Akt survival pathway. Methods.: The preventive effect of clusterin on reactive oxygen species (ROS) production and RPE cell death induced by hydrogen peroxide was determined in ARPE-19 cells. The ability of clusterin to protect RPE cells against ROS-mediated apoptosis was assessed by caspase-3 activity and DAPI staining. Furthermore, the protective effect of clusterin via the PI3K/Akt pathway was determined by Western blot analysis. Results.: Clusterin prevented ARPE-19 cells from H2O2-induced cell death and ROS production. H2O2-induced oxidative stress increased caspase-3 activity, which was significantly inhibited by clusterin, as determined by the abrogation of apoptotic bodies. Interestingly, clusterin induced Akt phosphorylation in human RPE cells under oxidative stress, which contributed to cell viability in ARPE-19 cells. This cell survival by clusterin was blocked by a PI3K inhibitor. Conclusions.: Clusterin may play a protective role in responding to the local redox environment of human RPE cells, which contributes to the cell survival via the PI3K/Akt pathway. Therefore, clusterin could be considered for the preventive approach to AMD.
Brain tumours: incidence, survival, and aetiology (2004)

he term ''brain tumours'' refers to a mixed group of neoplasms originating from intracranial tissues and the meninges with degrees of malignancy ranging from benign to aggressive. Each type of tumour has its own biology, treatment, and prognosis and each is likely to be caused by different risk factors. Even ''benign'' tumours can be lethal due to their site in the brain, their ability to infiltrate locally, and their propensity to transform to malignancy. This makes the classification of brain tumours a difficult science and creates problems in describing the epidemiology of these conditions. Public perception generally fails to distinguish between different tumour subtypes and although treatments and prognosis may vary, the functional neurological consequences are frequently similar. This article will give an overview of the burden of brain tumours in the population, looking at the major subtypes where possible, in addition to giving a summary of current views on possible causes.
Reversal of Subarachnoid Hemorrhage-induced Vasoconstriction with an Endothelin Receptor Antagonist (1994)

Increased concentrations of the vasoconstrictor endothelin have recently been demonstrated in the cerebrospinal fluid after subarachnoid hemorrhage (SAH). This observation is consistent with the hypothesis that SAH-induced vasopasm is mediated in part by enhanced constriction due to endothelin. To investigate the issue, an endothelin receptor antagonist (ETant), cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp), was tested for its ability to reverse vasoconstriction after SAH. A transclival surgical approach to the basilar artery in rabbits was used, and the arterial diameter was measured continuously by videomicroscopy. Rabbits were divided randomly into six groups: 1) normal rabbits treated with 40 nmol/L ETant only; 2) normal rabbits treated with 50 mmol/L KCl, then 50 mmol/L KCl + 40 nmol/L ETant; 3) normal rabbits treated with 20 nmol/L endothelin-1 (ET-1), then 20 nmol/L ET-1 + 40 nmol/L ETant; 4) rabbits treated with 20 nmol/L ET-1 only; 5) rabbits subjected to SAH and treated with 40 nmol/L ETant; and 6) rabbits subjected to SAH and treated with artificial cerebrospinal fluid only. In normal (non-SAH) rabbits, ETant: 1) had little or no effect on resting tone; 2) did not reverse potassium-induced constrictions; and 3) substantially reversed endothelin-induced constrictions. The diameter of normal rabbit basilar arteries was 832.1 +/- 20.0 microns (mean +/- standard error). After SAH (double hemorrhage model), the mean diameter was 517.4 +/- 18.3 microns. The addition of ETant reversed this SAH-induced constriction by 70.7%.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative studies on the transplantability of murine and human tumors into the brain and subcutaneous tissues of NCr/Sed nude mice. (1988)

The transplantability of experimental tumors into the brain (i.c.) and s.c. tissues of C3Hf/Sed and athymic NCr/Sed nude mice was examined using quantitative cell transplantation assays. Studies using the immune-competent C3H animals showed that brain is a more favorable site for the transplantation of syngeneic tumor than s.c. tissue and that this is true for nonimmunogenic as well as immunogenic tumors. The capacity of the brain to act as an immunological sanctuary can be overwhelmed by a strong, systemic, secondary immune response such as that evoked by the methylcholanthrene-induced sarcoma FSal. In studies performed using NCr/Sed nude mice, the allogeneic tumor MCaIV was found not to be demonstrably immunogenic. The cell dose required to transplant the tumor into 50% of recipients (TD50) could neither be increased by immunization procedures nor decreased by six Gy whole-body irradiation (WBI) prior to transplantation. Delayed-type hypersensitivity to this tumor was not expressed by nude mice after rechallenge with tumor antigen. The TD50 was again lower for i.c. than s.c. transplantation and the ratio s.c./i.c. was comparable to that found in syngeneic C3Hf/Sed hosts. Three human tumors have been similarly tested. They were: FaDu, a pharyngeal squamous carcinoma; HFSal, a fibrosarcoma; and U87, a malignant glioma. s.c. TD50 values were in all cases significantly higher than those obtained i.c. The ratios TD50 s.c./i.c. ranged from 6.4 to greater than 50 in five studies, substantially higher than those found for transplantation of murine tumors into either the syngeneic or the allogeneic recipients. Six Gy WBI reduced the s.c. TD50 for these tumors, but in each case the value remained significantly higher than that obtained i.c. 19.4 Gy WBI given in 10 equal fractions and followed by i.v. bone marrow rescue reduced further the s.c. TD50 for FaDu. NCr/Sed nude mice demonstrated cross-reacting delayed-type hypersensitivity against FaDu and HFSal. A small proportion of FaDu tumors (less than 2%) displayed a spontaneous halt in growth or even regression. When the host cell infiltrate of these tumors was analyzed, an increase was seen in the proportion of Thy 1.2 and asialo-GM1-positive cells as compared with progressively growing tumors. These data strongly suggest that a residual low level of immune reactivity exists in nude mice against xenotransplanted human tumors. This resistance to s.c. transplantation may be diminished by WBI and is less for intracerebral implantation.
The Growth and Aggressive Behavior of Human Osteosarcoma Is Regulated by a CaMKII-Controlled Autocrine VEGF Signaling Mechanism (2015)

Osteosarcoma (OS) is a hyperproliferative malignant tumor that requires a high vascular density to maintain its large volume. Vascular Endothelial Growth Factor (VEGF) plays a crucial role in angiogenesis and acts as a paracrine and autocrine agent affecting both endothelial and tumor cells. The alpha-Ca2+/Calmodulin kinase two (α-CaMKII) protein is an important regulator of OS growth. Here, we investigate the role of α-CaMKII-induced VEGF in the growth and tumorigenicity of OS. We show that the pharmacologic and genetic inhibition of α-CaMKII results in decreases in VEGF gene expression (50%) and protein secretion (55%), while α- CaMKII overexpression increases VEGF gene expression (250%) and protein secretion (1,200%). We show that aggressive OS cells (143B) express high levels of VEGF receptor 2 (VEGFR-2) and respond to exogenous VEGF (100nm) by increasing intracellular calcium (30%). This response is ameliorated by the VEGFR inhibitor CBO-P11, suggesting that secreted VEGF results in autocrine stimulated α-CaMKII activation. Furthermore, we show that VEGF and α-CaMKII inhibition decreases the transactivation of the HIF-1α and AP-1 reporter constructs. Additionally, chromatin immunoprecipitation assay shows significantly decreased binding of HIF-1α and AP-1 to their responsive elements in the VEGF promoter. These data suggest that α-CaMKII regulates VEGF transcription by controlling HIF-1α and AP-1 transcriptional activities. Finally, CBO-P11, KN-93 (CaMKII inhibitor) and combination therapy significantly reduced tumor burden in vivo. Our results suggest that VEGF-induced OS tumor growth is controlled by CaMKII and dual therapy by CaMKII and VEGF inhibitors could be a promising therapy against this devastating adolescent disease.