gebhart/patrepeval huggingface dataset:
The novel plant-derived agent silvestrol has B-cell selective activity in chronic lymphocytic leukemia and acute lymphoblastic leukemia in vitro and in vivo (2009)

Therapeutic options for advanced B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) are limited. Available treatments can also deplete T lymphocytes, leaving patients at risk of life-threatening infections. In the National Cancer Institute cell line screen, the structurally unique natural product silvestrol produces an unusual pattern of cytotoxicity that suggests activity in leukemia and selectivity for B cells. We investigated silvestrol efficacy using primary human B-leukemia cells, established B-leukemia cell lines, and animal models. In CLL cells, silvestrol LC(50) (concentration lethal to 50%) is 6.9 nM at 72 hours. At this concentration, there is no difference in sensitivity of cells from patients with or without the del(17p13.1) abnormality. In isolated cells and whole blood, silvestrol is more cytotoxic toward B cells than T cells. Silvestrol causes early reduction in Mcl-1 expression due to translational inhibition with subsequent mitochondrial damage, as evidenced by reactive oxygen species generation and membrane depolarization. In vivo, silvestrol causes significant B-cell reduction in Emu-Tcl-1 transgenic mice and significantly extends survival of 697 xenograft severe combined immunodeficient (SCID) mice without discernible toxicity. These data indicate silvestrol has efficacy against B cells in vitro and in vivo and identify translational inhibition as a potential therapeutic target in B-cell leukemias.
C19orf48 Encodes a Minor Histocompatibility Antigen Recognized by CD8+ Cytotoxic T Cells from Renal Cell Carcinoma Patients (2008)

Donor T-cell responses against the HLA-A*0201-restricted minor H antigen encoded by C19orf48 may contribute to RCC regression after MHC-matched allogeneic HCT.
The Changing Molecular Epidemiology of HIV Type 1 among Northern Thai Drug Users, 1999 to 2002 (2004)

CRF01_AE and subtype B have dominated the HIV-1 epidemic in Thailand since 1989. We reported a new circulating recombinant form of HIV-1, CRF15_01B, as well as other unique CRF01_AE/B recombinants among prevalent HIV infections in Thailand. We sought to study this challenging molecular picture through assessment of subtypes among recent HIV-1 seroconverters in northern Thai drug users. A total of 847 HIV-1 seronegative drug users (342 IDU and 505 non-IDU) were enrolled, from 1999 to 2002, in a prospective study; 39 HIV-1 incident cases were identified and characteristics were collected. The overall HIV-1 incidence rate was 2.54/100PY, but it was 10.0/100PY among male IDU. HIV was strongly associated with injection history; 38 of 39 seroconverters gave a history of IDU. A near full-length genome of HIV-1 was recovered by PCR amplification and sequenced from peripheral mononuclear cell extracted DNA of 38 seroconverters. Phylogenetic analysis revealed that 33 (86.8%) were CRF01_AE and 5 (13.2%) were CRF01_AE/B recombinants. These recombinants had different structure but shared some common breakpoints, indicating an ongoing recombination process. Recombinant infection increased with year of sampling (0 to 57.1%). The molecular epidemiology of HIV-1 among drug users in northern Thailand has thus entered a new era. CRF01_AE remains predominant while pure subtype B is becoming rare, and now a substantial component of the epidemic. These findings support the need for CRF01_AE and subtype B components in clade-matched vaccine strategies for Thai phase III trials. Ongoing molecular surveillance of circulating HIV-1 strains is imperative for the evaluation of HIV vaccine efficacy.
Differential Responses to CD40 Ligation Among Burkitt Lymphoma Lines That Are Uniformly Responsive to Epstein-Barr Virus Latent Membrane Protein 1 (1999)

Abstract Ligation of CD40 on the surface of B cells induces multiple phenotypic effects, many of which are mimicked by the EBV latent membrane protein 1 (LMP1) through its interaction with downstream components of the CD40 signaling pathway. Because the effects of LMP1 have been most closely studied in human Burkitt Lymphoma (BL) cell lines retaining a tumor biopsy-like phenotype in vitro, we have examined the response of a panel of such lines to CD40 ligation. Two distinct patterns of response were observed that were unrelated to the surface level of CD40 or to the EBV genome status of the lines. Following exposure to either CD40-specific mAbs or the soluble trimeric ligand (sCD40L), high responder (HR) lines showed rapid aggregation, activation of NF-κB, up-regulation of cell surface markers ICAM-1/CD54 and Fas/CD95, and growth inhibition. Aggregation was seen at lower doses than those required to elicit the other effects. By contrast, low responder (LR) lines showed no detectable response to CD40 mAbs, while their responses to sCD40L were limited to activation of NF-κB and up-regulation of CD95 only. However, in transfection experiments, LMP1 uniformly induced the full spectrum of phenotypic effects in both HR and LR lines. We conclude that some BL cell lines show a highly restricted response to CD40 ligation but remain fully susceptible to LMP1.
Activity of Lipases and Esterases towards Tertiary Alcohols: Insights into Structure���Function Relationships (2002)

A single amino acid pattern (GGG(A)X motif) in hydrolases controls their activity towards tertiary alcohols. Consequently, a range of active lipases and esterases which catalyze the efficient conversion of acetates of different tertiary alcohols (see scheme) and thereby facilitate access to this class of building blocks for organic synthesis, flavors, and fragrances was identified by sequence comparison. Hydrolases bearing an alternative GX motif were inactive. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z18885_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Model Fitting Using RANSAC for Surgical Tool Localization in 3-D Ultrasound Images (2010)

Ultrasound guidance is used for many surgical interventions such as biopsy and electrode insertion. We present a method to localize a thin surgical tool such as a biopsy needle or a microelectrode in a 3-D ultrasound image. The proposed method starts with thresholding and model fitting using random sample consensus for robust localization of the axis. Subsequent local optimization refines its position. Two different tool image models are presented: one is simple and fast and the second uses learned a priori information about the tool's voxel intensities and the background. Finally, the tip of the tool is localized by finding an intensity drop along the axis. The simulation study shows that our algorithm can localize the tool at nearly real-time speed, even using a MATLAB implementation, with accuracy better than 1 mm. In an experimental comparison with several alternative localization methods, our method appears to be the fastest and the most robust one. We also show the results on real 3-D ultrasound data from a PVA cryogel phantom, turkey breast, and breast biopsy.
Decreased Resting-State Connectivity between Neurocognitive Networks in Treatment Resistant Depression (2015)

Approximately one-third of patients with major depressive disorder (MDD) do not achieve remission after various treatment options and develop treatment resistant depression (TRD). So far, little is known about the pathophysiology of TRD. Studies in MDD patients showed aberrant functional connectivity (FC) of three "core" neurocognitive networks: the salience network (SN), cognitive control network (CCN), and default mode network (DMN). We used a cross-sectional design and performed resting-state FC MRI to assess connectivity of the SN, CCN, and both anterior and posterior DMN in 17 severe TRD, 18 non-TRD, and 18 healthy control (HC) subjects. Relative to both non-TRD and HC subjects, TRD patients showed decreased FC between the dorsolateral prefrontal cortex and angular gyrus, which suggests reduced FC between the CCN and DMN, and reduced FC between the medial prefrontal cortex and precuneus/cuneus, which suggests reduced FC between the anterior and posterior DMN. No significant differences in SN FC were observed. Our results suggest that TRD is characterized by a disturbance in neurocognitive networks relative to non-TRD and HC.
Control of Rho GTPase function by BAR-domains (2012)

Cytoskeletal dynamics are key to the establishment of cell polarity and the consequent coordination of protrusion and contraction that drives cell migration. During these events, the actin and microtubule cytoskeleton act in concert with the cellular machinery that controls endo-and exocytosis, thus regulating polarized traffic of membranes and membrane-associated proteins. Small GTPases of the Rho family orchestrate cytoskeletal dynamics. Rho GTPase signaling is tightly regulated and mislocalization or constitutive activation may lead to, for example, morphogenetic abnormalities, tumor cell metastasis or apoptosis. There is increasing evidence that traffic to and from the plasma membrane constitutes an important mechanism controlling Rho GTPase activation and signaling. This brief overview discusses a group of proteins that function at the interface between membrane dynamics and RhoGTPase signaling. These proteins all share a so-called BAR domain, which is a lipid and protein binding region that also harbors membrane deforming activity. In the past 15 years, a growing number of BAR domain proteins have been identified and found to regulate Rho GTPase signaling. The studies discussed here define several modes of RhoGTPase regulation through BAR-domain containing proteins, identifying the BAR domain as an important regulatory unit bridging membrane traffic and cytoskeletal dynamics.
RUNX1 positively regulates a cell adhesion and migration program in murine hemogenic endothelium prior to blood emergence (2014)

During ontogeny, the transcription factor RUNX1 governs the emergence of definitive hematopoietic cells from specialized endothelial cells called hemogenic endothelium (HE). The ultimate consequence of this endothelial-to-hematopoietic transition is the concomitant activation of the hematopoietic program and downregulation of the endothelial program. However, due to the rare and transient nature of the HE, little is known about the initial role of RUNX1 within this population. We, therefore, developed and implemented a highly sensitive DNA adenine methyltransferase identification-based methodology, including a novel data analysis pipeline, to map early RUNX1 transcriptional targets in HE cells. This novel transcription factor binding site identification protocol should be widely applicable to other low abundance cell types and factors. Integration of the RUNX1 binding profile with gene expression data revealed an unexpected early role for RUNX1 as a positive regulator of cell adhesion- and migration-associated genes within the HE. This suggests that RUNX1 orchestrates HE cell positioning and integration prior to the release of hematopoietic cells. Overall, our genome-wide analysis of the RUNX1 binding and transcriptional profile in the HE provides a novel comprehensive resource of target genes that will facilitate the precise dissection of the role of RUNX1 in early blood development.
Improving therapy options for patients with metastatic castrate-resistant prostate cancer (2014)

Metastatic castrate-resistant prostate cancer (mCRPC) is the second deadliest cancer in men in the Western world. Therapy options are limited, but expanding. In the current thesis, various aspects of (pre)clinical research are discussed, all sharing the ultimate aim to improve therapy options for this group of cancer patients. Both basic, translational, biomarker, clinical and epidemiological studies have been performed, focusing primarily on novel agents that have been introduced recently into clinical practice (cabazitaxel, abiraterone, radium-223), and agents that may become antitumor agents against mCRPC in the future, such as antimitotics (polo-like kinase 1 inhibitors, aurora kinase inhibitors, Eg5), histone deacetylase inhibitors, and agents that stimulate expression of the metastasis-suppressor gene NDRG1. Furthermore, minority enrollment in phase III studies with mCRPC patients is being evaluated.
A rapid mass spectrometric strategy for the characterization of N‐ and O‐glycan chains in the diagnosis of defects in glycan biosynthesis (2007)

Glycosylation of proteins is a very complex process which involves numerous factors such as enzymes or transporters. A defect in one of these factors in glycan biosynthetic pathways leads to dramatic disorders named congenital disorders of glycosylation (CDG). CDG can affect the biosynthesis of not only protein N-glycans but also O-glycans. The structural analysis of glycans on serum glycoproteins is essential to solving the defect. For this reason, we propose in this paper a strategy for the simultaneous characterization of both N- and O-glycan chains isolated from the serum glycoproteins. The serum (20 microL) is used for the characterization of N-glycans which are released by enzymatic digestion with PNGase F. O-glycans are chemically released by reductive elimination from whole serum glycoproteins using 10 microL of the serum. Using strategies based on mass spectrometric analysis, the structures of N- and O-glycan chains are defined. These strategies were applied on the sera from one patient with CDG type IIa, and one patient with a mild form of congenital disorder of glycosylation type II (CDG-II) that is caused by a deficiency in the Cog1 subunit of the complex.
Circulating Cytokine/Inhibitor Profiles Reshape the Understanding of the SIRS/CARS Continuum in Sepsis and Predict Mortality (2006)

Mortality in sepsis remains unacceptably high and attempts to modulate the inflammatory response failed to improve survival. Previous reports postulated that the sepsis-triggered immunological cascade is multimodal: initial systemic inflammatory response syndrome (SIRS; excessive pro-, but no/low anti-inflammatory plasma mediators), intermediate homeostasis with a mixed anti-inflammatory response syndrome (MARS; both pro- and anti-inflammatory mediators) and final compensatory anti-inflammatory response syndrome (CARS; excessive anti-, but no/low proinflammatory mediators). To verify this, we examined the evolution of the inflammatory response during the early phase of murine sepsis by repetitive blood sampling of septic animals. Increased plasma concentrations of proinflammatory (IL-6, TNF, IL-1beta, KC, MIP-2, MCP-1, and eotaxin) and anti-inflammatory (TNF soluble receptors, IL-10, IL-1 receptor antagonist) cytokines were observed in early deaths (days 1-5). These elevations occurred simultaneously for both the pro- and anti-inflammatory mediators. Plasma levels of IL-6 (26 ng/ml), TNF-alpha (12 ng/ml), KC (33 ng/ml), MIP-2 (14 ng/ml), IL-1 receptor antagonist (65 ng/ml), TNF soluble receptor I (3 ng/ml), and TNF soluble receptor II (14 ng/ml) accurately predicted mortality within 24 h. In contrast, these parameters were not elevated in either the late-deaths (day 6-28) or survivors. Surprisingly, either pro- or anti-inflammatory cytokines were also reliable in predicting mortality up to 48 h before outcome. These data demonstrate that the initial inflammatory response directly correlates to early but not late sepsis mortality. This multifaceted response questions the use of a simple proinflammatory cytokine measurement for classifying the inflammatory status during sepsis.
Single-Agent Monoclonal Antibody Efficacy in Bulky Non-Hodgkin's Lymphoma: Results of a Phase II Trial of Rituximab (1999)

PURPOSE: A phase II trial was performed to evaluate the safety and efficacy of rituximab, a chimeric anti-CD20 monoclonal antibody, in patients with bulky (&gt; 10-cm lesion) relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Thirty-one patients received intravenous infusions of rituximab 375 mg/m 2 weekly for four doses. All patients had at least one prior therapy (median, three; range, one to 13) and had progressive disease at study entry. Patients were a median of 4 years from diagnosis. RESULTS: No patient had treatment discontinued because of an adverse event. No patient developed human antichimeric antibody. The overall response rate in 28 assessable patients was 43% with a median time to progression of 8.1 months (range, 4.5 to 18.6+ months) and median duration of response of 5.9 months (range, 2.8 to 12.1+ months). The average decrease in lesion size in patients who achieved a partial response was 76%, and patients with stable disease had a decrease in average lesion size of 26%. Median serum antibody concentration was higher in responders compared with nonresponders, and a negative correlation was shown between antibody concentration and tumor bulk at baseline. CONCLUSION: Rituximab single-agent outpatient therapy is safe and shows significant clinical activity in patients with bulky relapsed or refractory low-grade or follicular B-cell NHL.
Similarity-based queries for time series data (1997)

We study a set of linear transformations on the Fourier series representation of a sequence that can be used as the basis for similarity queries on time-series data. We show that our set of transformations is rich enough to formulate operations such as moving average and time warping. We present a query processing algorithm that uses the underlying R-tree index of a multidimensional data set to answer similarity queries efficiently. Our experiments show that the performance of this algorithm is competitive to that of processing ordinary (exact match) queries using the index, and much faster than sequential scanning. We relate our transformations to the general framework for similarity queries of Jagadish et al.
From Genotypes to Genes: Doubling the Sample Size (1997)

This paper considers the analysis of genetic case-control data. One approach considers the allele frequency in cases and controls. Because each individual has two alleles at any autosomal locus, there will be twice as many alleles as people. Another approach considers the risk of the disease in those who do not have the allele of interest (A), those who have a single copy (heterozygous), and those who are homozygous for A. A third approach does not differentiate between individuals with one or two copies of A. This was common when alleles were determined serologically and one could not distinguish between homozygotes and those with one copy of A and one of an unknown allele. All three approaches have been used in the literature, but this is the first systematic comparison of them. The different interpretations of the odds ratios from such analyses are explored and conditions are given under which the first two approaches are asymptotically equivalent. The chi-squared statistics from the three approaches are discussed. Both the odds ratio and the chi-squared statistic from the analysis that treats alleles rather than genotypes as individual entities are appropriate only when the Hardy-Weinberg equilibrium holds. When the equilibrium holds, the allele-based test statistic is asymptotically equivalent to the test for trend using the genotype data. Thus, analyses that treat alleles rather than people as observations should not be used. Instead, we recommend that such data should be analyzed by genotype.
WD-40 Repeat Region Regulates Apaf-1 Self-association and Procaspase-9 Activation (1998)

The casp9 protein plays a critical role in apoptosis induced by a variety of death stimuli. A regulator of apoptosis, Apaf-1, binds to and activates pro-casp9 in the presence of cytochrome c and dATP, a requirement that is bypassed by deletion of the WD-40 repeats located in the C-terminal half of Apaf-1. In this report, we used constitutively active Apaf-1 mutant lacking the WD-40 repeat region to study the mechanism and regulation of pro-casp9 activation. Mutational analysis revealed that only a small portion of the CED-4 homologous region (residues 456-559) could be deleted without destroying the ability of Apaf-1-(1-559) to activate pro-casp9. Apaf-1 can self-associate to form oligomers. Disruption of Apaf-1 self-association by deletion (Delta109-559) or mutation of the P-loop region (K149R) abrogated Apaf-1-mediated pro-casp9 activation. Forced oligomerization of the caspase recruitment domain of Apaf-1 was sufficient for pro-casp9 activation. Dimerization of chimeric Fpk-pro-casp9 protein with the dimerizer drug FK1012 induced pro-casp9 processing and apoptosis in cells. Significantly, the C-terminal region containing WD-40 repeats interacted with its N-terminal CED-4 homologous region, as determined by immunoprecipitation experiments. Importantly, expression of the WD-40 repeat region inhibited Apaf-1 self-association and proteolytic activation of pro-casp9. These studies provide a mechanism by which Apaf-1 promotes autoactivation of pro-casp9 through Apaf-1 self-association, a process that is negatively regulated by the WD-40 repeats.
CARTILAGE OLIGOMERIC MATRIX PROTEIN: A NOVEL MARKER OF CARTILAGE TURNOVER DETECTABLE IN SYNOVIAL FLUID AND BLOOD (1992)

Cartilage oligomeric matrix protein (COMP) is a tissue specific non-collagenous matrix protein. We have developed an enzyme-linked immunosorbent assay for the detection of this protein in synovial fluid and serum. The protein has been quantified in these fluids in patients with rheumatoid arthritis (RA), reactive arthritis, juvenile chronic arthritis, osteoarthritis and in sera of control subjects. The protein was detectable in all fluids and the synovial fluid levels were always higher than in serum in paired samples. The highest knee joint synovial fluid levels were found in reactive arthritis patients and the lowest in RA patients with advanced destruction of the knee joint. However, the relative synovial fluid content of COMP was higher in these RA patients than in patients with advanced osteoarthritis. In patients with long-standing reactive synovitis the concentrations decreased. This decrease, however, was less marked than for proteoglycan concentrations. The serum concentrations were low in patients with juvenile chronic arthritis and in patients with RA with advanced cartilage destruction of the studied knee joint. In the other groups serum levels did not differ between groups or from controls.
Power laws, Pareto distributions and Zipf's law (2005)

When the probability of measuring a particular value of some quantity varies inversely as a power of that value, the quantity is said to follow a power law, also known variously as Zipf's law or the Pareto distribution. Power laws appear widely in physics, biology, earth and planetary sciences, economics and finance, computer science, demography and the social sciences. For instance, the distributions of the sizes of cities, earthquakes, solar flares, moon craters, wars and people's personal fortunes all appear to follow power laws. The origin of power-law behaviour has been a topic of debate in the scientific community for more than a century. Here we review some of the empirical evidence for the existence of power-law forms and the theories proposed to explain them.
Nanoscale Patterning and Electronics on Flexible Substrate by Direct Nanoimprinting of Metallic Nanoparticles (2008)

Nanoscale patterning and electronics fabrication on flexible polymer substrates via direct nanoimprinting of metal nanoparticles was demonstrated. The metal nanoparticle solution enables a simple one-step metal nanoimprinting with very low pressure and temperature. Electrical and structural characterizations on flexible substrate during cyclic bending deformations verify the robustness of the nanoimprinted structures to mechanical deformation conditions.