gebhart/patrepeval huggingface dataset:
A unique three-dimensional model for evaluating the impact of therapy on multiple myeloma (2008)

Although the in vitro expansion of the multiple myeloma (MM) clone has been unsuccessful, in a novel three-dimensional (3-D) culture model of reconstructed bone marrow (BM, n = 48) and mobilized blood autografts (n = 14) presented here, the entire MM clone proliferates and undergoes up to 17-fold expansion of malignant cells harboring the clonotypic IgH VDJ and characteristic chromosomal rearrangements. In this system, MM clone expands in a reconstructed microenvironment that is ideally suited for testing specificity of anti-MM therapeutics. In the 3-D model, melphalan and bortezomib had distinct targets, with melphalan targeting the hematopoietic, but not stromal com-partment. Bortezomib targeted only CD138(+)CD56(+) MM plasma cells. The localization of nonproliferating cells to the reconstructed endosteum, in contact with N-cadherin-positive stroma, suggested the presence of MM-cancer stem cells. These drug-resistant CD20(+) cells were enriched more than 10-fold by melphalan treatment, exhibited self-renewal, and generated clonotypic B and plasma cell progeny in colony forming unit assays. This is the first molecularly verified demonstration of proliferation in vitro by ex vivo MM cells. The 3-D culture provides a novel biologically relevant preclinical model for evaluating therapeutic vulnerabilities of all compartments of the MM clone, including presumptive drug-resistant MM stem cells.
Thin Diblock Copolymer Films on Chemically Heterogeneous Surfaces (1997)

We have used scanning force microscopy and transmission electron microscopy to study the microphase separation of P(S-b-2VP) block copolymers on chemically structured substrates. Gold was patterned by microcontact printing to form regions of self-assembled alkyl monolayers terminated by −CH3 or −OH. The differences in surface and interfacial energies between the coexisting phases and the boundary surfaces strongly influence the resulting domain structure. We find that excess material accumulates only on layers formed above the H3C-terminated SAM. For this to happen, single block copolymer molecules diffuse over distances of several micrometers. TEM investigations reveal that the block copolymer is well ordered into lamellae parallel to the substrate over the HO-terminated SAM but that the block copolymer layers on the H3C-terminated SAM are frequently oriented perpendicular to the substrate. This perpendicular orientation could decrease the edge free energy of the islands that form on this layer.
Watermarking digital images for copyright protection (1996)

A watermark is an invisible mark placed on an image that is designed to identify both the source of an image as well as its intended recipient. The authors present an overview of watermarking techniques and demonstrate a solution to one of the key problems in image watermarking, namely how to hide robust invisible labels inside grey scale or colour digital images.
Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: mechanism of cell death (2002)

Nutrient deprivation has been shown to cause cancer cell death. To exploit nutrient deprivation as anti-cancer therapy, we investigated the effects of the anti-metabolite 2-deoxy-D-glucose on breast cancer cells in vitro. This compound has been shown to inhibit glucose metabolism. Treatment of human breast cancer cell lines with 2-deoxy-D-glucose results in cessation of cell growth in a dose dependent manner. Cell viability as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide conversion assay and clonogenic survival are decreased with 2-deoxy-D-glucose treatment indicating that 2-deoxy-D-glucose causes breast cancer cell death. The cell death induced by 2-deoxy-D-glucose was found to be due to apoptosis as demonstrated by induction of caspase 3 activity and cleavage of poly (ADP-ribose) polymerase. Breast cancer cells treated with 2-deoxy-D-glucose express higher levels of Glut1 transporter protein as measured by Western blot analysis and have increased glucose uptake compared to non-treated breast cancer cells. From these results we conclude that 2-deoxy-D-glucose treatment causes death in human breast cancer cell lines by the activation of the apoptotic pathway. Our data suggest that breast cancer cells treated with 2-deoxy-D-glucose accelerate their own demise by initially expressing high levels of glucose transporter protein, which allows increased uptake of 2-deoxy-D-glucose, and subsequent induction of cell death. These data support the targeting of glucose metabolism as a site for chemotherapeutic intervention by agents such as 2-deoxy-D-glucose.
Reversible interconversion of carbon dioxide and formate by an electroactive enzyme (2008)

Carbon dioxide (CO(2)) is a kinetically and thermodynamically stable molecule. It is easily formed by the oxidation of organic molecules, during combustion or respiration, but is difficult to reduce. The production of reduced carbon compounds from CO(2) is an attractive proposition, because carbon-neutral energy sources could be used to generate fuel resources and sequester CO(2) from the atmosphere. However, available methods for the electrochemical reduction of CO(2) require excessive overpotentials (are energetically wasteful) and produce mixtures of products. Here, we show that a tungsten-containing formate dehydrogenase enzyme (FDH1) adsorbed to an electrode surface catalyzes the efficient electrochemical reduction of CO(2) to formate. Electrocatalysis by FDH1 is thermodynamically reversible--only small overpotentials are required, and the point of zero net catalytic current defines the reduction potential. It occurs under thoroughly mild conditions, and formate is the only product. Both as a homogeneous catalyst and on the electrode, FDH1 catalyzes CO(2) reduction with a rate more than two orders of magnitude faster than that of any known catalyst for the same reaction. Formate oxidation is more than five times faster than CO(2) reduction. Thermodynamically, formate and hydrogen are oxidized at similar potentials, so formate is a viable energy source in its own right as well as an industrially important feedstock and a stable intermediate in the conversion of CO(2) to methanol and methane. FDH1 demonstrates the feasibility of interconverting CO(2) and formate electrochemically, and it is a template for the development of robust synthetic catalysts suitable for practical applications.
Breastfeeding and the Use of Human Milk (2005)

Breastfeeding and human milk are the normative standards for infant feeding and nutrition. Given the documented short- and long-term medical and neurodevelopmental advantages of breastfeeding, infant nutrition should be considered a public health issue and not only a lifestyle choice. The American Academy of Pediatrics reaffirms its recommendation of exclusive breastfeeding for about 6 months, followed by continued breastfeeding as complementary foods are introduced, with continuation of breastfeeding for 1 year or longer as mutually desired by mother and infant. Medical contraindications to breastfeeding are rare. Infant growth should be monitored with the World Health Organization (WHO) Growth Curve Standards to avoid mislabeling infants as underweight or failing to thrive. Hospital routines to encourage and support the initiation and sustaining of exclusive breastfeeding should be based on the American Academy of Pediatrics-endorsed WHO/UNICEF "Ten Steps to Successful Breastfeeding." National strategies supported by the US Surgeon General's Call to Action, the Centers for Disease Control and Prevention, and The Joint Commission are involved to facilitate breastfeeding practices in US hospitals and communities. Pediatricians play a critical role in their practices and communities as advocates of breastfeeding and thus should be knowledgeable about the health risks of not breastfeeding, the economic benefits to society of breastfeeding, and the techniques for managing and supporting the breastfeeding dyad. The "Business Case for Breastfeeding" details how mothers can maintain lactation in the workplace and the benefits to employers who facilitate this practice.
Improved radiance gradient computation (2005)

We describe a new and accurate algorithm for computing translational gradients of incoming radiance in the context of a ray tracing-based global illumination solution. The gradient characterizes how the incoming directional radiance function changes with displacement on a surface. We use the gradient for a smoother radiance interpolation over glossy surfaces in the framework of the radiance caching algorithm. The proposed algorithm generalizes the irradiance gradient computation by [Ward and Heckbert 1992] to allow its use for non-diffuse, glossy, surfaces. Compared to previous method for radiance gradient computation, the new algorithm yields better gradient estimates in the presence of significant occlusion changes in the sampled environment, allowing a smoother indirect illumination interpolation.
Molecular Differentiation of Bacillus spp. Antagonistic Against Phytopathogenic Fungi Causing Damping-off Disease (2004)

Gram-positive antagonistic bacilli were isolated from agricultural soils for possible use in biocontrol of plant pathogenic fungi, Fusarium oxysporum, Rhizoctonia solani, and/or Pythium ultimum. Among the 65 antagonistic Gram-positive soil isolates, 22 strains were identified as Bacillus species by 16S rDNA sequence analyses. Four strains, including DF14, especially exhibited multiple antagonistic properties against the three damping-off fungi. Genotypic properties of the Bacillus isolates were characterized by rapid molecular fingerprinting methods using repetitive extragenic palindromic-PCR (REP-PCR), ribosomal intergenic spacer-length polymorphisms (RIS-LP), 16S rDNA PCR-restriction fragment length polymorphisms (PCR-RFLP), and strain-specific PCR assays. The results indicated that the REP-PCR method was more valuable than the RIS-LP and 16S rDNA PCR-RFLP analyses as a rapid and reliable approach for bacilli typing and identification. The use of strain-specific primers designed based on 16S rDNA sequence comparisons enabled it to be possible to selectively detect a strain, DF14, which is being used as a biocontrol agent against damping-off fungi.
Wnt signaling determines ventral spinal cord cell fates in a time-dependent manner (2008)

The identity of distinct cell types in the ventral neural tube is generally believed to be specified by sonic hedgehog (Shh) in a concentration-dependent manner. However, recent studies have questioned whether Shh is the sole signaling molecule determining ventral neuronal cell fates. Here we provide evidence that canonical Wnt signaling is involved in the generation of different cell types in the ventral spinal cord. We show that Wnt signaling is active in the mouse ventral spinal cord at the time when ventral cell types are specified. Furthermore, using an approach that stabilizes beta-catenin protein in small patches of ventral spinal cord cells at different stages, we show that Wnt signaling activates different subsets of target genes depending on the time when Wnt signaling is amplified. Moreover, disruption of Wnt signaling results in the expansion of ventrally located progenitors. Finally, we show genetically that Wnt signaling interacts with Hh signaling at least in part through regulating the transcription of Gli3. Our results reveal a novel mechanism by which ventral patterning is achieved through a coordination of Wnt and Shh signaling.
Preclinical Evidence That PD1 Blockade Cooperates with Cancer Vaccine TEGVAX to Elicit Regression of Established Tumors (2014)

Biomarker studies have shown that expression of the T-cell coregulatory ligand PDL1 on tumor cells correlates with clinical responsiveness to the PD1 antibody nivolumab. Here, we report the findings of a preclinical cancer vaccine study demonstrating vaccine-dependent PDL1 upregulation in the tumor microenvironment. We formulated an IFNγ-inducing cancer vaccine called TEGVAX that combined GM-CSF and multiple Toll-like receptor agonists to increase the number of activated dendritic cells. Treatment of established tumors with TEGVAX retarded tumor growth in a manner associated with enhanced systemic antitumor immunity. Unexpectedly, TEGVAX also upregulated PDL1 expression in the tumor microenvironment, possibly explaining why tumors were not eliminated completely. In support of this likelihood, PDL1 upregulation in this setting relied upon IFNγ-expressing tumor-infiltrating CD4(+) and CD8(+) T cells and administration of a PD1-blocking antibody with TEGVAX elicited complete regression of established tumors. Taken together, our findings provide a mechanistic rationale to combine IFNγ-inducing cancer vaccines with immune checkpoint blockade.
bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia (1993)

The bcl-2 gene becomes transcriptionally deregulated in the majority of low-grade non-Hodgkin lymphomas as a result of t(14;18) translocations that place the bcl-2 gene at 18q21 into juxtaposition with the Ig heavy-chain locus at 14q32. This chromosomal translocation or similar bcl-2 gene rearrangements involving the Ig light-chain genes have been reported to occur in some cases of B-cell chronic lymphocytic leukemia (B-CLL). We analyzed the structure, methylation, and expression of the bcl-2 gene in 20 cases of B-CLL or closely related variants of this lymphoproliferative disorder, including at least 16 typical examples of CD5+ B-CLL. None of the 20 specimens had evidence of bcl-2 gene rearrangements, based on Southern blot analysis using three different bcl-2 probes. However, immunoblot analysis using antibodies specific for the Bcl-2 protein showed that 14 of 20 cases (70%) contained levels of p26-Bcl-2 that were equal to or greater than those found in a t(14;18)-bearing lymphoma cell line. Furthermore, in 19 of 20 cases (95%), the Bcl-2 protein was present at levels that were 1.7- to 25-fold higher than in normal peripheral blood lymphocytes. These differences in the relative levels of Bcl-2 protein among cases of B-CLL appeared to be functionally significant, in that a preliminary analysis of 3 representative cases showed that CLL cells with higher levels of Bcl-2 protein survived longer in culture and were delayed in their onset of DNA degradation relative to CLL cells with lower Bcl-2 protein levels. Evaluation of the methylation status of the bcl-2 gene using the isoschizomers Msp I and Hpa II, and a probe corresponding to the first major exon of the gene showed complete demethylation of both copies of the bcl-2 gene in a region corresponding to a 2.4-kb Msp I fragment in all 20 cases of B-CLL. In contrast, analysis of 6 of 6 B-cell lines that harbor a t(14;18) was consistent with hypomethylation of only one of the two bcl-2 alleles. Neither copy of the bcl-2 gene was demethylated in this region in 5 of 5 lymphoid cell lines that lack this translocation. However, hypomethylation of the bcl-2 gene did not necessarily correlate with the relative levels of Bcl-2 protein present in the B-CLL cells, suggesting that additional mechanisms for regulating bcl-2 expression are involved.(ABSTRACT TRUNCATED AT 400 WORDS)
Identification of a MADS‐box gene, FLOWERING LOCUS M, that represses flowering (2001)

The timing of flowering is important for the reproductive success of plants. Here we describe the identification and characterization of a new MADS-box gene, FLOWERING LOCUS M (FLM), which is involved in the transition from vegetative to reproductive development. FLM is similar in amino-acid sequence to FLC, another MADS-box gene involved in flowering-time control. flm mutants are early flowering in both inductive and non-inductive photoperiods, and flowering time is sensitive to FLM dosage. FLM overexpression produces late-flowering plants. Thus FLM acts as an inhibitor of flowering. FLM is expressed in areas of cell division such as root and shoot apical regions and leaf primordia.
Evaluation of compiler optimizations for Fortran D on MIMD distributed memory machines (1992)

The Fortran D compiler uses data decomposition specifications to automatically translate Fortran programs for execution on MIMD distributed-memory machines. This paper introduces and classifies a number of advanced optimizations needed to achieve acceptable performance; they are analyzed and empirically evaluated for stencil computations. Profitability formulas are derived for each optimization. Results show that exploiting parallelism for pipelined computations, reductions, and scans is vital. Message vectorization, collective communication, and efficient coarse-grain pipelining also significantly affect performance.
THE ROTARY ELECTRORHEOLOGICAL EFFECT (1996)

The viscous response of electrorheological fluids is usually manipulated through the use of DC or uniaxial AC electric fields. The result is that fibrillated structures parallel to the field form in a quiescent fluid; the distortion of such structures in a flow determines the enhanced viscous response, at least at low and moderate flow rates. We have conducted preliminary studies of electrorheological response in a different field configuration-a rotating electric field. With respect to the uniaxial AC case, there are two new developments in this type of field. The structures formed are disk-like, in the plane of the rotating field. Furthermore, the structures rotate either with or against the field, depending on the dielectric or conductivity contrast with the surrounding fluid.
Role of Janus Kinase/Signal Transducers and Activators of Transcription in the Pathogenesis of Pancreatitis and Pancreatic Cancer (2012)

In the pathogenesis of pancreatitis, oxidative stress is involved in the activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and cytokine expression. High serum levels of cholecystokinin (CCK) have been reported in patients with acute pancreatitis, and treatment with cerulein, a CCK analogue, induces acute pancreatitis in a rodent model. Recent studies have shown that cerulein-activated nicotinamide adenine dinucleotide phosphate oxidase elicits reactive oxygen species, which trigger the phosphorylation of the JAK1, STAT1, and STAT3 proteins and induce the production of inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, in pancreatic acinar cells. The JAK/STAT pathway also stimulates cell proliferation and malignant transformation and inhibits apoptosis in the pancreas. This review discusses the possible role of the JAK/STAT pathway in the pathogenesis of pancreatitis and pancreatic cancer in response to oxidative stress.
Effect of tumour growth on the macrophage response to the antitumour agent 5,6-dimethylxanthenone-4-acetic acid. (1994)

Peritoneal macrophages from C3H/HeN mice bearing subcutaneous M-16/C or Spon-2 mammary carcinomas had enhanced tumouricidal activity over control macrophages from non-tumour bearers in response to 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA), a novel antitumour agent which has been scheduled for clinical evaluation. The effect of a palpable M-16/C tumour growing in C3H/HeN mice was similar to that of Bacillus Calmette-Guerin (BCG) infection, with macrophages being fully activated and tumouricidal without any further stimulus being required in culture. Macrophages from Spon-2 tumour bearing mice behaved like "primed" thioglycollate-elicited macrophages and produced a tumouricidal response to 5,6-MeXXA which was significantly higher than that obtained from resident peritoneal macrophages from non-tumour bearing mice. Resident and thioglycollate-elicited macrophages from C3H/HeJ mice were hyporesponsive not only to lipopolysaccharide (LPS), but to 5,6-MeXAA as well. Hyporesponsiveness was abrogated by BCG infection or by the presence of the M-16/C tumour, but not by the presence of the Spon-2 tumour. In response to LPS at low concentrations, or to 5,6-MeXAA at all concentrations, tumouricidal activity from macrophages from Spon-2-bearing C3H/HeJ mice was severely depressed compared with activity from their C3H/HeN counterparts. However, 5,6-MeXAA induced similar levels of haemorrhagic necrosis of tumours implanted in either C3H/HeJ or C3H/HeN hosts. LPS-induced haemorrhagic necrosis was significantly lower in C3H/HeJ than in C3H/HeN hosts. The results show that the presence of subcutaneous tumours modulates the activity of peritoneal macrophages in mice.
Incidence and Outcomes of Acute Lung Injury (2005)

Acute lung injury has a substantial impact on public health, with an incidence in the United States that is considerably higher than previous reports have suggested.
A layered approach for IN call modelling for the support of multimedia services in a B-ISDN environment (2002)

This paper deals with the integration between the intelligent network and the B-ISDN for the support of advanced multimedia services. The intelligent network (IN) introduces new capabilities for service provisioning and service handling. On the other hand, significant steps in the B-ISDN standardisation have been made, promoting an advanced signalling system to support multimedia services. These services call for new requirements and introduce more complexity on the control protocols. For these reasons, it is evident that an integration of these two architectures will be very useful for the realisation of a global network, service independent, flexible and efficient in resource utilisation. We investigate the different possibilities for an IN/B-ISDN interaction; in particular we propose a new architecture for the basic call state model and for the service switching function, in order to fully exploit the advantages introduced by B-ISDN signalling.
Decreased semaphorin 3A expression is associated with a poor prognosis in patients with epithelial ovarian carcinoma (2015)

Semaphorin 3A (SEMA3A) was initially identified to play an important role in axonal guidance. Recently, SEMA3A has also been considered as a candidate tumor suppressor, since it is often downregulated in numerous types of cancer, including prostate cancer, breast cancer and glioma. However, the biological role of SEMA3A in ovarian cancer is not clear. In the present study, the expression of SEMA3A in ovarian cancer and normal ovarian epithelial tissues was detected by immunofluorescence, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting, and the associations between the expression of SEMA3A with the development of ovarian cancer, clinicopathological characteristics and survival were also analyzed. Results from immunofluorescence, RT‑qPCR and western blotting showed that SEMA3A is significantly downregulated in epithelial ovarian carcinoma compared to normal ovarian epithelial specimens (P<0.05). The expression levels of SEMA3A were lower in the cancer tissues with III/IV stage [the International Federation of Gynecology and Obstetrics (FIGO) stage], poor histological grade, lymph node metastasis and distant metastasis compared to that in the cancer tissues with I/II stage (FIGO), well histological grade, or without lymph node metastasis and distant metastasis (P<0.05). A decreased expression of SEMA3A is associated with a poor prognosis (P<0.001). The present findings suggest that decreased SEMA3A expression may be associated with the development of epithelial ovarian carcinoma, and therefore, SEMA3A may be a valuable prognostic marker, as well as a potential molecular therapy target for ovarian cancer patients.