gebhart/patrepeval huggingface dataset:
Cancer vaccines: a critical review on clinical impact. (2004)

Developing cancer vaccines to treat solid tumors is not an easy task. As solid tumors develop, the immune system places cancer cells under selective pressure; it detects those that are more 'antigenically different', selecting those cells that are not recognized by the immune system and are therefore resistant to immune surveillance. Resistant cells survive, and in turn their clones will spread to distant sites. This phenomenon, called 'immune editing', is not novel, but is quite similar in principle to the selective pressure induced by chemotherapy and hormone therapy, and is molecularly based on the clonal heterogeneity and molecular instability present in most solid tumors. This explains, at least in part, why many cancer vaccines work in animal models but not in a clinical setting. The aim of this article is to review the most commonly used cancer vaccine strategies and to evaluate the evidence supporting their efficacy. This is not as easy at it may sound, as each research group involved in cancer vaccine development uses different technologies, targets different antigens, combines different carriers and adjuvants to obtain an immune response, and immunizes patients with different administration schedules. The final picture is somewhat confusing, and comparison of different vaccine strategies is almost impossible. Most of the vaccines are still experimental, far from being approved by regulatory authorities, and their clinical utility is almost negligible.
Unravelling the mysteries of virulence gene regulation in Salmonella typhimurium (2000)

Salmonella typhimurium, which causes gastroenteritis in calves and humans as well as a typhoid-like disease in mice, uses numerous virulence factors to infect its hosts. Genes encoding these factors are regulated by many environmental conditions and regulatory pathways in vitro. Many virulence genes are specifically induced at particular sites during infection or in cultured host cells. The complex regulation of virulence genes observed in vitro may be necessary to restrict their expression to specific locations within the host. In vitro and in vivo studies provide clues about how virulence genes might be regulated in vivo. Future studies must assess the actual environmental signals and regulators that modulate each virulence gene in vivo and determine how multiple regulatory pathways are integrated to co-ordinate the appropriate expression of virulence factors at specific sites in vivo.
High vaccination efficiency of low-affinity epitopes in antitumor immunotherapy (2004)

Most of the human tumor-associated antigens (TAAs) characterized thus far are derived from nonmutated "self"-proteins. Numerous strategies have been developed to break tolerance to TAAs, combining various forms of antigens with different vectors and adjuvants. However, no study has yet determined how to select epitopes within a given TAA to induce the highest antitumor effector response. We addressed this question by evaluating in HLA-A*0201-transgenic HHD mice the antitumor vaccination efficacy of high- and low-affinity epitopes from the naturally expressed murine telomerase reverse transcriptase (mTERT). Immunity against low-affinity epitopes was induced with heteroclitical variants. We show here that the CTL repertoire against high-affinity epitopes is partially tolerized, while that against low-affinity epitopes is composed of frequent CTLs with high avidity. The high-affinity p797 and p545 mTERT epitopes are not able to protect mice from a lethal challenge with the mTERT-expressing EL4-HHD tumor. In contrast, mice developing CTL responses against the p572 and p988 low-affinity epitopes exhibit potent antitumor immunity and no sign of autoimmune reactivity against TERT-expressing normal tissues. Our results strongly argue for new TAA epitope selection and modification strategies in antitumor immunotherapy applications in humans.
Applied Regression Analysis (2nd ed). (1981)

This book brings together a number of procedures developed for regression problems in current use. Since the emphasis is on practical application theoretical results are stated without proofs in many cases. This book provides a standard basic course in multiple linear regression but it also includes material that either has not previously appeared in a textbook or if it has appeared is not generally available. Chapters 1 and 3 together provide a course in fitting a straight line without using matrix algebra at all. If chapter 2 is added the idea of matrix representation of regression problems can be introduced as well. Chapter 4 covers 2 predictor variables and chapter 5 deals with more complicated models. Selecting the best regression equation is discussed in chapter 6. Chapter 7 covers specific problems. Chapters 8 and 9 discuss 1) multiple regression and mathematical model building and 2) multiple regression applied to analysis of variance problems. Chapter 10 contains an introduction to nonlinear estimation. The 2nd edition contains many new regression ideas and techniques. In particular new computational algorithms and new software regression packages have made it very easy to investigate the allequacy of conjectured models with many different techniques.
Transgenesis Techniques (1993)

Over the past twenty years, the disciplines of cellular and molecular biology have generated a bounty of information pertaining to the understanding of the structure and function of eukaryotic cells .
Dynamic On-Demand Virtual Extensible LAN Tunnels via Software-Defined Wide Area Networks (2022)

The world of information and communications technologies continues to evolve at an exponential rate, not only inaugurating numerous breakthroughs in research, but also changing the perception of interconnectivity and exchange of information. The increasing popularity of software-defined networks (SDN) and the related technologies have shattered the realm of corporate infrastructures. The traditional approach for employees to access the corporate headquarter data centers has experienced challenges due to the significant traffic volume and delay, as more services have been moved to the cloud, e.g., Software-as-a-Service (SaaS). Tunnel-splitting can mitigate the problem, but it is mostly static. The paper proposed a dynamic on-demand tunnels approach based on Extensible LAN Tunnels (VXLAN) and SDN. The primary objectives are to reduce the load on corporate network and delay for users to access SaaS. We conducted experiments for feasibility study using Mininet and the results showed that the delay could be significantly reduced and the approach allows for a single point of policy management, which it still preserved the benefit of split tunnels.
Anticancer &#945;-Helical Peptides and Structure / Function Relationships Underpinning Their Interactions with Tumour Cell Membranes (2006)

Cancer is a major cause of premature death and there is an urgent need for new anticancer agents with novel mechanisms of action. Here we review recent studies on a group of peptides that show much promise in this regard, exemplified by arthropod cecropins and amphibian magainins and aureins. These molecules are alpha-helical defence peptides, which show potent anticancer activity (alpha-ACPs) in addition to their established roles as antimicrobial factors and modulators of innate immune systems. Generally, alpha-ACPs exhibit selectivity for cancer and microbial cells primarily due to their elevated levels of negative membrane surface charge as compared to non-cancerous eukaryotic cells. The anticancer activity of alpha-ACPs normally occurs at micromolar levels but is not accompanied by significant levels of haemolysis or toxicity to other mammalian cells. Structure/function studies have established that architectural features of alpha-ACPs such as amphiphilicty levels and hydrophobic arc size are of major importance to the ability of these peptides to invade cancer cell membranes. In the vast majority of cases the mechanisms underlying such killing involves disruption of mitochondrial membrane integrity and/or that of the plasma membrane of the target tumour cells. Moreover, these mechanisms do not appear to proceed via receptor-mediated routes but are thought to be effected in most cases by the carpet/toroidal pore model and variants. Usually, these membrane interactions lead to loss of membrane integrity and cell death utilising apoptic and necrotic pathways. It is concluded that that alpha-ACPs are major contenders in the search for new anticancer drugs, underlined by the fact that a number of these peptides have been patented in this capacity.
NUP160–SLC43A3 Is a Novel Recurrent Fusion Oncogene in Angiosarcoma (2015)

Angiosarcoma is a malignant vascular tumor originating from endothelial cells of blood vessels or lymphatic vessels. The specific driver mutations in angiosarcoma remain unknown. In this study, we investigated this issue by transcriptome sequencing of patient-derived angiosarcoma cells (ISO-HAS), identifying a novel fusion gene NUP160-SLC43A3 found to be expressed in 9 of 25 human angiosarcoma specimens that were examined. In tumors harboring the fusion gene, the duration between the onset of symptoms and the first hospital visit was significantly shorter, suggesting more rapid tumor progression. Stable expression of the fusion gene in nontransformed human dermal microvascular endothelial cells elicited a gene-expression pattern mimicking ISO-HAS cells and increased cell proliferation, an effect traced in part to NUP160 truncation. Conversely, RNAi-mediated attenuation of NUP160 in ISO-HAS cells decreased cell number. Confirming the oncogenic effects of the fusion protein, subcutaneous implantation of NUP160-SLC43A3-expressing fibroblasts induced tumors resembling human angiosarcoma. Collectively, our findings advance knowledge concerning the genetic causes of angiosarcoma, with potential implications for new diagnostic and therapeutic approaches.
Confocal Laser Scanning Microscopy (1999)

Many technological advancements of the past decade have contributed to improvements in the photon efficiency of the confocal laser scanning microscope (CLSM). The resolution of images from the new generation of CLSMs is approaching that achieved by the microscope itself because of continued development in digital imaging methods, laser technology and the availability of brighter and more photostable fluorescent probes. Such advances have made possible novel experimental approaches for multiple label fluorescence, live cell imaging and multidimensional microscopy.
TravTek - Information and Services Center (1991)

&lt;div class="htmlview paragraph"&gt;The TravTek (travel-technology) project is being developed for the entire Orlando area. This project is a partnership consisting of the Federal Highway Administration, the Florida Department of Transportation, the City of Orlando, General Motors, and the American Automobile Association.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The objectives of the TravTek project are to:&lt;/div&gt; &lt;div class="htmlview paragraph"&gt; &lt;ul class="list disc"&gt; &lt;li class="list-item"&gt; &lt;div class="htmlview paragraph"&gt;Explore the feasibility of ADIS and their acceptability to drivers.&lt;/div&gt; &lt;/li&gt; &lt;li class="list-item"&gt; &lt;div class="htmlview paragraph"&gt;Determine whether Advanced Driver Information System (ADIS) can improve utilization of the highway system, increase safety, improve travel time, and reduce fuel consumption.&lt;/div&gt; &lt;/li&gt; &lt;li class="list-item"&gt; &lt;div class="htmlview paragraph"&gt;Gain insights into how to build the next generation of ADIS.&lt;/div&gt; &lt;/li&gt; &lt;/ul&gt; &lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The TravTek vehicle equipment will be installed in 100 General Motors 1992 Oldsmobile Toronados. Seventy-five or more of these automobiles will be dedicated for daily rental to travelers while the remaining vehicles will be leased to high mileage local drivers.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;The TravTek demonstration projects consists of three principal subsystems:&lt;/div&gt; &lt;div class="htmlview paragraph"&gt; &lt;ul class="list disc"&gt; &lt;li class="list-item"&gt; &lt;div class="htmlview paragraph"&gt;In-Vehicle System - the system in the vehicle which provides the driver with routing and other travel information. The in-vehicle system development is the responsibility of General Motors.&lt;/div&gt; &lt;/li&gt; &lt;li class="list-item"&gt; &lt;div class="htmlview paragraph"&gt;Traffic Management Center (TMC) - collects data concerning traffic conditions from various state and municipal agencies, including TravTek vehicles, and then transmits this information back to the car's In-Vehicle System. The TMC is the responsibility of the FHWA, Florida DOT, and the City of Orlando.&lt;/div&gt; &lt;/li&gt; &lt;li class="list-item"&gt; &lt;div class="htmlview paragraph"&gt;TravTek Information and Services Center (TISC) - The TravTek Information and Services Center will support day-to-day operations of the TravTek experiment. The TISC is is the responsibility of AAA.&lt;/div&gt; &lt;/li&gt; &lt;/ul&gt; &lt;/div&gt;
Vascular endothelial growth factor promotes tumor dissemination by a mechanism distinct from its effect on primary tumor growth. (1996)

Tumor growth is dependent on new blood vessel formation. Inhibition of vascular endothelial growth factor (VEGF), an endothelial cell mitogen and angiogenic factor secreted by a variety of tumors and tumor cell lines, is sufficient to inhibit primary tumor growth. In the present study, we examined the effect of inhibiting VEGF on tumor cell micrometastasis. A transfectant of A431 (a human epidermoid carcinoma cell line) expressing chloramphenicol acetyltransferase (CAT) was injected s.c. into severe combined immunodeficiency (scid) mice, which were then sacrificed after 6 weeks. The presence of A431 metastases at distant sites was demonstrated by detection of CAT activity in whole-organ lysates. Treatment of animals with VEGF-neutralizing antibodies not only inhibited primary tumor growth but also suppressed metastases, as determined by CAT activity in organ lysates. In experiments to determine the mechanism by which anti-VEGF antibody inhibited metastasis, control animals were sacrificed when their tumors had reached the same size as tumors in VEGF antibody-treated animals. Metastases were uniformly present in these control animals. These findings show that inhibition of VEGF alone is sufficient to prevent tumor growth and dissemination in vivo. The inhibitory effect on metastases appears to be distinct from that on primary tumor growth.
The subunit structure of methylmalonyl-CoA mutase from Propionibacterium shermanii (1986)

5'-Deoxyadenosylcobalamin-dependent methylmalonyl-CoA mutase was purified to homogeneity from Propionibacterium shermanii by a simplified procedure. The native enzyme has an apparent Mr of 165,000, similar to the enzyme from other sources but larger than previously reported. It consists of two non-identical subunits, of Mr 79,000 and 67,000 respectively. The smaller subunit is apparently not a proteolytic fragment of the larger one. The final preparation usually contained some inactive mutase, bearing a tenaciously bound cobalamin species. This protein proved to be readily separable from apoenzyme by fast protein liquid chromatography on anion-exchange columns.
On the morphology and orgin of the fibres observed in Nascent Ziegler polyethylene (1969)

Abstract Fibrils in nascent Z IEGLER polyethylene have been compared to those crystallised from stirred solutions, and similarities between the two types have been observed. It is concluded that both the Z IEGLER polyethylene and the stirring‐induced fibres have a composite extended chain and chain‐folded structure. The origin of the nascent polyethylene fibrils is discussed, and the possibility that they are flow‐induced is considered. An alternative mechanism is also envisaged, in which the proposed structure is accounted for in terms of unequal growth rates of molecules from clusters of active sites.
Essential Role of Arginine 235 in the Substrate-Binding of Lactobacillus plantarum D-Lactate Dehydrogenase1 (1994)

Substitutions of the conserved Arg-235 with Lys and Gln induced drastic decreases in the catalytic efficiency of Lactobacillus plantarum D-lactate dehydrogenase (D-LDH). Both the mutant enzymes showed a marked resistance to 2,3-butanedione, by which the wild-type enzyme is rapidly inactivated unless NADH and oxamate are present. The pKa of the catalytic His was markedly shifted to the alkaline side by the Arg-to-Gln substitution, while it was not significantly shifted by the Arg to Lys substitution. The Arg-to-Lys replacement, by which the catalytic efficiency was less damaged, also induced decreases in kcat/Km for alternative substrates, such as 2-ketobutyrate, by approximately 10,000-fold, virtually the same level as in the case of pyruvate. Although both the wild-type and mutant enzymes exhibited lower kcat/Km for the alternative substrates than that for pyruvate, in the case of the mutant enzyme, the decrease in kcat/Km for the alternative substrates was mostly due to a decrease in kcat, while it was caused mainly by an increase in Km in the wild-type enzyme, suggesting that the mutant enzyme tends to form a nonproductive enzyme-substrate complex, in particular with more unfavorable substrates. The pH-dependence of the kinetic constants also indicated that there is a nonproductive binding that does not require the protonated or deprotonated form of the catalytic His residue. These results strongly suggest that Arg-235 plays an essential role in the tight and correct binding of substrate to the binding site of D-LDH, as in the case of Arg-171 in L-LDH.
Plasticization of Metal Sulfonate-Containing EPDM with Stearic Acid Derivatives (1980)

Metal sulfonate-containing ethylene-propylene-diolefin terpolymers (EPDM) were plasticized with stearic acid and derivatives for the reduction of the melt viscosities of these ionomers through interaction with the very strong ionic associations. Substantial improvements in melt flow were achieved with stearic acid and the zinc, lead, and ammonium stearates, while other metal stearates were ineffective. Zinc stearate and lead stearate not only markedly improved melt flow but, remarkably, also enhanced the mechanical properties of the plasticized systems. These unique additives were fully compatible with the EPDM ionomers and provided thermoelastic systems with excellent physical properties and ready processability.
Ovarian expression of insulin-like growth factor-I (IGF-I), IGF binding proteins, and growth hormone (GH) receptor in heifers actively immunized against GH-releasing factors (1996)

Active immunization against GRF at 6 months of age delays puberty in beef heifers. The objectives of the present study were to determine whether active immunization against GRF at an earlier age would affect normal onset of puberty and follicular growth and to determine whether these changes were related to alterations in ovarian insulin-like growth factor I (IGF-I) or IGF binding protein (IG-FBP) messenger RNA (mRNA) levels. Heifers were immunized against human serum albumin (HSAi; n = 15) or against GRF conjugated to HSA (GRFi; n = 18) at 3 months of age. A third group of heifers was not immunized (CON; n = 16). Immunization against GRF delayed puberty beyond 13 months of age in 75% of treated heifers. Unilateral ovariectomy at 191 days of age revealed that the delay in puberty was associated with a reduction in the number of large ( > or = 7 mm in diameter) follicles. Large follicles were present in only 22% of GRFi heifers compared to 77% of HSAi heifers. The number of small ( < or = 3 mm in diameter) and medium (4 to 6 mm in diameter) follicles was not affected by GRFi. The percentage of 1- to 3-mm follicles that were atretic was not different between HSAi (65%) and GRFi (62%) heifers. Unilateral ovariectomy had no effect on age at puberty. Immunization against GRF decreased (P < 0.01) concentrations of IGF-I in serum (23 +/- 2 ng/ml) compared to HSAi heifers (109 +/- 11 ng/ml). IGF-I levels in follicular fluid (FFL) of medium and small follicles were also decreased by GRFi from 82 +/- 3 ng/ml in HSAi heifers to 48 +/- 6 ng/ml (P < 0.01). Levels of IGFBP-3 (determined by ligand blot analysis) in serum and FFL of small follicles were decreased by GRFi (P < 0.01). In contrast, IGFBP-2 serum levels were increased from 422 +/- 32 ng/ml in HSAi heifers to 657 +/- 6 ng/ml in GRFi heifers (P < 0.05). Likewise, IGFBP-2 levels in FFL from small and medium follicles were increased from 785 +/- 44 ng/ml to 926 +/- 44 ng/ml (P < 0.05). Ligand blot analysis indicated that IGFBP levels were lower in FFL from large vs. small follicles. The band intensities of IGFBP-4 and -5 were drastically reduced ( > 80%) while the decreases in IGFBP-2 and -3 were less marked ( < 50%). The decreased levels of IGFBP-5 in FFL from large follicles was not associated with an increase in proteolytic fragments detectable by immunoblot analysis. While mRNA transcripts for IGF-I, GH receptor, and IGFBP-2, -3, -4, and -5 were readily detectable in ovarian tissue, GRFi had no effect on ovarian levels of mRNA for each of these proteins. This suggests that the decrease in follicular development associated with GRFi may be related to changes in circulating IGF-I and/or IGFBPs.
Comparative epidemiology of porcine circovirus type 3 in pigs with different clinical presentations (2017)

The present study further extends evidence that newly described PCV3 widely circulates in six additional provinces of Southern and Northern China and has high similarity to previously reported isolates. As an emerging virus of swine, although the present case-control study reveals that PCV3 has a potential association with swine respiratory disease and diarrhea, further investigations into the pathogenesis are needed to ascertain the role of PCV3 in swine health.
The Ethylene Signal Transduction Pathway in Plants (1995)

Ethylene (C2H4), the chemically simplest plant hormone, is among the best-characterized plant growth regulators. It participates in a variety of stress responses and developmental processes. Genetic studies in Arabidopsis have defined a number of genes in the ethylene signal transduction pathway. Isolation of two of these genes has revealed that plants sense this gas through a combination of proteins that resemble both prokaryotic and eukaryotic signaling proteins. Ethylene signaling components are likely conserved for responses as diverse as cell elongation, cell fate patterning in the root epidermis, and fruit ripening. Genetic manipulation of these genes will provide agriculture with new tools to prevent or modify ethylene responses in a variety of plants.