gebhart/patrepeval huggingface dataset:
IL-15 cis Presentation Is Required for Optimal NK Cell Activation in Lipopolysaccharide-Mediated Inflammatory Conditions (2013)

Natural killer (NK) cells have antitumor, antiviral, and antibacterial functions, and efforts are being made to manipulate them in immunotherapeutic approaches. However, their activation mechanisms remain poorly defined, particularly during bacterial infections. Here, we show that upon lipopolysaccharide or E. coli exposure, dendritic cells (DCs) produce three cytokines-interleukin 2 (IL-2), IL-18, and interferon β (IFN-β)-necessary and sufficient for NK cell activation. IFN-β enhances NK cell activation by inducing IL-15 and IL-15 receptor α not only in DCs but, surprisingly, also in NK cells. This process allows the transfer of IL-15 on NK cell surface and its cis presentation. cis-presented NK cell-derived and trans-presented DC-derived IL-15 contribute equally to optimal NK cell activation.
mTOR Inhibition Potentiates HSP90 Inhibitor Activity via Cessation of HSP Synthesis (2014)

Collectively these data identify a novel strategy to optimize the therapeutic potential of HSP90 inhibitors.
Therapeutic Hypothermia: The Safar Vision (2009)

At the 2(nd) International Brain Hypothermia conference, in Miami, the late Dr. Peter Safar was honored for his many contributions to the field of therapeutic hypothermia. Therapeutic hypothermia played a central role in his overall vision for optimized resuscitation and neurointensive care, across a large number of potential insults. The successful use of therapeutic hypothermia in comatose patients after cardiac arrest, for example, was already included in the historic first "ABCs" of resuscitation, published by Safar in 1964. This review addresses key historical events in the development and implementation of therapeutic hypothermia across a number of central nervous system insults. A discussion of future potential uses of this therapy in a variety of applications as part of the Safar vision is also presented.
Clinical and biological impact of EphA2 overexpression and angiogenesis in endometrial cancer (2010)

Of 85 EEC samples, EphA2 was overexpressed in 47% of tumors and was significantly associated with high VEGF expression (p=0.001) and high MVD counts (p=0.02). High EphA2 expression, high VEGF expression and high MVD counts were significantly associated with shorter disease-specific survival. EA5 led to decrease in EphA2 expression and phosphorylation in vitro. In the murine model, while EA5 (33-88%) and docetaxel (23-55%) individually led to tumor inhibition over controls, combination therapy had the greatest efficacy (78-92%, p.
Matrix metalloproteinases in neuroinflammation (2002)

Matrix metalloproteinases (MMPs) are a gene family of neutral proteases that are important in normal development, wound healing, and a wide variety of pathological processes, including the spread of metastatic cancer cells, arthritic destruction of joints, atherosclerosis, and neuroinflammation. In the central nervous system (CNS), MMPs have been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB), and to contribute to the neuroinflammatory response in many neurological diseases. Brain cells express both constitutive and inducible MMPs in response to cellular stress. MMPs are tightly regulated to avoid unwanted proteolysis. Secreted as inactive enzymes, the MMPs require activation by other proteases and free radicals. The MMPs are part of a larger class of metalloproteinases (MPs), which includes the recently discovered ADAMs (a disintegrin and metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase thrombospondin) families. MPs have complex roles at the cell surface and within the extracellular matrix. At the cell surface, they act as sheddases, releasing growth factors, death receptors, and death-inducing ligands, making them important in cell survival and death. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that regulate the activity of the MMPs. Synthetic inhibitors have been developed for the treatment of arthritis and cancer. These hydroxymate-based compounds have been shown to reduce injury in experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), cerebral ischemia, intracerebral hemorrhage, and viral and bacterial infections. MPs have both beneficial and detrimental roles; understanding their expression in various CNS insults will allow for the use of MMP inhibitors in the treatment of neurological disorders.
Solvent Assisted Pressure-Free Surface Welding and Reprocessing of Malleable Epoxy Polymers (2016)

Covalent adaptable networks (CANs; also known as dynamic covalent networks or vitrimers) are appealing for developing simple and efficient techniques for recycling thermosetting polymers. In this paper, ethylene glycol (EG) is used as a solvent to enable pressure-free surface welding, surface repair, and recycling of a malleable epoxy where the transesterification-type bond exchange reaction (BER) imparts a dynamic nature to the covalent network. At a high temperature, the EG molecules participate in the BER, leading to dissolution of the epoxy network. If the EG is allowed to evaporate, the dissolved epoxy can re-form into a solid. The effects of EG content, temperature, and catalyst concentration on EG-assisted BERs are investigated. It is found that the amount of EG can be adjusted to tune the solution/solid transformation: An excessive amount of EG is required to dissolve the epoxy; on the other hand, a shortage of EG can shift the reaction back to re-form the polymer. Furthermore, the catalyst concentration defines the point at which dissolution initiates, while the degradation rate depends on temperature. This new EG-assisted method is further used for surface welding, surface damage repair, and powder-based reprocessing. The EG-assisted method does not require pressure and can achieve the properties of a fresh sample. It also provides potential opportunities to develop facile recycling techniques for thermosetting polymers.
Role of SUMO-1–modified PML in nuclear body formation (2000)

The tumor-suppressive promyelocytic leukemia (PML) protein of acute promyelocytic leukemia (APL) has served as one of the defining components of a class of distinctive nuclear bodies (NBs). PML is delocalized from NBs in APL cells and is degraded in cells infected by several viruses. In these cells, NBs are disrupted, leading to the aberrant localization of NB proteins. These results have suggested a critical role for the NB in immune response and tumor suppression and raised the question of whether PML is crucial for the formation or stability of NB. In addition, PML is, among other proteins, covalently modified by SUMO-1. However, the functional relevance of this modification is unclear. Here, we show in primary PML(-/-) cells of various histologic origins, that in the absence of PML, several NB proteins such as Sp100, CBP, ISG20, Daxx, and SUMO-1 fail to accumulate in the NB and acquire aberrant localization patterns. Transfection of PML in PML(-/-) cells causes the relocalization of NB proteins. By contrast, a PML mutant that can no longer be modified by SUMO-1 fails to do so and displays an aberrant nuclear localization pattern. Therefore, PML is required for the proper formation of the NB. Conjugation to SUMO-1 is a prerequisite for PML to exert this function. These data shed new light on both the mechanisms underlying the formation of the NBs and the pathogenesis of APL. (Blood. 2000;95:2748-2752)
Optimizing power consumption in large scale storage systems (2007)

Data centers are the backend for a large number of services that we take for granted today. A significant fraction of the total cost of ownership of these large-scale storage systems is the cost of keeping hundreds of thousands of disks spinning. We present a simple idea that allows the storage system to turn off a large fraction of its disks, without incurring unacceptable performance penalties. Of particular appeal is the fact that our solution is not application-specific, and offers power-savings for a very generic data center model. In this paper, we describe our solution, identify the parameters that determine its cost-benefit tradeoffs, and present a simulator that allows us to explore this parameter space. We also present some initial simulation results that add weight to our claim that our solution represents a new powersaving opportunity for large-scale storage systems. 1
Curing Chronic Hepatitis C — The Arc of a Medical Triumph (2014)

Interview with Dr. Raymond Chung on the science behind evolving treatments for hepatitis C and progress toward a cure. (16:14)Download The development of direct-acting antiviral agents has revolutionized the treatment of hepatitis C by offering genuine prospects for a comprehensive cure of a chronic viral infection. This success can be traced to important scientific, clinical, and regulatory developments.
Dectin-1 Mediates the Biological Effects of β-Glucans (2003)

The ability of fungal-derived beta-glucan particles to induce leukocyte activation and the production of inflammatory mediators, such as tumor necrosis factor (TNF)-alpha, is a well characterized phenomenon. Although efforts have been made to understand how these carbohydrate polymers exert their immunomodulatory effects, the receptors involved in generating these responses are unknown. Here we show that Dectin-1 mediates the production of TNF-alpha in response to zymosan and live fungal pathogens, an activity that occurs at the cell surface and requires the cytoplasmic tail and immunoreceptor tyrosine activation motif of Dectin-1 as well as Toll-like receptor (TLR)-2 and Myd88. This is the first demonstration that the inflammatory response to pathogens requires recognition by a specific receptor in addition to the TLRs. Furthermore, these studies implicate Dectin-1 in the production of TNF-alpha in response to fungi, a critical step required for the successful control of these pathogens.
Long-term 193-nm laser irradiation of thin-film-coated CaF2 in the presence of H2O (2005)

The final projection lens element in a 193-nm immersion-based lithographic tool will be in direct contact with water during irradiation. Thus, any lifetime considerations for the lens must include durability data of lens materials and thin films in a water ambient. We have previously shown that uncoated CaF<sub>2</sub> is attacked by water in a matter of hours, as manifested by a substantial increase in AFM-measured surface roughness.<sup>1</sup> Thus, CaF<sub>2</sub> lenses must be protected, possibly by a thin film, and the coatings tested for laser durability in water. To address the above lifetime concerns, we have constructed a marathon laser-irradiation system for testing thin film exposure to water under long-term laser irradiation. Coated substrates are loaded into a custom water cell, made of stainless steel and Teflon parts. Ultrapure water is delivered from a water treatment testbed that includes particle filtration, deionization and degassing stages. In-situ metrology includes 193-nm laser ratiometry, UV spectrophotometry and spectroscopic ellipsometry, all with spatial profiling capabilities. In-situ results are coupled with off-line microscopy, AFM measurements and spatial surface mapping with spectroscopic ellipsometry at multiple incidence angles. A variety of laser-induced changes have been observed, from complete adhesion loss of protective coatings to more subtle changes, such as laser-induced index changes of the thin films or surface roughening. Implications of the study on expected lifetimes of the protective coatings in the system will be discussed.
Gene Expression Patterns in Myelodyplasia Underline the Role of Apoptosis and Differentiation in Disease Initiation and Progression (2008)

The myelodysplastic syndromes (MDS) are clonal stem cell disorders, characterized by ineffective and dysplastic hematopoiesis. The genetic and epigenetic pathways that determine disease stage and progression are largely unknown. In the current study we used gene expression microarray methodology to examine the gene expression differences between normal hematopoietic cells and hematopoietic cells from patients with MDS at different disease stages, using both unselected and CD34+ selected cells. Significant differences between normal and MDS hematopoietic cells were observed for several genes and pathways. Several genes promoting or opposing apoptosis were dysregulated in MDS cases, most notably MCL1 and EPOR. Progression from RA to RAEB(T) was associated with increased expression of several histone genes. In addition, the RAR-RXR pathway, critical for maintaining a balance between self-renewal and differentiation of hematopoietic stem cells, was found to be deregulated in hematopoietic cells from patients with advanced MDS compared to patients with refractory anemia. These findings provide new insights into the understanding of the pathophysiology and progression of MDS, and may guide to new targets for therapy. Taken together with previous published data, the present results also underscore the considerable complexity of the regulation of gene expression in MDS.
Surfactant–Thermal Method to Synthesize a Novel Two‐Dimensional Oxochalcogenide (2013)

A new two-dimensional (2D) oxosulfide, (N2H4)2Mn3Sb4S8(μ3-OH)2 (1), has been successfully synthesized under surfactant-thermal conditions with hexadecyltributylphosphonium bromide as the surfactant. Compound 1 has a layered structure and contains a novel [Mn3(μ3-OH)2]n chain along the b-axis. The photocatalytic activity for compound 1 has been demonstrated under visible-light irradiation and continuous H2 evolution was observed. Our results indicate that surfactant-thermal synthesis could be a promising method for growing novel crystalline oxochalcogenides with interesting structures and properties.
Modification of antisense phosphodiester oligodeoxynucleotides by a 5' cholesteryl moiety increases cellular association and improves efficacy. (1993)

Phosphodiester oligodeoxynucleotides bearing a 5' cholesteryl (chol) modification bind to low density lipoprotein (LDL), apparently by partitioning the chol-modified oligonucleotides into the lipid layer. Both HL60 cells and primary mouse spleen T and B cells incubated with fluorescently labeled chol-modified oligonucleotide showed substantially increased cellular association by flow cytometry and increased internalization by confocal microscopy compared to an identical molecule not bearing the chol group. Cellular internalization of chol-modified oligonucleotide occurred at least partially through the LDL receptor; it was increased in mouse spleen cells by cell culture in lipoprotein-deficient medium and/or lovastatin, and it was decreased by culture in high serum medium. To determine whether chol-modified oligonucleotides are more potent antisense agents, we titered antisense unmodified phosphodiester and chol-modified oligonucleotides targeted against a mouse immunosuppressive protein. Murine spleen cells cultured with 20 microM phosphodiester antisense oligonucleotides had a 2-fold increase in RNA synthesis, indicating the expected lymphocyte activation. Antisense chol-modified oligonucleotides showed an 8-fold increase in relative potency: they caused a 2-fold increase in RNA synthesis at just 2.5 microM. The increased efficacy was blocked by heparin and was further increased by cell culture in 1% (vs. 10%) fetal bovine serum, suggesting that the effect may, at least in part, be mediated via the LDL receptor. Antisense chol-modified oligonucleotides are sequence specific and have increased potency as compared to unmodified oligonucleotides.
Amplification of genes within the chromosome 11q13 region is indicative of poor prognosis in patients with operable breast cancer. (1992)

Amplification of the chromosome 11q13 region, which harbors the BCL1 region and the PRAD1, EMS1, HSTF1, and INT2 genes, was found in 36 (16%) of a series of 226 breast carcinomas. In the 153 patients with stage I-IIIa disease who had received no therapy prior to surgery and who were treated with curative intent, 11q13 amplification was associated with the presence of lymph node metastases (P less than 0.002). The presence of an 11q13 amplification was associated with a significantly shorter relapse-free survival (P less than 0.002) and a higher breast cancer-specific mortality (P less than 0.003). Stepwise multivariate analysis showed that, in addition to lymph node status, 11q13 amplification was the best predictor for short survival. Stratified log-rank analysis indicated that, within the group of lymph node-positive breast cancer patients, 11q13 amplification identifies a subgroup at high risk.
Intrinsically reversible superglues via shape adaptation inspired by snail epiphragm (2019)

Adhesives are ubiquitous in daily life and industrial applications. They usually fall into one of two classes: strong but irreversible (e.g., superglues) or reversible/reusable but weak (e.g., pressure-sensitive adhesives and biological and biomimetic surfaces). Achieving both superstrong adhesion and reversibility has been challenging. This task is particularly difficult for hydrogels that, because their major constituent is liquid water, typically do not adhere strongly to any material. Here, we report a snail epiphragm-inspired adhesion mechanism where a polymer gel system demonstrates superglue-like adhesion strength (up to 892 N⋅cm<sup>-2</sup>) that is also reversible. It is applicable to both flat and rough target surfaces. In its hydrated state, the softened gel conformally adapts to the target surface by low-energy deformation, which is locked upon drying as the elastic modulus is raised from hundreds of kilopascals to ∼2.3 GPa, analogous to the action of the epiphragm of snails. We show that in this system adhesion strength is based on the material's intrinsic, especially near-surface, properties and not on any near-surface structure, providing reversibility and ease of scaling up for practical applications.
Study of sub-30nm thin film transistor (TFT) charge-trapping (CT) devices for 3D NAND flash application (2009)

Sub-30nm TFT CT NAND flash devices have been extensively studied. Although TFT devices were often believed to have much worse performance than bulk devices, our results show that as devices scale down to sub-30nm, the DC characteristics (such as read current and subthreshold slope (S.S.)) approach those of the bulk devices because sub-30 nm TFT devices often contain no grain boundaries. The memory window is also larger than the bulk planar devices due to the tri-gate structure that enhances the electric field during programming/erasing. However, a fair percentage of devices contain grain boundaries with poorer S.S. and g <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</inf> . Interestingly, this only affects the DC characteristics but does not impact the memory window. Furthermore, grain boundaries do not increase the random telegraph noise. The most serious drawback of grain boundaries is the impact on self-boosting window caused by junction leakage. A sub-30 nm TFT BE-SONOS NAND device with MLC capability and good retention is demonstrated
Evaluation of Molybdenum and Tungsten Metathesis Catalysts for Homogeneous Tandem Alkane Metathesis (2008)

Over 40 molybdenum and tungsten imido alkylidene mono(alkoxide) mono(pyrrolide) (MAP) or bis(alkoxide) olefin metathesis catalysts were examined in combination with Ir-based pincer-type catalysts for the metathesis of n-octane. The imido group, alkoxide, and metal in the metathesis catalysts were all found to be important variables. The best catalyst was W(NAr)(CHR)(OSiPh3)2 (Ar = 2,6-diisopropylphenyl), which performed about twice as well as the only previously employed catalyst, Mo(NAr)(CHR)[OCMe(CF3)2]2. Product yields decreased at temperatures greater than 125 °C, most likely because of the instability of the metathesis catalysts at such temperatures. POCOP Ir catalysts gave higher yields than PCP Ir catalysts, although the latter exhibited some selectivity for formation of tetradecane. Eight catalysts were synthesized in situ through addition of alcohols to bis(2,5-dimethylpyrrolide) complexes; in situ catalysts were shown to perform approximately as well as the isolated complexes, which suggests that 2,5-dimethylpyrrole is not detrimental to the alkane metathesis process and that potential catalysts can be screened more conveniently in this way.
The B7 Family and Cancer Therapy: Costimulation and Coinhibition (2007)

The activation and development of an adaptive immune response is initiated by the engagement of a T-cell antigen receptor by an antigenic peptide-MHC complex. The outcome of this engagement is determined by both positive and negative signals, costimulation and coinhibition, generated mainly by the interaction between the B7 family and their receptor CD28 family. The importance of costimulation and coinhibition of T cells in controlling immune responses is exploited by tumors as immune evasion pathways. Absence of the expression of costimulatory B7 molecules renders tumors invisible to the immune system, whereas enhanced expression of inhibitory B7 molecules protects them from effective T cell destruction. Therefore, the manipulation of these pathways is crucial for developing effective tumor immunotherapy. Translation of our basic knowledge of costimulation and coinhibition into early clinical trials has shown considerable promise.
Measurement of the rotational temperature of oxygen in a high-power inductively coupled plasma (1995)

In a high-power (30 kW), inductively coupled argon-oxygen plasma used as a tool to deposit high-temperature superconducting YBa2Cu3O7-x films rotational bands of the Schumann-Runge system B3 Sigma (u-)-X3 Sigma (g-) oxygen were detected in the spectral regions around 340 and 360 nm. After derivation of the line strength factors for the triplet system, rotational temperatures can be determined by fitting calculated relative intensities to those observed experimentally, and the contributions of R and P branches to the lines observed can be identified. The rotational temperature 7 at a distance of 34.5 cm from the exit of the plasma torch where the deposition of superconducting films takes place lies in the range 1850-2050 K depending on the RF power input which was varied in the range 8-27 kW. Near the torch exit, temperatures in the range 2600-3400 K are observed. They depend strongly on gas composition and gas flow rate, in contrast to positions far away from the torch exit. Excitation temperatures near the torch exit which were derived from Ar lines are considerably higher than the rotational temperatures, indicating that the latter are typical of the colder outer parts of the plasma.