gebhart/patrepeval huggingface dataset:
The role of relaxation times in monitoring proteoglycan depletion in articular cartilage (1999)

Various proton relaxation times (T2, T1rho, and gadolinium-diethylene triamine pentaacetic acid [Gd-DTPA]-enhanced T1) were measured in articular cartilage in vitro at 3 T to assess their role in visualizing proteoglycan depletion. Cartilage-bone specimens were obtained from patients who underwent total joint replacement and got a double dose of Gd-DTPA 2 hours prior surgery. In these specimens, regions of mechanically undamaged cartilage having a decreased content of proteoglycans showed about 15% lower T1 values compared with apparently normal cartilaginous tissue. The expected increase of the T2 relaxation time was not observed in these regions. On the other hand, the T2 and, to a lower degree, T1 relaxation times were found to be increased in regions of cartilage fibrillation. The T1rho relaxation times obtained were slightly longer than the corresponding T2 values, but both parameters showed almost identical spatial distributions. J. Magn. Reson. Imaging 1999;10:497-502.
Aberrant splicing in neuroblastoma generates RNA-fusion transcripts and provides vulnerability to spliceosome inhibitors (2021)

The paucity of recurrent mutations has hampered efforts to understand and treat neuroblastoma. Alternative splicing and splicing-dependent RNA-fusions represent mechanisms able to increase the gene product repertoire but their role in neuroblastoma remains largely unexplored. Here we investigate the presence and possible roles of aberrant splicing and splicing-dependent RNA-fusion transcripts in neuroblastoma. In addition, we attend to establish whether the spliceosome can be targeted to treat neuroblastoma. Through analysis of RNA-sequenced neuroblastoma we show that elevated expression of splicing factors is a strong predictor of poor clinical outcome. Furthermore, we identified >900 primarily intrachromosomal fusions containing canonical splicing sites. Fusions included transcripts from well-known oncogenes, were enriched for proximal genes and in chromosomal regions commonly gained or lost in neuroblastoma. As a proof-of-principle that these fusions can generate altered gene products, we characterized a ZNF451-BAG2 fusion, producing a truncated BAG2-protein which inhibited retinoic acid induced differentiation. Spliceosome inhibition impeded neuroblastoma fusion expression, induced apoptosis and inhibited xenograft tumor growth. Our findings elucidate a splicing-dependent mechanism generating altered gene products in neuroblastoma and show that the spliceosome is a potential target for clinical intervention.
Cancer-induced Defective Cytotoxic T Lymphocyte Effector Function: Another Mechanism How Antigenic Tumors Escape Immune-mediated Killing (2000)

The notion that a deficit in immune cell functions permits tumor growth has received experimental support with the discovery of several different biochemical defects in T lymphocytes that infiltrate cancers. Decreased levels of enzymes involved with T-cell signal transduction have been reported by several laboratories, suggesting that tumors or host cells recruited to the tumor site actively down-regulate antitumor T-cell immune response. This permits tumor escape from immune-mediated killing. The possibility that defects in T-cell signal transduction can be reversed, which would potentially permit successful vaccination or adoptive immunotherapy, motivates renewed interest in the field. Summarizing the literature concerning tumor-induced T-cell dysfunction, we focus on the end stage of immune response to human cancer, that of defective cytotoxic T lymphocyte killing function. Based on the data from several laboratories, we hypothesize a biochemical mechanism that accounts for the unusual phenotype of antitumor T-cell accumulation in tumors, but with defective killing function.
Update on the treatment of hypercholesterolemia, with a focus on hmg‐coa reductase inhibitors and combination regimens (1995)

Numerous studies involving patients with hypercholesterolemia have demonstrated that reduction of lipid levels markedly reduces morbidity and mortality from cardiovascular disease. Diet alone may enable patients without established disease to attain target lipid levels, but pharmacotherapy generally is necessary for those with coronary artery disease. Choice of a suitable agent for monotherapy--a bile acid resin, niacin, or an HMG-CoA reductase inhibitor--may be determined by patient phenotype. For resistant cases, therapy combining an HMG-CoA reductase inhibitor with another agent generally is effective and well tolerated.
Nature-inspired optimization of hierarchical porous media for catalytic and separation processes (2016)

Nature-inspired structuring at the meso-scale: broad macropores separate the mesoporous catalyst grains.
Frequency doubling of picosecond pulses in periodicallypoled D-shape silica fibre (1997)

D-shape silica fibres have been periodically poled at an elevated temperature by applying high voltage via a patterned electrode deposited on the plane side. The resulting nonlinear grating of 25 µm period, uniform over the whole 1.8 cm length, has been used for quasi-phase-matched second harmonic generation. With a mode-locked laser as a fundamental source, blue powers up to ~76 µW have been generated at ~422 nm with an average conversion efficiency of ~0.22%.
Rapid and Long‐Term Glycemic Regulation with a Balanced Charged Immune‐Evasive Hydrogel in T1DM Mice (2019)

Abstract Transplantation of encapsulated islets is a promising treatment for patients with type 1 diabetes mellitus. However, its long‐term clinical therapeutic efficacy is still hindered by serious immune rejection from the host immunological responses to the implanted materials, known as foreign body reaction (FBR). In this work, an anti‐biofouling balanced charged hydrogel is reported that can serve as an excellent immunoprotective material for islet transplantation therapy. It is found that the encapsulated islets can maintain their glucose‐responsive and insulin‐producing functions. Additionally, the hydrogel can effectively evade in vivo FBR after intraperitoneal implantation in an immunocompetent streptozotocin‐induced diabetic mouse model. As a result, 100% of the mice rapidly recover to normoglycemia within 2 d and stably maintain for at least 150 d without any immunosuppression treatment. These findings shed light on the “insulin independence and immunoisolation” encapsulation strategy, which can overcome the barrier of islet transplantation and holds the potential to improve current clinical therapeutic efficacy.
Properties of the human hepatitis B virus enhancer: position effects and cell-type nonspecificity (1988)

The genome of human hepatitis B virus (HBV) contains an enhancer element within a 360-base-pair transcribed region located between sequences encoding the virus surface and core antigens. Beyond the usual properties associated with enhancers (i.e., activity 5' or 3' of a heterologous promoter and relative orientation independence), DNA sequences encompassing this enhancer exhibited unexpected characteristics. Using gene expression assays in both stably and transiently transfected cells, we found that the HBV enhancer element, when located in a transcribed region of chimeric genes, dramatically increased expression levels of genes controlled by the simian virus 40 promoter/enhancer. This synergism was not observed, however, when the HBV enhancer was located outside of the transcribed region. When these transcribed sequences were reversed in orientation, expression levels decreased significantly. These data suggest that RNA stability and transcriptional activity may be affected by sequences associated with this DNA region. In contrast to the findings of others, we found that the HBV enhancer activated transcription in a relatively cell-type-independent manner when the enhancer was located either 5' of the promoter or in the 3' untranslated region of gene constructs. The implications of these and other properties of the HBV enhancer region on viral gene expression and its life cycle are discussed.
Electrochemistry of Poly(3,4‐alkylenedioxythiophene) Derivatives (2003)

Abstract An overview of the electrochemistry of poly(3,4‐alkylenedioxythiophene)s (PXDOTs) is presented. As a class of conducting and electroactive polymers that can exhibit high and quite stable conductivities, a high degree of optical transparency as a conductor, and the ability to be rapidly switched between conducting doped and insulating neutral states, PXDOTs have attracted attention across academia and industry. Numerous fundamental aspects are addressed here in detail, ranging from the electrochemical synthesis of PXDOTs, a variety of in‐situ characterization techniques, the broad array of properties accessible, and morphological aspects. Finally, two electrochemically‐driven applications, specifically electrochromism and chemical sensors of PXDOTs are discussed.
An Atom-Specific Look at the Surface Chemical Bond (1997)

High resolution x-ray emission spectroscopy is shown to reveal unprecedented details of the chemical bond formed between a molecule and a transition metal surface. An atom and symmetry projected view of the bonding orbitals is obtained. We find that all outer and inner valence orbitals of the molecule change due to the surface interaction. New types of molecular states are observed which are a direct signature of the surface chemical bond.
A Novel Monte-Carlo-Sampling-Based Receiver for Large-Scale Uplink Multiuser MIMO Systems (2013)

In this paper, we propose low-complexity algorithms based on Monte Carlo sampling for signal detection and channel estimation on the uplink in large-scale multiuser multiple-input-multiple-output (MIMO) systems with tens to hundreds of antennas at the base station (BS) and a similar number of uplink users. A BS receiver that employs a novel mixed sampling technique (which makes a probabilistic choice between Gibbs sampling and random uniform sampling in each coordinate update) for detection and a Gibbs-sampling-based method for channel estimation is proposed. The algorithm proposed for detection alleviates the stalling problem encountered at high signal-to-noise ratios (SNRs) in conventional Gibbs-sampling-based detection and achieves near-optimal performance in large systems with M-ary quadrature amplitude modulation ( M-QAM). A novel ingredient in the detection algorithm that is responsible for achieving near-optimal performance at low complexity is the joint use of a mixed Gibbs sampling (MGS) strategy coupled with a multiple restart (MR) strategy with an efficient restart criterion. Near-optimal detection performance is demonstrated for a large number of BS antennas and users (e.g., 64 and 128 BS antennas and users). The proposed Gibbs-sampling-based channel estimation algorithm refines an initial estimate of the channel obtained during the pilot phase through iterations with the proposed MGS-based detection during the data phase. In time-division duplex systems where channel reciprocity holds, these channel estimates can be used for multiuser MIMO precoding on the downlink. The proposed receiver is shown to achieve good performance and scale well for large dimensions.
Phenylbutyrate-induced glutamine depletion in humans: effect on leucine metabolism (1998)

The present study was designed to determine whether sodium phenylbutyrate (phi B) acutely induces a decrease in plasma glutamine in healthy humans, and, if so, will decrease estimates of whole body protein synthesis. In a first group of three healthy subjects, graded doses (0, 0.18, and 0.36 g.kg-1.day-1) of phi B were administered for 24 h before study: postabsorptive plasma glutamine concentration declined in a dose-dependent manner, achieving an approximately 25% decline for a dose of 0.36 g phi B.kg-1.day-1. A second group of six healthy adults received 5-h infusions of L-[1-14C]leucine and L-[1-13C]glutamine in the postabsorptive state on two separate days: 1) under baseline conditions and 2) after 24 h of oral treatment with phi B (0.36 g.kg-1.day-1) in a randomized order. The 24-h phenylbutyrate treatment was associated with 1) an approximately 26% decline in plasma glutamine concentration from 514 +/- 24 to 380 +/- 15 microM (means +/- SE; P < 0.01 with paired t-test) with no change in glutamine appearance rate or de novo synthesis; 2) no change in leucine appearance rate (Ra), an index of protein breakdown (123 +/- 7 vs. 117 +/- 5 mumol.kg-1.h-1; not significant); 3) an approximately 22% rise in leucine oxidation (Ox) from 23 +/- 2 to 28 +/- 2 mumol.kg-1.h-1 (P < 0.01), resulting in an approximately 11% decline in nonoxidative leucine disposal (NOLD = Ra-Ox), an index of protein synthesis, from 100 +/- 6 to 89 +/- 5 mumol.kg-1.h-1 (P < 0.05). The data suggest that, in healthy adults, 1) large doses of oral phenylbutyrate can be used as a "glutamine trap" to create a model of glutamine depletion; 2) a moderate decline in plasma glutamine does not enhance rates of endogenous glutamine production; and 3) a short-term depletion of plasma glutamine decrease estimates of whole body protein synthesis.
The Total Degumming Process – Theory and Industrial Application in Refining and Hydrogenation (1992)

Abstract The degumming of vegetable oils prior to physical refining is a crucial preliminary step. The degumming process is not only largely responsible for the quality of the final product, but it also determines the amount of bleaching earth to be used, which has a substantial effect on the yield improvement which can be attained by this route. Investigations show clearly that iron, as a pro‐oxidant, strongly influences the stability of refined oils, and that oil, degummed before bleaching and physical refining, may contain a maximum of 0.2 ppm Fe, if it is to yield a stable product. The Total Degumming Process has been developed on the basis of these findings, to make it possible to degum oil to a residual Fe‐level below 0.2 ppm and a residual phosphorus content below 10 ppm. The principles and industrial application of the process have been considered. The results of industrial production using different raw materials of various qualities have been used to make a comparison between the conventional refining process (neutralization – bleaching – deodorization) and the Total Degumming Process in combination with physical refining. The combination of the Total Degumming Process and a simplified caustic refining process, and the use of Totally Degummed Oil for hydrogenation have also been considered.
Phase 1 trials of PEGylated recombinant human hyaluronidase PH20 in patients with advanced solid tumours (2017)

The tumour stroma has emerging importance in the development of cancer therapeutics. PEGPH20 3.0 μg kg<sup>-1</sup> administered twice weekly is feasible in patients with advanced cancers; exploratory analyses indicate antitumour activity supporting further evaluation of PEGPH20 in solid tumours.
0.45 W diffraction-limited beam and single-frequency operation from antiguided phase-locked laser array with distributed feedback grating (1998)

A second-order diffraction grating placed below the active region of a phase-locked resonant antiguided array selects the in-phase array mode in addition to its role as a single-longitudinal-mode selector. This type of array-mode discrimination relies on the fact that the resonant in-phase array mode has significantly better field overlap with the grating region than nonresonant array modes. Furthermore, it eliminates the need for a conventional array-mode discriminator: interelement loss; which can cause self-pulsations. Diffraction-limited beam and single-frequency operation is obtained to at least 0.45 W peak pulsed power from 20 element, InGaAs/InGaP/GaAs structures (λ=0.97 μm) of 120-μm-wide aperture. Distributed-feedback operation is confirmed over the 20–40 °C temperature range. The results are in good agreement with theory.
Switch to the angiogenic phenotype during tumorigenesis. (1991)

Tumor growth and metastasis are angiogenesis-dependent. Virtually all solid tumors are neovascularized by the time they are detected. However, there is a prevascular phase during early tumor development where few or no tumor cells are angiogenic and expansion of the tumor is restricted to a few mm3. When enough tumor cells become angiogenic, the tumor can expand progressively and shed metastatic cells. This angiogenic switch has recently been quantitated for human breast cancer, as well as for prostate cancer. We have studied the problem of how tumors switch to the angiogenic phenotype by using transgenic mice in which tumors develop at a predictable time and in discrete prevascular and vascular stages. When the transgene is the bovine papilloma virus (BPV) genome, angiogenic fibrosarcomas develop from non-angiogenic precursors called fibromatoses. The fibrosarcomas secrete growth factors for capillary endothelial cells. In contrast, the fibromatoses do not secrete endothelial cell growth factors. When the transgene consists of the large "T" antigen of SV40 under the control of the rat insulin promoter, 70% of pancreatic islets become hyperplastic and 4-10% of these become angiogenic at 6-7 weeks. Tumors arise from these neovascularized hyperplastic islets and reach > 1000 x the volume of the preangiogenic islets. The onset of angiogenic activity coincides with the secretion of acidic fibroblast growth factor (aFGF) and other growth factors not fully identified at this writing. These studies help to explain the switch to the angiogenic phenotype during tumorigenesis and provide models to discover antiangiogenic therapies directed at the source of angiogenic activity. Such therapy, when developed, may be co-administered with currently available angiogenesis inhibitors which are directed at the target of angiogenic activity, vascular endothelial cells.
Lack of Siglec-7 expression identifies a dysfunctional natural killer cell subset associated with liver inflammation and fibrosis in chronic HCV infection (2015)

These findings identify Siglec-7<sup>neg</sup> NK cells as a dysfunctional subpopulation associated with severe liver disease in chronic HCV infection.
Corneal nerves are necessary for adrenergic reactivation of ocular herpes. (1988)

Herpes simplex virus type 1 (HSV-1) can infect the cornea and achieve ganglionic latency. HSV-1 can later be activated by a variety of effectors although the exact mechanism of reactivation is unknown. Rabbits harboring latent HSV-1 strain McKrae can be induced to shed virus by ocular iontophoresis of epinephrine to the cornea. No studies have been done to investigate if corneal nerves are necessary for epinephrine induction of HSV-1 ocular shedding. We did penetrating keratoplasty (PKP) in one eye each of 23 rabbits; the other eye served as an unoperated control. The surgery effectively denervates the area of the transplant for up to 90 days. Eighteen rabbits carrying latent HSV-1 strain McKrae received corneas from uninfected rabbits. Five uninfected rabbits with no latent virus received corneas from rabbits harboring latent HSV-1. On days 10-14 after penetrating keratoplasty, 24 eyes in the HSV-1 latent group and all ten uninfected eyes received iontophoresis of 0.01% epinephrine (0.8 mAmps for 8 min or 0.6 mAmps for 6 min) once daily for 3 days by means of an eye cup whose diameter was less than the diameter of the transplant. Six rabbits in the HSV-1 latent group received intravenous injections of cyclophosphamide (75 mg/kg) and dexamethasone (4 mg/kg). Following iontophoretic or immunosuppressive induction, the eyes were swabbed daily for 9 days. Of the 12 rabbits with latent virus which were treated by iontophoresis, one of the transplanted eyes and eight of the nontransplanted eyes were induced to shed virus. The mean duration of shedding in the nontransplanted eyes was 3.25 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Determining the Size of Non-A, Non-B Hepatitis Virus by Filtration (1987)

The approximate size of the H strain of non-A, non-B (NANB) hepatitis virus was determined by filtration through polycarbonate membranes. The accuracy and reproducibility of such filtrations were monitored by filtering selected reference viruses. These studies indicate that strain H, representative of the principal blood-borne NANB hepatitis virus, is 30-60 nm in diameter. It is therefore highly unlikely that NANB hepatitis virus is a retrovirus, as has been suggested.
Immunosuppression Enhances Oncolytic Adenovirus Replication and Antitumor Efficacy in the Syrian Hamster Model (2008)

We recently described an immunocompetent Syrian hamster model for oncolytic adenoviruses (Ads) that permits virus replication in tumor cells as well as some normal tissues. This model allows exploration of interactions between the virus, tumor, normal organs, and host immune system that could not be examined in the immunodeficient or nonpermissive animal models previously used in the oncolytic Ad field. Here we asked whether the immune response to oncolytic Ad enhances or limits antitumor efficacy. We first determined that cyclophosphamide (CP) is a potent immunosuppressive agent in the Syrian hamster and that CP alone had no effect on tumor growth. Importantly, we found that the antitumor efficacy of oncolytic Ads was significantly enhanced in immunosuppressed animals. In animals that received virus therapy plus immunosuppression, significant differences were observed in tumor histology, and in many cases little viable tumor remained. Notably, we also determined that immunosuppression allowed intratumoral virus levels to remain elevated for prolonged periods. Although favorable tumor responses can be achieved in immunocompetent animals, the rate of virus clearance from the tumor may lead to varied antitumor efficacy. Immunosuppression, therefore, allows sustained Ad replication and oncolysis, which leads to substantially improved suppression of tumor growth.
Complement in Antibody-Based Tumor Therapy (2014)

Monoclonal antibodies constitute a major treatment option for many tumor patients. Due to their specific recognition sites in their constant Fc regions, antibodies are able to trigger antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). While the contribution of ADCC to clinical efficacy has been strengthened by observations that patients with favorable Fcγ receptor polymorphisms display better response rates to therapeutic antibodies, the contribution of CDC to their clinical efficacy remains controversial. In the background of high expression of complement-regulatory proteins on tumor cells as well as of the fact that some therapeutic antibodies lack the capacity to trigger efficient CDC, strategies have been implemented to improve either the capacity of antibodies to initiate the complement cascade or to interfere with tumor cells' resistance mechanisms. Although both strategies have demonstrated therapeutic benefit in vitro and in murine models, CDC-enhanced antibodies-to the best of our knowledge-have not been clinically tested, and evidence for the potential of CDC-optimizing approaches has yet to be generated in humans. Hence, the potency of complement activation and its impact on the clinical efficacy of therapeutic antibodies still remains to be elucidated in clinical trials encompassing novel complement-enhancing molecules.