gebhart/patrepeval huggingface dataset:
Short-term succinic acid treatment mitigates cerebellar mitochondrial OXPHOS dysfunction, neurodegeneration and ataxia in a Purkinje-specific spinocerebellar ataxia type 1 (SCA1) mouse model (2017)

Mitochondrial dysfunction plays a significant role in neurodegenerative disease including ataxias and other movement disorders, particularly those marked by progressive degeneration in the cerebellum. In this study, we investigate the role of mitochondrial oxidative phosphorylation (OXPHOS) deficits in cerebellar tissue of a Purkinje cell-driven spinocerebellar ataxia type 1 (SCA1) mouse. Using RNA sequencing transcriptomics, OXPHOS complex assembly analysis and oxygen consumption assays, we report that in the presence of mutant polyglutamine-expanded ataxin-1, SCA1 mice display deficits in cerebellar OXPHOS complex I (NADH-coenzyme Q oxidoreductase). Complex I genes are upregulated at the time of symptom onset and upregulation persists into late stage disease; yet, functional assembly of complex I macromolecules are diminished and oxygen respiration through complex I is reduced. Acute treatment of postsymptomatic SCA1 mice with succinic acid, a complex II (succinate dehydrogenase) electron donor to bypass complex I dysfunction, ameliorated cerebellar OXPHOS dysfunction, reduced cerebellar pathology and improved motor behavior. Thus, exploration of mitochondrial dysfunction and its role in neurodegenerative ataxias, and warrants further investigation.
Design and Fabrication of a Multichannel Adaptive Optical Processor (MADOP) (1992)

We designed and built a multichannel adaptive optical processor (MADOP) for the purpose of adaptive cancellation of broadband jamming noise in C-Band antenna arrays. The processor operates at an intermediate frequency (IF) of 80 MHz and is designed to provide greater than 30 dB cancellation of two independent 10 MHz bandwidth noise jammers, where multiple reflections of the jamming energy collected in the sidelobes produce multipath delays of up to 5 usec. The MADOP architecture is portable and designed to function as an on-line 'smart filter' which adaptively cancels broadband noise in the sidelobes. Optical signal processing, Adaptive processing, Acousto-optics, Noise cancellation.
A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-gamma. (1986)

The addition of concanavalin A-stimulated supernatants of the helper T cell clone, D9.1, to cultures of lipopolysaccharide (LPS)-stimulated T-depleted mouse spleen cells caused more than a 100-fold increase in immunoglobulin (Ig) E production. These supernatants cause a 10-fold to 15-fold increase in IgG1, a fivefold to 10-fold increase in IgA, and a fivefold to 10-fold decrease in IgG3. These effects are optimal when the supernatants are added 1 to 2 days after stimulation with LPS. Cells from mouse strains that normally give little or no IgE response in vivo give normal IgE levels in response to LPS plus the supernatant of Concanavalin A-stimulated D9.1 cells in vitro. The enhancement of both IgE and IgG1 can be completely inhibited by relatively low concentrations of interferon-gamma (IFN-gamma). Both the IgE-enhancing activity and IFN-gamma act directly upon purified B cells.
Can We Afford to Waste Carbon Dioxide? Carbon Dioxide as a Valuable Source of Carbon for the Production of Light Olefins (2011)

Concerns about climate change have increased the amount of activity on carbon capture and sequestration (CCS) as one of the solutions to the problem of rising levels of CO(2) in the troposphere, while the reuse of CO(2) (carbon capture and recycling; CCR) has only recently received more attention. CCR is focused on the possibility of using CO(2) as a cheap (or even negative-value) raw material. This Concept paper analyzes this possibility from a different perspective: In a sustainable vision, can we afford to waste CO(2) as a source of carbon in a changing world faced with a fast depletion of natural carbon sources and in need of a low-carbon, resource-efficient economy? One of the points emerging from this discussion concerns the use of CO(2) for the production of olefins (substituting into or integrating with current energy-intensive methodologies that start from oil or syngas from other fossil fuel resources) if H(2) from renewable resources were available at competitive costs. This offers an opportunity to accelerate the introduction of renewable energy into the chemical production chain, and thus to improve resource efficiency in this important manufacturing sector.
Human Appropriation of Renewable Fresh Water (1996)

Humanity now uses 26 percent of total terrestrial evapotranspiration and 54 percent of runoff that is geographically and temporally accessible. Increased use of evapotranspiration will confer minimal benefits globally because most land suitable for rain-fed agriculture is already in production. New dam construction could increase accessible runoff by about 10 percent over the next 30 years, whereas population is projected to increase by more than 45 percent during that period.
Transglutaminase-Mediated PEGylation of Proteins: Direct Identification of the Sites of Protein Modification by Mass Spectrometry using a Novel Monodisperse PEG (2009)

Poly(ethylene glycol) (PEG) has been widely used to prolong the residence time of proteins in blood and to decrease their immunogenicity and antigenicity. A drawback of this polymer lies in its polydispersity that makes difficult the identification of the sites of protein modification. This is a mandatory requirement if a PEGylated protein should be approved as a drug. Here, a fast and reliable method is proposed to characterize proteins conjugated at the level of glutamine (Gln) residues using microbial transglutaminase (TGase). The novelty resides in the use of a monodisperse Boc-PEG-NH(2) for the derivatization that allows the direct identification of the sites of PEGylation by electrospray ionization mass spectrometry (ESI-MS). The procedure has been tested on three model proteins, namely, human granulocyte colony-stimulating factor, human growth hormone, and horse heart apomyoglobin. The Gln residues linked to the polymer chain were easily identified by ESI-MS and tandem MS analyses, demonstrating the advantage of using a monodisperse polymer in combination with mass spectrometry for an easy characterization of conjugated proteins. Interestingly, the PEGylation reaction led to the production only of mono- and bis-derivative products, indicating that the TGase-mediated PEGylation can be extremely selective and thus very useful for the derivatization of protein drugs.
Increasing Secretion of a Bivalent Anti-T-Cell Immunotoxin by Pichia pastoris (2004)

The bivalent anti-T-cell immunotoxin A-dmDT390-bisFv(G(4)S) was developed for treatment of T-cell leukemia and autoimmune diseases and for tolerance induction for transplantation. This immunotoxin was produced extracellularly in toxin-sensitive Pichia pastoris JW102 (Mut(+)) under control of the AOX1 promoter. There were two major barriers to efficient immunotoxin production, the toxicity of the immunotoxin for P. pastoris and the limited capacity of P. pastoris to secrete the immunotoxin. The immunotoxin toxicity resulted in a decrease in the methanol consumption rate, cessation of cell growth, and low immunotoxin productivity after the first 22 h of methanol induction. Continuous cell growth and continuous immunotoxin secretion after the first 22 h of methanol induction were obtained by adding glycerol to the methanol feed by using a 4:1 methanol-glycerol mixed feed as an energy source and by continuously adding a yeast extract solution during methanol induction. The secretory capacity was increased from 22.5 to 37 mg/liter by lowering the induction temperature. A low temperature reduced the methanol consumption rate and protease activity in the supernatant but not cell growth. The effects of adding glycerol and yeast extract to the methanol feed were synergistic. Adding yeast extract primarily enhanced methanol utilization and cell growth, while adding glycerol primarily enhanced immunotoxin production. The synergy was further enhanced by decreasing the induction temperature from 23 to 15 degrees C, which resulted in a robust process with a yield of 37 mg/liter, which was sevenfold greater than the yield previously reported for a toxin-resistant CHO cell expression system. This methodology should be applicable to other toxin-related recombinant proteins in toxin-sensitive P. pastoris.
Use of the glucose starvation-inducible glucose-regulated protein 78 promoter in suicide gene therapy of murine fibrosarcoma. (1999)

A new strategy in anticancer gene therapy uses stress-responsive cellular promoters that offer the advantage of enhanced gene expression in a variety of tumors. Although the feasibility of their selective expression has been demonstrated, functional evidence of their ability to activate therapeutic agents within the tumor environment leading to tumor eradication has not been established. Glucose deprivation, chronic anoxia, and acidic pH known to persist in poorly vascularized solid tumors strongly induce the transcription of the glucose-regulated protein 78 (grp78) gene, which encodes an Mr 78,000 stress-inducible protein. In this report, we tested directly the efficacy of the grp78 promoter in a retroviral system to drive the expression of the herpes simplex virus-thymidine kinase (HSVtk) suicide gene, using a murine fibrosarcoma model, in the context of their syngeneic, immunocompetent hosts. Our results showed that under glucose starvation conditions, the expression of HSVTK was enhanced in tumor cells where the HSVtk gene was driven by the internal grp78 promoter, in contrast to the Moloney murine leukemia virus long terminal repeat, where suppression was observed. We further demonstrated that in vivo, HSVTK expression was elevated to much higher levels inside tumors when driven by the internal grp78 promoter, resulting in complete eradication of sizable tumor mass, with no recurrence of tumor growth. Our study suggests that the glucose starvation-inducible grp78 promoter could be useful for enhanced expression of a variety of therapeutic agents within the solid tumor environment.
Interferon-beta sub 1b treatment decreases tumor necrosis factor-alpha and increases interleukin-6 production in multiple sclerosis (1996)

MS is presumed to be a T-cell-mediated chronic inflammatory disease of the CNS. We examined proliferation and cytokine secretion of mononuclear cells after stimulation with OKT3 [anti-CD3] monoclonal antibody (MAb) or concanavalin A (Con A) in subjects with stable relapsing-remitting MS (RR MS) before and after initiating interferon (IFN)-beta 1b treatment. There was no significant difference in pretreatment to on-treatment anti-CD3 mAb or Con A-induced proliferation in RR MS patients. There was significantly increased Con A-induced secretion of tumor necrosis factor (TNF)-alpha, IFN-gamma, interleukin (IL)-2, IL-6, and IL-10 and decreased IL-4 secretion in on-treatment compared with pretreatment peripheral blood mononuclear cell samples. However, on-treatment CD3-mediated secretion of TNF-alpha was significantly decreased, and IL-6 secretion was significantly increased compared with pretreatment values. IFN-gamma was also decreased in on-treatment cultures stimulated with anti-CD3 MAb, but these values did not reach statistical significance. Systemic side effects from IFN-beta 1b were associated with increased IL-6 secretion. There were no significant changes in CD3-mediated IL-4, IL-10, transforming growth factor (TGF)-beta, or IL-2 secretion or Con A-induced TGF-beta secretion. IFN-beta 1b (Betaseron) decreases CD3-mediated TNF-alpha secretion but increases another inflammatory cytokine, IL-6, that could potentially counteract its beneficial immunomodulatory effects.
Measurement and Control of Dissolved Carbon Dioxide in Mammalian Cell Culture Processes Using an in Situ Fiber Optic Chemical Sensor (2000)

At high viable cell concentrations in large-scale mammalian cell culture processes, the accumulation of dissolved carbon dioxide (dCO(2), typically quantified as an equilibrium gas-phase concentration) becomes problematic as a result of low CO(2) removal rates at reduced surface-to-volume ratios. High dCO(2) concentrations have previously been shown to inhibit cell growth and product formation in mammalian cells and to alter the glycosylation pattern of recombinant proteins. Therefore, reliable monitoring and control of dCO(2) are important for successful large-scale operation. Off-line measurements by instruments such as blood gas analyzers (BGA) are constrained by the low frequency of data collection and cannot be used for on-line control. In a preliminary evaluation of the YSI 8500 in situ sensor, a response time (t(90%)) of 6 min, sensitivity of 0.5% CO(2) (3.6 mmHg), and linearity of measurement (R(2) = 0.9997) between the equivalent gas-phase partial pressure of 0-180 mmHg (0% and 25% CO(2)) were established. Measurements were found to be unaffected by culture pH and typical mammalian cell culture concentrations of glucose, glutamine, glutamate, lactate, and ammonium. The sensor withstood repeated sterilization and cleaning cycles. The reliability of this sensor was demonstrated in microcarrier-based Chinese hamster ovary (CHO) cell perfusion cultures at reactor scales of 30, 40, 340, and 2000 L and was successfully implemented in a dCO(2) control strategy using N(2) sparging.
Weakly-supervised Disentangling with Recurrent Transformations for 3D View Synthesis (2016)

An important problem for both graphics and vision is to synthesize novel views of a 3D object from a single image. This is particularly challenging due to the partial observability inherent in projecting a 3D object onto the image space, and the ill-posedness of inferring object shape and pose. However, we can train a neural network to address the problem if we restrict our attention to specific object categories (in our case faces and chairs) for which we can gather ample training data. In this paper, we propose a novel recurrent convolutional encoder-decoder network that is trained end-to-end on the task of rendering rotated objects starting from a single image. The recurrent structure allows our model to capture long-term dependencies along a sequence of transformations. We demonstrate the quality of its predictions for human faces on the Multi-PIE dataset and for a dataset of 3D chair models, and also show its ability to disentangle latent factors of variation (e.g., identity and pose) without using full supervision.
Clinical NMR imaging of the brain: 140 cases (1982)

Cranial nuclear magnetic resonance (NMR) scans were performed on 13 healthy volunteers and 140 patients with a broad spectrum of neurologic disease and compared with x-ray computed tomography (CT) scans. The NMR scans included a variety of sequences reflecting proton density, blood flow, T1, and T2 as well as transverse, sagittal, and coronal images. White matter, gray matter, and cerebrospinal fluid were clearly distinguished in the normal brain with inversion-recovery (IR) sequences, and normal progressive myelination was demonstrated in infants and children. Acute hemorrhages displayed short T1 values, but other pathologic processes such as infarction, infection, demyelination, edema, and malignancy were associated with long T1 values. Cysts had very long T1 values (about that of cerebrospinal fluid). Spin-echo (SE) sequences showed increased values of T2 in a variety of conditions and highlighted lesions against the relatively featureless background of the remaining brain. With inversion-recovery scans, different stages of infarction were recognized in the hemispheres. NMR was more useful than CT in demonstrating brainstem infarction. The white matter lesions in demyelinating diseases were well demonstrated with NMR scans. Many more lesions were observed in multiple sclerosis with NMR than with CT. Benign tumors were well seen and usually had shorter T1 values than malignant tumors. Mass effects from tumors were generally better demonstrated with NMR than with CT, including more subtle mass effects such as displacement of the external capsule. Abnormalities were seen in diseases of the basal ganglia, including marked atrophy of the head of the caudate nucleus in Huntington chorea. Advantages of NMR imaging include the high level of gray-white matter contrast, lack of bone artifact, variety of possible sequences, transverse, sagittal, and coronal imaging, sensitivity to pathologic change, and lack of known hazard. Disadvantages include lack of bone detail, limited spatial resolution, lack of contrast agents, and cost. Promising directions for future clinical research include developmental neurology, tissue characterization with T1 and T2, assessment of blood flow, and the development of contrast agents. Much more detailed evaluation will be required, but NMR seems to be a potentially important addition to existing techniques of neurologic diagnosis.
Design, Synthesis, and Evaluation of Indolinones as Triple Angiokinase Inhibitors and the Discovery of a Highly Specific 6-Methoxycarbonyl-Substituted Indolinone (BIBF 1120) (2009)

Inhibition of tumor angiogenesis through blockade of the vascular endothelial growth factor (VEGF) signaling pathway is a new treatment modality in oncology. Preclinical findings suggest that blockade of additional pro-angiogenic kinases, such as fibroblast and platelet-derived growth factor receptors (FGFR and PDGFR), may improve the efficacy of pharmacological cancer treatment. Indolinones substituted in position 6 were identified as selective inhibitors of VEGF-, PDGF-, and FGF-receptor kinases. In particular, 6-methoxycarbonyl-substituted indolinones showed a highly favorable selectivity profile. Optimization identified potent inhibitors of VEGF-related endothelial cell proliferation with additional efficacy on pericyctes and smooth muscle cells. In contrast, no direct inhibition of tumor cell proliferation was observed. Compounds 2 (BIBF 1000) and 3 (BIBF 1120) are orally available and display encouraging efficacy in in vivo tumor models while being well tolerated. The triple angiokinase inhibitor 3 is currently in phase III clinical trials for the treatment of nonsmall cell lung cancer.
Improved Development to Blastocyst of Ovine Nuclear Transfer Embryos Reconstructed during the Presumptive S-Phase of Enucleated Activated Oocytes (1994)

The timing of pronuclear formation and the initiation and duration of the DNA synthetic period (S-phase) were determined during the first cell cycle of electrically activated ovine oocytes matured in vivo. Reconstructed embryos were produced by electro-fusion-mediated nuclear transfer of unsynchronized single blastomeres. These were derived from embryos produced in vivo at the 16-cell stage (Day 4) and transferred to enucleated metaphase II oocytes at the time of activation or to enucleated activated oocytes during early, mid, and late stages of the presumptive S-phase. The frequency of development to blastocyst was greatest in embryos reconstructed during the presumptive S-phase of enucleated activated oocytes than in embryos reconstructed at the time of activation (mean 55.4% vs. 21.3%). No significant differences were observed when embryos were reconstructed during early, mid, or late stages of the presumptive S-phase (61.3%, 45.7%, and 57.7%, respectively). The results indicate that the use of enucleated activated oocytes as cytoplasts for embryo reconstruction can increase the frequency of development to blastocyst of embryos reconstructed from unsynchronized donor blastomeres.
Schizophrenia and Drug Delivery Systems (2000)

Schizophrenia is a severe non-curable illness of the brain with serious consequences if not properly treated and kept under control. Antipsychotic drugs have revolutionised the therapy and management of schizophrenia. However, patient compliance rates are notoriously poor due to the nature of the disease and troublesome side-effects, and are major causes of symptom recurrence. Although some new antipsychotic agents have been marketed to offer broader efficacy with much reduced side-effect profiles, the drug delivery systems for antipsychotics are still in the stage of conventional dosage forms, such as tablets, capsules and solutions, and need to be dosed at the frequency of 2-4 times daily. Doubtless. novel drug delivery systems, such as sustained and controlled release systems, will be useful for antipsychotics. They should reduce the frequency of dosing. enhance drug bioavailability and improve patient compliance. In this article, the specificity and characterisation of schizophrenia and pathophysiology. drug therapy. and the development and future prospects of neuroleptic drug delivery systems are reviewed.
Opaque: an oblivious and encrypted distributed analytics platform (2017)

Many systems run rich analytics on sensitive data in the cloud, but are prone to data breaches. Hardware enclaves promise data confidentiality and secure execution of arbitrary computation, yet still suffer from access pattern leakage. We propose Opaque, a distributed data analytics platform supporting a wide range of queries while providing strong security guarantees. Opaque introduces new distributed oblivious relational operators that hide access patterns, and new query planning techniques to optimize these new operators. Opaque is implemented on Spark SQL with few changes to the underlying system. Opaque provides data encryption, authentication and computation verification with a performance ranging from 52% faster to 3.3x slower as compared to vanilla Spark SQL; obliviousness comes with a 1.6-46x overhead. Opaque provides an improvement of three orders of magnitude over state-of-the-art oblivious protocols, and our query optimization techniques improve performance by 2-5x.
Beyond paper (1998)

Reading frequently involves not just looking at words on a page, but also underlining, highlighting and commenting, either on the text or in a separate notebook. This combination of reading with critical thinking and learning is called active reading [2]. To explore the premise that computation can enhance active reading we have built the XLibris “active reading machine.” XLibris uses a commercial high-resolution pen tablet display along with a paper-like user interface to support the key affordances of paper for active reading: the reader can hold a scanned image of a page in his lap and mark on it with digital ink. To go beyond paper, XLibris monitors the free-form ink annotations made while reading, and uses these to organize and to search for information. Readers can review, sort and filter clippings of their annotated text in a “Reader's Notebook.” XLibris also searches for material related to the annotated text, and displays links to similar documents unobtrusively in the margin. XLibris demonstrates that computers can help active readers organize and find information while retaining many of the advantages of reading on paper.