gebhart/patrepeval huggingface dataset:
Response to Emotional Expressions in Generalized Social Phobia and Generalized Anxiety Disorder: Evidence for Separate Disorders (2008)

These results suggest that neural circuitry dysfunctions differ in generalized social phobia and generalized anxiety disorder.
CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells (2017)

Immunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize programmed cell death protein 1 [PD-1]) have both opened new avenues for cancer treatment, but the clinical potential of combined disruption of inhibitory checkpoints and CAR T cell therapy remains incompletely explored. Here we show that programmed death ligand 1 (PD-L1) expression on tumor cells can render human CAR T cells (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired tumor clearance in a sub-cutaneous xenograft model. To overcome this suppressed anti-tumor response, we developed a protocol for combined Cas9 ribonucleoprotein (Cas9 RNP)-mediated gene editing and lentiviral transduction to generate PD-1 deficient anti-CD19 CAR T cells. Pdcd1 (PD-1) disruption augmented CAR T cell mediated killing of tumor cells in vitro and enhanced clearance of PD-L1+ tumor xenografts in vivo. This study demonstrates improved therapeutic efficacy of Cas9-edited CAR T cells and highlights the potential of precision genome engineering to enhance next-generation cell therapies.
Linearization of Nonlinear Lexical Representations. (1997)

This paper presents a new schema for handling nonlinear morphology. The schema argues for linearizing nonlinear representations before applying phonological and morphological rules. 1 Introduction and Problem Statement Languages which exhibit templatic morphology have been lately treated using multi-tape finite state transducers, with one tape representing surface forms and the remaining tapes representing lexical forms (see (Kay, 1987; Kiraz, Forthcoming)). There are a number of advantages for using this multi-tape model. Not only does it accurately represent the linguistic insights behind the templatic nonlinear nature of these languages, it also allows the computational linguist to compile efficient, relatively small morphological lexica as opposed to lexica containing millions of entries. However, maintaining a nonlinear lexical representation has its own inconveniences and computational complexities. Firstly, the writer of multi-tape rules must keep track of multiple representat...
A Peptide Inhibiting the Collagen Binding Function of Integrin α2I Domain (1999)

Integrin alpha2 subunit forms in the complex with the beta1 subunit a cell surface receptor binding extracellular matrix molecules, such as collagens and laminin-1. It is a receptor for echovirus-1, as well. Ligands are recognized by the special "inserted" domain (I domain) in the integrin alpha2 subunit. Venom from a pit viper, Bothrops jararaca, has been shown to inhibit the interaction of platelet alpha2beta1 integrin with collagen because of the action of a disintegrin/metalloproteinase named jararhagin. The finding that crude B. jararaca venom could prevent the binding of human recombinant ralpha2I domain to type I collagen led us to study jararhagin further. Synthetic peptides representing hydrophilic and charged sequences of jararhagin, including the RSECD sequence replacing the well known RGD motif in the disintegrin-like domain, were synthesized. Although the disintegrin-like domain derived peptides failed to inhibit ralpha2I domain binding to collagen, a basic peptide from the metalloproteinase domain proved to be functional. In an in vitro assay, the cyclic peptide, CTRKKHDNAQC, was shown to bind strongly to human recombinant alpha2I domain and to prevent its binding to type I and IV collagens and to laminin-1. Mutational analysis indicated that a sequence of three amino acids, arginine-lysine-lysine (RKK), is essential for ralpha2I domain binding, whereas the mutation of the other amino acids in the peptide had little if any effect on its binding function. Importantly, the peptide was functional only in the cyclic conformation and its affinity was strictly dependent on the size of the cysteine-constrained loop. Furthermore, the peptide could not bind to alpha2I domain in the absence of Mg2+, suggesting that the conformation of the I domain was critical, as well. Cells could attach to the peptide only if they expressed alpha2beta1 integrin, and the attachment was inhibited by anti-integrin antibodies.
Implantable Cardioverter‐Defibrillator: Patient Selection and Implantation Protocol (1984)

The experience obtained from the clinical trials with the automatic implantable cardioverter-defibrillator have reemphasized the need for a detailed pathophysiologic evaluation of the patient preoperatively. This evaluation requires careful documentation of the probable cause of the ventricular tachyarrhythmia and evaluation of other surgical needs of the patient, as well as consideration of the interactive effects of pacemakers and concurrent pharmacologic therapy postoperatively.
Small, resting B cells can be induced to proliferate by direct signals from activated helper T cells. (1984)

We have investigated the role of T lymphocytes in the activation of small, resting B cells. Homogeneous populations of small human B cells were purified with a fluorescence-activated cell sorter by positive and negative immunofluorescent staining techniques. When these small B cells were cultured with mitogen-activated Leu-3+ T cells, significant B cell proliferation was observed. This T cell-dependent B cell proliferative response did not require cross-linkage of B cell surface immunoglobulin molecules or B cell exposure to the mitogens employed for T cell activation. Culture supernatants from activated helper T cells could neither induce small B cell proliferation nor augment the B cell response observed with limiting numbers of T cells. These data indicate that activated helper T cells can provide all the signals required for the activation and proliferation of small, resting B cells and suggest that direct T-B cell contact is a critical element for this T-B cell interaction.
AAV-mediated intravitreal gene therapy reduces lysosomal storage in the retinal pigmented epithelium and improves retinal function in adult MPS VII mice (2004)

The beta-glucuronidase-deficient mucopolysaccharidosis type VII (MPS VII) mouse accumulates partially degraded glycosaminoglycans in many cell types, including retinal pigmented epithelial (RPE) cells in the eye. This lysosomal storage in RPE cells leads to progressive retinal degeneration and reduced function as measured by flash electroretinography (ERG). The impact of AAV-mediated intraocular gene therapy on pathology and retinal function was examined in normal and MPS VII mice treated at 4 weeks of age, when lysosomal storage is evident but functional impairment is minimal in affected animals. At 16 weeks, an age at which untreated MPS VII mice have advanced histologic lesions and significantly reduced ERG amplitudes, treated eyes had nearly normal levels of beta-glucuronidase activity, preservation of cells in the outer nuclear layer of the retina, and decreased lysosomal storage within the RPE. The AAV-treated MPS VII mice also had significantly increased dark-adapted ERG amplitudes compared to untreated MPS VII mice. Although retinal function was improved, the efficacy of the treatment depended heavily on parameters related to the injection procedure, such as the injection volume, injection site, and vector dose. These data suggest that intraocular AAV-mediated therapy may be efficacious for treating the retinal disease associated with certain lysosomal storage diseases.
Simics: A full system simulation platform (2002)

Full system simulation seeks to strike a balance between accuracy and performance. Many of its possibilities have been obvious to practitioners in both academia and industry for quite some time, perhaps decades, but Simics supports more of these possibilities within a single framework than other tools do. Simics is a platform for full system simulation that can run actual firmware and completely unmodified kernel and driver code. It is sufficiently abstract to achieve tolerable performance levels, and it provides both functional accuracy for running commercial workloads and sufficient timing accuracy to interface to detailed hardware models. Simics can also run a heterogeneous network of systems from different vendors within the same framework. Exceptionally fast, Simics can easily add new components and leverage older ones within a practical abstraction level. It offers a platform with a rich API and a powerful scripting environment for use in a broad range of applications.
TNF-alpha, IL-6 and IFN-gamma secreted by bronchoalveolar leukocytes isolated from patients with bronchial asthma, complicated by fungal airways infections. (1998)

It is widely known that fungal airways infections may deteriorate the course of bronchial asthma. The mechanism of the phenomenon is still unclear. The aim of our study was to assess the effect of fungal infections on the secretion of selected cytokines by bronchoalveolar leukocytes. Five patients (group FA) with bronchial asthma and Candida albicans or Aspergillus fumigatus airways infections (confirmed by bronchoscopy and culture) were included in the study. All of them were on the chronic treatment with corticosteroids (10-20 mg of prednisone per day) and underwent several courses of therapy with antibiotics. The control groups comprised 5 previously untreated asthmatics without bronchial colonization with fungi (group A) as well as 5 healthy volunteers (group H). Leukocytes were isolated from bronchoalveolar lavage fluid (BALF) and cultured in the presence or absence of cytokine inducers such as phytohemagglutin L (PHA), lipo-polysaccharide (LPS) from E. coli. The activity of TNF-alpha, IL-6 and IFN-gamma were measured in the BAL cell culture supernatants by using specific bioassays. In comparison with healthy controls the spontaneous or induced secretion of cytokines were significantly augmented in patients from group A. In contrast the asthmatics who represented group FA demonstrated normal levels of spontaneous cytokine secretion. However, the tendency to increase LPS and PHA-induced production was observed in BAL leukocytes from the patients. The above results support the view that beneficial effect of corticosteroid treatment in bronchial asthma may act, at least in part, by inhibition of the high spontaneous secretion of proinflammatory cytokines. Nevertheless, fungal airways infections may lead to increase of LPS- or PHA-induced production of TNF-alpha, IL-6 or IFN-gamma (despite prednisone therapy) by prestimulation of the BAL cells with fungi.
Engineering Chemical Reactivity on Cell Surfaces Through Oligosaccharide Biosynthesis (1997)

Cell surface oligosaccharides can be engineered to display unusual functional groups for the selective chemical remodeling of cell surfaces. An unnatural derivative of N-acetyl-mannosamine, which has a ketone group, was converted to the corresponding sialic acid and incorporated into cell surface oligosaccharides metabolically, resulting in the cell surface display of ketone groups. The ketone group on the cell surface can then be covalently ligated under physiological conditions with molecules carrying a complementary reactive functional group such as the hydrazide. Cell surface reactions of this kind should prove useful in the introduction of new recognition epitopes, such as peptides, oligosaccharides, or small organic molecules, onto cell surfaces and in the subsequent modulation of cell-cell or cell-small molecule binding events. The versatility of this technology was demonstrated by an example of selective drug delivery. Cells were decorated with biotin through selective conjugation to ketone groups, and selectively killed in the presence of a ricin A chain-avidin conjugate.
Detection of Nanoscale Magnetic Activity Using a Single Carbon Nanotube (2008)

The ultimate conductometric sensor for ferromagnetic activity of nanoscale magnetic materials could be a single carbon nanotube. We show that the electrical conductance of an individual carbon nanotube is sensitive to magnetic transitions of nanoscale magnets embedded inside it. To establish this, multiwall carbon nanotubes were impregnated with cobalt nanoclusters. Temperature dependence of conductance (5 K < T <300 K) of these nanotubes shows the usual Lüttinger-liquid power law behavior at higher temperatures and an onset of Coulomb blockade at lower temperatures. At the lowest temperature (T approximately 6 K), the differential conductance (dI/dV versus V) develops aperiodic fluctuations under an external magnetic field B, the rms amplitude of which grows with the magnitude of the field itself. Low-temperature magnetoconductance, studied as function of temperature and bias, can be interpreted in terms of weak antilocalization effects due to the presence of the magnetized clusters. The temperature dependence of magnetoconductance further presents a "peak"-like feature and slow dynamics around T =55 K, which depend on the magnitude and history of the applied B field. These observations indicate a sensitivity of electronic transport in the multiwall nanotubes to the dynamics of nanoscale magnets at low temperature.
Vaccines against human papillomavirus (2006)

Human papillomavirus has been identified as an etiological factor for cervical cancer, anogenital cancers and a subset of head and neck cancers. These important observations suggest that HPV vaccines have potential in the prevention and treatment of cervical cancer and other HPV-associated malignancies. The HPV genome encodes two HPV late genes, L1 and L2, which form the viral capsid. Early viral proteins support viral genome replication, two of which (E6 and E7) are important for HPV associated malignant transformation. Prophylactic HPV vaccines prevent infection by inducing neutralizing antibodies against HPV capsid proteins L1 and L2. However, because HPV-infected basal keratinocytes and HPV-transformed cells generally do not express L1 or L2, therapeutic HPV vaccines aim to treat established HPV infections and HPV-associated malignancies by targeting non-structural early viral antigens of HPV such as E6 and E7. Results from preclinical HPV vaccine studies have led to several HPV vaccine clinical trials. If these prophylactic and therapeutic HPV vaccines prove as successful in patients as they have in animal models, vaccination may provide for control and eventually eradication of oncogenic HPV infection and HPV-related cancers.
Clinical Global Impression of Change in Physical Frailty: Development of a Measure Based on Clinical Judgment (2004)

The CGIC-PF is a structured assessment of change in physical frailty with defined content and process. It has strong face validity, reliability, and feasibility for use in clinical research. It may be useful as one criterion of change and as an anchor for change in other measures.
Oligosacáridos en la leche humana (2007)

La leche materna contiene mas de 130 oligosacaridos distintos, que constituyen el tercer componente de esta. Su concentracion total disminuye a medida que avanza el curso de lactancia, de modo que al ano contiene menos de la mitad que en las primeras semanas de vida. Los oligosacaridos mas abundantes en la leche humana son libres (no conjugados) y neutros y contienen fucosa. Los oligosacaridos fucosilados pueden tener un enlace 2-fucosa o 3-fucosa, composicion que varia segun la procedencia de las madres y el curso de la lactancia. Los oligosacaridos actuan como receptores competitivos sobre la superficie celular del huesped, previniendo asi la adherencia de determinados patogenos. La fraccion de oligosacaridos no digerida en la leche materna estimula el crecimiento de bifidobacterias en el colon, y esta flora podria tener efectos beneficiosos de proteccion frente a infecciones entericas. Asi, los oligosacaridos son un componente principal del sistema inmunologico innato por el cual la madre protege a su hijo de patogenos (entericos o de otra localizacion) durante la lactancia.
Low threshold oxide-confined InAs quantum dash ridge waveguide lasers on InP substrates (2002)

Oxide-confined ridge waveguide semiconductor lasers with a new type of low-dimensional active region - the self-assembled InAs "quantum dash" - are demonstrated. The name "dash" comes from a physical description of what is essentially an InAs QD that is elongated in one crystalline direction. They have room-temperature operation wavelength of 1.57 /spl mu/m, a high injection efficiency of 87%, and a low threshold current density of 450 A/cm/sup 2/.
Molecular and functional characterization of eight novel GAA mutations in Italian infants with Pompe disease (2008)

We characterized 29 unrelated patients presenting with the severe form of Pompe disease (Glycogen Storage Disease Type II, acid maltase deficiency) and identified 26 pathogenic mutations divided over 28 different genotypes. Among the eight new mutations, five were exonic point mutations (c.572A>G, c.1124G>T, c.1202A>G, c.1564C>G and c.1796C>A) leading to codon changes (p.Y191C, p.R375L, p.Q401R, p.P522A and p.S599Y); two were intronic point mutations (c.-32-3C>A and c.1636+5G>C) affecting mRNA processing; one was a single base deletion (c.742delC) generating a truncated protein (p.L248PfsX20). A comprehensive evaluation, based on different methodological approaches, confirmed the detrimental effect of the eight mutations on the protein and its function. Structural alterations potentially induced by the five missense mutations were also predicted through visual inspection of the atomic model of the GAA protein, in terms of both function and spatial orientation of specific residues as well as disturbance generated by amino acid substitutions. Although the remarkable heterogeneity of the mutational spectrum in Pompe disease was already known, our data demonstrate and confirm the power of molecular and functional analysis in predicting the natural course of Pompe disease.
Neuroprotective Effects ofClostridium butyricumagainst Vascular Dementia in Mice via Metabolic Butyrate (2015)

Probiotics actively participate in neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and vascular dementia (VaD) remains unclear. We used a mouse model of VaD induced by a permanent right unilateral common carotid arteries occlusion (rUCCAO) to investigate the neuroprotective effects and possible underlying mechanisms of Clostridium butyricum. Following rUCCAO, C. butyricum was intragastrically administered for 6 successive weeks. Cognitive function was estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The BDNF-PI3K/Akt pathway-related proteins were assessed by western blot and immunohistochemistry. The diversity of gut microbiota and the levels of butyrate in the feces and the brains were determined. The results showed that C. butyricum significantly attenuated the cognitive dysfunction and histopathological changes in VaD mice. C. butyricum not only increased the levels of BDNF and Bcl-2 and decreased level of Bax but also induced Akt phosphorylation (p-Akt) and ultimately reduced neuronal apoptosis. Moreover, C. butyricum could regulate the gut microbiota and restore the butyrate content in the feces and the brains. These results suggest that C. butyricum might be effective in the treatment of VaD by regulating the gut-brain axis and that it can be considered a new therapeutic strategy against VaD.
Molecular cloning and properties of a full-length putative thyroid hormone receptor coactivator. (1996)

Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that regulate target gene transcription. The conserved carboxy-terminal region of the ligand-binding domain (AF-2) has been thought to play a critical role in mediating ligand-dependent transactivation by the interaction with coactivator(s). Using bacterially-expressed TR as a probe, far-Western-based expression cDNA library screening identified cDNAs that encode, in part, the recently reported partial steroid receptor coactivator-1 (SRC-1) sequence. Additional work, including 5' RACE, has characterized a full-length cDNA that encodes a approximately 160 kD protein as a putative thyroid hormone receptor coactivator (F-SRC-1). In vitro binding studies show that F-SRC-1 binds to a variety of nuclear hormone receptors in a ligand-dependent manner, along with TBP and TFIIB, suggesting that F-SRC-1 may play a role as a bridging molecule between nuclear hormone receptors and general transcription factors. Interestingly, AF-2 mutants also retain ligand-dependent interaction with F-SRC-1. Although F-SRC-1 recognizes the ligand-induced conformational changes of nuclear hormone receptors, our observations suggest that F-SRC-1 may bind directly with subregion(s) in nuclear hormone receptors other than the AF-2 region.
A presentation of pulsed nuclear magnetic resonance with full quantization of the radio frequency magnetic field (2002)

We show that there is excellent quantitative agreement between the usual semiclassical predictions for nuclear magnetic resonance experiments (quantized spins interacting with a classical radio frequency magnetic field, including radiation damping), and the predictions of a fully quantized description of the same experiment. We also propose a pictorial description of the relevant dynamical quantum states, which helps to lead the intuition towards the same conclusion. Our model ignores spin relaxation, and simulates the equivalent damping resistor of the sample circuit by a very long piece of lossless coaxial cable. The classical rf field (pulses and free induction decay) is described quantum mechanically by means of Glauber’s “coherent” or “quasiclassical” states.
Synthesis of 3-Alkylfuropyridines via Palladium-catalyzed Cyclization of Iodopyridinyl Allyl Ethers (1996)

The palladium-catalyzed cyclization of iodopyridinyl ally1 ethers derived from dibalopyridines and sodium ally1 alkoxide provides furo[2,3-b]pyridines, furo[3.2-clpyridines,and furo[2,3-clpy~idines. Fumpyridines are chemically interesting molecules because of their structural similarity to quinoline, isoquinoline, and benzofuran which are important nuclei in many biologically active compounds.'W e arc inter~sted in using various furopyridines instead of pyridines to develope new omeprazole , analogue^.^representive a new class of effective gastric acid secr~tion inhibitors.Several synthetic / pathways exist in the literature ;or the preparatioydf f u r ~~~r i d i n e .~ However, the scope and usefulness of those procedures are often limited by the drastic reaction conditions, multi-steps, and difficulty in preparation of starting materials.Recently, the progress in the palladium-catalyzed carbon-carbon bond forming reactions in aromatic and heteroaromatic system is removing the restriction of the thermal approaches."t was reported that the reaction of 3-pyridinol with iodine substitution with variety of I-alkynes in the presence of palladium (11) and copper iodides as co-catalyst provided 2-substituted furopyridines (eq I).'However, the synthesis of 3-alkylfuropyridine by palladium-catalyzed cyclization has not yet been
P‐8: Effects of Active Thickness in Oxide Semiconductor TFTs (2009)

Abstract The effects of active thickness on the characteristics of oxide TFTs were investigated for the case of ZnO TFT and IGZO TFT. As the decrease of active thickness, the V on (Turn‐on Voltage of TFT) was shifted to near zero Volt and negative shift of V on as decrease of channel length was also diminished. The overall performance (including subthreshold swing and leakage currents) was improved with thinner active layer. This behavior could be explained under the consideration of unintentional n‐type doping in active layer. But, for the constant‐current stress, thinner active layer TFT showed less stable behavior.