gebhart/patrepeval huggingface dataset:
Dopamine Receptors: From Structure to Function (1998)

The diverse physiological actions of dopamine are mediated by at least five distinct G protein-coupled receptor subtypes. Two D1-like receptor subtypes (D1 and D5) couple to the G protein Gs and activate adenylyl cyclase. The other receptor subtypes belong to the D2-like subfamily (D2, D3, and D4) and are prototypic of G protein-coupled receptors that inhibit adenylyl cyclase and activate K+ channels. The genes for the D1 and D5 receptors are intronless, but pseudogenes of the D5 exist. The D2 and D3 receptors vary in certain tissues and species as a result of alternative splicing, and the human D4 receptor gene exhibits extensive polymorphic variation. In the central nervous system, dopamine receptors are widely expressed because they are involved in the control of locomotion, cognition, emotion, and affect as well as neuroendocrine secretion. In the periphery, dopamine receptors are present more prominently in kidney, vasculature, and pituitary, where they affect mainly sodium homeostasis, vascular tone, and hormone secretion. Numerous genetic linkage analysis studies have failed so far to reveal unequivocal evidence for the involvement of one of these receptors in the etiology of various central nervous system disorders. However, targeted deletion of several of these dopamine receptor genes in mice should provide valuable information about their physiological functions.
Extended-Wear Soft Contact Lenses for Aphakic Correction (1983)

Evaluation of an extended-wear perfilcon A soft contact lens (Permalens) in 299 eyes of 244 patients showed that 266 eyes (89%) were successfully fitted and wore the lenses without important complications (mean follow-up, 23 months; range, four to 48 months). Use of the lens in 33 eyes was discontinued because of transient lens-related problems. "Overcorrected" acuity of 6/12 (20/40) or better (with spectacles plus the contact lens) was achieved in all patients who were without vitreous, retinal, or optic nerve disease. Seventy-six percent of patients could wear the lens for longer than one-month intervals, and 30% removed the lens at four- to six-month intervals. There were no cases of infectious corneal ulcers or scarring or permanent visual loss. Our more limited experience with lidofilcon B lenses (Sauflon PW) (24 eyes) and the silicone lenses (Silsoft) (25 eyes) also showed beneficial results.
Autoconfigurable distributed control systems (2005)

This paper discusses ongoing research on automatically configurable distributed control systems. We are investigating the use of networks of relatively small controllers that contain intelligence and communication capabilities to perform factory automation. These systems are expected to be more robust, adaptable and flexible than conventional designs. To achieve these benefits, fundamental changes in the underlying control system architecture are needed. The system architecture is divided into two portions: the control infrastructure and the control algorithms. Requirements for the control infrastructure are described that implement basic services to support distributed control, including the ability for a new control node to announce its presence and capabilities to the system without disrupting ongoing activities. The control algorithms for this system must be designed with certain properties: autonomy and cooperativeness; that are able to respond to changes in the physical plant and its usage. A laboratory for studying autoconjigurable control systems is under development using prototype distributed controllers on a CAN-based network. Two experiments are described that demonstrate autoconfiguration capability. The potential applications and the future directions of this research are discussed.
Breath Tests in the Diagnosis of Small Intestine Bacterial Overgrowth (1984)

Analysis of breath specimens for volatile metabolites of orally administered substrates offers a simplified detection method for the presence of an abnormal small-intestinal flora. This technique is not only simpler and more acceptable to patients than jejunal aspiration, but also gives quicker information to the clinician than microbiologic culture of the jejunal aspirate. Experience with a probe which is usually completely absorbed before the colon is reached (1 g 14C-xylose) has demonstrated better test sensitivity (separating normal from abnormal) and test specificity (separating bacterial overgrowth from small-bowel malabsorption) than that seen with a probe which normally has substantial passage of substrate to the colonic bacteria (as seen with the 14C-bile acid breath test). Ongoing evaluation of nonradioactive probes (H2 generation from fermentable carbohydrate, 13CO2 generation from 13C-labeled substrate similar to the principle of the 14C-xylose breath test) offers promise for use of bacterial overgrowth breath tests in children and reproductive-age females.
The Dynamic Change in the Total Arable Land and its Driving Forces in Tongling City of Anhui Province (2014)

According to Anhui Statistical Yearbook (2003-2012) and the second national land survey data, this article analyzes the current situation of land use and the dynamic change in the total arable land in Tongling City. On the basis of this, using grey relational analysis, this article analyzes the driving forces for arable land changes in Tongling City. Studies show that population growth, the improvement of level of urbanization and the rapid development of the economy are the main driving forces for arable land changes. Based on the findings, the strategies are put forth in order to ensure the dynamic balance of total arable land.
Access Control with Delegated Authorization Policy Evaluation for Data-Driven Microservice Workflows (2017)

Microservices offer a compelling competitive advantage for building data flow systems as a choreography of self-contained data endpoints that each implement a specific data processing functionality. Such a ‘single responsibility principle’ design makes them well suited for constructing scalable and flexible data integration and real-time data flow applications. In this paper, we investigate microservice based data processing workflows from a security point of view, i.e., (1) how to constrain data processing workflows with respect to dynamic authorization policies granting or denying access to certain microservice results depending on the flow of the data; (2) how to let multiple microservices contribute to a collective data-driven authorization decision and (3) how to put adequate measures in place such that the data within each individual microservice is protected against illegitimate access from unauthorized users or other microservices. Due to this multifold objective, enforcing access control on the data endpoints to prevent information leakage or preserve one’s privacy becomes far more challenging, as authorization policies can have dependencies and decision outcomes cross-cutting data in multiple microservices. To address this challenge, we present and evaluate a workflow-oriented authorization framework that enforces authorization policies in a decentralized manner and where the delegated policy evaluation leverages feature toggles that are managed at runtime by software circuit breakers to secure the distributed data processing workflows. The benefit of our solution is that, on the one hand, authorization policies restrict access to the data endpoints of the microservices, and on the other hand, microservices can safely rely on other data endpoints to collectively evaluate cross-cutting access control decisions without having to rely on a shared storage backend holding all the necessary information for the policy evaluation.
Towards new applications using capillary waveguides (2015)

In this paper we demonstrate the enhancement of the sensing capabilities of glass capillaries. We exploit their properties as optical and acoustic waveguides to transform them potentially into high resolution minimally invasive endoscopic devices. We show two possible applications of silica capillary waveguides demonstrating fluorescence and optical-resolution photoacoustic imaging using a single 330 μm-thick silica capillary. A nanosecond pulsed laser is focused and scanned in front of a capillary by digital phase conjugation through the silica annular ring of the capillary, used as an optical waveguide. We demonstrate optical-resolution photoacoustic images of a 30 μm-thick nylon thread using the water-filled core of the same capillary as an acoustic waveguide, resulting in a fully passive endoscopic device. Moreover, fluorescence images of 1.5 μm beads are obtained collecting the fluorescence signal through the optical waveguide. This kind of silica-capillary waveguide together with wavefront shaping techniques such as digital phase conjugation, paves the way to minimally invasive multi-modal endoscopy.
Mechanisms of Teratogenesis (1984)

After a traumatic childhood in Europe during the Second World War, I found that scientific research in Israel was a pleasure beyond my expectations. Over the last 65 year, I have worked on the chemistry and pharmacology of natural products. During the ...Read More
MDM2-Recruiting PROTAC Offers Superior, Synergistic Antiproliferative Activity via Simultaneous Degradation of BRD4 and Stabilization of p53 (2018)

Although the number of proteins effectively targeted for posttranslational degradation by PROTAC has grown steadily, the number of E3 ligases successfully exploited to accomplish this has been limited to the few for which small-molecule ligands have been discovered. Although the E3 ligase MDM2 is bound by the nutlin class of small-molecule ligands, there are few nutlin-based PROTAC. Because a nutlin-based PROTAC should both knockdown its target protein and upregulate the tumor suppressor p53, we examined the ability of such a PROTAC to decrease cancer cell viability. A nutlin-based, BRD4-degrading PROTAC, A1874, was able to degrade its target protein by 98% with nanomolar potency. Given the complementary ability of A1874 to stabilize p53, we discovered that the nutlin-based PROTAC was more effective in inhibiting proliferation of many cancer cell lines with wild-type p53 than was a corresponding VHL-utilizing PROTAC with similar potency and efficacy to degrade BRD4. This is the first report of a PROTAC in which the E3 ligase ligand and targeting warhead combine to exert a synergistic antiproliferative effect. Our study highlights the untapped potential that may be unlocked by expanding the repertoire of E3 ligases that can be recruited by PROTAC. SIGNIFICANCE: These findings present the first BRD4-targeting MDM2-based PROTAC that possesses potent, distinct, and synergistic biological activities associated with both ends of this heterobifunctional molecule.
Increased potency of a novel d-Î²-naphthylalanine-substituted antimicrobial peptide against âfluconazole-resistant âfungal pathogens (2009)

The antifungal activities of the known antimicrobial peptide, P-113, as well as a new type of Trp-rich peptide, Ac-KWRRWVRWI-NH(2), Pac-525, and its modified peptide, D-Nal-Pac-525, were determined using the broth microdilution method in three different media. All peptides had similar activities against yeast pathogens in low-salt LYM media. However, only D-Nal-Pac-525 retained its antifungal activity in the media containing high concentrations of salt. Hence, D-Nal-Pac-525 has the potential of becoming a promising antifungal agent, especially for fungal pathogens with intrinsic resistance to fluconazole.
Functional comparison of spleen dendritic cells and dendritic cells cultured in vitro from bone marrow precursors (1996)

We have compared dendritic cells (DC) isolated from mouse spleen, or generated in vitro from bone marrow (BM) precursors cultured in granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), for the ability to process and present soluble antigen and stimulate major histocompatibility complex (MHC) Class II-restricted T cells. DC from spleen or BM cultures were equally able to stimulate the in vitro proliferation of allogeneic T cells or of antigen-specific T-cell receptor (TCR)-transgenic T cells. Both DC populations also induced comparable levels of IL-2 secretion by a T-cell hybridoma. Therefore, splenic and BM-derived DC express comparable levels of (Antigen + MHC Class II) ligands and/or costimulatory molecules and have comparable ability to stimulate T-cell responses. When presentation of a native protein antigen, rather than peptide, was evaluated, BM-derived DC were at least 50 times better than splenic DC at stimulating the proliferation of TCR-transgenic T cells. The antigen processing ability of the two populations was similar only when splenic DC were used immediately ex vivo. Therefore, unlike spleen DC, BM-derived DC maintain the capacity to process protein antigen for MHC Class II presentation during in vitro culture. Due to these characteristics, BM-derived DC may represent a useful tool in immunotherapy studies, as they combine high T-cell stimulatory properties with the capacity to process and present native antigen.
Transcranial Ultrasound Brain Perfusion Assessment With a Contrast Agent-Specific Imaging Mode (2005)

The study demonstrates that brain perfusion assessment with an ultrasound contrast-specific imaging mode is comparable between different centers using the same study protocol.
Challenges in reverse‐time migration (2004)

As a wave equation technique using two‐way hyperbolic wave equation, reverse‐time migration can handle not only multi‐arrivals but steep dips and overturned reflections also. For velocity modeling of complex geometry, reverse‐time migration is a quite attractive tool because of its capabilities of accurate imaging of salt flank and validation of built velocity model using wave equation forward modeling. Rapid development of computer hardware enables reverse‐time migration to be widely applied to production imaging problems. In this paper, we present several challenges to remove artifacts in reverse‐time migration.
Cytochrome P450 3A Inhibition by Ketoconazole Affects Prasugrel and Clopidogrel Pharmacokinetics and Pharmacodynamics Differently (2007)

Prasugrel and clopidogrel inhibit platelet aggregation through active metabolite formation. Prasugrel's active metabolite (R-138727) is formed primarily by cytochrome P450 (CYP) 3A and CYP2B6, with roles for CYP2C9 and CYP2C19. Clopidogrel's activation involves two sequential steps by CYP3A, CYP1A2, CYP2C9, CYP2C19, and/or CYP2B6. In a randomized crossover study, healthy subjects received a loading dose (LD) of prasugrel (60 mg) or clopidogrel (300 mg), followed by five daily maintenance doses (MDs) (15 and 75 mg, respectively) with or without the potent CYP3A inhibitor ketoconazole (400 mg/day). Subjects had a 2-week washout between periods. Ketoconazole decreased R-138727 and clopidogrel active metabolite Cmax (maximum plasma concentration) 34-61% after prasugrel and clopidogrel dosing. Ketoconazole did not affect R-138727 exposure or prasugrel's inhibition of platelet aggregation (IPA). Ketoconazole decreased clopidogrel's active metabolite AUC0-24 (area under the concentration-time curve to 24 h postdose) 22% (LD) to 29% (MD) and reduced IPA 28% (LD) to 33% (MD). We conclude that CYP3A4 and CYP3A5 inhibition by ketoconazole affects formation of clopidogrel's but not prasugrel's active metabolite. The decreased formation of clopidogrel's active metabolite is associated with reduced IPA.
The overexpression of RHAMM, a hyaluronan-binding protein that regulates ras signaling, correlates with overexpression of mitogen-activated protein kinase and is a significant parameter in breast cancer progression. (1998)

RHAMM is an oncogene that regulates signaling through ras and controls mitogen-activated protein kinase [extracellular signal-regulated protein kinase (ERK)] expression in embryonic murine fibroblasts. ERK is a dual-specificity kinase that controls expression of proteins relevant to tumorigenesis, proliferation, and motility. To assess whether RHAMM and ERK are involved in human breast tumor progression, we examined RHAMM, ras, and ERK expression in two cohorts of breast cancer patients using reverse transcription-PCR and immunocytochemistry. We show that overexpression of RHAMM in primary tumors of two patient cohorts was significantly prognostic of poor outcome in breast cancer progression. Furthermore, RHAMM overexpression occurred within subsets of tumor cells in the primary tumor, and this staining pattern was associated with lymph node metastases. The metastases exhibited a significantly higher level of staining for RHAMM than did the primary tumor. RHAMM expression strongly correlated with overexpression of both ras and ERK, although overexpression of either of these two signaling molecules was not by itself a prognostic indicator. These results identify a new parameter that is involved in lymph node metastasis of primary breast cancers and suggest that quantification of RHAMM overexpression may be a useful prognostic indicator for breast carcinoma progression.
Chimeric Capsid Proteins Impact Transduction Efficiency of Haploid Adeno-Associated Virus Vectors (2019)

Our previous studies have demonstrated that haploid AAV vectors made from capsids of two different serotypes induced high transduction and prevented serotype-specific antibody binding. In this study, we explored the transduction efficiency of several haploid viruses, which were made from the VP1/VP2 of one serotype and VP3 of another compatible serotype. After systemic injection of 2 × 10<sup>10</sup> vg of AAV vectors into mice, the haploid AAV vectors, composed of VP1/VP2 from serotypes 8 or 9, and VP3 from AAV2, displayed a two to seven-fold increase in liver transduction compared with those of parental AAV2 vectors. Furthermore, a chimeric AAV2/8 VP1/VP2 with N-terminus of VP1/VP2 from AAV2 and C-terminus (VP3 domain) from AAV8 was constructed, and produced the haploid vector 28m-2VP3 with AAV2 VP3. The haploid 28m-2VP3 vector showed a five-fold higher transduction than that of the vectors composed solely of AAV2 VPs. Remarkably, the 28m-2VP3 vectors also induced a significant increase in transgene expression compared to the vectors composed of AAV8 VP1/VP2 with AAV2 VP3. The results suggest that the difference in the VP1/VP2 N-terminal region between AAV2 and AAV8 may allow better "communication" between the VP1/VP2 N-terminus of AAV2 with its cognate VP3. Similarly, the haploid vectors, VP1/VP2 from serotypes 8 or 9 and VP3 from AAV3, achieved higher transductions in multiple tissue types beyond typical tropism compared with those of AAV3 vectors. Consistently, higher vector genome copy numbers were detected in these tissues, indicating that an incorporation of non-cognate VP1/VP2 might influence the cellular tropism of the haploid vectors. However, there was no significant difference or even decreased transductions when compared with those of parental AAV8 or AAV9 vectors. In summary, these studies provide insight into current development strategies of AAV vectors that can increase AAV transduction across multiple tissues.
Mast cell density is associated with angiogenesis and poor prognosis in pulmonary adenocarcinoma (2000)

These data indicate that MC infiltration may contribute to tumor angiogenesis and tumor progression, and that MCD is a useful prognostic marker in pulmonary adenocarcinoma.
Immunomodulatory effects of Vitamin D in multiple sclerosis (2009)

Although Vitamin D is best known as a modulator of calcium homeostasis, it also has immune modulating potential. A protective effect of Vitamin D on multiple sclerosis is supported by the reduced risk associated with sun exposure and use of Vitamin D supplements. Moreover, high circulating levels of Vitamin D have been associated with lower risk of multiple sclerosis. In this study, we measured 1,25 (OH)(2) Vitamin D and 25 (OH) Vitamin D levels in multiple sclerosis patients separated into different clinical subgroups according to disease status. In addition, direct effects of 1,25 (OH)(2) Vitamin D on ex vivo CD4+ T cells and myelin-peptide specific T cell lines were investigated to gain more insight into putative regulatory mechanisms in the disease pathogenesis. One hundred and thirty-two Hispanic patients with clinically definite multiple sclerosis were studied, 58 with relapsing remitting multiple sclerosis during remission, 34 during relapse and 40 primary progressive multiple sclerosis cases. Sixty healthy individuals matched with respect to place of residence, race/ethnicity, age and gender served as controls. Levels of 25(OH)D(3) and 1,25(OH)(2)D(3), measured by ELISA were significantly lower in relapsing-remitting patients than in controls. In addition, levels in patients suffering relapse were lower than during remissions. In contrast, primary progressive patients showed similar values to controls. Proliferation of both freshly isolated CD4+ T cells and MBP-specific T cells was significantly inhibited by 1,25(OH)(2)D(3). Moreover, activated Vitamin D enhanced the development of IL-10 producing cells, and reduced the number of IL-6 and IL-17 secreting cells. Notably, Vitamin D receptor expression was induced by 1,25(OH)(2)D(3) in both activated and resting cells. Interestingly, T cells were able to metabolize 25(OH)D(3) into biologically active 1,25(OH)(2)D(3), since T cells express alpha1-hydroxylase constitutively. Finally, 1,25(OH)(2)D(3) also increased the expression and biological activity of indoleamine 2,3-dioxygenase, mediating significant increase in the number of CD4+CD25+ T regulatory cells. Collectively, these data suggest that 1,25(OH)(2)D(3) plays an important role in T cell homeostasis during the course of multiple sclerosis, thus making correction of its deficiency may be useful during treatment of the disease.
Remission in psoriatic arthritis. (2001)

Remission does occur in PsA and may be prolonged. There are clinical characteristics of patients at their first clinic visit that are associated with future remission.
Expression of homeobox genes, including an insulin promoting factor, in the murine yolk sac at the time of hematopoietic initiation (1997)

The visceral yolk sac (YS), a simple bilayer structure formed during gastrulation, supplies blood cells and intestine- and liver-like functions to support embryonic growth. To better understand gene regulation in extraembryonic tissues, we examined the early murine YS for expression of the homeobox family of developmental transcription regulators. We identified a subset of known homeobox sequences (Hox 1l, b1, a9, c9, a7, b7, b8, a10, cdx-1, and PDX-1), as well as two novel homeodomains consisting of a fourth labial class Hox genes and one that matches the Antennapedia class on the amino acid level. The two most frequently isolated YS Hox genes, a9 and c9, are initially expressed only in the YS (E.5) and subsequently expressed in both the embryo and YS (E8.5). Another of the identified genes, PDX-1, is involved in pancreatic development and insulin regulation. Whereas the4 rodent YS is known to produce insulin from mid to late gestation, YS insulin expression had not been examined earlier in development . We detected insulin mRNA in the YS at both E7.5 and E8.5, prior to expression in the embryo proper or formation of the pancreas. However, other pancreatic products, such as glucagon, somatostatin, and carboxypeptidase A, are not expressed in the YS. In situ analysis indicates insulin is produced in YS mesothelial cells and endoderm cells, but not in blood cells. We hypothesize the early expression of insulin in the YS is required for the expansion of insulin responsive cells including primitive erythroblasts.
Characterization of human mesothelin transcripts in ovarian and pancreatic cancer (2004)

Mesothelin transcript variant 1 represents the predominant mature mRNA species expressed by both normal and tumor cells. This conclusion should be important for future development of cancer immunotherapies, diagnostic tests, and gene microarray studies targeting mesothelin.