gebhart/patrepeval huggingface dataset:
CREB4, a Transmembrane bZip Transcription Factor and Potential New Substrate for Regulation and Cleavage by S1P (2005)

Regulated intramembrane proteolysis of the factors SREBP and ATF6 represents a central control mechanism in sterol homeostasis and stress response within the endoplasmic reticulum. Here, we compare localization of ATF6-related bZip factors CREB4, CREB-H, Luman, and OASIS. These factors contain the defining features of a bZip domain, a predicted transmembrane domain and an adjacent cleavage site for the Golgi protease S1P, with conserved features which indicate that it represents a specific subclass of S1P sites. Each factor localizes to the endoplasmic reticulum (ER), but a population of CREB4 was also observed in the Golgi. Deletion of the transmembrane domain in CREB4 resulted in efficient nuclear accumulation. An N-terminal variant of CREB4 containing the BZIp domain potently activated expression from a target gene containing ATF6 binding sites and from the promoter for the ER chaperone GRP78/BIP. CREB4 was cleaved in a site-specific manner in response to brefeldin A disruption of the Golgi or by coexpression with S1P but only after deletion or substitution of its C-terminal lumenal domain. Thus, S1P cleavage of CREB4 may be suppressed by a determinant in the C-terminal region. Dithiothreitol induced more complete transport of CREB4 to the Golgi, but not cleavage. Together, the data identify at least one additional bZip factor whose localization responds to ER stress, and we propose a model based on these results that indicates additional levels of control of this novel class of transcription factors.
Spherical Crystallization: Direct Spherical Agglomeration of Salicylic Acid Crystals During Crystallization (1982)

Direct spherical agglomeration of salicylic acid crystals during crystallization is described. The needle-like salicylic acid crystals simultaneously form and agglomerate in a mixture of three partially miscible liquids, such as water, ethanol, and chloroform, with agitation. The agglomerates can be made directly into tablets because of their excellent flowability. Spherical crystallization could eliminate the usual separate agglomeration step after crystallization and may be adaptable to other pharmaceutical and chemical systems.
Transactivation of EGFR mediates insulin-stimulated ERK1/2 activation and enhanced cell migration in human corneal epithelial cells. (2006)

Inhibition of EGFR activity decreases cell migration involved in insulin-induced wound repair, an effect that mimics inhibition of MMP activation. Inhibition of MMP activity leads to decreased EGFR phosphorylation. Our data show that insulin stimulates wound healing in the corneal epithelium by activating EGFR, and point to a novel insulin signaling pathway that acts during corneal wound healing.
Interaction of the Sliding Clamp β-Subunit and Hda, a DnaA-Related Protein (2004)

In Escherichia coli, interactions between the replication initiation protein DnaA, the beta subunit of DNA polymerase III (the sliding clamp protein), and Hda, the recently identified DnaA-related protein, are required to convert the active ATP-bound form of DnaA to an inactive ADP-bound form through the accelerated hydrolysis of ATP. This rapid hydrolysis of ATP is proposed to be the main mechanism that blocks multiple initiations during cell cycle and acts as a molecular switch from initiation to replication. However, the biochemical mechanism for this crucial step in DNA synthesis has not been resolved. Using purified Hda and beta proteins in a plate binding assay and Ni-nitrilotriacetic acid pulldown analysis, we show for the first time that Hda directly interacts with beta in vitro. A new beta-binding motif, a hexapeptide with the consensus sequence QL[SP]LPL, related to the previously identified beta-binding pentapeptide motif (QL[SD]LF) was found in the amino terminus of the Hda protein. Mutants of Hda with amino acid changes in the hexapeptide motif are severely defective in their ability to bind beta. A 10-amino-acid peptide containing the E. coli Hda beta-binding motif was shown to compete with Hda for binding to beta in an Hda-beta interaction assay. These results establish that the interaction of Hda with beta is mediated through the hexapeptide sequence. We propose that this interaction may be crucial to the events that lead to the inactivation of DnaA and the prevention of excess initiation of rounds of replication.
Simultaneous EEG-fMRI for Functional Neurological Assessment (2019)

The increasing incidence of neurodegenerative and psychiatric diseases requires increasingly sophisticated tools for their diagnosis and monitoring. Clinical assessment takes advantage of objective parameters extracted by electroencephalogram and magnetic resonance imaging (MRI) among others, to support clinical management of neurological diseases. The complementarity of these two tools can be now emphasized by the possibility of integrating the two technologies in a hybrid solution, allowing simultaneous acquisition of the two signals by the novel EEG-fMRI technology. This review will focus on simultaneous EEG-fMRI technology and related early studies, dealing about issues related to the acquisition and processing of simultaneous signals, and including critical discussion about clinical and technological perspectives.
Improvement of Electrical Conductivity in Carbon Fiber-Concrete Composites Using Self Consolidating Technology (2010)

This paper presents the investigation of the effectiveness of self consolidating technology to improve the dispersion of carbon fibers and, therefore, electrical conductivity in concrete. The reduced working viscosity and void filling abilities of self-consolidating concrete (SCC) will be explored to address the problem of fiber dispersion. The practical results of this exploration will be applied to an electrical self-heating concrete system which uses resistive heating to provide heat to concrete in freezing environments for deicing or snow melting purposes. Resistivity of plain concrete with normal fiber, plain concrete with surfactant treated fiber, and SCC with plain fiber was experimentally determined over sample temperatures ranging from +20°C — –20°C. In all samples, it was observed that as temperature decreases, resistivity increases exponentially. Resistivity was also compared across sample types and carbon fiber composition. It was found that different mixing techniques had significant effects on sample resistivity, though there remain problems to be solved in using long carbon fibers in SCC.
Study of resonant modes of a periodic metallic array near a dielectric interface: evanescent-to-propagating coupling via surface plasmon excitation (2006)

The structural modes of a 2D periodic array of metallic cylinders near a dielectric interface are studied, for large and small wavelength-to-period ratios.We show that there are two clearly distinguished kinds of resonances: waveguide modes of the gap between the array and the interface, and eigenmode excitations (plasmons).While waveguide modes are present for both polarizations, surface plasmon polaritons (SPPs) only occur for p polarization, and, under particular conditions, this mechanism can produce an efficient coupling (about 60%) between the incident evanescent wave and the eigenmodes supported by the structure, which produces an enhanced transmitted propagating order.The response of the structure is analysed in detail by varying its relevant parameters, paying particular attention to the interplay between SPPs and Rayleigh anomalies, and its effect on the grating response.
Heterocyclization of Orthoaminoester and Orthoamino-nitrile-thieno[2, 3-<i>c</i>]pyridine: The Facile Synthesis of Fused Pyridothienopyrimidines (2006)

A highly efficient and versatile synthetic approach to the synthesis of pyrido[4′, 3′: 4]thieno[2,3-d]pyrimidines (4, 14, 15, 21) and their heterofused (e.g., triazolo-, triazino-, imidazo-, and tetrazolo-,) pyridothienopyrimidines (5–9, 16, 17, 22–24) is described utilizing 2-amino-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester ( 2 ) and diethyl 2-isothio-cyanate-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylate ( 10 ) as starting materials.
Running from Disease: Molecular Mechanisms Associating Dopamine and Leptin Signaling in the Brain with Physical Inactivity, Obesity, and Type 2 Diabetes (2017)

Physical inactivity is a primary contributor to diseases such as obesity, cardiovascular disease, and type 2 diabetes. Accelerometry data suggest that a majority of US adults fail to perform substantial levels of physical activity needed to improve health. Thus, understanding the molecular factors that stimulate physical activity, and physical inactivity, is imperative for the development of strategies to reduce sedentary behavior and in turn prevent chronic disease. Despite many of the well-known health benefits of physical activity being described, little is known about genetic and biological factors that may influence this complex behavior. The mesolimbic dopamine system regulates motivating and rewarding behavior as well as motor movement. Here, we present data supporting the hypothesis that obesity may mechanistically lower voluntary physical activity levels <i>via</i> dopamine dysregulation. In doing so, we review data that suggest mesolimbic dopamine activity is a strong contributor to voluntary physical activity behavior. We also summarize findings suggesting that obesity leads to central dopaminergic dysfunction, which in turn contributes to reductions in physical activity that often accompany obesity. Additionally, we highlight examples in which central leptin activity influences physical activity levels in a dopamine-dependent manner. Future elucidation of these mechanisms will help support strategies to increase physical activity levels in obese patients and prevent diseases caused by physical inactivity.
Laser-recrystallized silicon thin-film transistors on expansion-matched 800°C glass (1987)

Laser-recrystallized silicon thin-film transistors (TFT's) have been fabricated, for the first time, on a novel, potentially low-cost glass substrate, The 0.5-µm-thick silicon films were deposited along with appropiate dielectric layers on Corning Code 1729 glass substrates and recrystallized using an argon ion laser. The n-channel enhancement-mode transistors were made using conventional IC device fabrication procedures modified to have a maximum processing temperature of 800°C. Transistor's made in the recrystallized silicon show field-effect electron mobilities as high as 270 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> /V.s, approximately 15 times that of comparable devices made in as-deposited polycrystalline-silicon films. The recrystallized silicon devices also exhibit lower threshold voltages and lower leakage currents than do comparable polycrystalline-silicon devices.
Sharply tuned small force measurement with a biomimetic sensor (2011)

Hair cells in biological hearing organs transform mechanical stimuli into neuronal signals with great sensitivity, sharp frequency selectivity, and wide range of intensity. By combining principle of adaptation in hair cells with electronic engineering, we have produced a biomimetic force sensor under water showing all these features. For the nano-Newton force signal, the biomimetic sensor showed that more than an order of magnitude increases in sensitivity and frequency selectivity compared to the passive sensor. The nonlinear amplification mechanism in the hair cell is demonstrated by showing that the hair cell can precisely detect pulse signals weaker than noise.
Abstract 4558: FDG-PET uptake in breast cancer molecular subtypes (2012)

Abstract Background: Data on breast cancer FDG uptake in relation to clinically relevant molecular subtypes and their interaction is scarce. Some have shown higher standardized uptake values (SUV) in triple negative (TN) and HER2+ than hormone receptor (HR)+ disease. We hypothesize that FDG uptake in HER2+ disease depends on HR status. Methods: We identified 186 invasive breast cancer patients with a whole body FDG-PET/CT scan between 2005 and 2010 at UCSF (within 6 months prior to or after diagnosis but before therapy). Receptor expression was assessed on adjuvant therapy naïve specimens using IHC (HR [ER and PR], HER2) and FISH (HER2) according to clinical practice. We related routinely assessed (log-transformed) SUVmax to receptor expression with linear regression and analysis of covariance (ANCOVA), and adjusted for tumor grade. Results: SUVmax was reported for 160 primary breast cancers and 154 had complete data for HR and HER2. Median age at diagnosis was 52 years (range 21-87), and 34% had localized, 52% regional, and 14% distant disease. Average tumor size was 3.9 cm (SD 2.2), and 12% had good, 51% moderate and 37% poor grade. FDG uptake strongly depended on molecular subtype (Table). Uptake was lowest in HER2-HR+ and somewhat - but not significantly - higher in HER2+HR- disease. The highest SUVmax was found in HER2+HR+, followed by TN disease (both significantly higher than HER2-HR+). The interaction between HR and HER2 in relation to FDG uptake was significant (P=0.003). ANCOVA showed that the higher TN uptake could largely be explained by differences in grade, whereas SUVmax in HER2+HR+ disease remained significantly higher than in HER2-HR+ disease. Conclusion: This large series of advanced primary breast cancer showed FDG uptake to be comparably low in HER2-HR+ and HER2+HR- disease, but significantly higher in HER2+HR+ and TN disease. Tumor grade largely explained the higher FDG uptake in TN disease but not the results for HER2+HR+. FDG-PET may need evaluation at different settings taking into account uptake variation due to tumor biology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4558. doi:1538-7445.AM2012-4558
Declining Mortality Rates despite Increases in Clinical Coronary Artery Disease among US Dialysis Patients: A National Registry Study (2013)

Despite a rising burden of CAD among incident US dialysis patients, mortality rates have fallen for most groups. Substantial racial disparities remain.
Three-step cell search algorithm for broadband multi-carrier CDMA packet wireless access (2002)

This paper proposes a three-step cell search algorithm for a multi-carrier (MC)-CDMA broadband packet wireless access system with a 50-100 MHz bandwidth and evaluates the cell search time performance in a numerous-multipath fading channel. To achieve fast cell search, we introduce a continuously transmitted synchronization channel (SCH), which is multiplexed into sub-carriers with equal sub-carrier spacing and scrambled by the code common to all cell sites, and a common pilot channel (CPICH), which is continuously-transmitted in both the time and frequency domains and scrambled by a cell specific scrambling code (CSSC). In the proposed three-step algorithm, fast Fourier transform (FFT) window timing and packet frame timing are successively detected by using a guard interval and SCH and then, the CSSC of the target cell is identified by CPICH. Furthermore, in the proposed method, since the CSSC identification is performed for several candidates of the FFT window and packet frame timings, the best cell having the least path loss is precisely obtained despite the channel load, ie, the number of dedicated traffic channels (DTCH) in each cell. Computer simulation results show that by using the three-step cell search algorithm, the cell detection probability of 90% is achieved within approximately 77 msec (44 msec) when the number of DTCH with the information bit rate of 2 Mbit/s of each cell is distributed with the average of 20 and the standard deviation of 15 (0), when the FFT symbol-correlation of the SCH is averaged over N/sub PST//sup SCH/ = 20 (4) frames in the second step and the CPICH symbol-correlation is coherently averaged during N/sub CST//sup CPICH/ = 16 (10) symbols along the time axis and N/sub CSF//sup CPICH/ = 8 sub-carriers along the frequency axis CS-F in the third step.
Pathologic Features of Naturally Occurring Juvenile Polyarteritis in Beagle Dogs (1995)

Eighteen young Beagle dogs (eight males and 10 females), ages 6-40 months, with canine juvenile polyarteritis syndrome (CJPS), a naturally occurring vasculitis and perivasculitis of unknown etiology, were necropsied, and their tissues were examined by histopathologic and histochemical methods. The condition is characterized by recurring episodes of an acute onset of fever (> 40 C) and neck pain that persist for 3-7 days. The major histopathologic alterations were a systemic vasculitis and perivasculitis. During the febrile, painful period of CJPS, the vascular lesions ranged from a histiocytic-lymphocytic periarterial infiltration to transmural arterial inflammation with concomitant fibrinoid necrosis and vascular thrombosis. Massive periarterial accumulations of inflammatory cells were common and often extended into adjacent tissues. The small- to medium-sized muscular arteries of the heart, cranial mediastinum, and cervical spinal meninges were consistently involved. Vasculitis occasionally occurred in other organ systems. The vascular lesions in dogs examined during clinically normal periods consisted of intimal and medial fibrosis, ruptured elastic laminae, and mild perivasculitis; these lesions were probably related to previous episodes of vasculitis. Eight dogs that had experienced repeated acute episodes also developed splenic, hepatic, and renal amyloidosis. The clinical signs, laboratory abnormalities, and the vascular lesions suggest that the condition may be immune-system mediated. CJPS may serve as a naturally occurring animal model of human immune-system-mediated vasculitides such as polyarteritis nodosa, infantile polyarteritis, and Kawasaki disease.
Review of Drugs Approved via the 505(b)(2) Pathway: Uncovering Drug Development Trends and Regulatory Requirements (2020)

A 505(b)(2) application is a type of US new drug application (NDA) that contains full reports of investigations of safety and effectiveness, but where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference. Most 505(b)(2) applications consist of changes to a previously approved drug product (ie, a new dosage form, new routes of administration, etc). Sponsors often face challenges determining the studies to be conducted to support approval via 505(b)(2) pathway. This 5-year (2012-2016) retrospective analysis reviewed approved 505(b)(2) NDAs available on the FDA website, to determine the nature of studies (preclinical, clinical pharmacology, and efficacy/safety) conducted for various types of submissions and to better understand the trends in terms of regulatory requirements. The database consisted of 226 NDAs. One hundred twelve of those 226 had complete FDA review information, with the following FDA submission classes being more prevalent: type 3, new dosage form; type 4, new combination; and type 5, new formulation or new manufacturer. Therefore, only these 112 NDAs were further examined as they could show trends in terms of the studies conducted for various types of applications. Based on the investigation of NDA review documents, coupled with guidance documents, decision trees for studies to be conducted have been developed, which may serve as a guide of recommendations for a successful 505(b)(2) development program and NDA submission.
Treatment With Anti-T-Lymphocyte Antibodies Prevents Induction of Insulitis in Mice Given Multiple Doses of Streptozocin (1987)

The importance of T-lymphocytes in the induction of insulitis and hyperglycemia in certain strains of mice treated with multiple subdiabetogenic doses of streptozocin has been a matter of controversy. To understand the role of T-lymphocytes, we treated thymectomized BALB/c ByJ mice with five daily doses of streptozocin (45 mg/kg) and determined the effect of treatment with monoclonal antibodies against T-lymphocyte subsets on the development of diabetes and insulitis. Hyperglycemia (mean glucose of 321 +/- 29 vs. 167 +/- 15 mg/dl in controls) and insulitis were induced in BALB/c ByJ mice given streptozocin. Thy1.2+, L3T4, and Lyt2+ cells were all identified within the islets of diabetic mice. There was a relative paucity of L3T4+ cells and an overabundance of Lyt2+ cells compared with the frequency of these cells found in lymphatic tissues or peripheral blood. Treatment with anti-L3T4 or anti-Lyt2 monoclonal antibodies caused a reduction in splenic T-lymphocyte subsets and attenuated the hyperglycemia to 212 +/- 14 and 197 +/- 16 mg/dl (P less than .001 and .01), respectively, compared with controls and prevented the insulitis induced by streptozocin. Our studies support the hypothesis that an immune response is important to the development of multi-low-dose streptozocin diabetes and indicate that treatment with monoclonal antibodies against the L3T4+ or Lyt2+ T-lymphocyte subsets can attenuate this process.
The Empathic Physician (1994)

What a wonderful explication of the interpersonal phenomenon called empathy by Zinn. 1 In my own study of this clinical skill, at once (for me) diagnostic, therapeutic, and personally/ professionally rewarding, I cannot recall a more thoughtful analysis or lucid presentation. Zinn has contributed importantly to my understanding of doctoring, an interpersonal healing phenomenon shared, I believe, with our brothers and sisters in the major and minor healing and caring professions throughout history. Our equally wonderful biomedical technology has tended to marginalize doctoring and has distracted us from valuing and developing the skills of empathic understanding and responding. Not if, but when we demarginalize doctoring, we will also realize restored social approval, fewer malpractice claims, better patient cooperation, fewer tests ordered, fewer medications prescribed, and greater personal satisfaction with our work. Grandiose? Maybe. Wouldn't it be wonderful? Stay tuned. I also propose two questions for reflection: To what extent does
Measurement of I-V curves of silicon-on-insulator (SOI) MOSFET's without self-heating (1995)

A new method for measuring the output (I/sub D/-V/sub D/) characteristics of SOI MOSFET's without self-heating is described. The method uses short pulses with a low repetition rate, and a reverse transient loadline construction. The technique is demonstrated by measuring 0.25 μm bulk and SOI MOSFET's with 5-nm gate oxide. Application of the method to the extraction of device temperature as a function of DC power is also illustrated.