Miracle-dz/UniFAR-FTUs huggingface dataset:
Cells on a Chip - the Use of Electric Properties for Highly Sensitive Monitoring of Blood-Derived Factors Involved in Angiotensin II Type 1 Receptor Signalling

Background: We developed a highly sensitive cardiomyocyte based screening system for the non-destructive electronic detection of chronotropic drugs and tissue-secreted factors involved in AT1 receptor-mediated cardiovascular diseases. Methods: For this purpose we cultured spontaneously beating neonatal rat cardiomyocytes on microelectrode arrays (MEAs), and tested the optimised, stable culture parameters for a reproducible real-time recording of alterations in contraction frequency. After the evaluation of culture parameters, computer-based electronic measurement systems were used for counting of contractions by recording of the field potential of cardiomyocytes. Results: Using the biosensor, angiotensin II, the predominant ligand of the AT1 receptor, was detected at very low concentrations of 10-11 M via altered contractions of cardiomyocytes. Moreover, we demonstrated that cardiomyocyte coupled microarrays allow the detection of blood-derived low concentrated anti-AT1 receptor autoimmune antibodies of pregnant women suffering from preeclampsia. Conclusion: This study demonstrates the first well-suited electrophysiological recording of cardiomyocytes on multielectrode arrays as a benefit for functional biomonitoring for the detection of AT1 receptor/ligand interactions and other marker proteins in sera directed to cardiovascular diseases.
A Comparative in Vivo Study of Local Neurotoxicity of Lidocaine, Bupivacaine, 2‐Chloroprocaine, and a Mixture of 2‐Chloroprocaine and Bupivacaine

This study was undertaken because of several recent reports of adverse neurologic reactions following the use of 2-chloroprocaine. Carotid sheaths containing undisturbed vagus nerve were surgically exposed in rabbits and bathed in situ for up to 1 hour in one of the following isotonic solutions: physiologic salt solution, lidocaine 2%, bupivacaine 0.75%, 2-chloroprocaine 3%, or a mixture of 2-chloroprocaine 1.5% and bupivacaine 0.375%. Each solution contained epinephrine, 5 μ/ml, (1:200,000). In other animals the carotid sheaths were bathed in physiologic salt solution, or 2-chloroprocaine 3% without epinephrine. The nerves were excised 10 to 12 days later. C-fiber impulse conduction was normal in nerves that had been exposed to physiologic salt solution with or without epinephrine, to lidocaine, or to bupivacaine. Conduction was absent or markedly impaired in several nerve specimens following exposure to 2-chloroprocaine. Histologie sections revealed the presence of epineurial cellular infiltration and fibrosis, perineurial fibrosis, and axonal degeneration in nerves that had been exposed to 2-chloroprocaine or the mixture of 2-chloroprocaine and bupivacaine. Histologic abnormalities were minor or absent following exposure to lidocaine, to bupivacaine, or to physiologic salt solution. These findings suggest that, under the conditions of the experiments, 2-chloroprocaine is more neurotoxic than lidocaine or bupivacaine.
Differential genome-wide DNA methylation in association with nightshift work: From discovery to policy

Differential genome-wide DNA methylation in association with nightshift work: From discovery to policy Charleen Danielle Adams Chair of the Supervisory Committee: Parveen Bhatti, Research Associate Professor Department of Epidemiology Shift work, working outside the hours of 6 a.m. to 6 p.m. , is done by more than 21 million people in the United States and disproportionately done by the poor and by minorities. Many acute and chronic adverse health effects (including sleeplessness leading to injuries and accidents, cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes, and cancer) have been associated with working the nightshift. But because shift work is an integral part of our economy and unlikely to go away, owing to both the necessity of some services (e.g., hospital care, police patrol, and air traffic control) and the simple demand for around-the-clock conveniences (e.g., 24-hour grocery stores and gas stations), its prevalence, health effects, and burden on vulnerable populations makes shift work not only an exacerbating social determinant of health but a pressing public health concern. Yet scientific uncertainties remain about 1) the underlying mechanisms putting shift workers at risk for these health problems, 2) biomarkers that may help us ascertain earlier who is at greatest risk, 3) and best practices for limiting and/or mitigating shift work’s harms. As such, this dissertation was undertaken to tackle some of the unknowns in each of these areas of uncertainty. The first two chapters comprise exploratory (biomarker) analyses of DNA methylation, a potential mechanism linking shift work to cancer, among day and nightshift workers from the healthcare industry in the greater Seattle area. Chapter 1 explores the main effects of shift work on genome-wide DNA methylation among shift workers with an a priori focus on circadian genes, and Chapter 2 investigates whether DNA methylation of the top findings from Chapter 1 depends on two modifiable factors, chronotype (preference for activity in the morning or evening) and sleep duration (derived from actigraphy). Chapter 3 explores the policy landscape of the nightshift, using what we know and what we do not know about shift work and cancer as a case study. Applying the precautionary principle to motivate shared responsibility for shift work’s harms, we call for the convening of a consortium of shift work stakeholders and public deliberators to set, execute, and review the findings of a shift work research agenda aimed at speeding the discovery of mechanisms and biomarkers that can inform policy decisions to protect the lives of the many millions who work at night.
A digitized replica bitline delay technique for random-variation-tolerant timing generation of SRAM sense amplifiers

A digitized replica bitline delay technique has been proposed for random-variation-tolerant timing generation of SRAM sense amplifiers. The sense timing variation attributable to the random variation of transistor threshold voltage is reduced by sufficient count of multiple replica cells, and replica bitline delay is digitized and multiplied for adjusting it to the target sense timing. The variation of the generated timing was 34% smaller than that with a conventional technique and cycle time was reduced by 16% at the supply voltage of 0.6V in 40nm CMOS technology with this scheme.
The value of diagnostic information to patients with suspected multiple sclerosis. Rochester-Toronto MRI Study Group.

OBJECTIVE To determine the value of diagnostic information to patients with suspected multiple sclerosis (MS). Because treatment choices would be only minimally affected by earlier diagnosis for most patients with this clinical problem, this study assessed the "nondecisional" value of diagnosis. DESIGN Prospective survey of patients before and after diagnostic workup, including imaging with magnetic resonance scanning. We assessed the effect of diagnostic information on patients' sense of well-being, as well as direct measures of the utility of information (using time trade-off and willingness-to-pay techniques). SETTING Patients referred from primary care practices for diagnostic workup for suspected MS to neurology clinics and practices. PATIENTS Sixty-eight individuals, mean age 37.5 years, 53 female and 15 male. Thirty-one patients were classified as having "probable MS," and 37 were classified as having "possible MS" by the examining neurologist before workup. MEASUREMENTS Present and future health perception, uncertainty about diagnosis-prognosis, and level of anxiety. Willingness to pay for diagnostic information, quality of life as measured by the time trade-off technique, and psychological state of the patient before and after diagnosis. RESULTS Diagnostic uncertainty fell significantly as a result of the diagnostic workup. Most patients (59/62) said that they were better off having received diagnostic information. Although anxiety seemed to be reduced by testing, overall anxiety levels did not decrease as much as anticipated. Patients also became less optimistic about their future health after testing. On average, patients were willing to forgo 4.5 quality-adjusted life days to receive an earlier diagnosis and their quality of life after diagnosis improved slightly. Subgroups of patients differed in their response to diagnostic information. Those in whom no definitive diagnosis emerged tend to be more anxious rather than being reassured by the "negative" workup. Individuals with "positive" workups became less anxious and expressed favorable feelings about the diagnostic workup even though they often faced a chronic disease. CONCLUSIONS Overall, the diagnostic workup seemed to benefit patients and improve their sense of well-being. However, whether the effects were beneficial or not depended on the results of the diagnostic workup itself. In clinical practice the decision to undergo testing in situations in which definitive treatment is unavailable should be individualized. The potential for negative as well as positive consequences should be recognized.
The Cost of Economic Growth in Turkey: Unavoidable Increase in Current Deficit

In this study, the relationship between economic growth and current deficit is analyzed for Turkish economy with the annual data covering the period 1990-2015. Two variables; one is gross domestic product and the other one is current deficit, have taken place in the analyses. Time series data related to variables have been tested with ADF and PP Unit Root Tests, and it has been observed that the variables are stationary in the first level. In order to determine the causality relationship between variables, Granger Causality Test has been applied, and a unidirectional causality relationship from economic growth to current deficit has been found. Finally, Regression and Correlation Analyses have been applied in order to determine the direction and the degree of the relationship. The Regression Analysis has revealed that 1% increase in economic growth causes 3.43% increase in current deficit. In other words, the increase in growth causes increase in current deficit by affecting the balance of current account in a bad way.
Characterization of Transient Receptor Potential Vanilloid-1 (TRPV1) Variant Activation by Coal Fly Ash Particles and Associations with Altered Transient Receptor Potential Ankyrin-1 (TRPA1) Expression and Asthma*

Transient receptor potential (TRP) channels are activated by environmental particulate materials. We hypothesized that polymorphic variants of transient receptor potential vanilloid-1 (TRPV1) would be uniquely responsive to insoluble coal fly ash compared with the prototypical soluble agonist capsaicin. Furthermore, these changes would manifest as differences in lung cell responses to these agonists and perhaps correlate with changes in asthma symptom control. The TRPV1-I315M and -T469I variants were more responsive to capsaicin and coal fly ash. The I585V variant was less responsive to coal fly ash particles due to reduced translation of protein and an apparent role for Ile-585 in activation by particles. In HEK-293 cells, I585V had an inhibitory effect on wild-type TRPV1 expression, activation, and internalization/agonist-induced desensitization. In normal human bronchial epithelial cells, IL-8 secretion in response to coal fly ash treatment was reduced for cells heterozygous for TRPV1-I585V. Finally, both the I315M and I585V variants were associated with worse asthma symptom control with the effects of I315M manifesting in mild asthma and those of the I585V variant manifesting in severe, steroid-insensitive individuals. This effect may be due in part to increased transient receptor potential ankyrin-1 (TRPA1) expression by lung epithelial cells expressing the TRPV1-I585V variant. These findings suggest that specific molecular interactions control TRPV1 activation by particles, differential activation, and desensitization of TRPV1 by particles and/or other agonists, and cellular changes in the expression of TRPA1 as a result of I585V expression could contribute to variations in asthma symptom control.
Effect of COX-1 and COX-2 inhibition on induction and maintenance of carrageenan-evoked thermal hyperalgesia in rats.

Intrathecal administration of nonsteroidal anti-inflammatory drugs in the rat blocks the thermal hyperalgesia induced by tissue injury, which suggests a role for spinal cyclooxygenase (COX) products in this facilitated state. Two isozymes of the COX enzyme have been reported, COX-1 and COX-2, but the agents thus far examined are not isozyme selective. We examined the effects of intrathecally (i.t.) or systemically (i.p.) administered S(+)-ibuprofen (a nonselective COX inhibitor) or 1-[(4-methysulfonyl)phenyl]-3-tri-fluoromethyl-5-(4-fluorophenyl) pyrazole (SC58125; a COX-2 selective inhibitor) on carrageenan-induced thermal hyperalgesia (reduced hindpaw-withdrawal latency). The following observations were made: 1) Thermal hyperalgesia otherwise observed during the first 170 min was blocked in a dose-dependent manner by S(+)-ibuprofen or SC58125 administered i.t. or i.p. before carrageenan treatment. 2) Intraperitoneal, but not i.t. , administration of either inhibitor after the establishment of hyperalgesia (170 min after carrageenan injection) reversed thermal hyperalgesia in a dose-dependent manner. Thus, the initial component of thermal hyperalgesia after tissue injury was blocked by systemic or spinal administration of both COX inhibitors, whereas established hyperalgesia was reversed only by systemic inhibitors. This study demonstrates that at least spinal COX-2, if not both COX-1 and COX-2, are necessary for the initiation of thermal hyperalgesia, whereas nonspinal sources of prostanoids (synthesized by COX-2 and perhaps also COX-1) are important for the maintenance of thermal hyperalgesia associated with tissue injury and inflammation.
Expression of metastasis suppressor gene product, nm23 protein, is not inversely correlated with the tumour progression in human malignant melanomas

An inverse correlation between the nm23 RNA level and tumour progression of melanocytes has been reported. To elucidate whether the expression of nm23 gene product in malignant melanoma is also inversely correlated with metastatic potential, conventional prognostic parameters or the tumour suppressor protein p53, immunohistochemical studies using a monoclonal antibody against nm23‐H1 protein were performed on 138 benign and malignant melanocytic tumours. The expression of nm23 protein was compared with that of p53 protein and conventional clinicopathological prognostic factors. The nm23 protein level in benign melanocytes and metastatic melanoma cells was also studied by Western blot analysis. No significant difference regarding the protein was observed between naevi and melanomas, either at histological or protein levels. The expression correlated with local recurrence within 1 year after surgery, level of invasion and tumour thickness, but no parallels were observed between the nm23 and p53 proteins, suggesting that gene is regulated by independent mechanisms, although located on the same chromosome. There was no inverse correlation between the nm23 protein and melanoma metastasis which suggested that the nm23 protein does not appear to be lost during melanoma metastasis.
Brief Report on the Use of Radiolabeled Somatostatin Analogs for the Diagnosis and Treatment of Metastatic Small-Cell Lung Cancer Patients

Introduction: The demonstration of type 2 somatostatin receptors (SSTRs) in small-cell lung cancer (SCLC) represents the rationale for the use of positron emission tomography/computed tomography (PET/CT) to determine SSTR expression, and select patients suitable for peptide radioreceptor radionuclide therapy (PRRT) in extensive-disease stage (ED) SCLC. Methods: We evaluated 24 ED-SCLC patients with radiolabeled SST-analog PET/CT. Lesions at PET/CT scan were semiquantitatively scored (from 0 to 3+) and compared with contrast-enhanced CT findings. Patients scored as 3+ were admitted to PRRT after dosimetric evaluation. Average injected activity/cycle was 2.6 GBq (90yttrium-PRRT) or 6.0 GBq (177lutetium-PRRT). PRRT efficacy was clinically and radiologically assessed. Results: PET/CT was negative in four of 24 patients, whereas in the remaining 20 cases uptake was scored as 1+ in seven of 20, 2+ in one of 20, and 3+ in 12 of 20. Primary tumor lesions showed uptake in 16 of 24 patients. Uptake in metastatic lesions was observed in four of four adrenals, two of five brain, 12 of 16 bone, three of eight liver, and 17 of 20 lymph node lesions. Of the 12 patients eligible for PRRT, 11 were eventually treated and four of 11 patients received multiple PRRT administrations. Dosimetry resulted in a BED for kidney of 7.5 Gy (range, 4–21); bone marrow provisional dosage was 0.43 Gy (range, 0.1–1.7). Hematological PRRT toxicity occurred in three of 11 patients. No clinical or objective responses were observed with disease progression occurring approximately 48 days (range, 9–32) after PRRT. Conclusion: Radiolabeled SST-analog PET/CT demonstrated enhanced SSTR expression in 50% of cases. Nevertheless, PRRT in ED-SCLC was ineffective, suggesting the need to anticipate or combine PRRT in a multimodality approach.
Low dose dynamic CT myocardial perfusion imaging using a statistical iterative reconstruction method.

PURPOSE Dynamic CT myocardial perfusion imaging has the potential to provide both functional and anatomical information regarding coronary artery stenosis. However, radiation dose can be potentially high due to repeated scanning of the same region. The purpose of this study is to investigate the use of statistical iterative reconstruction to improve parametric maps of myocardial perfusion derived from a low tube current dynamic CT acquisition. METHODS Four pigs underwent high (500 mA) and low (25 mA) dose dynamic CT myocardial perfusion scans with and without coronary occlusion. To delineate the affected myocardial territory, an N-13 ammonia PET perfusion scan was performed for each animal in each occlusion state. Filtered backprojection (FBP) reconstruction was first applied to all CT data sets. Then, a statistical iterative reconstruction (SIR) method was applied to data sets acquired at low dose. Image voxel noise was matched between the low dose SIR and high dose FBP reconstructions. CT perfusion maps were compared among the low dose FBP, low dose SIR and high dose FBP reconstructions. Numerical simulations of a dynamic CT scan at high and low dose (20:1 ratio) were performed to quantitatively evaluate SIR and FBP performance in terms of flow map accuracy, precision, dose efficiency, and spatial resolution. RESULTS Forin vivo studies, the 500 mA FBP maps gave -88.4%, -96.0%, -76.7%, and -65.8% flow change in the occluded anterior region compared to the open-coronary scans (four animals). The percent changes in the 25 mA SIR maps were in good agreement, measuring -94.7%, -81.6%, -84.0%, and -72.2%. The 25 mA FBP maps gave unreliable flow measurements due to streaks caused by photon starvation (percent changes of +137.4%, +71.0%, -11.8%, and -3.5%). Agreement between 25 mA SIR and 500 mA FBP global flow was -9.7%, 8.8%, -3.1%, and 26.4%. The average variability of flow measurements in a nonoccluded region was 16.3%, 24.1%, and 937.9% for the 500 mA FBP, 25 mA SIR, and 25 mA FBP, respectively. In numerical simulations, SIR mitigated streak artifacts in the low dose data and yielded flow maps with mean error <7% and standard deviation <9% of mean, for 30 × 30 pixel ROIs (12.9 × 12.9 mm(2)). In comparison, low dose FBP flow errors were -38% to +258%, and standard deviation was 6%-93%. Additionally, low dose SIR achieved 4.6 times improvement in flow map CNR(2) per unit input dose compared to low dose FBP. CONCLUSIONS SIR reconstruction can reduce image noise and mitigate streaking artifacts caused by photon starvation in dynamic CT myocardial perfusion data sets acquired at low dose (low tube current), and improve perfusion map quality in comparison to FBP reconstruction at the same dose.
High-Performance Dual-Step Evanescently Coupled Uni-Traveling-Carrier Photodiodes

In this paper, we discuss a dual-step evanescently coupled photodiode (PD), which is composed of an improved evanescently coupled optical waveguide and a uni-traveling-carrier PD (UTC-PD). The hitherto serious dependence of the responsivity on the coupling length, which is determined by the cleaving process, or the necessity of a long (~ 700 mum) passive waveguide with a complex tapered structure, can be eliminated. The optimization of the waveguide structure, and the doping profile of the p-type absorption layer, allow the integrated UTC-PD to achieve a high responsivity (0.9 A/W, 1.04 A/W), with a large cleaving tolerance (~ 50 mum), a wide invariable electrical 3-dB bandwidth (60 GHz, 40 GHz) from a low (~ 0.5 mA) to a high output current (>13 mA), and a high saturation current-bandwidth product (around 780 mAGHz) simultaneously under a load of 50 Omega .
Personality and Perception of Tinnitus

Objectives: Tinnitus has high prevalence and a wide range of etiologies and of impacts on sufferers. Our objective was to develop understanding of the role of personality in the perception of tinnitus in the general population. As a theoretical basis for this, we combined elements of a general model of signal detection with the ideas of ignition (development) and promotion (neural transmission) of tinnitus, and considered plausible roles for personality factors within this conceptual framework. Design: We interviewed a birth cohort of 970 people aged 32 yr sampled from the general population. On the basis of questioning, we divided them into three groups, those without tinnitus, those with occasional tinnitus (including those with transient tinnitus of very brief duration), and those who experienced tinnitus most of the time. We also established how annoying or distressing the tinnitus was, and assessed personality using the Multidimensional Personality Questionnaire. Results: Tinnitus was experienced rarely by 38.2% and half the time or more by 6.8% of those studied. Men and women did not differ in the amount of tinnitus reported, but women were more likely to find it annoying. People from lower socioeconomic backgrounds were more likely to report tinnitus. People with tinnitus were more socially withdrawn, reactive to stress, alienated, and less Self-Controlled. People who were more annoyed by tinnitus were more socially withdrawn, and men were more stress reactive and alienated. Conclusions: Our interpretation of the findings is that personality influences the persistence of tinnitus by influencing the tendency to be aware of it. Consideration of personality factors may improve the ability to tailor tinnitus therapies, and the concept of awareness may benefit treatment outcomes by showing tinnitus sufferers a means of internalizing the locus of control over their symptoms.