Miracle-dz/UniFAR-FTUs huggingface dataset:
Mode of Action of Chronotropic Agents in Cardiac Purkinje Fibers

Hauswirth et al. (1968) proposed that epinephrine acts on i KK2 by adding its own positive charge to the external membrane surface near the i KK2 channel. This hypothesis was tested by using noncationic compounds, theophylline and R07-2956, which mimicked epinephrine's effects on pacemaker activity and on i KK2. In maximally effective doses, theophylline or R07-2956 occluded the effect of epinephrine, indicating a shared final common mechanism. Since theophylline and R07-2956 are noncationic at pH 7.4, the common mechanism cannot be a direct change in external surface charge. On the contrary, epinephrine does not interfere with the voltage shift produced by La+++, which is thought to modify the external surface charge. The results argue against the original hypothesis but leave open the possibility that an alteration in internal surface charge generates the observed voltage shift. The potency of theophylline and R07-2956 as phosphodiesterase inhibitors suggests that the final common mechanism begins with the elevation of intracellular cyclic AMP, leading to a saturable process which limits the voltage shift's magnitude. This hypothesis is used to generate dose-response curves describing the combined effects of epinephrine and theophylline, and these are compared with experimental data.
Metabolism of (+)-1,4-Dihydro-7-(trans-3-methoxy-4-methylamino-1-pyrrolidinyl)-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic Acid (Voreloxin; Formerly SNS-595), a Novel Replication-Dependent DNA-Damaging Agent

(+)-1,4-Dihydro-7-(trans-3-methoxy-4-methylamino-1-pyrrolidinyl)-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid (voreloxin; formerly SNS-595 or AG-7352) is currently under investigation for the treatment of platinum-resistant ovarian cancer and acute myeloid leukemia. In vitro voreloxin undergoes minimal cytochrome P450 (P450) and UDP glucuronosyltransferase (UGT)-mediated metabolism, and in vivo excretion of unchanged voreloxin as the major species is consistent with the slow rate of metabolism observed in vitro. The objective of the present study was to examine the cross-species metabolic profile of voreloxin and to identify and characterize the metabolites formed in rats. We also investigated baculovirus-expressed human P450s and UGTs to determine which isoforms participated in voreloxin metabolism. Incubations using human, monkey, and rat liver microsomes showed monkey and rat metabolism is similar to human. Voreloxin and metabolites collected from plasma, bile, and urine from rats administered radiolabeled voreloxin were separated by high-performance liquid chromatography, and their structures were elucidated by liquid chromatography/tandem mass spectrometry. Activity of metabolites was determined with authentic reference standards in cell-based cytotoxicity assays. The proposed structures of metabolites suggest that metabolic pathways for voreloxin include glucuronide conjugation, oxidation, N-dealkylation, and O-dealkylation.
Ce-emerin and LEM-2: essential roles in Caenorhabditis elegans development, muscle function, and mitosis

ETOC: Caenorhabditis elegans lacking both Ce-emerin and LEM-2 show that these proteins are essential for development of specific lineages, mitosis in somatic cells, and smooth muscle activity. Reduced life span and smooth muscle activity of LEM-2–null worms predicts human LEM2 gene links to diseases more severe than Emery-Dreifuss muscular dystrophy.
Origin of 1/f noise in bipolar transistors

In planar n-p-n transistors fabricated in IC technology, the dependence of 1/<tex>f</tex>noise on the base current density j<inf>B</inf>, the base width W<inf>B</inf>, and the emitter area F<inf>E</inf>was measured. The power spectrum<tex>S_{iB}(f)</tex>of the base current fluctuations i<inf>B</inf>can be represented by the empirical relation<tex>S_{iB} = const. j\min{B}\max{\gamma} \cdot F\min{E}\max{\beta} \cdot w\min{B}\max{-1} \cdot f^{-1}</tex>where<tex>1 \leq \gamma \leq 2</tex>and β has been found to be 1.3 or 2. The results of measurements on gate-controlled devices indicate that 1/<tex>f</tex>noise cannot be explained by McWhorter's surface model. Therefore, a new model is proposed which assumes resistance fluctuations in the base region as the cause of 1/<tex>f</tex>noise in bipolar transistors. The model establishes the relation for<tex>S_{iB}(f)</tex>as well as the magnitude of the coefficients β and γ.
P‐selectin inhibition suppresses muscle regeneration following injury

This investigation sought to determine if P‐selectin‐mediated mechanisms contributed to macrophage localization in damaged muscle, an essential process for muscle regeneration. Mice were injected intravenously (i.v.) with soluble P‐selectin glycoprotein ligand‐1 (sPSGL‐1) at 5, 50, or 200 μg/mouse or with 100 μl vehicle alone, and then, lengthening contractions were induced in hindlimb plantar‐flexor muscles. The contractions caused fiber damage in soleus muscles, with maximal invasion by CD11b+ mononuclear cells at 24 h post‐injury and substantial accumulation of CD11b+ mononuclear cells in the extracellular matrix up to 7 days post‐injury. sPSGL‐1 treatment caused a dose‐dependent decrease in the number of regenerating fibers (P=0.021), as determined by developmental myosin heavy chain (dMHC) expression. This expression was reduced 93% at 7 days post‐injury by the highest dose of sPSGL‐1, which had no significant influence on intrafiber or extracellular accumulation of cells expressing CD11b, a general marker for phagocytic cells. Additional mice were injected i.v. with 20 μg anti‐P‐selectin or isotype‐control immunoglobulin G and were then subjected to lengthening contractions as before. At 7 days post‐injury, soleus muscles from anti‐P‐selectin‐treated mice contained 48% fewer mononuclear cells that bound ER‐BMDM1 (P=0.019), a marker for mature macrophages and dendritic cells, and 84% fewer fibers expressing dMHC (P = 0.006), compared with muscles from isotype‐injected, control mice. The number of CD11b+ cells was not significantly different between groups. The results are consistent with the concept that P‐selectin is involved in the recruitment, maturation, and/or activation of cells that are critical for muscle fiber regeneration.
Sensorimotor Recalibration Depends on Attribution of Sensory Prediction Errors to Internal Causes

Sensorimotor learning critically depends on error signals. Learning usually tries to minimise these error signals to guarantee optimal performance. Errors can, however, have both internal causes, resulting from one’s sensorimotor system, and external causes, resulting from external disturbances. Does learning take into account the perceived cause of error information? Here, we investigated the recalibration of internal predictions about the sensory consequences of one’s actions. Since these predictions underlie the distinction of self- and externally produced sensory events, we assumed them to be recalibrated only by prediction errors attributed to internal causes. When subjects were confronted with experimentally induced visual prediction errors about their pointing movements in virtual reality, they recalibrated the predicted visual consequences of their movements. Recalibration was not proportional to the externally generated prediction error, but correlated with the error component which subjects attributed to internal causes. We also revealed adaptation in subjects’ motor performance which reflected their recalibrated sensory predictions. Thus, causal attribution of error information is essential for sensorimotor learning.
Budding yeast PDS5 plays an important role in meiosis and is required for sister chromatid cohesion

Budding yeast PDS5 is an essential gene in mitosis and is required for chromosome condensation and sister chromatid cohesion. Here we report that PDS also is required in meiosis. Pds5p localizes on chromosomes at all stages during meiotic cycle, except anaphase I. PDS5 plays an important role at first meiotic prophase. Failure in function of PDS5 causes premature separation of chromosomes. The loading of Pds5p onto chromosome requires the function of REC8, but the association of Rec8p with chromosome is independent of PDS5. Mutant analysis and live cell imaging indicate that PDS5 play a role in meiosis II as well.
Adversity and internalizing problems among rural Chinese adolescents

Throughout the developing world, adolescents living in rural poverty face multiple and inter-related adaptive challenges. Using longitudinal data from the Gansu Survey of Children and Families, we adopt an approach grounded in resilience theory to investigate the relationship between cumulative adversity and internalizing problems among 1,659 adolescents between the ages of 13 and 16 years in an interior Chinese province. We also investigate the compensatory roles of parental warmth and teacher support. Results of multivariate regression models suggest that internalizing problems increased in later adolescence in this sample. The rate of increase did not differ by gender, counter to most extant literature on sex differences in the developmental trajectory of internalizing problems. Along with parental warmth, teacher support emerged as an especially important compensatory factor, highlighting the significance of teachers as an often overlooked resource for poor rural adolescents.
Awareness of Cervical Cancer Screening among Paramedical Staff and Students in An Institution of Northern India

Introduction: Cervical cancer is one of the leading causes of morbidity and mortality worldwide. Most women with cervical cancer present with advanced disease, resulting in low cure rates. Factors contributing to high burden of disease and advanced stage at presentation include poor knowledge about the disease furthermore and lack of screening among general population. Objective: To assess the knowledge and awareness of cervical cancer and explore attitudes and practices of Pap smear screening among paramedical staff and students in Santosh Medical College & Hospitals, Ghaziabad. Methods: A pretested self administered questionnaire based survey was done on 500 paramedical staff and students of Santosh Medical College & Hospitals, Ghaziabad, UP containing simple questions about demographics, knowledge about cervical cancer, its risk factors, screening techniques, attitudes towards cervical cancer screening and its practices. Results: In this study, about 20% were not aware of cervical cancer as a disease.19% knew that Pap smear is used for detection of preinvasive cervical cancer. O About 80% of subjects did not know that it was possible to detect cervical cancer early nor were they aware of different screening methods like Paps smear and had limited understanding of the types of cervical cancer screening techniques and poor disposition towards undergoing cervical cancer screening. 30% of the respondents knew about HPV Vaccine.
Enhancement of the Neutrality in Recommendation

This paper proposes an algorithm for making recommendation so that the neutrality toward the viewpoint specified by a user is enhanced. This algorithm is useful for avoiding to make decisions based on biased information. Such a problem is pointed out as the filter bubble, which is the influence in social decisions biased by a personalization technology. To provide such a recommendation, we assume that a user specifies a viewpoint toward which the user want to enforce the neutrality, because recommendation that is neutral from any information is no longer recommendation. Given such a target viewpoint, we implemented information neutral recommendation algorithm by introducing a penalty term to enforce the statistical independence between the target viewpoint and a preference score. We empirically show that our algorithm enhances the independence toward the specified viewpoint by and then demonstrate how sets of recommended items are changed.
Preliminary report of a phase I study of combination chemotherapy and humanized A33 antibody immunotherapy in patients with advanced colorectal cancer.

PURPOSE In previous studies, humanized A33 (huA33) demonstrated modest antitumor activity in chemotherapy-resistant colorectal cancer patients. In addition, unexpected major tumor responses were observed in patients treated with a specific chemotherapy regimen [carmustine, vincristine, fluorouracil, and streptozocin (BOF-Strep)] administered after huA33 protocols. We designed the present Phase I, open label, cohort, dose-escalation study of huA33 and a fixed dose of BOF-Strep to (a) determine the maximum tolerated dose of huA33 immunotherapy administered with chemotherapy, (b) determine whether chemotherapy modifies huA33 immunogenicity, and (c) develop preliminary information regarding antitumor activity. EXPERIMENTAL DESIGN Stage IV fluorouracil/leucovorin and irinotecan-refractory colorectal cancer patients (n = 16) received escalating weekly doses of huA33 (5-40 mg/m(2)) with BOF-Strep chemotherapy. RESULTS Four patients requiring radiotherapy or surgery were removed early. Of 12 evaluable patients, grade 3 and 4 neutropenia (n = 2) and grade 3 thrombocytopenia (n = 1) were observed. Seven of 12 (58.3%) patients developed anti-huA33 activity. Three patients had radiographic partial responses for 7.5, 5.5, and 14 months with greater than 85% decline in serum carcinoembryonic antigen levels. One mixed response (4.5 months with a serum carcinoembryonic antigen decline of 38%) was also observed. CONCLUSIONS huA33 can be safely combined with BOF-Strep chemotherapy. The present report provides compelling evidence supporting our previous observations of major antitumor activity with the combination of huA33 and BOF-Strep chemotherapy. huA33 is still immunogenic when administered with chemotherapy. Future studies to evaluate the immunogenicity of new huA33 antibodies and identify which drugs in the BOF-Strep regimen are critical for enhanced antitumor efficacy are planned.
Proanthocyanidin Attenuation of Oxidative Stress and NF-κB Protects Apolipoprotein E-Deficient Mice against Diabetic Nephropathy

Hyperlipidemia and hyperglycemia result in oxidative stress and play a major role in the development of diabetic nephropathy (DN). We explored the effects of proanthocyanidin (PA) on the induction and progression of DN in apolipoprotein E-deficient mice. Diabetes Mellitus was induced in ten-week-old male apoE−/−mice using streptozotocin (STZ). Mice were fed with a high-fat diet in presence or absence of PA. PA treatment significantly reduced the high cholesterol levels, restored renal functions, and reduced albuminuria in the PA-treated diabetic mice compared with the diabetic untreated mice. In addition, the glomerular mesangial expansion in the diabetic mice was attenuated as a result of PA supplementation. Moreover, PA treatment restored the elevated levels of MDA and CML and the reduced activity of SOD and GSH in the diabetic mice. Furthermore, PA feeding reduced the activation and translocation of NF-κB to the nucleus compared with the diabetic untreated animals. Reduction of NF-κB activation resulted in the attenuation of the expression of IL-6, TGFβ, and RAGE which protected PA-treated mice against DN. The renoprotective effects of PA were found to be time independent regardless of whether the dietary feeding with PA was started pre-, co-, or post-STZ injection. In conclusion, part of the beneficial effects of PA includes the disruption of the detrimental AGE-RAGE-NFκB pathways.
Dynamic and Static Facial Expressions Decoded from Motion-Sensitive Areas in the Macaque Monkey

Humans adeptly use visual motion to recognize socially relevant facial information. The macaque provides a model visual system for studying neural coding of expression movements, as its superior temporal sulcus (STS) possesses brain areas selective for faces and areas sensitive to visual motion. We used functional magnetic resonance imaging and facial stimuli to localize motion-sensitive areas [motion in faces (Mf) areas], which responded more to dynamic faces compared with static faces, and face-selective areas, which responded selectively to faces compared with objects and places. Using multivariate analysis, we found that information about both dynamic and static facial expressions could be robustly decoded from Mf areas. By contrast, face-selective areas exhibited relatively less facial expression information. Classifiers trained with expressions from one motion type (dynamic or static) showed poor generalization to the other motion type, suggesting that Mf areas employ separate and nonconfusable neural codes for dynamic and static presentations of the same expressions. We also show that some of the motion sensitivity elicited by facial stimuli was not specific to faces but could also be elicited by moving dots, particularly in fundus of the superior temporal and middle superior temporal polysensory/lower superior temporal areas, confirming their already well established low-level motion sensitivity. A different pattern was found in anterior STS, which responded more to dynamic than to static faces but was not sensitive to dot motion. Overall, we show that emotional expressions are mostly represented outside of face-selective cortex, in areas sensitive to motion. These regions may play a fundamental role in enhancing recognition of facial expression despite the complex stimulus changes associated with motion.
Role of nociceptin/orphanin FQ in age-dependent cerebral hemodynamic effects of brain injury.

This study was designed to compare the role of the newly described endogenous opioid nociceptin/orphanin FQ (NOC/oFQ) in the reductions of cerebral blood flow (CBF) and pial artery diameter observed following fluid percussion brain injury (FPI) in chloralose anesthetized newborn and juvenile pigs as a function of time postinsult. FPI elevated CSF NOC/oFQ concentration from 70 +/- 3 to 444 +/- 51 within 1 h and to 1,931 +/- 112 pg/mL (n = 7) within 8 h, whereas concentrations returned to control value within 168 h in the newborn. In contrast, FPI elevated CSF NOC/oFQ from 77 +/- 4 to 202 +/- 16 pg/mL (n = 7) within 1 h, while values returned to control value within 8 h in the juvenile. Topical NOC/oFQ (10(-8), 10(-6) M) induced vasodilation was reversed to vasoconstriction by FPI in the newborn while such responses were only attenuated in the juvenile at 1 h post insult (control, 9 +/- 1 and 16 +/- 1%; FPI newborn, -8 +/- 1 and -14 +/- 1%; FPI juvenile, 2 +/- 1 and 5 +/- 1%, n = 7). Such altered dilation returned to control value within 168 h in newborns and 8 h in juveniles. Blood flow in the cerebrum was reduced from 57 +/- 4 to 23 +/- 3 mL x min(-1) x 100 g(-1) (n = 7) within 1 h and returned to control value with 168 h post FPI in newborns. In animals pretreated with [F/G] NOC/oFQ (1-13) NH2 (1 mg/kg, i.v.), a NOC/oFQ antagonist, however, CBF only fell to 39 +/- 4 mL x min(-1) x 100 g(-1) (n = 7) at 1 h post insult in newborns. In contrast, CBF was only reduced from 57 +/- 6 to 32 +/- 2 in untreated and to 39 +/- 3 mL/min(-1) x 100 g(-1) (n = 7) in treated juveniles within 1 h post FPI. Similar observations for reductions in pial artery diameter were made in untreated and treated newborns and juveniles. These data suggest that an elevated CSF NOC/oFQ concentration and altered vascular responsiveness to this opioid contribute to reductions in CBF and pial artery diameter observed following FPI. Because such NOC/oFQ changes were greater in newborns versus juveniles, these data further suggest that NOC/oFQ contributes to age-related cerebral hemodynamic differences in the effects of FPI.
Tobacco Smoking and Esophageal and Gastric Cardia Adenocarcinoma: A Meta-analysis

Background: Smoking has been related to esophageal and gastric cardia adenocarcinoma, but the magnitude of the association is uncertain. Methods: We conducted a meta-analysis of 33 studies published up to January 2010. We derived summary estimates using random-effects models. Results: Compared with never-smokers, the pooled relative risk (RR) was 1.76 (95% confidence interval = 1.54–2.01) for ever-smokers, 2.32 (1.96–2.75) for current smokers, and 1.62 (1.40–1.87) for ex-smokers. There was no important difference between esophageal (RR = 1.85 for ever- vs. never-smokers) and gastric cardia (RR = 1.76) adenocarcinoma. We found a direct association with dose (RR = 2.48 [2.14–2.86] for ≥20 cigarettes/d) and duration (RR = 2.32 [1.92–2.82] for ≥40 years) of cigarette consumption. Conclusions: This meta-analysis estimates the excess of esophageal and gastric cardia adenocarcinoma risk for smokers. This risk was similar for the 2 cancer sites.
Fast Hue and Range Preserving Histogram Specification: Theory and New Algorithms for Color Image Enhancement

Color image enhancement is a complex and challenging task in digital imaging with abundant applications. Preserving the hue of the input image is crucial in a wide range of situations. We propose simple image enhancement algorithms, which conserve the hue and preserve the range (gamut) of the R, G, B channels in an optimal way. In our setup, the intensity input image is transformed into a target intensity image whose histogram matches a specified, well-behaved histogram. We derive a new color assignment methodology where the resulting enhanced image fits the target intensity image. We analyze the obtained algorithms in terms of chromaticity improvement and compare them with the unique and quite popular histogram-based hue and range preserving algorithm of Naik and Murthy. Numerical tests confirm our theoretical results and show that our algorithms perform much better than the Naik-Murthy algorithm. In spite of their simplicity, they compete with well-established alternative methods for images where hue-preservation is desired.
The Decision of African American Students to Complete High School : An Application of the Theory of Planned Behavior

A longitudinal study explored high school completion among African Americans. Male and female high school students aged 14 to 17 (N 166) completed a theory of planned behavior (I. Ajzen, 1991) questionnaire early in their 2nd year. Intentions to complete the year were accurately predicted from attitudes, subjective norms, and perceived behavioral control (R .71; p .01). Attitudes were related to beliefs about shortand long-term consequences; subjective norms reflected perceived expectations of family, teachers, and friends; and control considerations included requisite academic abilities, conflict with peers and teachers, and distracting life conditions. Intentions and, to a lesser extent, perceived behavioral control, predicted graduation almost 3 years later (R .50; p .01). The findings indicate opportunities for early interventions.
Reward preferences for generations in selected Information and Communication Technology companies : original research

Orientation:Previous research suggests that different generations have different reward preferences based on differences in values, frames of reference and life goals. Research purpose: The focus of this study was to determine whether different generations prefer different rewards in the Information and Communication Technology (ICT) industry in South Africa. Motivation for the study: The rationale for this study was to obtain a better understanding of the reward preferences of Veterans, Baby Boomers, Generation X and Generation Y in the ICT industry. Research design, approach and method: The research was a quantitative, cross-sectional, correlational design. Participants from two ICT companies completed a structured electronic survey. One hundred and sixty four valid responses were received. A Cronbach's alpha of 0.821 indicates that the survey was reliable. Main findings: Contrary to previous research, the results show that generations do not display different reward preferences. Practical/managerial implications: It would be more beneficial to use individual inter-relationship factors to develop a reward strategy than generations. Contribution/value-add: The research has added insight and value to reward preferences for generations in the ICT sector.