Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual controls for screening pigment movement in photoreceptors of the Limulus lateral eye: Circadian efferent input and light

Abstract The radial and longitudinal distribution of retinular screening pigment in the lateral eye of the horseshoe crab Limulus polyphemus was quantified under a variety of experimental conditions. Pigment position was characterized by the center and width of the radial distribution at four levels in the ommatidium. Under diurnal lighting, intact animals show movement of pigment granules from the periphery of the retinular cell at night towards the junction of the arhabdomeral and rhabdomeral segments of the retinular cell in the day. In constant darkness, intact animals exhibit the same circadian rhythm in pigment migration. Animals with bilaterally cut optic nerves do not receive circadian efferent input from the brain and show little pigment movement in diurnal lighting. In all of these cases, pigment was either aggregated in a band just peripheral to the rays of the rhabdom or dispersed to the periphery of the retinular cell. When dark-adapted animals are exposed to a sudden large light increment, pigment moves inward between the rays of the rhabdom. During the day, this inward response begins immediately and reverses as the ommatidial aperture begins to close. At night, the onset of the inward movement is delayed, but then occurs more rapidly than during the day. No significant longitudinal movement of photoreceptor screening pigment was detected under any of these experimental conditions. Two opposing mechanisms control the movement of screening pigment in these cells. Release of neurotransmitters from the circadian efferents causes outward movement; large increments of light cause inward movement. In the absence of sudden changes in light intensity, circadian efferent input, not cyclic lighting, appears to be the major determinant of screening pigment position. A sudden and large increment of light triggers the rapid inward movement which appears to be a protective mechanism optimized for daytime performance.
A Skin-depth Analysis of Integrins: Role of the Integrin Network in Health and Disease

Abstract In the skin epidermis, adhesion to the underlying basement membrane is mediated through trans-membrane integrin receptors. In addition to a structural role, integrins can signal in a bi-directional manner though the membrane and thus play a crucial role in cell adhesion, migration, proliferation, and differentiation. In this review we will discuss the role of integrins and their network of partner proteins in normal skin development, and how dysregulation influences disease states such as skin blistering disorders and cancers. We also discuss major integrin-specific therapeutic advances that have been made over the past few years in treating these skin disorders as well as targeting angiogenesis, neo-vasculature, and tumorigenesis.
Genetical Structure of Populations

is not true if the education is carried out correctly. No general practitioner can doubt that the majority of the so-called neurotics who " live on his doorstep " do so in the hope that they may be told they have not got cancer, but are too frightened to mention the word. Cancer education is being carried out in many countries, and the Americans have done so on a very large scale; but what is the right method in one country will certainly not suit another. In Britain it is a statutory obligation on the part of the local authorities to carry out all health education. It is to be hoped that in the near future the local authorities will undertake this education in connexion with cancer, as with our present knowledge it is the only hope of making earlier diagnosis and lowering the appalling mortality of this disease. Meanwhile, it would seem a wise step to try out a pilot scheme in an area with a population of four or five million people. Such a scheme might be carried out in more than one area, with different methods. It should not take more than one or two years to obtain the results of such an experiment.
Repression of Farnesoid X Receptor during the Acute Phase Response*

The acute phase response is associated with changes in the hepatic expression of genes involved in lipid metabolism. Nuclear hormone receptors that heterodimerize with retinoid X receptor (RXR), such as thyroid receptors, peroxisome proliferator-activated receptors, and liver X receptors, modulate lipid metabolism. We recently demonstrated that these nuclear hormone receptors are repressed during the acute phase response induced by lipopolysaccharide (LPS), consistent with the known decreases in genes that they regulate. In the present study, we show that LPS significantly decreases farnesoid X receptor (FXR) mRNA in mouse liver as early as 8 h after LPS administration, and this decrease was dose-dependent with the half-maximal effect observed at 0.5 μg/100 g of body weight. Gel-shift experiments demonstrated that DNA binding activity to an FXR response element (IR1) is significantly reduced by LPS treatment. Supershift experiments demonstrated that the shifted protein-DNA complex contains FXR and RXR. Furthermore, the expression of FXR target genes, SHP and apoCII, were significantly reduced by LPS (70 and 60%, respectively). Also, LPS decreases hepatic LRH expression in mouse, which may explain the reduced expression of CYP7A1 in the face of SHP repression. In Hep3B human hepatoma cells, both tumor necrosis factor (TNF) and interleukin-1 (IL-1) significantly decreased FXR mRNA, whereas IL-6 did not have any effect. TNF and IL-1 also decreased the DNA binding activity to an IR1 response element and the expression of SHP and apoCII. Importantly, TNF and IL-1 almost completely blocked the expression of luciferase activity linked to a FXR response element promoter construct transfected into Hep3B cells. Together with our earlier studies on the repression of RXRs, peroxisome proliferator-activated receptors, LXRs, thyroid receptors, constitutive androstane receptor, and pregnane X receptor, these results suggest that decreases in nuclear hormone receptors are major contributors to the decreased gene expression that occurs in the negative acute phase response.
Mrad9 and Atm Haploinsufficiency Enhance Spontaneous and X-Ray-Induced Cataractogenesis in Mice

Abstract Kleiman, N. J., David, J., Elliston, C. D. , Hopkins, K. M. , Smilenov, L. B. , Brenner, D. J., Worgul, B. V. , Hall, E. J. and Lieberman, H. B. Mrad9 and Atm Haploinsufficiency Enhance Spontaneous and X-Ray-Induced Cataractogenesis in Mice. Radiat. Res. 168, 567–573 (2007). Rad9 and Atm regulate multiple cellular responses to DNA damage, including cell cycle checkpoints, DNA repair and apoptosis. However, the impact of dual heterozygosity for Atm and Rad9 is unknown. Using 50 cGy of X rays as an environmental insult and cataractogenesis as an end point, this study examined the effect of heterozygosity for one or both genes in mice. Posterior subcapsular cataracts, characteristic of radiation exposure, developed earlier in X-irradiated double heterozygotes than in single heterozygotes, which were more prone to cataractogenesis than wild-type controls. Cataract onset time and progression in single or double heterozygotes were accelerated even in unirradiated eyes. These findings indicate that the cataractogenic effect of combined heterozygosity is greater than for each gene alone and are the first to demonstrate the impact of multiple haploinsufficiency on radiation effects in an intact mammal. These observations may help explain observed interindividual differential radiosensitivity in human populations and have important implications for those undergoing radiotherapy or exposed to elevated levels of cosmic radiation, such as the astronaut corps. These findings demonstrate that Mrad9 and Atm are important determinants of lens opacification and, given the roles of Atm and Rad9 in maintaining genomic stability, are consistent with a genotoxic basis for radiation cataractogenesis.
Tracking characteristics of an adaptive IIR notch filter for sinusoidal frequency variation

Tracking behavior of a gradient-based simplified algorithm for an adaptive infinite impulse response (IIR) notch filter with a sinusoidally-varying input signal frequency is presented in this paper. A first-order difference equation with respect to a steady-state instantaneous frequency tracking error is derived. The difference equation is used to derive tracking error and tracking mean square error (MSE) expressions based on the power spectral density (PSD) method. Extensive computer simulations are included to substantiate the analysis and show its limits.
Differences in propensity for drinking alcohol are reflected in subunit‐ and region‐specific GABAA receptor levels

Enhancement of GABAA receptor activity within certain discrete brain areas can elicit increased ethanol consumption, supporting a regionally specific role for GABAergic mechanisms in modulating ethanol reinforcement. The present study investigated if rats, which were in the highest (HES) or lowest (LES) 15th percentile of ethanol self‐administration, had different GABAA receptor levels. MaleWistar rats (n=30) were trained to self‐administer ethanol for 8 weeks followed by assessment of GABAA receptor mRNAs. In the last operant session the HES rats (4/group) were consuming significantly more ethanol than the LES rats (1.31±‐0.31 g/kg versus 0.02±0.02 g/kg; p<0.001). Significant GABAA receptor mRNA differences were found between the groups, which were subunit‐ and brain region‐specific, with higher mRNA levels in the HES rats in the dorsal raphe (α2, α3, γ1), medial raphe (α3, α5, β1, β3, γ1), cerebellum (α1, α6, β3, γ2long) and hippocampus (β1, β3, γ1 and γ2long). The elevated cerebellum α1 mRNA level in the HES rats was confirmed using Western blotting (mean density units ±SEM; LES rats 0.460 ±0.005 versus HES rats 0.610 ± 0.006, p=0.03). These data suggest that the differences in GABA receptors were due either to the different propensities of the groups to consume ethanol or were caused by their differing ethanol exposure.
Nausea and Vomiting of Pregnancy: Prevalence, Severity and Relation to Psychosocial Health

Purpose:Symptoms of nausea and vomiting are commonly experienced during early pregnancy (nausea and vomiting of pregnancy or NVP) and have been associated with stress, anxiety, and depression in pregnancy. However, nausea and vomiting in late pregnancy is a little-studied phenomenon. The purpose of our study was to examine the prevalence, severity, and psychosocial determinants of NVP during early and late pregnancy. Study Design and Methods:Data were originally from a longitudinal and epidemiological study of depression in pregnancy and postpartum in a cohort of 648 Canadian women conducted from 2005 to 2008. Measures included the Nausea and Vomiting in Pregnancy Instrument (NVPI), the Cambridge Worry Scale (CWS), and the Edinburgh Postnatal Depression Scale (EPDS). Demographic, maternal/obstetrical, psychological, and behavioral variables related to NVP were also examined. Odds ratios and 95% confidence intervals were calculated for all risk factors investigated using multiple logistic regression, controlling for potential confounders. Results:The prevalence of NVP was 63.3% (n = 551) at Time 1 (early pregnancy) and 45.4% (n = 575) at Time 2 (late pregnancy). Severity of symptoms was associated with earlier gestation, antiemetic medication use, employment status, and symptoms of major depression. Maternal smoking and having the support of three or more persons were protective for NVP. Clinical Implications:This study suggests that screening for NVP should be ongoing throughout pregnancy and measures that address NVP, poor social support, and depression are warranted. Further research is needed in regard to effective management of this very common and distressing condition.
Scheduling Surgical Cases into Overflow Block Time— Computer Simulation of the Effects of Scheduling Strategies on Operating Room Labor Costs

“Overflow” block time is operating room (OR) time for a surgical group’s cases that cannot be completed in the regular block time allocated to each surgeon in the surgical group. Having such overflow block time increases OR utilization. The optimal way to schedule patients into a surgical group’s overflow block time is unknown. In this study, we developed a scheduling strategy that balances the OR manager’s need to reduce staffing costs and the needs of patients and surgeons for flexibility in choosing the dates and times of cases. We used computer simulation to evaluate our scheduling strategy. Surgeons and patients (i) can schedule the case into any overflow block within 2 wk; (ii) can only schedule the case into a “first case of the day” start time more than 2 wk in the future if there is not enough open time for the case within 2 wk; (iii) must schedule the case to be done within 4 wk; and (iv) are encouraged to perform the case on the earliest possible date. Staffing costs were lowest when the OR manager did not incorporate surgeon and patient preferences when scheduling cases into overflow block time. The strategy we developed provides surgeons and patients with some flexibility in scheduling, while only increasing OR staffing costs slightly over the minimum achieved when the OR manager controls scheduling. Implications: The strategy we developed provides surgeons and patients with some flexibility in scheduling, while increasing OR staffing costs only slightly over the minimum achieved when the OR manager controls scheduling. Staffing costs were lowest when the operating room (OR) manager did not incorporate surgeon and patient preferences when scheduling cases into overflow block time.
Concept of Crohn's disease being conditioned by four main components, and irritable bowel syndrome being an incomplete Crohn's disease

Several mechanisms have been proposed for the development of Crohn's disease. Evidence in favour of a unifying 4-component concept to explain the development of Crohn's disease is presented. The four components are a genetic predisposition to an increased intestinal permeability, the key and initial triggering factor being an oral-pharyngeal bacterium that increases the mucosal permeability of the small intestine with only a minimal inflammatory reaction, an adherent-invasive strain of Escherichia coli that penetrates the mucosa and causes an acute inflammatory reaction in the intestinal wall, and finally a secondary invasion of bacteria causing the chronic inflammatory characteristics. Irritable bowel syndrome (IBS) is a functional bowel disorder with intermittent symptoms of varying intensity. Clinically, there is evidence to suggest a link between IBS patients with diarrhoea and patients with Crohn's disease. The common denominator and initial trigger for IBS with diarrhoea and Crohn's disease seems to be an increased small intestinal permeability, probably caused by an oral-pharyngeal bacterial strain. The important missing factor in IBS patients seems to be the adherent-invasive strain of E. coli in the proximal colon, causing the acute inflammatory process in patients with Crohn's disease. IBS with diarrhoea can then be looked upon as an incomplete Crohn's disease.
A comparison of Er:YAG laser and mechanical debridement for the non-surgical treatment of chronic periodontitis: a randomized, prospective clinical study.

AIMS To compare a monotherapy of Er:YAG laser debridement (ERL), wavelength 2940 nm, with mechanical scaling and root planing (SRP) for the treatment of chronic periodontitis using clinical and patient-centred outcomes. METHODS Twenty-eight participants had two randomly assigned quadrants treated with ERL and two with SRP. Full-mouth plaque index, probing depth, bleeding on probing, clinical attachment level and gingival recession were recorded at baseline and 6- and 12-weeks post therapy. A questionnaire was used to assess pain, discomfort and satisfaction during and after treatment. RESULTS Twenty-two participants completed treatment and had 6- and 12-week clinical re-evaluations. SRP provided greater mean pocket depth reduction at 6- and 12-weeks (p = 0.01 and p = 0.003 respectively), and a greater reduction in pockets ≥ 4 mm at 6 weeks only (p = 0.03) compared with ERL. SRP also resulted in a significant reduction in bleeding on probing (BOP) sites at 12 weeks compared with ERL and a statistically significant greater reduction in mean clinical attachment level (CAL) at 6- (p = 0.02) and 12-weeks (p = 0.03). Patients expressed greater satisfaction with SRP on the day of treatment but were equally satisfied subsequently. CONCLUSION SRP resulted in a statistically significant greater short-term improvement in clinical parameters and patient satisfaction compared with ERL.
SGLT2 Inhibitors and the Diabetic Kidney

Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure–lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether SGLT2 inhibitors, in addition to their glycemic and blood pressure benefits, may provide nephroprotective effects.
Structure of CFA/I fimbriae from enterotoxigenic Escherichia coli

Adhesion pili (fimbriae) play a critical role in initiating the events that lead to intestinal colonization and diarrheal disease by enterotoxigenic Escherichia coli (ETEC), an E. coli pathotype that inflicts an enormous global disease burden. We elucidate atomic structures of an ETEC major pilin subunit, CfaB, from colonization factor antigen I (CFA/I) fimbriae. These data are used to construct models for 2 morphological forms of CFA/I fimbriae that are both observed in vivo: the helical filament into which it is typically assembled, and an extended, unwound conformation. Modeling and corroborative mutational data indicate that proline isomerization is involved in the conversion between these helical and extended forms. Our findings affirm the strong structural similarities seen between class 5 fimbriae (from bacteria primarily causing gastrointestinal disease) and class 1 pili (from bacteria that cause urinary, respiratory, and other infections) in the absence of significant primary sequence similarity. They also suggest that morphological and biochemical differences between fimbrial types, regardless of class, provide structural specialization that facilitates survival of each bacterial pathotype in its preferred host microenvironment. Last, we present structural evidence for bacterial use of antigenic variation to evade host immune responses, in that residues occupying the predicted surface-exposed face of CfaB and related class 5 pilins show much higher genetic sequence variability than the remainder of the pilin protein.
Wide-band efficiency-enhanced CMOS rectifier

We present in this paper the design of a wide-band efficiency-enhanced CMOS rectifier. A novel semi-active diode is proposed to minimize both the diode forward voltage drop and the reverse leakage current. This is achieved by dynamically configuring the rectification device as a threshold compensated diode in the on-state while a standard MOS diode in the offstate, respectively. The proposed rectifier is implemented in a 0. 35μm 4M/2P standard CMOS process. In simulation, with 5.5V AC input at 13.56MHz, the rectifier outputs 4.94V DC voltage across a 1. 2kΩ load resistor, achieving 87% power conversion efficiency (PCE) and 90% voltage conversion efficiency (VCE). The PCE and VCE can be maintained from 1MHz to 20MHz input frequency, with only 3% deviation in the PCE and 2% deviation in the VCE. In addition, the performance of the rectifier is self-compensated over temperature and process. From -40°C to +130°C, the simulated VCE varies within 2% from 89.6% to 87.7%, while the PCE stays almost constant at 86%. With 200 Monte Carlo samples, the standard deviation in the PCE and VCE are as low as 0.56% and 0.57%, respectively.
Identification of fibroblast heterogeneity in the tumor microenvironment

Tumors are unorganized organs that contain many different cell types. In the recent years, many studies have reported that primary tumors contain fibroblasts/myofibroblasts (carcinoma-associated fibroblasts), mesenchymal cells such as pericytes/mural cells and other vascular smooth muscle cells. Several different markers are used routinely to identify carcinoma-associated fibroblasts (CAFs) such as alpha-smooth muscle actin (α-SMA), vimentin, S100A4 protein/fibroblast specific protein-1 (FSP1) and type I collagen. Likewise markers such as platelet derived growth factor receptor-beta (PDGFRβ) and NG2 chondroitin sulfate proteoglycan (NG2) are used to identify mesenchymal cells such as pericytes and other vasculature associated smooth muscle cells. It is still unknown whether these markers overlap with each other or identify a unique population of cells within the tumor microenvironment. Therefore in the present study we utilized two different mouse models of cancer, the Rip1Tag2 mice that develop progressive pancreatic cancer and an orthotopic 4T1 breast cancer model, to study the overlap between six different mesenchymal markers commonly used in mouse cancer research. Our study demonstrates that among all the markers, S100A4/FSP1 identifies a unique population of fibroblasts with minimal overlap with markers for αSMA, PDGFRβ and NG2. Vimentin and type I collagen are not specific markers for fibroblasts in these tumors. αSMA, PDGFRβ and NG2 significantly overlap with each other in identifying a mixed population of fibroblasts (activated or resting), myofibroblasts, pericytes and vascular smooth muscle cells. Collectively, this study demonstrates that tumor microenvironment associated fibroblasts are a heterogeneous population and thus, the use of αSMA or vimentin as the only markers will not identify all the CAFs.