Miracle-dz/UniFAR-FTUs huggingface dataset:
Perceptual Learning Directs Auditory Cortical Map Reorganization through Top-Down Influences

The primary sensory cortex is positioned at a confluence of bottom-up dedicated sensory inputs and top-down inputs related to higher-order sensory features, attentional state, and behavioral reinforcement. We tested whether topographic map plasticity in the adult primary auditory cortex and a secondary auditory area, the suprarhinal auditory field, was controlled by the statistics of bottom-up sensory inputs or by top-down task-dependent influences. Rats were trained to attend to independent parameters, either frequency or intensity, within an identical set of auditory stimuli, allowing us to vary task demands while holding the bottom-up sensory inputs constant. We observed a clear double-dissociation in map plasticity in both cortical fields. Rats trained to attend to frequency cues exhibited an expanded representation of the target frequency range within the tonotopic map but no change in sound intensity encoding compared with controls. Rats trained to attend to intensity cues expressed an increased proportion of nonmonotonic intensity response profiles preferentially tuned to the target intensity range but no change in tonotopic map organization relative to controls. The degree of topographic map plasticity within the task-relevant stimulus dimension was correlated with the degree of perceptual learning for rats in both tasks. These data suggest that enduring receptive field plasticity in the adult auditory cortex may be shaped by task-specific top-down inputs that interact with bottom-up sensory inputs and reinforcement-based neuromodulator release. Top-down inputs might confer the selectivity necessary to modify a single feature representation without affecting other spatially organized feature representations embedded within the same neural circuitry.
Role of T Cell Receptor Affinity in the Efficacy and Specificity of Adoptive T Cell Therapies

Over the last several years, there has been considerable progress in the treatment of cancer using gene modified adoptive T cell therapies. Two approaches have been used, one involving the introduction of a conventional αβ T cell receptor (TCR) against a pepMHC cancer antigen, and the second involving introduction of a chimeric antigen receptor (CAR) consisting of a single-chain antibody as an Fv fragment linked to transmembrane and signaling domains. In this review, we focus on one aspect of TCR-mediated adoptive T cell therapies, the impact of the affinity of the αβ TCR for the pepMHC cancer antigen on both efficacy and specificity. We discuss the advantages of higher-affinity TCRs in mediating potent activity of CD4 T cells. This is balanced with the potential disadvantage of higher-affinity TCRs in mediating greater self-reactivity against a wider range of structurally similar antigenic peptides, especially in synergy with the CD8 co-receptor. Both TCR affinity and target selection will influence potential safety issues. We suggest pre-clinical strategies that might be used to examine each TCR for possible on-target and off-target side effects due to self-reactivities, and to adjust TCR affinities accordingly.
Increased expression of sex determining region Y-box 11 (SOX11) in cutaneous malignant melanoma

Objectives: To observe sex determining region Y-box 11 (SOX11) gene expression in cutaneous malignant melanoma and its effect on tumour cell proliferation. Methods: Clinicopathological data and tissue samples from patients with cutaneous malignant melanoma, together with tissue samples from healthy volunteers (controls), were retrospectively reviewed. Protein levels of SOX11 and the antigen identified by monoclonal antibody Ki-67 (Ki-67) in skin lesions were analysed using immunohistochemistry. The correlation between protein levels and clinipathological parameters was investigated. Results: Out of 40 patient samples, 25 (62.5%) were positive for SOX11 protein in malignant melanoma tissue. This was significantly higher than in 40 control tissue samples, in which no SOX11 protein was detected. Presence of SOX11 protein was positively related to the proliferation index of cutaneous malignant melanoma tumour cells. Presence of SOX11 protein in cutaneous malignant melanoma was related to tumour type, tumour location, lymph node metastasis and 5-year survival rate. Conclusion: Human cutaneous malignant melanoma tissues expressed high levels of SOX11 compared with healthy controls, suggesting that SOX11 may be a new prognostic marker for malignant melanoma.
Rock glaciers : II models and mechanisms

This second part of a review deals with the mechanisms of rock glacier formation and flow. The presence of a copious debris supply is important in all models, although the source of ice necessary for deformation of the debris is in dispute. Evidence for the three main models: permafrost creep, debris-covered glaciers and talus deformation (rockslide), are reviewed. Seismic and resistivity evidence suggests a nonglacial (permafrost) origin where such measurements have been made. There is also good evidence that glacier ice can be seen and its extent determined in other examples. Morphological characteristics are presented; in some cases they seem to be applicable to the permafrost creep model but can also be explained by the debris-covered glacier model. The consequences of both these models are discussed in the light of the appropriate flow law models. Several different ways in which talus deformation have been suggested and these can be applied in some cases. Because of confusion in the designation of 'valley side rock glaciers' these are here termed 'protalus lobes'. The origin of these features is still problematical and may not be the same as for rock glaciers sensu stricto. It is argued that there is still no conclusive evidence for a single flow mechanism for all the features ascribed as rock glacier or protalus lobes.
Transmission of the BSE Agent to Mice in the Absence of Detectable Abnormal Prion Protein

The agent responsible for transmissible spongiform encephalopathies (TSEs) is thought to be a malfolded, protease-resistant version (PrPres) of the normal cellular prion protein (PrP). The interspecies transmission of bovine spongiform encephalopathy (BSE) to mice was studied. Although all of the mice injected with homogenate from BSE-infected cattle brain exhibited neurological symptoms and neuronal death, more than 55 percent had no detectable PrPres. During serial passage, PrPres appeared after the agent became adapted to the new host. Thus, PrPres may be involved in species adaptation, but a further unidentified agent may actually transmit BSE.
Variability in energy expenditure and its components

Purpose of reviewTo review factors contributing to variation in total daily energy expenditure and its primary components: (1) resting metabolic rate; (2) diet-induced thermogenesis; and (3) activity thermogenesis, including exercise energy expenditure and nonexercise activity. For each component, the expected magnitude of intra-individual variability is also considered. We also reviewed studies that quantified the variability in 24 h energy expenditure. Recent findingsIn humans, the coefficient of variation in the components of total daily energy expenditure is around 5-8% for resting metabolic rate, 1-2% for exercise energy expenditure, and around 20% for diet-induced thermogenesis. The coefficient of variance for 24 h energy expenditure measured using a room calorimeter for resting metabolic rate is around 5-10%. Thus, these measures are all rather reproducible. Total daily energy expenditure varies several-fold in humans, not due to variation in resting metabolic rate, diet-induced thermogenesis, or exercise thermogenesis, but rather, due to variations in nonexercise activity. A variety of factors impact nonexercise activity, including occupation, environment, education, genetics, age, gender, and body composition, but little is known about the magnitude of effect. SummaryResting metabolic rate, diet-induced thermogenesis, exercise energy expenditure, and 24 h energy expenditure are highly reproducible. Coefficient of variation is smallest for exercise energy expenditure, followed by resting metabolic rate, 24 h energy expenditure, and diet-induced thermogenesis. There is considerable variability in total daily energy expenditure, largely due to variations in nonexercise activity. Although the factors that impact upon nonexercise activity are understood, their contribution to variation in total daily energy expenditure is unclear.
Linkage of photoreceptor degeneration by apoptosis with inherited defect in phototransduction.

PURPOSE To investigate the developing retina of normal and rd/rd mice to establish if the inherited defect in the retinal degeneration (rd) gene, encoding the beta subunit of the cascade phosphodiesterase, is associated with rd photoreceptor degeneration by apoptosis. METHODS DNA content of developing normal and rd/rd retinas was measured spectrophotometrically and analyzed for differential loss during the course of photoreceptor degeneration. Degenerating rd photoreceptors were evaluated by electron microscopy for cytoplasmic features and chromosomal condensation. DNA fragmentation was analyzed by agarose gel electrophoresis at daily intervals during the developmental period in which rd/rd cell death occurs. RESULTS DNA loss from developing rd/rd retinas is maximal between 10 and 15 postnatal days. Photoreceptor cells die individually throughout the postnatal period of degeneration, with pycnotic nuclei dispersed among morphologically normal rd photoreceptors. DNA fragmentation into 200 base pair multiples occurs maximally in rd/rd retinas between 10 and 15 postnatal days. CONCLUSION Photoreceptor cell death in developing rd/rd retinas occurs by a mechanism that links a defect in the phototransduction cascade with a program for cell death, called apoptosis.
Plasma insulin in pancreatic disease

Pancreatic exocrine function tests and plasma insulin curves after a glucose load have been performed in 74 patients, 32 with no significant pancreatic disease, 31 with various disorders of the pancreas, and 11 with postmature diabetes mellitus. Exocrine function was impaired in all patients with chronic pancreatitis and chronic relapsing pancreatitis, whereas insulin production was defective in seven of 10 of those with chronic pancreatitis, and in one of seven with chronic relapsing pancreatitis. The findings in other examples of pancreatic disease are mentioned. Two out of four patients presenting with diabetes mellitus, who were found to have a flat plasma insulin curve, proved on investigation to have chronic pancreatitis. The results of plasma insulin response curves in this series are discussed in relation to pancreatic disease and their possible value in diagnosis.
Coxiella burnetii Shedding Routes and Antibody Response after Outbreaks of Q Fever-Induced Abortion in Dairy Goat Herds

ABSTRACT Q fever is a zoonosis caused by Coxiella burnetii, a bacterium largely carried by ruminants and shed into milk, vaginal mucus, and feces. The main potential hazard to humans and animals is due to shedding of bacteria that can then persist in the environment and be aerosolized. The purpose of this study was to evaluate shedding after an outbreak of Q fever abortion in goat herds and to assess the relationship with the occurrence of abortions and antibody responses. Aborting and nonaborting goats were monitored by PCR for C. burnetii shedding 15 and 30 days after the abortion episodes. PCR analysis of all samples showed that 70% (n = 50) of the aborting and 53% (n = 70) of the nonaborting goats were positive. C. burnetii was shed into vaginal mucus, feces, and milk of 44%, 21%, and 38%, respectively, of goats that aborted and 27%, 20%, and 31%, respectively, of goats that delivered normally. Statistical comparison of these shedding results did not reveal any difference between these two groups. PCR results obtained for the vaginal and fecal routes were concordant in 81% of cases, whereas those for milk correlated with only 49% of cases with either vaginal or fecal shedding status. Serological analysis, using enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and complement fixation tests, showed that at least 24% of the seronegative goats shed bacteria. Positive vaginal and fecal shedding, unlike positive milk shedding, was observed more often in animals that were weakly positive or negative by ELISA or IFA. Two opposite shedding trends were thus apparent for the milk and vaginal-fecal routes. Moreover, this study showed that a nonnegligible proportion of seronegative animals that delivered normally could excrete C. burnetii.
High voltage control of power system by changing generator transformer tap positions case study

This paper presents a case study to control high voltage in power system with changing tap position of generator transformer. Rajasthan power system having two 765 kV GSS, twenty one 400 kV GSS and seven thermal plants have been selected to carry out case study and simulated in PSSE software. Simulation model consists of 85 buses, 62 transmission lines and 86 transformers. Total system load is 5656.60 MW & 907.02 MVAR. Five cases have been simulated considering the effect of generator transformer tap position on power system voltage and generator MVAR loading. From simulation studies it is found out that transmission network voltage profile is significantly reduced with increase of generator transformer tap position and injection of reactive power in National Grid is significantly reduced.
A low-power programmable DLL-based clock generator with wide-range anti-harmonic lock

A delay-locked loop (DLL)-based clock generator for dynamic frequency scaling has been developed in a 0.13um CMOS technology. The proposed clock generator can generate a wide-range of the multiplied clock signals ranging from 125MHz to 2GHz. In addition, thanks to the proposed anti-harmonic lock block, the clock generator can change the frequency dynamically in one cycle time of the reference clock. The proposed DLL-based clock generator occupies 0.019mm2 and consumes 21mW at 2GHz. The ratio of power consumption to frequency of the proposed clock generator is smaller than those of conventional ones.
Soy protein reduces hepatic lipotoxicity in hyperinsulinemic obese Zucker fa/fa rats Published, JLR Papers in Press, July 1, 2005. DOI 10.1194/jlr.M500067-JLR200

Hepatic steatosis is commonly present during the development of insulin resistance, and it is a clear sign of lipotoxicity attributable in part to an accelerated lipogenesis. There is evidence that a soy protein diet prevents the overexpression of hepatic sterol-regulatory element binding protein-1 (SREBP-1), decreasing lipid accumulation. Therefore, the aim of the present work was to study whether a soy protein diet may prevent the development of fatty liver through the regulation of transcription factors involved in lipid metabolism in hyperinsulinemic and hyperleptinemic Zucker obese fa/fa rats. Serum and hepatic cholesterol and triglyceride levels, as well as VLDL-triglyceride and LDL-cholesterol, were significantly lower in rats fed soy protein than in rats fed a casein diet for 160 days. The reduction in hepatic cholesterol was associated with a low expression of liver X receptor-α and its target genes, 7-α hydroxylase and ABCA1. Soy protein also decreased the expression of SREBP-1 and several of its target genes, FAS, stearoyl-CoA desaturase-1, and Δ5 and Δ6 desaturases, decreasing lipogenesis even in the presence of hyperinsulinemia. Reduction in SREBP-1 was not associated with the presence of soy isoflavones. Finally, soy protein reduced SREBP-1 expression in adipocytes, preventing hypertrophy, which also helps prevent the development of hepatic lipotoxicity.
Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML.

BACKGROUND The molecular causes of many hematologic cancers remain unclear. Among these cancers are chronic neutrophilic leukemia (CNL) and atypical (BCR-ABL1-negative) chronic myeloid leukemia (CML), both of which are diagnosed on the basis of neoplastic expansion of granulocytic cells and exclusion of genetic drivers that are known to occur in other myeloproliferative neoplasms and myeloproliferative-myelodysplastic overlap neoplasms. METHODS To identify potential genetic drivers in these disorders, we used an integrated approach of deep sequencing coupled with the screening of primary leukemia cells obtained from patients with CNL or atypical CML against panels of tyrosine kinase-specific small interfering RNAs or small-molecule kinase inhibitors. We validated candidate oncogenes using in vitro transformation assays, and drug sensitivities were validated with the use of assays of primary-cell colonies. RESULTS We identified activating mutations in the gene encoding the receptor for colony-stimulating factor 3 (CSF3R) in 16 of 27 patients (59%) with CNL or atypical CML. These mutations segregate within two distinct regions of CSF3R and lead to preferential downstream kinase signaling through SRC family-TNK2 or JAK kinases and differential sensitivity to kinase inhibitors. A patient with CNL carrying a JAK-activating CSF3R mutation had marked clinical improvement after the administration of the JAK1/2 inhibitor ruxolitinib. CONCLUSIONS Mutations in CSF3R are common in patients with CNL or atypical CML and represent a potentially useful criterion for diagnosing these neoplasms. (Funded by the Leukemia and Lymphoma Society and others.).
Location Search Based on Subarea Fingerprinting and Surface Fitting for Indoor Positioning System

The fingerprinting technique based on received signal strength (RSS) has been intensively researched for indoor localization in the last decade. Instead of using discrete reference points to build a fingerprint database, this paper applies the surface fitting technique to construct RSS spatial distribution functions and proposes two location search methods to find the target location. We also propose to use subarea division and determination to improve the fitting accuracy and search efficiency. In the offline phase, we divide the whole indoor environment into several subareas, construct a fingerprint for each subarea, and build a RSS fitting function for each access point in each subarea. In the online phase, we first determine to which subarea a target belongs, and then search its location according to the proposed exhaustive location search or gradient descent based search algorithm. We conduct both simulations and field experiments to verify the proposed scheme. The experiment results show that for the same reference point granularity, the proposed scheme can achieve on average 10% to 22% localization accuracy improvements, compared with the classical nearest neighbor-based fingerprinting method.
Evolutionary quantitative genetics of nonlinear developmental systems

In quantitative genetics, the effects of developmental relationships among traits on microevolution are generally represented by the contribution of pleiotropy to additive genetic covariances. Pleiotropic additive genetic covariances arise only from the average effects of alleles on multiple traits, and therefore the evolutionary importance of nonlinearities in development is generally neglected in quantitative genetic views on evolution. However, nonlinearities in relationships among traits at the level of whole organisms are undeniably important to biology in general, and therefore critical to understanding evolution. I outline a system for characterizing key quantitative parameters in nonlinear developmental systems, which yields expressions for quantities such as trait means and phenotypic and genetic covariance matrices. I then develop a system for quantitative prediction of evolution in nonlinear developmental systems. I apply the system to generating a new hypothesis for why direct stabilizing selection is rarely observed. Other uses will include separation of purely correlative from direct and indirect causal effects in studying mechanisms of selection, generation of predictions of medium‐term evolutionary trajectories rather than immediate predictions of evolutionary change over single generation time‐steps, and the development of efficient and biologically motivated models for separating additive from epistatic genetic variances and covariances.
Causes of SLIT discontinuation and strategies to improve the adherence: a pragmatic approach

Sublingual immunotherapy (SLIT) is often discontinued, and many patients do not renew the prescription. We evaluated the reasons for discontinuation and set up an educational/follow‐up plan to improve the adherence. In a first phase, the adherence at 4 months was directly assessed. Based on those results, an action plan (education, frequent contacts, and strictly scheduled visits) was developed and tested in other patients. A group of matched patients did not undergo the follow‐up plan (controls). In the first phase, involving 252 subjects, at 4 months, there were 30% dropouts, mainly due to side‐effects. In the second phase, 149 patients underwent education/follow‐up and 90 received no intervention. In the first group, discontinuations at 4 months were 5%, vs 18% in the controls (P = 0.01). After one year, 12% of patients were lost in the first group and 35% in the control group (P < 0.001). An adequate education and a strict follow‐up can significantly reduce SLIT's discontinuations.
The clustering of telomeres and colocalization with Rap1, Sir3, and Sir4 proteins in wild-type Saccharomyces cerevisiae

We have developed a novel technique for combined immunofluorescence/in situ hybridization on fixed budding yeast cells that maintains the three-dimensional structure of the nucleus as monitored by focal sections of cells labeled with fluorescent probes and by staining with a nuclear pore antibody. Within the resolution of these immunodetection techniques, we show that proteins encoded by the SIR3, SIR4, and RAP1 genes colocalize in a statistically significant manner with Y' telomere- associated DNA sequences. In wild-type cells the Y' in situ hybridization signals can be resolved by light microscopy into fewer than ten foci per diploid nucleus. This suggests that telomeres are clustered in vegetatively growing cells, and that proteins essential for telomeric silencing are concentrated at their sites of action, i.e., at telomeres and/or subtelomeric regions. As observed for Rap1, the Sir4p staining is diffuse in a sir3- strain, and similarly, Sir3p staining is no longer punctate in a sir4- strain, although the derivatized Y' probe continues to label discrete sites in these strains. Nonetheless, the Y' FISH is altered in a qualitative manner in sir3 and sir4 mutant strains, consistent with the previously reported phenotypes of shortened telomeric repeats and loss of telomeric silencing.
Remotely sensed primary production in the western Ross Sea: results of in situ tuned models

The Southern Ocean plays an important role in the global carbon cycle and, as a consequence, in the planetary climate equilibrium. The Ross Sea is one of the more productive regions in the Southern Ocean, due to strong phytoplankton blooms occurring during summer. Satellite remote sensing is a powerful tool for investigating such phenomena, especially if the bio-optical algorithms are tuned with in situ data. In this paper, after having compared the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) and the ENEA Lidar Fluorosensor (ELF), the SeaWiFS chlorophyll a (Chl a) algorithm is tuned in the Ross Sea by means of the ELF measurements. The Chl a concentrations obtained in this way have been the basis for estimating productivity values and their evolution during summer 1997–98. Three primary production models have been used, providing information on their accuracy and performance in the Antarctic environment. Our investigations suggest that the primary production was lower than usual during the period 3 December 1997–16 January 1998.